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Anomalies in past neutrino measurements have led to the discovery that these particles have non-zero mass and oscillate between their three flavours when they propagate. In the 2010s, similar anomalies observed in the antineutrino spectra emitted by nuclear reactors have triggered the hypothesis of the existence of a supplementary neutrino state that would be sterile, that is, not interacting by means of the weak interaction 1 . The STEREO experiment 2 – 6 was designed to investigate this conjecture, which would potentially extend the standard model of particle physics. Here we present an analysis of the full set of data generated by STEREO, confirming observed anomalies while rejecting the hypothesis of a light sterile neutrino. Installed at the Institut Laue–Langevin (ILL) research reactor, STEREO accurately measures the antineutrino energy spectrum associated to the fission of 235 U. The segmentation of the detector and its very short distance to the compact core are crucial properties of STEREO for our analysis. The measured antineutrino energy spectrum suggests that anomalies originate from biases in the nuclear experimental data used for the predictions 7 , 8 . Our result supports the neutrino content of the standard model and establishes a new reference for the 235 U antineutrino energy spectrum. We anticipate that this result will allow progress towards finer tests of the fundamental properties of neutrinos but also to benchmark models and nuclear data of interest for reactor physics 9 , 10 and for observations of astrophysical or geoneutrinos 11 , 12 . Accurate measurements of the antineutrino energy spectrum of 235 U fission by the STEREO detector reject the sterile neutrino hypothesis and point to biases in the nuclear data to explain the discrepancies with the prediction.

Epidermal growth factor receptor (EGFR) mutation is frequently observed in human cancer and contributes to the growth, survival and therapeutic resistance of tumors. EGFRvIII is an oncogenic EGFR mutant resulting from the deletion of exons 2–7 and is the most common EGFR mutant observed in glioblastoma multiforme, an aggressive brain tumor. EGFRvIII is constitutively active but poorly ubiquitinated, leading to inefficient receptor trafficking to lysosomes and unattenuated oncogenic signaling. The mechanism by which EGFRvIII evades downregulation is not fully understood although recent studies suggest that its interaction with the ubiquitin ligase Cbl may be compromised. In this study, we examine the regulation of EGFRvIII by the recently identified negative regulator, LRIG1, which targets EGFR through recognition of its extracellular domain. Here, we determine whether the extracellular domain deletion in EGFRvIII renders it refractory to LRIG1 regulation. We find that EGFRvIII retains interaction with LRIG1 and is in fact more sensitive to LRIG1 action than wild-type receptor. We demonstrate that LRIG1 regulation of EGFRvIII is distinct from the only other known mechanism of EGFR regulation, Cbl-mediated degradation. Ectopic expression of LRIG1 in EGFRvIII(+) glioblastoma cells opposes EGFRvIII-driven tumor cell proliferation, survival, motility and invasion. Finally, RNAi-mediated silencing of LRIG1 alters EGFRvIII intracellular trafficking and leads to enhanced EGFRvIII expression, suggesting that loss of LRIG1 in tumors may contribute to a permissive environment for EGFRvIII overexpression, contributing to EGFRvIII oncogenesis.

The precise modeling of the de-excitation of Gd isotopes is of great interest for experimental studies of neutrinos using Gd-loaded organic liquid scintillators. The FIFRELIN code was recently used within the purposes of the STEREO experiment for the modeling of the Gd de-excitation after neutron capture in order to achieve a good control of the detection efficiency. In this work, we report on the recent additions in the FIFRELIN de-excitation model with the purpose of enhancing further the de-excitation description. Experimental transition intensities from the EGAF database are now included in the FIFRELIN cascades, in order to improve the description of the higher energy part of the spectrum. Furthermore, the angular correlations between γ rays are now implemented in FIFRELIN, to account for the relative anisotropies between them. In addition, conversion electrons are now treated more precisely in the whole spectrum range, while the subsequent emission of X rays is also accounted for. The impact of the aforementioned improvements in FIFRELIN is tested by simulating neutron captures in various positions inside the STEREO detector. A repository of up-to-date FIFRELIN simulations of the Gd isotopes is made available for the community, with the possibility of expanding for other isotopes which can be suitable for different applications.

A professional behavioral witness to more than a hundred capital trials explores the making of a murderer.   CSI shows us where a crime is committed. Forensic detectives show us how. But what really goes on in the mind of killer? What is it in each potential victim that sparks in them the urge to take a life? What are the reasons behind a quick thrill kill, or slow torture? Between choosing someone they know, or a stranger? As they stand before a jury, after reams of graphic evidence, the question is no longer whether or not they committed the unthinkable. The question posed to Wanda Draper, expert in behavioral science and child development, and key witness in more than a hundred high-profile trials, is why? The answer is all that stands between a sentence of life in prison or death row.   In this unique true-crime investigation, Draper shares some of the darkest cases of her career. She sheds light on the personal circumstances and critical life events that perverted childhoods and brought convicted murderers to trial. She reveals how the past casts a grave shadow over one's future. And in doing so, explores one irrefutable fact: killers aren't born, they're made.

To determine optimal power settings on the Centurion Vision System during the grooving step in cataract surgery. Intact porcine lenses hardened by formalin and placed in a chamber designed to simulate the anterior chamber of the eye were used to test longitudinal power at 40%, 70%, and 100% and torsional power at 0%. Flow rate was set at 40 mL/min. Vacuum was set at 400 mmHg, intraocular pressure was set at 50 mmHg, and a balanced phacoemulsification tip with a 20 degree tip and a 30 degree bevel was used. Efficiency (time to groove the lens in half) was determined. Increasing longitudinal power from 40% to 70% increased efficiency by 28% ( <0.05), and by 32% ( <0.05) when increasing longitudinal power from 40% to 100%. There was no statistically significant increase in efficiency from 70% to 100%. For the tested variables, a longitudinal power of 70% was determined to be most efficient during the grooving step of cataract surgery for equivalent 3-4+ nuclei. Further increases in power demonstrated no statistically significant improvement in efficiency.

Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis affect millions of people worldwide. Interferon regulatory factor 5 (IRF5) contains polymorphisms associated with these autoimmune diseases. Two of these functional polymorphisms are found upstream of the IRF5 gene. rs2004640, which is a single nucleotide polymorphism and the CGGGG insertion/deletion (indel) were studied. IRF5 uses four different promoters for its four first exons: 1A, 1B, 1C, and 1D. Each promoter was analyzed, including functional differences due to the autoimmune-risk polymorphisms. IRF5 promoters were analyzed using ChIP-Seq data (ENCODE database) and the FactorBook database to define transcription factor binding sites. To verify promoter activity, the promoters were cloned into luciferase plasmids. Each construct exhibited luciferase activity. Exons 1A and 1D contain putative PU.1 and NFkB binding sites. Imiquimod, a Toll-like receptor 7 (TLR7) ligand, was used to activate these transcription factors. IRF5 levels were doubled after imiquimod treatment (p < 0.001), with specific increases in the 1A promoter (2.2-fold, p = 0.03) and 1D promoter (2.8-fold, p = 0.03). A putative binding site for p53, which affects apoptosis, was found in the promoter for exon 1B. However, site-directed mutagenesis of the p53 site showed no effect in a reporter assay. The IRF5 exon 1B promoter has been characterized, and the responses of each IRF5 promoter to TLR7 stimulation have been determined. Changes in promoter activity and gene expression are likely due to specific and distinct transcription factors that bind to each promoter. Since high expression of IRF5 contributes to the development of autoimmune disease, understanding the source of increased IRF5 levels is key to understanding autoimmune etiology.

