Multi-purpose wind tunnel reaction control model block

A reaction control system nozzle block is provided for testing the response characteristics of space vehicles to a variety of reaction control thruster configurations. A pressurized air system is connected with the supply lines which lead to the individual jet nozzles. Each supply line terminates in a compact cylindrical plenum volume, axially perpendicular and adjacent to the throat of the jet nozzle. The volume of the cylindrical plenum is sized to provide uniform thrust characteristics from each jet nozzle irrespective of the angle of approach of the supply line to the plenum. Each supply line may be plugged or capped to stop the air supply to selected jet nozzles, thereby enabling a variety of nozzle configurations to be obtained from a single model nozzle block

Electron Stimulated Surface Chemistry

When an electron beam of less than 1000 eV interacts with a surface layer a variety of phenomena may occur. In this paper I will discuss those interactions that lead to either chemical changes on the surface and/or desorption of species or fragments from the surface. Theoretical models of electron stimulated desorption, (ESD) will be presented, specifically the Menzel, Gomer, and Redhead model, the Knotek, Feibelman model and the Ramaker, White and Murday model. Experiments that display the angular distribution of the desorbing ionic or metastable fragments, (referred to as ESDIAD for Electron Stimulated Desorption: Ion Angular Distributions) are the primary emphasis. The process of electron beam induced conversion of CO on metal surfaces (Pt (111) and Ni (110)) with the emission of O+, CO+, and CO* from the surface as seen in ESDIAD experiments shows a change of phase of the surface CO on the nickel surface above 0.75 CO/Ni and an interesting change in the bonding configuration in the coverage range of 0.50 - 0.66 CO/Pt on the platinum surface. The ESDIAD data show that NH2 adsorbed on the silicon (100) reconstructed surface yields a very broad elliptical ESDIAD distribution that is peaked normal to the (100) surface and oriented with its major axis perpendicular to the Si surface dimers. The hydroxyl group, OH, has a four beam ESDIAD pattern that indicates off normal orientations for the H bond of OH on Si (100). Fluorine is emitted from the Si (100) surface along the direction of the Si dangling bond. The conversion of NH3 to NH2 on Ni (110) is a beam induced effect in a surface layer as seen by ESDIAD. The electron beam dissociates the NH3 by releasing an H+ ion and leaving NH2 which produces a two lobed ESDIAD pattern. The conversion of PF3 (another surface rotor) to PF2 and PF on Ni (111) surfaces is manifest in a six lobed ESDIAD pattern that rotates 30° and acquires a strong central beam as a result of electron bombardment. These ESDIAD beams are correlated with bonding orientation and sites for PF2 and PF on the Ni (111) surface. The surface spectroscopy of electron energy loss spectroscopy, EELS, is presented to demonstrate the electron beam induced decomposition of dimethyl and difluoromethyl ether on an alumina (Al2O3) surface. The resultant surface species from the fluorinated ether appears to contain a very stable form of an AI-F bond

Changes in Nest Density and Daily Nest Survival of Two Woodpecker Species in Relation to a Mountain Pine Beetle Epidemic

The Mountain pine beetle (Dendrotonus ponderosae) is a bark beetle native to western North America capable of large-scale population eruptions, resulting in high tree (Pinus spp.) mortality that alters resource availability to wildlife, particularly snag-associated species. Many woodpecker species rely on conifer snags for nesting and foraging substrate. We studied nesting survival of two woodpecker species in relation to a recent mountain pine beetle outbreak in western Montana. American three-toed woodpecker (Picoides dorsalis) is a bark-drilling specialist that feeds on beetle larvae and frequently nests in conifer snags, whereas red-naped sapsucker (Sphyrapicus nuchalis) specializes on consuming sap of live trees and rarely nests in conifer snags. Based on a priori hypotheses we modeled daily nest survival (DSR) as a function of biotic (nest height) and temporal (beetle period [before and after outbreak], date trend, and a quadratic date trend) factors using seven competing models. Results for both species showed high model uncertainty and the constant DSR model was the most parsimonious model. These results did not support our predictions about beetle period or nest height affecting DSR, although DSR was lower during pre-outbreak (0.985, 95% CL [0.965, 0.995]) versus post-outbreak (0.993, 95% CL [0.981, 0.997]) for American three-toed woodpecker. Future analyses will investigate the effects of other covariates such as snag density, daily temperature, and precipitation on DSR. Our results will inform management activities for post-beetle forests that will help maintain habitat of disturbance specialist species

Lithium peroxide test program Final report

Experimental design and performance data on carbon dioxide and oxygen control for portable life support system using lithium peroxid

