Search results for: chitin binding domain

Authors: Sadiya S. Silvee

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.

Keywords: death reference, sentencing factor, sentencing guideline, criminal justice system and constitution

Procedia PDF Downloads 176

Authors: Deepshikha Verma, V. N. Rajasekharan Pillai

Abstract:

The present study reports the synthesis of cyclic PNC-28 peptides with solid-phase peptide synthesis method. In the first step, we synthesize the linear PNC-28 Peptide and in the second step, we cyclize (N-to-C or head-to-tail cyclization) the linear PNC-28 peptide. The molecular formula of cyclic PNC-28 peptide is C64H88N12O16 and its m/z mass is ≈1233.64. Elemental analysis of cyclic PNC-28 is C, 59.99; H, 6.92; N, 13.12; O, 19.98. The characterization of LC-MS, CD, FT-IR, and 1HNMR has been done to confirm the successful synthesis and cyclization of linear PNC-28 peptides.

Keywords: CD, FTIR, 1HNMR, cyclic peptide

Procedia PDF Downloads 130

Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

Abstract:

Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST, and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands, cannabinol, and cannabidiol, were obtained from PubChem. After the necessary process of the obtained files, AutoDock Vina was used to perform molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

Procedia PDF Downloads 110

Authors: Sofia Meacham

Abstract:

In this abstract paper, the Domain-Specific Languages (DSL) evaluation will be presented based on existing literature and years of experience developing DSLs for several domains. The domains we worked on ranged from AI, business applications, and finances/accounting to health. In general, DSLs have been utilised in many domains to provide tailored and efficient solutions to address specific problems. Although they are a reputable method among highly technical circles and have also been used by non-technical experts with success, according to our knowledge, there isn’t a commonly accepted method for evaluating them. There are some methods that define criteria that are adaptations from the general software engineering quality criteria. Other literature focuses on the DSL usability aspect of evaluation and applies methods such as Human-Computer Interaction (HCI) and goal modeling. All these approaches are either hard to introduce, such as the goal modeling, or seem to ignore the domain-specific focus of the DSLs. From our experience, the DSLs have domain-specificity in their core, and consequently, the methods to evaluate them should also include domain-specific criteria in their core. The domain-specific criteria would require synergy between the domain experts and the DSL developers in the same way that DSLs cannot be developed without domain-experts involvement. Methods from agile and other software engineering practices, such as co-creation workshops, should be further emphasised and explored to facilitate this direction. Concluding, our latest experience and plans for DSLs evaluation will be presented and open for discussion.

Keywords: domain-specific languages, DSL evaluation, DSL usability, DSL quality metrics

Procedia PDF Downloads 103

Authors: H. Kelkoul, Y. Zaz

Abstract:

Nowadays, the vigorous popularity of video processing techniques has resulted in an explosive growth of multimedia data illegal use. So, watermarking security has received much more attention. The purpose of this paper is to explore some watermarking techniques in order to observe their specificities and select the finest methods to apply in digital cinema domain against movie piracy by creating an invisible watermark that includes the date, time and the place where the hacking was done. We have studied three principal watermarking techniques in the frequency domain: Spread spectrum, Wavelet transform domain and finally the digital cinema watermarking transform domain. In this paper, a detailed technique is presented where embedding is performed using direct sequence spread spectrum technique in DWT transform domain. Experiment results shows that the algorithm provides high robustness and good imperceptibility.

Keywords: digital cinema, watermarking, wavelet DWT, spread spectrum, JPEG2000 MPEG4

Procedia PDF Downloads 251

Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

Abstract:

Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis, were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands cannabinol and cannabidiol were obtained from PubChem. After a necessary process of the obtained files, AutoDock Vina was used to performing molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

Procedia PDF Downloads 118

Authors: So-Young Ju, Sung-Mi Jo, Eui-Rim Jeong

Abstract:

In this paper, based on the conventional single carrier frequency domain equalization (SC-FDE) structure, we propose a new SC-FDE structure to cope with narrowband jammer. In the conventional SC-FDE structure, channel estimation is performed in the time domain. When a narrowband jammer exists, time-domain channel estimation is very difficult due to high power jamming interference, which degrades receiver performance. To relieve from this problem, a new SC-FDE frame is proposed to enable channel estimation under narrow band jamming environments. In this paper, we proposed a modified SC-FDE structure that can perform channel estimation in the frequency domain and verified the performance via computer simulation.

