Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

The psychopathological and psychosocial outcome of early-onset schizophrenia: Preliminary data of a 13-year follow-up

<p>Abstract</p> <p>Background</p> <p>Relatively little is known about the long-term psychopathological and psychosocial outcome of early-onset schizophrenia. The existing literature describes more severe courses of illness in these patients compared with adult-onset schizophrenia. This article reports preliminary data of a study exploring the outcome of early-onset schizophrenia 13.4 years (mean) after first admission. Predictors for interindividual outcomes were investigated.</p> <p>Methods</p> <p>We retrospectively assessed 27 former patients (mean age at first admission 15.5 years, SD = 2.0) that were consecutively admitted to the Department of Child and Adolescent Psychiatry at the University of Wuerzburg between 1990 and 2000. A multidimensional approach was chosen to assess the outcome consisting of a mail survey including different questions about psychopathological symptoms, psychosocial parameters, and standardized self-reports (ESI and ADS).</p> <p>Results</p> <p>Concerning the psychopathological outcome, 22.2% reported having acute schizophrenic symptoms. Almost one third (30.8%) described symptoms of depression and 37.0% reported having tried to commit suicide or seriously thought about it. 77.8% of the former patients were still in outpatient treatment. Compared to the general population, the number of patients without a school graduation was relatively high (18.5%). Almost half of participants still live with their parents (48.1%) or in assisted or semi-assisted living conditions (33.3%). Only 18.5% were working in the open market.</p> <p>Conclusion</p> <p>Schizophrenia with an early onset has an unfavourable prognosis. Our retrospective study of the psychopathological and psychosocial outcome concludes with a generally poor rating.</p

Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides

Background: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. Methodology/Prinicipal Findings: Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. Conclusions: SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

Background: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion

Sequence of the hyperplastic genome of the naturally competent Thermus scotoductus SA-01

<p>Abstract</p> <p>Background</p> <p>Many strains of <it>Thermus </it>have been isolated from hot environments around the world. <it>Thermus scotoductus </it>SA-01 was isolated from fissure water collected 3.2 km below surface in a South African gold mine. The isolate is capable of dissimilatory iron reduction, growth with oxygen and nitrate as terminal electron acceptors and the ability to reduce a variety of metal ions, including gold, chromate and uranium, was demonstrated. The genomes from two different <it>Thermus thermophilus </it>strains have been completed. This paper represents the completed genome from a second <it>Thermus </it>species - <it>T. scotoductus</it>.</p> <p>Results</p> <p>The genome of <it>Thermus scotoductus </it>SA-01 consists of a chromosome of 2,346,803 bp and a small plasmid which, together are about 11% larger than the <it>Thermus thermophilus </it>genomes. The <it>T. thermophilus </it>megaplasmid genes are part of the <it>T. scotoductus </it>chromosome and extensive rearrangement, deletion of nonessential genes and acquisition of gene islands have occurred, leading to a loss of synteny between the chromosomes of <it>T. scotoductus and T. thermophilus</it>. At least nine large inserts of which seven were identified as alien, were found, the most remarkable being a denitrification cluster and two operons relating to the metabolism of phenolics which appear to have been acquired from <it>Meiothermus ruber</it>. The majority of acquired genes are from closely related species of the Deinococcus-Thermus group, and many of the remaining genes are from microorganisms with a thermophilic or hyperthermophilic lifestyle. The natural competence of <it>Thermus scotoductus </it>was confirmed experimentally as expected as most of the proteins of the natural transformation system of <it>Thermus thermophilus </it>are present. Analysis of the metabolic capabilities revealed an extensive energy metabolism with many aerobic and anaerobic respiratory options. An abundance of sensor histidine kinases, response regulators and transporters for a wide variety of compounds are indicative of an oligotrophic lifestyle.</p> <p>Conclusions</p> <p>The genome of <it>Thermus scotoductus </it>SA-01 shows remarkable plasticity with the loss, acquisition and rearrangement of large portions of its genome compared to <it>Thermus thermophilus</it>. Its ability to naturally take up foreign DNA has helped it adapt rapidly to a subsurface lifestyle in the presence of a dense and diverse population which acted as source of nutrients. The genome of <it>Thermus scotoductus </it>illustrates how rapid adaptation can be achieved by a highly dynamic and plastic genome.</p