The aim of this study was to determine optimal bottle height, vacuum, aspiration rate, and power settings of the Oertli CataRhex 3 phacoemulsification machine. Porcine lens nuclei were hardened with formalin and cut into 2.0 mm cubes. Lens cubes were emulsified using the easyTip 2.2 mm at 30°. Fragment removal time (efficiency) and fragment bounces off the tip (chatter) were measured. Settings tested included bottle height of 60, 80, 100 and 120 cm; aspiration rate of 40, 45, and 50 mL/min; vacuum of 400, 500, and 600 mmHg; and power of 50, 60, 70, 80, 90, and 100%. Efficiency and chatter increased in a linear fashion with increasing vacuum to 600 mmHg ( =0.017, =0.046, respectively). The most efficient aspiration rate was 50 mL/min, although this finding lacked statistical significance ( =0.66). Increasing power increased efficiency up to 80% without increasing chatter ( =0.042, =0.71, respectively). Compared to all other power settings, chatter was increased at 100% ( =0.014). The most efficient machine settings were vacuum at 600 mmHg, aspiration rate at 50 mL/min, and power at 80%.

Anomalies in past neutrino measurements have led to the discovery that these particles have non-zero mass and oscillate between their three flavors when they propagate. In the 2010's, similar anomalies observed in the antineutrino spectra emitted by nuclear reactors have triggered the hypothesis of the existence of a supplementary neutrino state that would be sterile i.e. not interacting via the weak interaction. The STEREO experiment was designed to study this scientific case that would potentially extend the Standard Model of Particle Physics. Here we present a complete study based on our full set of data with significantly improved sensitivity. Installed at the ILL (Institut Laue Langevin) research reactor, STEREO has accurately measured the antineutrino energy spectrum associated to the fission of 235U. This measurement confirms the anomalies whereas, thanks to the segmentation of the STEREO detector and its very short mean distance to the core (10~m), the same data reject the hypothesis of a light sterile neutrino. Such a direct measurement of the antineutrino energy spectrum suggests instead that biases in the nuclear experimental data used for the predictions are at the origin of the anomalies. Our result supports the neutrino content of the Standard Model and establishes a new reference for the 235U antineutrino energy spectrum. We anticipate that this result will allow to progress towards finer tests of the fundamental properties of neutrinos but also to benchmark models and nuclear data of interest for reactor physics and for observations of astrophysical or geo-neutrinos.

The probability of in-vivo failure of ceramic hip joint implants is very low (0.05–0.004 per cent). Besides material flaws and overloading, improper handling during implantation may induce fractures of the ceramic ball head in the long term. This study focuses on the influence of contaminants located in the stem—ball interface and on the use of damaged metal tapers on the strength of ceramic ball heads. Mechanical tests on alumina ball heads according to the standard ISO 7206-10 were performed to identify their effect on the static fracture load. A decrease of up to 90 per cent with respect to the reference static fracture load was found when contaminants such as bone chips, soft tissue, or blood were present. Reductions of 57 per cent and 27 per cent were observed for deformed stem cross-sections (from circular to elliptical) and for flattened stems respectively, making deformed stems another influential parameter. Since any alteration of the interface between the metal taper and the ceramic ball head yields a non-uniform load introduction and hence results in stress concentrations, its presence has to be avoided.

Abstract A proof test procedure for the rejection of defective ceramic hip ball heads in the production line is presented. The procedure consists of applying a load to each ceramic ball head. This load, being somewhat higher than the maximum physiological load, should not cause any damage in cases where the highly stressed areas are free of flaws. In this procedure, a polymer ring is positioned inside the ball head bore between a socket and the head of a tie bolt. Once the tie bolt is pulled downwards, the ring creates a radial pressure on the inner bore surface of the ball head. With an iterative approach based on finite element analysis, the proof test design was optimized in order to obtain a stress distribution in the ball head similar to that resulting in in vivo conditions. The calculated results were validated by strain gauge measurements performed on an assembled proof test apparatus. Several polymers were considered for the ring. Ultrahigh-molecular-weight polyethylene (UHMWPE grade RCH 1000) showed the best durability properties and lowest wear rates. The requirement to perform 1000 reruns without significant reduction of stress in the ball head was fulfilled. Although other proof test procedures for ceramic femoral heads already exist, the procedure presented in this article shows advantages concerning maintenance and operating costs.