COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning-based Vaxign-ML reverse vaccinology tools to predict COVID-19 vaccine candidates. Our Vaxign analysis found that the SARS-CoV-2N protein sequence is conserved with SARS-CoV and MERS-CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and the predicted linear B-cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID-19 vaccine development. We also propose that an “Sp/Nsp cocktail vaccine” containing a structural protein(s) (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses.http://deepblue.lib.umich.edu/bitstream/2027.42/156072/1/fimmu-11-01581.pdfSEL

CIDO, a community-based ontology for coronavirus disease knowledge and data integration, sharing, and analysis

Ontologies, as the term is used in informatics, are structured vocabularies comprised of human- and computer-interpretable terms and relations that represent entities and relationships. Within informatics fields, ontologies play an important role in knowledge and data standardization, representation, integra- tion, sharing and analysis. They have also become a foundation of artificial intelligence (AI) research. In what follows, we outline the Coronavirus Infectious Disease Ontology (CIDO), which covers multiple areas in the domain of coronavirus diseases, including etiology, transmission, epidemiology, pathogenesis, diagnosis, prevention, and treatment. We emphasize CIDO development relevant to COVID-19

Synthesis and characterization of binuclear tantalum hydride complexes

Reduction of the quadruply-bridged (2Cl, 2H) tantalum(IV) dimer, Ta2Cl6 (PMe3)4H2 (2) with sodium amalgam in glyme or THF at 0[deg]C provides deep green Ta2Cl4(PMe3)4H2 (3) in 70% yield. Dimer 3 has a D2d Ta2Cl4(PMe3)4 substructure which closely resembles that of the quadruply metal-metal-bonded dimer W2Cl4(PMe3)4. The hydride ligands of 3 are located on a diagonal plane, bridging the two tantalum atoms and the Ta-Ta separation is 2.545(1) A. 3 reacts cleanly with Cl2, HCl and H2 in diethyl ether to provide the quadruply-bridged dimers 2, Ta2Cl5(PMe3)4H3 (4), and Ta2Cl4(PMe3)4H4 (5), respectively, in high yield. Dimer 5 can also be prepared in high yield via thermolysis of the tantalum(IV) hydride TaCl2H2(PMe3)4 (6) in refluxing methylcyclohexane. The X-ray structure of 5 shows that the ([mu]-H)4 group is staggered by 45[deg] with respect to the eclipsed pyramidal TaCl2(PMe3)2 end groups. The molecular symmetry of 5 is D2d and the Ta-Ta separation is 2.511(2)A. Multiple-scattering X[alpha] calculations on the model compounds Ta2Cl4(PH3)4H2 and Ta2Cl4(PH3)4 are used to elucidate the ground-state electronic structures of 3 and 5, and to probe the question of ([mu]-H)x rotation about the metal-metal bonds in these complexes. Crystal data (at 160[deg]C) are as follows: for 3, monoclinic space group C2/c, a = 18.371(5) A, b = 9.520(3) A, c = 18.942(6) A, [beta] = 125.36(2)[deg], V = 2701.8 A3, Z = 4,dcalc. = 1.991 g cm-3; for 5, tetragonal space group P4/nbm, a = b = 12.579(2) A, c = 10.205(2) A, V = 1614.7 A3, Z = 2, dcalc. = 1.670 g cm-3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26987/1/0000554.pd

Small arms combat modeling: a superior way to evaluate marksmanship data

Purpose – Marksmanship data is a staple of military and law enforcement evaluations. This ubiquitous nature creates a critical need to use all relevant information and to convey outcomes in a meaningful way for the end users. The purpose of this study is to demonstrate how simple simulation techniques can improve interpretations of marksmanship data. Design/methodology/approach – This study uses three simulations to demonstrate the advantages of small arms combat modeling, including (1) the benefits of incorporating a Markov Chain into Monte Carlo shooting simulations; (2) how small arms combat modeling is superior to point-based evaluations; and (3) why continuous-time chains better capture performance than discrete-time chains. Findings – The proposed method reduces ambiguity in low-accuracy scenarios while also incorporating a more holistic view of performance as outcomes simultaneously incorporate speed and accuracy rather than holding one constant. Practical implications – This process determines the probability of winning an engagement against a given opponent while circumventing arbitrary discussions of speed and accuracy trade-offs. Someone wins 70% of combat engagements against a given opponent rather than scoring 15 more points. Moreover, risk exposure is quantified by determining the likely casualties suffered to achieve victory. This combination makes the practical consequences of human performance differences tangible to the end users. Taken together, this approach advances the operations research analyses of squad-level combat engagements. Originality/value – For more than a century, marksmanship evaluations have used point-based systems to classify shooters. However, these scoring methods were developed for competitive integrity rather than lethality as points do not adequately capture combat capabilities. The proposed method thus represents a major shift in the marksmanship scoring paradigm

Development of a ‘clickable’ non-natural nucleotide to visualize the replication of non-instructional DNA lesions

The misreplication of damaged DNA is an important biological process that produces numerous adverse effects on human health. This report describes the synthesis and characterization of a non-natural nucleotide, designated 3-ethynyl-5-nitroindolyl-2′-deoxyriboside triphosphate (3-Eth-5-NITP), as a novel chemical reagent that can probe and quantify the misreplication of damaged DNA. We demonstrate that this non-natural nucleotide is efficiently inserted opposite an abasic site, a commonly formed and potentially mutagenic non-instructional DNA lesion. The strategic placement of the ethynyl moiety allows the incorporated nucleoside triphosphate to be selectively tagged with an azide-containing fluorophore using ‘click’ chemistry. This reaction provides a facile way to quantify the extent of nucleotide incorporation opposite non-instructional DNA lesions. In addition, the incorporation of 3-Eth-5-NITP is highly selective for an abasic site, and occurs even in the presence of a 50-fold molar excess of natural nucleotides. The biological applications of using 3-Eth-5-NITP as a chemical probe to monitor and quantify the misreplication of non-instructional DNA lesions are discussed

VIGET: A web portal for study of vaccine-induced host responses based on Reactome pathways and ImmPort data

Host responses to vaccines are complex but important to investigate. To facilitate the study, we have developed a tool called Vaccine Induced Gene Expression Analysis Tool (VIGET), with the aim to provide an interactive online tool for users to efficiently and robustly analyze the host immune response gene expression data collected in the ImmPort/GEO databases. VIGET allows users to select vaccines, choose ImmPort studies, set up analysis models by choosing confounding variables and two groups of samples having different vaccination times, and then perform differential expression analysis to select genes for pathway enrichment analysis and functional interaction network construction using the Reactome’s web services. VIGET provides features for users to compare results from two analyses, facilitating comparative response analysis across different demographic groups. VIGET uses the Vaccine Ontology (VO) to classify various types of vaccines such as live or inactivated flu vaccines, yellow fever vaccines, etc. To showcase the utilities of VIGET, we conducted a longitudinal analysis of immune responses to yellow fever vaccines and found an intriguing complex activity response pattern of pathways in the immune system annotated in Reactome, demonstrating that VIGET is a valuable web portal that supports effective vaccine response studies using Reactome pathways and ImmPort data

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente