Learning flexible sensori-motor mappings in a complex network

Given the complex structure of the brain, how can synaptic plasticity explain the learning and forgetting of associations when these are continuously changing? We address this question by studying different reinforcement learning rules in a multilayer network in order to reproduce monkey behavior in a visuomotor association task. Our model can only reproduce the learning performance of the monkey if the synaptic modifications depend on the pre- and postsynaptic activity, and if the intrinsic level of stochasticity is low. This favored learning rule is based on reward modulated Hebbian synaptic plasticity and shows the interesting feature that the learning performance does not substantially degrade when adding layers to the network, even for a complex problem.

Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography

The presynaptic terminal contains a complex network of filaments whose precise organization and functions are not yet understood. The cryoelectron tomography experiments reported in this study indicate that these structures play a prominent role in synaptic vesicle release. Docked synaptic vesicles did not make membrane to membrane contact with the active zone but were instead linked to it by tethers of different length. Our observations are consistent with an exocytosis model in which vesicles are first anchored by long (>5 nm) tethers that give way to multiple short tethers once vesicles enter the readily releasable pool. The formation of short tethers was inhibited by tetanus toxin, indicating that it depends on soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor complex assembly. Vesicles were extensively interlinked via a set of connectors that underwent profound rearrangements upon synaptic stimulation and okadaic acid treatment, suggesting a role of these connectors in synaptic vesicle mobilization and neurotransmitter release.

Reticulate eruptions. Part 1: Vascular networks and physiology

Reticulate pattern is one of the most important dermatological signs of a pathological process involving the superficial vascular networks. Vascular malformations, such as cutis marmorata congenita telangiectasia and benign forms of livedo reticularis, and sinister conditions, such as meningococcal meningitis or Sneddon's syndrome, can all present with a reticulate pattern. The clinical presentation and morphology is determined by the nature and extent of the underlying pathology and the involvement of a particular vascular network. This review has been divided into four instalments. In the present paper, we discuss the anatomy and physiology of the complex network of vascular structures that support the function of the skin and subcutis.

Tight junctions in brain barriers during central nervous system inflammation

Homeostasis within the central nervous system (CNS) is a prerequisite to elicit proper neuronal function. The CNS is tightly sealed from the changeable milieu of the blood stream by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the BBB is established by specialized endothelial cells of CNS microvessels, the BCSFB is formed by the epithelial cells of the choroid plexus. Both constitute physical barriers by a complex network of tight junctions (TJs) between adjacent cells. During many CNS inflammatory disorders, such as multiple sclerosis, human immunodeficiency virus infection, or Alzheimer's disease, production of pro-inflammatory cytokines, matrix metalloproteases, and reactive oxygen species are responsible for alterations of CNS barriers. Barrier dysfunction can contribute to neurological disorders in a passive way by vascular leakage of blood-borne molecules into the CNS and in an active way by guiding the migration of inflammatory cells into the CNS. Both ways may directly be linked to alterations in molecular composition, function, and dynamics of the TJ proteins. This review summarizes current knowledge on the cellular and molecular aspects of the functional and dysfunctional TJ complexes at the BBB and the BCSFB, with a particular emphasis on CNS inflammation and the role of reactive oxygen species.

Muster, Entwicklungstypen und Persönlichkeit

Studien zu Sozialisationswirkungen sportlicher Aktivitäten auf Facetten der Persönlichkeit (z. B. Selbstkonzept) haben sich bislang in der Regel auf die Analyse isolierter Effekte des Sports konzentriert, ohne weitere Entwicklungskontexte (wie z. B. die Familie) angemessen zu berücksichtigen. Da hierin eine wesentliche Ursache für die unbefriedigende Befundlage gesehen wird, bemüht sich der Beitrag darum, die Rolle des Sports für das Selbstkonzept im komplexen Wirkungsgeflecht verschiedener Entwicklungskontexte herauszuarbeiten. 121 Heranwachsende wurden in einer personorientierten Längsschnittsstudie untersucht und die Daten mit der LICUR-Methode (z. B. Bergman, Magnusson & El-Khouri, 2003) ausgewertet. Die dabei identifizierten Subgruppen unterscheiden sich in allen untersuchten Facetten des Selbstkonzepts bedeutsam, zeigen sowohl zeitstabile als auch dynamische Werteprofile ihrer Entwicklungsfaktoren und folgen überzufällig häufig einzelnen Entwicklungswegen. Aus diesen Befunden werden Konsequenzen für eine ganzheitliche und funktionale Selbstkonzeptförderung durch Sport abgeleitet.

Regulation of androgen biosynthesis - A short review and preliminary results from the hyperandrogenic starvation NCI-H295R cell model

Regulation of androgen production is poorly understood. Adrenarche is the physiologic event in mid-childhood when the adrenal zona reticularis starts to produce androgens through specific expression of genes for enzymes and cofactors necessary for androgen synthesis. Similarly, expression and activities of same genes and products are deregulated in hyperandrogenic disorders such as the polycystic ovary syndrome (PCOS). Numerous studies revealed involvement of several signaling pathways stimulated through G-protein coupled receptors or growth factors transmitting their effects through cAMP- or non-cAMP-dependent signaling. Overall a complex network regulates androgen synthesis targeting involved genes and proteins at the transcriptional and post-translational levels. Newest players in the field are the DENND1A gene identified in PCOS patients and the MAPK14 which is the kinase phosphorylating CYP17 for enhanced lyase activity. Next generation sequencing studies of PCOS patients and transcriptome analysis of androgen producing tissues or cell models provide newer tools to identify modulators of androgen synthesis.

CT scan based determination of optimal bone corridor for atlantoaxial ventral screw fixation in miniature breed dogs

OBJECTIVE: To describe the most reliable insertion angle, corridor length and width to place a ventral transarticular atlantoaxial screw in miniature breed dogs. STUDY DESIGN: Retrospective CT imaging study. SAMPLE POPULATION: Cervical CT scans of toy breed dogs (n = 21). METHODS: Dogs were divided into 2 groups--group 1: no atlantoaxial abnormalities; group 2: atlantoaxial instability. Insertion angle in medial to lateral and ventral to dorsal direction was measured in group 1. Corridor length and width were measured in groups 1 and 2. Corridor width was measured at 3 points of the corridor. Each variable was measured 3 times and the mean used for statistical analysis. RESULTS: Mean +/- SD optimal transarticular atlantoaxial insertion angle was determined to be 40 +/- 1 degrees in medial to lateral direction from the midline and 20 +/- 1 degrees in ventral to dorsal direction from the floor of the neural canal of C2. Mean corridor length was 7 mm (range, 4.5-8.0 mm). Significant correlation was found between corridor length, body weight, and age. Mean bone corridor width ranged from 3 to 5 mm. Statistically significant differences were found between individuals, gender and measured side. CONCLUSIONS: Optimal placement of a transarticular screw for atlantoaxial joint stabilization is very demanding because the screw path corridor is very narrow.

NetCodCCN: a Network Coding approach for Content-Centric Networks

Content-Centric Networking (CCN) naturally supports multi-path communication, as it allows the simultaneous use of multiple interfaces (e.g. LTE and WiFi). When multiple sources and multiple clients are considered, the optimal set of distribution trees should be determined in order to optimally use all the available interfaces. This is not a trivial task, as it is a computationally intense procedure that should be done centrally. The need for central coordination can be removed by employing network coding, which also offers improved resiliency to errors and large throughput gains. In this paper, we propose NetCodCCN, a protocol for integrating network coding in CCN. In comparison to previous works proposing to enable network coding in CCN, NetCodCCN permit Interest aggregation and Interest pipelining, which reduce the data retrieval times. The experimental evaluation shows that the proposed protocol leads to significant improvements in terms of content retrieval delay compared to the original CCN. Our results demonstrate that the use of network coding adds robustness to losses and permits to exploit more efficiently the available network resources. The performance gains are verified for content retrieval in various network scenarios.

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

Heart failure gene therapy: the path to clinical practice

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Functional brain network efficiency predicts intelligence

The neuronal causes of individual differences in mental abilities such as intelligence are complex and profoundly important. Understanding these abilities has the potential to facilitate their enhancement. The purpose of this study was to identify the functional brain network characteristics and their relation to psychometric intelligence. In particular, we examined whether the functional network exhibits efficient small-world network attributes (high clustering and short path length) and whether these small-world network parameters are associated with intellectual performance. High-density resting state electroencephalography (EEG) was recorded in 74 healthy subjects to analyze graph-theoretical functional network characteristics at an intracortical level. Ravens advanced progressive matrices were used to assess intelligence. We found that the clustering coefficient and path length of the functional network are strongly related to intelligence. Thus, the more intelligent the subjects are the more the functional brain network resembles a small-world network. We further identified the parietal cortex as a main hub of this resting state network as indicated by increased degree centrality that is associated with higher intelligence. Taken together, this is the first study that substantiates the neural efficiency hypothesis as well as the Parieto-Frontal Integration Theory (P-FIT) of intelligence in the context of functional brain network characteristics. These theories are currently the most established intelligence theories in neuroscience. Our findings revealed robust evidence of an efficiently organized resting state functional brain network for highly productive cognitions.