Open Science Research Excellence

Open Science Index

Commenced in January 2007 Frequency: Monthly Edition: International Abstract Count: 66727

200
90334
Study of Exciton Binding Energy in Photovoltaic Polymers and Non-Fullerene Acceptors
Abstract:
The excitonic effect in organic semiconductors plays a key role in determining the electronic devices performance. Strong exciton binding energy has been regarded as the detrimental factor limiting the further improvement in organic photovoltaic cells. To the best of our knowledge, only limited reported can be found in measuring the exciton binding energy in organic photovoltaic materials. Conventional sophisticated approach using photoemission spectroscopy (UPS and IPES) would limit the wide access of the investigation. Here, we demonstrate a facile approach to study the electrical and optical quantum efficiencies of a series of conjugated photovoltaic polymer, fullerene and non-fullerene materials. Quantitative values of the exciton binding energy in those prototypical materials were obtained with concise photovoltaic device structure. And the extracted binding energies have excellent agreement with those determined by the conventional photoemission technique. More importantly, our findings can provide valuable information on the excitonic dissociation in the first excited state. Particularly, we find that the high binding energy of some non-fullerene acceptors limits the combination of polymer acceptors for efficiency exciton dissociation. The results bring insight into the engineering of excitonic effect for the development of efficient organic photovoltaic cells.
199
130061
In-Silico Investigation of Phytochemicals from Ocimum Sanctum as Plausible Antiviral Agent in COVID-19
Abstract:
COVID-19 has ravaged the globe, and it is spreading its Spectre day by day. In the absence of established drugs, this disease has created havoc. Some of the infected persons are symptomatic or asymptomatic. The respiratory system, cardiac system, digestive system, etc. in human beings are affected by this virus. In our present investigation, we have undertaken a study of the Indian Ayurvedic herb, Ocimum sanctum against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. MM-GBSA based binding free energy calculations also suggest the most favorable binding affinities of carvacrol, β elemene, and β caryophyllene with binding energies of −61.61, 58.23, and −54.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. It rekindles our hope for the design and development of new drug candidates for the treatment of COVID19.
198
14127
Insight into the Binding Theme of CA-074Me to Cathepsin B: Molecular Dynamics Simulations and Scaffold Hopping to Identify Potential Analogues as Anti-Neurodegenerative Diseases
Abstract:
To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.
197
46649
Modelling Ibuprofen with Human Albumin
Abstract:
The binding of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) to human serum albumin (HSA) is investigated using density functional theory (DFT) calculations within a fragmentation strategy. Crystallographic data for the IBU–HSA supramolecular complex shows that the ligand is confined to a large cavity at the subdomain IIIA and at the interface between the subdomains IIA and IIB, whose binding sites are FA3/FA4 and FA6, respectively. The interaction energy between the IBU molecule and each amino acid residue of these HSA binding pockets was calculated using the Molecular Fractionation with Conjugate Caps (MFCC) approach employing a dispersion corrected exchange–correlation functional. Our investigation shows that the total interaction energy of IBU bound to HSA at binding sites of the fatty acids FA3/FA4 (FA6) converges only for a pocket radius of at least 8.5 °A, mainly due to the action of residues Arg410, Lys414 and Ser489 (Lys351, Ser480 and Leu481) and residues in nonhydrophobic domains, namely Ile388, Phe395, Phe403, Leu407, Leu430, Val433, and Leu453 (Phe206, Ala210, Ala213, and Leu327), which is unusual. Our simulations are valuable for a better understanding of the binding mechanism of IBU to albumin and can lead to the rational design and the development of novel IBU-derived drugs with improved potency.
196
17280
Understanding the Dynamics of Linker Histone Using Mathematical Modeling and FRAP Experiments
Abstract:
Linker histones or histones H1 are highly mobile nuclear proteins that regulate the organization of chromatin and limit DNA accessibility by binding to the chromatin structure (DNA and associated proteins). It is known that this binding process is driven by both slow (strong binding) and rapid (weak binding) interactions. However, the exact binding mechanism has not been fully described. Moreover, the existing models only account for one type of bound population that does not distinguish explicitly between the weakly and strongly bound proteins. Thus, we propose different systems of reaction-diffusion equations to describe explicitly the rapid and slow interactions during a FRAP (Fluorescence Recovery After Photobleaching) experiment. We perform a model comparison analysis to characterize the binding mechanism of histone H1 and provide new meaningful biophysical information on the kinetics of histone H1.
195
86388
Energy Service Companies as a Facilitator for Implementation of Energy-Environment Conventions
Abstract:
The establishment of rules and regulations for more effective energy-environment interactions are essential to achieving sustainable development. Sustainable development requires mechanisms that can promote compliance in energy-environment conventions. There are many binding agreements and non-binding instruments at regional and international levels on energy and the environment. These conventions try to decrease conflicts of interest between energy, environment and economic by legal principles and practical mechanisms. The major core of conventions is their implementations because the poor implementation and enforcement power affect their success. In this regard, the main goal of this study is proposing the effective implementation mechanisms. Energy service companies' (ESCOs) activities can improve energy efficiency and decrease the environmental degradations. Therefore, it can be proposed and assessed the merit mechanism of ESCO performance as a facilitator to implement energy-environment conventions. An assessment of ESCO performance, including its potentials, problems, and limitations, as a facilitator for effective implementation of the energy-environment convention, is included. This study is oriented towards effective development and application of laws and the function of ESCOs as appropriate economic instruments and facilitator for implementation of energy-environment conventions. The resulting system of close cooperation between the energy-environment conventions and ESCOs is geared toward advancing environmental protection and economic factors by the transfer of environmentally-sound technologies that meet sustainable development objectives.
194
19875
Effects of Bacteria on Levels of AFM1 in Phosphate Buffer at Different Level of Energy Source
Abstract:
The binding of AFM1 to bacteria in phosphate buffer solution depended on many factors such as: availability of energy, incubation period, species and strain of bacteria. Increase in concentration of sugar showed higher removal of AFM1 and faster than in phosphate buffer alone. With 1.0% glucose lactic acid bacteria and bifidobacteria showed toxin removal ranging from 7.7 to 39.7% whereas with 10.0% glucose the percentage removal was 21.8 to 45.4% at 96 hours of incubation.
193
50468
An Energy Transfer Fluorescent Probe System for Glucose Sensor at Biomimetic Membrane Surface
Abstract:
Concanavalin A (conA) is a protein has been widely used in sensor system based on its specific binding to α-D-Glucose or α-D-Manose. For glucose sensor using conA, either fluoresence based techniques with intensity based or lifetime based are used. In this research, liposomes made from phospholipids were used as a biomimetic membrane system. In a first step, novel building blocks containing perylene labeled glucose units were added to the system and used to decorate the surface of the liposomes. Upon the binding between rhodamine labeled con A to the glucose units at the biomimetic membrane surface, a Förster resonance energy transfer system can be formed which combines unique fluorescence properties of perylene (e.g., high fluorescence quantum yield, no triplet formation) and its high hydrophobicity for efficient anchoring in membranes to form a novel probe for the investigation of sugar-driven binding reactions at biomimetic surfaces. Two glucose-labeled perylene derivatives were synthesized with different spacer length between the perylene and glucose unit in order to probe the binding of conA. The binding interaction was fully characterized by using high-end fluorescence techniques. Steady-state and time-resolved fluorescence techniques (e.g., fluorescence depolarization) in combination with single-molecule fluorescence spectroscopy techniques (fluorescence correlation spectroscopy, FCS) were used to monitor the interaction with conA. Base on the fluorescence depolarization, the rotational correlation times and the alteration in the diffusion coefficient (determined by FCS) the binding of the conA to the liposomes carrying the probe was studied. Moreover, single pair FRET experiments using pulsed interleaved excitation are used to characterize in detail the binding of conA to the liposome on a single molecule level avoiding averaging out effects.
192
37502
Insight into Structure and Functions of of Acyl CoA Binding Protein of Leishmania major
Abstract:
Acyl-CoA binding protein (ACBP) is a housekeeping protein which functions as an intracellular carrier of acyl-CoA esters. Given the fact that the amastigote stage (blood stage) of Leishmania depends largely on fatty acids as the energy source, of which a large part is derived from its host, these proteins might have an important role in its survival. In Leishmania major, genome sequencing suggests the presence of six ACBPs, whose function remains largely unknown. For functional and structural characterization, one of the ACBP genes was cloned, and the protein was expressed and purified heterologously. Acyl-CoA ester binding and stoichiometry were analyzed by isothermal titration calorimetry and Dynamic light scattering. Our results shed light on high affinity of ACBP towards longer acyl-CoA esters, such as myristoyl-CoA to arachidonoyl-CoA with single binding site. To understand the binding mechanism & dynamics, Nuclear magnetic resonance assignments of this protein are being done. The protein's crystal structure was determined at 1.5Å resolution and revealed a classical topology for ACBP, containing four alpha-helical bundles. In the binding pocket, the loop between the first and the second helix (16 – 26AA) is four residues longer from other extensively studied ACBPs (PfACBP) and it curls upwards towards the pantothenate moiety of CoA to provide a large tunnel space for long acyl chain insertion.
191
9190
The Influence of Physical-Mechanical and Thermal Properties of Hemp Filling Materials by the Addition of Energy Byproducts
Abstract:
This article describes to what extent the addition of energy by-products into the structures of the technical hemp filling materials influence their properties. The article focuses on the changes in physical-mechanical and thermal technical properties of materials after the addition of ash or FBC ash or slag in the binding component of material. Technical hemp filling materials are made of technical hemp shives bonded by the mixture of cement and dry hydrate lime. They are applicable as fillers of vertical or horizontal structures or roofs. The research used eight types of energy by-products of power or heating plants in the Czech Republic. Secondary energy products were dispensed in three different percentage ratios as a replacement of cement in the binding component. Density, compressive strength and determination of the coefficient of thermal conductivity after 28, 60 and 90 days of curing in a laboratory environment were determined and subsequently evaluated on the specimens produced.
190
76195
Antitrypanosomal Activity of Stigmasterol: An in silico Approach
Abstract:
Stigmasterol has previously been reported to possess antitrypanosomal activity using in vitro and in vivo models. However, the mechanism of antitrypanosomal activity is yet to be elucidated. In the present study, molecular docking was used to decipher the mode of interaction and binding affinity of stigmasterol to three known antitrypanosomal drug targets viz; adenosine kinase, ornithine decarboxylase and triose phosphate isomerase. Stigmasterol was found to bind to the selected trypanosomal enzymes with minimum binding energy of -4.2, -6.5 and -6.6 kcal/mol for adenosine kinase, ornithine decarboxylase, and triose phosphate isomerase respectively. However, hydrogen bond was not involved in the interaction of stigmasterol with all the three enzymes, but hydrophobic interaction seemed to play a vital role in the binding phenomenon which was predicted to be non-competitive like type of inhibition. It was concluded that binding to the three selected enzymes, especially triose phosphate isomerase, might be involved in the antitrypanosomal activity of stigmasterol but not mediated via a hydrogen bond interaction.
189
15681
Quantum Fisher Information of Bound Entangled W-Like States
Authors:
Abstract:
Quantum Fisher information (QFI) is a multipartite entanglement witness and recently it has been studied extensively with separability and entanglement in the focus. On the other hand, bound entanglement is a special phenomena observed in mixed entangled states. In this work, we study the QFI of W states under a four-dimensional entanglement binding channel. Starting with initally pure W states of several qubits, we find how the QFI decreases as two qubits of the W state is subject to entanglement binding. We also show that as the size of the W state increases, the effect of entanglement binding is decreased.
188
27370
A Platform to Screen Targeting Molecules of Ligand-EGFR Interactions
Abstract:
Epidermal growth factor receptor (EGFR) is often constitutively stimulated in cancer owing to the binding of ligands such as epidermal growth factor (EGF), so it is necessary to investigate the interaction between EGFR and its targeting biomolecules which were over ligands binding. This study would focus on the binding affinity and adhesion force of two targeting products anti-EGFR monoclonal antibody (mAb) and peptide A to EGFR comparing with EGF. Surface plasmon resonance (SPR) was used to obtain the equilibrium dissociation constant to evaluate the binding affinity. Atomic force microscopy (AFM) was performed to detect adhesion force. The result showed that binding affinity of mAb to EGFR was higher than that of EGF to EGFR, and peptide A to EGFR was lowest. The adhesion force between EGFR and mAb that was higher than EGF and peptide A to EGFR was lowest. From the studies, we could conclude that mAb had better adhesion force and binding affinity to EGFR than that of EGF and peptide A. SPR and AFM could confirm the interaction between receptor and targeting ligand easily and carefully. It provide a platform to screen ligands for receptor targeting and drug delivery.
187
20180
Isotope Effects on Inhibitors Binding to HIV Reverse Transcriptase
Abstract:
In order to understand in details the interactions between ligands and the enzyme isotope effects were studied between clinically used drugs that bind in the active site of Human Immunodeficiency Virus Reverse Transcriptase, HIV-1 RT, as well as triazole-based inhibitor that binds in the allosteric pocket of this enzyme. The magnitudes and origins of the resulting binding isotope effects were analyzed. Subsequently, binding isotope effect of the same triazole-based inhibitor bound in the active site were analyzed and compared. Together, these results show differences in binding origins in two sites of the enzyme and allow to analyze binding mode and place of newly synthesized inhibitors. Typical protocol is described below on the example of triazole ligand in the allosteric pocket. Triazole was docked into allosteric cavity of HIV-1 RT with Glide using extra-precision mode as implemented in Schroedinger software. The structure of HIV-1 RT was obtained from Protein Data Bank as structure of PDB ID 2RKI. The pKa for titratable amino acids was calculated using PROPKA software, and in order to neutralize the system 15 Cl- were added using tLEaP package implemented in AMBERTools ver.1.5. Also N-terminals and C-terminals were build using tLEaP. The system was placed in 144x160x144Å3 orthorhombic box of water molecules using NAMD program. Missing parameters for triazole were obtained at the AM1 level using Antechamber software implemented in AMBERTools. The energy minimizations were carried out by means of a conjugate gradient algorithm using NAMD. Then system was heated from 0 to 300 K with temperature increment 0.001 K. Subsequently 2 ns Langevin−Verlet (NVT) MM MD simulation with AMBER force field implemented in NAMD was carried out. Periodic Boundary Conditions and cut-offs for the nonbonding interactions, range radius from 14.5 to 16 Å, are used. After 2 ns relaxation 200 ps of QM/MM MD at 300 K were simulated. The triazole was treated quantum mechanically at the AM1 level, protein was described using AMBER and water molecules were described using TIP3P, as implemented in fDynamo library. Molecules 20 Å apart from the triazole were kept frozen, with cut-offs established on range radius from 14.5 to 16 Å. In order to describe interactions between triazole and RT free energy of binding using Free Energy Perturbation method was done. The change in frequencies from ligand in solution to ligand bounded in enzyme was used to calculate binding isotope effects.
186
43699
Investigation of Corrosion Inhibition Potential of Acalypha chamaedrifolia Leaves Extract towards Mild Steel in Acid Medium
Abstract:
Corrosion inhibition of mild steel in acid medium using Acalypha chamaedrifolia leaves extract as potential green inhibitor was investigated. Gravimetric (weight loss) technique was used for the corrosion studies. Mild steel coupons of 2cm × 1cm × 0.27 cm dimensions were exposed for varying durations of between 24 to 120 hours, in 1M HCl medium containing a varying concentrations of the leaves extract (0.25g/L, - 1.25g/L). The results show that corrosion rates dropped from a value of 0.49 mgcm-2hr-1 for the uninhibited medium to a value of 0.15 mgcm-2hr-1 for the inhibited medium of 1M HCl in 0.25 g/l of the extract. Values of corrosion inhibition efficiencies of 70.38-85.11% were observed as the concentration of the inhibitor were increased from 0.25g/L, - 1.25g/L. Corrosion Inhibition was found to increase with increase in immersion time and temperature. The magnitude of the Ea indicates that the interaction between the metal surface and the inhibitor was chemisorptions. The Adsorption process fit into the Langmuir isotherm model with a correlation coefficient of 0.97. Evidence from molecular dynamics model shows that Methyl stearate (Line 5) and (3Z, 13Z)-2-methyloctadeca-3,13-dien-1-ol (line 11) were found to have the highest binding energy of -197.69 ± 3.12 and-194.56 ± 10.04 in kcal/mol respectively. The binding energy of these compounds indicates that they would be a very good corrosion inhibitor for mild steel and other Fe related materials.
185
20154
Interaction of Low-Energy Positrons with Mg Atoms: Elastic Scattering, Bound States, and Annihilation
Abstract:
Annihilations, phase shifts, scattering lengths, and elastic cross sections of low energy positrons scattering from magnesium atoms were studied using the least-squares variational method (LSVM). The possibility of positron binding to the magnesium atoms is investigated. A trial wavefunction is suggested to represent e+-Mg elastic scattering and scattering parameters were derived to estimate the binding energy and annihilation rates. The trial function is taken to depend on several adjustable parameters and is improved iteratively by increasing the number of terms. The present results have the same behavior as reported semi-empirical, theoretical, and experimental results. Especially, the estimated positive scattering length supports the possibility of positron-magnesium bound state system that was confirmed in previous experimental and theoretical work.
184
78173
Effect of Low Temperature on Structure and RNA Binding of E.coli CspA: A Molecular Dynamics Based Study
Abstract:
Cold shock protein A (CspA) is major cold inducible protein present in Escherichia coli. The protein is involved in stabilizing secondary structure of RNA by working as chaperone during cold temperature. Two RNA binding motifs play key role in the stabilizing activity. This study aimed to investigate implications of low temperature on structure and RNA binding activity of E. coli CspA. Molecular dynamics simulations were performed to compare the stability of the protein at 37°C and 10 °C. The protein was mutated at RNA binding motifs and docked with RNA to assess the stability of both complexes. Results suggest that CspA as well as CspA-RNA complex is more stable at low temperature. It was also confirmed that RNP1 and RNP2 play key role in RNA binding.
183
46098
Studies on Mechanisms of Corrosion Inhibition of Acalypha chamaedrifolia Leaves Extract towards Mild Steel in Acid Medium
Abstract:
The mechanisms of corrosion inhibition of mild steel in acid medium using Acalypha chamaedrifolia leaves extract as potential green inhibitor were investigated. Gravimetric (weight loss) technique was used for the corrosion studies. Mild steel coupons of 2cm × 1cm × 0.27 cm dimensions were exposed for varying durations of between 24 to 120 hours, in 1M HCl medium containing a varying concentrations of the leaves extract (0.25g/L, - 1.25g/L). The results show that corrosion rates dropped from a value of 0.49 mgcm-2hr-1 for the uninhibited medium to a value of 0.15 mgcm-2hr-1 for the inhibited medium of 1M HCl in 0.25 g/l of the extract. Values of corrosion inhibition efficiencies of 70.38-85.11% were observed as the concentration of the inhibitor were increased from 0.25g/L, - 1.25g/L. Corrosion Inhibition was found to increase with increase in immersion time and temperature. The magnitude of the Ea indicates that the interaction between the metal surface and the inhibitor was chemisorptions. The Adsorption process fit into the Langmuir isotherm model with a correlation coefficient of 0.97. Evidence from molecular dynamics model shows that Methyl stearate (Line 5) and (3Z, 13Z)-2-methyloctadeca-3,13-dien-1-ol (line 11) were found to have the highest binding energy of -197.69 ± 3.12 and-194.56 ± 10.04 in kcal/mol respectively. The binding energy of these compounds indicates that they would be a very good corrosion inhibitor for mild steel and other Fe related materials.
182
38418
Synthesis, Characterization and in vitro DNA Binding and Cleavage Studies of Cu(II)/Zn(II) Dipeptide Complexes
Abstract:
Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.
181
104750
Understanding Inhibitory Mechanism of the Selective Inhibitors of Cdk5/p25 Complex by Molecular Modeling Studies
Abstract:
Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.
180
2503
Dimensionless Binding Values in the Evaluation of Paracetamol Tablet Formulation
Abstract:
Mechanical properties of paracetamol tablets containing Neem (Azadirachta indica) gum were compared with standard Acacia gum BP as binder. Two dimensionless binding quantities BEN and BEC were used in assessing the influence of binder type on two mechanical properties, Tensile Strength (TS) and Brittle Fracture Index (BFI). The two quantities were also used to assess the influence of relative density and binder concentration on TS and BFI as well as compare Binding Efficiencies (BE). The result shows that TS is dependent on relative density, binder type and binder concentration while BFI is dependent on the binder type and binder concentration; and that although, the inclusion of NMG in a paracetamol tablet formulation may not enhance the TS of the tablets produced, however it will decrease the tendency of the tablets to cap or laminate. This work concludes that BEN may be useful in quantitative assessment while BEC may be appropriate for qualitative assessment.
179
11825
Tail-Binding Effect of Kinesin-1 Auto Inhibition Using Elastic Network Model
Abstract:
Kinesin-1 (hereafter called kinesin) is a molecular motor protein that moves cargos toward the end of microtubules using the energy of adenosine triphosphate (ATP) hydrolysis. When kinesin is inactive, its tail autoinhibits the motor chain in order to prevent from reacting with the ATP by cross-linking of the tail domain to the motor domains at two positions. However, the morphological study of kinesin during autoinhibition is yet remained obscured. In this study, we report the effect of the binding site of the tail domain using the normal mode analysis of the elastic network model on kinesin in the tail-free form and tail-bind form. Considering the relationship between the connectivity of conventional network model with respect to the cutoff length and the functionality of the binding site of the tail, we revaluated the network model to observe the key role of the tail domain in its structural aspect. Contingent on the existence of the tail domain, the results suggest the morphological stability of the motor domain. Furthermore, employing the results from normal mode analysis, we have determined the strain energy of the neck linker, an essential portion of the motor domain for ATP hydrolysis. The results of the neck linker also converge to the same indication, i.e. the morphological analysis of the motor domain.
