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.
Abstract NAPA-p1 is a prototype Monolithic Active Pixel Sensor 'MAPS' developed as a first iteration towards meeting the detectors general requirements for future e + e - colliders. Long-term ...objective is to develop a wafer-scale sensor in MAPS with an area ∼ 10 cm × 10 cm. This article presents the motivations for the design choices of NAPA-p1, translating the physics requirement into circuit specifications. Simulations show a pixel jitter of < 400 ps-rms and an equivalent noise charge of 13 e - rms with an average power consumption of 1.15 mW/cm 2 assuming a 1% duty cycle, meeting the target specifications. The prototype is designed in 65 nm CMOS imaging technology, with dimensions of 1.5 mm × 1.5 mm and a pixel pitch of 25 μm. The prototype chip has been fabricated and characterization results will be available soon.
A search for Lorentz- and CPT-violating signals in the double beta decay spectrum of super(136) Xe has been performed using an exposure of 100kgmiddotyr with the EXO-200 detector. No significant ...evidence of the spectral modification due to isotropic Lorentz-violation was found, and a two-sided limit of -2.65x10 super(-5)GeV(ProQuest: Formulae and/or non-USASCII text omitted) <7.60x10 super(-6)GeV (90% C.L.) is placed on the relevant coefficient within the Standard-Model Extension (SME). This is the first experimental study of the effect of the SME-defined oscillation-free and momentum-independent neutrino coupling operator on the double beta decay process.
A high-resolution beam telescope is one of the most important and demanding infrastructure components at any test beam facility. Its main purpose is to provide reference particle tracks from the ...incoming test beam particles to the test beam users, which allows measurement of the performance of the device-under-test (DUT). LYCORIS, a six-plane compact beam telescope with an active area of ∼ 10 × 10 cm2 (extensible to 10× 20 cm2) was installed at the DESY II Test Beam Facility in 2019, to provide a precise momentum measurement in a 1 T solenoid magnet or to provide tracking over a large area. The overall design of Lycoris will be described as well as the performance of the chosen silicon sensor. The 25 μm pitch micro-strip sensor used for Lycoris was originally designed for the SiD detector concept for the International Linear Collider. It adopts a second metallization layer to route signals from strips to the bump-bonded KPiX ASIC and uses a wire-bonded flex cable for the connection to the DAQ and the power supply system. This arrangement eliminates the need for a dedicated hybrid PCB. Its performance was tested for the first time in this project. The system has been evaluated at the DESY II Test Beam Facility in several test-beam campaigns and has demonstrated an average single-point resolution of 7.07 μm.
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, Letnik:
608, Številka:
1
Journal Article
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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.
The energy resolution of the EXO-200 detector is limited by electronics noise in the measurement of the scintillation response. Here we present a new technique to extract optimal scintillation energy ...measurements for signals split across multiple channels in the presence of correlated noise. The implementation of these techniques improves the energy resolution of the detector at the neutrinoless double beta decay Q-value from 1.9641 + or - 0.0039% to 1.5820 + or - 0.0044%.
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