A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore

10.1371/journal.pone.0017468PLoS ONE63

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (frst detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the fndings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.info:eu-repo/semantics/acceptedVersio

Production of Single W Bosons at LEP

We report on the observation of single W boson production in a data sample collected by the L3 detector at LEP2. The signal consists of large missing energy final states with a single energetic lepton or two hadronic jets. The cross-section is measured to be $0.61^{+0.43}_{-0.33} \pm 0.05 \; \rm{pb}$ at the centre of mass energy \sqrt{s}=172 \GeV{}, consistent with the Standard Model expectation. From this measurement the following limits on the anomalous $\gamma$WW gauge couplings are derived at 95\% CL: $\rm -3.6 \Delta \kappa_\gamma 1.5$ and $\rm -3.6 \lambda_\gamma 3.6$

Search for neutral B meson decays to two charged leptons

The decays $\mathrm{B_d^0,\,B_s^0 \rightarrow e^+e^-,\,\mu^+\mu^-,\, e^\pm\mu^\mp}$ are searched for in 3.5 million hadronic ${\mathrm{Z}}$ events, which constitute the full LEP I data sample collected by the L3 detector. No signals are observed, therefore upper limits at the 90\%(95\%) confidence levels are set on the following branching fractions: % \begin{center}% {\setlength{\tabcolsep}{2pt} \begin{tabular}{lccccclcccc}% % Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $1.4(1.8)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $5.4(7.0)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $1.0(1.4)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $3.8(5.1)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $1.6(2.0)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $4.1(5.3)$ & $\times$ & $10^{-5}$. \\% % \end{tabular}% } \end{center}% % The results for ${\mathrm{B_s^0\rightarrow{\mathrm{e^+e^-}}}}$ and ${\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}}$ are the first limits set on these decay modes

Study of the Weak Charged Hadronic Current in b Decays

Charged and neutral particle multiplicities of jets associated with identified semileptonic and hadronic b decays are studied. The observed differences between these jets are used to determine the inclusive properties of the weak charged hadronic current. The average charged particle multiplicity of the weak charged hadronic current in b decays is measured for the first time to be 2.69$\pm$0.07(stat.)$\pm$0.14(syst.). This result is in good agreement with the JETSET hadronization model of the weak charged hadronic current if 40$\pm$17\% of the produced mesons are light--flavored tensor (L=1) mesons. This level of tensor meson production is consistent with the measurement of the $\pi^0$ multiplicity in the weak charged hadronic current in b decays. \end{abstract

HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis <it>in vivo </it>unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that <it>chronic </it>HIV-<it>replication in non-endothelial cells </it>may produce novel factors that provoke angiogenic pathways.</p> <p>Methods</p> <p>Genome-wide proteins from HIV-infected and uninfected T-lymphocytes were tested by subtractive proteomics analyses at various stages of virus and cell growth <it>in vitro </it>over a period of two years. Several thousand differentially regulated proteins were identified by mass spectrometry (MS) and >200 proteins were confirmed in multiple gels. Each protein was scrutinized extensively by protein-interaction-pathways, bioinformatics, and statistical analyses.</p> <p>Results</p> <p>By functional categorization, 31 proteins were identified to be associated with various signaling events involved in angiogenesis. 88% proteins were located in the plasma membrane or extracellular matrix and >90% were found to be essential for regeneration, neovascularization and angiogenic processes during embryonic development.</p> <p>Conclusion</p> <p>Chronic HIV-infection of T-cells produces membrane receptor-PTKs, serine-threonine kinases, growth factors, adhesion molecules and many diffusible signaling proteins that have not been previously reported in HIV-infected cells. Each protein has been associated with endothelial cell-growth, morphogenesis, sprouting, microvessel-formation and other biological processes involved in angiogenesis (p = 10^-4to 10^-12). Bioinformatics analyses suggest that overproduction of PTKs and other kinases in HIV-infected cells has <it>suppressed </it>VEGF/VEGFR-PTK expression and promoted <it>VEGFR-independent </it>pathways. This unique mechanism is similar to that observed in neovascularization and angiogenesis during embryogenesis. Validation of clinically relevant proteins by gene-silencing and translational studies <it>in vivo </it>would identify specific targets that can be used for early diagnosis of angiogenic disorders and future development of inhibitors of angiopathies. This is the first comprehensive study to demonstrate that HIV-infection alone, without any co-infection or treatment, can induce numerous "embryonic" proteins and kinases capable of generating novel <it>VEGF-independent </it>angiogenic pathways.</p

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe