scholarly journals SMOG 2 and OpenSMOG: Extending the limits of structure-based models

2021 ◽  
Author(s):  
Antonio B Oliveira ◽  
Vinicius Contessoto ◽  
Asem Hassan ◽  
Sandra Byju ◽  
Ailun Wang ◽  
...  
Keyword(s):  
Large Scale ◽  
Broad Class ◽  
Common Element ◽  
Biomolecular Systems ◽  
Biomolecular Dynamics ◽  
Hybrid Class ◽  
The Common ◽  
Recent Version ◽  
Hiv 1 ◽  
Polymer Ligand

Applying simulations with structure-based (Go-like) models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally-determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e. SMOG) models for any type of polymer-ligand system. Since its original release, user feedback has driven the implementation of numerous enhancements. Here, we describe recent extensions to the software and demonstrate the capabilities of the most recent version, SMOG v2.4. Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.0). To illustrate the utility of these advances, we present several applications of SMOG2 and OpenSMOG, which include systems with millions of atoms, long polymers and explicit ions. We also highlight how one can incorporate non-structure-based (e.g. AMBER-based) energetics to define a hybrid class of models. The representative applications include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid in the presence of explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to apply structure-based models to large and/or intricate biomolecular systems.

Student Perceptions of Community: A Different Perspective

NASPA Journal ◽  
1998 ◽  
Vol 35 (4) ◽  
Author(s):  
Jackie Clark ◽  
Joan Hirt
Keyword(s):  
Student Perceptions ◽  
Large Scale ◽  
Research University ◽  
Small Scale ◽  
Social Environments ◽  
Common Assumption ◽  
Small Communities ◽  
Public Research University ◽  
The Common ◽  
Using Data

The creation of small communities has been proposed as a way of enhancing the educational experience of students at large institutions. Using data from a survey of students living in large and small residences at a public research university, this study does not support the common assumption that small-scale social environments are more conducive to positive community life than large-scale social environments.

Iterative algorithm for a split equilibrium problem and fixed problem for finite asymptotically nonexpansive mappings in Hlbert space

Filomat ◽  
2017 ◽  
Vol 31 (5) ◽  
pp. 1423-1434 ◽  
Author(s):  
Sheng Wang ◽  
Min Chen
Keyword(s):  
Equilibrium Problem ◽  
Iterative Algorithm ◽  
Nonexpansive Mappings ◽  
Common Element ◽  
Fixed Point Set ◽  
Split Equilibrium Problem ◽  
Asymptotically Nonexpansive Mappings ◽  
Asymptotically Nonexpansive ◽  
Point Set ◽  
The Common

In this paper, we propose an iterative algorithm for finding the common element of solution set of a split equilibrium problem and common fixed point set of a finite family of asymptotically nonexpansive mappings in Hilbert space. The strong convergence of this algorithm is proved.

scholarly journals Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 241
Author(s):  
Shaden A. M. Khalifa ◽  
Eslam S. Shedid ◽  
Essa M. Saied ◽  
Amir Reza Jassbi ◽  
Fatemeh H. Jamebozorgi ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Biomedical Applications ◽  
Large Scale ◽  
Biological Activities ◽  
Scale Production ◽  
Pharmacological Activities ◽  
Large Scale Production ◽  
Marine Products ◽  
Hiv 1 ◽  
Successful Phase

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.

scholarly journals A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency

2021 ◽  
pp. 247255522110181
Author(s):  
Andreas Vogt ◽  
Samantha L. Eicher ◽  
Tracey D. Myers ◽  
Stacy L. Hrizo ◽  
Laura L. Vollmer ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Large Scale ◽  
Protein Quality ◽  
Fluorescent Protein ◽  
Triose Phosphate Isomerase ◽  
Pharmacological Intervention ◽  
Screening Assay ◽  
Triose Phosphate ◽  
The Common ◽  
Green Fluorescent

