146 research outputs found

    Search for sterile neutrino mixing in the MINOS long-baseline experiment

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    A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

    Neighborhood level risk factors for type 1 diabetes in youth: the SEARCH case-control study

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    <p>Abstract</p> <p>Background</p> <p>European ecologic studies suggest higher socioeconomic status is associated with higher incidence of type 1 diabetes. Using data from a case-control study of diabetes among racially/ethnically diverse youth in the United States (U.S.), we aimed to evaluate the independent impact of neighborhood characteristics on type 1 diabetes risk. Data were available for 507 youth with type 1 diabetes and 208 healthy controls aged 10-22 years recruited in South Carolina and Colorado in 2003-2006. Home addresses were used to identify Census tracts of residence. Neighborhood-level variables were obtained from 2000 U.S. Census. Multivariate generalized linear mixed models were applied.</p> <p>Results</p> <p>Controlling for individual risk factors (age, gender, race/ethnicity, infant feeding, birth weight, maternal age, number of household residents, parental education, income, state), higher neighborhood household income (p = 0.005), proportion of population in managerial jobs (p = 0.02), with at least high school education (p = 0.005), working outside the county (p = 0.04) and vehicle ownership (p = 0.03) were each independently associated with increased odds of type 1 diabetes. Conversely, higher percent minority population (p = 0.0003), income from social security (p = 0.002), proportion of crowded households (0.0497) and poverty (p = 0.008) were associated with a decreased odds.</p> <p>Conclusions</p> <p>Our study suggests that neighborhood characteristics related to greater affluence, occupation, and education are associated with higher type 1 diabetes risk. Further research is needed to understand mechanisms underlying the influence of neighborhood context.</p

    Development of Highly Organized Lymphoid Structures in Buruli Ulcer Lesions after Treatment with Rifampicin and Streptomycin

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    Buruli ulcer (BU) is a debilitating disease of the skin presenting with extensive tissue destruction and suppression of local host defence mechanisms. Surgical removal of the affected area has been the standard therapy until in 2004 WHO recommended eight weeks' treatment with the anti-mycobacterial drugs rifampicin and streptomycin. We performed a detailed histological analysis of the local immune response in biopsies from five children medicated according to WHO provisional guidelines. One patient still revealed all histopathological signatures of an active BU lesion with huge bacterial clusters in areas of fatty tissue necrosis. Different factors can contribute to treatment failure, such as poor patient compliance and resistant bacterial strains. In four patients, different compartments of the skin presented active immune processes with only limited residues of bacterial material persisting. We demonstrated that antibiotic treatment not only directly controls the infectious agent but is also associated with fulminant host immune responses. Characterization of the healing process in BU due to therapy is highly relevant to increase our knowledge of the impact of treatment strategies to fight the disease

    Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

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    BACKGROUND: Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. METHODS: Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine) or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF)-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and liver histopathology. RESULTS: A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. CONCLUSION: Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury

    Ecoregional Analysis of Nearshore Sea-Surface Temperature in the North Pacific

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    The quantification and description of sea surface temperature (SST) is critically important because it can influence the distribution, migration, and invasion of marine species; furthermore, SSTs are expected to be affected by climate change. To better understand present temperature regimes, we assembled a 29-year nearshore time series of mean monthly SSTs along the North Pacific coastline using remotely-sensed satellite data collected with the Advanced Very High Resolution Radiometer (AVHRR) instrument. We then used the dataset to describe nearshore (<20 km offshore) SST patterns of 16 North Pacific ecoregions delineated by the Marine Ecoregions of the World (MEOW) hierarchical schema. Annual mean temperature varied from 3.8°C along the Kamchatka ecoregion to 24.8°C in the Cortezian ecoregion. There are smaller annual ranges and less variability in SST in the Northeast Pacific relative to the Northwest Pacific. Within the 16 ecoregions, 31–94% of the variance in SST is explained by the annual cycle, with the annual cycle explaining the least variation in the Northern California ecoregion and the most variation in the Yellow Sea ecoregion. Clustering on mean monthly SSTs of each ecoregion showed a clear break between the ecoregions within the Warm and Cold Temperate provinces of the MEOW schema, though several of the ecoregions contained within the provinces did not show a significant difference in mean seasonal temperature patterns. Comparison of these temperature patterns shared some similarities and differences with previous biogeographic classifications and the Large Marine Ecosystems (LMEs). Finally, we provide a web link to the processed data for use by other researchers

    Learning environment, attitudes and anxiety across the transition from primary to secondary school mathematics

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    Past research has revealed that, relative to primary-school students, high-school students have less-positive attitudes to mathematics and perceive their classroom environments and teacher–student relationships less favourably. This study involved the transition experience of 541 students in 47 classes in 15 primary (year 7) and secondary (year 8) government and Catholic schools in metropolitan and regional South Australia. Scales were adapted from three established instruments, namely, the What Is Happening In this Class?, Test of Mathematics Related Attitudes and Revised Mathematics Anxiety Ratings Scale, to identify changes across the transition from primary to secondary school in terms of the classroom learning environment and students’ attitude/anxiety towards mathematics. Relative to year 7 students, year 8 students reported less Involvement, less positive Attitude to Mathematical Inquiry, less Enjoyment of Mathematics and greater Mathematics Anxiety. Differences between students in Years 7 and 8 were very similar for male and female students, although the magnitude of sex differences in attitudes was slightly different in Years 7 and 8

    Nitric Oxide Antagonizes the Acid Tolerance Response that Protects Salmonella against Innate Gastric Defenses

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    Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood.The genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment.Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses
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