Effects of eplerenone on resistance to antihypertensive medication in patients with primary or secondary hyperaldosteronism

Background and Objectives: Resistant hypertension is an important problem; nearly half of diagnosed hypertensives are not controlled to target blood pressure levels, and approximately 90% of strokes occur among patients with resistant hypertension. Primary aldosteronism accounts for approximately 20% of resistant hypertension, but the role of secondary hyperaldosteronism in resistant hypertension is seldom considered. We assessed the effects of eplerenone in patients with hypertension and either primary or secondary hyperaldosteronism. Methods: Patients with a history of resistant hypertension and a supine plasma aldosterone level ≥ 360 pmol/L were randomized to eplerenone versus placebo in a fully blinded study for one year. A medication intensity score was developed to assess the resistance of hypertension to medication (blood pressure × medication intensity). We assessed the effects of eplerenone on blood pressure and on resistance to concomitant medication. Results: Final results were available in 37 patients (19 on eplerenone and 18 on placebo). Resistance to medication, as assessed by the intensity of concomitant medication required to maintain blood pressure control, was markedly reduced by eplerenone: medication intensity scores declined by −0.50 ± 1.04 (SD) on placebo versus −2.11 ± 1.45 with eplerenone (P = 0.0001), the Systolic Resistance Score declined by −80.00 ± 122.93 on placebo versus −334.05 ± 21.73 on eplerenone (P = 0.0001), and the Diastolic Resistance Score increased by 1.28 ± 31.65 on placebo and declined by −40.74 ± 57.08 on eplerenone (P = 0.009). Conclusions: Eplerenone significantly reduced resistance to concomitant antihypertensive medication in both primary and secondary hyperaldosteronism

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against <it>agr </it>functional and dysfunctional HA-MRSA and CA-MRSA.</p> <p>Methods</p> <p>40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of <it>agr </it>function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10⁶and 10⁸cfu/ml of <it>agr </it>functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.</p> <p>Results</p> <p>15% isolates were <it>agr </it>dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10⁶cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among <it>agr </it>functional and dysfunctional strains. However, against a high initial inoculum of 10⁸cfu/ml, killing activity was notably attenuated against <it>agr </it>dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log₁₀CFU/ml for <it>agr </it>functional vs. 2.41 log₁₀CFU/ml for <it>agr </it>dysfunctional MRSA (p = 0.0007).</p> <p>Conclusions</p> <p>Dysfunction in <it>agr </it>was less common among CA-MRSA vs. HA-MRSA. <it>agr </it>dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.</p

Molecular Mechanisms Involved in Vascular Interactions of the Lyme Disease Pathogen in a Living Host

Hematogenous dissemination is important for infection by many bacterial pathogens, but is poorly understood because of the inability to directly observe this process in living hosts at the single cell level. All disseminating pathogens must tether to the host endothelium despite significant shear forces caused by blood flow. However, the molecules that mediate tethering interactions have not been identified for any bacterial pathogen except E. coli, which tethers to host cells via a specialized pillus structure that is not found in many pathogens. Furthermore, the mechanisms underlying tethering have never been examined in living hosts. We recently engineered a fluorescent strain of Borrelia burgdorferi, the Lyme disease pathogen, and visualized its dissemination from the microvasculature of living mice using intravital microscopy. We found that dissemination was a multistage process that included tethering, dragging, stationary adhesion and extravasation. In the study described here, we used quantitative real-time intravital microscopy to investigate the mechanistic features of the vascular interaction stage of B. burgdorferi dissemination. We found that tethering and dragging interactions were mechanistically distinct from stationary adhesion, and constituted the rate-limiting initiation step of microvascular interactions. Surprisingly, initiation was mediated by host Fn and GAGs, and the Fn- and GAG-interacting B. burgdorferi protein BBK32. Initiation was also strongly inhibited by the low molecular weight clinical heparin dalteparin. These findings indicate that the initiation of spirochete microvascular interactions is dependent on host ligands known to interact in vitro with numerous other bacterial pathogens. This conclusion raises the intriguing possibility that fibronectin and GAG interactions might be a general feature of hematogenous dissemination by other pathogens

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy

Immunohistochemical expression and prognostic value of PD-L1 in Extrapulmonary small cell carcinoma: a single institution experience

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors. METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution. RESULTS: Twelve out 34 cases (35%) had PD-L1 CPS scores \u3e /=1. Ten cases had CPS scores ranging 1-5, whereas 2 cases had CPS scores \u3e 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group (p-value 0.34). Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage (p-value 0.80). CONCLUSIONS: This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients