Differences in External and Internal Cortical Strain with Prosthesis in the Femur

The contact between a femoral stem prosthesis and the internal surface of the cortical bone with the stress in the interface is of crucial importance with respect to loosening. However, there are no reports of strain patterns at this site, and the main aim of the current study was to investigate differences of internal and external cortical strain in the proximal femur after insertion of a stem prosthesis. The external cortical strain of a human cadaveric femur was measured with strain gauges before and after implantation of a stem prosthesis. By use of optical fibres embedded longitudinally in the endosteal cortex, deformations at the implant–internal cortex interface could also be measured. The main external deformation during loading of the intact femur occurred as compression of the medial cortex; both at the proximal and distal levels. The direction of the principal strain on the medial and lateral aspects was close to the longitudinal axis of the bone. After resection of the femoral neck and insertion of a stem prosthesis, the changes in external strain values were greatest medially at the proximal level, where the magnitude of deformation in compression was reduced to about half the values measured on the intact specimen. Otherwise, there were rather small changes in external principal strain. However, by comparing vertical strain in the external and internal cortex of the proximal femur, there were great differences in values and patterns at all positions. The transcortical differences in strain varied from compression on one side to distraction on the other and vice versa in some of the positions with a correlation coefficient of 0.07. Our results show that differences exist between the external and internal cortical strain when loading a stem prosthesis. Hence, strain at the internal cortex does not correspond and can not be deducted from measured strain at the external cortex

Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (<it>SMN1</it>). <it>SMN2 </it>is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two <it>SMN2 </it>copies while most SMA type II patients carry three <it>SMN2 </it>copies and SMA III patients have three or four <it>SMN2 </it>copies. The <it>SMN1 </it>gene produces a full-length transcript (FL-SMN) while <it>SMN2 </it>is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.</p> <p>Methods</p> <p>In this study we performed quantification of the <it>SMN2 </it>gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the <it>SMN1 </it>gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.</p> <p>Results</p> <p>Comparison of the <it>SMN2 </it>copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the <it>SMN2 </it>gene. In both asymptomatic cases we found an increased number of <it>SMN2 </it>copies in the healthy carriers and a biallelic <it>SMN1 </it>absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.</p> <p>Conclusions</p> <p>We suggest that the <it>SMN2 </it>gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.</p

Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7

Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7

Effective field theory analysis of the first LUX dark matter search

The Large Underground Xenon (LUX) dark matter search was a 250-kg active mass dual-phase time projection chamber that operated by detecting light and ionization signals from particles incident on a xenon target. In December 2015, LUX reported a minimum 90% upper C.L. of 6×10-46 cm2 on the spin-independent WIMP-nucleon elastic scattering cross section based on a 1.4×104 kg·day exposure in its first science run. Tension between experiments and the absence of a definitive positive detection suggest it would be prudent to search for WIMPs outside the standard spin-independent/spin-dependent paradigm. Recent theoretical work has identified a complete basis of 14 independent effective field theory (EFT) operators to describe WIMP-nucleon interactions. In addition to spin-independent and spin-dependent nuclear responses, these operators can produce novel responses such as angular-momentum-dependent and spin-orbit couplings. Here we report on a search for all 14 of these EFT couplings with data from LUX's first science run. Limits are placed on each coupling as a function of WIMP mass

Ultra-Low Energy Calibration of LUX Detector using 127^{127}Xe Electron Capture

We report an absolute calibration of the ionization yields(\textit{Q_y}) and fluctuations for electronic recoil events in liquid xenon at discrete energies between 186 eV and 33.2 keV. The average electric field applied across the liquid xenon target is 180 V/cm. The data are obtained using low energy $^{127}$Xe electron capture decay events from the 95.0-day first run from LUX (WS2013) in search of Weakly Interacting Massive Particles (WIMPs). The sequence of gamma-ray and X-ray cascades associated with $^{127}$I de-excitations produces clearly identified 2-vertex events in the LUX detector. We observe the K- (binding energy, 33.2 keV), L- (5.2 keV), M- (1.1 keV), and N- (186 eV) shell cascade events and verify that the relative ratio of observed events for each shell agrees with calculations. The N-shell cascade analysis includes single extracted electron (SE) events and represents the lowest-energy electronic recoil $\textit{in situ}$ measurements that have been explored in liquid xenon

