187 research outputs found

    Advancing Interoperable Connectivity Deployment: Connected Vehicle Pilot Deployment Results and Findings

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    DTFH6116F00019In September 2015, the U.S. Department of Transportation (USDOT) Intelligent Transportation Systems (ITS) Joint Program Office (JPO) awarded three deployment sites under the Connected Vehicle (CV) Pilot Deployment Program to: the New York City Department of Transportation (NYCDOT); the Tampa Hillsborough Expressway Authority (THEA); and the Wyoming Department of Transportation (WYDOT). Each site planned, built, tested, deployed, and operated a tailored suite of CV applications addressing stakeholder-identified transportation needs in diverse systems, ranging from dense urban grid networks to isolated high-plains interstates. Safety, mobility, environmental, and public agency efficiency impacts of CV applications were assessed by both the sites themselves and independent evaluators. All three sites overcame significant technical and non-technical challenges to integrate still-maturing CV technology within their deployed transportation systems. Due to the limitations of working with emerging technologies, impacts for many applications were reduced. Despite these challenges, the program achieved key goals related to interoperability, cybersecurity, and replicability and demonstrated that CV technologies and foundational standards can be utilized to mount multiple large-scale operational deployments. This report serves as an entry point for readers seeking to understand the objectives, successes, and insights gained from the CV Pilot Deployment Program

    Synesthesia and Migraine: Case Report

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    <p>Abstract</p> <p>Background</p> <p>Synesthesia is, as visual migraine aura, a common and fascinating perceptual phenomenon. Here we present a unique case with synesthesias exclusively during visual migraine auras.</p> <p>Case presentation</p> <p>A 40-year-old woman with a cyclic mood disorder had suffered from migraine with visual aura for several years. On several occasions she had experienced "mixing of senses" during the aura phase. Staring at strong bright light she could experience intense taste of lemon with flow from the salivary glands.</p> <p>Conclusion</p> <p>Acquired synesthesia, exclusively coincident with migraine aura, gives support to the idea of an anomalous cortical processing underlying the phenomenon.</p

    On the cosmic ray bound for models of extragalactic neutrino production

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    We obtain the maximum diffuse neutrino intensity predicted by hadronic photoproduction models of the type which have been applied to the jets of active galactic nuclei or gamma ray bursts. For this, we compare the proton and gamma ray fluxes associated with hadronic photoproduction in extragalactic neutrino sources with the present experimental upper limit on cosmic ray protons and the extragalactic gamma ray background, employing a transport calculation of energetic protons traversing cosmic photon backgrounds. We take into account the effects of the photon spectral shape in the sources on the photoproduction process, cosmological source evolution, the optical depth for cosmic ray ejection, and discuss the possible effects of magnetic fields in the vicinity of the sources. For photohadronic neutrino sources which are optically thin to the emission of neutrons we find that the cosmic ray flux imposes a stronger bound than the extragalactic gamma ray background in the energy range between 10^5 GeV and 10^11 GeV, as previously noted by Waxman & Bahcall (1999). We also determine the maximum contribution from the jets of active galactic nuclei, using constraints set to their neutron opacity by gamma-ray observations. This present upper limit is consistent with the jets of active galactic nuclei producing the extragalactic gamma ray background hadronically, but we point out future observations in the GeV-to-TeV regime could lower this limit. We also briefly discuss the contribution of gamma ray bursts to ultra-high energy cosmic rays as it can be inferred from possible observations or limits on their correlated neutrino fluxes.Comment: 16 pages, includes 7 figures, using REVtex3.1, accepted for publication in Phys.Rev.D after minor revision

    Deficiency of FLCN in Mouse Kidney Led to Development of Polycystic Kidneys and Renal Neoplasia

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    The Birt–Hogg–Dubé (BHD) disease is a genetic cancer syndrome. The responsible gene, BHD, has been identified by positional cloning and thought to be a novel tumor suppressor gene. BHD mutations cause many types of diseases including renal cell carcinomas, fibrofolliculomas, spontaneous pneumothorax, lung cysts, and colonic polyps/cancers. By combining Gateway Technology with the Ksp-Cre gene knockout system, we have developed a kidney-specific BHD knockout mouse model. BHDflox/flox/Ksp-Cre mice developed enlarged kidneys characterized by polycystic kidneys, hyperplasia, and cystic renal cell carcinoma. The affected BHDflox/flox/Ksp-Cre mice died of renal failure at approximate three weeks of age, having blood urea nitrogen levels over tenfold higher than those of BHD flox/+/Ksp-Cre and wild-type littermate controls. We further demonstrated that these phenotypes were caused by inactivation of BHD and subsequent activation of the mTOR pathway. Application of rapamycin, which inhibits mTOR activity, to the affected mice led to extended survival and inhibited further progression of cystogenesis. These results provide a correlation of kidney-targeted gene inactivation with renal carcinoma, and they suggest that the BHD product FLCN, functioning as a cyst and tumor suppressor, like other hamartoma syndrome–related proteins such as PTEN, LKB1, and TSC1/2, is a component of the mTOR pathway, constituting a novel FLCN-mTOR signaling branch that regulates cell growth/proliferation

