Publications by authors named "Muhammad Suleman"

61 Publications

Photocatalytic Approach for Construction of 5,6-Dihydroimidazo[2,1-]isoquinolines and Their Luminescent Properties.

J Org Chem 2021 Jun 1. Epub 2021 Jun 1.

Department of Chemistry, Zhejiang University, Hangzhou, P. R. China.

A visible-light-driven photoredox reaction of tetrahydroisoquinoline with 2-azirines is described. 4,7-Bis(4-methoxyphenyl)benzo[][1,2,5]thiadiazole, a benzothiadiazole (BTD) derived fluorophore, is used as an organic photoredox catalyst, and the reaction offers an efficient access to 5,6-dihydroimidazo[2,1-]isoquinolines with a broad range of functional groups. The resulting 5,6-dihydroimidazo[2,1-]isoquinolines present strong photoluminecence in solutions and powders and could be applied in the fabrication of blue OLED devices.
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http://dx.doi.org/10.1021/acs.joc.1c00590DOI Listing
June 2021

Computational Modeling of Immune Response Triggering Immunogenic Peptide Vaccine Against the Human Papillomaviruses to Induce Immunity Against Cervical Cancer.

Viral Immunol 2021 May 10. Epub 2021 May 10.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China.

Papillomaviruses are placed within the family Papillomaviride, and the members of this family have a double-stranded circular DNA genome. Every year, ∼30% of cancers are reported to be human papillomavirus (HPV) related, which represents 63,000 cancers of all infectious agent-induced cancers. HPV16 and HPV18 are reported to be associated with 70% of cervical cancers. The quest for an effective drug or vaccine candidate still continues. In this study, we aim to design B cell and T cell epitope-based vaccine using the two structural major capsid protein L1 and L2 as well as other three important proteins (E1, E2, and E6) against HPV strain 16 (HPV16). We used a computational pipeline to design a multiepitope subunit vaccine and tested its efficacy using computational modeling approaches. Our analysis revealed that the multiepitope subunit vaccine possesses antigenic properties, and using cloning method revealed proper expression and downstream processing of the vaccine construct. Besides this, we also performed immune simulation to check the immune response upon the injection. Our results strongly suggest that this vaccine candidate should be tested immediately for the immune response against the cervical cancer-causing agent. The safety, efficacy, expression, and immune response profiling makes it the first choice for experimental and setup.
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http://dx.doi.org/10.1089/vim.2020.0306DOI Listing
May 2021

Genome-wide screening of vaccine targets prioritization and reverse vaccinology aided design of peptides vaccine to enforce humoral immune response against Campylobacter jejuni.

Comput Biol Med 2021 Jun 18;133:104412. Epub 2021 Apr 18.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China. Electronic address:

Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104412DOI Listing
June 2021

Immunogenomics guided design of immunomodulatory multi-epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation.

Comput Biol Med 2021 06 24;133:104420. Epub 2021 Apr 24.

Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China. Electronic address:

Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant. Our investigation revealed that 12 different epitopes imparted a critical role in immune response induction. This was validated by an exploration of physiochemical properties and experimental feasibility. In silico and host immune simulation confirmed the expression and induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064902PMC
June 2021

BC-TFdb: a database of transcription factor drivers in breast cancer.

Database (Oxford) 2021 Apr;2021

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.

Transcription factors (TFs) are DNA-binding proteins, which regulate many essential biological functions. In several cancer types, TF function is altered by various direct mechanisms, including gene amplification or deletion, point mutations, chromosomal translocations, expression alterations, as well as indirectly by non-coding DNA mutations influencing the binding of the TF. TFs are also actively involved in breast cancer (BC) initiation and progression. Herein, we have developed an open-access database, BC-TFdb (Breast Cancer Transcription Factors database), of curated, non-redundant TF involved in BC. The database provides BC driver TFs related information including genomic sequences, proteomic sequences, structural data, pathway information, mutations information, DNA binding residues, survival and therapeutic resources. The database will be a useful platform for researchers to obtain BC-related TF-specific information. High-quality datasets are downloadable for users to evaluate and develop computational methods for drug designing against BC. Database URL: https://www.dqweilab-sjtu.com/index.php.
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http://dx.doi.org/10.1093/database/baab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060005PMC
April 2021

Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data.

J Cell Physiol 2021 Mar 23. Epub 2021 Mar 23.

Department of Bioinformatics and Biological Statistics, Shanghai Jiao Tong University, Shanghai, P.R. China.

The evolution of the SARS-CoV-2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor-binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS-CoV-2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y), and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.
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http://dx.doi.org/10.1002/jcp.30367DOI Listing
March 2021

Phase-field simulation of dose rate effect on the Cu precipitation with neutron irradiation.

Phys Chem Chem Phys 2021 Feb;23(7):4217-4229

School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China. and MIIT Key Laboratory of Advanced Metallic and Intermetallic Materials Technology, Nanjing, 210094, China.

Radiation-enhanced precipitation (REP) of Cu in Fe-Cu alloys results in hardening and degradation of the mechanical properties. By combining the CALPHAD-based free energy for phase-field modeling, and radiation-enhanced diffusion (RED) with neutron irradiating energetic particle, the precipitation of Cu in binary Fe-Cu alloys is studied under different dose rates, concentrations, and temperatures. Rate theory (RT) provides the RED that serves as an input parameter for the phase-field simulation to capture the morphology of the precipitates. The REP results agree with the theoretical predictions: the increase in the dose rates increases the concentration of defects, and accelerates the kinetics of precipitation. The simulation predicts the stability of the precipitates even under high damage rates. The increase in radius is achieved for high damage rates. Precipitate dissolution is observed to be dependent on the combination of dose rate, concentration, and temperature. The work also outlines the limitations of the model and the potential future improvements.
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http://dx.doi.org/10.1039/d0cp05777kDOI Listing
February 2021

Proteome wide vaccine targets prioritization and designing of antigenic vaccine candidate to trigger the host immune response against the Mycoplasma genitalium infection.

Microb Pathog 2021 Mar 29;152:104771. Epub 2021 Jan 29.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Centre on Antibacterial Resistances, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China. Electronic address:

Mycoplasma genitalium is a small size, sexually transmitted bacterial pathogen that causes urethritis in males and cervicitis in females. Being resistant to antibiotics, difficulty in diagnosis, treatment, and control of this cosmopolitan infection, vaccination is the alternating method for its effective management. Herein, this study was conducted to computationally design a multi-epitope vaccine to boost host immune responses against M. genitalium. To achieve the study aim, immunoinformatics approaches were applied to the said pathogen's proteomics sequence data. B and T cell epitopes were projected from the three shortlisted vaccine proteins; MG014, MG015, Hmw3MG317. The final vaccine ensemble comprises cytotoxic and helper T cell epitopes fused through appropriate linkers. The epitopes peptide is then liked to an adjuvant for efficient recognition and processing by the host immune system. The various physicochemical parameters such as allergenicity, antigenicity, theoretical pI, GRAVY, and molecular weight of the vaccine were checked and found safe and effective to be used in post-experimental studies. The stability and binding affinity of the vaccine with the TLR1/2 heterodimer were ensured by performing molecular docking. The best-docked complex was considered, ranked top having the lowest binding energy and strong intermolecular binding and stability. Finally, the vaccine constructs better expression was obtained by in silico cloning into the pET28a (+) vector in Escherichia coli K-12 strain, and immune simulation validated the immune response. In a nutshell, all these approaches lead to developing a multi-epitope vaccine that possessed the ability to induce cellular and antibody-mediated immune responses against the pathogen used.
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http://dx.doi.org/10.1016/j.micpath.2021.104771DOI Listing
March 2021

Base Promoted Three-Component Annulation of 4-Diazoisochroman-3-imines with Dimethylsulfonium Ylides: Synthesis of Highly Functionalized Isochromeno[4,3-]pyridazines.

J Org Chem 2021 Jan 16;86(1):455-465. Epub 2020 Dec 16.

Department of Chemistry, Zhejiang University, Hangzhou, 310027, P. R. China.

A novel method has been developed to synthesize a unique class of highly functionalized isochromeno[4,3-]pyridazines. This reaction features an intermolecular functionalization of terminal nitrogen atom of diazo group of 4-diazoisochoman-3-imine with two dimethylsulfonium ylide components, followed by a base promoted 6-exo-trig cyclization step. Readily available starting materials, a broad substrate scope, and operationally simple, mild, and catalyst-free reaction conditions are the prominent features of this method.
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http://dx.doi.org/10.1021/acs.joc.0c02204DOI Listing
January 2021

In silico study of enhanced permeation and retention effect and hyperthermia of porous tumor.

Med Eng Phys 2020 12 12;86:128-137. Epub 2020 Nov 12.

Department of Mathematics, University of Engineering and Technology, Lahore 54890, Pakistan.

Nanotechnology has recently gained fame for its extensive use in biomedical applications particularly in magnetic fluid hyperthermia (MFH) of tumors. The magnetic nanoparticles (MNPs) are usually injected into the tumor either intravenously or through direct needle injection. Depending on the location of the tumor, the needle approach may not be appropriate and in the case, when the nanoflow rate is higher, it may produce cracks in the tumor. In this scenario, the intravenous approach following the enhanced permeation and retention effect (EPR) effect proves advantageous. In this paper, we have simulated the EPR effect of nanofluid flowing from blood vessels to the tumor through epithelial cells spacing and then its diffusion in the tumor interstitium using COMSOL Multiphysics. The velocity in the blood vessel and diffusion in the tumor have been simulated and analyzed using Finite Element Method (FEM) based models of Navier-Stokes equations and convection-diffusion equation. The simulation results show that the velocity and concentration are higher in the blood vessel and it decreases slowly while moving through epithelial spacing to the tumor interstitium. The heat transfer in the tumor interstitium is simulated and analyzed for temperature distribution quantitatively.
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http://dx.doi.org/10.1016/j.medengphy.2020.11.003DOI Listing
December 2020

Humoral and Cell-Mediated Immune Response Validation in Calves after a Live Attenuated Vaccine of .

Pathogens 2020 Nov 11;9(11). Epub 2020 Nov 11.

Department of Parasitology, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan.

The current vaccines to control bovine () infection are not fully protective and vaccination failures incur heavy losses to the cattle industry around the world. Using modified micro-aerophilous stationary phase, we developed a culture-derived attenuated live vaccine against and tested a single subcutaneous inoculation of 2 × 10 infected erythrocytes in calves. The protection was measured after a lethal intravenous challenge with 5 × 10 virulent calf-derived . Our results demonstrated that a single shot of attenuated vaccine was capable of inducing robust humoral and cell-mediated immune responses in calves. We found a significant increase in the IgG antibody titers post-challenge and a strong proliferation of both CD4+ and CD8+ T cells contributing towards the protection. Our vaccine provided complete protection and parasitic clearance, which was followed for more than 100 days post-challenge. This immunity against babesiosis was directly linked to strong humoral responses; however, the parasitic clearance was attributed to significant T cells effector responses in vaccinated calves as compared to the infected control calves. We anticipate that these results will be helpful in the development of more efficient culture-derived vaccines against infections, thus reducing significant global economic losses to farmers and the cattle industry.
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http://dx.doi.org/10.3390/pathogens9110936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698288PMC
November 2020

Development of multi-epitope subunit vaccine for protection against the norovirus' infections based on computational vaccinology.

J Biomol Struct Dyn 2020 Nov 10:1-12. Epub 2020 Nov 10.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China.

Human Norovirus belongs to a family , and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease." Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1845799DOI Listing
November 2020

TfOH-promoted synthesis of 4,5-dihydrooxazolo[5,4-]isoquinolines formal [3 + 2] cycloaddition of 4-diazoisoquinolin-3-one and benzonitriles.

Org Biomol Chem 2020 Oct;18(38):7671-7676

Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.

A facile and efficient method for the synthesis of novel 2-substituted 4-tosyl-4,5-dihydrooxazolo[5,4-c]isoquinolines from 4-diazoisoquinolin-3-ones and nitriles is reported. The reaction proceeded through a TfOH-promoted formal [3 + 2] cycloaddition and the products could be conveniently converted to 2-aryloxazolo[5,4-c]isoquinolines and the subsequent 2-(oxazolo[5,4-c]isoquinolin-2-yl)phenol which emitted bright green light in dilute dichloromethane solution and in solid form as well. Simple operation, metal-free and mild reaction conditions, short reaction time and broad substrate scope are the prominent features of this methodology.
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http://dx.doi.org/10.1039/d0ob01748eDOI Listing
October 2020

Phase-field crystal modeling of crystal growth patterns with competition of undercooling and atomic density.

Phys Chem Chem Phys 2020 Oct;22(38):21858-21871

College of Physics and Information Technology, Shaanxi Normal University, Xi'an 710119, Shaanxi, P. R. China.

Crystal growth with various patterns, hexagonal, circular, square, rectangular, star-like, and faceted, was investigated using the one-mode approximation of phase-field crystal (PFC) modeling. The simulations were carried out at different temperatures and average densities of the diverse patterns. The pattern selection of crystal growth is caused by the competition between undercooling temperature ε and average density ψ. When the undercooling temperature reaches ε = -0.75, the crystal evolves into a stable striped phase. Further increasing from ε = -0.75 to -0.25, a combination of a triangular-striped coexistence pattern, a triangular-liquid coexistence phase and a stable triangular pattern forms with average densities ψ = -0.130, -0.185 and -0.285, respectively. In particular, when the time, undercooling temperature and average density increase, the crystal grows to a secondary pattern. The introduction of noise terms breaks the symmetry in the growth morphology. For a hexagonal lattice, a large undercooling temperature ε leads to faster crystallization. Finally, a morphological phase diagram under the effect of ε and ψ with star-like dendrite and compact spherical shape (CSS) is constructed as a function of the phase-field crystal parameters.
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http://dx.doi.org/10.1039/d0cp03901bDOI Listing
October 2020

Genetic characterization of structural and open reading Fram-8 proteins of SARS-CoV-2 isolates from different countries.