178
18004
MICA-TM Peptide Selectively Binds to HLAs Associated with Behçet's Disease
Abstract:
Behçet’s disease (BD) is a genetic autoimmune expressed by multisystemic inflammatory disorder mostly occurred at the skin, joints, gastrointestinal tract, and genitalia, including ocular, oral, genital, and central nervous systems. Most BD patients in Japan and Korea were strongly indicated by the genetic factor namely HLA-B*51 (especially, HLA-B*51:01) marker in HMC class I, while HLA-A*26:01 allele has been detected from the BD patients in Greek, Japan, and Taiwan. To understand the selective binding of the MICA-TM peptide towards the HLAs associated with BD, the molecular dynamics simulations were applied on the four HLA alleles (B*51:01, B*35:01, A*26:01, and A*11:01) in complex with such peptide. As a result, the key residues in the binding groove of HLA protein which play an important role in the MICA-TM peptide binding and stabilization were revealed. The Van der Waals force was found to be the main protein-protein interaction. Based on the binding free energy prediction by MM/PBSA method, the MICA-TM peptide interacted stronger to the HLA alleles associated to BD in the identical class by 7-12 kcal/mol. The obtained results from the present study could help to differentiate the HLA alleles and explain a source of Behçet’s disease.
177
94563
Functional Characteristics of Chemosensory Proteins in the Sawyer Beetle Monochamus alternatus Hope
Abstract:
The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae), is a major pest of pines and it is also the key vector of the exotic pinewood nematode in China. In the present study, we cloned, expressed, and purified a chemosensory protein (CSP) in M. alternatus. We surveyed its expression in various developmental stages of male and female adult tissues and determined its binding affinities for different pine volatiles using a competitive binding fluorescence assay. A CSP known as CSP5 in M. alternatus was obtained from an antennal cDNA library and expressed in Escherichia coli. Quantitative reverse transcription polymerase chain reaction results indicated that the CSP5 gene was mainly expressed in male and female antennae. Competitive binding assays were performed to test the binding affinity of recombinant CSP5 to 13 odour molecules of pine volatiles. The results showed that CSP5 showed very strong binding abilities to myrcene, (+)-β-pinene, and (−)-isolongifolene, whereas the volatiles 2-methoxy-4-vinylphenol, p-cymene, and (+)-limonene oxide have relatively weak binding affinity at pH 5.0. Three volatiles myrcene, (+)-β-pinene, and (−)-isolongifolene may play crucial roles in CSP5 binding with ligands, but this needs further study for confirmation. The sensitivity of insect to host plant volatiles can effectively be used to control and monitor the population through mass trapping as part of integrated pest management programs.
176
55814
Biophysical Study of the Interaction of Harmalol with Nucleic Acids of Different Motifs: Spectroscopic and Calorimetric Approaches
Authors:
Abstract:
Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.
175
72938
Activation of Caspase 3 by Terpenoids and Flavonoids in Cancer Cell Lines
Abstract:
Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.
174
37833
The Role of Metallic Mordant in Natural Dyeing Process: Experimental and Quantum Study on Color Fastness
Abstract:
It is known that the natural dyeing of cloth results moderate color, but with poor color fastness. This study points out the correlation between the macroscopic color fastness of natural dye to the cotton fiber and the microscopic binding energy of dye molecule to the cellulose. With the additive metallic mordant, the new-formed coordination bond bridges the dye to the fiber surface and thus affects the color fastness as well as the color appearance. The density functional theory (DFT) calculation is therefore used to explore the most possible mechanism during the dyeing process. Finally, the experimental results reflect the strong effect of three different metal ions on the natural dyeing clothes.
173
56288
A System Dynamics Model for Assessment of Alternative Energy Policy Measures: A Case of Energy Management System as an Energy Efficiency Policy Tool
Abstract:
European Union Energy Efficiency Directive provides a set of binding energy efficiency measures to reach. Each of the member states can use either energy efficiency obligation scheme or alternative policy measures or combination of both. Latvian government has decided to divide savings among obligation scheme (65%) and alternative measures (35%). This decision might lead to significant energy tariff increase hence impact on the national economy. To assess impact of alternative policy measures focusing on energy management scheme based on ISO 50001 and ability to decrease share of obligation scheme a System Dynamics modeling was used. Simulation results show that energy efficiency goal can be met with alternative policy measure to large energy consumers in industrial, tertiary and public sectors by applying the energy tax exemption for implementers of energy management system. A delay in applying alternative policy measures plays very important role in reaching the energy efficiency goal. One year delay in implementation of this policy measure reduces cumulative energy savings from 2016 to 2017 from 5200 GWh to 3000 GWh in 2020.
172
101783
Iron Response Element-mRNA Binding to Iron Response Protein: Metal Ion Sensing
Abstract:
Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.
171
73822
Investigation of Mutagenicity and DNA Binding Properties of Metal-Free and Metallophthalocyanines Containing α-Napththolbenzein Groups on the Peripheral Positions
Abstract:
In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.
170
75253
Application of New Sprouted Wheat Brine for Delicatessen Products From Horse Meat, Beef and Pork
Abstract:
The main task of the meat-processing industry is the production of meat products as the main source of animal protein, ensuring the vital activity of the human body, in the required volumes, high quality, diverse assortment. Providing the population with high-quality food products what are biologically full, balanced in composition of basic nutrients and enriched by targeted physiologically active components, is one of the highest priority scientific and technical problems to be solved. In this regard, the formulation of a new brine from sprouted wheat for meat delicacies from horse meat, beef and pork has been developed. The new brine contains flavored aromatic ingredients, juice of the germinated wheat and vegetable juice. The viscosity of meat of horse meat, beef and pork were studied during massaging. Thermodynamic indices, water activity and binding energy of horse meat, beef and pork with application of new brine are investigated. A recipe for meat products with vegetable additives has been developed. Organoleptic evaluation of meat products was carried out. Physicochemical parameters of meat products with vegetable additives are carried out. Analysis of the obtained data shows that the values of the index aw (water activity) and the binding energy of moisture in the experimental samples of meat products are higher than in the control samples. It has been established by investigations that with increasing water activity and the binding energy of moisture, the tenderness of ready meat delicacies increases with the use of a new brine.
169
28265
Investigating Anti-Tumourigenic and Anti-Angiogenic Effects of Resveratrol in Breast Carcinogenesis Using in-Silico Algorithms
Abstract:
Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.
168
7525
Metal-Based Anticancer Agents: In vitro DNA Binding, Cleavage and Cytotoxicity
Abstract:
Two new metal-based anticancer chemotherapeutic agents, [(Ph2Sn)2(HGuO)2(phen)Cl2] 1 and [(Ph3Sn)(HGuO)(phen)]- Cl.CH3OH.H2O 2, were designed, prepared and characterized by analytical and spectral (IR, ESI-Mass, 1H, 13C and 119Sn NMR) techniques. The proposed geometry of Sn(IV) in 1 and 2 is distorted octahedral and distorted trigonal-bipyramidal, respectively. Both 1 and 2 exhibit potential cytotoxicity in vitro against MCF-7, HepG-2 and DU-145 cell lines. The intrinsic binding constant (Kb) values of 1 (2.33 × 105 M-1) and 2 (2.46 × 105 M-1) evaluated from UV-Visible absorption studies suggest non-classical electrostatic mode of interaction via phosphate backbone of DNA double helix. The Stern-Volmer quenching constant (Ksv) of 1 (9.74 × 105 M-1) and 2 (2.9 × 106 M-1) determined by fluorescence studies suggests the groove binding and intercalation mode for 1 and 2, respectively. Effective cleavage of pBR322 DNA is induced by 1. Their interaction with DNA of cancer cells may account for potency.
167
10237
The Effect of Hydrogen on the Magnetic Properties of ZnO: A Density Functional Tight Binding Study
Abstract:
The ferromagnetic properties of carbon-doped ZnO (ZnO:CO) and hydrogenated carbon-doped ZnO (ZnO:CO+H) are investigated using the density functional tight binding (DFTB) method. Our results reveal that CO-doped ZnO is a ferromagnetic material with a magnetic moment of 1.3 μB per carbon atom. The presence of hydrogen in the material in the form of CO-H complex decreases the total magnetism of the material without suppressing ferromagnetism. However, the system in this case becomes quickly antiferromagnetic when the C-C separation distance was increased.
166
6727
In silico Analysis of Isoniazid Resistance in Mycobacterium tuberculosis
Abstract:
Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.
165
95277
N₂O₂ Salphen-Like Ligand and Its Pd(II), Ag(I) and Cu(II) Complexes as Potentially Anticancer Agents: Design, Synthesis, Antimicrobial, CT-DNA Binding and Molecular Docking
Abstract:
In this investigation, Cu(II), Pd(II) and Ag(I) complexes with the tetra-dentate DSPH Schiff base ligand were synthesized. The DSPH Schiff base and its complexes were characterized by using different physicochemical and spectral analysis. The results revealed that the metal ions coordinated with DSPH ligand through azomethine nitrogen and phenolic oxygen. Cu(II), Pd(II) and Ag(I) complexes are present in a 1:1 molar ratio. Pd(II) and Ag(I) complexes have square planar geometries while, Cu(II) has a distorted octahedral (Oh) geometry. All investigated complexes are nonelectrolytes. The investigated compounds were tested against different strains of bacteria and fungi. Both prepared compounds showed good results of inhibition against the selected pathogenic microorganism. Moreover, the interaction of investigated complexes with CT-DNA was studied via various techniques and the binding modes are mainly intercalative and grooving modes. Operating Environment MOE package was used to do docking studies for the investigated complexes to explore the potential binding mode and energy. Furthermore, the growth inhibitory effect of the investigated compounds was examined on some cancer cells lines.
164
67617
Accelerated Molecular Simulation: A Convolution Approach
Abstract:
Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be "steared" out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind "stearing" is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.
163
115037
Prediction of Binding Free Energies for Dyes Removal Using Computational Chemistry
Abstract:
Dye removal is an environmental concern because the textile industries have been increasing by world population and industrialization. Adsorption is the technique to find adsorbents to remove dyes from wastewater. This method is low-cost and effective for dye removal. This work tries to develop effective adsorbents using the computational approach because it will be able to predict the possibility of the adsorbents for specific dyes in terms of binding free energies. The computational approach is faster and cheaper than the experimental approach in case of finding the best adsorbents. All starting structures of dyes and adsorbents are optimized by quantum calculation. The complexes between dyes and adsorbents are generated by the docking method. The obtained binding free energies from docking are compared to binding free energies from the experimental data. The calculated energies can be ranked as same as the experimental results. In addition, this work also shows the possible orientation of the complexes. This work used two experimental groups of the complexes of the dyes and adsorbents. In the first group, there are chitosan (adsorbent) and two dyes (reactive red (RR) and direct sun yellow (DY)). In the second group, there are poly(1,2-epoxy-3-phenoxy) propane (PEPP), which is the adsorbent, and 2 dyes of bromocresol green (BCG) and alizarin yellow (AY).
162
63194
A Computational Approach to Screen Antagonist’s Molecule against Mycobacterium tuberculosis Lipoprotein LprG (Rv1411c)
Abstract:
Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).
161
2333
Molecular Docking of Marrubiin in Candida Rugosa Lipase
Abstract:
Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. These Candida species have been reported to have lipolytic activity by secretion of lipolytic enzymes such as esterases, lipases and phospholipases. These Extracellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin, which bind to a major component of the fungal cell membrane (ergosterol). This binding forms pores in the membrane that lead to death of the fungus. Due to their secondary effects, scientists have thought of another treatment basing on lipase inhibition but we haven’t found any lipase inhibitors used as candidiasis treatment. In this work, we are interested to lipases inhibitors such as alkaloids as another candidiasis treatment. In the first part, we have proceeded to optimize the alkaloid structures and protein 3D structure using Hyperchem software. Secondly, we have docked inhibitors using Genetic algorithm with GOLD software. The results have shown ten possibilities of binding inhibitor to Candida rugosa lipase (CRL) but only one possibility has been accepted depending on the weakest binding energy.
160
18350
Hyaluronic Acid Binding to Link Domain of Stabilin-2 Receptor
Abstract:
Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.
159
20360
On the Homology Modeling, Structural Function Relationship and Binding Site Prediction of Human Alsin Protein
Abstract:
Amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”. It is a neurodegenerative disease associated with degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord characterized by distal muscle weakness, atrophy, normal sensation, pyramidal signs and progressive muscular paralysis reflecting. ALS2 is a juvenile autosomal recessive disorder, slowly progressive, that maps to chromosome 2q33 and is associated with mutations in the alsin gene, a putative GTPase regulator. In this paper we have done homology modeling of alsin2 protein using multiple templates (3KCI_A, 4LIM_A, 402W_A, 4D9S_A, and 4DNV_A) designed using the Prime program in Schrödinger software. Further modeled structure is used to identify effective binding sites on the basis of structural and physical properties using sitemap program in Schrödinger software, structural and function analysis is done by using Prosite and ExPASy server that gives insight into conserved domains and motifs that can be used for protein classification. This paper summarizes the structural, functional and binding site property of alsin2 protein. These binding sites can be potential drug target sites and can be used for docking studies.
158
60080
The Effect of Inulin on Aflatoxin M1 Binding Ability of Probiotic Bacteria in Yoghurt
Abstract:
Aflatoxin M1 (AFM1) represents mutagenic, carcinogenic, hepatotoxic and immunosuppressive properties, and shows adverse effect on human health. Recently the use of probiotics are focused on AFM1 detoxification because of the fact that probiotic strains have a binding ability to AFM1. Moreover, inulin is a prebiotic to improve the ability of probiotic bacteria. Therefore, the aim of the study is to investigate the effect of inulin on AFM1 binding ability of some probiotic bacteria. Yoghurt samples were manufactured by using skim milk powder artificially contaminated with AFM1 at concentration 100 pg/ml. Different samples were prepared for the study as: first sample consists of yoghurt starter bacteria (L. bulgaricus and S. thermophilus), the second sample consists of starter and L. plantarum, starter and B. bifidum ATCC were added to the third sample, starter and B. animalis ATCC 27672 were added to the forth sample, and the fifth sample is a binary culture consisted of starter and B. bifidum and B. animalis. Moreover, the same work groups were prepared with inulin (4%). The samples were incubated at 42°C for 4 hours, then stored for three different time interval (1,5 and 10 days). The toxin was measured by the ELISA. When inulin was added to work groups, there was significant change on AFM1 binding ability at least one sample in all groups except the one with L. plantarum (p< 0.05). The highest levels of AFM1 binding ability (68.7%) in samples with inulin were found in the group which B. bifidum was added, whereas the lowest levels of AFM1 binding ability (44.4%) in samples with inulin was found in the fifth sample. The most impressive effect of inulin was found on B.bifidum. In this study, it was obtained that there was a significant effect of storage on AFM1 binding ability in the all groups with inulin except the one with L. plantarum (p< 0.05). Consequently, results show that AFM1 detoxification by probiotics have a potential application to reduce toxin concentrations in yoghurt. Besides, inulin has different effects on AFM1 binding ability of each probiotic bacteria strain.
157
53589
In-Silico Fusion of Bacillus Licheniformis Chitin Deacetylase with Chitin Binding Domains from Chitinases
Abstract:
Chitin, the biopolymer of the N-acetylglucosamine, is the most abundant biopolymer on the planet after cellulose. Industrially, chitin is isolated and purified from the shell residues of shrimps. A deacetylated derivative of chitin i.e. chitosan has more market value and applications owing to it solubility and overall cationic charge compared to the parent polymer. This deacetylation on an industrial scale is performed chemically using alkalis like sodium hydroxide. This reaction not only is hazardous to the environment owing to negative impact on the marine ecosystem. A greener option to this process is the enzymatic process. In nature, the naïve chitin is converted to chitosan by chitin deacetylase (CDA). This enzymatic conversion on the industrial scale is however hampered by the crystallinity of chitin. Thus, this enzymatic action requires the substrate i.e. chitin to be soluble which is technically difficult and an energy consuming process. We in this project wanted to address this shortcoming of CDA. In lieu of this, we have modeled a fusion protein with CDA and an auxiliary protein. The main interest being to increase the accessibility of the enzyme towards crystalline chitin. A similar fusion work with chitinases had improved the catalytic ability towards insoluble chitin. In the first step, suitable partners were searched through the protein data bank (PDB) wherein the domain architecture were sought. The next step was to create the models of the fused product using various in silico techniques. The models were created by MODELLER and evaluated for properties such as the energy or the impairment of the binding sites. A fusion PCR has been designed based on the linker sequences generated by MODELLER and would be tested for its activity towards insoluble chitin.
156
55863
Surface Characterization and Femtosecond-Nanosecond Transient Absorption Dynamics of Bioconjugated Gold Nanoparticles: Insight into the Warfarin Drug-Binding Site of Human Serum Albumin
Abstract:
We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.
155
117814
In-silico Analysis of Plumbagin against Cancer Receptors
Abstract:
Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.
154
5618
Study of Functional Relevant Conformational Mobility of β-2 Adrenoreceptor by Means of Molecular Dynamics Simulation
Abstract:
The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behaviour.
153
15176
Drug-Drug Plasma Protein Binding Interactions of Ivacaftor
Abstract:
Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.
152
100647
The Application of Article 111 of the Constitution of Bangladesh in the Criminal Justice System as a Sentencing Guideline
Abstract:
Generally, the decision of the higher court is binding on its subordinate courts. As provided in Article 111 of the Constitution, 'the law declared by the Appellate Division (AD) shall be binding on the High Court Division (HCD) and the law declared by either division of the Supreme Court shall be binding on all courts subordinate to it.' This means the judicial discipline requires the HCD to follow the decision of the AD and that it is necessary for the lower tiers of courts to accept the decision of the higher tiers as a binding precedent. Analyzing the application of Article 111 of the Constitution in the criminal justice system as a sentencing guideline, the paper, by examining whether there is any consistency in decision between one HC Bench and another HC Bench, explores whether HCD can per incuriam its previous decision. In doing so, the Death Reference (DR) Cases are contemplated. Furthermore, the paper shall examine whether the Court of Session follows the decision of the HCD while using their discretion to make the choice between death and imprisonment for life under section 302 of PC. The paper argues due to the absence of any specific direction for sentencing and inconsistency in jurisprudence among the HCD; the subordinate courts are in a dilemma.
151
23247
Calculation of Electronic Structures of Nickel in Interaction with Hydrogen by Density Functional Theoretical (DFT) Method
Abstract:
Hydrogen-Materials interaction and mechanisms can be modeled at nano scale by quantum methods. In this work, the effect of hydrogen on the electronic properties of a cluster material model «nickel» has been studied by using of density functional theoretical (DFT) method. Two types of clusters are optimized: Nickel and hydrogen-nickel system. In the case of nickel clusters (n = 1-6) without presence of hydrogen, three types of electronic structures (neutral, cationic and anionic), have been optimized according to three basis sets calculations (B3LYP/LANL2DZ, PW91PW91/DGDZVP2, PBE/DGDZVP2). The comparison of binding energies and bond lengths of the three structures of nickel clusters (neutral, cationic and anionic) obtained by those basis sets, shows that the results of neutral and anionic nickel clusters are in good agreement with the experimental results. In the case of neutral and anionic nickel clusters, comparing energies and bond lengths obtained by the three bases, shows that the basis set PBE/DGDZVP2 is most suitable to experimental results. In the case of anionic nickel clusters (n = 1-6) with presence of hydrogen, the optimization of the hydrogen-nickel (anionic) structures by using of the basis set PBE/DGDZVP2, shows that the binding energies and bond lengths increase compared to those obtained in the case of anionic nickel clusters without the presence of hydrogen, that reveals the armor effect exerted by hydrogen on the electronic structure of nickel, which due to the storing of hydrogen energy within nickel clusters structures. The comparison between the bond lengths for both clusters shows the expansion effect of clusters geometry which due to hydrogen presence.
150
34892
A Study of Binding Methods and Techniques in Safavid Era Emphasizing on Iran Shahnamehs (16-18th Century AD/10-12th Century AH)
Abstract:
The art of binding was simple and elementary at the beginning of Islam. This art thrived gradually and continued its development as an independent art. Identification of the binding techniques and used materials in covers and investigation of the arrays give us indexes for the better identification of different doctrines and methods of that time. The catalogers of the manuscripts usually pay attention to four items: gender, color, art elegances, injury, and exquisiteness of the cover. The criterion for classification of the covers is their art nature and gender. 15th century AD (9th century AH) was the period of the binding art development in which the most beautiful covers were produced by the so-called method of ‘burning’. At 16th century AD (10th century AH), in Safavid era, art changed completely and a fundamental evolution occurred in the technique and method of binding. The greatest change in this art was the extensive use of stamp that was made mostly of steel and copper. Theses stamps were presses against leather. These covers were called ‘beat’. In this paper, writing and bookbinding of about 32 Shahnamehs of Safavid era available in the Iranian libraries and museums are studied. An analytical-statistical study shows that four methods have been used including beat, burning, mosaic, and oily. 69 percent of the covers of these copies are cardboards with a leathery coating (goatskin) and have been produced by burning and beat methods. Its reasons are that these two methods have been common methods in Safavid era and performing them was only feasible on leather and the most desirable and commonly used leather of that time was goatskin which was the best option for cover legend durability and preserving the book and it was more durable because it had been made of goat skin. In addition, it had prepared a suitable opportunity for the binding artist’s creativity and innovation.
