49 research outputs found

    Stress-induced anxiety- and depressive-like phenotype associated with transient reduction in neurogenesis in adult Nestin-CreERT2/diphtheria toxin fragment A transgenic mice

    No full text
    Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient-rather than permanent-inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreERT2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12-30 days post-TAM displayed indices of a stress-induced anxiety phenotype-longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype-longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety and a depressive phenotype, and recovery of DCX+ cell number corresponds to normalization of these behaviors

    Qualitative Identification of the Components of the Okra Pod Polysaccharide Fraction by Paper Chromatography

    No full text
    The research or Dr. Hiram Benjamin of the Marquette University Medical School on the intravenous injection of an aqueous solution of\u27 okra powder for ulcer therapy resulted in investigations concerning its suitability as a · p1asma extender. Transfusion trials on dogs were so encouraging that its potential as a human volemic was readily recognized. Since such use would require detailed knowledge of the polysaceharide\u27s constitution for toxicity and metabolic evaluations, research was needed to elucidate the nature or the polysaccharide macromolecule. Observing the lack of any reported data concerning okra, Dr. Kenneth Brown or the Biochemistry Department or the Marquette Medical School. saw the feasibility of hydrolyzing the polysaccharide obtained from the okra pods and of the use of chromatography to detect the sugars formed. Initially Dr. Brown and the author tried several chromatographic columns in hopes of isolating sufficient quantities of the sugars for derivative formation. As will be shown it was found necessary to employ paper chromatography to obtain the desired information

    Emerg Infect Dis

    No full text
    We report 2 fatal exacerbations of systemic capillary leak syndrome (SCLS), also known as Clarkson disease, associated with coronavirus disease (COVID-19) in the United States. One patient carried an established diagnosis of SCLS and the other sought treatment for new-onset hypotensive shock, hemoconcentration, and anasarca, classic symptoms indicative of an SCLS flare. Both patients had only mild-to-moderate symptoms of COVID-19. This clinical picture suggests that these patients succumbed to complications of SCLS induced by infection with severe acute respiratory syndrome coronavirus 2. Persons with known or suspected SCLS may be at increased risk for developing a disease flare in the setting of mild-to-moderate COVID-19 infection

    The Timing of Product Innovation and Regulatory Delay

    No full text
    This paper endogenizes the interplay between innovation by a regulated â?¦rm and regulatory delay. In the signaling model, the â?¦rm times its innovation to communicate its private information about the MC of delay to the regulator. When product innovation costs fall over time, an extra day of regulatory delay increases time to introduction by more than a day. Successful signaling leads the regulator to adjust regulatory delay. The separating equilibrium of the signaling model generates testable predictions for how innovation and regulatory delay evolve over time. The model is consistent with data gathered from one of the Bell telecommunications â?¦rms.

    De berekening van getijden en stormvloeden op benedenrivieren

    No full text
    Ter oplossing van het, aan de "Staatscommissie inzake hooge waterstanden als gevolg van de afsluiting der Zuiderzee" voorgelegde probleem, heeft de voorzitter dezer commissie, de groote natuurkundige H. A. Lorentz, als eerste een betrouwbare en practisch uitvoerbare methode gegeven tot het berekenen. van getijverschijnselen in zeeannen. Deze methode benadert de totale getijbeweging door het hoofdgetij Mz en gaat niet in op den juisten vorm van de getiilijn, welke beperking voor practische doeleinden in het algemeen geen bezwaren oplevert (vergelijk § 15). Daarbij is het mogelijk, het M2getij ook voor ingewikkelde gebieden met een hoogen graad van nauwkeurigheid te berekenen. Aangetoond kan worden, hoe deze betrouwbaarheid reeds ligt opgesloten in het karakter van de vereenvoudigingen, welke Lorentz aan de strenge differentiaalvergelijkingen aanbracht. Behalve het getijprobleem heeft Lorentz het hem gestelde stormvloedsvraagstuk eveneens tot een goed resultaat gebracht. Bij getijden en stormvloeden op benedenrivieren treden deze van de zee uitgaande verschijnselen in wisselwerking met de door den afvoer van opperwater veroorzaakte stroomen en verhangen. Beide groepen van verschijnselen verloopen dientengevolge anders dan indien zij alleen zouden optreden en de theorie van de waterbeweging op benedenrivieren zal daarom ingewikkelder moeten zijn dan die voor zeearmen. Aanvankelijk heeft men in Nederland de gevolgen van het practisch ingrijpen in den toestand op de benedenrivieren slechts op het gevoel beoordeeld, doch later heeft men getracht deze gevolgen te berekenen. Eenerzijds kwam men daarbij tot Z.g. "exacte" methoden, berustende op reeksontwikkeling of differentievergelijkingen. Deze methoden staan theoretisch het hoogst, daar zij niet dwingen tot het verwaarloozen of benaderen van invloeden, welke in de differentiaalvergelijkingen zijn weer te geven en omdat in principe met behulp ervan het g e heel eve r 100 p van den waterstand op elk punt van een benedenrivier kan worden berekend. Het eraan verbonden werk is echter zoo groot, dat, behoudens voor zeer eenvoudige gebieden, het uitvoeren van de berekening practisch ondoenlijk is. Daarom is het begrijpelijk, dat anderzijds Z.g. "eenvoudige" methoden opkwamen, welke op minder bewerkelijke wijze tot berekening van de hoofddzaken der getijbeweging wilden geraken. Bij de analyse van deze methoden in § 9 bleken echter de door Krey, Bonnet en van Veen geg'even rekenwijzen niet aan den eisch van algemeene betrouwbaarheid te voldoen. Een methode, zooals die van Lorentz voor zeearmen vormt, welke een betrouwbare en practisch goed uitvoerbare berekening van de hoofdzaken van het getijverschijnsel mogelijk maakt, was voor benedenrivieren niet aanwezig, tenvijl toch ongehvijfeld behoefte eraan wordt gevoeld.Hydraulic EngineeringCivil Engineering and Geoscience

