Airborne Measurements of Gravity Wave Breaking at the Tropopause

2000 FLORIDA AVE NW, WASHINGTON, DC, 2000

Thinking in Terms of Structure-Activity-Relationships (T-SAR): A Tool to Better Understand Nanofiltration Membranes

A frontier to be conquered in the field of membrane technology is related to the very limited scientific base for the rational and task-specific design of membranes. This is especially true for nanofiltration membranes with properties that are based on several solute-membrane interaction mechanisms. “Thinking in terms of Structure-Activity-Relationships” (T-SAR) is a methodology which applies a systematic analysis of a chemical entity based on its structural formula. However, the analysis become more complex with increasing size of the molecules considered. In this study, T-SAR was combined with classical membrane characterization methods, resulting in a new methodology which allowed us not only to explain membrane characteristics, but also provides evidence for the importance of the chemical structure for separation performance. We demonstrate an application of the combined approach and its potential to discover stereochemistry, molecular interaction potentials, and reactivity of two FilmTec nanofiltration membranes (NF-90 and NF-270). Based on these results, it was possible to predict both properties and performance in the recovery of hydrophobic ionic liquids from aqueous solution

Amyloidogenicity assessment of transthyretin gene variants

Objective: Hereditary transthyretin-mediated amyloidosis is a treatable condition caused by amyloidogenic variants in the transthyretin-gene resulting in severe peripheral neuropathy or cardiomyopathy. Only about a third of over 130 known variants are clearly pathogenic, most are classified as variants of uncertain significance. A clear delineation of these into pathogenic or non-pathogenic is highly desirable but hampered by low frequency and penetrance. We thus sought to characterize their amylogenic potential by an unbiased in vitro approach. Methods: Thioflavin T and turbidity assays were used to compare the potential of mammalian cell expressed wt-transthyretin and 12 variant proteins (either variants of uncertain significance, benign, pathogenic) to aggregate and produce amyloid fibrils in vitro. As proof of principle, the assays were applied to transthyretin-Ala65Val, a variant that was newly detected in a family with peripheral neuropathy and amyloid deposits in biopsies. In silico analysis was performed to compare the position of the benign and pathogenic variants. Results: Transthyretin-Ala65Val showed a significantly higher amyloidogenic potential than wt-transthyretin, in both turbidity- and Thioflavin T-assays, comparable to known pathogenic variants. The other eight tested variants did not show an increased amyloidogenic potential. In silico structural analysis further confirmed differences between pathogenic and benign variants in position and interactions. Interpretation: We propose a biochemical approach to assess amyloidogenic potential of transthyretin variants. As exemplified by transthyretin-Ala65Val, data of three assays together with histopathology clearly demonstrates its amyloidogenicity

Strange Hadron Spectroscopy with Secondary KL Beam in Hall D

Final version of the KLF Proposal [C12-19-001] approved by JLab PAC48. The intermediate version of the proposal was posted in arXiv:1707.05284 [hep-ex]. 103 pages, 52 figures, 8 tables, 324 references. Several typos were fixedWe propose to create a secondary beam of neutral kaons in Hall D at Jefferson Lab to be used with the GlueX experimental setup for strange hadron spectroscopy. The superior CEBAF electron beam will enable a flux on the order of $1\times 10^4~K_L/sec$, which exceeds the flux of that previously attained at SLAC by three orders of magnitude. The use of a deuteron target will provide first measurements ever with neutral kaons on neutrons. The experiment will measure both differential cross sections and self-analyzed polarizations of the produced $\Lambda$, $\Sigma$, $\Xi$, and $\Omega$ hyperons using the GlueX detector at the Jefferson Lab Hall D. The measurements will span CM $\cos\theta$ from $-0.95$ to 0.95 in the range W = 1490 MeV to 2500 MeV. The new data will significantly constrain the partial wave analyses and reduce model-dependent uncertainties in the extraction of the properties and pole positions of the strange hyperon resonances, and establish the orbitally excited multiplets in the spectra of the $\Xi$ and $\Omega$ hyperons. Comparison with the corresponding multiplets in the spectra of the charm and bottom hyperons will provide insight into he accuracy of QCD-based calculations over a large range of masses. The proposed facility will have a defining impact in the strange meson sector through measurements of the final state $K\pi$ system up to 2 GeV invariant mass. This will allow the determination of pole positions and widths of all relevant $K^\ast(K\pi)$ $S$-,$P$-,$D$-,$F$-, and $G$-wave resonances, settle the question of the existence or nonexistence of scalar meson $\kappa/K_0^\ast(700)$ and improve the constrains on their pole parameters. Subsequently improving our knowledge of the low-lying scalar nonet in general

Maraviroc for previously treated patients with R5 HIV-1 infection

Background CC chemokine receptor 5 antagonists are a new class of antiretroviral agents.Methods We conducted two double- blind, placebo- controlled, phase 3 studies - Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment- Experienced Patients ( MOTIVATE) 1 and MOTIVATE 2 - with patients who had R5 human immunodeficiency virus type 1 ( HIV- 1) only. They had been treated with or had resistance to three antiretroviral- drug classes and had HIV- 1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy ( OBT) based on treatment history and drug- resistance testing. Safety and efficacy were assessed after 48 weeks.Results A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV- 1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV- 1 RNA from baseline was greater with maraviroc than with placebo: - 1.66 and - 1.82 log(10) copies per milliliter with the once- daily and twice- daily regimens, respectively, versus - 0.80 with placebo in MOTIVATE 1, and - 1.72 and - 1.87 log(10) copies per milliliter, respectively, versus - 0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV- 1 RNA levels of less than 50 copies per milliliter ( 42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P< 0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo ( increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P< 0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups.Conclusions Maraviroc, as compared with placebo, resulted in significantly greater suppression of HIV- 1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV- 1 who were receiving OBT. (ClinicalTrials. gov numbers, NCT00098306 and NCT00098722.)