Singularities in optimal structural design

Singularity conditions that arise during structural optimization can seriously degrade the performance of the optimizer. The singularities are intrinsic to the formulation of the structural optimization problem and are not associated with the method of analysis. Certain conditions that give rise to singularities have been identified in earlier papers, encompassing the entire structure. Further examination revealed more complex sets of conditions in which singularities occur. Some of these singularities are local in nature, being associated with only a segment of the structure. Moreover, the likelihood that one of these local singularities may arise during an optimization procedure can be much greater than that of the global singularity identified earlier. Examples are provided of these additional forms of singularities. A framework is also given in which these singularities can be recognized. In particular, the singularities can be identified by examination of the stress displacement relations along with the compatibility conditions and/or the displacement stress relations derived in the integrated force method of structural analysis

Far-Infrared Blocked Impurity Band Detector Development

DRS Sensors & Targeting Systems, supported by detector materials supplier Lawrence Semiconductor Research Laboratory, is developing far-infrared detectors jointly with NASA Langley under the Far-IR Detector Technology Advancement Partnership (FIDTAP). The detectors are intended for spectral characterization of the Earth's energy budget from space. During the first year of this effort we have designed, fabricated, and evaluated pilot Blocked Impurity Band (BIB) detectors in both silicon and germanium, utilizing pre-existing customized detector materials and photolithographic masks. A second-year effort has prepared improved silicon materials, fabricated custom photolithographic masks for detector process, and begun detector processing. We report the characterization results from the pilot detectors and other progress

West Nile Virus Detection in American Crows

A dipstick immunochromatographic assay used for West Nile virus (WNV) detection in mosquitoes was investigated for application to testing of fecal, saliva, and tissue samples from dead American Crows (Corvus brachyrhynchos). Results suggest that VecTest may be an efficient method for WNV detection in field-collected, dead American Crows, although confirmation of results and further investigation are warranted

West Nile Virus Detection in American Crows

A dipstick immunochromatographic assay used for West Nile virus (WNV) detection in mosquitoes was investigated for application to testing of fecal, saliva, and tissue samples from dead American Crows (Corvus brachyrhynchos). Results suggest that VecTest may be an efficient method for WNV detection in field-collected, dead American Crows, although confirmation of results and further investigation are warranted

First-in-Human Studies of MW01-6-189WH, a Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Studies in Healthy Adult Volunteers

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose-proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low-dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury

Recommendations for myasthenia gravis clinical trials

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Canine Leptospirosis, United States, 2002–2004

The proportion of positive Leptospira microscopic agglutination tests for 23,005 dogs significantly increased from 2002 to 2004 (p<0.002) regardless of the positive cutoff titer used and was highest (p<0.05) for serovars Autumnalis and Grippotyphosa. The strongest positive serologic correlation (r = 0.72) was between serovars Autumnalis and Pomona

Multi-Locus Sequence Typing of Bartonella henselae Isolates from Three Continents Reveals Hypervirulent and Feline-Associated Clones

Bartonella henselae is a zoonotic pathogen and the causative agent of cat scratch disease and a variety of other disease manifestations in humans. Previous investigations have suggested that a limited subset of B. henselae isolates may be associated with human disease. In the present study, 182 human and feline B. henselae isolates from Europe, North America and Australia were analysed by multi-locus sequence typing (MLST) to detect any associations between sequence type (ST), host species and geographical distribution of the isolates. A total of 14 sequence types were detected, but over 66% (16/24) of the isolates recovered from human disease corresponded to a single genotype, ST1, and this type was detected in all three continents. In contrast, 27.2% (43/158) of the feline isolates corresponded to ST7, but this ST was not recovered from humans and was restricted to Europe. The difference in host association of STs 1 (human) and 7 (feline) was statistically significant (P≤0.001). eBURST analysis assigned the 14 STs to three clonal lineages, which contained two or more STs, and a singleton comprising ST7. These groups were broadly consistent with a neighbour-joining tree, although splits decomposition analysis was indicative of a history of recombination. These data indicate that B. henselae lineages differ in their virulence properties for humans and contribute to a better understanding of the population structure of B. henselae