cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Brain gain versus brain drain: the effects of universities’ mobile students on territorial inequalities
Creators: name: Etzo, Ivan
name: Paci, Raffaele
name: Usala, Cristian
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Plant Biology
subject: FOS: Biological sciences

description: This study examines the relationship between university student mobility and local economic dynamics. Universities shape societies and economies as hubs of knowledge creation and innovation. While recent research highlights the significant impact of university students on local development, there is a gap in understanding the distinct effects of mobile versus resident students. Using data from 90 NUTS-3 provinces in Italy (2013–19), we investigate spatial inequalities generated by students’ mobility. Employing a fixed effects growth model, we find that incoming students boost economic growth in the Centre–North regions (brain gain), while southern provinces suffer reduced growth due to the brain drain.
Optimization of tetanus toxoid ammonium sulfate precipitation process using response surface methodology
Creators: name: Brgles, Marija
name: Prebeg, Pero
name: Kurtović, Tihana
name: Ranić, Jelena
name: Marchetti-Deschmann, Martina
name: Allmaier, Günter
name: Halassy, Beata
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biochemistry
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: Cell Biology
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer

description: Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization–mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation.
Discovery of AcrAB-TolC pump inhibitors: Virtual screening and molecular dynamics simulation approach
Creators: name: Phan, Thien-Vy
name: Nguyen, Vu-Thuy-Vy
name: Nguyen, Cao-Hoang-Hao
name: Vu, Thanh-Thao
name: Tran, Thanh-Dao
name: Le, Minh-Tri
name: Trinh, Dieu-Thuong Thi
name: Tran, Viet-Hung
name: Thai, Khac-Minh
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Virology

description: AcrAB-TolC tripartite efflux pump, which belongs to the RND superfamily, is a main multi-drug efflux system of Escherichia coli (E. coli) because of the broad resistance on various antibiotics. With the discovering of efflux pump inhibitors (EPIs), a combination between these and antibiotics is one of the most promising therapies. Therefore, building a virtual screening model with prediction capacities for the efflux pump inhibitory activities of candidates from DrugBank and ZINC15 dataset, is one of the key goals of this project. Based on the database of 170 diverse chemical structures collected from 28 research journals, two 2D-QSAR models and a 3D-pharmacophore model have been performed. On the AcrB protein (PDB 4DX7), two binding sites have been discovered that match to the hydrophobic trap in the distal pocket and the switch loop in the proximal pocket. After virtual screening processes, twenty candidate AcrAB-TolC inhibitors have been subjected to molecular dynamics simulations, binding free energy calculations and ADMET predictions. The results indicate that three compounds namely DB09233, DB02581, and DB15224 are potential inhibitors with ΔGbind of −42.30 ± 4.58, −40.76 ± 7.30 and −31.06 ± 7.63 kcal.mol−1, respectively. Communicated by Ramaswamy H. Sarma
Stereoselective synthesis of (+)-1-deoxyaltronojirimycin
Creators: name: Righi, Giuliana
name: Mandic’, Emanuela
name: Tirotta, Ilaria
name: Naponiello, Gaia Clara Mercedes
name: Sappino, Carla
name: Marucci, Cristina
name: Tomei, Michela
name: Bovicelli, Paolo
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biochemistry
subject: Medicine
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Ecology
subject: FOS: Biological sciences
subject: Developmental Biology

description: A stereocontrolled, facile and high-yield approach for producing (+)-altroDNJ, has been developed starting from the inexpensive commercial cis 2-butene-1,4-diol. Sharpless epoxidation and a subsequent dihydroxylation were used for the introduction of all stereocentres; finally, the ring closure under basic conditions afforded the piperidine heterocycle.
An Artificial Neural Network based decision support system for cargo vessel operations
Creators: name: Fam, Mei Ling
name: Tay, Zhi Yung
name: Konovessis, Dimitrios
Publisher: name: Singapore Institute of Technology
Year: 2022
Subjects: Naval architecture

description: There is increasing interest in understanding fuel consumption from the perspective of increasing energy efficiency on a vessel. Thus the aim of this paper is to present a new framework for data-driven estimation of fuel consumption by employing a combination of (i) traditional statistical analysis and (ii) Artificial Neural Networks. The output of the analysis is the most frequently occurring fuel-speed curves corresponding to the respective operational profile. The inputs to the model consider important explanatory variables like draft, sea current and wind. The methodology is applied to a case study of a fleet of 9000 TEU vessels, in which telemetry data on the fuel consumption, vessel speed, current, wind direction and strength were analysed. The performance of the method is validated in terms of error estimation criterion like R2 values and against physical phenomena obtained from the data. The results can be used to study the economic and environmental benefits of slow-steaming and or fuel levies, or by extending this part of the model into exergy analysis for a more holistic review of energy saving initiatives.
Acetylcholinesterase inhibition of Alzheimer’s disease: identification of potential phytochemicals and designing more effective derivatives to manage disease condition
Creators: name: Koly, Hazera Khatun
name: Sutradhar, Kakan
name: Rahman, Md Sajjadur
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Molecular Biology
Neuroscience
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified

description: Alzheimer’s disease (AD) is a brain disease characterized by gradual memory loss and cognitive impairments. Acetylcholinesterase (AChE) inhibitors—such as donepezil, memantine, and tacrine—are FDA-approved medications for AD treatment. Due to the lack of their efficacy and higher side effects, many researchers have been searching for effective and safer alternatives. In this study, experimentally proved phytochemicals against brain diseases were screened based on their binding energies to the target site of AChE, pharmacokinetic properties, and drug-likeness. Although some phytochemicals showed higher binding affinities than the control drug (donepezil), they did not show permeability across the blood-brain barrier (BBB). However, berberine, anthocyanin, and diterpene alkaloid can cross the BBB and showed good binding affinities of −10.3, −10.1, and −10.2 kcal/mol, respectively. MD simulation and PCA of the simulation data of the protein and protein-ligand complexes proved that the complexes are stable in the biological environment. A total of 16 derivatives of berberine and 3 derivatives of anthocyanin also showed higher binding energies compared to the binding affinity (−11.5 kcal/mol) of the donepezil. The derivatives were designed by substituting –F, –CF3, –CN, and –NH2, and provided higher docking scores due to increasing of nonbonding interactions. MM/GBSA calculations show that the binding free energies of the best predicted derivatives of diterpene alkaloid, anthocyanin, and berberine (DA22, AC11, and BB40) are −100.4 ± 8.4, −79.3 ± 8.7, and −78.3 ± 10.7 kcal/mol, respectively, with the protein. Overall, this study was successful in finding new, highly effective, and possibly safer inhibitors of AChE. Communicated by Ramaswamy H. Sarma Schematic representation of the drug design process for this study.
ESREL2021_Redacted_v1.pdf
Creators: name: Tay, Zhi Yung
name: Fam, Mei Ling
name: Konovessis, Dimitrios
Publisher: name: Singapore Institute of Technology
Year: 2022
Subjects: Naval architecture

description: There is increasing interest in understanding fuel consumption from the perspective of increasing energy efficiency on a vessel. Thus the aim of this paper is to present a new framework for data-driven estimation of fuel consumption by employing a combination of (i) traditional statistical analysis and (ii) Artificial Neural Networks. The output of the analysis is the most frequently occurring fuel-speed curves corresponding to the respective operational profile. The inputs to the model consider important explanatory variables like draft, sea current and wind. The methodology is applied to a case study of a fleet of 9000 TEU vessels, in which telemetry data on the fuel consumption, vessel speed, current, wind direction and strength were analysed. The performance of the method is validated in terms of error estimation criterion like R2 values and against physical phenomena obtained from the data. The results can be used to study the economic and environmental benefits of slow-steaming and or fuel levies, or by extending this part of the model into exergy analysis for a more holistic review of energy saving initiatives.
Drugs swapping in coronavirus strains: a structural biology view
Creators: name: Gurjar, Vaishali
name: Kamil, Saiyada Iqra
name: Chandra, Anshuman
name: Qamar, Imteyaz
name: Singh, Nagendra
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: Evolutionary Biology
subject: Immunology
subject: FOS: Clinical medicine
subject: Mental Health
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: Coronavirus belongs to the coronaviridae family, having a single-stranded RNA as genetic material of 26–42 kb in size. The first coronavirus infection emerged in 2002, caused by SARS-CoV1. Since then, genome sequences and three-dimensional structures of crucial proteins and enzymes of the virus have been studied in detail. The novel coronavirus (nCoV) outbreak has caused the COVID19 pandemic, which is responsible for the deaths of millions of people worldwide. The nCoV was later renamed as SARS-CoV2. The details of most of the COV proteins are available at the atomic and molecular levels. The entire genome is made up of 12 open reading frames that code for 27 different proteins. The spike surface glycoprotein, the envelope protein, the nucleocapsid protein, and the membrane protein are the four structural proteins which are required for virus attachment, entrance, assembly, and pathogenicity. The remaining proteins encoded are called non-structural (NSPs) and support the survival of the virus. Several non-structural proteins are also validated targets for drug development against coronavirus and are being used for drug design purposes. To perform a comparative study, sequences and three-dimensional structures of four crucial viral enzymes, Mpro, PLpro, RdRp, and EndoU from SARS-CoV1 and SARS-CoV2 variants were analyzed. The key structural elements and ligands recognizing amino acid residues were found to be similar in enzymes from both strains. The significant sequences and structural resemblance also suggest that a drug developed either for SARS-CoV1 or SARS-CoV2 using these enzymes may also have the potential to cross-react. Communicated by Ramaswamy H. Sarma
Solving the Milk Addiction Paradox
Creators: name: Dragone, Davide
name: Raggi, Davide
Publisher: name: Alma Mater Studiorum - Università di Bologna
Year: 2020
Subjects: SECS-P/02 Politica economica

