Schizophrenia: An Integrative Study of Biological Liabilities and Neurological Causes

Society has become increasingly aware of the frustrating and confusing disorders that can result when the brain loses control of its intricate mechanisms. One such disorder that continues to baffle experts is schizophrenia. Schizophrenia is a serious thought disorder characterized by a broad spectrum of cognitive and emotional dysfunctions that disrupts a person\u27s perception of the world into one of tormenting psychotic experience. Schizophrenia results from a variety of complex causes with each possibly contributing something to the disorder. A multifactorial threshold model explains causation by demonstrating that a sum of biological liabilities (genetics and prenatal developmental problems) may take a person over the threshold and into psychosis. Psychological stress can not be considered a direct cause, but it can serve as a bridge between a person being vulnerable to schizophrenia to actually manifesting the disorder. Once a person becomes schizophrenic, we can attribute the complex symptoms to a malfunctioning brain. With current neuroimaging techniques such as MRI and PET, we are expanding our knowledge of the complex neural circuits and integrated neurotransmitter systems involved in creating psychosis. However, many secrets remain unanswered in our quest to understand the disease and treat the individual

Endogenous Sigma-Augmenting Technological Change: An R&D-Based Approach

There is now increasing evidence that for the U.S. economy, the elasticity of substitution between capital and labor, “sigma”, is rising over time. To account for this, we propose a microfounded model, where the evolution of “sigma”, and, hence, the shape of the aggregate production function occur endogenously. We develop a Schumpeterian growth model in which firms can undertake R&D activities that stochastically lead to the discovery of production technologies characterized by a higher elasticity of substitution between capital and labor. Improved possibilities for factor substitution mitigate the diminishment of the marginal product of capital and spur capital accumulation. Due to successful innovations, the steady state of the economy entails higher levels of the capital stock and the output good. Moreover, our numerical simulations show that the timing of innovations is important: two economies with the same steady-state elasticity of substitution between capital and labor can differ in terms of their steady-state levels of the capital stock and the output good

How to Shape Noise Spectra for Continuous System Simulation

Noise for continuous-time system simulation is relevant for many applications, where time-domain results are required. Simulating such noise raises the need to consistently shape the frequency content of the signal. However, the methods for this task are not obvious and often state space implementations of form filters are approximated. In this paper, we address the problem with a new method relying on directly using the specified power spectral density for a convolution filter. For the example of railway track irregularities, we explain how to derive the required filters, implement them in the open-source Noise library, and verify the results. The new method produces correct results, is very simple to use, and enables new features for time simulation of physical systems

Skill-Biased Technological Change, Endogenous Labor Supply, and the Skill Premium

The evolution of the U.S. skill premium over the past century has been characterized by a U-shaped pattern. The previous literature has attributed this observation mainly to the existence of exogenous, unexpected technological shocks or changes in institutional factors. In contrast, this paper demonstrates that a U-shaped evolution of the skill premium can also be obtained using a simple two-sector growth model that comprises both variants of skill-biased technological change (SBTC): technological change (TC) that is favorable to high-skilled labor and capital-skill complementarity (CSC). Within this framework, we derive the conditions necessary to achieve a non-monotonic evolution of relative wages and analyze the dynamics of such a case. We show that in the short run for various parameter constellations an educational, a relative substitutability, and a factor intensity effect can induce a decrease in the skill premium despite moderate growth in the relative productivity of high-skilled labor. In the long run, as the difference in labor productivity increases, the skill premium also rises. To underpin our theoretical results, we conduct a comprehensive simulation study

Robust Performance Analysis for Gust Loads Computation

In the design process of modern aircraft, a comprehensive analysis of worst case structural gust loads is imperative. Because this analysis requires to consider millions of cases, the examination is extremely time consuming. To solve this problem, a new approach based on robust performance analysis is introduced: the worst case energy-to-peak gain is used to efficiently determine worst case loads of nominal, uncertain, and linear parameter varying gust loads models

Skill-Biased Technological Change, Endogenous Labor Supply, and the Skill Premium

The evolution of the U.S. skill premium over the past century has been characterized by a U-shaped pattern. The previous literature has attributed this observation mainly to the existence of exogenous, unexpected technological shocks or changes in institutional factors. In contrast, this paper demonstrates that a U-shaped evolution of the skill premium can also be obtained using a simple two-sector growth model that comprises both variants of skill-biased technological change (SBTC): technological change (TC) that is favorable to high-skilled labor and capital-skill complementarity (CSC). Within this framework, we derive the conditions necessary to achieve a non-monotonic evolution of relative wages and analyze the dynamics of such a case. We show that in the short run for various parameter constellations an educational, a relative substitutability, and a factor intensity effect can induce a decrease in the skill premium despite moderate growth in the relative productivity of high-skilled labor. In the long run, as the difference in labor productivity increases, the skill premium also rises. To underpin our theoretical results, we conduct a comprehensive simulation study

Das Cytomegalievirus IE1-Protein als Regulator des humanen Transkriptoms und Zielstruktur RNAi-basierter Therapiestrategien

