Design of an Activity-Based Probe for Human Neutrophil Elastase: Implementation of the Lossen Rearrangement To Induce Förster Resonance Energy Transfers.

Human neutrophil elastase is an important regulator of the immune response and plays a role in host defense mechanisms and further physiological processes. The uncontrolled activity of this serine protease may cause severe tissue alterations and impair inflammatory states. The design of an activity-based probe for human neutrophil elastase reported herein relies on a sulfonyloxyphthalimide moiety as a new type of warhead that is linker-connected to a coumarin fluorophore. The inhibitory potency of the activity-based probe was assessed against several serine and cysteine proteases, and the selectivity for human neutrophil elastase (Ki = 6.85 nM) was determined. The adequate fluorescent tag of the probe allowed for the in-gel fluorescence detection of human neutrophil elastase in the low nanomolar range. The coumarin moiety and the anthranilic acid function of the probe, produced in the course of a Lossen rearrangement, were part of two different Förster resonance energy transfers

Trajectories of self-rated health in people with diabetes: Associations with functioning in a prospective community sample

© 2013 Schmitz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Self-rated health (SRH) is a single-item measure that is one of the most widely used measures of general health in population health research. Relatively little is known about changes and the trajectories of SRH in people with chronic medical conditions. The aims of the present study were to identify and describe longitudinal trajectories of self-rated health (SRH) status in people with diabetes. Methods: A prospective community study was carried out between 2008 and 2011. SRH was assessed at baseline and yearly at follow-ups (n=1288). Analysis was carried out through trajectory modeling. The trajectory groups were subsequently compared at 4 years follow-up with respect to functioning. Results: Four distinct trajectories of SRH were identified: 1) 72.2% of the participants were assigned to a persistently good SRH trajectory; 2) 10.1% were assigned to a persistently poor SRH trajectory; 3) mean SRH scores changed from good to poor for one group (7.3%); while 4) mean SRH scores changed from poor to medium/good for another group (10.4%). Those with a persistently poor perception of health status were at higher risk for poor functioning at 4 years follow-up than those whose SRH scores decreased from good to poor. Conclusions: SRH is an important predictor for poor functioning in diabetes, but the trajectory of SRH seems to be even more important. Health professionals should pay attention to not only SRH per se, but also changes in SRH over time.This work was supported by Operating Grant MOP-84574 from the Canadian Institutes of Health Research (CIHR). GG was supported by a doctoral fellowship from the CIHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Solving the Shortest Vector Problem in Lattices Faster Using Quantum Search

By applying Grover's quantum search algorithm to the lattice algorithms of Micciancio and Voulgaris, Nguyen and Vidick, Wang et al., and Pujol and Stehl\'{e}, we obtain improved asymptotic quantum results for solving the shortest vector problem. With quantum computers we can provably find a shortest vector in time $2^{1.799n + o(n)}$, improving upon the classical time complexity of $2^{2.465n + o(n)}$ of Pujol and Stehl\'{e} and the $2^{2n + o(n)}$ of Micciancio and Voulgaris, while heuristically we expect to find a shortest vector in time $2^{0.312n + o(n)}$, improving upon the classical time complexity of $2^{0.384n + o(n)}$ of Wang et al. These quantum complexities will be an important guide for the selection of parameters for post-quantum cryptosystems based on the hardness of the shortest vector problem.Comment: 19 page

Digital Astronaut Project Biomechanical Models: Biomechanical Modeling of Squat, Single-Leg Squat and Heel Raise Exercises on the Hybrid Ultimate Lifting Kit (HULK)

The NASA Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and to enhance countermeasure development. The DAP Musculoskeletal Modeling effort is developing computational models to inform exercise countermeasure development and to predict physical performance capabilities after a length of time in space. For example, integrated exercise device-biomechanical models can determine localized loading, which will be used as input to muscle and bone adaptation models to estimate the effectiveness of the exercise countermeasure. In addition, simulations of mission tasks can be used to estimate the astronaut's ability to perform the task after exposure to microgravity and after using various exercise countermeasures. The software package OpenSim (Stanford University, Palo Alto, CA) (Ref. 1) is being used to create the DAP biomechanical models and its built-in muscle model is the starting point for the DAP muscle model. During Exploration missions, such as those to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Therefore, the crew must have access to exercise countermeasures that can maintain their musculoskeletal and aerobic health. Exploration vehicles may have very limited volume and power available to accommodate such capabilities, even more so than the International Space Station (ISS). The exercise devices flown on Exploration missions must be designed to provide sufficient load during the performance of various resistance and aerobic/anaerobic exercises while meeting potential additional requirements of limited mass, volume and power. Given that it is not practical to manufacture and test (ground, analog and/or flight) all candidate devices, nor is it always possible to obtain data such as localized muscle and bone loading empirically, computational modeling can estimate the localized loading during various exercise modalities performed on a given device to help formulate exercise prescriptions and other operational considerations. With this in mind, NASA's Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) laboratory and NSBRI-funded researchers by developing and implementing well-validated computational models of exercises with advanced exercise device concepts. This report focuses specifically on lower-body resistance exercises performed with the Hybrid Ultimate Lifting Kit (HULK) device as a deliverable to the AEC Project

Implementation of a High Throughput Soft MIMO Detector on GPU

Multiple-input multiple-output (MIMO) significantly increases the throughput of a communication system by employing multiple antennas at the transmitter and the receiver. To extract maximum performance from a MIMO system, a computationally intensive search based detector is needed. To meet the challenge of MIMO detection, typical suboptimal MIMO detectors are ASIC or FPGA designs. We aim to show that a MIMO detector on Graphic processor unit (GPU), a low-cost parallel programmable co-processor, can achieve high throughput and can serve as an alternative to ASIC/FPGA designs. However, careful architecture aware software design is needed to leverage the performance offered by GPU. We propose a novel soft MIMO detection algorithm, multi-pass trellis traversal (MTT), and show that we can achieve ASIC/FPGA-like performance and handle different configurations in software on GPU. The proposed design can be used to accelerate wireless physical layer simulations and to offload MIMO detection processing in wireless testbed platforms.NokiaNokia Siemens Networks (NSN)Texas InstrumentsXilinxNational Science Foundatio

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes

A High Throughput Configurable SDR Detector for Multi-user MIMO Wireless Systems

Spatial division multiplexing (SDM) in MIMO technology significantly increases the spectral efficiency, and hence capacity, of a wireless communication system: it is a core component of the next generation wireless systems, e.g. WiMAX, 3GPP LTE and other OFDM-based communication schemes. Moreover, spatial division multiple access (SDMA) is one of the widely used techniques for sharing the wireless medium between different mobile devices. Sphere detection is a prominent method of simplifying the detection complexity in both SDM and SDMA systems while maintaining BER performance comparable with the optimum maximum-likelihood (ML) detection. On the other hand, with different standards supporting different system parameters, it is crucial for both base station and handset devices to be configurable and seamlessly switch between different modes without the need for separate dedicated hardware units. This challenge emphasizes the need for SDR designs that target the handset devices. In this paper, we propose the architecture and FPGA realization of a configurable sort-free sphere detector, Flex-Sphere, that supports 4, 16, 64-QAM modulations as well as a combination of 2, 3 and 4 antenna/user configuration for handsets. The detector provides a data rate of up to 857.1 Mbps that fits well within the requirements of any of the next generation wireless standards. The algorithmic optimizations employed to produce an FPGA friendly realization are discussed.Xilinx Inc.National Science Foundatio

Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within normal ranges found in healthy subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of this study. Tissue Doppler imaging of the right ventricle revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower-extremity interstitial and vascular space after only 10 minutes of application. This report demonstrates that Braslet application affects right ventricular physiology in long-duration space flight based on TDI and that this effect is in part due to venous hemodynamics

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal