62 research outputs found
Characterization of the radiation tolerance of cryogenic diodes for the High Luminosity LHC inner triplet circuit
Cryogenic bypass diodes are part of the baseline powering layout for the circuits of the new Nb3Sn based final focus magnets of the high luminosity Large Hadron Collider. They will protect the magnets against excessive transient voltages during a nonuniform quenching process. The diodes are located inside an extension to the magnet cryostat, operated in superfluid helium and exposed to ionizing radiation. Therefore, the radiation tolerance of different types of diodes has been tested at cryogenic temperatures in CERN’s CHARM irradiation test facility during its 2018 run. The forward bias characteristics, the turn-on voltage and the reverse blocking voltage of each diode were measured weekly at 4.2 K and 77 K, as a function of the accumulated radiation dose. The diodes were submitted to a total dose close to 12 kGy and a 1 MeV neutron equivalent fluence of 2.2×1014  cm−2. After the end of the irradiation program the annealing behavior of the diodes was tested by increasing the temperature slowly to 293 K. This paper describes the experimental setup, the measurement procedure and the analysis of the measurements performed during the irradiation program as well as the results of the annealing study
Experimental Setup to Characterize the Radiation Hardness of Cryogenic Bypass Diodes for the HL-LHC Inner Triplet Circuits
For the high luminosity upgrade of the Large Hadron Collider (LHC), it is planned to replace the existing triplet quadrupole magnets with Nb₃Sn quadrupole magnets, which provide a comparable integrated field gradient with a significantly increased aperture. These magnets will be powered through a novel superconducting link based on MgB₂ cables. One option for the powering layout of this triplet circuit is the use of cryogenic bypass diodes, where the diodes are located inside an extension to the magnet cryostat and operated in superfluid helium. Hence, they are exposed to radiation. For this reason the radiation hardness of existing LHC type bypass diodes and more radiation tolerant prototype diodes needs to be tested up to the radiation doses expected at their planned position during their lifetime. A first irradiation test is planned in CERN's CHARM facility starting in spring 2018. Therefore, a cryo-cooler based cryostat to irradiate and test LHC type diodes in-situ has been designed and constructed. This paper will describe the properties of the sample diodes, the experimental roadmap and the setup installed in CHARM. Finally, the first measurement results will be discussed
Characterisation of the radiation hardness of cryogenic bypass diodes for the HL-LHC inner triplet circuit
CD40L Deficiency Attenuates Diet-Induced Adipose Tissue Inflammation by Impairing Immune Cell Accumulation and Production of Pathogenic IgG-Antibodies
BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease
CD40 Is Essential in the Upregulation of TRAF Proteins and NF-KappaB-Dependent Proinflammatory Gene Expression after Arterial Injury
Despite extensive investigations, restenosis, which is characterized primarily by neointima formation, remains an unsolved clinical problem after vascular interventions. A recent study has shown that CD40 signaling through TNF receptor associated factor 6 (TRAF6) plays a key role in neointima formation after carotid artery injury; however, underlying mechanisms are not clearly elucidated. Because neointima formation may vary significantly depending on the type of injury, we first assessed the effect of CD40 deficiency on neointima formation in 2 injury models, carotid artery ligation and femoral artery denudation injury. Compared with wild-type mice, CD40 deficiency significantly reduced neointima formation and lumen stenosis in two different models. Further, we investigated the mechanism by which CD40 signaling affects neointima formation after arterial injury. In wild-type mice, the expression levels of CD40, several TRAF proteins, including TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6, as well as total NF-kB p65 and phospho-NF-kB p65, in the carotid artery were markedly upregulated within 3–7 days after carotid ligation. Deficiency of CD40 abolished the injury-induced upregulation of TRAFs including TRAF6 and NF-kB-p65 in the injured vessel wall. Further, CD40−/− mice showed a significant decrease in the recruitment of neutrophils (at 3, 7d) and macrophages (at 7, 21d) into injured artery; this effect was most likely attributed to inhibition of NF-kB activation and marked downregulation of NF-kB-related gene expression, including cytokines (TNFα, IL-1β, IL-6), chemokines (MCP-1), and adhesion molecules (ICAM-1, VCAM-1). Moreover, neutrophil recruitment in a model of thioglycollate-induced peritonitis is impaired in CD40-deficient mice. In vitro data revealed that CD40 deficiency blocked CD40L-induced NF-kB p65 nuclear translocation in leukocytes. Altogether, our data identified for the first time that CD40 is essential in the upregulation of TRAF6, NF-kB activation, and NF-kB-dependent proinflammatory genes in vivo. Our findings firmly established the role for CD40 in neointima formation in 2 distinct injury models
