Despite its extreme toxicity, botulinum neurotoxin is widely utilized in low doses as a treatment for several neurological disorders; higher doses cause the neuroparalytic syndrome botulism. The ...toxin blocks neurotransmitter release by preferentially attaching to pre-synaptic membrane receptors at neuromuscular junctions and subsequently delivering a Zn ²⁺-dependent protease component to presynaptic neuronal cytosol. These highly specialized enzymes exclusively hydrolyze peptide bonds within SNARE (soluble N-ethylmaleiamide sensitive factor attachment protein receptor) proteins. In this review we discuss the structural basis for botulinum toxin's exquisite specificity for its neuronal cell-surface receptors and intracellular SNARE targets.
The Enriched Xenon Observatory (EXO) will search for double beta decays of
136Xe. We report the results of a systematic study of trace concentrations of radioactive impurities in a wide range of raw ...materials and finished parts considered for use in the construction of EXO-200, the first stage of the EXO experimental program. Analysis techniques employed, and described here, include direct gamma counting, alpha counting, neutron activation analysis, and high-sensitivity mass spectrometry.
Adenovirus (Ad)-based cancer gene therapy is a promising, novel approach for treating cancer resistant to established treatment modalities. Unfortunately, the efficacy of nonreplicative first ...generation Ads was low and data from clinical trials were disappointing. To address this problem, conditionally replicating Ads have been constructed. Infection of tumor cells with conditionally replicating Ads results in tumor-specific replication, subsequent oncolysis and release of the virus progeny. Recently, it has been suggested that the low expression of the coxsackie-Ad receptor is the rate-limiting factor for infectivity with serotype 5 (Ad5). Unfortunately, coxsackie-Ad receptor expression is highly variable and often low on many tumor types. Consequently, molecular strategies have been applied for the development of coxsackie-Ad receptor-independent oncolytic Ads. This review describes recent developments of Ad-based cancer gene therapy, including novel engineering techniques of the Ad capsid for efficient tumor targeting, as well as targeting techniques, to restrict transgene expression to cancer cells.
We present an update of the development of an electromagnetic calorimeter for the Silicon Detector concept for a future linear electron-positron collider. Mechanical progress for a full barrel ...calorimeter that provides a more complete basis for simulation is discussed. Crosstalk problems in the first version of the sensor were found in a first testbeam study, and a second version of the sensor is now beginning testing.
Obesity is thought to negatively impact bone quality and strength, despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high fat, high sugar (HFS) diet would ...impair bone quality and strength; and 2) a change from a HFS diet to a low fat, low sugar (LFS) would reverse HFS-induced impairments to bone quality and strength.
Six-week-old male C57Bl/6 mice (n = 10/group) with access to a running wheel were randomized to a LFS diet or a HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 weeks. HFS mice were subsequently randomized to continuing HFS feeding (HFS/HFS) or transition to the LFS diet (HFS/LFS) for four additional weeks.
HFS/HFS mice exhibited superior femoral cancellous microarchitecture (i.e., greater BV/TV, Tb.N, Tb.Th and decreased Tb.Sp) and cortical bone geometry (i.e., lower Ct.CSA and pMOI) compared to all other groups. At the femoral mid-diaphysis, structural, but not material, mechanical properties were greatest in HFS/HFS mice. However, HFS/HFS exhibited greater femoral neck strength only when compared to mice assigned to diet transition (HFS/LFS). Osteoclast surface and the percentage of osteocytes staining positive for interferon-gamma were greater in HFS/LFS mice, consistent with reduced cancellous microarchitecture post-diet transition.
HFS feeding enhanced bone anabolism and structural, but not material, mechanical properties in exercising mice. A change from a HFS to LFS diet returned the bone structure to that of continuously LFS-fed mice while compromising strength. Our results indicate rapid weight loss from obese states should be performed with caution to prevent bone fragility. A deeper analysis into the altered bone phenotype in diet-induced obesity from a metabolic standpoint is needed.
Characterization of large area APDs for the EXO-200 detector Neilson, R.; LePort, F.; Pocar, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
09/2009, Volume:
608, Issue:
1
Journal Article
Peer reviewed
Open access
Enriched Xenon Observatory (EXO)-200 uses 468 large area avalanche photodiodes (LAAPDs) for detection of scintillation light in an ultra-low-background liquid xenon (LXe) detector. We describe ...initial measurements of dark noise, gain and response to xenon scintillation light of LAAPDs at temperatures from room temperature to 169
K—the temperature of liquid xenon. We also describe the individual characterization of more than 800 LAAPDs for selective installation in the EXO-200 detector.
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