Somatodendritic integration under increased network activity in layer 5 pyramidal cells of the somatosensory cortex

Integrative properties of single neurons have been extensively studied in acute brain slices. However, these preparations are characterized by extremely low levels of synaptic and action potential activity. In comparison to in vivo, reduced intracortical input and lack of subcortical modulation increase the effective difference between mean membrane potential and spiking threshold, preventing self-sustained network activity in vitro. To elicit an increased and stable network activity (INA) in vitro comparable to that found in awake animals, we mimicked subcortical cholinergic and serotoninergic inputs using carbachol or barium alone or in combination with serotonin in layer 5 pyramidal cells in slices of mouse somatosensory cortex. INA is primarily induced by a modulation of intrinsic conductances resulting in a depolarization of the membrane potential. We studied the impact of INA on synaptic and somatodendritic integration using extracellular stimulation and dendritic calcium imaging. Synaptic inhibition is strengthened due to an increased driving force for chloride. The critical frequency at which somatic action potentials induce a dendritic calcium action potential is lowered. Simultaneous inhibitory synaptic input is powerful enough to suppress dendritic calcium action potential generation. Pharmacologically induced INA enables the study of neuronal integration in well-accessible cortical slices within an active networ

Information Security Risk Management: In Which Security Solutions Is It Worth Investing?

As companies are increasingly exposed to information security threats, decision makers are permanently forced to pay attention to security issues. Information security risk management provides an approach for measuring the security through risk assessment, risk mitigation, and risk evaluation. Although a variety of approaches have been proposed, decision makers lack well-founded techniques that (1) show them what they are getting for their investment, (2) show them if their investment is efficient, and (3) do not demand in-depth knowledge of the IT security domain. This article defines a methodology for management decision makers that effectively addresses these problems. This work involves the conception, design, and implementation of the methodology into a software solution. The results from two qualitative case studies show the advantages of this methodology in comparison to established methodologies

Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression.

Spike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is still elusive and strongly debated. To elucidate their function, we show that bath application of the eCB 2-arachidonylglycerol (2-AG) induces a preNMDAR-dependent form of chemically induced LTD (eCB-LTD) in L2/3 pyramidal neurons in the juvenile somatosensory cortex of rats. Presynaptic Ca2+ imaging from L4 spiny stellate axons revealed that action potential (AP) evoked Ca2+ transients show a preNMDAR-dependent broadening during eCB-LTD induction. However, blockade of voltage-dependent Ca2+ channels (VDCCs) did not uncover direct preNMDAR-mediated Ca2+ transients in the axon. This suggests that astrocyte-mediated glutamate release onto preNMDARs does not result in a direct Ca2+ influx, but that it instead leads to an indirect interaction with presynaptic VDCCs, boosting axonal Ca2+ influx. These results reveal one of the main remaining missing pieces in the signaling cascade of t-LTD at developing cortical synapses

Comparison of Intravitreal Bevacizumab versus Triamcinolone for the Treatment of Diffuse Diabetic Macular Edema

Background: Our purpose was to compare the effect of triamcinolone and bevacizumab (Avastin) on the retinal thickness and functional outcome in patients with diabetic macular edema. Methods and Materials: A collective of 32 patients, who had been treated by a single 4.0-mg intravitreal triamcinolone injection (group 1), was matched to 32 patients ('matched pairs'), who had received 3 injections of 1.25 mg of bevacizumab within 3 months in 4-week intervals (group 2). The outcome variables were changes in best corrected visual acuity (VA) and central retinal thickness 3 months after therapy. Results: Both groups did not differ regarding preoperative VA and central retinal thickness measured by optical coherence tomography. The baseline mean VA was 0.72 +/- 0.39 logMAR in group 1 and 0.73 +/- 0.39 logMAR in group 2 (p = 0.709). The mean central retinal thickness measured by optical coherence tomography was 548 +/- 185 mu m in group 1 and 507 +/- 192 mu m in group 2. While the patients in group 1 experienced a slight increase in VA of on average 0.7 lines following a single triamcinolone injection to a mean of 0.64 +/- 0.40 logMAR (p = 0.066) after 3 months, the patients in group 2 showed almost no effect on VA with an average increase of 0.2 lines to a mean VA of 0.72 +/- 0.30 logMAR (p = 0.948) following 3 intravitreal injections of bevacizumab. Comparing the effect on VA between both groups no statistically significant difference (p = 0.115) was noted. Concerning decrease in central retinal thickness both therapies were highly effective (p < 0.001 each), again, without statistically significant difference between the groups (p < 0.128). Conclusion: Our data suggest that a single triamcinolone injection may be as effective as a 3 times repeated intravitreal administration of bevacizumab for the treatment of diabetic macular edema. Further prospective trials should be performed. Copyright (C) 2010 S. Karger AG, Base

Inhalte von Zeitperspektiven - Beiträge zur Veränderung von Zeitperspektiven

Sind Zeitperspektiven veränderbar? Wie muss das sozialpsychologische Konstrukt der Zeitperspektiven verstanden werden, wenn es um die Veränderung dessen gehen soll? In der Dissertationsschrift wird ein bildungstheoretisch fundiertes Verständnis des sozialpsychologischen Konstrukts der Zeitperspektiven (Zimbardo & Boyd, 1999; Buhl, 2014; Mello & Worrell 2015) erarbeitet und empirisch ergründet. Es zeigt sich, dass eine Veränderung von Zeitperspektiven über den Blick auf ihre inhaltlich-individuelle Gestalt geschehen kann. Wichtig ist, dass die ambivalenten Manifestationen der Zeitperspektiven in Form der jeweils positiven und der negativen Vorstellungen zu den einzelnen Zeitdimensionen berücksichtigt werden müssen. Nur eine Auflösung der Eindeutigkeit und die Arbeit mit der dahinterliegenden Mehrdeutigkeit kann zur Veränderung und Neuausrichtung der eigenen Zeitperspektive führen. Die empirische Analyse der inhaltlichen Ausprägungen der Zeitperspektiven zeigt, dass sich das Konstrukt entlang der Dimension der Ambivalenz analysieren lässt. Es ergeben sich vier latente Typen zeitperspektivischer Ambivalenz. Außerdem zeigen sich verschiedene Modifikationsmuster der zeitperspektivischen Vorstellungen, wenn man auf deren jeweiliges Vorkommen im Rahmen der einzelnen Zeitdimensionen blickt. Die Dissertationsarbeit besteht aus einem grundlagentheoretischen Abschnitt und drei aufeinander aufbauenden, dennoch separaten empirischen Arbeiten zur Erforschung der inhaltlichen Gestalten von Zeitperspektiven. Zusammengehalten werden die Abschnitte durch die Frage nach der Veränderung und Veränderbarkeit von Zeitperspektiven. Die Arbeit ist in einem erziehungswissenschaftlichen Diskurs zu verorten

Automated Transformation of Semi-Structured Text Elements

Interconnected systems, such as electronic health records (EHR), considerably improved the handling and processing of health information while keeping the costs at a controlled level. Since the EHR virtually stores all data in digitized form, personal medical documents are easily and swiftly available when needed. However, multiple formats and differences in the health documents managed by various health care providers severely reduce the efficiency of the data sharing process. This paper presents a rule-based transformation system that converts semi-structured (annotated) text into standardized formats, such as HL7 CDA. It identifies relevant information in the input document by analyzing its structure as well as its content and inserts the required elements into corresponding reusable CDA templates, where the templates are selected according to the CDA document type-specific requirements

A Machine Learning-Based Raman Spectroscopic Assay for the Identification of Burkholderia mallei and Related Species

Burkholderia (B.) mallei, the causative agent of glanders, and B. pseudomallei, the causative agent of melioidosis in humans and animals, are genetically closely related. The high infectious potential of both organisms, their serological cross-reactivity, and similar clinical symptoms in human and animals make the differentiation from each other and other Burkholderia species challenging. The increased resistance against many antibiotics implies the need for fast and robust identification methods. The use of Raman microspectroscopy in microbial diagnostic has the potential for rapid and reliable identification. Single bacterial cells are directly probed and a broad range of phenotypic information is recorded, which is subsequently analyzed by machine learning methods. Burkholderia were handled under biosafety level 1 (BSL 1) conditions after heat inactivation. The clusters of the spectral phenotypes and the diagnostic relevance of the Burkholderia spp. were considered for an advanced hierarchical machine learning approach. The strain panel for training involved 12 B. mallei, 13 B. pseudomallei and 11 other Burkholderia spp. type strains. The combination of top- and sub-level classifier identified the mallei-complex with high sensitivities (>95%). The reliable identification of unknown B. mallei and B. pseudomallei strains highlighted the robustness of the machine learning-based Raman spectroscopic assay

Complete high-quality genome sequence of Clostridium limosum (Hathewaya limosa) isolate 14S0207, recovered from a cow with suspected blackleg in Germany

Clostridium limosum can be found in soil and the intestinal tract of animals. In 2014, C. limosum was isolated from a suspected blackleg outbreak in cattle in Schleswig-Holstein, Germany. We present a complete genome sequence of a C. limosum strain represented by a circular chromosome and three plasmids

Quantifying evolution

Diese Untersuchung behandelt Evolutionsprozesse und Umweltveränderungen anhand eines mittel-miozänen Aufschlusses im Sinj-Becken (Dalmatien, SO Kroatien), das die Ablagerungsgeschichte eines langlebigen Süßwassersees widerspiegelt. Trotz einer weit reichenden Untersuchung fehlten bisher quantitative Daten, um Einsicht in Artenverteilungen, taxonomische Beziehungen und die Ursachen der morphologischen Veränderungen zu erhalten. Die taxonomische Diversifikation der Süßwasser-Gastropoden in Verbindung mit morphologischen Disparitäts-Events wurde anhand eines ca. 100 m dicken Profils, das den obersten Teil der Beckenfüllung umfasst, dokumentiert. Basierend auf dem bestehenden Altersmodell passieren diese Änderungen in nur wenigen zehntausend Jahren, was erneut die Bedeutung langlebiger Seen für die Evolutionsforschung belegt. Des Weiteren lässt die Gleichzeitigkeit der morphologischen Abwandlungen bei voneinander systematisch unabhängigen Taxa auf einen engen Konnex zu Umweltveränderungen schließen. Höchstwahrscheinlich sind klimatische Fluktuationen, die zu Schwankungen des Seespiegels und der Habitattypen führte, treibende Faktoren für diese Radiationsevents. Diese Studie beinhaltet die Anwendung statistischer Methoden auf quantifizierte Proben und eine taxonomische Revision der auftretenden Taxa. Anschließend folgt eine Interpretation des Paläoenvironments auf Basis der Molluskenverteilung. Dies wird unterstützt durch sedimentologische Daten und frühere palynologische Analysen. Tatsächlich wird das frühere Modell der Gliederung in zwei Kalkstein-Kohle-Zyklen bestätigt, die vom seichten Milieu mit mittlerer Wasserenergie und hohem Süßwassereintrag über fossilarme Transgressionskalksteine zu einem seichten, niedrigenergetischen Setting reichen und zuletzt die komplette Austrocknung des Sees am Profiltop dokumentieren. Die Diskussion setzt einen Schwerpunkt auf die Evolutionslinien von vier Arten, je zwei der Gattungen Melanopsis und Prososthenia (Kapitel 4.5.). Alle vier Arten kommen nahezu im ganzen Profil vor und können in mehrere Morphotypen untergliedert werden, basierend auf ihrer Skulpturierung; in wenigen Fällen auch ob ihrer Größe. Es wird gezeigt, dass die Morphotypen sequentiell auftreten, jeder mehr oder weniger beschränkt auf einen bestimmten Abschnitt. Diese morphologischen Veränderungen passieren zeitgleich in unterschiedlichen Taxa.The present investigation deals with the mollusk evolutionary patterns and environmental change in a lower Middle Miocene succession in the Sinj Basin (Dalmatia, SE Croatia) reflecting the depositional history of a long-lived freshwater lake. Despite its mature investigation stage, an analysis of a quantified mollusk record, providing insight into species contributions, taxonomic relationships and the nature of the morphologic changes, is completely missing up to now. The taxonomic diversification of freshwater gastropods and its connection with morphologic disparity events are documented for a ca. 100-m-thick section representing the topmost infill of the Sinj Basin. Based on the available age model, these alterations occur extremely fast on a millennial scale, re-proving the significance of long-lived lakes for evolutionary research. Furthermore, the simultaneity of morphologic shifts in systematically independent taxa suggests them to be tightly linked to environmental changes. Most probably, climatic fluctuations leading to variations in lake-level and habitat types are the driving factors for these radiation events. The study provides statistical treatment of quantified samples accompanied by a taxonomic revision of the taxa. Additionally, based on the mollusk distribution a paleoenvironmental interpretation is given, supported by sedimentological data and previous palynological analysis. Actually, it supports previous results of the section’s division into two limestone-coal cycles, grading from shallow intermediate-energy settings with high freshwater input via fossil-poor transgressive limestones to shallow low-energy conditions, resulting finally in a total lake drought at the section top. The discussion will focus on the evolutionary lineages of four species, two of Melanopsis and two of Prososthenia (chapter 4.5.). All four species appear almost continuously and can be divided into several morphotypes based on different sculpture features; in some cases also size plays a role. It will be demonstrated that the morphs occur sequentially, each more or less limited to a special interval. Moreover, the changes in morphology appear at the same time in different taxa