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish

Purpose: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. Methods: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. Results: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1−/− knockouts. Conclusion: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets

INFLUÊNCIA DA COMPOSIÇÃO CORPORAL REGIONAL E TOTAL SOBRE O DESEMPENHO DE NADO E ÍNDICES AERÓBIOS

RESUMO Introdução: Poucos estudos analisaram a contribuição da composição regional de nadadores para o perfil aeróbio, anaeróbio e o desempenho de nado. Objetivo: Verificar a influência da composição corporal regional e total sobre índices da aptidão aeróbia e anaeróbia em nado atado e livre, bem como sobre o desempenho de curta e média duração. Métodos: Onze nadadores (18,0 ± 4,0 anos) foram submetidos a: (1) teste incremental em nado atado, com coleta de gases respiração-a-respiração (K4b2 associado ao novo-AquaTrainerâ); e (2) tempo limite nos desempenhos de 200, 400 e 800 metros de nado livre. A regressão linear entre distância e tempo (d-tLim) empregou o método dos quadrados mínimos. O coeficiente de Pearson (r) averiguou as correlações da composição corporal regional e total com índices da aptidão aeróbica e anaeróbica em nado atado e livre. Resultados: Os valores da massa isenta de gordura (MIG) foram: 61,7 ± 7,4 kg; 7,5 ± 1,1 kg; 28,3 ± 3,7 kg; 22,1 ± 2,5 kg, respectivamente para corpo todo, membros superiores (MS), tronco (T) e membros inferiores (MI). O consumo máximo de oxigênio (VO2max) foi 52,1 ± 5,3 ml×kg-1×min-1, sendo a carga correspondente (iVO2max) de 93,9 ± 12,2 N. O tempo em 200 (132,2 ± 9,7 s), 400 (296,8 ± 17,2 s) e 800 metros (619,5 ± 26,9 s) forneceu velocidade crítica (VC = 1,23 ± 0,06 m×s-1) e capacidade anaeróbica de nado (CNA = 35,8 ± 15,1 m). Observaram-se correlações de iVO2max, CAN e v200m com MIG para MS (r = 0,64; 0,67 e 0,76), porém a MIG para T, MI e corporal demonstraram correlações apenas com v200m (r = 0,75; 0,69 e 0,75) e CAN (r = 0,71; 0,69 e 0,75). Conclusão: Houve, portanto, influência da MIG regional e corporal sobre o desempenho de curta distância e reservas anaeróbias, sendo a MIG-MS também influente sobre a iVO2max, e assim relacionada ao aprimoramento do desempenho de nado

Measurement of inclusive very forward jet cross sections in proton-lead collisions at \sqrt{sNN} = 5:02 TeV

Measurements of differential cross sections for inclusive very forward jet production in proton-lead collisions as a function of jet energy are presented. The data were collected with the CMS experiment at the LHC in the laboratory pseudorapidity range −6.6 < η < −5.2. Asymmetric beam energies of 4 TeV for protons and 1.58 TeV per nucleon for Pb nuclei were used, corresponding to a center-of-mass energy per nucleon pair of \sqrt{sNN} = 5:02 TeV. Collisions with either the proton (p+Pb) or the ion (Pb+p) traveling towards the negative η hemisphere are studied. The jet cross sections are unfolded to stable-particle level cross sections with p_{T} ≳ 3 GeV, and compared to predictions from various Monte Carlo event generators. In addition, the cross section ratio of p+Pb and Pb+p data is presented. The results are discussed in terms of the saturation of gluon densities at low fractional parton momenta. None of the models under consideration describes all the data over the full jet-energy range and for all beam configurations. Discrepancies between the differential cross sections in data and model predictions of more than two orders of magnitude are observed

A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