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23207
Cellular Energy Metabolism Decreases with Age in the Trophocytes and Oenocytes of Honeybees (Apis Mellifera)
Abstract:
The expression, concentration, and activity of mitochondrial energy-utilized molecules and cellular energy-regulated molecules decreased with age in the trophocytes and oenocytes of honeybees (Apis mellifera), but those of cellular energy-metabolized molecules is unknown. In this study, the expression, concentration, and activity of cellular energy-metabolized molecules were assayed in the trophocytes and fat cells of young and old worker bees by using the techniques of cell and biochemistry. The results showed that (i) the •-hydroxylacyl-coenzyme A dehydrogenase (HOAD) activity/citrate synthase (CS) activity ratio, non-esterified fatty acids concentrations, the expression of eukaryotic initiation factor 4E, and the expression of phosphorylated eIF4E binding protein 1 decreased with age; (ii) fat and glycogen accumulation increased with age; and (iii) the pyruvate dehydrogenase (PDH) activity/citrate synthase (CS) activity ratio was not correlated with age. These finding indicated that •-oxidation (HOAD/CS) and protein synthsis decreased with age. Glycolysis (PDH/CS) was unchanged with age. The most likely reason is that sugars are the vital food of worker bees. Taken together these data reveal that young workers have higher cellular energy metabolism than old workers and that aging results in a decline in the cellular energy metabolism in worker honeybees.
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13748
Single Pass Design of Genetic Circuits Using Absolute Binding Free Energy Measurements and Dimensionless Analysis
Abstract:
Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.
147
28092
Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study
Abstract:
The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.
146
45390
Preparation and Visible Light Photoactivity of N-Doped ZnO/ZnS Photocatalysts
Abstract:
Semiconductor nanoparticles such as TiO₂ and ZnO as photocatalysts are very efficient catalysts for wastewater treatment by the chemical utilization of light energy, which is capable of converting the toxic and nonbiodegradable organic compounds into carbon dioxide and mineral acids. ZnO semiconductor has a wide bandgap energy of 3.37 eV and a relatively large exciton binding Energy (60 meV), thus can absorb only UV light with the wavelength equal to or less than 385 nm. It exhibits low efficiency under visible light illumination due to its wide band gap energy. In order to improve photocatalytic activity of ZnO under visible light, band gap of ZnO may be narrowed by doping such as N, C, S nonmetal ions and coupled two separate semiconductors possessing different energy levels for their corresponding conduction and valence bands. ZnS has a wider band gap (Eg=3.7 eV) than ZnO and generates electron–hole pairs by photoexcitation rapidly. In the present work, N doped ZnO/ZnS nano photocatalysts with visible-light response were synthesized by microwave-hydrothermal method using thiourea as N source. The prepared photocatalysts were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and UV–visible (UV–vis). The photocatalytic activities samples and undoped ZnO have been studied for the degradation of dye, and have also been compared with together.
145
62501
Predicting Potential Protein Therapeutic Candidates from the Gut Microbiome
Abstract:
Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.
144
57898
In-Silico Evaluation and Antihyperglycemic Potential of Leucas Cephalotes
Abstract:
The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.
143
12031
Design and Preliminary Evaluation of Benzoxazolone-Based Agents for Targeting Mitochondrial-Located Translocator Protein
Abstract:
Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.
142
18520
Ab Initio Studies of Organic Electrodes for Li and Na Ion Batteries Based on Tetracyanoethylene
Abstract:
Organic electrodes are a way to achieve high rate (high power) and environment-friendly batteries. We present a computational density functional theory study of Li and Na storage in tetracyanoethylene based molecular and crystalline materials. Up to five Li and Na atoms can be stored on TCNE chemisorbed on doped graphene (corresponding to ~1000 mAh/gTCNE), with binding energies stronger than cohesive energies of the Li and Na metals by 1-2 eV. TCNE has been experimentally shown to form a crystalline material with Li with stoichiometry Li-TCNE. We confirm this computationally and also predict that a similar crystal based of Na-TCNE is also stable. These crystalline materials have well defined channels for facile Li or Na ion insertion and diffusion. Specifically, Li and Na binding energies in Li-TCNE and Na-TCNE crystals are about 1.5 eV and stronger than the cohesive energy of Li and Na, respectively. TCNE immobilized on conducting graphene-based substrates and Li/Na-TCNE crystals could therefore become efficient anode materials for organic Li and Na ion batteries, with which it should also be possible to avoid reduction of common battery electrolytes.
141
2229
Characterization of a Novel Hemin-Binding Protein, HmuX, in Porphyromonas gingivalis W50
Abstract:
Porphyromonas gingivalis is a black-pigmented, anaerobic Gram-negative bacterium that is important in the progression of chronic and severe periodontitis. This organism has an essential requirement for iron, which is usually obtained from hemin, using specific membrane receptors, proteases, and lipoproteins. In this study, we report the characterization of a novel 24 kDa hemin-binding protein, HmuX, in P. gingivalis W50. The hmuX gene is 651 bp long which encodes for a 217 amino acid protein. HmuX was found to be identical at the C-terminus to the previously reported HmuY protein, differing by an additional 74 amino acids at the N-terminus. Recombinant HmuX demonstrated hemin-binding ability by LDS- PAGE and TMBZ staining. Sequence analysis of HmuX revealed a putative lipoprotein attachment site, suggesting its possible role as a lipoprotein. HmuX was also localized to the outer cell surface by transmission electron microscopy. Northern analysis showed hmuX to be transcribed as a single gene and that hmuX mRNA was tightly regulated by the availability of extra-cellular hemin. P. gingivalis isogenic mutant deficient in hmuX gene exhibited significant growth retardation under hemin-limited conditions. Taken together, these results suggest that HmuX is a hemin-binding lipoprotein, important in hemin utilization for the growth of P. gingivalis.
140
46327
Interaction Evaluation of Silver Ion and Silver Nanoparticles with Dithizone Complexes Using DFT Calculations and NMR Analysis
Abstract:
Silver has distinct antibacterial properties and has been used as a component of commercial products with many applications. An increasing number of commercial products cause risks of silver effects for human and environment such as the symptoms of Argyria and the release of silver to the environment. Therefore, the detection of silver in the aquatic environment is important. The colorimetric chemosensor is designed by the basic of ligand interactions with a metal ion, leading to the change of signals for the naked-eyes which are very useful method to this application. Dithizone ligand is considered as one of the effective chelating reagents for metal ions due to its high selectivity and sensitivity of a photochromic reaction for silver as well as the linear backbone of dithizone affords the rotation of various isomeric forms. The present study is focused on the conformation and interaction of silver ion and silver nanoparticles (AgNPs) with dithizone using density functional theory (DFT). The interaction parameters were determined in term of binding energy of complexes and the geometry optimization, frequency of the structures and calculation of binding energies using density functional approaches B3LYP and the 6-31G(d,p) basis set. Moreover, the interaction of silver–dithizone complexes was supported by UV–Vis spectroscopy, FT-IR spectrum that was simulated by using B3LYP/6-31G(d,p) and 1H NMR spectra calculation using B3LYP/6-311+G(2d,p) method compared with the experimental data. The results showed the ion exchange interaction between hydrogen of dithizone and silver atom, with minimized binding energies of silver–dithizone interaction. However, the result of AgNPs in the form of complexes with dithizone. Moreover, the AgNPs-dithizone complexes were confirmed by using transmission electron microscope (TEM). Therefore, the results can be the useful information for determination of complex interaction using the analysis of computer simulations.
139
85324
Cellular RNA-Binding Domains with Distant Homology in Viral Proteomes
Abstract:
Until today, viruses remain controversial and poorly understood; about their origin, this problem represents an enigma and one of the great challenges for the contemporary biology. Three main theories have tried to explain the origin of viruses: regressive evolution, escaped host gene, and pre-cellular origin. Under the perspective of the escaped host gene theory, it can be assumed a cellular origin of viral components, like protein RNA-binding domains. These universal distributed RNA-binding domains are related to the RNA metabolism processes, including transcription, processing, and modification of transcripts, translation, RNA degradation and its regulation. In the case of viruses, these domains are present in important viral proteins like helicases, nucleases, polymerases, capsid proteins or regulation factors. Therefore, they are implicated in the replicative cycle and parasitic processes of viruses. That is why it is possible to think that those domains present low levels of divergence due to selective pressures. For these reasons, the main goal for this project is to create a catalogue of the RNA-binding domains found in all the available viral proteomes, using bioinformatics tools in order to analyze its evolutionary process, and thus shed light on the general virus evolution. ProDom database was used to obtain larger than six thousand RNA-binding domain families that belong to the three cellular domains of life and some viral groups. From the sequences of these families, protein profiles were created using HMMER 3.1 tools in order to find distant homologous within greater than four thousand viral proteomes available in GenBank. Once accomplished the analysis, almost three thousand hits were obtained in the viral proteomes. The homologous sequences were found in proteomes of the principal Baltimore viral groups, showing interesting distribution patterns that can contribute to understand the evolution of viruses and their host-virus interactions. Presence of cellular RNA-binding domains within virus proteomes seem to be explained by closed interactions between viruses and their hosts. Recruitment of these domains is advantageous for the viral fitness, allowing viruses to be adapted to the host cellular environment.
138
36834
Drug Delivery of Cyclophosphamide Functionalized Zigzag (8,0) CNT, Armchair (4,4) CNT, and Nanocone Complexes in Water
Abstract:
In this work, using density functional theory (DFT) thermodynamic stability and quantum molecular descriptors of cyclophoshphamide (an anticancer drug)-functionalized zigzag (8,0) CNT, armchair (4,4) CNT and nanocone complexes in water, for two attachment namely the sidewall and tip, is considered. Calculation of the total electronic energy (Et) and binding energy (Eb) of all complexes indicates that the most thermodynamic stability belongs to the sidewall-attachment of cyclophosphamide into functional nanocone. On the other hand, results from chemical hardness show that drug-functionalized zigzag (8,0) and armchair (4,4) complexes in the tip-attachment configuration possess the smallest and greatest chemical hardness, respectively. By computing the solvation energy, it is found that the solution of the drug and all complexes are spontaneous in water. Furthermore, chirality, type of nanovector (nanotube or nanocone), or attachment configuration have no effects on solvation energy of complexes.
137
2137
Energy Initiatives for Turkey
Abstract:
Dependency of humanity on the energy is ever-increasing today and the energy policies are reaching undeniable and un-ignorable dimensions steering the political events as well. Therefore, energy has the highest priority for Turkey like any other country. In this study, the energy supply security for Turkey evaluated according to the strategic criteria of energy policy. Under these circumstances, different alternatives are described and assessed with in terms of the energy expansion of Turkey. With this study, different opportunities in the energy expansion of Turkey is clarified and emphasized.
136
121800
Identification of Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists for Treatment of Metabolic Disorders, Insilico Screening, and Molecular Dynamics Simulation
Abstract:
Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.
135
117283
Computational Investigation of V599 Mutations of BRAF Protein and Its Control over the Therapeutic Outcome under the Malignant Condition
Abstract:
The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.
134
98813
Development of Fluorescence Resonance Energy Transfer-Based Nanosensor for Measurement of Sialic Acid in vivo
Abstract:
Sialic acid (5-Acetylneuraminic acid, Neu5Ac) is a common sugar found as a terminal residue on glycoconjugates in many animals. Humans brain and the central nervous system contain the highest concentration of sialic acid (as N-acetylneuraminic acid) where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis. Due to its important biological function, sialic acid is attracting increasing attention. To understand metabolic networks, fluxes and regulation, it is essential to be able to determine the cellular and subcellular levels of metabolites. Genetically-encoded fluorescence resonance energy transfer (FRET) sensors represent a promising technology for measuring metabolite levels and corresponding rate changes in live cells. Taking this, we developed a genetically encoded FRET (fluorescence resonance energy transfer) based nanosensor to analyse the sialic acid level in living cells. Sialic acid periplasmic binding protein (sia P) from Haemophilus influenzae was taken and ligated between the FRET pair, the cyan fluorescent protein (eCFP) and Venus. The chimeric sensor protein was expressed in E. coli BL21 (DE3) and purified by affinity chromatography. Conformational changes in the binding protein clearly confirmed the changes in FRET efficiency. So any change in the concentration of sialic acid is associated with the change in FRET ratio. This sensor is very specific to sialic acid and found stable with the different range of pH. This nanosensor successfully reported the intracellular level of sialic acid in bacterial cell. The data suggest that the nanosensors may be a versatile tool for studying the in vivo dynamics of sialic acid level non-invasively in living cells
133
77448
Designing Active Sites on Amicyanin Using Histidine S Plus Cobalt, and Measuring Their Functional Activity
Abstract:
There is a growing interest in introducing a desired functional group on enzymes in the field of protein engineering. In here, various redox centers were newly created using histidine tag, which is widely used for protein purification, plus cobalt in one of cupredoxins, amicyanin. The coordination of Cobalt-His tag and reactivity of the Co²⁺ loaded His-tag also were characterized. 3xHis-tag, 6xHis-tag, and 9xHis-tag were introduced on amicyanin by site-directed mutagenesis, and then Co²⁺ was loaded on each His-tagged amicyanin. The spectral changes at 330 nm corresponding to cobalt binding on His-tag site indicated the binding ratio of 3xHis-tag, 6xHis-tag, and 9xHis-tag to cobalt as 1:1, 1:2, 1:3 respectively. Based on kinetic studies of binding cobalt to 3xHis-tag, 6xHis-tag, and 9xHis-tagged amicyanin, the nature of the sites was elucidated. In addition, internal electron transfer properties between Cu¹⁺ site and engineered site of amicyanin were determined. These results provide insight into improvement of metal coordination and alternation of the redox properties of metal as a new catalytic site on proteins.
132
55703
Discovery of New Inhibitors for Colorectal Cancer Treatment
Abstract:
Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of
131
12135
The Antitumor Activity of Eu (III) and Er (III) Complexes of 3 - (1H-Benzimidazol-2-Yl) - 6 - Methyl - 2 (1H) - Quinolinone
Abstract:
[Eu(BMQ)2(NO3)3(CH3OH)(H2O)] (1),and [Er(BMQ)2(NO3)3(CH3OH)(H2O)] (2),were synthesized. Compounds 1 and 2 exhibit a certain extent cytotoxicity against Hep G2, Hela 229, MGC80-3 and BEL-7404 cell lines invitro, with IC50 values in the14.51±1.41μM to 52.49±4.01μM range. Compound 1 exhibited significantly enhanced cytotoxicity against MGC80-3 cell line, comparing with free 3-(1H-benzimidazol-2-yl)-6-methyl-2(1H)- quinolinone. The binding abilities of 1 to DNA were stronger than that of 2. Intercalation is the most probable binding mode for both the complexes.
130
43676
A Molecular Modelling Approach for Identification of Lead Compound from Rhizomes of Glycosmis Pentaphylla for Skin Cancer Treatment
Abstract:
Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.
129
40733
Novel Pyrimidine Based Semicarbazones: Confirmation of Four Binding Site Pharmacophoric Model Hypothesis for Antiepileptic Activity
Abstract:
A series of novel pyrimidine based semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to satisfy the structural prerequisite crucial for antiepileptic activity. The semicarbazones based pharmacophoric model consists of following four essential binding sites: (i) An aryl hydrophobic binding site with halo substituent; (ii) A hydrogen bonding domain; (iii) An electron donor group and (iv) Another hydrophobic-hydrophilic site controlling the pharmacokinetic features of the anticonvulsant. The aryl semicarbazones has been recognized as a structurally novel class of compounds with remarkable anticonvulsant activity. In the present study, all the test semicarbazones were subjected to molecular docking using Glide v5.8. Some of the compounds were found to interact with ARG192, GLU270 and THR353 residues of 1OHV protein, present in GABA-AT receptor. The chemical structures of the synthesized molecules were characterized by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. The neurotoxicity was evaluated in mice by the rotorod test. The attempts were also made to establish structure-activity relationships among synthesized compounds. The results of the present study confirmed that the pharmacophore model with four binding sites is essential for antiepileptic activity.
128
8485
Analysis of Osmotin as Transcription Factor/Cell Signaling Modulator Using Bioinformatic Tools
Abstract:
Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.
127
90902
Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer
Abstract:
Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.
126
78825
Investigation of Chlorophylls a and b Interaction with Inner and Outer Surfaces of Single-Walled Carbon Nanotube Using Molecular Dynamics Simulation
Abstract:
In this work, adsorption of chlorophylls a and b pigments in aqueous solution on the inner and outer surfaces of single-walled carbon nanotube (SWCNT) has been studied using molecular dynamics simulation. The linear interaction energy algorithm has been used to calculate the binding free energy. The results show that the adsorption of two pigments is fine on the both positions. Although there is the close similarity between these two pigments, their interaction with the nanotube is different. This result is useful to separate these pigments from one another. According to interaction energy between the pigments and carbon nanotube, interaction between these pigments-SWCNT on the inner surface is stronger than the outer surface. The interaction of SWCNT with chlorophylls phytol tail is stronger than the interaction of SWCNT with porphyrin ring of chlorophylls.
125
116871
Biophysical Characterization of the Inhibition of cGAS-DNA Sensing by KicGAS, Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS
Abstract:
Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.
124
64381
Improving Energy Efficiency through Industrial Symbiosis: A Conceptual Framework of Energy Management in Energy-Intensive Industries
Abstract:
Rising energy prices have drawn a focus to global energy issues, and the severe pollution that has resulted from energy-intensive industrial sectors has yet to be addressed. By combining Energy Efficiency with Industrial Symbiosis, the practices of efficient energy utilization and improvement can be not only enriched at the factory level but also upgraded into “within and/or between firm level”. The academic contribution of this paper provides a conceptual framework of energy management through IS. The management of waste energy within/between firms can contribute to the reduction of energy consumption and provides a solution to the environmental issues.
123
35592
Study of Interaction between Ascorbic Acid and Bovine Hemoglobin by Multispectroscopic Methods
Abstract:
Ascorbic acid is an essential component in the diet of humans, and also is a typical long used pharmaceutical agent. In the present contribution, we have carried out a detailed study on the binding interaction of ascorbic acid (AA) with bovine hemoglobin (BHb) using steady state emission, time resolved fluorescence, UV-Vis absorption, circular dichroism (CD), Fourier transform infra-red (FT-IR) and three dimensional emission (3D) spectral studies. The results from the emission spectral studies unveiled that the quenching of BHb emission by AA is attributed to the formation of a complex in the ground state (static in nature) after correcting for inner filter effect. The binding parameters calculated from corrected emission quenching data revealed that BHb exhibited a significant binding affinity towards AA. Moreover, AA induced tertiary and secondary conformational changes of BHb were monitored by UV-Vis absorption, CD, FT-IR and 3D emission spectral studies. The results presented here will help to further understand the credible mechanism of BHb-AA system which is expected to provide insights into conformational and microenvironmental changes of BHb.
122
23535
Binding Studies of Complexes of Anticancer Drugs with DNA and Enzymes Involved in DNA Replication Using Molecular Docking and Cell Culture Techniques
Abstract:
The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.
121
121158
Electronic Structure Calculation of AsSiTeB/SiAsBTe Nanostructures Using Density Functional Theory
Abstract:
The electronic structure calculation for the nanoclusters of AsSiTeB/SiAsBTe quaternary semiconductor alloy belonging to the III-V Group elements was performed. Motivation for this research work was to look for accurate electronic and geometric data of small nanoclusters of AsSiTeB/SiAsBTe in the gaseous form. The two clusters, one in the linear form and the other in the bent form, were studied under the framework of Density Functional Theory (DFT) using the B3LYP functional and LANL2DZ basis set with the software packaged Gaussian 16. We have discussed the Optimized Energy, Frontier Orbital Energy Gap in terms of HOMO-LUMO, Dipole Moment, Ionization Potential, Electron Affinity, Binding Energy, Embedding Energy, Density of States (DoS) spectrum for both structures. The important findings of the predicted nanostructures are that these structures have wide band gap energy, where linear structure has band gap energy (Eg) value is 2.375 eV and bent structure (Eg) value is 2.778 eV. Therefore, these structures can be utilized as wide band gap semiconductors. These structures have high electron affinity value of 4.259 eV for the linear structure and electron affinity value of 3.387 eV for the bent structure form. It shows that electron acceptor capability is high for both forms. The widely known application of these compounds is in the light emitting diodes due to their wide band gap nature.
120
60204
Microbiological Activity and Molecular Docking Study of Selected Steroid Derivatives of Biomedical Importance
Abstract:
This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).
119
70840
Development of Immuno-Modulators: Application of Molecular Dynamics Simulation
Abstract:
The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.
118
4120
SWOT Analysis of Renewable Energy
Abstract:
Being one of the most important elements of social evolution, energy has a vital role for a sustainable economy and development. Energy has great importance to level up the welfare. By this importance, countries having rich resources can apply energy as an political instrument. While needs of energy is increasing, sources to respond this need is very limited. Therefore, countries seek for alternative resources to meet their needs. Renewable energy sources have firstly taken into consideration. Being clean and belonging to countries own sources, renewable energy resources have been widely applied during the last decades. However, renewable energy cannot meet all the expectation of energy needs. In this respect, energy efficiency can be seen as an alternative. Energy efficiency can minimize energy consumption without degrading standard of living, lessening quality of products and without increasing energy bills. In this article, energy resources, SWOT analysis of renewable sources, and energy efficiency topics are mainly discussed.