Gene Rep 2020 Dec 14;21:100886. Epub 2020 Sep 14.

Centre for Biotechnology and Microbiology, University of Swat, Pakistan.

Since December 2019, a severe pandemic of pneumonia, COVID-19 associated with a novel coronavirus (SARS-CoV-2), have emerged in Wuhan, China and spreading throughout the world. As RNA viruses have a high mutation rate therefore we wanted to identify whether this virus is also prone to mutations. For this reason we selected four major structural (Spike protein (S), Envelope protein (E), Membrane glycoprotein (M), Nucleocapsid phosphoprotein (N)) and ORF8 protein of 100 different SARS-CoV-2 isolates of fifteen countries from NCBI database and compared these to the reference sequence, Wuhan NC_045512.2, which was the first isolate of SARS-CoV-2 that was sequenced. By multiple sequence alignment of amino acids, we observed substitutions and deletion in S protein at 13 different sites in the isolates of five countries (China, USA, Finland, India and Australia) as compared to the reference sequence. Similarly, alignment of N protein revealed substitutions at three different sites in isolates of China, Spain and Japan. M protein exhibits substitution only in one isolates from USA, however, no mutation was observed in E protein of any isolate. Interestingly, in ORF8 substitution of Leucine, a nonpolar to Serine a polar amino acid at same position (aa84 L to S) in 23 isolates of five countries i.e. China, USA, Spain, Taiwan and India were observed, which may affect the conformation of peptides. Thus, we observed several mutations in the isolates thereafter the first sequencing of SARS-CoV-2 isolate, NC_045512.2, which suggested that this virus might be a threat to the whole world and therefore further studies are needed to characterize how these mutations in different proteins affect the functionality and pathogenesis of SARS-CoV-2.
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http://dx.doi.org/10.1016/j.genrep.2020.100886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487737PMC
December 2020

Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vaccine designing for immune response reinforcement against .

J Biomol Struct Dyn 2020 Sep 14:1-15. Epub 2020 Sep 14.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R China.

a prominent pathogen responsible for acute periodontal diseases, is widely studied by the scientific community for its successful evasion of the host immune system. is associated with rheumatoid arthritis, dementia, and Alzheimer's. The pathogen successfully survives itself against the heavy load of conventional antibiotics because of its ability to evade the host immune system. Subtractive proteomics and reverse vaccinology approaches were employed in order to prioritize the best proteins for vaccine designing. Three vaccine candidates with Uniprot ID: Q7MWZ2 (histidine Kinase), Q7MVL1 (Fe (2+) transporter), and Q7MWZ2 (Capsular polysaccharide transport protein) were identified for vaccine designing. These proteins are antigenic and essential for pathogen survival. A wide range of immunoinformatics tools was applied for the prediction of epitopes, B, and T cells, for the vaccine candidate proteins. Molecular docking of the predicted epitopes against the MHC molecules were carried out. vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 2. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-2 docked complex, Molecular Dynamics simulations were performed. The reverse-translated nucleotide sequence cloned in to attain the maximal expression of the vaccine protein. The maximal expression was ensured by CAI score of 0.96. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against associated infections.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1819423DOI Listing
September 2020

Drug similarity and structure-based screening of medicinal compounds to target macrodomain-I from SARS-CoV-2 to rescue the host immune system: a molecular dynamics study.

J Biomol Struct Dyn 2020 Sep 8:1-15. Epub 2020 Sep 8.

Center for Biotechnology and Microbiology, University of Swat, Swat, Khyber Pakhtunkhwa, Pakistan.

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22, Ala38, Asn40, Val44, Phe144, Gly46, Gly47, Leu127, Ser128, Gly130, Ile131, Phe132 and Ala155 which are the critical active site residues. Here, we also used ADPr as a positive control to compare our results. Our results suggest that our identified hits by using such a complicated computational pipeline could inhibit the SARs-CoV-2 by targeting the macrodomain-1. We strongly recommend the experimental testing of these compounds, which could rescue the host immune system and could help to contain the disease caused by SARs-CoV-2.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1815583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544951PMC
September 2020

3D in silico study of magnetic fluid hyperthermia of breast tumor using FeO magnetic nanoparticles.

