2,192 research outputs found

    Predicting Partisan Redistricting Disputes

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    Partisan redistricting disputes are relatively rare occurrences. This paper explores the factors that lead to partisan disputes over congressional redistricting plans. In previous work single party control of both houses of the state legislature and the governorship emerged as a key correlate of partisan redistricting in the 1980s. This paper presents an interactive statistical model of partisan redistricting plans. The basic conclusion is that in addition to single party control, the nature of the voting role and the political competitiveness of the states effect the likelihood of partisan redistricting

    The Mohawk

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    A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.

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    We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer's disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels

    GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6).

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    CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE: The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender

    On the action potential as a propagating density pulse and the role of anesthetics

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    The Hodgkin-Huxley model of nerve pulse propagation relies on ion currents through specific resistors called ion channels. We discuss a number of classical thermodynamic findings on nerves that are not contained in this classical theory. Particularly striking is the finding of reversible heat changes, thickness and phase changes of the membrane during the action potential. Data on various nerves rather suggest that a reversible density pulse accompanies the action potential of nerves. Here, we attempted to explain these phenomena by propagating solitons that depend on the presence of cooperative phase transitions in the nerve membrane. These transitions are, however, strongly influenced by the presence of anesthetics. Therefore, the thermodynamic theory of nerve pulses suggests a explanation for the famous Meyer-Overton rule that states that the critical anesthetic dose is linearly related to the solubility of the drug in the membranes.Comment: 13 pages, 8 figure

    Electronic structure of REREAuMg and REREAgMg (RERE = Eu, Gd, Yb)

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    We have investigated the electronic structure of the equiatomic EuAuMg, GdAuMg, YbAuMg and GdAgMg intermetallics using x-ray photoelectron spectroscopy. The spectra revealed that the Yb and Eu are divalent while the Gd is trivalent. The spectral weight in the vicinity of the Fermi level is dominated by the mix of Mg ss, Au/Ag spsp and RERE spdspd bands, and not by the RERE 4f4f. We also found that the Au and Ag dd bands are extraordinarily narrow, as if the noble metal atoms were impurities submerged in a low density spsp metal host. The experimental results were compared with band structure calculations, and we found good agreement provided that the spin-orbit interaction in the Au an Ag dd bands is included and correlation effects in an open 4f4f shell are accounted for using the local density approximation + Hubbard UU scheme. Nevertheless, limitations of such a mean-field scheme to explain excitation spectra are also evident.Comment: 4 pages, 3 figures, Brief Repor

    Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections

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    Background: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. Methods: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64. 1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. Results: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. Conclusions: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found

    Testing the performance of a blind burst statistic

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    In this work we estimate the performance of a method for the detection of burst events in the data produced by interferometric gravitational wave detectors. We compute the receiver operating characteristics in the specific case of a simulated noise having the spectral density expected for Virgo, using test signals taken from a library of possible waveforms emitted during the collapse of the core of Type II Supernovae.Comment: 8 pages, 6 figures, Talk given at the GWDAW2002 worksho

    Ultrafine particle distribution and chemical composition assessment during military operative trainings

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    The assessment of airborne particulate matter (PM) and ultrafine particles (UFPs) in battlefield scenarios is a topic of particular concern; (2) Methods: Size distribution, concentration, and chemical composition of UFPs during operative military training activities (target drone launches, ammunition blasting, and inert bomb impact) were investigated using an electric low-pressure impactor (ELPI+) and a scanning electron microscope (SEM), equipped with energy-dispersive spectroscopy (EDS); (3) Results: The median of UFPs, measured for all sampling periods and at variable distance from sources, was between 1.02 × 103 and 3.75 × 103 particles/cm3 for drone launches, between 3.32 × 103 and 15.4 × 103 particles/cm3 for the ammunition blasting and from 7.9 × 103 to 1.3 × 104 particles/cm3 for inert launches. Maximum peak concentrations, during emitting sources starting, were 75.5 × 106 and 17.9 × 106 particles/cm3, respectively. Particles from the drone launches were predominantly composed of silicon (Si), iron (Fe) and calcium (Ca), and those from the blasting campaigns by magnesium (Mg), sulphur (S), aluminum (Al), iron (Fe), barium (Ba) and silicon (Si); (4) Conclusions: The investigated sources produced UFPs with median values lower than other anthropogenic sources, and with a similar chemical compositio
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