description: The milk addiction paradox refers to an empirical finding in which commodities that are typically considered to be non addictive, such as milk, appear instead to be addictive. This result seems more likely when there is persistence in consumption and when using aggregate data, and it suggests that the AR(2) model typically used in the addiction literature is prone to produce spurious result in favor of rational addiction. Using both simulated and real data, we show that the milk addiction paradox disappears when estimating the data using an AR(1) linear specification that describes the saddle-path solution of the rational addiction model. The AR(1) specification is able to correctly discriminate between rational addiction and simple persistence in the data, to test for the main features of rational addiction, and to produce unbiased estimates of the short and long-run elasticity of demand. These results hold both with individual and aggregated data, and they suggest that, for testing rational addiction, the AR(1) model is a better empirical alternative than the canonical AR(2) model.
Potential molecular mechanism of Guishao Pingchan Recipe in the treatment of Parkinson’s disease based on network pharmacology and molecular docking-Supplementary File 1.zip
Creators: name: Tan, Lijuan
name: liu, hongjie
Publisher: name: figshare
Year: 2022
Subjects: Uncategorized

description: The supplementary files, including main components of GPR, GO enrichment analysis and KEGG Pathway enrichment analysis and molecular docking results, were the content to be uploaded for the article
Potential molecular mechanism of Guishao Pingchan Recipe in the treatment of Parkinson’s disease based on network pharmacology and molecular docking-Supplementary File 2.zip
Creators: name: Tan, Lijuan
name: liu, hongjie
Publisher: name: figshare
Year: 2022
Subjects: Uncategorized

description: The supplementary files, including main components of GPR, GO enrichment analysis and KEGG Pathway enrichment analysis and molecular docking results, were the content to be uploaded for the article
Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F
Creators: name: Nisar, Haseeb
name: Attique, Syed Awais
name: Javaid, Anum
name: Ain, Qurat Ul
name: Butt, Fatima
name: Zaid, Muhammad
name: Shahid, Samiah
name: Nasir, Muhammad Hassan
name: Sadaf, Saima
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Space Science
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger’s Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex. Communicated by Ramaswamy H. Sarma
Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM
Creators: name: Díaz-Pérez, Francisca Isidora
name: Hiden, Ursula
name: Gauster, Martin
name: Lang, Ingrid
name: Konya, Viktoria
name: Akos Heinemann
name: Lögl, Jelena
name: Saffery, Richard
name: Desoye, Gernot
name: Cvitic, Silvija
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Physiology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: Plant Biology
subject: Computational Biology

description: Maternal gestational diabetes (GDM) is associated with hyperglycaemia and hyperinsulinemia in the fetal circulation which consequently may induce endothelial dysfunction in the feto-placental vasculature. In fact, feto-placental vasculature reveals various morphological changes in response to GDM. The cell adhesion molecules (CAMs) ICAM-1, VCAM-1 and E-selectin promote attachment and trans-endothelial migration of leukocytes, and are up regulated in inflammation and endothelial dysfunction. Thus, we hypothesized that the GDM environment upregulates ICAM-1, VCAM-1 and E-selectin in the feto-placental endothelium. We isolated primary feto-placental endothelial cells (fpEC) after normal (n=18) and GDM pregnancy (n=11) and analyzed mRNA (RT-qPCR) and protein expression (Immunoblot) of ICAM-1, VCAM-1 and E-selectin. While other CAMs were unchanged on mRNA and protein levels, ICAM-1 protein was decreased by GDM. Further analysis revealed also a decrease in the release of soluble ICAM-1 (sICAM-1), whose levels correlated negatively with maternal BMI. We conclude that this reduction of ICAM-1 protein species is the result of post-translational regulation, since ICAM-1 mRNA expression was unchanged. In fact, miRNAs targeting ICAM-1 were upregulated in GDM fpEC. Immunohistochemistry showed weaker ICAM-1 staining in the placental endothelium after GDM pregnancies, and demonstrated ICAM-1 binding partners CD11a and CD18 expressed on leukocytes in fetal circulation and on placental tissue macrophages. This study identified reduction of ICAM-1 protein in fpEC in GDM pregnancy, which was regulated post-transcriptionally. Low ICAM-1 protein production may represent a protective, placenta-specific mechanism to avoid leukocyte transmigration into the placenta in response to GDM.
Professional Quality of Life and Empathy Among Nurses in a Selected Hospital in the United Kingdom
Creators: name: Melencio, John Alex M.
Publisher: name: Zenodo
Year: 2019
Subjects: PROQOL
Empathy
Fatigue
Burnout
Compassion of nurses
Nurses' satisfaction.

description: Nurses have a duty to care empathetically and compassionately for their
 patients. However, there are instances that their delivery of services could either
 induce satisfaction or rob the nurses of their compassion about their job that will
 eventually lead to burnout. This could contribute to lower quality patient care and
 patient satisfaction. It was deemed necessary by the researcher to understand how
 their Professional Quality of Life (PROQOL) which depicts satisfaction, fatigue and
 burnout has relationship with empathy and demographic profile. The study employed descriptive and correlational methods. The study used the
 PROQOL questionnaire and the Toronto Empathy Questionnaire to measure the
 variables included in the study. Referral sampling was utilized. The tool was
 administered to 150 employed nurses from the chosen NHS hospital in UK where
 Pearson R was used as the statistical treatment. Most of the respondents are predominantly 25-29 years old, female, single, with
 5-9 years of experience, Filipino and working in medical wards. An average level was
 seen with the nurses’ PROQOL and empathy. CS is affected by age, sex and civil
 status and CF is affected by the two latter factors. Meanwhile, age is a factor for
 burnout. Demographic profile is not a variable that can impact empathy. The
 respondent’s PROQOL revealed a significant relationship with empathy of the nurses.
 Compassion fatigue and burnout showed a negative relationship while compassion
 satisfaction showed otherwise. Decreasing compassion fatigue and burnout and increasing compassion
 satisfaction can increase the degree of empathy among nurses. Support for nurses
 with continuous and adequate in-service trainings that could focus on self-care is
 necessary to develop the empathetic skills of the nurses.
Herbivory-inducible lipid-transfer proteins (LTPs) of Cicer arietinum as potential human allergens
Creators: name: Negi, Harshita
name: Saxena, Harshita
name: Singh, Indrakant K.
name: Singh, Archana
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Molecular Biology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Plant Biology

description: Lipid-transfer proteins (LTPs) are lipid-binding small proteins, ubiquitously distributed amongst plant kingdom. Apart from their involvement in plant defense, it has also been discovered that they induce allergic reactions in humans. A plethora of LTPs have been identified in vegetables, fruits, pollens, nuts, and latex, among which Pru p 3, a LTP allergen from peach fruit, is extensively studied and exhibits cross-reactivity with potential allergens from different species. In Cicer arietinum, a family of LTPs (CaLTPs) has been identified and their importance in plant defense during Helicoverpa armigera-infestation has been recognized. However, the determination of the allergenicity potential of CaLTPs has not been attempted. In this study, we aim to decipher the allergenicity potential of defense-related CaLTPs. The allergenicity potential prediction, and identification of B-cell epitope binding regions showed that the CaLTPs had conserved domains and B-cell epitopes in the same regions as Prup3 (a marker allergen for LTPs). Using molecular docking and simulations, we observed that the CaLTPs successfully interacted with the Immunoglobin E(IgE)with docking energies ranging from −315.5 to −268.4 and the structures were stabilized within 10 ns of simulation. Through this study, we intend to embellish our present knowledge and understanding of the sensitization and allergenicity potential of CaLTPs. Communicated by Ramaswamy H. Sarma
Evaluation of Portable Dilution System for Aerosol Measurement from Stationary and Mobile Combustion Sources
Creators: name: Jaiprakash
name: Gazala Habib
name: Samresh Kumar
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: Science Policy
subject: Biological Sciences
subject: Ecology
subject: FOS: Biological sciences
subject: Chemistry
subject: Earth and Environmental Sciences
subject: Microbiology
subject: Medicine
subject: Biochemistry

description: ABSTRACTThis study presents the emission factor of PM2.5, EC, OC and water soluble ions for biomass fired induced downdraft gasifier and light duty diesel vehicle. A portable dilution system (PDS) developed for on-field measurement of aerosol and their precursors from combustion sources is used for quenching of aerosol at near atmospheric condition before collection on filters. PDS consists of a heated duct and particle sampling probe, dilution tunnel, zero air assembly and a power supply unit. PDS was evaluated under controlled conditions in laboratory for low emitter (gasifier cookstove) and high emitter (light duty diesel vehicle, LDDV) over wide range of dilution ratio to understand the effect of dilution on mixing, particle formation and loss. The invariability in CO2, recorded along the length and at radial distances of cross section of dilution tunnel confirmed the rapid and homogenous mixing inside the dilution tunnel. The particle loss and nucleation inside the dilution tunnel accounted for ∼6–20% at different dilution ratios (30:1–90:1). PM2.5 emission factors for wood combustion in gasifier cook-stove showed a decrease of 55% (117–52 mgkg−1) with increase in dilution ratio from 52:1 to 140:1. Similarly, a decrease of 75% (306 to 74 mgkm−1) was observed for LDDV for increase in dilution ratio from 39:1 to 144:1. Similar decrease in particulate organic carbon emission rate were observed indicating scarcity of sorptive organics, and insufficient residence time for condensation limited the particle formation from vapor phase organic compounds at high dilution ratios.
Molecular dynamics simulations depict structural motions of the whole human aryl hydrocarbon receptor influencing its binding of ligands and HSP90
Creators: name: Rosales-Hernández, Martha Cecilia
name: Bello, Martiniano
name: Toledano, Jazziel Velazquez
name: Feregrino, Barbara Citlali Escudero
name: Basurto, José Correa
name: Morales, Leticia Guadalupe Fragoso
name: Torres-Ramos, Mónica Adriana
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Chemical Sciences not elsewhere classified
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Computational Biology

description: The aryl hydrocarbon receptor (AhR) has broad biological functions when its ligands activate it; the non-binding interactions with AhR have not been fully elucidated due to the absence of a complete tridimensional (3D) structure. Therefore, utilization of the whole 3D structure from Homo sapiens AhR by in silico studies will allow us to better study and analyze the binding mode of its full and partial agonists, and antagonists, as well as its interaction with the HSP90 chaperone. The 3D AhR structure was obtained from I-TASSER and subjected to molecular dynamics (MD) simulations to obtain different structural conformations and determine the most populated AhR conformer by clustering analyses. The AhR-3D structures selected from MD simulations and those from clustering analyses were used to achieve docking studies with some of its ligands and protein–protein docking with HSP90. Once the AhR-3D structure was built, its Ramachandran maps and energy showed a well-qualified 3D model. MD simulations showed that the per-Arnt-Sim homology (PAS) PAS A, PAS B, and Q domains underwent conformational changes, identifying the conformation when agonists were binding also, and HSP90 was binding near the PAS A, PAS B, and Q domains. However, when antagonists are binding, HSP90 does not bind near the PAS A, PAS B, and Q domains. These studies show that the complex agonist-AhR-HSP90 can be formed, but this complex is not formed when an antagonist is binding. Knowing the conformations when the ligands bind to AHR and the behavior of HSP90 allows for an understanding of its activity. Communicated by Ramaswamy H. Sarma
Highlights in TMPRSS2 inhibition mechanism with guanidine derivatives approved drugs for COVID-19 treatment
Creators: name: Tachoua, Wafa
name: Kabrine, Mohamed
name: Mushtaq, Mamona
name: Selmi, Ahmed
name: Ul-Haq, Zaheer
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Molecular Biology
subject: Neuroscience
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: Transmembrane protease serine 2 (TMPRSS2) has been identified as a critical key for the entry of coronaviruses into human cells by cleaving and activating the spike protein of SARS-CoV-2. To block the TMPRSS2 function, 18 approved drugs, containing the guanidine group were tested against TMPRSS2’s ectodomain (7MEQ). Among these drugs, Famotidine, Argatroban, Guanadrel and Guanethidine strongly binds with TMPRSS2 S1 pocket with estimated Fullfitness energies of −1847.12, −1630.87, −1605.81 and −1600.52 kcal/mol, respectively. A significant number of non-covalent interactions such as hydrogen bonding, hydrophobic and electrostatic interactions were detected in protein-ligand complexes. In addition, the ADMET analysis revealed a perfect concurrence with the aptitude of these drugs to be developed as an anti-SARS-CoV-2 therapeutics. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior and stability of protein-ligand complexes. The results obtained herein highlight the enhanced stability and good binding affinities of the Argatroban and Famotidine towards the target protein, hence might act as new scaffolds for TMPRSS2 inhibition. Communicated by Ramaswamy H. Sarma
General-purpose ranking and selection for computer simulation
Creators: name: Soonhui Lee
name: Nelson, Barry L.
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Biotechnology
subject: Evolutionary Biology
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics

description: Many indifference-zone Ranking-and-Selection (R&S) procedures have been invented for choosing the best simulated system. To obtain the desired Probability of Correct Selection (PCS), existing procedures exploit knowledge about the particular combination of system performance measure (e.g., mean, probability, variance, quantile) and assumed output distribution (e.g., normal, exponential, Poisson). In this article, we take a step toward general-purpose R&S procedures that work for many types of performance measures and output distributions, including situations where different simulated alternatives have entirely different output distribution families. There are only two versions of our procedure: with and without the use of common random numbers. To obtain the required PCS we exploit intense computation via bootstrapping, and to mitigate the computational effort we create an adaptive sample-allocation scheme that guides the procedure to quickly reach the necessary sample size. We establish the asymptotic PCS of these procedures under very mild conditions and provide a finite-sample empirical evaluation of them as well.
Structural organization of RDGB (retinal degeneration B), a multi-domain lipid transfer protein: a molecular modelling and simulation based approach
Creators: name: Krishnan, Harini
name: Basak, Bishal
name: Nath, Vaisaly R
name: Mishra, Shirish
name: Raghu, Padinjat
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Neuroscience
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer

description: Lipid transfer proteins (LTPs) that shuttle lipids at membrane contact sites (MCS) play an important role in maintaining cellular homeostasis. One such important LTP is the Retinal Degeneration B (RDGB) protein. RDGB is localized at the MCS formed between the endoplasmic reticulum (ER) and the apical plasma membrane (PM) in Drosophila photoreceptors where it transfers phosphatidylinositol (PI) during G-protein coupled phospholipase C signalling. Previously, the C-terminal domains of RDGB have been shown to be essential for its function and accurate localization. In this study, using in-silico integrative modelling we predict the structure of entire RDGB protein in complex with the ER membrane protein VAP. The structure of RDGB has then been used to decipher the structural features of the protein important for its orientation at the contact site. Using this structure, we identify two lysine residues in the C-terminal helix of the LNS2 domain important for interaction with the PM. Using molecular docking, we also identify an unstructured region USR1, immediately c-terminal to the PITP domain that is important for the interaction of RDGB with VAP. Overall the 10.06 nm length of the predicted RDGB-VAP complex spans the distance between the PM and ER and is consistent with the cytoplasmic gap between the ER and PM measured by transmission electron microscopy in photoreceptors. Overall our model explains the topology of the RDGB-VAP complex at this ER-PM contact site and paves the way for analysis of lipid transfer function in this setting. Communicated by Ramaswamy H. Sarma
General-purpose Ranking & Selection for Computer Simulation
Creators: name: Nelson, Barry L.
name: Soonhui Lee
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Mathematics
subject: FOS: Mathematics
subject: Biological Sciences
subject: Biotechnology
subject: Molecular Biology
subject: Genetics
subject: FOS: Biological sciences

description: Many indifference-zone ranking-and-selection (R&S) procedures have been invented for choosing the best simulated system. To obtain the desired probability of correct selection (PCS), existing procedures exploit knowledge about the particular combination of system performance measure (e.g., mean, probability, variance, quantile) and assumed output distribution (e.g., normal, exponential, Poisson). In this paper we take a step toward general-purpose R&S procedures that work for many types of performance measures and output distributions, including situations in which different simulated alternatives have entirely different output distribution families. There are only two versions of our procedure: with and without the use of common random numbers. To obtain the required PCS we exploit intense computation via bootstrapping, and to mitigate the computational effort we create an adaptive sample-allocation scheme that guides the procedure to quickly reach the necessary sample size. We establish the asymptotic PCS of these procedures under very mild conditions, and provide a finite-sample empirical evaluation of them as well.
A new early Pliocene species of Mesoplodon: a calibration mark for the radiation of this species-rich beaked whale genus
Creators: name: Lambert, Olivier
name: Louwye, Stephen
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Evolutionary Biology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: Ecology
subject: Developmental Biology
subject: Inorganic Chemistry
subject: FOS: Chemical sciences