J Therm Biol 2020 Jul 5;91:102635. Epub 2020 Jun 5.

Department of Mathematics, University of Engineering and Technology, Lahore, 54890, Pakistan.

Modeling and simulation of the temperature distribution, the mass concentration, and the heat transfer in the breast tissue are hot issues in magnetic fluid hyperthermia treatment of cancer. The breast tissue can be visualized as a porous matrix with saturated blood. In this paper, 3D in silico study of breast cancer hyperthermia using magnetic nanoparticles (MNPs) is conducted. The 3D FEM models are incorporated to investigate the infusion and backflow of nanofluid in the breast tumor, the diffusion of nanofluid, temperature distribution during the treatment, and prediction of the fraction of tumor necrosis while dealing with the thermal therapy. All the hyperthermia procedures are simulated and analyzed on COMSOL Multiphysics. The sensitivity of frequency and amplitude of the applied magnetic field (AMF) is investigated on the heating effect of the tumor. The mesh dependent solution of Penne's bioheat model is also analyzed. The simulated results demonstrate successful breast cancer treatment using MNPs with minimum side effects. Validation of current simulations results with experimental studies existing in literature advocates the success of our therapy. The increase in the amplitude and frequency of the AMF increases of the temperature in the tumor. The variation of mesh from coarser to finer increased the temperature through small fractions. We have also simulated the magnetic induction problem where the magnetic field is generated by current-carrying coil conductors induce heat in nearby breast tumors due to excitation of MNPs by magnetic flux. This research will aid treatment protocols and real-time clinical breast cancer treatments.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102635DOI Listing
July 2020

Identifying the Symptom Severity in Obsessive-Compulsive Disorder for Classification and Prediction: An Artificial Neural Network Approach.

Behav Neurol 2020 22;2020:2678718. Epub 2020 Jun 22.

Department of Statistics, University of Gujrat, Pakistan.

The present study is aimed at identifying the most prominent determinants of OCD along with their strength to classify the OCD patients from healthy controls. The data for this cross-sectional study were collected from 200 diagnosed OCD patients and 400 healthy controls. The respondents were selected through purposive sampling and interviewed by using the Y-BOCS scale with the addition of a factor, worth of an individual in his family. The validity and reliability of data were assessed through Cronbach's alpha and confirmatory factor analysis. Artificial Neural Network (ANN) modeling was adopted to determine threatening determinants along with their strength to predict OCD in an individual. The results of ANN modeling depicted 98% accurate classification of OCD patients from healthy controls. The most contributing factors in determining the OCD patients according to normalized importance were the contamination and cleaning (100%); symmetric and perfection (72.5%); worth of an individual in the family (71.1%); aggressive, religious, and sexual obsession (50.5%); high-risk assessment (46.0%); and somatic obsessions and checking (24.0%).
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http://dx.doi.org/10.1155/2020/2678718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327615PMC
June 2020

Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro).

J Biomol Struct Dyn 2020 Jun 18:1-12. Epub 2020 Jun 18.

State Key Lab of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1779128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309305PMC
June 2020

Complete Genome Sequences of 16 Mycoplasma bovis Isolates from Canadian Bison and Cattle.

Microbiol Resour Announc 2020 Jun 4;9(23). Epub 2020 Jun 4.

Infectious Bacterial Diseases Research Unit, USDA, Agricultural Research Service, National Animal Disease Center, Ames, Iowa, USA.

Here, we report the complete genome sequences of 12 isolates cultured from Canadian bison and 4 cultured from Canadian cattle. The sequences are of value for understanding the phylogenetic relationship between cattle and bison isolates and will aid in elucidating the genetic basis for virulence and host specificity.
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http://dx.doi.org/10.1128/MRA.00325-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272552PMC
June 2020

First-principles search for half-metallic ferromagnetism in CsCrZ (Z = O, S, Se or Te) Heusler alloys.

J Mol Graph Model 2020 07 11;98:107620. Epub 2020 Apr 11.

Department of Physics, Abdul Wali Khan University, Mardan, 23200, KPK, Pakistan; School of Materials Science & Engineering, Nanjing University of Science & Technology, Nanjing, 210094, PR China.

Exploring highly spin-polarized materials is crucial for the development of spin-based devices. In this paper, we investigate the atomic structure, electronic, half-metallic and magnetic properties of the CsCrZ (Z = O, S, Se or Te) Heusler alloys, by performing first-principles calculations based on density functional theory (DFT). The geometry optimization process shows that the alloys are more stable in CuMnAl type structure than in HgCuTi one. To find a magnetic ground state, the total energy of the alloys is calculated in the non-magnetic (NM), ferromagnetic (FM) and anti-ferromagnetic (AFM) ordering. We find that, the FM ordering yields the lowest energy, thereby confirming that the alloys are FM in the ground state. On computing the cohesive and formation energy in the ground state, it is found that alloys are chemically and thermodynamically stable, respectively. Spin polarized band structures and density of states (DOS) demonstrate that the CsCrO, CsCrS and CsCrSe alloys are true half-metals with 100% spin-polarization at the Fermi level, while the CsCrTe alloy is predicted as highly spin polarized material. Furthermore, the CsCrO, CsCrS and CsCrSe alloys possess 2.529, 2.250 and 2.050 eV gaps in the spin down band structure, respectively. The calculated total magnetic moments reveal that half-metallic alloys have an integral total magnetic moment of 3.000 μ, which satisfies the Slater-Pauling rule M = Z-16. The main contribution to the total magnetic moment comes from the Cr atoms (about 3.9 μ). Furthermore, the Curie temperature T calculated within classical Heisenberg model is estimated to be about 822 K (CsCrO), 685 K (CsCrS), 753 K (CsCrSe) and 636 K (CsCrTe). The obtained high spin polarization and above room temperature FM ordering make the materials as promising materials to be used in spintronic technology.
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http://dx.doi.org/10.1016/j.jmgm.2020.107620DOI Listing
July 2020

Stable half-metallicity in the (001)-oriented thin films of Co-doped full-Heusler alloys TiFe Co Sn (x=0.00, 0.25, 0.50, 0.75 or 1.00).

J Phys Condens Matter 2020 Mar 25;32(32):325001. Epub 2020 Mar 25.

College of Physics and Information Technology, Shaanxi Normal University, Xian 710119, Shaanxi, People's Republic of China.

Thin films with stable half-metallic (HM) character and 100% spin-polarization (SP) are required to be used in spintronic devices. The HM character has been predicted theoretically in many Heusler alloys thin films and confirmed by experiments. Full-Heusler alloy TiFeSn has been studied extensively. It has been reported that their (001)-oriented thin films with TiFe or TiSn terminations preserve 100% SP, but the HM character is unstable because the edge of the bandgap is closed to the Fermi level E . Therefore, we investigate the effects of the Co-doping on the structural, electronic and magnetic properties of the bulk full-Heusler alloys TiFe Co Sn (x = 0.00, 0.25, 0.50, 0.75 or 1.00) and their (001)-oriented thin films. The bulk TiFe Co Sn (x = 0.00, 0.25, 0.50, 0.75 or 1.00) alloys are all HM ferromagnets. We investigate twelve possible terminations and show that five of them preserve HM character with 100% SP at the Fermi level E , while in the remaining seven, surface states emerge in the spin-down channel at the Fermi level E , significantly reducing their SP. The Co-doping significantly increases the stability of the TiSn slab, also increases its spin-down bandgap [Formula: see text] and HM gap [Formula: see text] at x = 0.50. The stable HM character makes it is a slab of maximum benefit in the applications of spintronic devices, especially in magnetic tunnel junctions.
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http://dx.doi.org/10.1088/1361-648X/ab832dDOI Listing
March 2020

c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3.

Cell Rep 2020 03;30(12):4235-4249.e6

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Increased glycolysis intermediates replenish non-oxidative pentose phosphate pathway (PPP) and serine pathway for biosynthesis of cancer cells. PFKFB3 knockout (KO) cells and their counterpart reconstituted with PFKFB3-Y194F show comparably impaired abilities for proliferation, migration, and xenograft formation. Furthermore, PFKFB3-Y194F knockin mice show impaired glycolysis and, mating of these mice with APC mice attenuates spontaneous colon cancer formation in APC mice. In summary, we identify a specific mechanism by which c-Src mediates glucose metabolism to meet cancer cells' requirements for maximal biosynthesis and proliferation. The PFKFB3-Tyr194 phosphorylation level highly correlates with c-Src activity in clinical tumor samples, indicating its potential as an evaluation for tumor prognosis.
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http://dx.doi.org/10.1016/j.celrep.2020.03.005DOI Listing
March 2020

Tendency Towards Eating Disorders and Associated Sex-specific Risk Factors Among University Students.

Noro Psikiyatr Ars 2019 Dec 5;56(4):258-263. Epub 2019 Sep 5.