    Genome-Wide Analysis of Müller Glial Differentiation Reveals a Requirement for Notch Signaling in Postmitotic Cells to Maintain the Glial Fate

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    Previous studies have shown that Müller glia are closely related to retinal progenitors; these two cell types express many of the same genes and after damage to the retina, Müller glia can serve as a source for new neurons, particularly in non-mammalian vertebrates. We investigated the period of postnatal retinal development when progenitors are differentiating into Müller glia to better understand this transition. FACS purified retinal progenitors and Müller glia from various ages of Hes5-GFP mice were analyzed by Affymetrix cDNA microarrays. We found that genes known to be enriched/expressed by Müller glia steadily increase over the first three postnatal weeks, while genes associated with the mitotic cell cycle are rapidly downregulated from P0 to P7. Interestingly, progenitor genes not directly associated with the mitotic cell cycle, like the proneural genes Ascl1 and Neurog2, decline more slowly over the first 10–14 days of postnatal development, and there is a peak in Notch signaling several days after the presumptive Müller glia have been generated. To confirm that Notch signaling continues in the postmitotic Müller glia, we performed in situ hybridization, immunolocalization for the active form of Notch, and immunofluorescence for BrdU. Using genetic and pharmacological approaches, we found that sustained Notch signaling in the postmitotic Müller glia is necessary for their maturation and the stabilization of the glial identity for almost a week after the cells have exited the mitotic cell cycle

    Multimorbidity Patterns in the Elderly: A New Approach of Disease Clustering Identifies Complex Interrelations between Chronic Conditions

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    Objective: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients ’ quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. Methods: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence $ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. Results: Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78 % and 75%, respectively). The patterns were largely age-dependent an

    Trehalose-6-phosphate-mediated toxicity determines essentiality of OtsB2 in Mycobacterium tuberculosis in vitro and in mice

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    Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2. We found that otsB2 is essential for growth of M. tuberculosis in vitro as well as for the acute infection phase in mice following aerosol infection. By contrast, otsB2 is not essential for the chronic infection phase in mice, highlighting the substantial remodelling of trehalose metabolism during infection by M. tuberculosis. Blocking OtsB2 resulted in the accumulation of its substrate T6P, which appears to be toxic, leading to the self-poisoning of cells. Accordingly, blocking T6P production in a ΔotsA mutant abrogated otsB2 essentiality. T6P accumulation elicited a global upregulation of more than 800 genes, which might result from an increase in RNA stability implied by the enhanced neutralization of toxins exhibiting ribonuclease activity. Surprisingly, overlap with the stress response caused by the accumulation of another toxic sugar phosphate molecule, maltose-1-phosphate, was minimal. A genome-wide screen for synthetic lethal interactions with otsA identified numerous genes, revealing additional potential drug targets synergistic with OtsB2 suitable for combination therapies that would minimize the emergence of resistance to OtsB2 inhibitors

    A Synoptical Classification of the Bivalvia (Mollusca)

