Snowballs in Euclid and WFIRST Detectors

Snowballs are transient events observed in HgCdTe detectors with a sudden increase of charge in a few pixels. They appear between consecutive reads of the detector, after which the affected pixels return to their normal behavior. The origin of the snowballs is unknown, but it was speculated that they could be the result of alpha decay of naturally radioactive contaminants in the detectors, but a cosmic ray origin cannot be ruled out. Even though previous studies predicted a low rate of occurrence of these events, and consequently, a minimal impact on science, it is interesting to investigate the cause or causes that may generate snowballs and their impact in detectors designed for future missions. We searched for the presence of snowballs in the dark current data in Euclid and Wide Field Infrared Survey Telescope (WFIRST) detectors tested in the Detector Characterization Laboratory at Goddard Space Flight Center. Our investigation shows that for Euclid and WFIRST detectors, there are snowballs that appear only one time, and others that repeat in the same spatial localization. For Euclid detectors, there is a correlation between the snowballs that repeat and bad pixels in the operational masks (pixels that do not fulfill the requirements to pass spectroscopy noise, photometry noise, quantum efficiency, and/or linearity). The rate of occurrence for a snowball event is about 0.9 snowballs/hr. in Euclid detectors (for the ones that do not have associated bad pixels in the mask), and about 0.7 snowballs/hr. in PV3 Full Array Lot WFIRST detectors

Micro-CT study of male genitalia and reproductive system of the Asian citrus psyllid, Diaphorina citri Kuwayama, 1908 (Insecta: Hemiptera, Liviidae)

The Asian citrus psyllid (ACP), Diaphorina citri, is a major vector of the bacteria Candidatus Liberibacter asiaticus and C.L. americanus, which cause Huanglongbing disease (HLB) (aka Citrus greening disease), considered the most serious bacterial disease of citrus trees. As part of a multidisciplinary project on psyllid biology (www.citrusgreening.org), the results presented here concern a detailed anatomical study of the male reproductive system (testes, seminal vesicles, accessory glands, sperm pump, connecting ducts, and aedeagus) using micro-computed tomography (micro-CT). The study summarizes current knowledge on psyllids male reproductive system and represents significant advances in the knowledge of ACP anatomy.This work was supported by USDA-NIFA Award 2014-70016-23028 ªDeveloping an Infrastructure and Product Test Pipeline to Deliver Novel Therapies for Citrus Greening Diseaseº, 2015-2020

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Single molecule study of RecA recombinase enzyme activity

Homologous recombination is an essential pathway in the repair of DNA damage during the DNA replication process. RecA protein promotes the central steps in homologous recombination, after coating single-stranded DNA (ssDNA), RecA carries out a pairing and strand exchange reaction involving homologous DNA. This research project aims to characterize RecA function in homologous recombination using single molecule tethered particle motion (TPM). Using TPM to observe RecA extension along DNA, the RecA extension rate on ssDNA was determined for the first time. The rate obtained for dsDNA was similar, implying that RecA polymerizes along only one strand of a DNA substrate. The nucleation behaviour of RecA on DNA was also obtained from the extension trace, confirming the hypothesis that rapid nucleation on ssDNA is pH independent, while nucleation on dsDNA is pH dependent. Several pilot single molecule experiments aimed at monitoring the pairing and strand exchange reaction in real time were attempted. Although these experiments were unsuccessful, successful ensemble biochemical analogues of these experiments proved the feasibility of the single molecule experiments. These attempts gave insights into possible factors hindering success and led to experimental suggestions essential to the success of future experiments.La recombinaison Homologue est un chemin essentiel dans la réparation de dommages d'ADN pendant le procédé de réplication d'ADN. La protéine de RecA promeut les étapes centrales dans la recombinaison homologue, après avoir revêtu ADN seul-abandonné (ssDNA), RecA exécute un mettre et la réaction d'échange de brin impliquant ADN homologue. Ce projet de recherche vise à caractériser la fonction de RecA dans la recombinaison homologue utilisant la molécule seule mouvement de particule attaché (TPM). TPM d'utilisation pour observer l'extension de RecA le long d'ADN, le taux d'extension de RecA sur ssDNA a été déterminé pour la première fois. Le taux obtenu pour dsDNA était similaire, impliquant ce RecA polymerizes le long de seulement un brin d'un substrat d'ADN. Le comportement de nucleation de RecA sur ADN a été aussi obtenu de la trace d'extension, confirmant l'hypothèse ce nucleation rapide sur ssDNA est indépendant du pH, pendant que nucleation sur dsDNA est dépendant du pH. Plusieurs pilote plusieurs expériences de molécule seules ont visé à contrôlant le mettre et la réaction d'échange de brin a été tentée en temps réel. Bien que ces expériences étaient les ensembles infructueuses et réussies analogues biochimiques de ces expériences ont prouvé la possibilité des expériences de molécule seules. Ces tentatives ont donné de l'aux perspicacités dans les facteurs possibles freinant le succès et a mené à l'élément essentiel de suggestions expérimental au succès d'expériences future

On the nonlinear dynamics of a space platform based mobile flexible manipulator

The thesis aims at development of a rather versatile tool for studying dynamics and control of an orbiting flexible manipulator. It is motivated by the Canadian contribution, in the form of the Mobile Servicing System (MSS), to the U.S. led Space Station (Freedom) program, scheduled to be operational by the turn of the century. To begin, a relatively general dynamical formulation is developed for a large class of systems characterized by interconnected beam and/or rigid articulating members forming a chain-type geometry. As can be expected, the governing nonlinear, nonautonomous and coupled equations of motion, extremely long even in matrix notation, are not amenable to any known closed form solution. Hence the attention is focused towards development of an efficient numerical code, in a modular format to help assess relative importance of the various system parameters. Validity of the formulation and the computer code are assessed and their operational aspects demonstrated through a parametric response analysis. Emphasis throughout is on methodology and general approach leading to understanding of the multibody dynamics problem at the fundamental level.Applied Science, Faculty ofMechanical Engineering, Department ofGraduat

On the dynamics of spacecraft with a slewing appendage

A relatively general formulation for studying librational dynamics of a rigid satellite with a rigid appendage free to undergo any arbitrary slewing motion is developed. The governing nonlinear, nonautonomous and coupled equations are solved numerically. A parametric study suggests that the system can become unstable under critical combinations of inertia, geometric, orbital and slewing time history parameters. The fundamental information is relevant to the design of satellites and the Orbiter based experiments, and construction of the proposed space station, which would involve complex slewing motion of structural components.Applied Science, Faculty ofMechanical Engineering, Department ofGraduat