Department of Soil & Environmental Sciences, the University of Agriculture, Peshawar, Pakistan.

Introduction: Eating disorders have frequently been reported among young adults including university students. Detailed information on the prevalence and associated gender-specific determinants of eating disorders are lacking, particularly among students in the north western region of Pakistan. The current cross-sectional study was designed to fill this gap in the literature.

Methods: Total of 672 students (female: 56%, age range: 18-26 years) were enrolled and data collected between October 2016 and December 2017. The 26 items Eating Attitude Test (EAT-26), Diet quality Index-International (DQI-I), 10 items Rosenberg's self-esteem scale (SES), Stunkard Figure Rating Scale, 19-items Pittsburgh Sleep Quality Index (PSQI) and Global Physical Activity Questionnaire (GPAQ) were used. Body composition and anthropometry were determined using standardized tools. A cut-off of ≥20 EAT-26 score was used to assess the tendency towards eating disorders (EDT). Data was analyzed using appropriate statistical tests.

Results: Mean (SD) age of the respondents was 21.7±2 years. Total of 103 (15.3%) students showed EDT with no statistical difference between sexes. Students with EDT had a much lower diet quality than normal students (p<0.001). Risk factors for EDT, in female students included young age (<20 years), on-campus residency, discordant body image and poor sleep quality, while those for males were vigorous lifestyle, insufficient monthly allowance, poor sleep quality and peer pressure.

Conclusions: A significant number of students showed a tendency towards an unhealthy eating attitude with some sex-specific risk factors. These students had poorer diet quality than normal students. Support to encourage healthy attitudes to eating and better diet quality could help to avert the development of clinical eating disorders.
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http://dx.doi.org/10.29399/npa.23609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927083PMC
December 2019

Genetic Screening and Expression Analysis of Psychrophilic spp. Reveal Their Potential to Alleviate Cold Stress and Modulate Phytohormones in Wheat.

Microorganisms 2019 Sep 10;7(9). Epub 2019 Sep 10.

Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, China.

Abiotic stress in plants pose a major threat to cereal crop production worldwide and cold stress is also notorious for causing a decrease in plant growth and yield in wheat. The present study was designed to alleviate cold stress on plants by inoculating psychrophilic PGPR bacteria belonging to Bacillus genera isolated from extreme rhizospheric environments of Qinghai-Tibetan plateau. The genetic screening of psychrophilic spp. CJCL2, RJGP41 and temperate FZB42 revealed presence of genetic features corresponding to cold stress response, membrane transport, signal transduction and osmotic regulation. Subsequently, the time frame study for the expression of genes involved in these pathways was also significantly higher in psychrophilic strains as analyzed through qPCR analysis at 4 ℃. The inoculated cold tolerant Bacillus strains also aided in inducing stress response in wheat by regulating abscisic acid, lipid peroxidation and proline accumulation pathways in a beneficial manner. Moreover, during comparative analysis of growth promotion in wheat all three Bacillus strains showed significant results at 25 ℃. Whereas, psychrophilic Bacillus strains CJCL2 and RJGP41 were able to positively regulate the expression of phytohormones leading to significant improvement in plant growth under cold stress.
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http://dx.doi.org/10.3390/microorganisms7090337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780275PMC
September 2019

PIR promotes tumorigenesis of breast cancer by upregulating cell cycle activator E2F1.

Cell Cycle 2019 Nov 10;18(21):2914-2927. Epub 2019 Sep 10.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University , Xiamen , Fujian , China.

Pirin (PIR) protein belongs to the superfamily of cupin and is highly conserved between eukaryotic and prokaryotic organisms. It has been reported that PIR is upregulated in various tumors and involved in tumorigenesis. However, its biological functions particularly in promoting tumorigenesis are, to date, poorly characterized. Here we report that knockdown of in MCF7 and MDA-MB-231 cell lines causes a dramatic decrease in cell proliferation and xenograft tumor growth in mice. Mechanistically, the cell cycle activator E2F1 and its target genes , cycD and are remarkably downregulated in PIR depleted cells, leading to G1/S phase arrest. Luciferase reporter assay and chromatin immunoprecipitation assay indicate that PIR can activate E2F1 transcription by binding to its promoter region. Consistent with the observation in knockdown cells, PIR inhibitors markedly inhibit the proliferation of both cell lines. Furthermore, knockdown of significantly decreases the abilities of MCF7 cells for mobility and invasion in vitro and their metastasis in mice, which may be attributed to the decrease of DDR1. In conclusion, PIR stimulates tumorigenesis and progression by activating E2F1 and its target genes. Our finding thus suggests PIR as a potential druggable target for the therapy of cancers with high expression level of PIR.
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http://dx.doi.org/10.1080/15384101.2019.1662259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791709PMC
November 2019

MHD flow of Maxwell fluid with nanomaterials due to an exponentially stretching surface.

