Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol

Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also exhibited age-dependent neurodegeneration of sensory neurons, which was preceded by severe progressive chemosensory defects. A focussed chemical screen revealed that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required, as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases

Reliability of a novel thermal imaging system for temperature assessment of healthy feet

Abstract Background Thermal imaging is a useful modality for identifying preulcerative lesions (“hot spots”) in diabetic foot patients. Despite its recognised potential, at present, there is no readily available instrument for routine podiatric assessment of patients at risk. To address this need, a novel thermal imaging system was recently developed. This paper reports the reliability of this device for temperature assessment of healthy feet. Methods Plantar skin foot temperatures were measured with the novel thermal imaging device (Diabetic Foot Ulcer Prevention System (DFUPS), constructed by Photometrix Imaging Ltd) and also with a hand-held infrared spot thermometer (Thermofocus® 01500A3, Tecnimed, Italy) after 20 min of barefoot resting with legs supported and extended in 105 subjects (52 males and 53 females; age range 18 to 69 years) as part of a multicentre clinical trial. The temperature differences between the right and left foot at five regions of interest (ROIs), including 1st and 4th toes, 1st, 3rd and 5th metatarsal heads were calculated. The intra-instrument agreement (three repeated measures) and the inter-instrument agreement (hand-held thermometer and thermal imaging device) were quantified using intra-class correlation coefficients (ICCs) and the 95% confidence intervals (CI). Results Both devices showed almost perfect agreement in replication by instrument. The intra-instrument ICCs for the thermal imaging device at all five ROIs ranged from 0.95 to 0.97 and the intra-instrument ICCs for the hand-held-thermometer ranged from 0.94 to 0.97. There was substantial to perfect inter-instrument agreement between the hand-held thermometer and the thermal imaging device and the ICCs at all five ROIs ranged between 0.94 and 0.97. Conclusions This study reports the performance of a novel thermal imaging device in the assessment of foot temperatures in healthy volunteers in comparison with a hand-held infrared thermometer. The newly developed thermal imaging device showed very good agreement in repeated temperature assessments at defined ROIs as well as substantial to perfect agreement in temperature assessment with the hand-held infrared thermometer. In addition to the reported non-inferior performance in temperature assessment, the thermal imaging device holds the potential to provide an instantaneous thermal image of all sites of the feet (plantar, dorsal, lateral and medial views). Trial registration Diabetic Foot Ulcer Prevention System NCT02317835, registered December 10, 201

Ferromagnetic Semiconductors: Moving Beyond (Ga,Mn)As

The recent development of MBE techniques for growth of III-V ferromagnetic semiconductors has created materials with exceptional promise in spintronics, i.e. electronics that exploit carrier spin polarization. Among the most carefully studied of these materials is (Ga,Mn)As, in which meticulous optimization of growth techniques has led to reproducible materials properties and ferromagnetic transition temperatures well above 150 K. We review progress in the understanding of this particular material and efforts to address ferromagnetic semiconductors as a class. We then discuss proposals for how these materials might find applications in spintronics. Finally, we propose criteria that can be used to judge the potential utility of newly discovered ferromagnetic semiconductors, and we suggest guidelines that may be helpful in shaping the search for the ideal material.Comment: 37 pages, 4 figure

Slepian functions and their use in signal estimation and spectral analysis

It is a well-known fact that mathematical functions that are timelimited (or spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the finite precision of measurement and computation unavoidably bandlimits our observation and modeling scientific data, and we often only have access to, or are only interested in, a study area that is temporally or spatially bounded. In the geosciences we may be interested in spectrally modeling a time series defined only on a certain interval, or we may want to characterize a specific geographical area observed using an effectively bandlimited measurement device. It is clear that analyzing and representing scientific data of this kind will be facilitated if a basis of functions can be found that are "spatiospectrally" concentrated, i.e. "localized" in both domains at the same time. Here, we give a theoretical overview of one particular approach to this "concentration" problem, as originally proposed for time series by Slepian and coworkers, in the 1960s. We show how this framework leads to practical algorithms and statistically performant methods for the analysis of signals and their power spectra in one and two dimensions, and on the surface of a sphere.Comment: Submitted to the Handbook of Geomathematics, edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verla

Scalar and vector Slepian functions, spherical signal estimation and spectral analysis

It is a well-known fact that mathematical functions that are timelimited (or spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the finite precision of measurement and computation unavoidably bandlimits our observation and modeling scientific data, and we often only have access to, or are only interested in, a study area that is temporally or spatially bounded. In the geosciences we may be interested in spectrally modeling a time series defined only on a certain interval, or we may want to characterize a specific geographical area observed using an effectively bandlimited measurement device. It is clear that analyzing and representing scientific data of this kind will be facilitated if a basis of functions can be found that are "spatiospectrally" concentrated, i.e. "localized" in both domains at the same time. Here, we give a theoretical overview of one particular approach to this "concentration" problem, as originally proposed for time series by Slepian and coworkers, in the 1960s. We show how this framework leads to practical algorithms and statistically performant methods for the analysis of signals and their power spectra in one and two dimensions, and, particularly for applications in the geosciences, for scalar and vectorial signals defined on the surface of a unit sphere.Comment: Submitted to the 2nd Edition of the Handbook of Geomathematics, edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verlag. This is a slightly modified but expanded version of the paper arxiv:0909.5368 that appeared in the 1st Edition of the Handbook, when it was called: Slepian functions and their use in signal estimation and spectral analysi

The development and implementation of an oxygen treatment solution for health facilities in low and middle-income countries

Background Oxygen reduces mortality from severe pneumonia and is a vital part of case management, but achieving reliable access to oxygen is challenging in low and middle-income country (LMIC) settings. We developed and field tested two oxygen supply solutions suitable for the realities of LMIC health facilities. Methods A Health Needs Assessment identified a technology gap preventing reliable oxygen supplies in Gambian hospitals. We used simultaneous engineering to develop two solutions: a Mains-Power Storage (Mains-PS) system consisting of an oxygen concentrator and batteries connected to mains power, and a Solar-Power Storage (Solar-PS) system (with batteries charged by photovoltaic panels) and evaluated them in health facilities in The Gambia and Fiji to assess reliability, usability and costs. Results The Mains-PS system delivered the specified ≥85% (±3%) oxygen concentration in 100% of 1-2 weekly measurements over 12 months, which was available to 100% of hypoxaemic patients, and 100% of users rated ease-of-use as at least ‘good’ (90% very good or excellent). The Solar-PS system delivered ≥85% ± 3%) oxygen concentration in 100% of 1-2 weekly measurements, was available to 100% of patients needing oxygen, and 100% of users rated ease-of-use at least very good. Costs for the systems (in US dollars) were: PS$9519, Solar-PS standard version$20 718. The of oxygen for a standardised 30-bed health facility using 1.7 million litres of oxygen per year was: for cylinders 3.2 cents (c)/L in The Gambia and 6.8 c/L in Fiji, for the PS system 1.2 c/L in both countries, and for the Solar-PS system 1.5 c/L in both countries. Conclusions The oxygen systems developed and tested delivered high-quality, reliable, cost-efficient oxygen in LMIC contexts, and were easy to operate. Reliable oxygen supplies are achievable in LMIC health facilities like those in The Gambia and Fiji

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models