192 research outputs found

    A systems immunology approach to GVHD defines skin-autonomous control of donor T cells

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    Carcinoma Arising from Brunner's Gland in the Duodenum after 17 Years of Observation – A Case Report and Literature Review

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    A 60-year-old man presented with melena and hematemesis in 1984. Esophagogastroduodenoscopy (EGD) detected a small protruding lesion in the duodenal bulb, which was diagnosed as Brunner's adenoma. No significant change was detected in subsequent annual EGD and biopsies for 10 years, after which the patient was not observed for 7 years. The patient presented with melena again in 2001. The lesion had changed shape to become a 10 mm sessile tumor with a central depression, and following a biopsy was diagnosed as an adenocarcinoma. The patient underwent partial resection of the duodenum. Histopathological assessment showed acidophilic cells with swollen nuclei, and clear cells forming a tubular or papillary tubule in the mucosal lamina propria and submucosal layer. The tumor cells stained positive for lysozyme, indicating that they arose from Brunner's gland. The patient showed no sign of recurrence and was disease-free for more than 34 months after surgery. The patient died of pneumonia. This is an extremely rare case of primary duodenal carcinoma arising from Brunner's gland in a patient observed for 17 years

    UBA1/GARS-dependent pathways drive sensory-motor connectivity defects in spinal muscular atrophy

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    Deafferentation of motor neurons as a result of defective sensory-motor connectivity is a critical early event in the pathogenesis of spinal muscular atrophy, but the underlying molecular pathways remain unknown. We show that restoration of ubiquitin-like modifier-activating enzyme 1 (UBA1) was sufficient to correct sensory-motor connectivity in the spinal cord of mice with spinal muscular atrophy. Aminoacyl-tRNA synthetases, including GARS, were identified as downstream targets of UBA1. Regulation of GARS by UBA1 occurred via a non-canonical pathway independent of ubiquitylation. Dysregulation of UBA1/GARS pathways in spinal muscular atrophy mice disrupted sensory neuron fate, phenocopying GARS-dependent defects associated with Charcot-Marie-Tooth disease. Sensory neuron fate was corrected following restoration of UBA1 expression and UBA1/GARS pathways in spinal muscular atrophy mice. We conclude that defective sensory motor connectivity in spinal muscular atrophy results from perturbations in a UBA1/GARS pathway that modulates sensory neuron fate, thereby highlighting significant molecular and phenotypic overlap between spinal muscular atrophy and Charcot-Marie-Tooth disease

    Enantioselective Dynamic Process Reduction of α- and β-Tetralone and Stereoinversion of Resulting Alcohols in a Selected Strain Culture

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    α-Tetralone and β-tetralone were subjected to biotransformation by 14 fungal strains. Enantiomeric purity of the products depended on the reaction time. 3-Day transformation of α-tetralone in Absidia cylindrospora culture gave S-(+)-1,2,3,4-tetrahydro-1-naftol of 92 % ee, whereas longer biotransformation time resulted in decrease of ee value. 3-Day transformation of β-tetralone by the same strain gave predominantly S-(−)-1,2,3,4-tetrahydro-2-naftol, whereas after 9 days of the reaction, the R-enantiomer with 85 % ee was isolated. Transformation of β-tetralone by Chaetomium sp. KCh 6651 gave pure (S)-(−)-1,2,3,4-tetrahydro-2-naftol in high yield at the concentration of 1 g/l. In this process, a non-selective carbonyl reduction was observed, followed by a selective oxidation of the R-alcohol

    Intra-Operative Assessment of Cancer with X-Ray Phase Contrast Computed Tomography

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    X-ray Phase-Contrast Computed Tomography (PC-CT) increases contrast in weakly attenuating samples, such as soft tissues. In Edge-Illumination (EI) PC-CT, phase effects are accessed from amplitude modulation of the x-ray beam using alternating transmitting and attenuating masks placed prior to the sample and detector. A large field of view PC-CT scanner using this technique was applied to two areas of cancer assessment, namely excised breast and esophageal tissue. For the breast tissue, Wide Local Excisions (WLEs) were studied intra-operatively using PC-CT for the evaluation of tumor removal in breast conservation surgery. Images were acquired in 10 minutes without compromising on image quality, showing this can be used in a clinical setting. Longer, higher resolution PC-CT images were also taken, with analysis showing previously undetected thinning of tumor strands. This would allow a second use of the system for “virtual histopathology”, outside of surgery. For the esophagus samples, tissues were taken from esophagectomy surgery, where the lower part of the esophagus is removed, and the stomach relocated. For the assessment of ongoing therapy, accurate staging of tumors in the removed esophagus is essential, with the current gold standard provided by histopathology. PCCT images were acquired on several samples and compare well with histopathology, with both modalities showing similar features. Examples are shown where staging of tumor penetration is possible with PC-CT images alone, which is hoped will be an important step in performing the imaging and staging intra-operatively

    Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation γ rays

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    Neutrino- and antineutrino-oxygen neutral-current quasielastic-like interactions are measured at Super-Kamiokande using nuclear de-excitation γ\gamma-rays to identify signal-like interactions in data from a $14.94 \ (16.35)\times 10^{20}protonsontargetexposureoftheT2Kneutrino(antineutrino)beam.Themeasuredfluxaveragedcrosssectionsonoxygennucleiare protons-on-target exposure of the T2K neutrino (antineutrino) beam. The measured flux-averaged cross sections on oxygen nuclei are \langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+ {\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}withafluxaveragedenergyof0.82GeVand with a flux-averaged energy of 0.82 GeV and \langle \sigma_{\bar{\nu} {\rm -NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are the most precise to date, and the antineutrino result is the first cross section measurement of this channel. They are compared with various theoretical predictions. The impact on evaluation of backgrounds to searches for supernova relic neutrinos at present and future water Cherenkov detectors is also discussed

    Search for electron antineutrino appearance in a long-baseline muon antineutrino beam

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    Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions
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