Sci Rep 2019 May 13;9(1):7312. Epub 2019 May 13.

School of Materials Science and Engineering, Jiangsu University, Zhenjiang, 212013, China.

In many industrial products stretching surfaces and magnetohydrodynamics are being used. The purpose of this article is to analyze magnetohydrodynamics (MHD) non-Newtonian Maxwell fluid with nanomaterials in a surface which is stretching exponentially. Thermophoretic and Brownian motion effects are incorporated using Buongiorno model. The given partial differential system is converted into nonlinear ordinary differential system by employing adequate self-similarity transformations. Locally series solutions are computed using BVPh 2.0 for wide range of governing parameters. It is observed that the flow is expedite for higher Deborah and Hartman numbers. The impact of thermophoresis parameter on the temperature profile is minimal. Mathematically, this study describes the reliability of BVPh 2.0 and physically we may conclude the study of stretching surfaces for non-Newtonian Maxwell fluid in the presence of nanoparticles can be used to obtain desired qualities.
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http://dx.doi.org/10.1038/s41598-019-43549-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513985PMC
May 2019

Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses.

Virus Res 2019 01 5;260:151-162. Epub 2018 Dec 5.

Western College of Veterinary Medicine, University of Saskatchewan, S7N 5B4, Canada. Electronic address:

Although porcine reproductive and respiratory syndrome virus (PRRSV) readily crosses the maternal fetal interface (MFI) in third trimester, fetal resilience varies within litters. The aim of this study was to characterize PRRSV-2 concentration in MFI and fetuses at five time points after experimental inoculation of late gestation gilts and use this information to classify potentially resistant, resilient and susceptible fetuses. The secondary objective was to verify the relationship between PRRS viral load and intrauterine growth retardation (IUGR). Three PRRSV-inoculated pregnant gilts and 1 sham-inoculated control were euthanized at five time points in days post infection (DPI; 2, 5, 8, 12, 14). The preservation status of each fetus was determined and MFI samples adjacent to the umbilical stump of each fetus, as well as serum, thymus, umbilical cord and amniotic fluid were collected. Viral load was quantified using probe-based reverse-transcriptase quantitative PCR (RT-qPCR) targeting PRRSV NVSL 97-7895 ORF7. Our result show the MFI was largely PRRSV infected by 2 DPI and virus was first detected in fetal sera and umbilical cord by 5 DPI, and in fetal thymus and amniotic fluid by 8 DPI. This indicates that PRRSV-2 quickly crossed the placenta and traveled toward the fetus via umbilical circulation within one week of the dam's inoculation. Fetal compromise was first observed on 8 DPI and increased progressively through to 14 DPI. However, several factors were associated with fetal resilience. The random forest model identified that 'viral load in fetal thymus' and duration of infection ('DPI') as the most important factors predicting fetal resilience and resistance. Moreover, IUGR fetuses had lower viral load and were less frequently compromised or dead compared to non-IUGR and average cohorts. Understanding the mechanisms of fetal resilience to PRRSV will improve selection strategies for replacement gilts.
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http://dx.doi.org/10.1016/j.virusres.2018.12.002DOI Listing
January 2019

Entropy Analysis of 3D Non-Newtonian MHD Nanofluid Flow with Nonlinear Thermal Radiation Past over Exponential Stretched Surface.

Entropy (Basel) 2018 Dec 5;20(12). Epub 2018 Dec 5.

Department of Mathematics, Faculty of Science, Jiangsu University, Zhenjiang 212013, China.

The present study characterizes the flow of three-dimensional viscoelastic magnetohydrodynamic (MHD) nanofluids flow with entropy generation analysis past an exponentially permeable stretched surface with simultaneous impacts of chemical reaction and heat generation/absorption. The analysis was conducted with additional effects nonlinear thermal radiation and convective heat and mass boundary conditions. Apposite transformations were considered to transform the presented mathematical model to a system of differential equations. Analytical solutions of the proposed model were developed via a well-known homotopy analysis scheme. The numerically calculated values of the dimensionless drag coefficient, local Nusselt number, and mass transfer Nusselt number are presented, with physical insights. The graphs depicting the consequences of numerous parameters on involved distributions with requisite deliberations were also a part of this model. It is seen that the Bejan number is an increasing function of the thermal radiation parameter.
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http://dx.doi.org/10.3390/e20120930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512516PMC
December 2018