Keywords: channel estimation, jammer, pilot, SC-FDE

Procedia PDF Downloads 475

Authors: Ashrafosadat Mousavi Laer, Elaheh Moravej

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.

Keywords: Shahnameh, Safavid era, bookbinding, beat cover, burning cover

Procedia PDF Downloads 238

Authors: Sonam Kumari

Abstract:

Tuberculosis is the deadliest disease worldwide. Millions of people lose their lives every year due to this disease. It has turned lethal due to the erratic nature of its causative organism, Mycobacterium tuberculosis (Mtb). Mtb tends to enter into an inactive, dormant state and emerge to replicating state upon encountering favorable conditions. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes. Mtb has seven such proteins (WhiB1 to WhiB7). WhiB proteins are transcriptional regulators; they regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical parameters of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: mycobacterium tuberculosis, TB, whiB proteins, ITC

Procedia PDF Downloads 97

Authors: Ishan Tank, Ashmita Rupal, Sanjay Kumar Sharma

Abstract:

Concrete, a widely used building material, has cement as its main constituent. An excessive amount of emissions are released into the atmosphere during the manufacture of cement, which is detrimental to the environment. To minimize this problem, innovative materials like geopolymer mortar (GPM) seem to be a better alternative. By using fly ash-based geopolymer instead of standard cement mortar as a binding ingredient, this concept has been successfully applied to the building sector. The advancement of this technology significantly reduces greenhouse gas emissions and helps in source reduction, thereby minimizing pollution of the environment. In order to produce mortar and use this geopolymer mortar in the development of building materials, the current investigation is properly introducing this geopolymeric material, namely fly ash, as a binder in place of standard cement. In the domain of the building material industry, fly ash based geopolymer is a new and optimistic replacement for traditional binding materials because it is both environmentally sustainable and has good durability. The setting behaviour and strength characteristics of fly ash, when mixed with alkaline activator solution with varied concentration of sodium hydroxide solution, alkaline liquids mix ratio, and curing temperature, must be investigated, though, in order to determine its suitability and application in comparison with the traditional binding material, by activating the raw materials, which include various elements of silica and alumina, finer material known as geopolymer mortar is created. The concentration of the activator solution has an impact on the compressive strength of the geopolymer concrete formed. An experimental examination of compressive strength after 7, 14, and 28 days of fly ash-based geopolymer concrete is presented in this paper. Furthermore, the process of geopolymerization largely relies on the curing temperature. So, the setting time of Geopolymer mortar due to different curing temperatures has been studied and discussed in this paper.

Keywords: geopolymer mortar, setting time, flyash, compressive strength, binder material

Procedia PDF Downloads 71

Authors: Mohan Li

Abstract:

Nowadays, intelligent research technology is more and more important than traditional research methods in urban research work, and this proportion will greatly increase in the next few decades. Frequently such analyzing work cannot be carried without some software engineering knowledge. And here, domain models of urban research will be necessary when applying software engineering knowledge to urban work. In many urban plan practice projects, making rational models, feeding reliable data, and providing enough computation all make indispensable assistance in producing good urban planning. During the whole work process, domain models can optimize workflow design. At present, human beings have entered the era of big data. The amount of digital data generated by cities every day will increase at an exponential rate, and new data forms are constantly emerging. How to select a suitable data set from the massive amount of data, manage and process it has become an ability that more and more planners and urban researchers need to possess. This paper summarizes and makes predictions of the emergence of technologies and technological iterations that may affect urban research in the future, discover urban problems, and implement targeted sustainable urban strategies. They are summarized into seven major domain models. They are urban and rural regional domain model, urban ecological domain model, urban industry domain model, development dynamic domain model, urban social and cultural domain model, urban traffic domain model, and urban space domain model. These seven domain models can be used to guide the construction of systematic urban research topics and help researchers organize a series of intelligent analytical tools, such as Python, R, GIS, etc. These seven models make full use of quantitative spatial analysis, machine learning, and other technologies to achieve higher efficiency and accuracy in urban research, assisting people in making reasonable decisions.

Keywords: big data, domain model, urban planning, urban quantitative analysis, machine learning, workflow design

Procedia PDF Downloads 177

Authors: Thandar Zaw Win, Cho Win Aung, Gaurav Khandal, Sabyasachi Ghosh

Abstract:

Systematic and comparative research on Lorenz ratios for graphene and nonrelativistic systems has been studied to identify their Wiedemann-Franz law violation domain. Fermi energy and temperature are the main governing parameters for deciding the values of the Lorenz ratio, which is basically thermal conductivity divided by electrical conductivity times temperature times Lorenz number. Metals as three-dimensional nonrelativistic electron gas are located at higher Fermi-energy by temperature domain, where Lorenz ratio remains one. Hence, they obey the Wiedemann-Franz law. By creating higher doping in a two-dimensional graphene system, one can again reach a higher Fermi-energy by temperature domain and get a constant Lorenz ratio. For both graphene and nonrelativistic systems, the Lorenz ratio goes below one if we go lower Fermi-energy by temperature domain, which is possible for the graphene system by decreasing the doping concentration. Experimentally observed greater than one Lorenz ratio in this lower Fermi-energy by temperature domain or Dirac Fluid domain indicates that nonfluid expressions of Lorenz ratio should be replaced by fluidtype expressions. We have noticed a divergent trend of Lorenz ratio in the Dirac Fluid domain using its fluid-type expression, and it matches the trend of experimental data.

Keywords: graphene, Lorentz ratio, specific heat, Wiedeann-Franz law

Procedia PDF Downloads 32

Authors: Sang-Hoon Park, Yeji Ho, Gwang-Moon Eom

Abstract:

Fast and accurate detection of Freezing of Gait (FOG) is desirable for appropriate application of cueing which has been shown to ameliorate FOG. Utilization of frequency spectrum of leg acceleration to derive the freeze index requires much calculation and it would lead to delayed cueing. We hypothesized that FOG can be reasonably detected from the time domain amplitude of foot acceleration. A time instant was recognized as FOG if the mean amplitude of the acceleration in the time window surrounding the time instant was in the specific FOG range. Parameters required in the FOG detection was optimized by simulated annealing. The suggested time domain methods showed performances comparable to those of frequency domain methods.

Keywords: freezing of gait, detection, Parkinson's disease, time-domain method

Procedia PDF Downloads 444

Authors: Jun Hong Lee

Abstract:

Background: Many dementia patients complain insomnia and depressive mood, and hypnotics and antidepressants are being prescribed. As prevalence of dementia is increasing, insomnia and depressive mood are becoming more important. Objective: We evaluated insomnia and depression in outpatients of dementia center. Patients and Methods/Material and Methods: We reviewed medical records of the patients who visited outpatients clinic of NHIS Ilsan Hospital Dementia Center during 2016. Results: Total 716 patients are included; Subjective Memory Impairment (SMI) : 143 patients (20%), non-amnestic Mild Cognitive Impairment (MCI): single domain 70 (10%), multiple domain 34 (5%), amnestic MCI: single domain 74 (10%), multiple domain 159 (22%), Early onset Alzheimer´s disease (AD): 9 (1%), AD 121 (17%), Vascular dementia: 62 (9%), Mixed dementia 44 (6%). Hypnotics and antidepressants are prescribed as follows; SMI : hypnotics 14 patients (10%), antidepressants 27 (19%), non-amnestic MCI: single domain hypnotics 9 (13%), antidepressants 12 (17%), multiple domain hypnotics 4 (12%), antidepressants 6 (18%), amnestic MCI: single domain hypnotics 10 (14%), antidepressants 16 (22%), multiple domain hypnotics 22 (14%), antidepressants 24 (15%), Early onset Alzheimer´s disease (AD): hypnotics 1 (11%), antidepressants 2 (22%), AD: hypnotics 10 (8%), antidepressants 36 (30%), Vascular dementia: hypnotics 8 (13%), antidepressants 20 (32%), Mixed dementia: hypnotics 4 (9%), antidepressants 17 (39%). Conclusion: Among the outpatients of Dementia Center, MCI and SMI are majorities, and the number of MCI patients are almost half. Depression is more prevalent in AD, and Vascular dementia than MCI and SMI, and about 22% of patients are being prescribed by antidepressants and 11% by hypnotics.

Keywords: insomnia, depression, dementia, antidepressants, hypnotics

Procedia PDF Downloads 168

Authors: Rupinder Pal Kaur, Vishal Goyal

Abstract:

In this research, a systematic and quantitative engineering-based approach is followed by applying well-known international standards and guidelines to develop a web quality model (PH.WQT- Punjabi and Hindi Website Quality Tester) to measure external quality for websites of government domain that are developed in Punjabi and Hindi. Correspondingly, the model can be used for websites developed in other languages also. The research is valuable to researchers and practitioners interested in designing, implementing and managing websites of government domain Also, by implementing PH.WQT analysis and comparisons among web sites of government domain can be performed in a consistent way.

Keywords: external quality, PH.WQT, indian languages, punjabi and hindi, quality model, websites of government

Procedia PDF Downloads 306

Authors: Volkan Kaya, Ersin Elbasi

Abstract:

Watermarking and stenography are getting importance recently because of copyright protection and authentication. In watermarking we embed stamp, logo, noise or image to multimedia elements such as image, video, audio, animation and text. There are several works have been done in watermarking for different purposes. In this research work, we used watermarking techniques to embed patient information into the medical magnetic resonance (MR) images. There are two methods have been used; frequency domain (Digital Wavelet Transform-DWT, Digital Cosine Transform-DCT, and Digital Fourier Transform-DFT) and spatial domain (Least Significant Bits-LSB) domain. Experimental results show that embedding in frequency domains resist against one type of attacks, and embedding in spatial domain is resist against another group of attacks. Peak Signal Noise Ratio (PSNR) and Similarity Ratio (SR) values are two measurement values for testing. These two values give very promising result for information hiding in medical MR images.

Keywords: watermarking, medical image, frequency domain, least significant bits, security

Procedia PDF Downloads 288

Authors: Tareq Hamadneh, Jochen Merker, Hassan Al-Zoubi

Abstract:

Bernstein's expansion for exponentials in Taylor functions provides lower and upper optimization values for the range of its original function. these values converge to the original functions if the degree is elevated or the domain subdivided. Taylor polynomial can be applied so that the exponential is a polynomial of finite degree over a given domain. Bernstein's basis has two main properties: its sum equals 1, and positive for all x 2 (0; 1). In this work, we prove the existence of fixed points for exponential functions in a given domain using the optimization values of Bernstein. The Bernstein basis of finite degree T over a domain D is defined non-negatively. Any polynomial p of degree t can be expanded into the Bernstein form of maximum degree t ≤ T, where we only need to compute the coefficients of Bernstein in order to optimize the original polynomial. The main property is that p(x) is approximated by the minimum and maximum Bernstein coefficients (Bernstein bound). If the bound is contained in the given domain, then we say that p(x) has fixed points in the same domain.

Keywords: Bernstein polynomials, Stability of control functions, numerical optimization, Taylor function

Procedia PDF Downloads 135

Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

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.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

Procedia PDF Downloads 376

Authors: Kakali Bhadra

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.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

Procedia PDF Downloads 228

Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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.

Keywords: TSPO, molecular modeling, imaging, docking

Procedia PDF Downloads 462

Authors: Sirilak Kongkaew, Pathumwadee Yodmanee, Nopporn Kaiyawet, Arthitaya Meeprasert, Thanyada Rungrotmongkol, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuch, Nawee Kungwan, Supot Hannongbua

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.

Keywords: Behçet’s disease, MD simulations, HMC class I, autoimmune

Procedia PDF Downloads 399

Authors: Niv Papo

Abstract:

Characterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a distinct and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein–protein interactions.

Keywords: drug design, directed evolution, protein engineering, protease inhibition.

Procedia PDF Downloads 24

Authors: Karolis Leonavičius, Dalius Kučiauskas, Dangiras Lukošius, Arnoldas Jasiūnas, Kostas Zdanys, Rokas Stanislovas, Emilis Gegevičius, Žana Kapustina, Juozas Nainys

Abstract:

Screening throughput is a common bottleneck in many research areas, including functional genomics, drug discovery, and directed evolution. High-throughput screening techniques can be classified into two main categories: (i) affinity-based screening and (ii) functional screening. The first one relies on binding assays that provide information about the affinity of a test molecule for a target binding site. Binding assays are relatively easy to establish; however, they reveal no functional activity. In contrast, functional assays show an effect triggered by the interaction of a ligand at a target binding site. Functional assays might be based on a broad range of readouts, such as cell proliferation, reporter gene expression, downstream signaling, and other effects that are a consequence of ligand binding. Screening of large cell or gene libraries based on direct activity rather than binding affinity is now a preferred strategy in many areas of research as functional assays more closely resemble the context where entities of interest are anticipated to act. Droplet sorting is the basis of high-throughput functional biological screening, yet its applicability is limited due to the technical complexity of integrating high-performance droplet analysis and manipulation systems. As a solution, the Droplet Genomics Styx platform enables custom droplet sorting workflows, which are necessary for the development of early-stage or complex biological therapeutics or industrially important biocatalysts. The poster will focus on the technical design considerations of Styx in the context of its application spectra.

