247 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

    Hemispheric Asymmetries in Speech Perception: Sense, Nonsense and Modulations

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    Background: The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'.Methodology: A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds.Conclusions: Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features

    Differential Regulation of Horizontally Acquired and Core Genome Genes by the Bacterial Modulator H-NS

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    Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization

    A Class Representative Model for Pure Parsimony Haplotyping under Uncertain Data

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    The Pure Parsimony Haplotyping (PPH) problem is a NP-hard combinatorial optimization problem that consists of finding the minimum number of haplotypes necessary to explain a given set of genotypes. PPH has attracted more and more attention in recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from mapping complex disease genes to inferring population histories, passing through designing drugs, functional genomics and pharmacogenetics. In this article we investigate, for the first time, a recent version of PPH called the Pure Parsimony Haplotype problem under Uncertain Data (PPH-UD). This version mainly arises when the input genotypes are not accurate, i.e., when some single nucleotide polymorphisms are missing or affected by errors. We propose an exact approach to solution of PPH-UD based on an extended version of Catanzaro et al. [1] class representative model for PPH, currently the state-of-the-art integer programming model for PPH. The model is efficient, accurate, compact, polynomial-sized, easy to implement, solvable with any solver for mixed integer programming, and usable in all those cases for which the parsimony criterion is well suited for haplotype estimation

    Immunomodulation with Recombinant Interferon-γ1b in Pulmonary Tuberculosis

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    BACKGROUND:Current treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-gamma1b (rIFN-gammab) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance. METHODOLOGY/PRINCIPAL FINDINGS:We performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-gamma1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1beta, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-gamma1b group from baseline to week 16. Both rIFN-gamma1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-gamma1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-gamma1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-gamma1b versus DOTS alone. CONCLUSION:Recombinant interferon-gamma1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms. TRIAL REGISTRATION:ClinicalTrials.gov NCT00201123

    Hepatitis B virus genotypes and evolutionary profiles from blood donors from the northwest region of China

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    Hepatitis B virus (HBV) is prevalent in China and screening of blood donors is mandatory. Up to now, ELISA has been universally used by the China blood bank. However, this strategy has sometimes failed due to the high frequency of nucleoside acid mutations. Understanding HBV evolution and strain diversity could help devise a better screening system for blood donors. However, this kind of information in China, especially in the northwest region, is lacking. In the present study, serological markers and the HBV DNA load of 11 samples from blood donor candidates from northwest China were determined. The HBV strains were most clustered into B and C genotypes and could not be clustered into similar types from reference sequences. Subsequent testing showed liver function impairment and increasing virus load in the positive donors. This HBV evolutionary data for China will allow for better ELISA and NAT screening efficiency in the blood bank of China, especially in the northwest region

    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

    Field-study science classrooms as positive and enjoyable learning environments

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    We investigated differences between field-study classrooms and traditional science classrooms in terms of the learning environment and students’ attitudes to science, as well as the differential effectiveness of field-study classrooms for students differing in sex and English proficiency. A modified version of selected scales from the What Is Happening In this Class? questionnaire was used to assess the learning environment, whereas students’ attitudes were assessed with a shortened version of a scale from the Test of Science Related Attitudes. A sample of 765 grade 5 students from 17 schools responded to the learning environment and attitude scales in terms of both their traditional science classrooms and classrooms at a field-study centre in Florida. Large effect sizes supported the effectiveness of the field-studies classroom in terms of both the learning environment and student attitudes. Relative to the home school science class, the field-study class was considerably more effective for students with limited English proficiency than for native English speakers

    Humans and Insects Decide in Similar Ways

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    Behavioral ecologists assume that animals use a motivational mechanism for decisions such as action selection and time allocation, allowing the maximization of their fitness. They consider both the proximate and ultimate causes of behavior in order to understand this type of decision-making in animals. Experimental psychologists and neuroeconomists also study how agents make decisions but they consider the proximate causes of the behavior. In the case of patch-leaving, motivation-based decision-making remains simple speculation. In contrast to other animals, human beings can assess and evaluate their own motivation by an introspection process. It is then possible to study the declared motivation of humans during decision-making and discuss the mechanism used as well as its evolutionary significance. In this study, we combine both the proximate and ultimate causes of behavior for a better understanding of the human decision-making process. We show for the first time ever that human subjects use a motivational mechanism similar to small insects such as parasitoids [1] and bumblebees [2] to decide when to leave a patch. This result is relevant for behavioral ecologists as it supports the biological realism of this mechanism. Humans seem to use a motivational mechanism of decision making known to be adaptive to a heterogeneously distributed resource. As hypothesized by Hutchinson et al. [3] and Wilke and Todd [4], our results are consistent with the evolutionary shaping of decision making because hominoids were hunters and gatherers on food patches for more than two million years. We discuss the plausibility of a neural basis for the motivation mechanism highlighted here, bridging the gap between behavioral ecology and neuroeconomy. Thus, both the motivational mechanism observed here and the neuroeconomy findings are most likely adaptations that were selected for during ancestral times
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