791 research outputs found

    Purine metabolism in cultured endothelial cells

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    Coulomb field of an accelerated charge: physical and mathematical aspects

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    The Maxwell field equations relative to a uniformly accelerated frame, and the variational principle from which they are obtained, are formulated in terms of the technique of geometrical gauge invariant potentials. They refer to the transverse magnetic (TM) and the transeverse electric (TE) modes. This gauge invariant "2+2" decomposition is used to see how the Coulomb field of a charge, static in an accelerated frame, has properties that suggest features of electromagnetism which are different from those in an inertial frame. In particular, (1) an illustrative calculation shows that the Larmor radiation reaction equals the electrostatic attraction between the accelerated charge and the charge induced on the surface whose history is the event horizon, and (2) a spectral decomposition of the Coulomb potential in the accelerated frame suggests the possibility that the distortive effects of this charge on the Rindler vacuum are akin to those of a charge on a crystal lattice.Comment: 27 pages, PlainTex. Related papers available at http://www.math.ohio-state.edu/~gerlac

    Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia

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    Background: The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG. Methods: This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders (n = 30) or non-responders (n = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated. Results: SVM did not reach sufficient overall predictive accuracies (38.0–54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by post hoc univariate comparisons. Conclusion: In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique

    A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice

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    BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice. CONCLUSIONS/SIGNIFICANCE: Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches

    Posttraumatische Belastungsstörung infolge eines Suizidversuchs

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    Zusammenfassung:Hintergrund: Erste Studien legen nahe, dass ein selbstdurchgeführter Suizidversuch überraschend häufig eine PTBS-Symptomatik verursachen könnte. Die berichteten Prävalenzangaben der Studien variieren jedoch erheblich. Methode: In der vorliegenden Online-Studie wurden N = 50 Suizidversuchsüberlebenden zu suizidversuchsbezogenen PTBS-Symptomen und gegenwärtigen Suizidgedanken befragt. Zur Falldefinition diente eine modifizierte Version der Posttraumatischen Checkliste für DSM-5 (PCL-5) entweder auf Basis eines Cut-off Wertes oder auf Syndrom-Basis. Ergebnisse: In Abhängigkeit von der Falldefinition wurden 52 % (n = 26) bzw. 42 % (n = 21) der Teilnehmenden als Personen identifiziert, welche potenziell die Diagnosekriterien einer PTBS infolge eines eigenen Suizidversuchs erfüllten. Teilnehmende mit suizidversuchsbezogener PTBS-Symptomatik berichteten teilweise über mehr gegenwärtige Suizidgedanken. Schlussfolgerung: Die Ergebnisse legen nahe, dass Personen nach einem selbstdurchgeführten Suizidversuch eine PTBS-Symptomatik entwickeln. Aufgrund der Relevanz dieser Ergebnisse für eine wirksame Behandlung von Suizidversuchsüberlebenden sind weitere Studien an größeren deutschen Stichproben und unter Nutzung klinischer Interviews zu empfehlen

    Dynamics on expanding spaces: modeling the emergence of novelties

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    Novelties are part of our daily lives. We constantly adopt new technologies, conceive new ideas, meet new people, experiment with new situations. Occasionally, we as individuals, in a complicated cognitive and sometimes fortuitous process, come up with something that is not only new to us, but to our entire society so that what is a personal novelty can turn into an innovation at a global level. Innovations occur throughout social, biological and technological systems and, though we perceive them as a very natural ingredient of our human experience, little is known about the processes determining their emergence. Still the statistical occurrence of innovations shows striking regularities that represent a starting point to get a deeper insight in the whole phenomenology. This paper represents a small step in that direction, focusing on reviewing the scientific attempts to effectively model the emergence of the new and its regularities, with an emphasis on more recent contributions: from the plain Simon's model tracing back to the 1950s, to the newest model of Polya's urn with triggering of one novelty by another. What seems to be key in the successful modelling schemes proposed so far is the idea of looking at evolution as a path in a complex space, physical, conceptual, biological, technological, whose structure and topology get continuously reshaped and expanded by the occurrence of the new. Mathematically it is very interesting to look at the consequences of the interplay between the "actual" and the "possible" and this is the aim of this short review.Comment: 25 pages, 10 figure

    A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old Mice

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    Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons.Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice.Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches

    Coincidence of paroxysmal supraventricular tachycardia and panic disorder: two case reports

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    Panic disorder (PD) is characterised by sudden attacks of intense fear with somatic symptoms including palpitations and tachycardia. Reciprocally, palpitations caused by paroxysmal supraventricular tachycardia (PSVT) are commonly associated with anxiety and may therefore be misdiagnosed as PD. As demonstrated by two case reports, PSVT and PD can occur comorbidly in a chronological sequence, with PSVT possibly precipitating and maintaining PD via interoceptive processes or, alternatively, with PD increasing the risk for PSVT by elevating stress levels. As both PSVT and PD require different treatments, potentially helpful differential clinical diagnostic criteria are proposed
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