    IceCube-Gen2: A Vision for the Future of Neutrino Astronomy in Antarctica

    No full text
    20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)The recent observation by the IceCube neutrino observatory of an astrophysical flux of neutrinos represents the "first light" in the nascent field of neutrino astronomy. The observed diffuse neutrino flux seems to suggest a much larger level of hadronic activity in the non-thermal universe than previously thought and suggests a rich discovery potential for a larger neutrino observatory. This document presents a vision for an substantial expansion of the current IceCube detector, IceCube-Gen2, including the aim of instrumenting a 10km310\,\mathrm{km}^3 volume of clear glacial ice at the South Pole to deliver substantial increases in the astrophysical neutrino sample for all flavors. A detector of this size would have a rich physics program with the goal to resolve the sources of these astrophysical neutrinos, discover GZK neutrinos, and be a leading observatory in future multi-messenger astronomy programs

    A copula model for dependent competing risks

    No full text
    "Many popular estimators for duration models require independent competing risks or independent censoring. In contrast, copula based estimators are also consistent in presence of dependent competing risks. In this paper we suggest a computationally convenient extension of the Copula Graphic Estimator (Zheng and Klein, 1995) to a model with more than two dependent competing risks. We analyse the applicability of this estimator by means of simulations and real world unemployment duration data from Germany. We obtain evidence that our estimator yields nice results if the dependence structure is known and that it is a powerful tool for the assessment of the relevance of (in-)dependence assumptions in applied duration research." (Author's abstract, IAB-Doku) ((en)) Additional Information Appendix for the FDZ-Methodenreport No. 02/2009Risikoabschätzung - Modell, Wirkungsforschung - Methode, Methodologie, Arbeitsmarktpolitik - Erfolgskontrolle, ältere Arbeitnehmer, Leistungsanspruch - Dauer, Arbeitslosigkeitsdauer, IAB-Beschäftigtenstichprobe

    Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice

    No full text
    Background: 
There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. 

Methodology/Principal Findings: 
The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels, although some up-regulation was observed in rested losers. Significant positive correlations were found between the total time of avoidance behavior demonstrated by the 21-day defeaters in agonistic interactions and Sert, Maoa, Bdnf, Gapdh and 18S mRNA levels. 

Conclusions: 
CSDS experience inducing the development of mixed anxious/depression-like state in male mice down-regulates the serotonergic genes expression associated with the synthesis, inactivation and reception of serotonin. The Bdnf and Creb genes as well as the cell and metabolic Cphn, Gapdh, Hprt, B2M, Actb and 18S genes in the midbrain raphe nuclei are also down-regulated under CSDS. Period of relative rest is not enough for most genes to recover expression to the control levels

    Nonparametric Identification of Multivariate Mixtures

    No full text
    This article analyzes the identifiability of k-variate, M-component finite mixture models in which each component distribution has independent marginals, including models in latent class analysis. Without making parametric assumptions on the component distributions, we investigate how one can identify the number of components and the component distributions from the distribution function of the observed data. We reveal an important link between the number of variables (k), the number of values each variable can take, and the number of identifiable components. A lower bound on the number of components (M) is nonparametrically identifiable if k >= 2, and the maximum identifiable number of components is determined by the number of different values each variable takes. When M is known, the mixing proportions and the component distributions are nonparametrically identified from matrices constructed from the distribution function of the data if (i) k >= 3, (ii) two of k variables take at least M different values, and (iii) these matrices satisfy some rank and eigenvalue conditions. For the unknown M case, we propose an algorithm that possibly identifies M and the component distributions from data. We discuss a condition for nonparametric identi fication and its observable implications. In case M cannot be identified, we use our identification condition to develop a procedure that consistently estimates a lower bound on the number of components by estimating the rank of a matrix constructed from the distribution function of observed variables.finite mixture, latent class analysis, latent class model, model selection, number of components, rank estimation
    corecore