117
14481
Fluorescence Spectroscopy of Lysozyme-Silver Nanoparticles Complex
Abstract:
Identifying the nature of protein-nanoparticle interactions and favored binding sites is an important issue in functional characterization of biomolecules and their physiological responses. Herein, interaction of silver nanoparticles with lysozyme as a model protein has been monitored via fluorescence spectroscopy. Formation of complex between the biomolecule and silver nanoparticles (AgNPs) induced a steady state reduction in the fluorescence intensity of protein at different concentrations of nanoparticles. Tryptophan fluorescence quenching spectra suggested that silver nanoparticles act as a foreign quencher, approaching the protein via this residue. Analysis of the Stern-Volmer plot showed quenching constant of 3.73 µM−1. Moreover, a single binding site in lysozyme is suggested to play role during interaction with AgNPs, having low affinity of binding compared to gold nanoparticles. Unfolding studies of lysozyme showed that complex of lysozyme-AgNPs has not undergone structural perturbations compared to the bare protein. Results of this effort will pave the way for utilization of sensitive spectroscopic techniques for rational design of nanobiomaterials in biomedical applications.
116
97969
Spectrofluorimetric Investigation of Copper (II), Cobalt (II), Calcium (II), and Ferric (III) Influence on the Ciprofloxacin Binding to Bovine Serum Albumin
Abstract:
The interaction between ciprofloxacin and bovine serum albumin (BSA) was investigated by UV-Visible absorption and fluorescence spectroscopy. The influence of Cu²⁺ Ca²⁺, Co²⁺, and Fe³⁺ on the Cip-BSA interaction was investigated. The quenching of the BSA fluorescence emission in presence of ciprofloxacin as well as the influence of metal ions on the interaction was analyzed using the Stern-Volmer equation. The Stern-Volmer quenching constant, Kₛᵥ was calculated in presence and absence of the metal ions at the physiological pH of 7.4 using phosphate buffer. The experimental results showed that interaction mainly static in nature and quenching rate constant is decreased in presence of the studied metal ions with exception of Cu²⁺ ions. The decrease observed in the Kₛᵥ values in presence of Co²⁺, Ca²⁺, and Fe³⁺ can be understood on basis of competition between these metal and Cip when both of them existed in the BSA solution. Cu²⁺ induces interaction between Cip and BSA at faster quenching rates as inferred from the observed increase in the Kₛᵥ value. This allowed us to propose that copper (II) ions are directly involved in the process of Cip binding to BSA. The binding constant for Cip on BSA was determined and the metal ions effect on it was examined as well and their values were in line with the Kₛᵥ values.
115
51877
An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients
Abstract:
Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.
114
67557
The Growth Role of Natural Gas Consumption for Developing Countries
Abstract:
Carbon emissions have emerged as global concerns. Intergovernmental Panel of Climate Change (IPCC) have published reports about Green House Gases (GHGs) emissions regularly. United Nations Framework Convention on Climate Change (UNFCCC) have held a conference yearly since 1995. Especially, COP21 held at December 2015 made the Paris agreement which have strong binding force differently from former COP. The Paris agreement was ratified as of 4 November 2016, they finally have legal binding. Participating countries set up their own Intended Nationally Determined Contributions (INDC), and will try to achieve this. Thus, carbon emissions must be reduced. The energy sector is one of most responsible for carbon emissions and fossil fuels particularly are. Thus, this paper attempted to examine the relationship between natural gas consumption and economic growth. To achieve this, we adopted the Cobb-Douglas production function that consists of natural gas consumption, economic growth, capital, and labor using dependent panel analysis. Data were preprocessed with Principal Component Analysis (PCA) to remove cross-sectional dependency which can disturb the panel results. After confirming the existence of time-trended component of each variable, we moved to cointegration test considering cross-sectional dependency and structural breaks to describe more realistic behavior of volatile international indicators. The cointegration test result indicates that there is long-run equilibrium relationship between selected variables. Long-run cointegrating vector and Granger causality test results show that while natural gas consumption can contribute economic growth in the short-run, adversely affect in the long-run. From these results, we made following policy implications. Since natural gas has positive economic effect in only short-run, the policy makers in developing countries must consider the gradual switching of major energy source, from natural gas to sustainable energy source. Second, the technology transfer and financing business suggested by COP must be accelerated. Acknowledgement—This work was supported by the Energy Efficiency & Resources Core Technology Program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) granted financial resource from the Ministry of Trade, Industry & Energy, Republic of Korea (No. 20152510101880) and by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-205S1A3A2046684).
113
134382
Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development
Abstract:
Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.
112
28190
Effect of Oxidative Stress from Smoking on Erythrocyte Phosphatidylserine Externalization
Abstract:
The smoking is one of the major risk factors in Non-Communicable Disease. Free radicals from cigarette smoke can cause oxidative stress. The oxidative insults can lead to red blood cell (RBC) senescence and are involved in the clearance of red blood cells. The objective of the present study is to assess the association between smoke, oxidative stress evaluated with serum Malondialdehyde (MDA) level and phosphatidylserine (PS) externalization (biomarker of RBC senescence) evaluated with annexin V binding. A total of sixty-four male volunteers aged 25-60 years old were recruited in this study. MDA was measured by colorimetric method. Annexin V binding was detected by flow cytometry. Our results show that there was a significant increase in MDA levels in cigarette smokers as compared to non-smokers (p < 0.001). However, there was no significant different between annexin V binding (% gate) in cigarette smokers and non-smokers (p = 0.978). These results provide evidence of free radical from smoking is associated with oxidative damage to erythrocytes. However, our results suggest that PS externalization is unlikely to have a role in RBC senescence pathway of stressed erythrocytes from cigarette smoke. The other biomarker of RBC senescence should be determined on cigarette smoker erythrocytes.
111
100743
Thermal Hysteresis Activity of Ice Binding Proteins during Ice Crystal Growth in Sucrose Solution
Abstract:
Ice recrystallization (IR) which occurs especially during frozen storage is an undesired process due to the possible influence on the quality of products. As a result of recrystallization, the total volume of ice remains constant, but the size, number, and shape of ice crystals change. For instance, as indicated in the literature, the size of ice crystals in ice cream increases due to recrystallization. This results in texture deterioration. Therefore, the inhibition of ice recrystallization is of great importance, not only for food industry but also for several other areas where sensitive products are stored frozen, like pharmaceutical products or organs and blood in medicine. Ice-binding proteins (IBPs) have the unique ability to inhibit ice growth and in consequence inhibit recrystallization. This effect is based on their ice binding affinity. In the presence of IBP in a solution, ice crystal growth is inhibited during temperature decrease until a certain temperature is reached. The melting during temperature increase is not influenced. The gap between melting and freezing points is known as thermal hysteresis (TH). In literature, the TH activity is usually investigated under laboratory conditions in IBP buffer solutions. In product applications (e.g., food) there are many other solutes present which may influence the TH activity. In this study, a subset of IBPs, so-called antifreeze proteins (AFPs), is used for the investigation of the influence of sucrose solution concentration on the TH activity. For the investigation, a polarization microscope (Nikon Eclipse LV100ND) equipped with a digital camera (Nikon DS-Ri1) and a cold stage (Linkam LTS420) was used. In a first step, the equipment was established and validated concerning the accuracy of TH measurements based on literature data.
110
124737
Analysis of Splicing Methods for High Speed Automated Fibre Placement Applications
Abstract:
The focus in the automotive industry is to reduce human operator and machine interaction, so manufacturing becomes more automated and safer. The aim is to lower part cost and construction time as well as defects in the parts, sometimes occurring due to the physical limitations of human operators. A move to automate the layup of reinforcement material in composites manufacturing has resulted in the use of tapes that are placed in position by a robotic deposition head, also described as Automated Fibre Placement (AFP). The process of AFP is limited with respect to the finite amount of material that can be loaded into the machine at any one time. Joining two batches of tape material together involves a splice to secure the ends of the finishing tape to the starting edge of the new tape. The splicing method of choice for the majority of prepreg applications is a hand stich method, and as the name suggests requires human input to achieve. This investigation explores three methods for automated splicing, namely, adhesive, binding and stitching. The adhesive technique uses an additional adhesive placed on the tape ends to be joined. Binding uses the binding agent that is already impregnated onto the tape through the application of heat. The stitching method is used as a baseline to compare the new splicing methods to the traditional technique currently in use. As the methods will be used within a High Speed Automated Fibre Placement (HSAFP) process, this meant the parameters of the splices have to meet certain specifications: (a) the splice must be able to endure a load of 50 N in tension applied at a rate of 1 mm/s; (b) the splice must be created in less than 6 seconds, dictated by the capacity of the tape accumulator within the system. The samples for experimentation were manufactured with controlled overlaps, alignment and splicing parameters, these were then tested in tension using a tensile testing machine. Initial analysis explored the use of the impregnated binding agent present on the tape, as in the binding splicing technique. It analysed the effect of temperature and overlap on the strength of the splice. It was found that the optimum splicing temperature was at the higher end of the activation range of the binding agent, 100 °C. The optimum overlap was found to be 25 mm; it was found that there was no improvement in bond strength from 25 mm to 30 mm overlap. The final analysis compared the different splicing methods to the baseline of a stitched bond. It was found that the addition of an adhesive was the best splicing method, achieving a maximum load of over 500 N compared to the 26 N load achieved by a stitching splice and 94 N by the binding method.
109
26038
Systematic Approach for Energy-Supply-Orientated Production Planning
Abstract:
The efficient and economic allocation of resources is one main goal in the field of production planning and control. Nowadays, a new variable gains in importance throughout the planning process: Energy. Energy-efficiency has already been widely discussed in literature, but with a strong focus on reducing the overall amount of energy used in production. This paper provides a brief systematic approach, how energy-supply-orientation can be used for an energy-cost-efficient production planning and thus combining the idea of energy-efficiency and energy-flexibility.
108
88237
Mitochondrial Apolipoprotein A-1 Binding Protein Promotes Repolarization of Inflammatory Macrophage by Repairing Mitochondrial Respiration
Abstract:
Objective: Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is highly associated with mitochondrial respiration. Recent studies have suggested that mitochondrial apolipoprotein A-1 binding protein (APOA1BP) was essential for the cellular metabolite NADHX repair to NADH, which is necessary for the mitochondrial function. The exact role of APOA1BP in the repolarization of M1 to M2, however, is uncertain. Material and method: THP-1-derived macrophages were incubated with LPS (10 ng/ml) or/and IL-4 (100 U/ml) for 24 hours. Biochemical parameters of oxidative phosphorylation and M1/M2 markers were analyzed after overexpression of APOA1BP in cells. Results: Compared with control and IL-4-exposed M2 cells, APOA1BP was downregulated in M1 macrophages. APOA1BP restored the decline in mitochondrial function to improve metabolic and phenotypic reprogramming of M1 to M2 macrophages. Blocking oxidative phosphorylation by oligomycin blunts the effects of APOA1BP on M1 to M2 repolarization. Mechanistically, LPS triggered the hydration of NADH and increased its hydrate NADHX which inhibit cellular NADH dehydrogenases, a key component of electron transport chain for oxidative phosphorylation. APOA1BP decreased the level of NADHX via converting R-NADHX to biologically useful S-NADHX. The mutant of APOA1BP aspartate188, the binding site of NADHX, fail to repair oxidative phosphorylation, thereby preventing repolarization. Conclusions: Restoring mitochondrial function by increasing mitochondrial APOA1BP might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control inflammatory diseases.
107
98839
Preventing Neurodegenerative Diseases by Stabilization of Superoxide Dismutase by Natural Polyphenolic Compounds
Abstract:
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1). The use of small molecules has been shown to stabilize the SOD1 dimer and preventing its dissociation and aggregation. In this study, we employed molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) to study the interactions between SOD1 and natural polyphenolic compounds. In order to explore the noncovalent interaction between SOD1 and natural polyphenolic compounds, molecular docking and molecular dynamic (MD) simulations were employed to gain insights into the binding modes and free energies of SOD1-polyphenolic compounds. MM/PBSA methods were used to calculate free energies from obtained MD trajectories. The compounds, Hesperidin, Ergosterol, and Rutin showed the excellent binding affinity in micromolar range with SOD1. Ergosterol and Hesperidin have the strongest binding affinity to SOD1 and was subjected to further characterization. Biophysical experiments using Circular Dichroism and Thioflavin T fluorescence spectroscopy results show that the binding of these two compounds can stabilize SOD1 dimer and inhibit the aggregation of SOD1. Molecular simulation results also suggest that these compounds reduce the dissociation of SOD1 dimers through direct interaction with the dimer interface. This study will be helpful to develop other drug-like molecules which may have the effect to reduce the aggregation of SOD1.
106
63196
Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis
Abstract:
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.
105
28025
Impact of Design Choices on the Life Cycle Energy of Modern Buildings
Abstract:
Traditionally the embodied energy of design choices which reduce operational energy were assumed to have a negligible impact on the life cycle energy of buildings. However with new buildings having considerably lower operational energy, the significance of embodied energy increases. A life cycle assessment of a population of house designs was conducted in a mild and mixed climate zone. It was determined not only that embodied energy dominates life cycle energy, but that the impact on embodied of design choices was of equal significance to the impact on operational energy.
104
19854
Comprehensive Study of Renewable Energy Resources and Present Scenario in India
Abstract:
Renewable energy sources also called non-conventional energy sources that are continuously replenished by natural processes. For example, solar energy, wind energy, bio-energy- bio-fuels grown sustain ably), hydropower etc., are some of the examples of renewable energy sources. A renewable energy system converts the energy found in sunlight, wind, falling-water, sea-waves, geothermal heat, or biomass into a form, we can use such as heat or electricity. Most of the renewable energy comes either directly or indirectly from sun and wind and can never be exhausted, and therefore they are called renewable. This paper presents a review about conventional and renewable energy scenario of India. The paper also presents current status, major achievements and future aspects of renewable energy in India and implementing renewable for the future is also been presented.
103
30778
QSAR Study and Haptotropic Rearrangement in Estradiol Derivatives
Abstract:
In this work, we have developed QSAR model for Relative Binding Affinity (RBA) of a large diverse set of estradiol among these derivatives, the organometallic derivatives. By dividing the dataset into a training set of 24 compounds and a test set of 6 compounds. The DFT method was used to calculate quantum chemical descriptors and physicochemical descriptors (MR and MLOGP) were performed using E-Dragon. All the validations indicated that the QSAR model built was robust and satisfactory (R2 = 90.12, Q2LOO = 86.61, RMSE = 0.272, F = 60.6473, Q2ext =86.07). We have therefore apply this model to predict the RBA, for two isomers β and α wherein Mn(CO)3 complex with the aromatic ring of estradiol, and the two isomers show little appreciation for the estrogenic receptor (RBAβ = 1.812 and RBAα = 1.741).
102
43288
Exploring Valproic Acid (VPA) Analogues Interactions with HDAC8 Involved in VPA Mediated Teratogenicity: A Toxicoinformatics Analysis
Abstract:
Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.
101
13497
Ground State Properties of Neutron Magic Isotones
Abstract:
In the present investigation, we have employed RMF+BCS (relativistic mean-field plus BCS) approach to carry out a systematic study for the ground state properties of the entire chains of even-even neutron magic nuclei represented by isotones of traditional neutron magic numbers N = 8, 20, 40, 50, 82, and 126. The main body of the results of our calculations includes the binding energy, deformation, two proton separation energies, rms radii of the proton and neutron distributions as well as the proton and neutron density profiles etc. Several of these results have been given in the form of a series of graphs for a ready reference. In addition, the possible locations of the proton and neutron drip-lines as well as the (Z,N) values for the shell closures as suggested by the detailed analyzes of the single particle spectra, and the two proton and two-neutron separation energies for the different isotonic chains are also discussed in detail.
100
54917
Revealing the Structural and Dynamic Properties of Betaine Aldehyde Dehydrogenase 2 from Rice (Oryza sativa): Simulation Studies
Abstract:
Betaine aldehyde dehydrogenase 2 (BADH2) is an enzyme that inhibits the accumulation of 2-acetyl-1-pyrroline (2AP), a potent flavor compound in rice fragrance. BADH2 contains three domains (NAD-binding, substrate-binding, and oligomerization domains). It catalyzes the oxidation of amino aldehydes. The lack of BADH2 results in the formation of 2AP and consequently an increase in rice fragrance. To date, inadequate data on BADH2 structure and function are available. An insight into the nature of BADH2 can serve as one of key starting points for the production of high quality fragrant rice. In this study, we therefore constructed the homology model of BADH2 and employed 500-ns Molecular Dynamics simulations (MD) to primarily understand the structural and dynamic properties of BADH2. Initially, Ramachandran plot confirms the good quality of modeled protein structure. Principle Component Analysis (PCA) was also calculated to capture the protein dynamics. Among 3 domains, the results show that NAD binding site is found to be more flexible. Moreover, interactions from key amino acids (N162, E260, C294, and Y419) that are crucial for function are investigated.
99
85878
Economic Analysis of Policy Instruments for Energy Efficiency
Authors:
Abstract:
Energy efficiency improvement is one of the means to reduce energy consumption and carbon emissions. Recently, some developed countries have implemented the tradable white certificate scheme (TWC) as a new policy instrument based on market approach to support energy efficiency improvements. The major focus of this paper is to compare the White Certificates (TWC) scheme as an innovative policy instrument for energy efficiency improvement to other policy instruments: energy taxes and regulations setting a minimum level of energy efficiency. On the basis of our theoretical discussion and numerical simulation, we show that the white certificates system is the most interesting policy instrument for saving energy because it generates the most important level of energy savings and the least increase in energy service price.
98
19186
Design and Synthesis of Novel Benzamides as Non-Ulcerogenic Anti-Inflammatory Agents
Abstract:
In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.
97
15596
Energy Policy and Interactions with Politics and Economics
Abstract:
Demand on production and thereby the global need of energy is growing continuously. Each country has different trends on energy demand and supply according to their geopolitical and geographical locations, underground reserves, weather conditions and level of industrialization. Conventional energy resources such as oil, gas and coal –in other words fossil resources- remain dominant on primary energy supply in spite of causing of environmental problems. Energy supply and demand securities are essential within the energy importing and exporting countries. This concept affected all sectors, but especially impressed on political aspects of the countries and also global economic views.
96
84651
In-Depth Analysis on Sequence Evolution and Molecular Interaction of Influenza Receptors (Hemagglutinin and Neuraminidase)
Abstract:
Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.
95
7112
In-Vivo Association of Multivalent 11 Zinc Fingers Transcriptional Factors CTCF and Boris to YB-1 in Multiforme Glioma-RGBM Cell Line
Abstract:
CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.
94
99585
Renewable Energy and Energy Security in Malaysia: A Quantitative Analysis
Abstract:
Robust economic growth, increasing population, and personal consumption are the main drivers for the rapid increase of energy demand in Malaysia. Increasing demand has compounded the issue of national energy security due to over-dependence on fossil fuel, depleting indigenous domestic conventional energy resources which in turns has increased the country’s energy import dependence. In order to improve its energy security, Malaysia has seriously embarked on a renewable energy journey. Many initiatives on renewable energy have been introduced in the past decade. These strategies have resulted in the exploding growth of renewable energy deployment in Malaysia. Therefore, this study investigated the impact of renewable energy deployment on energy security. Secondary data was used to calculate the energy security indicators. The study also compared the results of applying different energy security indicators namely availability, applicability, affordability and acceptability dimension of energy resources. The evaluation shows that Malaysia will experience slight improvement in availability and acceptability dimension of energy security. This study suggests that energy security level could be further enhanced by efficient utilization of energy, reducing carbon content of energy and facilitating low-carbon industries.
93
85752
Antimicrobial Action and Its Underlying Mechanism by Methanolic Seed Extract of Syzygium cumini on Bacillus subtilis
Abstract:
The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.
92
2074
Genome-Wide Isoform Specific KDM5A/JARID1A/RBP2 Location Analysis Reveals Contribution of Chromatin-Interacting PHD Domain in Protein Recruitment to Binding Sites
Abstract:
RBP2 has shown to be important for cell differentiation control through epigenetic mechanism. The main aim of the present study is genome-wide location analysis of human RBP2 isoforms that differ in a histone-binding domain by ChIPseq. It is conceivable that the larger isoform (LI) of RBP2, which contains a specific H3K4me3 interacting domain, differs from the smaller isoform (SI) in genomic location, may account for the observed diversity in RBP2 function. To distinguish the two RBP2 isoforms, we used the fact that the SI lacks the C-terminal PHD domain and hence used the antibodies detecting both RBP2 isoforms (AI) through a common central domain, and the antibodies detecting only LI but not SI, through a C-terminal PHD domain. Overall our analysis suggests that RBP2 occupies about 77 nucleotides and binds GC rich motifs of active genes, does not bind to centromere, telomere, or enhancer regions, and binding sites are conserved compare to random. A striking difference between the only-SI and only-LI is that a large number of only-SI peaks are located in CpG islands and close to TSS compared to only-LI peaks. Enrichment analysis of the related genes indicates that several oncogenic pathways and metabolic pathways/processes are significantly enriched among only-SI/AI targets, but not LI/only-LI peak’s targets.
