An Analysis of Nuclear-Rocket Nozzle Cooling

A nuclear-rocket regenerative-cooling analysis was conducted over a range of reactor power of 46 to 1600 megawatts and is summarized herein. Although the propellant (hydrogen) is characterized by a large heat-sink capacity, an analysis of the local heat-flux capability of the coolant at the nozzle throat indicated that, for conventional values of system pressure drop, the cooling capability was inadequate to maintain a selected wall temperature of 1440 R. Several techniques for improving the cooling capability were discussed, for example, high pressure drop, high wall temperature, refractory wall coatings, thin highly conductive walls, and film cooling. In any specific design a combination of methods will probably be utilized to achieve successful cooling

Using Xenon as a Heavy Atom for Determining Phases in Sperm Whale Metmyoglobin

Xenon gas can be used as a heavy atom for determining phases in a protein. We demonstrate that an interpretable electron density map can be obtained for sperm whale metmyoglobin from a single xenon derivative using iterative single isomorphous replacement with the anomalous scattering method

Using Xenon as a Heavy Atom for Determining Phases in Sperm Whale Metmyoglobin

Xenon gas can be used as a heavy atom for determining phases in a protein. We demonstrate that an interpretable electron density map can be obtained for sperm whale metmyoglobin from a single xenon derivative using iterative single isomorphous replacement with the anomalous scattering method

The Ursinus Weekly, January 15, 1962

Shadowy figure of Ursinus\u27 past publishes volume of 66 poems • Dr. Snyder, Forum speaker, outlines seven strong forces in Africa today • Spontaneous fun object of new social committee • Prof casts critical eye over Lantern; Discovers sound creative instincts • Bursting water pipe sends Alumni Office to 620 Main • Student teachers\u27 light-hearted talk explains what\u27s not in the Ed. book • Best-dressed co-ed sought by Weekly • Shares of the pecuniary pie • Pre-medders hear about corneal transplant work • Editorial: Appeal of wrestling • Ursinus in the past • Letters to the editor • Obituary for a timid intellectual • Dryfoos sets two Ursinus cage marks; Dean ties record with quick pin • Pair of heartbreaking losses catch grapplers last week • Basketball begins • Frymen flounder; Lose to PMC, 92-80; Drop thriller to Swarthmore, 89 to 85 • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1309/thumbnail.jp

Characterization of carbonic anhydrase isozyme specific inhibition by sulfamated 2-ethylestra compounds

Sulfamated 2-ethylestra compounds have demonstrated strong anticancer activity, high bioavailability and an ability to bypass liver metabolism by reversibly binding carbonic anhydrase (CA) II in erythrocytes. Another CA isoform, CA IX, is overexpressed in many cancers. The CA domain of CA IX is oriented extracellularly, which may permit targeting inhibitors to tumors. Presented here is the characterization of three 2-ethylestra compounds bound to both CA II and a CA IX mimic protein. Inhibition by 18O exchange showed that compound 16 demonstrated an approximately 12-fold higher affinity for CA II over CA IX mimic. Structurally, compounds 15 and 16 showed alternate binding modes between CA II and CA IX mimic, apparently due to a water-mediated hydrogen bond to the isozyme-specific residue 67. Though the specificity was demonstrated for CA II over CA IX, this study reveals insights that may be key to developing isozyme specific CA inhibitors for novel anticancer therapies.This work was supported by NIH Grant GM25154 and by grants from the Medical Research Council of South Africa (AG374, AK076), the Cancer Association of South Africa (AK246), the Struwig-Germeshuysen Cancer Research Trust of South Africa (AJ038) and RESCOM University of Pretoria (A0R984).http://www.benthamscience.com/lddd/nf201

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The Victorian Newsletter (Spring 1967)

The Victorian Newsletter is edited for the English X Group of the Modern Language Association by William E. Buckler, New York University, New York, N.Y. 10003

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS