Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis

Structural characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from B. bovis in the apo state and complexed with antifolate inhibitors in both enzymatic active sites is reported

Progress of irrigation research on Willamette Valley soils

Published April 1968. Facts and recommendations in this publication may no longer be valid. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalo

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

On the Implementation of a European Space Traffic Management System III. Technical Requirements.

This third paper (Paper III) concludes the mini series of papers which presents results from an ESA-funded evaluation study that has been collected by DLR GfR and its partner institutes and companies. The objective of this study is to generate a roadmap for the implementation of a European STM system within the next two decades under consideration of an evolving Air Traffic Management (ATM) system. In Paper I (Tüllmann et al. 2017a), we introduced the implementation approach by focussing on the commercial Space Travel market which is expected to develop into a multi-billion Euro business in the coming years and could become a major driver for STM in general. We provided proof of concept that this suborbital space travel is generally possible, given that significant advances in heat and collision shielding technologies can be achieved. The envisioned technical, conceptual and organisational setups were discussed regarding Space Debris, Space Surveillance & Tracking, Space Weather Monitoring, Flight Planning and Scheduling and ATM and STM integration. This work is supplemented by Paper II (Tüllmann et al. 2017b), which discussed Safety & Reliability (S&R) aspects that should be reflected in a S&R concept for the STM system. In this context relevant Safety Management Systems in aviation business were investigated to check to what extent their S&R concepts and good-practices are applicable to STM operations. A first Risk Classification Scheme was presented and initial values for the acceptable levels of safety for the identified hazards were presented and an outline of the envisaged Space Navigation Service Provider (SNSP) certification process was given. In this present work (Paper III) we focus on deriving initial technical high-level requirements and recommendations for a European contribution to Space Traffic Management and define relevant interfaces in the global context. The proposed requirements and interfaces presented here are neither complete nor final and are meant to provide a first rough guidance for space agencies, manufacturers or policy makers and shall stimulate discussions on how a European STM system could be realised

Improving the Culture of Ethical Behavior in the Financial Sector: Time to Expressly Provide for Private Enforcement Against Aiders and Abettors of Securities Fraud

Financial markets do not function well when fraud is pervasive. It has been well documented that financial fraud has increased following changes in securities law that occurred in the 1990\u27s. Also around September of 2009, the investigations into the SEC examinations of Bernard Madoff Investment Securities, LLC were completed and released to the public. The simple facts reveal an alarming level of incompetence and lack offinancial literacy on the part of the guardians of the integrity of our financial markets. I suggest two important tools for addressing these problems. One is to supplement enforcement of anti-fraud rules with more private attorney generals by expressly creating a private right of action for aiding and abetting violations of securities laws. This will foster a stronger culture of integrity and ethical conduct in the auditing profession. An additional tool is to increase financial literacy in our law schools which supply the regulators of our markets

Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimenResearch in context

Summary: Background: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. Methods: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C). Findings: Model A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0–12 months post-DTG initiation (p < 0.005). This was confirmed with models B and C; for instance, model B estimated a significant decay pre-DTG initiation with a half-life of 6.9 years, and an ∼1.7-fold increase in the size of the RC-LVR post-DTG initiation. There was no evidence of viral failure or consistent evolution in the cohort. Interpretation: These data suggest that the change from NNRTI- to DTG-based ART is associated with a significant temporary increase in the circulating RC-LVR. Funding: Supported by the NIH (grant 1-UM1AI164565); Gilead HIV Cure Grants Program (90072171); Canadian Institutes of Health Research (PJT-155990); and Ontario Genomics-Canadian Statistical Sciences Institute