91
46884
A Review on Modeling and Optimization of Integration of Renewable Energy Resources (RER) for Minimum Energy Cost, Minimum CO₂ Emissions and Sustainable Development, in Recent Years
Abstract:
The rising economic activities, growing population and improving living standards of world have led to a steady growth in its appetite for quality and quantity of energy services. As the economy expands the electricity demand is going to grow further, increasing the challenges of the more generation and stresses on the utility grids. Appropriate energy model will help in proper utilization of the locally available renewable energy sources such as solar, wind, biomass, small hydro etc. to integrate in the available grid, reducing the investments in energy infrastructure. Further to these new technologies like smart grids, decentralized energy planning, energy management practices, energy efficiency are emerging. In this paper, the attempt has been made to study and review the recent energy planning models, energy forecasting models, and renewable energy integration models. In addition, various modeling techniques and tools are reviewed and discussed.
90
52879
Amyloid-β Fibrils Remodeling by an Organic Molecule: Insight from All-Atomic Molecular Dynamics Simulations
Abstract:
Alzheimer’s disease (AD) is one of the most common forms of dementia, which is caused by misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid-β fibrils (Aβ fibrils). To disrupt the remodeling of Aβ fibrils, a number of candidate molecules have been proposed. To study the molecular mechanisms of Aβ fibrils remodeling we performed a series of all-atom molecular dynamics simulations, a total time of 3µs, in explicit solvent. Several previously undiscovered candidate molecule-Aβ fibrils binding modes are unraveled; one of which shows the direct conformational change of the Aβ fibril by understanding the physicochemical factors responsible for binding and subsequent remodeling of Aβ fibrils by the candidate molecule, open avenues into structure-based drug design for AD can be opened.
89
61213
Energy Potential of Turkey and Evaluation of Solar Energy Technology as an Alternative Energy
Abstract:
Emerging demand for energy in developing countries rapid population growth and industrialization are causing a rapid increase, such as Turkey. Energy is an important and indispensable factor in the industry. At the same time, energy is one of the main indicators that reflect a country's economic and social development potential. There is a linear relationship between the energy consumption and social development, and in parallel this situation, it is seen that energy consumption increase with economic growth and prosperity. In recent year’s, energy sources consumption is increasingly continuing, because of population growth and economy in Turkey. 80% of the energy used in Turkey is supplied from abroad. At the same time, while almost all of the energy obtained from our country is met by hydropower. Alternatively, studies of determining and using potential renewable energy sources such as solar energy have been realized for recent years. In this study, first of all, the situation of energy sources was examined in Turkey. Information of reserve/capacity, production and consumption values of energy sources were emphasized. For this purpose, energy production and consumption, CO2 emission and electricity energy consumption of countries were investigated. Energy consumption and electricity energy consumption per capita were comparatively analyzed.
88
67026
A First-Principles Investigation of Magnesium-Hydrogen System: From Bulk to Nano
Abstract:
Bulk MgH2 has drawn much attention for the purpose of hydrogen storage because of its high hydrogen storage capacity (~7.7 wt %) as well as low cost and abundant availability. However, its practical usage has been hindered because of its high hydrogen desorption enthalpy (~0.8 eV/H2 molecule), which results in an undesirable desorption temperature of 3000C at 1 bar H2 pressure. To surmount the limitations of bulk MgH2 for the purpose of hydrogen storage, a detailed first-principles density functional theory (DFT) based study on the structure and stability of neutral (Mgm) and positively charged (Mgm+) Mg nanoclusters of different sizes (m = 2, 4, 8 and 12), as well as their interaction with molecular hydrogen (H2), is reported here. It has been found that due to the absence of d-electrons within the Mg atoms, hydrogen remained in molecular form even after its interaction with neutral and charged Mg nanoclusters. Interestingly, the H2 molecules do not enter into the interstitial positions of the nanoclusters. Rather, they remain on the surface by ornamenting these nanoclusters and forming new structures with a gravimetric density higher than 15 wt %. Our observation is that the inclusion of Grimme’s DFT-D3 dispersion correction in this weakly interacting system has a significant effect on binding of the H2 molecules with these nanoclusters. The dispersion corrected interaction energy (IE) values (0.1-0.14 eV/H2 molecule) fall in the right energy window, that is ideal for hydrogen storage. These IE values are further verified by using high-level coupled-cluster calculations with non-iterative triples corrections i.e. CCSD(T), (which has been considered to be a highly accurate quantum chemical method) and thereby confirming the accuracy of our ‘dispersion correction’ incorporated DFT calculations. The significance of the polarization and dispersion energy in binding of the H2 molecules are confirmed by performing energy decomposition analysis (EDA). A total of 16, 24, 32 and 36 H2 molecules can be attached to the neutral and charged nanoclusters of size m = 2, 4, 8 and 12 respectively. Ab-initio molecular dynamics (AIMD) simulation shows that the outermost H2 molecules are desorbed at a rather low temperature viz. 150 K (-1230C) which is expected. However, complete dehydrogenation of these nanoclusters occur at around 1000C. Most importantly, the host nanoclusters remain stable up to ~500 K (2270C). All these results on the adsorption and desorption of molecular hydrogen with neutral and charged Mg nanocluster systems indicate towards the possibility of reducing the dehydrogenation temperature of bulk MgH2 by designing new Mg-based nano materials which will be able to adsorb molecular hydrogen via this weak Mg-H2 interaction, rather than the strong Mg-H bonding. Notwithstanding the fact that in practical applications, these interactions will be further complicated by the effect of substrates as well as interactions with other clusters, the present study has implications on our fundamental understanding to this problem.
87
14126
Mechanism of Melanin Inhibition of Morello Flavone- 7″- Sulphate and Sargaol extracts from Garcinia livingstonei (Clusiaceae): Homology Modelling, Molecular Docking, and Molecular Dynamics Simulations
Abstract:
Garcinia livingstonei (Clusiaceae) extracts, morelloflavone- 7″- sulphate and sargaol were shown to be effective against hyper-pigmentation through inhibition of tyrosinase enzyme, in vitro . The aim of this study is to elucidate the structural mechanism through which morelloflavone- 7″- sulphate and sargaol binds human tyrosinase. Implementing a homology model to construct a tyrosinase model using the crystal structure of a functional unit from Octopus hemocyanin (PDB: 1JS8) as a reference template enabled us to create a human tyrosinase model. Molecular dynamics and binding free energy calculations were optimized to enable molecular dynamics simulation of the copper dependent inhibitors. Results show the importance of the hydrogen bond formation morelloflavone- 7″- sulphate and sargaol between compound and active site residues. Both complexes demonstrated the metallic coordination between compound and arginine residue as well as copper ions within the active site. The comprehensive molecular insight gained from this study should be vital in understanding the binding mechanism morelloflavone- 7″- sulphate and sargaol. Moreover, these results will assist in the design of novel of metal ion dependent enzyme inhibitors as potential anti-hyper-pigmentation disorder therapies.
86
32438
Green Synthesis (Using Environment Friendly Bacteria) of Silver-Nanoparticles and Their Application as Drug Delivery Agents
Abstract:
The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.
85
111351
Comparative Analysis of Fused Deposition Modeling and Binding-Jet 3D Printing Technologies
Abstract:
Purpose: Large numbers of 3D printing technologies are now available for sophisticated applications in different fields. Additive manufacturing has established its dominance in design, development, and customisation of the product. In the era of developing technologies, there is a need to identify the appropriate technology for different application. In order to fulfil this need, two widely used printing technologies such as Fused Deposition Modeling (FDM), and Binding-Jet 3D Printing are compared for effective utilisation in the current scenario for different applications. Methodology: Systematic literature review conducted for both technologies with applications and associated factors enabling for the same. Appropriate MCDM tool is used to compare critical factors for both the technologies. Findings: Both technologies have their potential and capabilities to provide better direction to the industry. Additionally, this paper is helpful to develop a decision support system for the proper selection of technologies according to their continuum of applications and associated research and development capability. The vital issue is raw materials, and research-based material development is key to the sustainability of the developed technologies. FDM is a low-cost technology which provides high strength product as compared to binding jet technology. Researcher and companies can take benefits of this study to achieve the required applications in lesser resources. Limitations: Study has undertaken the comparison with the opinion of experts, which may not always be free from bias, and some own limitations of each technology. Originality: Comparison between these technologies will help to identify best-suited technology as per the customer requirements. It also provides development in this different field as per their extensive capability where these technologies can be successfully adopted. Conclusion: FDM and binding jet technology play an active role in industrial development. These help to assist the customisation and production of personalised parts cost-effectively. So, there is a need to understand how these technologies can provide these developments rapidly. These technologies help in easy changes or in making revised versions of the product, which is not easily possible in the conventional manufacturing system. High machine cost, the requirement of skilled human resources, low surface finish, and mechanical strength of product and material changing option is the main limitation of this technology. However, these limitations vary from technology to technology. In the future, these technologies are to be commercially viable for efficient usage in direct manufacturing of varied parts.
84
60083
The Effect of Probiotic Bacteria on Aflatoxin M1 Detoxification in Phosphate Buffer Saline
Abstract:
Aflatoxin M1 (AFM1) is a major toxic and carcinogenic molecule in milk and milk products. Therefore, it poses a risk for public health. Probiotics can be biological agent to remove AFM1. The aim of this study is to evaluate the effect of probiotic bacteria on AFM1 detoxification in phosphate buffer saline. The PBS samples artificially contaminated with AFM1 at concentration 100 pg/ml were prepared with probiotics bacteria that including monoculture (L. plantarum, B. bifidum ATCC, B. animalis ATCC 27672) and binary culture (L. bulgaricus + S. thermophiles, B. bifidum ATCC + B. animalis ATCC 27672, L. plantarum+B. bifidum ATCC, L. plantarum+ B. animalis ATCC 27672). The samples were incubated at 37°C for 4 hours and stored for 1, 5 and 10 days. The toxin was measured by the ELISA. The highest levels of AFM1 binding ability (63.6%) in PBS were detected yoghurt starter bacteria, while L. plantarum had the lowest levels of AFM1 binding ability (35.5%) in PBS. In addition, it was found that there was significant effect of storage on AFM1 binding ability in all groups except the one including B. animalis (p < 0.05). Consequently, results demonstrate that AFM1 detoxification by probiotic bacteria has a potential application to reduce toxin concentrations in yoghurt. Moreover, probiotic strains can react with itself as synergic or antagonist.
83
25172
Energy Audit: A Case Study of a Hot Rolling Mill in Steel Industry
Abstract:
As the energy demands rise and the pollution levels grow, it becomes imperative for us to save energy in all the fields in which it is used. The industrial sector is the major commercial energy consuming sector in India, where electrical energy is the most common and widely used type of energy. As the demand and price of energy are increasing day by day, therefore, the subject of energy conservation is a concern for most energy users particularly industry. Judicious use of energy becomes imperative for third world developing country being presence of energy crisis. This paper provides some measure for energy saving that can be commonly recommended for a rolling unit of steel industry. A case of hot rolling unit in JSL Stainless Ltd., Hisar for energy conservation is given. Overall improvement in energy consumption in light of the stated recommendation is illustrated along with the proposed utilization of the techniques and their applications. Energy conservation in conventional motor with replacement or use of star delta star converter, reduction in cable losses, replacement of filament of LED lamps, replacement of conventional transformer with cast resin dry type transformer and provision of energy management system for energy conservation and per unit production cost reduction are elaborated in this paper.
82
6027
Prevalence of Anemia and Iron Deficiency in Women of Childbearing Age in the North-West of Libya
Abstract:
Iron deficiency anemia is characterized by a decrease of Hb (hemoglobin), serum iron, ferritin, and RBC (red blood cells) (shape and size). Also, it is characterized by an increase in total iron binding capacity (TIBC). Red blood cells become microctytic and hypochromic due to a decrease in iron content. This study was conducted in the north west of Libya and included 210 women in childbearing age (18-45 years) who were visiting women clinic. After filling the questionnaire, blood samples were taken and analyzed for hematological and biochemical profiles. Biochemical tests included measurement of serum iron, ferritin, and total iron binding capacity (TIBC). Among the total sample (210 women), there were 87 (41.42%) pregnant and 123 (58.57%) non-pregnant women (includes married and single). Pregnant women (87) were classified according to the gestational age into first, second, and third trimesters. The means of biochemical and hematological parameters in the studied samples were: Hb = 10.37± 2.02 g/dl, RBC = 3.78± 1.037 m/m3, serum iron 61.86± 40.28 µg/dl, and TIBC = 386.01 ± 94.91 µg/dl. In this study, we considered that any women have hemoglobin below 11.5 g/dl is anemic. 89.1%, 69.5%, and 47.8% of pregnant women who belong to third trimester had low (below normal value) Hb, serum iron, and ferritin, i.e. iron deficiency anemia was more common in third trimester among the first and the second trimesters. Third trimester pregnant women also had high TIBC more than first and second trimesters.
81
78541
Interaction of Phytochemicals Present in Green Tea, Honey and Cinnamon to Human Melanocortin 4 Receptor
Abstract:
Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.
80
86012
Highly Specific DNA-Aptamer-Based Electrochemical Biosensor for Mercury (II) and Lead (II) Ions Detection in Water Samples
Abstract:
Aptamers are single-strand of DNA or RNA nucleotides sequence which is designed in vitro using selection process known as SELEX (systematic evolution of ligands by exponential enrichment) were developed for the selective detection of many toxic materials. In this work, we have developed an electrochemical biosensor for highly selective and sensitive detection of Hg2+ and Pb2+ using a specific aptamer probe (SAP) labelled with ferrocene (or methylene blue) in (5′) end and the thiol group at its (3′) termini, respectively. The SAP has a specific coil structure that matching with G-G for Pb2+ and T-T for Hg2+ interaction binding nucleotides ions, respectively. Aptamers were immobilized onto surface of screen-printed gold electrodes via SH groups; then the cyclic voltammograms were recorded in binding buffer with the addition of the above metal salts in different concentrations. The resulted values of anode current increase upon binding heavy metal ions to aptamers and analyte due to the presence of electrochemically active probe, i.e. ferrocene or methylene blue group. The correlation between the anodic current values and the concentrations of Hg2+ and Pb2+ ions has been established in this work. To the best of our knowledge, this is the first example of using a specific DNA aptamers for electrochemical detection of heavy metals. Each increase in concentration of 0.1 μM results in an increase in the anode current value by simple DC electrochemical test i.e (Cyclic Voltammetry), thus providing an easy way of determining Hg2+ and Pb2+concentration.
79
16341
Novel Aminoglycosides to Target Resistant Pathogens
Abstract:
Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.
78
17698
Towards Achieving Energy Efficiency in Kazakhstan
Abstract:
Kazakhstan is currently one of the dynamically developing states in its region. The stable growth in all sectors of the economy leads to a corresponding increase in energy consumption. Thus, country consumes a significant amount of energy due to the high level of industralisation and the presence of energy-intensive manufacturing such as mining and metallurgy which in turn leads to low energy efficiency. With allowance for this the Government has set several priorities to adopt a transition of Republic of Kazakhstan to a “green economy”. This article provides an overview of Kazakhstan’s energy efficiency situation in for the period of 1991-2014. First, the dynamics of production and consumption of conventional energy resources are given. Second, the potential of renewable energy sources is summarised, followed by the description of GHG emissions trends in the country. Third, Kazakhstan’ national initiatives, policies and locally implemented projects in the field of energy efficiency are described.
77
21339
Pharmacokinetics, Dosage Regimen and in Vitro Plasma Protein Binding of Danofloxacin following Intravenous Administration in Adult Buffaloes
Abstract:
The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.
76
55979
Apoptotic Induction Ability of Harmalol and Its Binding: Biochemical and Biophysical Perspectives
Authors:
Abstract:
Harmalol administration caused remarkable reduction in proliferation of HepG2 cells with GI50 of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG2 cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub Go/G1 population made the cancer cell, HepG2, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.
75
33623
Development of a Mathematical Theoretical Model and Simulation of the Electromechanical System for Wave Energy Harvesting
Abstract:
As a result of the studies performed on the wave energy resource worldwide, a research project was set up to harvest wave energy for its conversion into electrical energy. Within this framework, a theoretical model of the electromechanical energy harvesting system, developed with MATLAB&rsquo;s Simulink software, will be provided. This tool recreates the site conditions where the device will be installed and offers valuable information about the amount of energy that can be harnessed. This research provides a deeper understanding of the utilization of wave energy in order to improve the efficiency of a 1:1 scale prototype of the device.
74
9895
The Environmental Impact of Geothermal Energy and Opportunities for Its Utilization in Hungary
Abstract:
According to the International Energy Association the previous principles of the energy sector should be reassessed, in which renewable energy sources have a significant role. We might witness the exchange of roles of countries from importer to exporter, which look for the main resources of market needs. According to the World Energy Outlook 2013, the duration of high oil prices is exceptionally long in the history of the energy market. Forecasts also point at the expected great differences between the regional prices of gas and electric energy. The energy need of the world will grow by its third. two thirds of which will appear in China, India, and South-East Asia, while only 4 per cent of which will be related to OECD countries. Current trends also forecast the growth of the price of energy sources and the emission of glasshouse gases. As a reflection of these forecasts alternative energy sources will gain value, of which geothermic energy is one of the cheapest and most economical. Hungary possesses outstanding resources of geothermic energy. The aim of the study is to research the environmental effects of geothermic energy and the opportunities of its exploitation in Hungary, related to „Horizon 2020” project.
73
54485
Role of Non-Renewable and Renewable Energy for Sustainable Electricity Generation in Malaysia
Abstract:
The main objective of this paper is to give a comprehensive review of non-renewable energy and renewable energy utilization in Malaysia, including hydropower, solar photovoltaic, biomass and biogas technologies. Malaysia mainly depends on non-renewable energy (natural gas, coal and crude oil) for electricity generation. Therefore, this paper provides a comprehensive review of the energy sector and discusses diversification of electricity generation as a strategy for providing sustainable energy in Malaysia. Energy policies and strategies to protect the non-renewable energy utilization also are highlighted, focusing in the different sources of energy available for high and sustained economic growth. Emphasis is also placed on a discussion of the role of renewable energy as an alternative source for the increase of electricity supply security. It is now evident that to achieve sustainable development through renewable energy, energy policies and strategies have to be well designed and supported by the government, industries (firms), and individual or community participation. The hope is to create a positive impact on sustainable development through renewable sources for current and future generations.
72
19089
Introduction of PMMA-Tag to VHH for Improving Recovery and Immobilization Rate of VHHS
Abstract:
The PMMA-tag was genetically fused with the C-terminal region of VHH molecules. This antibody, VHH, is known as a single-chain domain, which is devoid of light chains. The PMMA-tag, which could affect the isoelectric point (pI) changeable with a charge of amino acid in VHHs were closely related to the solubility of VHH molecules during refolding. The genetic fusion of PMMA-tag to C-terminal region of VHHs significantly affects the recovery of their soluble protein during refolding by 50 mM TAPS at pH 8.5. It could be refolded with a recovery of more than 95% by dialysis at pH 8.5. A marked difference in the antigen-binding activities in the adsorption state was significantly high in VHH-PM compared to the wild type of VHH. There are approximately 8-fold differences in the antigen-binding activities in the adsorption state between VHH-PM and VHH.
71
73228
Design Analysis of Solar Energy Panels for Tropical Nigeria
Abstract:
More than ever human activity relating to uncontrolled greenhouse gas (GHG) and its effects on the earth is gaining greater attention in the global academic and policy discussions. Activities of man have greatly influenced climate change over the years as a result of a consistent increase in the use of fossil fuel energy. Scientists and researchers globally are making significant and devoted efforts towards the development and implementation of renewable energy technologies that are harmless to the environment. One of such energy is solar energy with its source from the sun. There are currently two primary ways of harvesting this energy from the sun: through photovoltaic (PV) panels and through thermal collectors. This work discusses solar energy as the abundant renewable energy in the tropical Nigeria, processes of harvesting the energy and recommends solar energy as an alternative means of electric power generation in a time the demand for power in Nigeria supersedes supply.
70
60811
Binding Studies and Structure Determination of the Recombinantly Produced Type-II 3-Dehydroquinate Dehydratase from Acinetobacter Baumannii
Abstract:
Dehydroquinase (3-dehydroquinate dehydratase, DHQD, EC 4.2.1.10) is involved in shikimate pathway and catalyzes the conversion of dehydroquinate to dehydroshikimate. Shikimate pathway is important drug target as this pathway is absent in mammals. DHQD from Acinetobacter baumannii (AbDHQD) was cloned, expressed and purified to homogeneity. The binding studies showed that compounds quinic acid and citrazinic acid bound to AbDHQD at micromolar concentrations. AbDHQD was crystallized using 30% PEG-3350, 50mM tris-HCl, and 1.0M MgSO4 at PH 8.0. Crystals of AbDHQD were stabilized by transferring them into reservoir solution to which 25% glycerol was added for data collection at 100K. The X-ray intensity data were collected to 2.0Å resolution. The crystals belong to monoclinic space group P21 with cell dimensions, a = 82.3, b = 95.3, c = 132.3Å and β = 95.7°. The structure was solved with molecular replacement method and refined to Rcryst/Rfree factors of 0.200/0.232. The structures of 12 crystallographically independent molecules in the asymmetry unit were identical with r.m.s shifts for the C atoms ranging from 0.3 Å to 0.8 Å. They formed a dodecamer with four trimers arranged in a tetrahedral manner. The classical lid adopted an open conformation although a sulfate ion was observed in the substrate binding site. As a result of which, the compounds quinic acid and citrazinic acid did not bind to AbDHQD.