Triose phosphate isomerase deficiency (TPI Df) is an untreatable, childhood-onset glycolytic enzymopathy. Patients typically present with frequent infections, anemia, and muscle weakness that quickly progresses with severe neuromusclar dysfunction requiring aided mobility and often respiratory support. Life expectancy after diagnosis is typically ~5 years. There are several described pathogenic mutations that encode functional proteins; however, these proteins, which include the protein resulting from the “common” TPIE105D mutation, are unstable due to active degradation by protein quality control (PQC) pathways. Previous work has shown that elevating mutant TPI levels by genetic or pharmacological intervention can ameliorate symptoms of TPI Df in fruit flies. To identify compounds that increase levels of mutant TPI, we have developed a human embryonic kidney (HEK) stable knock-in model expressing the common TPI Df protein fused with green fluorescent protein (HEK TPIE105D-GFP). To directly address the need for lead TPI Df therapeutics, these cells were developed into an optical drug discovery platform that was implemented for high-throughput screening (HTS) and validated in 3-day variability tests, meeting HTS standards. We initially used this assay to screen the 446-member National Institutes of Health (NIH) Clinical Collection and validated two of the hits in dose–response, by limited structure–activity relationship studies with a small number of analogs, and in an orthogonal, non-optical assay in patient fibroblasts. The data form the basis for a large-scale phenotypic screening effort to discover compounds that stabilize TPI as treatments for this devastating childhood disease.

scholarly journals A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS

2006 ◽  
Vol 04 (03) ◽  
pp. 639-647 ◽  
Author(s):  
ELEAZAR ESKIN ◽  
RODED SHARAN ◽  
ERAN HALPERIN
Keyword(s):  
Large Scale ◽  
Computational Cost ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Novel Approach ◽  
Maximum Likelihood Criterion ◽  
The Common ◽  
Genomic Regions ◽  
High Computational Cost ◽  
Combining Information

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .

scholarly journals Strong and Weak Convergence Theorems for Equilibrium Problems and Weak Relatively Uniformly Nonexpansive Multivalued Mappings in Banach Spaces

2012 ◽  
Vol 2012 ◽  
pp. 1-13
Author(s):  
Zi-Ming Wang
Keyword(s):  
Weak Convergence ◽  
Equilibrium Problem ◽  
Equilibrium Problems ◽  
Fixed Point Problem ◽  
Common Element ◽  
Multivalued Mappings ◽  
Point Problem ◽  
Strong And Weak Convergence ◽  
Convergence Results ◽  
The Common

Equilibrium problem and fixed point problem are considered. A general iterative algorithm is introduced for finding a common element of the set of solutions to the equilibrium problem and the common set of fixed points of two weak relatively uniformly nonexpansive multivalued mappings. Furthermore, strong and weak convergence results for the common element in the two sets mentioned above are established in some Banach space.

scholarly journals MiDRMpol: A High-Throughput Multiplexed Amplicon Sequencing Workflow to Quantify HIV-1 Drug Resistance Mutations against Protease, Reverse Transcriptase, and Integrase Inhibitors

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 806
Author(s):  
Shambhu G. Aralaguppe ◽  
Anoop T. Ambikan ◽  
Manickam Ashokkumar ◽  
Milner M. Kumar ◽  
Luke Elizabeth Hanna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Polymorphism Analysis ◽  
Resistance Mutations ◽  
Subtype C ◽  
Bioinformatics Pipeline ◽  
Drug Resistance Mutations ◽  
Hiv 1

The detection of drug resistance mutations (DRMs) in minor viral populations is of potential clinical importance. However, sophisticated computational infrastructure and competence for analysis of high-throughput sequencing (HTS) data lack at most diagnostic laboratories. Thus, we have proposed a new pipeline, MiDRMpol, to quantify DRM from the HIV-1 pol region. The gag-vpu region of 87 plasma samples from HIV-infected individuals from three cohorts was amplified and sequenced by Illumina HiSeq2500. The sequence reads were adapter-trimmed, followed by analysis using in-house scripts. Samples from Swedish and Ethiopian cohorts were also sequenced by Sanger sequencing. The pipeline was validated against the online tool PASeq (Polymorphism Analysis by Sequencing). Based on an error rate of <1%, a value of >1% was set as reliable to consider a minor variant. Both pipelines detected the mutations in the dominant viral populations, while discrepancies were observed in minor viral populations. In five HIV-1 subtype C samples, minor mutations were detected at the <5% level by MiDRMpol but not by PASeq. MiDRMpol is a computationally as well as labor efficient bioinformatics pipeline for the detection of DRM from HTS data. It identifies minor viral populations (<20%) of DRMs. Our method can be incorporated into large-scale surveillance of HIV-1 DRM.

scholarly journals Comorbidities associated with HPV and HSV infections among people living with HIV-1 in the Southeastern US: a retrospective clinical cohort study

2019 ◽  
Author(s):  
Yuanfan Ye ◽  
Greer A. Burkholder ◽  
Howard W. Wiener ◽  
Russell Griffin ◽  
Stella Aslibekyan ◽  
...  
Keyword(s):  
Large Scale ◽  
White Women ◽  
Incidence Rates ◽  
People Living With Hiv ◽  
Anogenital Warts ◽  
Gender And Race ◽  
Clinical Cohort ◽  
Southeastern Us ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background The southeastern US is a domestic epicenter for incident HIV with high prevalence of human papillomavirus (HPV) and herpes simplex virus (HSV) co-infections. However, epidemics of HPV and HSV- associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. Methods Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH’s clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and HSV- related CC including anogenital herpetic ulcers were estimated in per 10000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. Results Of the 4,484 PLWH eligible individuals (3,429 men, 1,031 women, and 24 transgender), we observed 1,038 and 425 patients with HPV-and HSV-related CC respectively, and 163 patients with both conditions. The mean log10 viral load (VL) was higher in all of the case groups than the non-cases with neither conditions (5.0) (whereas the median nadir CD4 counts (cells/uL) was higher in the non-cases than in any of the case groups (P<0.05). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P<0.03). White women were also more likely to be diagnosed with cervical HSIL (P=0.023) and cancer (P=0.037) than black women By contrast, herpetic ulcers were more frequent in women than men. Conclusions There were significant differences between gender and race with incidence of HPV- and HSV-related CC among HIV patients. EMR-based studies provide insights on understudied epidemics; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.

PARAMETER IDENTIFICATION FOR ELECTROCHEMICAL MODELS OF LITHIUM ION BATTERIES USING SENSITIVITY ANALYSIS

2021 ◽  
pp. 1-33
Author(s):  
Chitra Dangwal ◽  
Marcello Canova
Keyword(s):  
Parameter Identification ◽  
Large Scale ◽  
Initial Conditions ◽  
Lithium Ion ◽  
Optimization Methods ◽  
Particle Model ◽  
Aerospace Applications ◽  
Novel Approach ◽  
Consistent Solution ◽  
The Common

Abstract Predicting the chemical and physical processes occurring in Lithium-ion cells with high-fidelity electrochemical models is today a critical requirement to accelerate the design and optimization of battery packs for automotive and aerospace applications. One of the common issues associated with electrochemical models is the complexity of parameter identification, particularly when relying only on experimental data obtained via non-invasive techniques. This paper presents a novel approach to improve the common methods of parameter calibration that consists of matching the predicted terminal voltage to test data via optimization methods. The study is conducted for an NMC-graphite cell, modeled using a reduced order Extended Single Particle Model (ESPM). The proposed approach relies on using a large-scale Particle Swarm Optimization (PSO), modified by including a term that accounts for the parameter sensitivity information, such that the rate of convergence and robustness of the algorithm to obtain a consistent solution in the presence of uncertainties in the initial conditions are significantly improved.

Sign in / Sign up

Export Citation Format

Share Document