Detecting 22q11.2 deletion in Chinese children with conotruncal heart defects and single nucleotide polymorphisms in the haploid TBX1 locus
<p>Abstract</p> <p>Background</p> <p>Conotruncal heart defects (CTDs) are present in 75-85% of patients suffering from the 22q11.2 deletion syndrome. To date, no consistent phenotype has been consistently correlated with the 22q11.2 deletions. Genetic studies have implicated <it>TBX1 </it>as a critical gene in the pathogenesis of the syndrome. The aim of study was to determine the incidence of the 22q11.2 deletion in Chinese patients with CTDs and the possible mechanism for pathogenesis of CTDs.</p> <p>Methods</p> <p>We enrolled 212 patients with CTDs and 139 unrelated healthy controls. Both karyotypic analysis and multiplex ligation-dependent probe amplification were performed for all CTDs patients. Fluorescence <it>in situ </it>hybridization was performed for the patients with genetic deletions and their relatives. The <it>TBX1 </it>gene was sequenced for all patients and healthy controls. The <it>χ</it><sup>2 </sup>and Fisher's exact test were used in the statistical analysis.</p> <p>Results</p> <p>Thirteen of the 212 patients with CTDs (6.13%) were found to have the 22q11.2 deletion syndrome. Of the 13 cases, 11 presented with a hemizygous interstitial microdeletion from <it>CLTCL1 </it>to <it>LZTR1</it>; one presented with a regional deletion from <it>CLTCL1 </it>to <it>DRCR8</it>; and one presented with a regional deletion from <it>CDC45L </it>to <it>LZTR1</it>. There were eight sequence variants in the haploid <it>TBX1 </it>genes of the del22q11 CTDs patients. The frequency of one single nucleotide polymorphism (SNP) in the del22q11 patients was different from that of the non-del patients (<it>P </it>< 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>CTDs, especially pulmonary atresia with ventricular septal defect and tetralogy of Fallot, are the most common disorders associated with the 22q11.2 deletion syndrome. Those patients with both CTDs and 22q11.2 deletion generally have a typical or atypical deletion region within the <it>TBX1 </it>gene. Our results indicate that <it>TBX1 </it>genetic variants may be associated with CTDs.</p
Peripheral Immune Cell Gene Expression Predicts Survival of Patients with Non-Small Cell Lung Cancer
Prediction of cancer recurrence in patients with non-small cell lung cancer (NSCLC) currently relies on the assessment of clinical characteristics including age, tumor stage, and smoking history. A better prediction of early stage cancer patients with poorer survival and late stage patients with better survival is needed to design patient-tailored treatment protocols. We analyzed gene expression in RNA from peripheral blood mononuclear cells (PBMC) of NSCLC patients to identify signatures predictive of overall patient survival. We find that PBMC gene expression patterns from NSCLC patients, like patterns from tumors, have information predictive of patient outcomes. We identify and validate a 26 gene prognostic panel that is independent of clinical stage. Many additional prognostic genes are specific to myeloid cells and are more highly expressed in patients with shorter survival. We also observe that significant numbers of prognostic genes change expression levels in PBMC collected after tumor resection. These post-surgery gene expression profiles may provide a means to re-evaluate prognosis over time. These studies further suggest that patient outcomes are not solely determined by tumor gene expression profiles but can also be influenced by the immune response as reflected in peripheral immune cells
Beam Impact Experiment of 440GeV/p Protons on Superconducting Wires and Tapes in a Cryogenic Environment
Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome
<p>Abstract</p> <p>Background</p> <p>Chromosome 22q11 deletion syndrome (22q11DS) causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions.</p> <p>Methods</p> <p>We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH), quantitative real-time polymerase chain reaction (qPCR) and multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (<it>p </it>< 0.01). An identical deletion was shown in three affected infants by MLPA. These reduced DNA dosages were also obtained partially using array-CGH and confirmed by qPCR but with some differences in deletion size.</p> <p>Conclusion</p> <p>Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.</p
Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement
This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)
- …