Das humane Cytomegalievirus (hCMV) ist ein medizinisch hoch relevantes Herpesvirus, das bei Menschen mit geschwächtem Immunsystem (z.B. AIDS- und Transplantationspatienten) lebensbedrohliche Krankheiten auslösen kann und zudem die wichtigste infektiöse Ursache für embryonale Defekte ist. Bisher steht jedoch kein wirksamer hCMV-Impfstoff zur Verfügung und das Spektrum geeigneter Therapeutika ist äußerst begrenzt. Das immediate-early 1 Protein (IE1) ist ein viraler Schlüsselregulator, der Proteine und übergeordnete Strukturen des infizierten Wirtszellkerns in vielfältiger Weise manipuliert und in der initialen Phase der Infektion in entscheidender Weise den weiteren Verlauf der hCMV-Replikation und Pathogenese bestimmt. Ein Ziel dieser Arbeit war es, das Potential der RNA-Interferenz-Technologie als neues Therapiekonzept gegen hCMV zu untersuchen. Hierfür wurde ein Luciferase-Reportervirus hergestellt, welches das schnelle Screening antiviraler Effekte ermöglicht. Aus insgesamt 40 getesteten hCMV-gerichteten siRNAs konnten acht Moleküle identifiziert werden, die eine spezifische Inhibition der Virusvermehrung um mehr als 90% bewirkten. Die effektivsten Kandidaten wurden in Richtung einer therapeutischen Nutzung optimiert. In diesem Zusammenhang wurden IE1- und/oder IE2-spezifische siRNAs mit Zielsequenzen, die innerhalb aller annotierten hCMV-Stämme konserviert vorliegen und auch gegen klinisch relevante hCMV-Isolate antiviral aktiv waren, ausgewählt und chemisch modifiziert. Im zweiten Teil der vorliegenden Arbeit wurde der Einfluss von IE1 auf das humane Transkriptom untersucht. Dazu wurde mit einem im Rahmen dieser Arbeit etablierten induzierbaren Expressionssystem, welches die Analyse von funktionellem IE1 außerhalb der komplexen Situation einer Virusinfektion ermöglicht, eine systematische Genexpressions-Analyse durchgeführt. Dadurch konnten 25 IE1-induzierbare humane Gene identifiziert werden, die zugleich überwiegend in Zusammenhang mit der zellulären Typ II Interferon (IFN)-Antwort stehen. Mit Hilfe verschiedener Techniken wie der quantitativen reversen Transkriptase-PCR, Immunfluoreszenz-Analysen, zellulären Fraktionierungen, Chromatin-Immunpräzipitationen sowie der Herstellung transgener Zellen, konnte ein zweiphasiger Mechanismus der IE1-vermittelten Genregulation mit Beteiligung löslicher Faktoren ermittelt werden. Des Weiteren wurde gezeigt, dass die IE1-abhängige Induktion der normalerweise durch Typ II IFN regulierten Gene interessanterweise IFN-unabhängig erfolgt. Sie ist aber dennoch abhängig vom aktivierten (Y701-phosphorylierten) signal transducer and activator of transcription 1 (STAT1), einem kritischen zellulären Mediator der IFN-Antwort. In Korrelation dazu konnte eine IE1-vermittelte nukleäre Akkumulation sowie eine spezifische Assoziation des STAT1-Proteins mit den Promotoren Typ II IFN-stimulierter Gene beobachtet werden. Aufgrund der gewonnenen Daten ließ sich schließlich ein vorläufiges Modell für die IE1-induzierte Typ II IFN-artige Antwort entwickeln. Die Ergebnisse dieser Arbeit identifizieren IE1 als vielversprechende neue Zielstruktur für die hCMV-Therapie und offenbaren eine bisher noch unbekannte Funktion des viralen Proteins, die im Zusammenhang mit der hCMV-vermittelten Pathogenese oder der Virusreaktivierung stehen könnte

Von Schwellbalken und Telegraphenmasten: Überlegungen zur Gründungsweise und Lebensdauer eisenzeitlicher Holzgebäude

Zur besseren Beurteilung der Lebensdauer unterschiedlich gegründeter prähistorischer Holzgebäude werden Ausgrabungsbefunde, archäologische Experimente, volks- und völkerkundliche Daten und erstmals Literatur zum historischen Telegraphenbau herangezogen. Es ergibt sich eine übliche Lebenserwartung von 20-30 Jahren für prähistorische Holzgebäude verschiedener Bauweise. Der Pfostenbau, obwohl technisch spätestens seit der Eisenzeit ein Anachronismus, lebte bis ins Mittelalter fort, während nicht-erdfeste Bauweisen die Ausnahme blieben, offenbar weil kurze Lebensspannen von Gebäuden den Erfordernissen der Erbauer genügten und immaterielle Gründe wohl ohnehin häufige Neubauten erforderten.For a more precise assessment of the life expectancy of different types of prehistoric wooden buildings a short evaluation was made of excavation results, archaeological experiments, ethnological and folklore evidence and – for the first time – of literature on historical telegraph lines. The result was a normal life expectancy of some 20-30 years for prehistoric wooden buildings of different construction types. Post construction, although technically an anachronism by the Iron Age at the latest, persisted into the Middle Ages, while overground construction types remained exceptions, obviously because short life-spans of buildings met the requirements of their builders and immaterial reasons might have demanded frequent rebuilding anyway

What determines the elasticity of substitution between capital and labor? A literature review

This paper reviews the status quo of the empirical and theoretical literature on the determinants of the elasticity of substitution between capital and labor. Our focus is on the two-input constant elasticity of substitution (CES) production function. By example of the U.S., we highlight the distinctive heterogeneity in empirical estimates of σ at both the aggregate and industrial level and discuss potential methodological explanations for this variation. The main part of this survey then focuses on the determinants of σ. We first review several approaches to the microfoundation of production functions, especially the CES production function. Second, we outline the construction of an aggregate elasticity of substitution (AES) in a multi-sectoral framework and investigate its dependence on underlying sectoral elasticities. Third, we discuss the influence of the institutional framework on the determination of σ. The concluding section of this review identifies a number of potential empirical and theoretical avenues for future research. Overall, we demonstrate that the effective elasticity of substitution (EES), which is typically estimated in empirical studies, is generally not an immutable deep parameter but depends on a multitude of technological, non-technological and institutional determinants