Characterization of the near-Earth Asteroid 2002NY40

In August 2002, the near-Earth asteroid 2002 NY40, made its closest approach to the Earth. This provided an opportunity to study a near-Earth asteroid with a variety of instruments. Several of the telescopes at the Maui Space Surveillance System were trained at the asteroid and collected adaptive optics images, photometry and spectroscopy. Analysis of the imagery reveals the asteroid is triangular shaped with significant self-shadowing. The photometry reveals a 20-hour period and the spectroscopy shows that the asteroid is a Q-type

Oxidation of Thiols to Disulfides using an Environmentally “Green” Organocatalyst and New Mechanistic Insights

The selective oxidation of thiols to disulfides is an area of great importance in the areas of materials and medicinal chemistry research. The production of polymers, rubber, pharmaceuticals, and the folding of proteins in biological systems all rely on the formation of disulfide bonds. Herein, we introduce a stoichiometric and electrocatalytic method for the oxidation of various pharmaceutically and biologically relevant thiols into their respective disulfides in more environmentally benign solvents such as water and alcohol solvents. The scope of the transformation was evaluated and a detailed mechanistic study involving control experiments, experimental kinetic studies, and computational investigations led to new insights into how the oxidation takes place via an unusual anionic process

Small-molecule inhibitors of ferrochelatase are antiangiogenic agents

Activity of the heme synthesis enzyme ferrochelatase (FECH) is implicated in multiple diseases. In particular, it is a mediator of neovascularization in the eye and thus an appealing therapeutic target for preventing blindness. However, no drug-like direct FECH inhibitors are known. Here, we set out to identify small-molecule inhibitors of FECH as potential therapeutic leads using a high-throughput screening approach to identify potent inhibitors of FECH activity. A structure-activity relationship study of a class of triazolopyrimidinone hits yielded drug-like FECH inhibitors. These compounds inhibit FECH in cells, bind the active site in cocrystal structures, and are antiangiogenic in multiple in vitro assays. One of these promising compounds was antiangiogenic in vivo in a mouse model of choroidal neovascularization. This foundational work may be the basis for new therapeutic agents to combat not only ocular neovascularization but also other diseases characterized by FECH activity

Managerial Power, Stock-Based Compensation, and Firm Performance: Theory and Evidence

We study theoretically and empirically the relation among CEO power, CEO pay and firm performance. Our theoretical model follows the rent extraction view of CEO compensation put forward by the managerial power theory. We test our theoretical findings using the sample of S&P1500 firms. The predicted relation between power and pay is largely supported. However, the relation between power and firm performance has mixed support, suggesting that, while the managerial power theory has relevance in explaining the relation between power and pay, the scope of power needs to be broadened for better understanding of how managerial power affects firm performance

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Decreased Lactobacillus populations after erythromycin treatment hinders the induction of oral tolerance to fed ovalbumin

Oral tolerance is an immunologic hyporesponsiveness to an orally administered antigen. Probiotics (beneficial intestinal bacteria), T regulatory cells (Tregs), and dendritic cells (DCs) are all essential for generating tolerance and suppressing immune responses toward harmless antigens. Antibiotics are commonly prescribed to fight infections and often necessary for maintaining health, but they can disrupt the normal intestinal microbial populations. There is increasing epidemiologic evidence that suggests that antibiotic usage correlates with the development of irritable bowel disorders, which often result due to a breakdown in immune tolerance. This study investigated the effect of the antibiotic erythromycin on oral tolerance induction to ovalbumin (OVA). The results demonstrate that antibiotic treatment prior to exposure to fed antigen prevents tolerance to that antigen, and this correlated with a reduction in intestinal Lactobacillus populations. Furthermore, antibiotic treatment resulted in a significant decrease in the tolerogenic CD11c+/CD11b+/CD8α- MLN DCs independent of tolerizing treatment.Thesis (M.S.)Department of Biolog

Therapeutic aid to the sexually abused child in the family, a psychological educational perspective

Terapeutiese hulpverlening aan die seksueel gemolesteerde kind binne gesinsverband vanuit 'n Sielkundige Opvoedkundige perspektief is in hierdie studie onderneem. 'n Oorsig oor seksuele kindermolestering binne gesinsverband het getoon dat dit reeds vanaf die vroegste tye voorgekom het en tans kommerwekkende afmetings aanneem in die Republiek van Suid-Afrika, sonder dat die opvoedkundige sielkundige as lid van 'n multi-professionele span betrek word by terapeutiese hulpverlening. 'n Beskrywing van seksuele kindermolestering binne gesinsverband het getoon dat seksuele kindermolestering verskeie vorme aanneem en dat die oortreders daarvoor verantwoordelik is dat ouerskap en gesinstrukture ontoereikend verwerklik word. Dit bied aan die opvoedkundige sielkundige die moontlikheid om vanwee sy toeganklikheid en professionele deskundigheid as lid van 'n multiprofessionele span toereikend terapeutiese hulp te verleen aan die seksueel gemolesteerde kind. Terapeutiese hulpverlening aan die seksueel gemolesteerde kind binne gesinsverband is onderneem vanuit 'n Sielkundige Opvoedkundige benadering met relasie terapie as wyse van hulpverleningThis study investigates therapeutic aid to the child who is sexually abused by a family member, from the viewpoint of Psychology of Education. An overview of sexual abuse of children in the family context indicates a long history of occurence and present statistics show an alarming increase in reported cases with educational psychologists seldom being included in a multi-discipl inary thera-peutic team. A description of sexual abuse of children in the family context suggests that this may take different forms and the perpetrators are responsible for the breakdown in parenting and family structures. Educational psychologists are, because of their professional expertise and accessibility, able to offer thera-peutic aid to the sexually abused child as a member of a multi-professional team. Therapeutic aid to the sexually abused child in the family context is undertaken with Relationship Therapy as a medium of aidPsychology of EducationM.Ed. (Sielkundige Opvoedkunde