69
132954
Analytical Similarity Assessment of Bevacizumab Biosimilar Candidate MB02 Using Multiple State-of-the-Art Assays
Abstract:
MB02 (Alymsys®) is a candidate biosimilar to bevacizumab, which was developed against the reference product (RP) Avastin® sourced from both the European Union (EU) and United States (US). MB02 has been extensively characterized comparatively to Avastin® at a physicochemical and biological level using sensitive orthogonal state-of-the-art analytical methods. MB02 has been demonstrated similar to the RP with regard to its primary and higher-order structure, post- and co-translational profiles such as glycosylation, charge, and size variants. Specific focus has been put on the characterization of Fab-related activities, such as binding to VEGF A 165, which directly reflect the bevacizumab mechanism of action. Fc-related functionality was also investigated, including binding to FcRn, which is indicative of antibodies' half-life. The data generated during the analytical similarity assessment demonstrate the high analytical similarity of MB02 to its RP.
68
32304
Covalent Binding of Cysteine to a Sol-Gel Material for Cadmium Biosorption from Aqueous Solutions
Abstract:
Heavy metal pollution has become a more serious environmental problem in the last several decades as a result of its toxicity and insusceptibility to the environment. Methods for removing metal ions from aqueous solution mainly consist of physical, chemical and biochemical procedures. Biosorption is defined as the removal of metal or metalloid species, compounds and particulates from solution by a biological material. Biosorption represents a very attractive method for the removal of toxic metal ions from aqueous effluents because it uses the ability of various biomass to bind the metal ions without the risk of releasing other toxic chemical compounds into the environment. The problem with using biomass or living cells as biosorbents is that their regeneration/reuse is often either impossible or very laborious. One of the most common chelating group found in biosorbents is the thiol group in cysteine. Therefore, we immobilized cysteine using covalent binding using glutaraldehyde as a linker on a synthetic sol-gel support obtained using 3-amino-propyl-trimetoxysilane and trimetoxysilane as precursors. The obtained adsorbents were used for removal of cadmium from aqueous solutions and the removal capacity was investigated in relation to the composition of the sol-gel hybrid composite, the loading of the biomolecule and the physical parameters of the biosorption process. In the same conditions, the bare sol-gel support without cysteine had no Cd removal effect, while the adsorbent with cysteine had an adsorption capacity up to 25.8 mg Cd/g adsorbent at pH 2.0 and 119 mg Cd/g adsorbent at pH 6.6, depending on cadmium concentration and adsorption conditions. We used atomic adsorption spectrometry to assess the cadmium concentration in the samples after the biosorbtion process. The parameters for the Freundlich and Langmuir adsorption isotherms where calculated from plotting the results of the adsorption experiments. The results for cysteine immobilization show a good loading capacity of the sol-gel support which indicates it could be used to immobilize metal binding proteins and by doing so boosting the heavy metal adsorption capacity of the biosorbent.
67
96568
Stochastic Modeling of Secretion Dynamics in Inner Hair Cells of the Auditory Pathway
Abstract:
Glutamate release of the cochlear inner hair cell (IHC) ribbon synapse is a fundamental step in transferring sound information in the auditory pathway. Otoferlin is the calcium sensor in the IHC and its activity has been related to many auditory disorders. In order to simulate secretion dynamics occurring in the IHC in a few milliseconds timescale and with high spatial resolution, we proposed an active-zone model solved with Monte Carlo algorithms. We included models for calcium buffered diffusion, calcium-binding schemes for vesicle fusion, and L-type voltage-gated calcium channels. Our results indicate that calcium influx and calcium binding is managing IHC secretion as a function of voltage depolarization, which in turn mean that IHC response depends on sound intensity.
66
92985
Microwave Synthesis and Molecular Docking Studies of Azetidinone Analogous Bearing Diphenyl Ether Nucleus as a Potent Antimycobacterial and Antiprotozoal Agent
Abstract:
The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.
65
103773
Energy Planning Analysis of an Agritourism Complex Based on Energy Demand Simulation: A Case Study of Wuxi Yangshan Agritourism Complex
Abstract:
China is experiencing the rural development process, with the agritourism complex becoming one of the significant modes. Therefore, it is imperative to understand the energy performance of agritourism complex. This study focuses on a typical case of the agritourism complex and simulates the energy consumption performance on condition of the regular energy system. It was found that HVAC took 90% of the whole energy demand range. In order to optimize the energy supply structure, the hierarchical analysis was carried out on the level of architecture with three main factors such as construction situation, building types and energy demand types. Finally, the energy planning suggestion of the agritourism complex was put forward and the relevant results were obtained.
64
24956
Pharmacokinetic Model of Warfarin and Its Application in Personalized Medicine
Abstract:
In this study, we evaluated the impact of CYP2C9*2 and CYP2C9*3 variants on binding and hydroxylation of warfarin. In silico data revealed that warfarin forms two hydrogen bonds with protein backbone i.e. I205 and S209, one hydrogen bond with protein side chain i.e. T301 and stacking interaction with F100 in CYP2C9*1. In CYP2C9*2 and CYP2C9*3 variants, two hydrogen bonds with protein backbone are disrupted. In double variant, all the hydrogen bonds are disrupted. The distances between C7 of S-warfarin and Fe-O in CYP2C9*1, CYP2C9*2, CYP2C9*3 and CYP2C9*2/*3 were 5.81A°, 7.02A°, 7.43° and 10.07°, respectively. The glide scores (Kcal/mol) were -7.698, -7.380, -6.821 and -6.986, respectively. Increase in warfarin/7-hydroxy warfarin ratio was observed with increase in variant alleles. To conclude, CYP2C9*2 and CYP2C9*3 variants result in disruption of hydrogen bonding interactions with warfarin and longer distance between C7 and Fe-O thus impairing warfarin 7-hydroxylation due to lower binding affinity of warfarin.
63
36215
Stochastic Energy and Reserve Scheduling with Wind Generation and Generic Energy Storage Systems
Abstract:
Energy storage units can play an important role to provide an economic and secure operation of future energy systems. In this paper, a stochastic energy and reserve market clearing scheme is presented considering storage energy units. The approach is proposed to deal with stochastic and non-dispatchable renewable sources with a high level of penetration in the energy system. A two stage stochastic programming scheme is formulated where in the first stage the energy market is cleared according to the forecasted amount of wind generation and demands and in the second stage the real time market is solved according to the assumed scenarios.
62
46632
Illuminating the Policies Affecting Energy Security in Malaysia’s Electricity Sector
Abstract:
For the past few decades, the Malaysian economy has expanded at an impressive pace, whilst, the Malaysian population has registered a relatively high growth rate. These factors had driven the growth of final energy demand. The ballooning energy demand coupled with the country&rsquo;s limited indigenous energy resources have resulted in an increased of the country&rsquo;s net import. Therefore, acknowledging the precarious position of the country&rsquo;s energy self-sufficiency, this study has identified three main concerns regarding energy security, namely; over-dependence on fossil fuel, increasing energy import dependency, and increasing energy consumption per capita. This paper discusses the recent energy demand and supply trends, highlights the policies that are affecting energy security in Malaysia and suggests strategic options towards achieving energy security. The paper suggested that diversifying energy sources, reducing carbon content of energy, efficient utilization of energy and facilitating low-carbon industries could further enhance the effectiveness of the measures as the introduction of policies and initiatives will be more holistic.
61
24319
In Silico Studies on Selected Drug Targets for Combating Drug Resistance in Plasmodium Falcifarum
Abstract:
With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.
60
20735
Development of Adhesive from Prosopis african Seed Endosperm (OKPEYI)
Abstract:
An experimental study was carried out to develop an adhesive from Prosopis africana seed endosperm. The Prosopis seeds for this work were obtained from Enugu State in the South East part of Nigeria. The Prosopis seeds were prepared by separating the Prosopis endosperm from the seed coat and cotyledon. The dry adhesive gotten from the endosperm was later dissolved to get the adhesive solution. Confirmatory tests like viscosity, density, pH, and binding strength were carried out. The effect of time, temperature, concentration on the yield and properties of the adhesive were investigated. The results obtained showed that increase in concentration, time, temperature decreases the viscosity of the Prosopis adhesive and yield of Prosopis endosperm. It was also deduced that increase in viscosity increases the binding strength of the Prosopis adhesive. The percentage of the adhesive yield from Prosopis endosperm showed that the commercialization of the seed in Nigeria will be possible and profitable.
59
120700
Structure, Bioinformatics Analysis and Substrate Specificity of a 6-Phospho-β-Glucosidase Glycoside Hydrolase 1 Enzyme from Bacillus licheniformis
Abstract:
In bacteria, mono and disaccharides are phosphorylated during uptake into the cell via the widely used phosphoenolpyruvate (PEP)-dependent phosphotransferase transport system. As an initial step in the phosphorylated disaccharide metabolism pathway, certain glycoside hydrolase family 1 (GH1) enzymes play a crucial role in releasing phosphorylated and non-phosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified. GH1 enzymes are known to have a wide array of functions. According to the CAZy database, there are twenty-one different enzymatic activities in the GH1 family. Here, the structure and substrate specificity of a GH1 enzyme from Bacillus licheniformis, hereafter known as BlBglH, was investigated. The sequence of the enzyme BlBglH was compared to the sequences of other characterized GH1 enzymes using sequence alignment, sequence identity calculations, phylogenetic analysis, and motif discovery. Through these various analyses, BlBglH was found to have sequence features characteristic of the 6-phospho-β-glucosidase activity enzymes. Additionally, motif and structure comparisons of the three most commonly studied GH1 enzyme-activities revealed a shared loop amongst the different structures that consist of different sequence motifs – this loop is thought to guide specific substrates (depending on activity) towards the active-site. To further affirm BlBglH enzyme activity, molecular docking and molecular dynamics simulations were performed. Docking was carried out using 6-phospho-β-glucosidase enzyme-activity positive (p-Nitrophenyl-beta-D-glucoside-6-phosphate) and negative (p-Nitrophenyl-beta-D-galactoside-6-phosphate) control ligands, followed by 400 ns molecular dynamics simulations. The positive-control ligand maintained favourable interactions within the active site until the end of the simulation. The negative-control ligand was observed exiting the enzyme at 287 ns. Binding free energy calculations showed that the positive-control complex had a substantially more favourable binding energy compared to the negative-control complex. Jointly, the findings of this study suggest that the BlBglH enzyme possesses 6-phospho-β-glucosidase enzymatic activity.
58
88981
Investigating the Invalidity of the Law of Energy Conservation Based on Waves Interference Phenomenon Inside a Ringed Waveguide
Authors:
Abstract:
Law of energy conservation is one of the fundamental laws of physics. Energy is conserved, and the total amount of energy is constant. It can be transferred from one object to another and changed from one state to another. However, in the case of wave interference, this law faces important contradictions. Based on the presented mathematical relationship in this paper, it seems that validity of this law depends on the path of energy wave, like light, in which it is located. In this paper, by using some fundamental concepts in physics like the constancy of the electromagnetic wave speed in a specific media and wave theory of light, it will be shown that law of energy conservation is not valid in every condition and in some circumstances, it is possible to increase energy of a system with a determined amount of energy without any input.
57
89632
Modified Acetamidobenzoxazolone Based Biomarker for Translocator Protein Mapping during Neuroinflammation
Abstract:
The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.
56
30722
The Effect of Surface Wave on the Performance Characteristic of a Wave-Tidal Integral Turbine Hybrid Generation System
Abstract:
More than 70% of the Earth is covered by oceans, which are considered to possess boundless renewable energy, such as tidal energy, tidal current energy, wave energy, thermal energy, and chemical energy. The hybrid system help in improving the economic and environmental sustainability of renewable energy systems to fulfill the energy demand. The concept of hybridizing renewable energy is to meet the desired system requirements, with the lowest value of the energy cost. This paper propose a hybrid power generation system suitable for remote area application and highlight the impact of surface waves on turbine design and performance, and the importance of understanding the site-specific wave conditions.
55
51335
[Keynote Talk]: Wave-Tidal Integral Turbine Hybrid Generation Approach for Characterizing Performance of Surface Wave
Abstract:
Boundless renewable energy, such as tidal energy, tidal current energy, wave energy, thermal energy and chemical energy are covered and possessed by oceans. The hybrid system helps in improving the economic and environmental sustainability of renewable energy systems to fulfill the energy demand. The objective and concept of hybridizing renewable energy is to meet the desired system requirements, with the lowest value of the energy cost. This paper reviews applications of using hybrid power generation system for remote area. It also highlights the future directions to investigate the impacts of surface waves on turbine design and performance. The importance of understanding the site-specific wave conditions could also been explored.
54
35904
The Use of Energy Efficiency and Renewable Energy in Building for Sustainable Development
Abstract:
High energy consumptions of urban settlements in Nigeria are escalating due to strong population growth and migration as a result of crises. The demand for lighting, heating, ventilation and air conditioning (LHVAC) is becoming higher. Conversely, there is a poor electricity supply to both rural and urban settlement in Nigeria. Generators were mostly used in Nigeria as a source of energy for LHVAC. Energy efficiency can be defined as any measure taken to reduce the amount of energy consumed for heating ventilation and air-conditioning (HVAC), and house hold appliances like computers, stoves, refrigerators, televisions etc. The aim of the study was to minimize energy consumption in building through the integration of energy efficiency and renewable energy in building sector. Some of the energy efficient buildings within the study area were identified, the study covers there major cities of Nigeria namely, Abuja, Kaduna and Lagos city. The cost of investment on the energy efficiency and renewable energy was determined and compared with other fossil energy source for conventional building. Findings revealed that the low energy and energy efficient buildings in Nigeria are cheaper than the conventional ones. Based on the finding of the research, construction stake holders are strongly encouraged to abandon the conventional buildings and consider energy efficiency and renewable energy in buildings.
53
10913
Input Energy Requirements and Performance of Different Soil Tillage Systems on Yield of Maize Crop
Abstract:
The aims of this study were to determine direct input energy and indirect energy in maize production, to evaluate the inputs energy consumption and outputs energy gained for maize production in Islamabad, Pakistan for spring 2013. Results showed that grain yield was maximum under deep tillage as compared to conventional and zero tillage. Total energy input/output were maximum in deep tillage as compared to conventional tillage while lowest in zero tillage, net energy gain were found maximum under deep tillage.
52
23200
Comprehensive Assessment of Energy Efficiency within the Production Process
Abstract:
The importance of energy efficiency within the production process increases steadily. Unfortunately, so far no tools for a comprehensive assessment of energy efficiency within the production process exist. Therefore the Institute for Factory Automation and Production Systems of the Friedrich-Alexander-University Erlangen-Nuremberg has developed two methods with the goal of achieving transparency and a quantitative assessment of energy efficiency: EEV (Energy Efficiency Value) and EPE (Energetic Process Efficiency). This paper describes the basics and state of the art as well as the developed approaches.
51
76700
Promotion of Renewable Marines Energies in Morocco: Perspectives and Strategies
Abstract:
The current energy policy recommends the subject of energy efficiency and to phase out fossil energy as a master question for the prospective years. The kingdom requires restructuring its power equipment by improving the percentage of renewable energy supply and optimizing power systems and storage. Developing energy efficiency, therefore, obliges as a consubstantial objection to reducing energy consumption. The objective of this work is to show the energy transition in Morocco towards renewable energies, in particular, to show the great potential of renewable marine energies in Morocco, This goes back to the advantages of cost and non-pollution in addition to that of the independence of fossil energies. Bearing in mind the necessity of the balance of the Moroccan energy mix, hydraulic and thermal power plants have also been installed which will be added to the power stations already established as a prospect for a balanced network that is flexible to fluctuate demand.
50
14229
Energy Efficiency Factors in Toll Plazas
Abstract:
Energy efficiency is one of the most important issues for green buildings and their sustainability. This is not only due to the environmental impacts, but also because of significantly high energy cost. The aim of this study is to identify the potential actions required for toll plaza that lead to energy reduction. The data were obtained through set of questionnaire and interviewing targeted respondents, including the employees at toll plaza, and architects and engineers who are directly involved in design of highway projects. The data was analyzed using descriptive statistics analysis method. The findings of this study are the critical elements that influence the energy usage and factors that lead to energy wastage. Finally, potential actions are recommended to reduce energy consumption in toll plazas.
49
26176
Anti-Obesity Effects of Pteryxin in Peucedanum japonicum Thunb Leaves through Different Pathways of Adipogenesis In-Vitro
Abstract:
Pteryxin from the partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as the active compound related to anti-obesity. Thus, in this study we investigated the mechanisms related to anti-obesity activity in-vitro. The HP was fractionated, and effect on the triglyceride (TG) content was evaluated in 3T3-L1 and HepG2 cells. Comprehensive spectroscopic analyses were used to identify the structure of the active compound. The dose dependent effect of active constituent on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis and lipogenesis (20 μg/mL) were examined in-vitro. Furthermore, higher dosage of pteryxin (50μg/mL) was tested against 20μg/mL in 3T3-L1 adipocytes. The mRNA were subjected to SOLiD next generation sequencer and the obtained data were analyzed by Ingenuity Pathway Analysis (IPA). The active constituent was identified as pteryxin, a known compound in PJT. However, its biological activities against obesity have not been reported previously. Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes and HepG2 hepatocytes (P < 0.05). Sterol regulatory element-binding protein-1 (SREBP1 c), Fatty acid synthase (FASN), and acetyl-CoA carboxylase-1 (ACC1) were downregulated in pteryxin-treated adipocytes (by 18.0, 36.1 and 38.2%; P < 0.05, respectively) and hepatocytes (by 72.3, 62.9 and 38.8%, respectively; P < 0.05) indicating its suppressive effects on fatty acid synthesis. The hormone-sensitive lipase (HSL), a lipid catabolising gene was upregulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes suggesting improved lipolysis. Concordantly, the adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was downregulated (by 42.8%; P < 0.05), further accelerating the lipolytic activity. The upregulated trend of uncoupling protein 2 (UCP2; by 77.5%; P < 0.05) reflected the improved energy expenditure due to pteryxin. The 50μg/mL dosage of pteryxin completely suppressed PPARγ, MEST, SREBP 1C, HSL, Adiponectin, Fatty Acid Binding Protein (FABP) 4, and UCP’s in 3T3-L1 adipocytes. The IPA suggested that pteryxin at 20μg/mL and 50μg/mL suppress obesity in two different pathways, whereas the WNT signaling pathway play a key role in the higher dose of pteryxin in preadipocyte stage. Pteryxin in PJT play the key role in regulating lipid metabolism related gene network and improving energy production in vitro. Thus, the results suggests pteryxin as a new natural compound to be used as an anti-obesity drug in pharmaceutical industry.
48
89543
The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation
Abstract:
In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).
47
14600
Structural and Binding Studies of Peptidyl-tRNA Hydrolase from Pseudomonas aeruginosa Provide a Platform for the Structure Based Inhibitor Design against Peptidyl-tRNA Hydrolase
Abstract:
Peptidyl-tRNA hydrolase (Pth) Pth is an essential bacterial enzyme that catalyzes the release of free tRNA and peptide moeities from peptidyl tRNAs during stalling of protein synthesis. In order to design inhibitors of Pth from Pseudomonas aeruginosa (PaPth), we have determined the structures of PaPth in its native state and in the bound states with two compounds, amino acylate-tRNA analogue (AAtA) and 5-azacytidine (AZAC). The peptidyl-tRNA hydrolase gene from Pseudomonas aeruginosa was amplified by Phusion High-Fidelity DNA Polymerase using forward and reverse primers, respectively. The E. coliBL21 (λDE3) strain was used for expression of the recombinant peptidyl-tRNA hydrolase from Pseudomonas aeruginosa. The protein was purified using a Ni-NTA superflow column. The crystallization experiments were carried out using hanging drop vapour diffusion method. The crystals diffracted to 1.50 Å resolution. The data were processed using HKL-2000. The polypeptide chain of PaPth consists of 194 amino acid residues from Met1 to Ala194. The centrally located β-structure is surrounded by α-helices from all sides except the side that has entrance to the substrate binding site. The structures of the complexes of PaPth with AAtA and AZAC showed the ligands bound to PaPth in the substrate binding cleft and interacted with protein atoms extensively. The residues that formed intermolecular hydrogen bonds with the atoms of AAtA included Asn12, His22, Asn70, Gly113, Asn116, Ser148, and Glu161 of the symmetry related molecule. The amino acids that were involved in hydrogen bonded interactions in case of AZAC included, His22, Gly113, Asn116, and Ser148. As indicated by fittings of two ligands and the number of interactions made by them with protein atoms, AAtA appears to be a more compatible with the structure of the substrate binding cleft. However, there is a further scope to achieve a better stacking than that of O-tyrosyl moiety because it is not still ideally stacked. These observations about the interactions between the protein and ligands have provided the information about the mode of binding of ligands, nature and number of interactions. This information may be useful for the design of tight inhibitors of Pth enzymes.
