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Cool season precipitation plays a critical role in regional water resource management in the western United States. Throughout the twenty-first century, regional precipitation will be impacted by rising temperatures and changing circulation patterns. Changes to precipitation magnitude remain challenging to project; however, precipitation phase is largely dependent on temperature, and temperature predictions from global climate models are generally in agreement. To understand the implications of this dependence, we investigate projected patterns in changing precipitation phase for mountain areas of the western United States over the twenty-first century and how shifts from snow to rain may impact runoff. We downscale two bias-corrected global climate models for historical and end-century decades with the Weather Research and Forecasting (WRF) regional climate model to estimate precipitation phase and spatial patterns at high spatial resolution (9 km). For future decades, we use the RCP 8.5 scenario, which may be considered a very high baseline emissions scenario to quantify snow season differences over major mountain chains in the western U.S. Under this scenario, the average annual snowfall fraction over the Sierra Nevada decreases by >45% by the end of the century. In contrast, for the colder Rocky Mountains, the snowfall fraction decreases by 29%. Streamflow peaks in basins draining the Sierra Nevada are projected to arrive nearly a month earlier by the end of the century. By coupling WRF with a water resources model, we estimate that California reservoirs will shift towards earlier maximum storage by 1–2 months, suggesting that water management strategies will need to adapt to changes in streamflow magnitude and timing.

COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has exhibited mixed results in the treatment of COVID-19. Given that the therapeutic effect of CCP may extend beyond the ability of SARS-CoV-2-specific antibody binding and neutralization to influence the evolution of the endogenous antibody response, we took a systematic and comprehensive approach to analyze SARS-CoV-2 functional antibody profiles of participants in a randomized controlled trial of CCP treatment of individuals hospitalized with COVID-19 pneumonia where CCP was associated with both decreased mortality and improved clinical severity. Using systems serology, we found that the clinical benefit of CCP is related to a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We found CCP had the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function, rather than S or N antibody levels or participant demographic features. Further, CCP induced immunomodulatory changes to recipient humoral profiles persisted for at least two months, marked by the selective evolution of anti-inflammatory Fc-glycan profiles and persistently expanded nucleocapsid-specific humoral immunity following CCP therapy. Together, our findings identify a novel mechanism of action of CCP, suggest optimal patient characteristics for CCP treatment, identify long-last immunomodulatory effects of CCP, and provide guidance for development of novel N-focused antibody therapeutics for severe COVID-19 hyperinflammation., Here are the code scripts to generate the figures in this manuscript.

Transfer of convalescent plasma (CP) was proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody isotype, subclass, Fc-receptor binding, and Fc-mediated functional assays in CP units, and also in plasma from hospitalized COVID-19 patients before and after CP administration. Though recipients exhibit expanded SARS-CoV-2 specific humoral immune responses, CP units possess more functional antibodies than recipient plasma. CP functional profiles influence recipient humoral immune profiles, depending on their pre-CP SARS-CoV2 specific antibody titers. Specifically, CP-derived SARS-CoV-2 Spike-specific and Nucleocapsid-specific antibody functions both are important for the antiviral activity of CP in patients with varying levels of anti-spike protein IgG. These insights into functional antibodies in CP may inform a better understanding of correlates of immunity in ongoing large-scale CP trials and for the design of next generation monoclonal antibody therapeutic cocktails., Here are the R scripts to generate the figures in our recently published paper.

Version control systems track the history of code as it is committed (saved) by any number of developers. Have you made a coding error and cannot debug it? Version control systems allow for resetting code back to when it worked, and show what code has changed since previous commits. The contents of this lecture provide an introduction to the git version control language, GitHub for cloud hosting open source code repositories, and tutorials that demonstrate common and useful git and GitHub practices. This lecture is intended to be coupled with a discussion on creating reproducible computational research.The zipped folder contains: 1. pre-meeting software installation instructions, 2. references for discussion on reproducibility, coding best practices, and legal issues, and 3. slideshow with tutorial. Commands needed for the tutorial are in the slide notes. Links to additional video tutorials are provided in a slide. Combined, the presentation + reproducibility discussion + tutorial are designed to take about 50 minutes to complete. If used in a course, the tutorial information on the hidden slides could be used as part of a student assignment.

We introduce the notion of a weak (homotopy) moment map associated to a Lie group action on a multisymplectic manifold. We show that the existence/uniqueness theory governing these maps is a direct generalization from symplectic geometry. We use weak moment maps to extend Noether's theorem from Hamiltonian mechanics by exhibiting a correspondence between multisymplectic conserved quantities and continuous symmetries on a multi-Hamiltonian system. We find that a weak moment map interacts with this correspondence in a way analogous to the moment map in symplectic geometry. We define a multisymplectic analog of the classical momentum and position functions on the phase space of a physical system by introducing momentum and position forms. We show that these differential forms satisfy generalized Poisson bracket relations extending the classical bracket relations from Hamiltonian mechanics. We also apply our theory to derive some identities on manifolds with a closed $G_2$ structure., Comment: Waterloo University PhD thesis. This thesis is a synthesis of 10.1016/j.geomphys.2018.05.001 [arXiv:1711.02572] and 10.1016/j.difgeo.2017.09.003 [arXiv:1705.05818]

Copyright © 2015, American Association for the Advancement of Science., The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for developing next-generation antimalarial drugs. Using an integrated chemogenomics approach that combined drug resistance selection, whole-genome sequencing, and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA (transfer RNA) synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivative halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the Plasmodium berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses and represents a promising lead for the development of dual-stage next-generation antimalarials., We gratefully acknowledge financial support from the Gates Foundation (D.F.W. and R.M., OPP1086203), the NIH (D.F.W.) AI105786 (W.J.S.), 5F32AI084440-02 (L.R.P.), CA92577 (P.S.), and GM099796 (E.R.D.), the Center for Rare and Neglected Diseases at the University of Notre Dame (O.W. and G.E.), generous allocation of computing resources by the NSF through TeraGrid grant TG-CHE090124 (O.W.), a fellowship from the National Foundation for Cancer Research (P.S.), SFRH/BD/80162/2011 (S.A.S.), PTDC/SAU-MIC/113697/2009 (V.Z.-L.), and EXCL/IMI-MIC/0056/2012 (M.M.M.) (Fundação para a Ciência e Tecnologia, Portugal), Howard Hughes Medical Institute (S.L.), and start-up funding provided by the Center for Systems Biology, Massachusetts General Hospital (R.M.).