Keywords: functional screening, droplet microfluidics, droplet sorting, dielectrophoresis

Procedia PDF Downloads 135

Authors: Matineh Sadat Hosseini Gheidari, Vahid Reza Yazdanpanah

Abstract:

In this paper, we used the empirical tight-binding method (ETBM) with sp3s* approximation and considering the first nearest neighbor with spin-orbit interactions in order to model superlattice structure (SLS) of (AlₓGa₁₋ₓAs)ₘ/(GaAs)ₙ grown on GaAs (100) substrate at 300K. In the next step, we investigated the behavior of the energy gap and wavelength of this superlattice in terms of different thicknesses of core materials and Al mole fractions. As a result of this survey, we found out that as the Al composition increases, the energy gap of this superlattice has an upward trend and ranges from 1.42-1.63 eV. Also, according to the wavelength range that we gained from this superlattice in different Al mole fractions and various thicknesses, we can find a suitable semiconductor for a special light-emitting diode (LED) application.

Keywords: energy gap, empirical tight-binding method, light-emitting diode, superlattice, wavelength

Procedia PDF Downloads 206

Authors: Syed Asif Hassan, Tabrej Khan

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.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

Procedia PDF Downloads 256

Authors: Praveena Nair Sivasankaran, Thomas Arthur Ward, Rubentheren Viyapuri

Abstract:

Paper describes a methodology to fabricate a simplified dragonfly wing structure using balsa wood and red prepreg fibre glass. These simplified wing structures were created for use in Biomimetic Micro Air Vehicles (BMAV). Dragonfly wings are highly corrugated and possess complex vein structures. In order to mimic the wings function and retain its properties, a simplified version of the wing was designed. The simplified dragonfly wing structure was created using a method called spatial network analysis which utilizes Canny edge detection method. The vein structure of the wings were carved out in balsa wood and red prepreg fibre glass. Balsa wood and red prepreg fibre glass was chosen due to its ultra- lightweight property and hence, highly suitable to be used in our application. The fabricated structure was then immersed in a nanocomposite solution containing chitosan as a film matrix, reinforced with chitin nanowhiskers and tannic acid as a crosslinking agent. These materials closely mimic the membrane of a dragonfly wing. Finally, the wings were subjected to a bending test and comparisons were made with previous research for verification. The results had a margin of difference of about 3% and thus the structure was validated.

Keywords: dragonfly wings, simplified, Canny edge detection, balsa wood, red prepreg, chitin, chitosan, tannic acid

Procedia PDF Downloads 331

Authors: Kah Yan How, Peh Fern Ong, Keang Peng Song

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.

Keywords: Porphyromonas gingivalis, periodontal diseases, HmuX, protein characterization

Procedia PDF Downloads 222

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

Abstract:

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

Procedia PDF Downloads 69

Authors: Mona Alharbi

Abstract:

Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.

Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis

Procedia PDF Downloads 248

Authors: G. Levacic, A. Zupan

Abstract:

Application of new technological solutions and installation of new elements into the network requires special attention when investigating its interaction with the existing power system. Special attention needs to be devoted to the occurrence of harmonic resonance. Sources of increasing harmonic penetration could be wind power plants, Flexible Alternating Current Transmission System (FACTS) devices, underground and submarine cable installations etc. Calculation in frequency domain with various software, for example, the software for power systems transients EMTP-RV presents one of the most common ways to obtain the harmonic impedance of the system. Along calculations in frequency domain, such software allows performing of different type of calculations as well as steady-state domain. This paper describes a power system modeling with software EMTP-RV based on data from SCADA/EMS system. The power flow results on 220 kV and 400 kV voltage levels retrieved from EMTP-RV are verified by comparing with power flow results from power transmissions system planning software PSS/E. The determination of the harmonic impedance for the case of remote power plant connection with cable up to 2500 Hz is presented as an example of calculations in frequency domain.

Keywords: power system modeling, frequency domain, steady state, EMTP-RV, PSS/E

Procedia PDF Downloads 322