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    The following classification summarizes the suprageneric taxono-my of the Bivalvia for the upcoming revision of the Bivalvia volumes of the Treatise on Invertebrate Paleontology, Part N. The development of this classification began with Carter (1990a), Campbell, Hoeks-tra, and Carter (1995, 1998), Campbell (2000, 2003), and Carter, Campbell, and Campbell (2000, 2006), who, with assistance from the United States National Science Foundation, conducted large-scale morphological phylogenetic analyses of mostly Paleozoic bivalves, as well as molecular phylogenetic analyses of living bivalves. Dur-ing the past several years, their initial phylogenetic framework has been revised and greatly expanded through collaboration with many students of bivalve biology and paleontology, many of whom are coauthors. During this process, all available sources of phylogenetic information, including molecular, anatomical, shell morphological, shell microstructural, bio- and paleobiogeographic as well as strati-graphic, have been integrated into the classification. The more recent sources of phylogenetic information include, but are not limited to, Carter (1990a), Malchus (1990), J. Schneider (1995, 1998a, 1998b, 2002), T. Waller (1998), Hautmann (1999, 2001a, 2001b), Giribet and Wheeler (2002), Giribet and Distel (2003), Dreyer, Steiner, and Harper (2003), Matsumoto (2003), Harper, Dreyer, and Steiner (2006), Kappner and Bieler (2006), Mikkelsen and others (2006), Neulinger and others (2006), Taylor and Glover (2006), Kříž (2007), B. Morton (2007), Taylor, Williams, and Glover (2007), Taylor and others (2007), Giribet (2008), and Kirkendale (2009). This work has also benefited from the nomenclator of bivalve families by Bouchet and Rocroi (2010) and its accompanying classification by Bieler, Carter, and Coan (2010).This classification strives to indicate the most likely phylogenetic position for each taxon. Uncertainty is indicated by a question mark before the name of the taxon. Many of the higher taxa continue to undergo major taxonomic revision. This is especially true for the superfamilies Sphaerioidea and Veneroidea, and the orders Pectinida and Unionida. Because of this state of flux, some parts of the clas-sification represent a compromise between opposing points of view. Placement of the Trigonioidoidea is especially problematic. This Mesozoic superfamily has traditionally been placed in the order Unionida, as a possible derivative of the superfamily Unionoidea (see Cox, 1952; Sha, 1992, 1993; Gu, 1998; Guo, 1998; Bieler, Carter, & Coan, 2010). However, Chen Jin-hua (2009) summarized evi-dence that Trigonioidoidea was derived instead from the superfamily Trigonioidea. Arguments for these alternatives appear equally strong, so we presently list the Trigonioidoidea, with question, under both the Trigoniida and Unionida, with the contents of the superfamily indicated under the Trigoniida.Fil: Carter, Joseph G.. University of North Carolina; Estados UnidosFil: Altaba, Cristian R.. Universidad de las Islas Baleares; EspañaFil: Anderson, Laurie C.. South Dakota School of Mines and Technology; Estados UnidosFil: Araujo, Rafael. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Ciencias Naturales; EspañaFil: Biakov, Alexander S.. Russian Academy of Sciences; RusiaFil: Bogan, Arthur E.. North Carolina State Museum of Natural Sciences; Estados UnidosFil: Campbell, David. Paleontological Research Institution; Estados UnidosFil: Campbell, Matthew. Charleston Southern University; Estados UnidosFil: Chen, Jin Hua. Chinese Academy of Sciences. Nanjing Institute of Geology and Palaeontology; República de ChinaFil: Cope, John C. W.. National Museum of Wales. Department of Geology; Reino UnidoFil: Delvene, Graciela. Instituto Geológico y Minero de España; EspañaFil: Dijkstra, Henk H.. Netherlands Centre for Biodiversity; Países BajosFil: Fang, Zong Jie. Chinese Academy of Sciences; República de ChinaFil: Gardner, Ronald N.. No especifica;Fil: Gavrilova, Vera A.. Russian Geological Research Institute; RusiaFil: Goncharova, Irina A.. Russian Academy of Sciences; RusiaFil: Harries, Peter J.. University of South Florida; Estados UnidosFil: Hartman, Joseph H.. University of North Dakota; Estados UnidosFil: Hautmann, Michael. Paläontologisches Institut und Museum; SuizaFil: Hoeh, Walter R.. Kent State University; Estados UnidosFil: Hylleberg, Jorgen. Institute of Biology; DinamarcaFil: Jiang, Bao Yu. Nanjing University; República de ChinaFil: Johnston, Paul. Mount Royal University; CanadáFil: Kirkendale, Lisa. University Of Wollongong; AustraliaFil: Kleemann, Karl. Universidad de Viena; AustriaFil: Koppka, Jens. Office de la Culture. Section d’Archéologie et Paléontologie; SuizaFil: Kříž, Jiří. Czech Geological Survey. Department of Sedimentary Formations. Lower Palaeozoic Section; República ChecaFil: Machado, Deusana. Universidade Federal do Rio de Janeiro; BrasilFil: Malchus, Nikolaus. Institut Català de Paleontologia; EspañaFil: Márquez Aliaga, Ana. Universidad de Valencia; EspañaFil: Masse, Jean Pierre. Universite de Provence; FranciaFil: McRoberts, Christopher A.. State University of New York at Cortland. Department of Geology; Estados UnidosFil: Middelfart, Peter U.. Australian Museum; AustraliaFil: Mitchell, Simon. The University of the West Indies at Mona; JamaicaFil: Nevesskaja, Lidiya A.. Russian Academy of Sciences; RusiaFil: Özer, Sacit. Dokuz Eylül University; TurquíaFil: Pojeta, John Jr.. National Museum of Natural History; Estados UnidosFil: Polubotko, Inga V.. Russian Geological Research Institute; RusiaFil: Pons, Jose Maria. Universitat Autònoma de Barcelona; EspañaFil: Popov, Sergey. Russian Academy of Sciences; RusiaFil: Sanchez, Teresa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Sartori, André F.. Field Museum of National History; Estados UnidosFil: Scott, Robert W.. Precision Stratigraphy Associates; Estados UnidosFil: Sey, Irina I.. Russian Geological Research Institute; RusiaFil: Signorelli, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Silantiev, Vladimir V.. Kazan Federal University; RusiaFil: Skelton, Peter W.. Open University. Department of Earth and Environmental Sciences; Reino UnidoFil: Steuber, Thomas. The Petroleum Institute; Emiratos Arabes UnidosFil: Waterhouse, J. Bruce. No especifica;Fil: Wingard, G. Lynn. United States Geological Survey; Estados UnidosFil: Yancey, Thomas. Texas A&M University; Estados Unido

    The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm

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    OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy

    Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

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