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The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.
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BACKGROUND: Spleen-preserving distal pancreatectomy with resection of the splenic vessels (VR-SPDP) is an effective procedure. However, hemodynamic changes in splenogastric circulation may lead to the development of gastric varices (GV) with a risk of gastrointestinal (GI) bleeding. This retrospective study aimed to assess the long-term postoperative clinical follow-up of patients and review the late postoperative abdominal computed tomography (CT) or endoscopic examination. METHODS: From 1988 to 2015, 48 consecutive VR-SPDP for benign or low-grade malignant disease were included. Late postoperative follow-up was undertaken with the use of a prospective database and assessment undertaken by CT and/or endoscopy. RESULTS: The median follow-up was 76 months (range: 12-334 months). Two patients were lost to follow-up. Gastrointestinal hemorrhage occurred in one patient. Endoscopy and abdominal CT showed submucosal GV in five patients. Ten patients had perigastric varices (27%), but none developed clinical complications from their varices. All varices occurred within one year after distal pancreatectomy and remained stable during follow-up. DISCUSSION: Asymptomatic varices frequently occurred in patients who underwent VR-SPDP, but bleeding risk seemed low. Abdominal CT could identify GV and distinguish submucosal varices with a higher risk of gastric bleeding.
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Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/etiología , Tratamientos Conservadores del Órgano/efectos adversos , Pancreatectomía/efectos adversos , Arteria Esplénica/cirugía , Vena Esplénica/cirugía , Gastropatías/etiología , Adulto , Anciano , Bases de Datos Factuales , Várices Esofágicas y Gástricas/diagnóstico , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/diagnóstico , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Gastropatías/diagnóstico , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN/dS, of extragalactic γ-ray sources at E>50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (â¼8×10^{-12} ph cm^{-2} s^{-1}). We employ a one-point photon fluctuation analysis to constrain the behavior of dN/dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, S_{b}, in the range [8×10^{-12},1.5×10^{-11}] ph cm^{-2} s^{-1} and power-law indices below and above the break of α_{2}∈[1.60,1.75] and α_{1}=2.49±0.12, respectively. Integration of dN/dS shows that point sources account for at least 86_{-14}^{+16}% of the total extragalactic γ-ray background. The simple form of the derived source count distribution is consistent with a single population (i.e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.
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We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12} GeV^{-1} for ALP masses 0.5â²m_{a}â²5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the γ-ray opacity of the Universe.
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Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.
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Trastorno Autístico/patología , Encéfalo/patología , Modelos Animales de Enfermedad , Familia de Multigenes/genética , Animales , Trastorno Autístico/genética , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Ratones TransgénicosRESUMEN
The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass â²100 GeV annihilating via quark and τ-lepton channels.
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A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximately 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximately 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves. Here we report the detection of emission up to approximately 31 GeV from the distant and short GRB 090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space-time on a very small scale linearly alters the speed of light.
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Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range â¼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above â¼200 GeV, respectively.
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We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy.
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Satellite galaxies of the Milky Way are among the most promising targets for dark matter searches in gamma rays. We present a search for dark matter consisting of weakly interacting massive particles, applying a joint likelihood analysis to 10 satellite galaxies with 24 months of data of the Fermi Large Area Telescope. No dark matter signal is detected. Including the uncertainty in the dark matter distribution, robust upper limits are placed on dark matter annihilation cross sections. The 95% confidence level upper limits range from about 10(-26) cm3 s(-1) at 5 GeV to about 5×10(-23) cm3 s(-1) at 1 TeV, depending on the dark matter annihilation final state. For the first time, using gamma rays, we are able to rule out models with the most generic cross section (â¼3×10(-26) cm3 s(-1) for a purely s-wave cross section), without assuming additional boost factors.
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UNLABELLED: Toxic microbial secondary metabolites have been proposed to be related to adverse health effects observed in moisture-damaged buildings. Initial steps in assessing the actual risk include the characterization of the exposure. In our study, we applied a multi-analyte tandem mass spectrometry-based methodology on sample materials of severely moisture-damaged homes, aiming to qualitatively and quantitatively describe the variety of microbial metabolites occurring in building materials and different dust sample types. From 69 indoor samples, all were positive for at least one of the 186 analytes targeted and as many as 33 different microbial metabolites were found. For the first time, the presence of toxic bacterial metabolites and their co-occurrence with mycotoxins were shown for indoor samples. The bacterial compounds monactin, nonactin, staurosporin and valinomycin were exclusively detected in building materials from moist structures, while chloramphenicol was particularly prevalent in house dusts, including settled airborne dust. These bacterial metabolites are highly bioactive compounds produced by Streptomyces spp., a group of microbes that is considered a moisture damage indicator in indoor environments. We show that toxic bacterial metabolites need to be considered as being part of very complex and diverse microbial exposures in 'moldy' buildings. PRACTICAL IMPLICATIONS: Bacterial toxins co-occur with mycotoxins in moisture-damaged indoor environments. These compounds are measurable also in settled airborne dust, indicating that inhalation exposure takes place. In attempts to characterize exposures to microbial metabolites not only mycotoxins but also bacterial metabolites have to be targeted by the analytical methods applied. We recommend including analysis of samples of outdoor air in the course of future indoor assessments, in an effort to better understand the outdoor contribution to the indoor presence of microbial toxins. There is a need for a sound risk assessment concerning the exposure to indoor microbial toxins at concentrations detectable in moisture-damaged indoor environments.
