122 research outputs found

    Molecular profiles of gastroenteropancreatic endocrine tumors

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    Neuroendocrine tumors of the gastroenteropancreatic system are defined by their endocrine phenotype and share many histopathological and clinical features. However, the fact that the hormone production of tumors depends on their site of origin, that the tumors differ in their biology, and that the association with familial syndromes is nonrandom suggests heterogeneity. It is therefore conceivable that the gastroenteropancreatic neuroendocrine tumors also differ in their molecular profile. This review summarizes and discusses the available data in this fiel

    Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway

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    OBJECTIVE—Xenin, a 25–amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin

    Next-to-Leading QCD Corrections to B\to X_s \gamma in Supersymmetry

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    We compute the QCD next-to-leading order matching conditions of the (chromo)-magnetic operators relevant for B\to X_s \gamma in supersymmetric models with minimal flavour violation. The calculation is performed under the assumption that the charginos and one stop are lighter than all other squarks and the gluino. In the parameter region where a light charged Higgs boson is consistent with measurements of BR(B\to X_s \gamma), we find sizeable corrections to the Wilson coefficients. As a consequence, there is a significant reduction of the stop-chargino mass region where the supersymmetric contribution has a large destructive interference with the charged-Higgs boson contribution.Comment: LaTeX,21 pages, 2 figures. Typos corrected in appendi

    Trans-Pacific transport of reactive nitrogen and ozone to Canada during spring

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    We interpret observations from the Intercontinental Chemical Transport Experiment, Phase B (INTEX-B) in spring 2006 using a global chemical transport model (GEOS-Chem) to evaluate sensitivities of the free troposphere above the North Pacific Ocean and North America to Asian anthropogenic emissions. We develop a method to use satellite observations of tropospheric NO<sub>2</sub> columns to provide timely estimates of trends in NO<sub>x</sub> emissions. NO<sub>x</sub> emissions increased by 33% for China and 29% for East Asia from 2003 to 2006. We examine measurements from three aircraft platforms from the INTEX-B campaign, including a Canadian Cessna taking vertical profiles of ozone near Whistler Peak. The contribution to the mean simulated ozone profiles over Whistler below 5.5 km is at least 7.2 ppbv for Asian anthropogenic emissions and at least 3.5 ppbv for global lightning NO<sub>x</sub> emissions. Tropospheric ozone columns from OMI exhibit a broad Asian outflow plume across the Pacific, which is reproduced by simulation. Mean modelled sensitivities of Pacific (30° N–60° N) tropospheric ozone columns are at least 4.6 DU for Asian anthropogenic emissions and at least 3.3 DU for lightning, as determined by simulations excluding either source. Enhancements of ozone over Canada from Asian anthropogenic emissions reflect a combination of trans-Pacific transport of ozone produced over Asia, and ozone produced in the eastern Pacific through decomposition of peroxyacetyl nitrates (PANs). A sensitivity study decoupling PANs globally from the model's chemical mechanism establishes that PANs increase ozone production by removing NO<sub>x</sub> from regions of low ozone production efficiency (OPE) and injecting it into regions with higher OPE, resulting in a global increase in ozone production by 2% in spring 2006. PANs contribute up to 4 ppbv to surface springtime ozone concentrations in western Canada. Ozone production due to PAN transport is greatest in the eastern Pacific; commonly occurring transport patterns advect this ozone northeastward into Canada. Transport events observed by the aircraft confirm that polluted airmasses were advected in this way

    Delta-like protein 3 expression in paired chemonaive and chemorelapsed small cell lung cancer samples

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    Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available. The aim of this study was to investigate the expression of DLL3 in chemorelapsed (but untreated with Rova-T) SCLC samples and compare the results with chemonaive counterparts. Two evaluation methods to assess DLL3 expression were explored. Additionally, we assessed if DLL3 expression of chemorelapsed and/or chemonaive samples has prognostic impact and if it correlates with other clinicopathological data. The study included 30 paired SCLC samples, which were stained with an anti DLL3 antibody. DLL3 expression was assessed using tumor proportion score (TPS) and H-score and was categorized as DLL3 low (TPS < 50%, H-score ≤ 150) and DLL3 high (TPS ≥ 50%, H-score > 150). Expression data were correlated with clinicopathological characteristics. Kaplan-Meier curves were used to illustrate overall survival (OS) depending on DLL3 expression in chemonaive and chemorelapsed samples, respectively, and depending on dynamics of expression during course of therapy. DLL3 was expressed in 86.6% chemonaive and 80% chemorelapsed SCLC samples without significant differences between the two groups. However, the extent of expression varied in a substantial proportion of pairs (36.6% with TPS, 43.3% with H-score), defined as a shift from low to high or high to low expression. TPS and H-score provided comparable results. There were no profound correlations with clinicopathological data. Survival analysis revealed a trend toward a more favorable OS in DLL low-expressing chemonaive SCLC (p = 0.57) and, in turn, in DLL3 high-expressing chemorelapsed SCLC (p = 0.42) as well as in SCLC demonstrating a shift from low to high expression (p = 0.56) without being statistically significant. This is the first study to investigate DLL3 expression in a large cohort of rare paired chemonaive-chemorelapsed SCLC specimens. Comparative analysis revealed that DLL3 expression was not stable during the course of therapy, suggesting therapy-based alterations. Unlike in chemonaive samples, a high DLL3 expression in chemorelapsed samples indicated a trend for a more favorable prognosis. Our results highlight the importance to investigate DLL3 in latest chemorelapsed SCLC tumor tissue

    |Delta B|=1 Weak Effective Lagrangian in the Minimal Flavor Violation Supersymmetry

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    To evaluate the weak decays of b-hadrons, the ΔB=1\Delta B=1 weak effective Lagrangian is the foundation. Any new physics beyond the standard model (SM) would contribute to the effective Lagrangian through the loop integration at the weak scale and evolution from the weak scale down to the hadronic scale. In this work we present a systematic analysis on the effective Lagrangian which mediates hadronic ΔB=1|\Delta B|=1 processes in the framework of the minimal flavor violation supersymmetry as well as a numerical evaluation of the Wilson coefficients in the effective theory.Comment: Latex,16 pages plus 5 figures, PRD versio

    Yukawa Unified Supersymmetric SO(10) Model: Cosmology, Rare Decays and Collider Searches

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    It has recently been pointed out that viable sparticle mass spectra can be generated in Yukawa unified SO(10) supersymmetric grand unified models consistent with radiative breaking of electroweak symmetry. Model solutions are obtained only if tanβ50\tan\beta \sim 50, μ<0\mu <0 and positive DD-term contributions to scalar masses from SO(10) gauge symmetry breaking are used. In this paper, we attempt to systematize the parameter space regions where solutions are obtained. We go on to calculate the relic density of neutralinos as a function of parameter space. No regions of the parameter space explored were actually cosmologically excluded, and very reasonable relic densities were found in much of parameter space. Direct neutralino detection rates could exceed 1 event/kg/day for a 73^{73}Ge detector, for low values of GUT scale gaugino mass m1/2m_{1/2}. We also calculate the branching fraction for bsγb\to s \gamma decays, and find that it is beyond the 95% CL experimental limits in much, but not all, of the parameter space regions explored. However, recent claims have been made that NLO effects can reverse the signs of certain amplitudes in the bsγb\to s\gamma calculation, leading to agreement between theory and experiment in Yukawa unified SUSY models. For the Fermilab Tevatron collider, significant regions of parameter space can be explored via bbˉAb\bar{b}A and bbˉHb\bar{b}H searches. There also exist some limited regions of parameter space where a trilepton signal can be seen at TeV33. Finally, there exist significant regions of parameter space where direct detection of bottom squark pair production can be made, especially for large negative values of the GUT parameter A0A_0.Comment: Added comparison to Blazek/Raby results and added Comments on de Boer et al. b->s gamma result

    Precision Physics at LEP

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    1 - Introduction 2 - Small-Angle Bhabha Scattering and the Luminosity Measurement 3 - Z^0 Physics 4 - Fits to Precision Data 5 - Physics at LEP2 6 - ConclusionsComment: Review paper to appear in the RIVISTA DEL NUOVO CIMENTO; 160 pages, LateX, 70 eps figures include

    Colonic Biopsies to Assess the Neuropathology of Parkinson's Disease and Its Relationship with Symptoms

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    The presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms.A total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation.Analysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms
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