46
15793
Solar Energy: The Alternative Electric Power Resource in Tropical Nigeria
Abstract:
More than ever human activity relating to uncontrolled greenhouse gas (GHG) and its effects on the earth is gaining greater attention in the global academic and policy discussions. Activities of man has greatly influenced climate change over the years as a result of consistent increase in the use of fossil fuel energy. Scientists and researchers globally are making significant and devoted efforts towards the development and implementation of renewable energy technologies that are harmless to the environment. One of such energy is solar energy with its source from the sun. There are currently two primary ways of harvesting this energy from the sun: through photovoltaic (PV) panels and through thermal collectors. This work discuses solar energy the abundant renewable energy in the tropical Nigeria, processes of harvesting and recommends same as an alternative means of electric power generation in a time the demand for power supersedes supply.
45
36260
Structural and Functional Comparison of Untagged and Tagged EmrE Protein
Abstract:
EmrE, a member of the small multidrug resistance protein family in bacteria is considered to be the archetypical member of its family. It confers host resistance to a wide variety of quaternary cation compounds (QCCs) driven by proton motive force. Generally, purification yield is a challenge in all membrane proteins because of the difficulties in their expression, isolation and solubilization. EmrE is extremely hydrophobic which make the purification yield challenging. We have purified EmrE protein using two different approaches: organic solvent membrane extraction and hexahistidine (his6) tagged Ni-affinity chromatographic methods. We have characterized changes present between ligand affinity of untagged and his6-tagged EmrE proteins in similar membrane mimetic environments using biophysical experimental techniques. Purified proteins were solubilized in a buffer containing n-dodecyl-β-D-maltopyranoside (DDM) and the conformations in the proteins were explored in the presence of four QCCs, methyl viologen (MV), ethidium bromide (EB), cetylpyridinium chloride (CTP) and tetraphenyl phosphonium (TPP). SDS-Tricine PAGE and dynamic light scattering (DLS) analysis revealed that the addition of QCCs did not induce higher multimeric forms of either proteins at all QCC:EmrE molar ratios examined under the solubilization conditions applied. QCC binding curves obtained from the Trp fluorescence quenching spectra, gave the values of dissociation constant (Kd) and maximum specific one-site binding (Bmax). Lower Bmax values to QCCs for his6-tagged EmrE shows that the binding sites remained unoccupied. This lower saturation suggests that the his6-tagged versions provide a conformation that prevents saturated binding. Our data demonstrate that tagging an integral membrane protein can significantly influence the protein.
44
75907
Energy Management Techniques in Mobile Robots
Abstract:
Today, the developing features of technological tools with limited energy resources have made it necessary to use energy efficiently. Energy management techniques have emerged for this purpose. As with every field, energy management is vital for robots that are being used in many areas from industry to daily life and that are thought to take up more spaces in the future. Particularly, effective power management in autonomous and multi robots, which are getting more complicated and increasing day by day, will improve the performance and success. In this study, robot management algorithms, usage of renewable and hybrid energy sources, robot motion patterns, robot designs, sharing strategies of workloads in multiple robots, road and mission planning algorithms are discussed for efficient use of energy resources by mobile robots. These techniques have been evaluated in terms of efficient use of existing energy resources and energy management in robots.
43
78480
Energy Efficiency Analysis of Crossover Technologies in Industrial Applications
Authors:
Abstract:
Industry accounts for one-third of global final energy demand. Crossover technologies (e.g. motors, pumps, process heat, and air conditioning) play an important role in improving energy efficiency. These technologies are used in many applications independent of the production branch. Especially electrical power is used by drives, pumps, compressors, and lightning. The paper demonstrates the algorithm of the energy analysis by some selected case studies for typical industrial processes. The energy analysis represents an essential part of energy management systems (EMS). Generally, process control system (PCS) can support EMS. They provide information about the production process, and they organize the maintenance actions. Combining these tools into an integrated process allows the development of an energy critical equipment strategy. Thus, asset and energy management can use the same common data to improve the energy efficiency.
42
38242
A Novel Concept of Optical Immunosensor Based on High-Affinity Recombinant Protein Binders for Tailored Target-Specific Detection
Abstract:
Recently, novel strategies based on so-called molecular evolution were shown to be effective for the production of various peptide ligand libraries with high affinities to molecular targets of interest comparable or even better than monoclonal antibodies. The major advantage of these peptide scaffolds is mainly their prevailing low molecular weight and simple structure. This study describes a new high-affinity binding molecules based immunesensor using a simple optical system for human serum albumin (HSA) detection as a model molecule. We present a comparison of two variants of recombinant binders based on albumin binding domain of the protein G (ABD) performed on micropatterned glass chip. Binding domains may be tailored to any specific target of interest by molecular evolution. Micropatterened glass chips were prepared using UV-photolithography on chromium sputtered glasses. Glass surface was modified by (3-aminopropyl)trietoxysilane and biotin-PEG-acid using EDC/NHS chemistry. Two variants of high-affinity binding molecules were used to detect target molecule. Firstly, a variant is based on ABD domain fused with TolA chain. This molecule is in vivo biotinylated and each molecule contains one molecule of biotin and one ABD domain. Secondly, the variant is ABD domain based on streptavidin molecule and contains four gaps for biotin and four ABD domains. These high-affinity molecules were immobilized to the chip surface via biotin-streptavidin chemistry. To eliminate nonspecific binding 1% bovine serum albumin (BSA) or 6% fetal bovine serum (FBS) were used in every step. For both variants range of measured concentrations of fluorescently labelled HSA was 0 – 30 µg/ml. As a control, we performed a simultaneous assay without high-affinity binding molecules. Fluorescent signal was measured using inverse fluorescent microscope Olympus IX 70 with COOL LED pE 4000 as a light source, related filters, and camera Retiga 2000R as a detector. The fluorescent signal from non-modified areas was substracted from the signal of the fluorescent areas. Results were presented in graphs showing the dependence of measured grayscale value on the log-scale of HSA concentration. For the TolA variant the limit of detection (LOD) of the optical immunosensor proposed in this study is calculated to be 0,20 µg/ml for HSA detection in 1% BSA and 0,24 µg/ml in 6% FBS. In the case of streptavidin-based molecule, it was 0,04 µg/ml and 0,07 µg/ml respectively. The dynamical range of the immunosensor was possible to estimate just in the case of TolA variant and it was calculated to be 0,49 – 3,75 µg/ml and 0,73-1,88 µg/ml respectively. In the case of the streptavidin-based the variant we didn´t reach the surface saturation even with the 480 ug/ml concentration and the upper value of dynamical range was not estimated. Lower value was calculated to be 0,14 µg/ml and 0,17 µg/ml respectively. Based on the obtained results, it´s clear that both variants are useful for creating the bio-recognizing layer on immunosensors. For this particular system, it is obvious that the variant based on streptavidin molecule is more useful for biosensing on glass planar surfaces. Immunosensors based on this variant would exhibit better limit of detection and wide dynamical range.
41
59410
Prediction-Based Midterm Operation Planning for Energy Management of Exhibition Hall
Abstract:
Large exhibition halls require a lot of energy to maintain comfortable atmosphere for the visitors viewing inside. One way of reducing the energy cost is to have thermal energy storage systems installed so that the thermal energy can be stored in the middle of night when the energy price is low and then used later when the price is high. To minimize the overall energy cost, however, we should be able to decide how much energy to save during which time period exactly. If we can foresee future energy load and the corresponding cost, we will be able to make such decisions reasonably. In this paper, we use machine learning technique to obtain models for predicting weather conditions and the number of visitors on hourly basis for the next day. Based on the energy load thus predicted, we build a cost-optimal daily operation plan for the thermal energy storage systems and cooling and heating facilities through simulation-based optimization.
40
62532
Improved Signal-To-Noise Ratio by the 3D-Functionalization of Fully Zwitterionic Surface Coatings
Abstract:
False outcomes of diagnostic tests are a major concern in medical health care. To improve the reliability of surface-based diagnostic tests, it is of crucial importance to diminish background signals that arise from the non-specific binding of biomolecules, a process called fouling. The aim is to create surfaces that repel all biomolecules except the molecule of interest. This can be achieved by incorporating antifouling protein repellent coatings in between the sensor surface and it’s recognition elements (e.g. antibodies, sugars, aptamers). Zwitterionic polymer brushes are considered excellent antifouling materials, however, to be able to bind the molecule of interest, the polymer brushes have to be functionalized and so far this was only achieved at the expense of either antifouling or binding capacity. To overcome this limitation, we combined both features into one single monomer: a zwitterionic sulfobetaine, ensuring antifouling capabilities, equipped with a clickable azide moiety which allows for further functionalization. By copolymerizing this monomer together with a standard sulfobetaine, the number of azides (and with that the number of recognition elements) can be tuned depending on the application. First, the clickable azido-monomer was synthesized and characterized, followed by copolymerizing this monomer to yield functionalizable antifouling brushes. The brushes were fully characterized using surface characterization techniques like XPS, contact angle measurements, G-ATR-FTIR and XRR. As a proof of principle, the brushes were subsequently functionalized with biotin via strain-promoted alkyne azide click reactions, which yielded a fully zwitterionic biotin-containing 3D-functionalized coating. The sensing capacity was evaluated by reflectometry using avidin and fibrinogen containing protein solutions. The surfaces showed excellent antifouling properties as illustrated by the complete absence of non-specific fibrinogen binding, while at the same time clear responses were seen for the specific binding of avidin. A great increase in signal-to-noise ratio was observed, even when the amount of functional groups was lowered to 1%, compared to traditional modification of sulfobetaine brushes that rely on a 2D-approach in which only the top-layer can be functionalized. This study was performed on stoichiometric silicon nitride surfaces for future microring resonator based assays, however, this methodology can be transferred to other biosensor platforms which are currently being investigated. The approach presented herein enables a highly efficient strategy for selective binding with retained antifouling properties for improved signal-to-noise ratios in binding assays. The number of recognition units can be adjusted to a specific need, e.g. depending on the size of the analyte to be bound, widening the scope of these functionalizable surface coatings.
39
1751
Development of Mobile Application for Energy Consumption Assessment of University Buildings
Abstract:
With an increase in the interest in the energy conservation for buildings, and the emergence of many methods and easily-understandable approaches to it, energy conservation has now become the public’s main interest, as compared to in the past when it was only focused upon by experts. This study aims to help the occupants of a building to understand the energy efficiency and consumption of the building by providing them information on the building’s energy efficiency through a mobile application. The energy performance assessment models are proposed on the basis of the actual energy usage and building characteristics such as the architectural scheme and the building equipment. The university buildings in Korea are used as a case to demonstrate the mobile application.
38
26626
“It Isn’t a State Problem”: The Minas Conga Mine Controversy and Exemplifying the Need for Binding International Obligations on Corporate Actors
Authors:
Abstract:
After years of implacable neoliberal globalization, multinational corporations have moved from the periphery to the center of the international legal agenda. Human rights advocates have long called for greater corporate accountability in the international arena. The creation of the Global Compact in 2000, while aimed at fostering greater corporate respect for human rights, did not silence these calls. After multiple unsuccessful attempts to adopt a set of norms relating to the human rights responsibilities of transnational corporations, the United Nations succeeded in 2008 with the Guiding Principles on Business and Human Rights (Guiding Principles). The Guiding Principles, praised by some within the international human rights community for their recognition of an individual corporate responsibility to respect human rights, have not escaped their share of criticism. Many view the Guiding Principles to be toothless, failing to directly impose obligations upon corporations, and call for binding international obligations on corporate entities. After decades of attempting to promulgate human rights obligations for multinational corporations, the existing legal frameworks in place fall short of protecting individuals from the human rights abuses of multinational corporations. The Global Compact and Guiding Principles are proof of the United Nations’ unwillingness to impose international legal obligations on corporate actors. In June 2014, the Human Rights Council adopted a resolution to draft international legally binding human rights norms for business entities; however, key players in the international arena have already announced they will not cooperate with such efforts. This Note, through an overview of the existing corporate accountability frameworks and a study of Newmont Mining’s Minas Conga project in Peru, argues that binding international human rights obligations on corporations are necessary to fully protect human rights. Where states refuse to or simply cannot uphold their duty to protect individuals from transnational businesses’ human rights transgressions, there must exist mechanisms to pursue justice directly against the multinational corporation.
37
43068
Critical Role of Lipid Rafts in Influenza a Virus Binding to Host Cell
Abstract:
Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.
36
81952
Biomimetic Building Envelopes to Reduce Energy Consumption in Hot and Dry Climates
Abstract:
Energy shortage became a worldwide major problem since the 1970s, due to high energy consumption. Buildings are the primary energy users which consume 40% of global energy consumption, in which, 40%-50% of building’s energy usage is consumed due to its envelope. In hot and dry climates, 40% of energy is consumed only for cooling purpose, which implies major portion of energy savings can be worked through the envelopes. Biomimicry can be one solution for extracting efficient thermoregulation strategies found in nature. This paper aims to identify different biomimetic building envelopes which shall offer a higher potential to reduce energy consumption in hot and dry climates. It focuses on investigating the scope for reducing energy consumption through biomimetic approach in terms of envelopes. An in-depth research on different biomimetic building envelopes will be presented and analyzed in terms of heat absorption, in addition to, the impact it had on reducing the buildings energy consumption. This helps to understand feasible biomimetic building envelopes to mitigate heat absorption in hot and dry climates.
35
37694
A Comparative Case Study of the Impact of Square and Yurt-Shape Buildings on Energy Efficiency
Abstract:
Regions with extreme climate conditions such as Astana city require energy saving measures to increase the energy performance of buildings which are responsible for more than 40% of total energy consumption. Identification of optimal building geometry is one of the key factors to be considered. The architectural form of a building has the impact on space heating and cooling energy use, however, the interrelationship between the geometry and resultant energy use is not always readily apparent. This paper presents a comparative case study of two prototypical buildings with compact building shape to assess its impact on energy performance.
34
13000
Difference in the Expression of CIRBP, RBM3 and HSP70 in the Myocardium and Cerebellum after Death by Hypothermi a and Carbon Monoxide Poisoning
Abstract:
We studied the expression of hypoxia-related antigens (e.g., cold-inducible antigens and apoptotic antigens) in the myocardium and the cerebellumthat were obtained from individuals after death by carbon monoxide or hypothermia. The immunohistochemistry results revealed that expression of cold-inducible RNA binding protein (CIRBP) and RNA-binding protein 3 (RBM3) may be associated with hpyothermic and the hypoxic conditions. The expression of CIRBP and RBM3 in the myocardium was different from their expression in the cerebellum, especially in the Purkinje cells. The results indicate that agonal duration influences antigen expression. In the hypothermic condition, the myocardium uses more ATP since the force of the excitation-contraction coupling of the myocardium increases by more than 400% when the experimental temperature is reduced from 35°C to 25°C. The results obtained in this study indicate that physicians should pay attention to the myocardium when cooling the patient’s body to protect the brain.
33
40892
Performance of Environmental Efficiency of Energy Consumption in OPEC Countries
Abstract:
Global awareness on energy security and climate change has created much interest in assessing energy efficiency performance. A number of previous studies have contributed to evaluate energy efficiency performance using different analytical techniques among which data envelopment analysis (DEA) has recently received increasing attention. Most of DEA-related energy efficiency studies do not consider undesirable outputs such as CO2 emissions in their modeling framework, which may lead to biased energy efficiency values. Within a joint production frame work of desirable and undesirable outputs, in this paper we construct energy efficiency performance index for measuring energy efficiency performance by using environmental DEA model with CO2 emissions. We finally apply the index proposed to assess the energy efficiency performance in OPEC over time.
32
20166
Synthesis and Characterization of Mixed ligand complexes of Bipyridyl and Glycine with Different Counter Anions as Functional Antioxidant Enzyme Mimics
Abstract:
A series of mixed ligand complexes, viz., [Cu(BPy)(Gly)X]Y {X = Cl (1), Y = 0; X = 0, Y = ClO4- (2); X = H2O, Y = NO3- (3); X = H2O, Y = CH3COO- (4); and [Cu(BPy)(Gly)-(H2O)]2(SO4) (5) have been synthesized. Their structures and properties were characterized by elemental analysis, thermal analaysis, IR, UV–vis, and ESR spectroscopy, as well as electrochemical measurements including cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. Complexes 1 and 2 formed slightly distorted square-pyramidal coordination geometries of CuN3OCl and CuN3O2, respectively in which the N,O-donor glycine and N,N-donor bipyridyl bind at the basal plane with chloride ion or water as the axial ligand. Complex 3 shows square planar CuN3O coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The superoxide dismutase and catalase-like activities of all complexes were tested and were found to be promising candidates as durable electron-transfer catalyst being close to the efficiency of the mimicking enzymes displaying either catalase or tyrosinase activity to serve for complete reactive oxygen species (ROS) detoxification, both with respect to superoxide radicals and related peroxides. The DNA binding interaction with super coiled pGEM-T plasmid DNA was investigated by using spectral (absorption and emission) titration and electrochemical techniques. The results revealed that DNA intercalate with complexes 1 and 2 through the groove binding mode. The calculated intrinsic binding constant (Kb) of 1 and 2 were 4.71 and 2.429 × 105 M−1, respectively. Gel electrophoresis study reveals the fact that both complexes cleave super coiled pGEM-T plasmid DNA to nicked and linear forms in the absence of any additives. On the other hand, the interaction of both complexes with DNA, the quasi-reversible CuII/CuI redox couple slightly improves its reversibility with considerable decrease in current intensity. All the experimental results indicate that the bipyridyl mixed copper(II) complex (1) intercalate more effectively into the DNA base pairs.
31
20279
Comparative in silico and in vitro Study of N-(1-Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent
Abstract:
Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.
30
42935
Environment Problems of Energy Exploitation and Utilization in Nigeria
Abstract:
The problems placed on the environment as a result of energy generation and usage in Nigeria is: potential damage to the environment health by CO, CO2, SOx, and NOx, effluent gas emissions and global warming. For instance in the year 2004 in Nigeria energy consumption was 58% oil and 34% natural gas but about 94 million metric tons of CO2 was emitted out of which 64% came from fossil fuels while about 35% came from fuel wood. The findings from this research on how to alleviate these problems are that long term sustainable development solutions should be enhanced globally; energy should be used more rationally renewable energy resources should be exploited and the existing emissions should be controlled to tolerate limits because the increase in energy demand in Nigeria places enormous strain on current energy facilities.
29
61802
Nearly Zero Energy Building: Analysis on How End-Users Affect Energy Savings Targets
Abstract:
One of the most important energy challenge of the European policies is the transition to a Net Zero Energy Building (NZEB) model. A NZEB is a new concept of building that has the aim of reducing both the energy consumption and the carbon emissions to nearly zero of the course of a year. To achieve this nearly zero consumption, apart from being buildings with high efficiency levels, the energy consumed by the building has to be produced on-site. This paper is focused on presenting the results of the analysis developed on basis of real projects’ data in order to quantify the impact of end-users behavior. The analysis is focused on how the behavior of building’s occupants can vary the achievement of the energy savings targets and how they can be limited. The results obtained show that on this kind of project, with very high energy performance, is required to limit the end-users interaction with the system operation to be able to reach the targets fixed.
28
48750
Adsorption Cooling Using Hybrid Energy Resources
Abstract:
HVAC represents a significant part of energy needs in buildings. Integrating renewable energy in cooling processes contributes to reducing primary energy consumption. Sorption refrigeration allows cold production through the use of solar/biomass/geothermal energy or even valuation of waste heat. This work presents an analysis of an experimental bench incorporating an adsorption chiller driven by hybrid energy resources associating solar thermal collectors with a cogeneration gas engine and a geothermal heat pump.
27
8462
Smart Grid Simulator
Abstract:
The Smart Grid Simulator is a computer software based on advanced algorithms which has as the main purpose to lower the energy bill in the most optimized price efficient way as possible for private households, companies or energy providers. It combines the energy provided by a number of solar modules and wind turbines with the consumption of one household or a cluster of nearby households and information regarding weather conditions and energy prices in order to predict the amount of energy that can be produced by renewable energy sources and the amount of energy that will be bought from the distributor for the following day. The user of the system will not only be able to minimize his expenditures on energy fractures, but also he will be informed about his hourly consumption, electricity prices fluctuation and money spent for energy bought as well as how much money he saved each day and since he installed the system. The paper outlines the algorithm that supports the Smart Grid Simulator idea and presents preliminary test results that support the discussion and implementation of the system.
26
53080
Molecular Design and Synthesis of Heterocycles Based Anticancer Agents
Abstract:
Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.
25
33896
Energy Consumption and Energy Conservation Potential for HVAC System in Commercial Buildings Sector in India
Abstract:
In order to reduce energy consumption for sustainable development, continuous energy consumption tracking of building energy systems are essential. In this paper an assessment study has been done to identify the energy consumption & energy conservation potential for commercial buildings sector in Karnataka state, India. There are a total of 326 commercial buildings in the state of Karnataka who has qualified as designated consumers (i.e., having a Contract Demand ≥ 600 KVA), was consider for the study. It has estimated that the annual electricity sale to commercial sector is 3.62 Billion Units (BU) in alone Karnataka State, India, which is an account for 9.57 % of the total electricity sold. The commercial sector constitutes Government & private establishments, hospitals, hotels, restaurants, educational institutions, malls etc. Total 326 commercial buildings in the state accounting for annual energy consumption of 1295.72 Million Units (MU) which works out to about 35% of the sectoral consumption. The annual energy savings potential for 326 commercial buildings is assessed to be 0.25 BU.
24
110705
Intriguing Modulations in the Excited State Intramolecular Proton Transfer Process of Chrysazine Governed by Host-Guest Interactions with Macrocyclic Molecules
Abstract:
Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.