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Contaminación del Aire Interior/análisis , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Microbiología Ambiental , Monitoreo del Ambiente , Hongos/aislamiento & purificación , Micotoxinas/metabolismo , Bacterias/crecimiento & desarrollo , Toxinas Bacterianas/aislamiento & purificación , Toxinas Bacterianas/metabolismo , Materiales de Construcción/análisis , Materiales de Construcción/microbiología , Polvo/análisis , Hongos/crecimiento & desarrollo , Hongos/metabolismo , Micotoxinas/aislamiento & purificación , Espectrometría de Masas en Tándem/métodosRESUMEN
We have analyzed the immune system in Stat5-deficient mice. Although Stat5a-/- splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b-/- splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor beta chain (IL-2Rbeta), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation in activated splenocytes, freshly isolated splenocytes from Stat5b-/- mice exhibited greatly diminished proliferation in response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2- and IL-15-mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell-mediated proliferation and cytolytic activity.
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Citotoxicidad Inmunológica , Proteínas de Unión al ADN/inmunología , Células Asesinas Naturales/inmunología , Activación de Linfocitos/inmunología , Proteínas de la Leche , Transactivadores/inmunología , Animales , División Celular/inmunología , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica/inmunología , Interleucina-15/inmunología , Interleucina-2/inmunología , Ratones , Ratones Noqueados , Factor de Transcripción STAT5 , Transactivadores/genéticaRESUMEN
We report on the first Fermi Large Area Telescope (LAT) measurements of the so-called "extragalactic" diffuse gamma-ray emission (EGB). This component of the diffuse gamma-ray emission is generally considered to have an isotropic or nearly isotropic distribution on the sky with diverse contributions discussed in the literature. The derivation of the EGB is based on detailed modeling of the bright foreground diffuse Galactic gamma-ray emission, the detected LAT sources, and the solar gamma-ray emission. We find the spectrum of the EGB is consistent with a power law with a differential spectral index gamma = 2.41 +/- 0.05 and intensity I(>100 MeV) = (1.03 +/- 0.17) x 10(-5) cm(-2) s(-1) sr(-1), where the error is systematics dominated. Our EGB spectrum is featureless, less intense, and softer than that derived from EGRET data.
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Dark matter (DM) particle annihilation or decay can produce monochromatic gamma rays readily distinguishable from astrophysical sources. gamma-ray line limits from 30 to 200 GeV obtained from 11 months of Fermi Large Area Space Telescope data from 20-300 GeV are presented using a selection based on requirements for a gamma-ray line analysis, and integrated over most of the sky. We obtain gamma-ray line flux upper limits in the range 0.6-4.5x10{-9} cm{-2} s{-1}, and give corresponding DM annihilation cross-section and decay lifetime limits. Theoretical implications are briefly discussed.
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The diffuse galactic gamma-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess gamma-ray emission greater, > or approximately equal to 1 GeV relative to diffuse galactic gamma-ray emission models consistent with directly measured CR spectra (the so-called "EGRET GeV excess"). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse gamma-ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV and galactic latitudes 10 degrees < or = |b| < or = 20 degrees. The LAT spectrum for this region of the sky is well reproduced by a diffuse galactic gamma-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess.
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Although neuron generation is precisely regulated during ontogeny, little is known about underlying mechanisms. In addition, relationships between precursor proliferation and the apparent sequence of developmental processes, including cell migration, neurite elaboration, transmitter expression and synaptogenesis remain unknown. To address these issues, we used a fully defined neuronal cell culture system derived from embryonic rat sympathetic ganglia (DiCicco-Bloom, E., and I. B. Black. 1988. Proc. Natl. Acad. Sci. USA. 85:4066-4070) in which precursors enter the mitotic cycle. We now find that, in addition to synthesizing DNA, neuroblasts also underwent division in culture, allowing analysis of developmental relationships and mitotic regulation. Our observations indicate that mitotic neuroblasts expressed a wide array of neuron-specific characteristics including extension of neuritic processes with growth cones, elaboration of neurotransmitter enzyme, synthesis and transport of transmitter vesicles and organization of transmitter release sites. These data suggest that neuroblasts in the cell cycle may simultaneously differentiate. Consequently, the apparent sequence of ontogenetic processes is not an immutable, intrinsic neuronal program. How, then, are diverse developmental events coordinated? Our observations indicate that neuroblast mitosis is regulated by a small number of epigenetic factors, including insulin and EGF. Since these signals also influence other processes in developing neurons, epigenetic regulation normally may synchronize diverse ontogenetic events.
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Ganglios/citología , Mitosis/efectos de los fármacos , Neuronas/citología , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , ADN/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Factores de Crecimiento de Fibroblastos/farmacología , Ganglios/metabolismo , Ganglios/ultraestructura , Insulina/farmacología , Microscopía Electrónica , Neuronas/metabolismo , Neuronas/ultraestructura , Ratas , Sinapsis/metabolismo , Sinapsis/ultraestructura , Timidina/metabolismoRESUMEN
UNLABELLED: Dust collected in New Orleans homes mold-contaminated because of the flooding after hurricane Katrina was analyzed for molds and mycotoxins. The mycoflora was studied by cultivation and quantitative PCR for selected molds. The most commonly found mold taxa were Aspergillus, Cladosporium, and Penicillium. Verrucarol, a hydrolysis product of macrocyclic trichothecenes predominately produced by Stachybotrys spp. was identified in three dust samples by gas chromatography-tandem mass spectrometry, and sterigmatocystin (produced by various Aspergillus spp.) was found in two samples by high pressure liquid chromatography-tandem mass spectrometry. This is the first demonstration of mycotoxins in Katrina-associated dust samples. The analytical methods used represent valuable tools in further studies on bioaerosol exposure and health risks. PRACTICAL IMPLICATIONS: In the aftermath of natural disasters like hurricane Katrina water-damages on infrastructure and public and private property are often associated with health risks for remediation workers and returning residents. In the case of New Orleans evaluations of health hazards, health studies, and assessments of bioaerosol have been conducted previously. However, until now mycotoxins have not been addressed. Our study shows, for the first time, the presence of mycotoxins in dust collected in houses in New Orleans mold-contaminated because of the hurricane Katrina. The results may highlight the potential health threats posed by mold aerosols in post-disaster inhabited areas.
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Microbiología del Aire , Contaminación del Aire Interior/análisis , Polvo/análisis , Hongos/crecimiento & desarrollo , Micotoxinas/análisis , Tormentas Ciclónicas , Desastres , Vivienda , Humanos , Nueva OrleansRESUMEN
Natriuretic peptides such as brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are commonly used in the diagnosis and evaluation of heart failure. However, their utility in patients with chronic kidney disease (CKD) is less clear as renal dysfunction itself can be associated with elevated concentrations of these biomarkers. Given the high prevalence of left ventricular hypertrophy and left ventricular systolic dysfunction in patients with CKD, diagnosis or exclusion of heart failure becomes important in this population. Most studies to date indicate that upward adjustment of diagnostic cut points preserves the usefulness of both BNP and NT-proBNP in the CKD patient, with similar clinical performance of each biomarker. We review the role of natriuretic peptide in heart failure in the setting of chronic renal disease.
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Insuficiencia Cardíaca/diagnóstico , Enfermedades Renales/complicaciones , Péptidos Natriuréticos/metabolismo , Biomarcadores/metabolismo , Enfermedad Crónica , GMP Cíclico/biosíntesis , Humanos , Enfermedades Renales/metabolismo , Diálisis RenalRESUMEN
Although proliferation is fundamental to the generation of neuronal populations, little is known about the function of trophic mechanisms during neurogenesis. We now describe a novel role for neurotrophin-3 (NT-3): the neurotrophin stimulates proliferation of sympathetic neuroblasts through trophic mechanisms. NT-3 promotes survival of the dividing precursors, but does not directly stimulate mitosis. NT-3 trophic effects differ markedly from those of the sympathetic mitogen, insulin. Furthermore, whereas NT-3 exhibits trophic activity for dividing neuroblasts, nerve growth factor characteristically promotes survival of postnatal sympathetic neurons. The stage-specific activity of NT-3 and nerve growth factor in culture parallels the sequence of trkC and trkA receptor gene expression detected in vivo. Thus, neurotrophins apparently serve as trophic factors during ontogeny, acting sequentially during establishment of individual populations.