description: Including at least 15 extant species, the beaked whale genus Mesoplodon (Cetacea, Odontoceti, Ziphiidae) is by far the most species-rich cetacean genus. Such a high diversity reflects one or several pulses of radiation, most likely involving a sexual selection mechanism affecting shape, size, and position of mandibular tusks. However, the tempo of this diversification is currently poorly constrained due to the scarce fossil record. Based on the reassessment of five partial skulls discovered in Antwerp (north of Belgium), a new fossil species of the genus Mesoplodon, M. posti, sp. nov., is described. Only the second fossil species of the genus currently recognized, it is characterized (among other features) by: transverse sections of the rostrum higher than wide (a feature proposed to correspond to the presence of lower tusks more posterior than the apex of the mandibles); the presence of a basirostral groove at the rostrum base; pentagonal joined nasals; the posterior projection of the premaxilla in the vertex shorter than the nasal backward; and a strong transverse compression of the frontals behind the nasals. Our phylogenetic analysis results in M. posti being nested among extant species of Mesoplodon. Palynological study of the organic-walled phytoplankton from sediment retained in cranial cavities of several specimens indicates an age between 4.86 and 3.9 Ma (Zanclean, early Pliocene). Constituting the first temporally well-constrained fossil species of Mesoplodon, M. posti provides an upper calibration point for the beginning of the radiation(s), having produced a surprisingly high number of extant species in this genus. http://zoobank.org/urn:lsid:zoobank.org:pub:7407D183-BC8A-466B-8934-F7BE05611ED6 SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at www.tandfonline.com/UJVP Citation for this article: Lambert, O., and S. Louwye. 2016. A new early Pliocene species of Mesoplodon: a calibration mark for the radiation of this species-rich beaked whale genus. Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2015.1055754.
Molecular dynamics simulations reveal the effect of mutations in the RING domains of BRCA1-BARD1 complex and its relevance to the prognosis of breast cancer
Creators: name: Kiewhuo, Kikrusenuo
name: Priyadarsinee, Lipsa
name: Sarma, Himakshi
name: Sastry, G. Narahari
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Physical Sciences not elsewhere classified
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: The N-terminal RING-RING domain of BRCA1-BARD1 is an E3 ubiquitin ligase complex that plays a critical role in tumor suppression through DNA double stranded repair mechanism. Mutations in the BRCA1-BARD1 heterodimer RING domains were found to have an association with breast and ovarian cancer by a way of hampering the E3 ubiquitin ligase activity. Herein, the molecular mechanism of interaction, conformational change due to the specific mutations on the BRCA1-BARD1 complex at atomic level has been examined by employing molecular modeling techniques. Sixteen mutations have been selected for the study. Molecular dynamics simulation results reveal that the mutant complexes have more local perturbation with a high residual fluctuation in the zinc binding sites and central helix. A few of the BRCA1 (V11A, I21V, I42V, R71G, I31M and L51W) mutants have been experimentally identified that do not impair E3 ligase activity, display an enhanced number of H-bonds and non-bonded contacts at the interacting interface as revealed by MD simulation. The mutation of BRCA1 (C61G, C64Y, C39Y and C24R) and BARD1 (C53W, C71Y and C83R) zinc binding residues displayed a smaller number of significant H-bonds, other interactions and also loss of some of the hotspot residues. Additionally, most of the mutant complexes display relatively lower electrostatic energy, H-bonding and total stabilizing energy as compared to wild-type. The current study attempts to unravel the role of BRCA1-BARD1 mutations and delineates the structural and conformational dynamics in the progression of breast cancer. Communicated by Ramaswamy H. Sarma
Effectiveness of a community-delivered pneumatic machine resistance training programme (Gym Tonic) for older adults at neighbourhood senior centres – a randomized controlled trial
Creators: name: Wee, Shiou Liang
name: Lee, Shuen Yee
name: Choo, Pei Ling
name: Ong, Peck Hoon
name: Wong, Wai Pong Alan
Publisher: name: Singapore Institute of Technology
Year: 2022
Subjects: Physiotherapy

description: Background: Resistance training with pneumatic machines attenuates the age-associated loss in muscle strength and function in older adults. However, effectiveness of scaled-up pneumatic machine resistance training in the community is not known. We evaluated the effectiveness of a multi-site community-delivered 12-week pneumatic machine resistance programme (Gym Tonic (GT)) on muscle strength and physical function in older adults. Methods: Three hundred eighteen community-dwelling older adults aged ≥65 years were randomized into 12-week (twice/week) coach-supervised-community-based-GT-programme(n = 168) and wait-list control groups(n = 150). After 12 weeks, the intervention group continued with GT-training and the control group received supervised-GT-programme for further 12 weeks (partial-crossover-design). Fried frailty score, lower-extremity muscle strength and physical function (i.e., fast and habitual gait-speed, balance, repeated-chair-sit-to-stand, short physical performance battery (SPPB)) were determined at baseline, 12 and 24 weeks. Analysis adopted a modified-intentionto-treat-approach. Results: After 12 weeks, lower-extremity muscle strength improved by 11–26%(all p < 0.05) and fast gait-speed improved by 7%(p = 0.008) in GT-intervention group(n = 132) than controls(n = 118), regardless of frailty status. Other physical function performance did not differ between control and intervention groups after 12 weeks (all p > 0.05). Frailty score improved by 0.5 in the intervention but not control group(p = 0.004). Within the intervention group, lower-extremity muscle strength and physical function outcomes improved at 24 weeks compared with baseline (all p < 0.001). Within controls, lower-extremity muscle strength, SPPB, repeated-chair-sit-to-stand and fast gait-speed improved post-GT (24-week) compared to both pre-GT (12-week) and baseline. Programme adherence was high in intervention [0–12-weeks,90%(SD,13%); 12–24-weeks,89%(SD,17%)] and control [12–24- weeks,90%(SD,19%)] groups.Conclusion: Community-delivered GT resistance training programme with pneumatic machines has high adherence, improves muscle strength and fast gait-speed, and can be effectively implemented at scale for older adults. Future studies could examine if including other multi-modal function-specific training to complement GT can achieve better physical/functional performance in power, balance and endurance tasks.Trial registration: ClinicalTrials.gov, NCT04661618, Registered 10 December 2020 - Retrospectively registered.
Effectiveness of a community-delivered pneumatic machine resistance training programme (Gym Tonic) for older adults at neighbourhood senior centres – a randomized controlled trial
Creators: name: Lee, Shuen Yee
name: Goh, Alycia
name: Tan, Ken
name: Choo, Pei Ling
name: Ong, Peck Hoon
name: Wong, Wai Pong Alan
name: Wee, Shiou Liang
Publisher: name: Singapore Institute of Technology
Year: 2022
Subjects: Physiotherapy

description: Background: Resistance training with pneumatic machines attenuates the age-associated loss in muscle strength and function in older adults. However, effectiveness of scaled-up pneumatic machine resistance training in the community is not known. We evaluated the effectiveness of a multi-site community-delivered 12-week pneumatic machine resistance programme (Gym Tonic (GT)) on muscle strength and physical function in older adults. Methods: Three hundred eighteen community-dwelling older adults aged ≥65 years were randomized into 12-week (twice/week) coach-supervised-community-based-GT-programme(n = 168) and wait-list control groups(n = 150). After 12 weeks, the intervention group continued with GT-training and the control group received supervised-GT-programme for further 12 weeks (partial-crossover-design). Fried frailty score, lower-extremity muscle strength and physical function (i.e., fast and habitual gait-speed, balance, repeated-chair-sit-to-stand, short physical performance battery (SPPB)) were determined at baseline, 12 and 24 weeks. Analysis adopted a modified-intentionto-treat-approach. Results: After 12 weeks, lower-extremity muscle strength improved by 11–26%(all p < 0.05) and fast gait-speed improved by 7%(p = 0.008) in GT-intervention group(n = 132) than controls(n = 118), regardless of frailty status. Other physical function performance did not differ between control and intervention groups after 12 weeks (all p > 0.05). Frailty score improved by 0.5 in the intervention but not control group(p = 0.004). Within the intervention group, lower-extremity muscle strength and physical function outcomes improved at 24 weeks compared with baseline (all p < 0.001). Within controls, lower-extremity muscle strength, SPPB, repeated-chair-sit-to-stand and fast gait-speed improved post-GT (24-week) compared to both pre-GT (12-week) and baseline. Programme adherence was high in intervention [0–12-weeks,90%(SD,13%); 12–24-weeks,89%(SD,17%)] and control [12–24- weeks,90%(SD,19%)] groups.Conclusion: Community-delivered GT resistance training programme with pneumatic machines has high adherence, improves muscle strength and fast gait-speed, and can be effectively implemented at scale for older adults. Future studies could examine if including other multi-modal function-specific training to complement GT can achieve better physical/functional performance in power, balance and endurance tasks.Trial registration: ClinicalTrials.gov, NCT04661618, Registered 10 December 2020 - Retrospectively registered.