Investigation of background electron emission in the LUX detector

Dual-phase xenon detectors, as currently used in direct detection dark matter experiments, have observed elevated rates of background electron events in the low energy region. While this background negatively impacts detector performance in various ways, its origins have only been partially studied. In this paper we report a systematic investigation of the electron pathologies observed in the LUX dark matter experiment. We characterize different electron populations based on their emission intensities and their correlations with preceding energy depositions in the detector. By studying the background under different experimental conditions, we identified the leading emission mechanisms, including photoionization and the photoelectric effect induced by the xenon luminescence, delayed emission of electrons trapped under the liquid surface, capture and release of drifting electrons by impurities, and grid electron emission. We discuss how these backgrounds can be mitigated in LUX and future xenon-based dark matter experiments

First direct detection constraint on mirror dark matter kinetic mixing using LUX 2013 data

We present the results of a direct detection search for mirror dark matter interactions, using data collected from the Large Underground Xenon experiment during 2013, with an exposure of 95 live-days × 118 kg. Here, the calculations of the mirror electron scattering rate in liquid xenon take into account the shielding effects from mirror dark matter captured within the Earth. Annual and diurnal modulation of the dark matter flux and atomic shell effects in xenon are also accounted for. Having found no evidence for an electron recoil signal induced by mirror dark matter interactions we place an upper limit on the kinetic mixing parameter over a range of local mirror electron temperatures between 0.1 and 0.6 keV. This limit shows significant improvement over the previous experimental constraint from orthopositronium decays and significantly reduces the allowed parameter space for the model. We exclude mirror electron temperatures above 0.3 keV at a 90% confidence level, for this model, and constrain the kinetic mixing below this temperature

Fast and flexible analysis of direct dark matter search data with machine learning

We present the results from combining machine learning with the profile likelihood fit procedure, using data from the Large Underground Xenon (LUX) dark matter experiment. This approach demonstrates reduction in computation time by a factor of 30 when compared with the previous approach, without loss of performance on real data. We establish its flexibility to capture nonlinear correlations between variables (such as smearing in light and charge signals due to position variation) by achieving equal performance using pulse areas with and without position-corrections applied. Its efficiency and scalability furthermore enables searching for dark matter using additional variables without significant computational burden. We demonstrate this by including a light signal pulse shape variable alongside more traditional inputs, such as light and charge signal strengths. This technique can be exploited by future dark matter experiments to make use of additional information, reduce computational resources needed for signal searches and simulations, and make inclusion of physical nuisance parameters in fits tractable

An effective field theory analysis of the first LUX dark matter search

The Large Underground Xenon (LUX) dark matter search was a 250-kg active mass dual-phase time projection chamber that operated by detecting light and ionization signals from particles incident on a xenon target. In December 2015, LUX reported a minimum 90% upper C.L. of 6e-46 cm^2 on the spin-independent WIMP-nucleon elastic scattering cross section based on a 1.4e4 kg*day exposure in its first science run. Tension between experiments and the absence of a definitive positive detection suggest it would be prudent to search for WIMPs outside the standard spin-independent/spin-dependent paradigm. Recent theoretical work has identified a complete basis of 14 independent effective field theory (EFT) operators to describe WIMP-nucleon interactions. In addition to spin-independent and spin-dependent nuclear responses, these operators can produce novel responses such as angular-momentum-dependent and spin-orbit couplings. Here we report on a search for all 14 of these EFT couplings with data from LUX's first science run. Limits are placed on each coupling as a function of WIMP mass

Search for two neutrino double electron capture of ¹²⁴Xe and ¹²⁶Xe in the full exposure of the LUX detector

Two-neutrino double electron capture is a process allowed in the standard model of particle physics. This rare decay has been observed in 78Kr, 130Ba and more recently in 124Xe. In this publication we report on the search for this process in 124Xe and 126Xe using the full exposure of the large underground xenon (LUX) experiment, in a total of 27769.5 kg-days. No evidence of a signal was observed, allowing us to set 90% C.L. lower limits for the half-lives of these decays of 2.0 × 1021 years for 124Xe and 1.9 × 1021 years for 126Xe