23
90415
Detection and Quantification of Ochratoxin A in Food by Aptasensor
Abstract:
Governments and international instances are trying to improve the food safety system to prevent, reduce or avoid the increase of food borne diseases. This food risk is one of the major concerns for the humanity. The contamination by mycotoxins is a threat to the health and life of humans and animals. One of the most common mycotoxin contaminating feed and foodstuffs is Ochratoxin A (OTA), which is a secondary metabolite, produced by Aspergillus and Penicillium strains. OTA has a chronic toxic effect and proved to be mutagenic, nephrotoxic, teratogenic, immunosuppressive, and carcinogenic. On the other side, because of their high stability, specificity, affinity, and their easy chemical synthesis, aptamer based methods are applied to OTA biosensing as alternative to traditional analytical technique. In this work, five aptamers have been tested to confirm qualitatively and quantitatively their binding with OTA. In the same time, three different analytical methods were tested and compared based on their ability to detect and quantify the OTA. The best protocol that was established to quantify free OTA from linked OTA involved an ultrafiltration method in green coffee solution with. OTA was quantified by HPLC-FLD to calculate the binding percentage of all five aptamers. One aptamer (The most effective with 87% binding with OTA) has been selected to be our biorecognition element to study its electrical response (variation of electrical properties) in the presence of OTA in order to be able to make a pairing with a radio frequency identification (RFID). This device, which is characterized by its low cost, speed, and a simple wireless information transmission, will implement the knowledge on the mycotoxins molecular sensors (aptamers), an electronic device that will link the information, the quantification and make it available to operators.
22
77563
Contribution to the Success of the Energy Audit in the Industrial Environment: A Case Study about Audit of Interior Lighting for an Industrial Site in Morocco
Abstract:
The energy audit is the essential initial step to ensure a good definition of energy control actions. The in-depth study of the various energy-consuming equipments makes it possible to determine the actions and investments with best cost for the company. The analysis focuses on the energy consumption of production equipment and utilities (lighting, heating, air conditioning, ventilation, transport). Successful implementation of this approach requires, however, to take into account a number of prerequisites. This paper proposes a number of useful recommendations concerning the energy audit in order to achieve better results, and a case study concerning the lighting audit of a Moroccan company by showing the gains that can be made through this audit.
21
90768
Development of Electrochemical Biosensor Based on Dendrimer-Magnetic Nanoparticles for Detection of Alpha-Fetoprotein
Abstract:
Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.
20
26286
Measuring Environmental Efficiency of Energy in OPEC Countries
Abstract:
Data envelopment analysis (DEA) has recently gained popularity in energy efficiency analysis. A common feature of the previously proposed DEA models for measuring energy efficiency performance is that they treat energy consumption as an input within a production framework without considering undesirable outputs. However, energy use results in the generation of undesirable outputs as byproducts of producing desirable outputs. Within a joint production framework of both desirable and undesirable outputs, this paper presents several DEA-type linear programming models for measuring energy efficiency performance. In addition to considering undesirable outputs, our models treat different energy sources as different inputs so that changes in energy mix could be accounted for in evaluating energy efficiency. The proposed models are applied to measure the energy efficiency performances of 12 OPEC countries and the results obtained are presented.
19
107231
Binding of Avian Excreta-Derived Enteroccoci to a Streptococcocus mutans: Implications for Avian to Human Transmission
Abstract:
Since Enterococci has been implicated in oral disease, we hypothesized the transmission of avian Enterococci to humans via fecal-oral transmission facilitated by adherence to dental plaque. To demonstrate the capability of Enterococci to bind to a dental plaque we filtered avian excreta and incubated the filtrate on a sucrose-induced, Streptococcus mutans biofilm. The biofilm was washed several times with a detergent to remove bacteria binding non-specifically to the biofilm, DNA was isolated from the biofilm, 16S rDNA was amplified, sequenced by Ion Torrent DNA sequencing and analyzed with bioinformatics. Enterococci and other known bacterial pathogens were shown to adhere to the biofilm. Culturing the washed biofilm with Bile Esculin Azide (BEA) agar also confirmed the presence of Enterococci as verified with Sanger sequencing. The results suggest that Enteroccoci in avian excreta has the ability to adhere to human dental plaque and may be a mechanism of entry when humans encounter contaminated aerosols, water or food.
18
16574
Temperature and Substrate Orientation Effects on the Thermal Stability of Graphene Sheet Attached on the Si Surface
Abstract:
The graphene binding with silicon substrate has apparently Schottky barriers property, which can be used in the application of solar cell and light source. Because graphene has only one atom layer, the atomistic structure of graphene binding with the silicon surface plays an important role to affect the properties of graphene. In this work, temperature effect on the morphology of graphene sheet attached on different crystal planes of silicon substrates are investigated by Molecular dynamics (MD) (LAMMPS, developed by Sandia National Laboratories). The results show that the covered graphene sheet would cause the structural deformation of the surface Si atoms of stubtrate. To achieve a stable state in the binding process, the surface Si atoms would adjust their position and fit the honeycomb structure of graphene after the graphene attaches to the Si surface. The height contour of graphene on different plane of silicon surfaces presents different pattern, leading the local residual stress at the interface. Due to the high density of dangling bond on the Si (111)7x7 surface, the surface of Si(111)7x7 is not matching with the graphene so well in contrast with Si(100)2x1and Si(111)2x1. Si(111)7x7 is found that only partial silicon adatoms are rearranged on surface after the attachment when the temperature is lower than 200K, As the temperature gradually increases, the deformation of surface structure becomes significant, as well as the residue stress. With increasing temperature till the 815K, the graphene sheet begins to destroy and mixes with the silicon atoms. For the Si(100)2x1 and Si(111)2x1, the silicon surface structure keep its structural arrangement with a higher temperature. With increasing temperature, the residual stress gradually decrease till a critical temperatures. When the temperature is higher than the critical temperature, the residual stress gradually increases and the structural deformation is found on the surface of the Si substrates.
17
62192
Synergy Effect of Energy and Water Saving in China's Energy Sectors: A Multi-Objective Optimization Analysis
Abstract:
The ‘11th five-year’ and ‘12th five-year’ plans have clearly put forward to strictly control the total amount and intensity of energy and water consumption. The synergy effect of energy and water has rarely been considered in the process of energy and water saving in China, where its contribution cannot be maximized. Energy sectors consume large amounts of energy and water when producing massive energy, which makes them both energy and water intensive. Therefore, the synergy effect in these sectors is significant. This paper assesses and optimizes the synergy effect in three energy sectors under the background of promoting energy and water saving. Results show that: From the perspective of critical path, chemical industry, mining and processing of non-metal ores and smelting and pressing of metals are coupling points in the process of energy and water flowing to energy sectors, in which the implementation of energy and water saving policies can bring significant synergy effect. Multi-objective optimization shows that increasing efforts on input restructuring can effectively improve synergy effects; relatively large synergetic energy saving and little water saving are obtained after solely reducing the energy and water intensity of coupling sectors. By optimizing the input structure of sectors, especially the coupling sectors, the synergy effect of energy and water saving can be improved in energy sectors under the premise of keeping economy running stably.
16
24799
Comparative DNA Binding of Iron and Manganese Complexes by Spectroscopic and ITC Techniques and Antibacterial Activity
Abstract:
Interaction of Schiff base complexes of iron and manganese (iron [N, N’ Bis (5-(triphenyl phosphonium methyl) salicylidene) -1, 2 ethanediamine) chloride, [Fe Salen]Cl, manganese [N, N’ Bis (5-(triphenyl phosphonium methyl) salicylidene) -1, 2 ethanediamine) acetate) with DNA were investigated by spectroscopic and isothermal titration calorimetry techniques (ITC). The absorbance spectra of complexes have shown hyper and hypochromism in the presence of DNA that is indication of interaction of complexes with DNA. The linear dichroism (LD) measurements confirmed the bending of DNA in the presence of complexes. Furthermore, isothermal titration calorimetry experiments approved that complexes bound to DNA on the base of both electrostatic and hydrophobic interactions. Furthermore, ITC profile exhibits the existence of two binding phases for the complex. Antibacterial activity of ligand and complexes were tested in vitro to evaluate their activity against the gram positive and negative bacteria.
15
70600
Renewable Energy in Morocco: Photovoltaic Water Pumping System
Abstract:
Renewable energies have a major importance of Morocco's new energy strategy. The geographical location of the Kingdom promotes the development of the use of solar energy. The use of this energy reduces the dependence on imports of primary energy, meets the growing demand for water and electricity in remote areas encourages the deployment of a local industry in the renewable energy sector and Minimize carbon emissions. Indeed, given the importance of the radiation intensity received and the duration of the sunshine, the country can cover some of its solar energy needs. The use of solar energy to pump water is one of the most promising application, this technique represents a solution wherever the grid does not exist. In this paper, we will present a presentation of photovoltaic pumping system components, and the important solar pumping projects installed in Morocco to supply water from remote area.
14
24234
Technical and Economic Environment in the Polish Power System as the Basis for Distributed Generation and Renewable Energy Sources Development
Abstract:
The article raises the issue of the development of local renewable energy sources and the production of distributed energy in context of improving the reliability of the Polish Power System and the beneficial impact on local and national energy security. The paper refers to the current problems of local governments in the process of investment in the area of distributed energy projects, and discusses the issues of the future role and cooperation within the local power plants and distributed energy. Attention is paid to the local communities the chance to raise their own resources and management of energy fuels (biomass, wind, gas mining) and improving the local energy balance. The material presented takes the issue of the development of the energy potential of municipalities and future cooperation with professional energy. As an example, practical solutions used in one of the communes in Silesia.
13
13368
Reproducibility of Dopamine Transporter Density Measured with I-123-N-ω-Fluoropropyl-2β-Carbomethoxy-3β-(4-Iodophenyl)Nortropane SPECT in Phantom Studies and Parkinson’s Disease Patients
Abstract:
Objectives: The objective of this study was to evaluate the reproducibility of I-123-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4- iodophenyl) nortropane (I-123 FP-CIT) SPECT by using specific binding ratio (SBR) in phantom studies and Parkinson’s Disease (PD) patients. Methods: We made striatum phantom originally and confirmed reproducibility. The phantom studies changed head position and accumulation of FP-CIT, each. And image processing confirms influence on SBR by 30 cases. 30 PD received a SPECT for 3 hours post injection of I-123 FP-CIT 167MBq. Results: SBR decreased in rotatory direction by the patient position by the phantom studies. And, SBR improved the influence after the attenuation and the scatter correction in the cases (y=0.99x+0.57 r2=0.83). However, Stage II recognized dispersion in SBR by low accumulation. Conclusion: Than the phantom studies that assumed the normal cases, the SPECT image after the attenuation and scatter correction had better reproducibility.
12
10443
Disperse Innovation in the Turning German Energy Market
Authors:
Abstract:
German energy market is under historical change. Turning-off the nuclear power plants and intensive subsidization of the renewable energies causes a paradigm change from big central energy production and distribution to more local structures, bringing the energy production near to the consumption. The formerly big energy market with only a few big energy plants and grid operating companies is changing into a disperse market with growing numbers of small and medium size companies (SME) generating new value-added products and services. This change in then energy market, in Germany called the “Energiewende”, inverts also the previous innovation system. Big power plants and large grids required also big operating companies. Innovations in the energy market focused mainly on big projects and complex energy technologies. Innovation in the new energy market structure is much more dispersed. Increasing number of SME is now able to develop energy production and storage technologies, smart technologies to control the grids, and numerous new energy related services. Innovation is now regional distributed, which is a remarkable problem for the old big energy companies. The paper will explain the change in the German energy market and the paradigm change as well as the consequences for the innovation structure in the German energy market. It will show examples how SME participate from this change and how innovation systems, as well for the big companies and for SME, can be adapted.
11
20261
A Paradigm Shift in Energy Policy and Use: Exergy and Hybrid Renewable Energy Technologies
Abstract:
Sustainable energy use is exploiting energy resources within acceptable levels of global resource depletion without destroying the ecological balance of an area. In the context of sustainability, the rush to quell the energy crisis of the fossil fuels of the 1970's by embarking on nuclear energy technology has now been seen as a disaster. In the circumstance, action (policy) suggested in this study to avoid future occurrence is exergy maximization/entropy generation minimization and the use is renewable energy technologies that are hybrid based. Thirty-two (32) selected hybrid renewable energy technologies were assessed with respect to their energetic efficiencies and entropy generation. The results indicated that determining which of the hybrid technologies is the most efficient process and sustainable is a matter of defining efficiency and knowing which of them possesses the minimum entropy generation.
10
61200
An Electromechanical Device to Use in Road Pavements to Convert Vehicles Mechanical Energy into Electrical Energy
Abstract:
With the growing need for alternative energy sources, research into energy harvesting technologies has increased considerably in recent years. The particular case of energy harvesting on road pavements is a very recent area of research, with different technologies having been developed in recent years. However, none of them have presented high conversion efficiencies nor technical or economic viability. This paper deals with the development of a mechanical system to implement on a road pavement energy harvesting electromechanical device, to transmit energy from the device surface to an electrical generator. The main goal is to quantify the energy harvesting, transmission and conversion efficiency of the proposed system and compare it with existing systems. Conclusions about the system’s efficiency are presented.
9
4778
Initiation of Paraptosis-Like PCD Pathway in Hepatocellular Carcinoma Cell Line by Hep88 mAb through the Binding of Mortalin (HSPA9) and Alpha-Enolase
Abstract:
Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.
8
30590
Identifying the Factors affecting on the Success of Energy Usage Saving in Municipality of Tehran
Abstract:
For the purpose of optimizing and developing energy efficiency in building, it is required to recognize key elements of success in optimization of energy consumption before performing any actions. Surveying Principal Components is one of the most valuable result of Linear Algebra because the simple and non-parametric methods are become confusing. So that energy management system implemented according to energy management system international standard ISO50001:2011 and all energy parameters in building to be measured through performing energy auditing. In this essay by simulating used of data mining, the key impressive elements on energy saving in buildings to be determined. This approach is based on data mining statistical techniques using feature selection method and fuzzy logic and convert data from massive to compressed type and used to increase the selected feature. On the other side, influence portion and amount of each energy consumption elements in energy dissipation in percent are recognized as separated norm while using obtained results from energy auditing and after measurement of all energy consuming parameters and identified variables. Accordingly, energy saving solution divided into 3 categories, low, medium and high expense solutions.
7
8079
Realization of Sustainable Urban Society by Personal Electric Transporter and Natural Energy
Abstract:
In regards to the energy sector in the modern period, two points were raised. First is a vast and growing energy demand, and second is an environmental impact associated with it. The enormous consumption of fossil fuel to the mobile unit is leading to its rapid depletion. Nuclear power is not the only problem. A modal shift that utilizes personal transporters and independent power, in order to realize a sustainable society, is very effective. The paper proposes that the world will continue to work on this. Energy of the future society, innovation in battery technology and the use of natural energy is a big key. And it is also necessary in order to save on energy consumption.
6
99827
Generating a Multiplex Sensing Platform for the Accurate Diagnosis of Sepsis
Abstract:
Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.
5
67473
Optimal Planning and Design of Hybrid Energy System for Taxila University
Abstract:
Renewable energy resources are being realized as suitable options in hybrid energy planning for on-grid and micro grid. In this paper, operation, planning and optimal design of on-grid distributed energy resources based hybrid system are investigated. The aim is to minimize the cost of the overall energy system keeping in view the environmental emission and minimum penetration of conventional energy resources. Seven grid connected different case studies including diesel only, diesel-renewable based, and renewable based only are designed to perform economic analysis, operational planning and emission. Sensitivity analysis is implemented to investigate the impact of different parameters on the performance of energy resources.
4
70831
Antiplasmodial Activity of Drimane Sesquiterpene Isolated from Warburgia salutaris
Abstract:
Background: Malaria remains a life-threatening disease in tropical regions despite the advances in the treatment of this disease, it still remains a significant burden as some parasites have become resistant to the currently available drugs. This has created a necessity for the development of alternative, more efficient antimalarial drugs. Warburgia salutaris is a traditional medicinal plant used in malaria treatment by Zulu traditional healers. Materials and methods: The W. salutaris stem-bark was extracted with dichloromethane and the compound was isolated through column chromatography. The compound was identified and characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and MS) and the structure was also confirmed by x-ray crystallography. The anti-plasmodial activity (in vitro) was studied on NF54 Plasmodium falciparum strain (CQS). Cytotoxicity was measured using the MTT assay on HEK239 and HEPG2 cell lines. Docking of Mukaadial acetate was conducted in AutoDock Vina. Structural modifications were conducted in UCSF Chimera and molecular interactions examined in LigPlot. Results: The compound, Mukaadial Acetate showed appreciable inhibition (IC50 0.44±0.10 µg/ml) of the parasite growth and cytotoxicity activity of 0.124±0.109 and 0.199±0.083 (µg/ml) on HEK293 and HEPG2 cells respectively. Molecular docking revealed that Mukaadial Acetate binds to the purine, pyrophosphate and ribose binding sites of the PfHGXPRT with an optimum binding conformation and forms hydrogen bond, steric and hydrophobic interactions with the residues inhabiting the respective binding sites. Conclusion: It is apparent that W. salutaris contains components (including Mukaadial Acetate) that exhibit antimalarial activity. This study scientifically validates the use of this plant in folk medicine.
3
15622
Energy Consumption in China’s Urban Water Supply System
Abstract:
In a water supply system, a great deal of care goes into sourcing, treating and delivering water to consumers, but less thought is given to the energy consumed during these processes. This study uses 2011 data to quantify energy use for urban water supply in China and investigates population density as a possible influencing factor. The objective is to provide information that can be used to develop energy-conscious water infrastructure policy, calculate the energy co-benefits of water conservation and compare energy use between China and other countries. The average electrical energy intensity and per capita electrical energy consumption for urban water supply in China in 2011 were 0.29 kWh/m3 and 33.2 kWh/cap•yr, respectively. Comparison between provinces revealed a direct correlation between energy intensity of urban water supply and population served per unit length of pipe. This could imply energy intensity is lower when more densely populated areas are supplied by relatively dense networks of pipes. This study also found that whereas the percentage of energy used for urban water supply tends to increase with the percentage of population served this increase is slower where water supply is more energy efficient and where a larger percentage of population is already supplied.
2
14080
Rice Serine/Threonine Kinase 1 Is Required for the Stimulation of OsNug2 GTPase Activity
Abstract:
Several GTPases are required for ribosome biogenesis and assembly. We recently characterized rice (Oryza sativa) nuclear/nucleolar GTPase 2 (OsNug2), belonging to the YlqF/YawG family of GTPases, as playing a role in pre-60S ribosomal subunit maturation. To investigate the potential factors involved in regulating the function of OsNug2, yeast two-hybrid screens were carried out using OsNug2 as bait. Rice serine/threonine kinase 1 (OsSTK1) was identified as a potential interacting protein candidate. In vitro pull down and bimolecular fluorescence complementation assays confirmed the interaction between OsNug2 and OsSTK1, and like green fluorescent protein-tagged OsNug2, green fluorescent protein-tagged OsSTK1 was targeted to the nucleus of Arabidopsis protoplasts. OsSTK1 was not found to affect the GTP-binding activity of OsNug2; however, when recombinant OsSTK1 was included in OsNug2 assay reaction mixtures, OsSTK1 increased the GTPase activity of OsNug2. To test whether OsSTK1 phosphorylates OsNug2 in vitro, a kinase assay was performed. OsSTK1 was found to have weak autophosphorylation activity and strongly phosphorylated serine 209 of OsNug2. Yeast complementation testing resulted in a GAL::OsNug2(S209N) mutant-harboring yeast strain exhibiting a growth-defective phenotype on galactose medium at 39°C, divergent from that of a yeast strain harboring GAL::OsNug2. The intrinsic GTPase activity of mutant OsNug2(S209N) was found to be similar to that of OsNug2, was not fully enhanced upon weak binding of OsSTK1. Our findings reported here indicate that OsSTK1 functions as a positive regulator protein of OsNug2 by enhancing the GTPase activity of OsNug2, and that the phosphorylation of serine 209 of OsNug2 is essential for the complete function of OsNug2 in ribosome biogenesis.
1
112034
A Comparison of Energy Calculations for a Single-Family Detached Home with Two Energy Simulation Methods
Authors:
Abstract:
For newly produced houses and energy renovations, an energy calculation needs to be conducted. This is done to verify whether the energy consumption criteria of the house -to reach the energy targets by 2020 and 2050- are in-line with the norms. The main purpose of this study is to confirm whether easy to use energy calculation software or hand calculations used by small companies or individuals give logical results compared to advanced energy simulation program used by researchers or bigger companies. There are different methods for calculating energy consumption. In this paper, two energy calculation programs are used and the relation of energy consumption with solar radiation is compared. A hand calculation is also done to validate whether the hand calculations are still reasonable. The two computer programs which have been used are TMF Energi (the easy energy calculation variant used by small companies or individuals) and IDA ICE - Indoor Climate and Energy (the advanced energy simulation program used by researchers or larger companies). The calculations are done for a standard house from the Swedish house supplier Fiskarhedenvillan. The method is based on having the same conditions and inputs in the different calculation forms so that the results can be compared and verified. The house has been faced differently to see how the orientation affects energy consumption in different methods. The results for the simulations are close to each other and the hand calculation differs from the computer programs by only 5%. Even if solar factors differ due to the orientation of the house, energy calculation results from different computer programs and even hand calculation methods are in line with each other.