Exploiting bounded signal flow for graph orientation based on cause-effect pairs

Background: We consider the following problem: Given an undirected network and a set of sender–receiver pairs, direct all edges such that the maximum number of “signal flows ” defined by the pairs can be routed respecting edge directions. This problem has applications in understanding protein interaction based cell regulation mechanisms. Since this problem is NP-hard, research so far concentrated on polynomial-time approximation algorithms and tractable special cases. Results: We take the viewpoint of parameterized algorithmics and examine several parameters related to the maximum signal flow over vertices or edges. We provide several fixed-parameter tractability results, and in one case a sharp complexity dichotomy between a linear-time solvable case and a slightly more general NP-hard case. We examine the value of these parameters for several real-world network instances. Conclusions: Several biologically relevant special cases of the NP-hard problem can be solved to optimality. In this way, parameterized analysis yields both deeper insight into the computational complexity and practical solving strategies. Background Current technologies [1] like two-hybrid screening ca

DEVELOPMENT OF THE VELOCITY FOR VAULT RUNS IN ARTISTIC GYMNASTICS FOR THE LAST DECADE

The last decade in gymnastics is affected by two revolutionary changes. The introductions of the new vaulting table replacing the former vaulting horse and the 2006 code of points for the evaluation of the competition exercises with an unlimited system removing the maximum value of 10 points are unprecedented large changes in the history of gymnastics. Using competition analysis of the world championships 1997 and 2007 the development on the apparatus vault focused on the running velocity (laser velocity measuring) is described. The main results are: For Yurchenko vaults 2007 women are as fast as men. There has been an important increase in vault run speed since 1997 for men and women. There is one remarkable exception: On Yurchenko vaults men are as fast as ten years before and there is no effect of the new vault table

Dealing with Imperfection Sensitivity of Composite Structures Prone to Buckling

The Space industry demands for lighter and cheaper launcher transport systems. Structural weight reduction by exploitation of structural reserves in composite launcher structures contributes to this aim, however, it requires accurate, fast and experimentally validated stability analysis of real structures under realistic loading conditions. Structures in space applications can be imperfection sensitive because their maximum load is often equal or close to the first buckling load. The current design guidelines were developed only for metallic structures and are from 1968. For composites structures no appropriate guidelines exist. To fill this gap DLR developed a promising “Single Perturbation Load Approach” which exploits the worst imperfections idea efficiently. In the running EU project DESICOS (New Robust DESIgn Guideline for Imperfection Sensitive COmposite Launcher Structures) this approach will be further investigated and combined with a stochastic approach resulting in a future design approach. This chapter deals with the state-of-the-art in buckling of imperfection sensitive composite structures, recent investigations on the new design approach, and the DESICOS project. It describes the line of actions of the new design approach, and specifies the theoretical and experimental work to be carried out

3 DECADES OF FORCE MEASUREMENT ON VAULT IN GYMNASTICS

Force measurement on gymnastics apparatuses can give useful knowledge about technique of gymnasts, but also on injury prevention and stress on the human body. Since 1986 direct force measurements on vault horse and tables were applied by our researchers. Aim of this paper is to publish information about the technology we used for direct force measurements. All measuring systems were customized to the apparatuses from different manufacturers. Most measures were arranged in training sessions, but we report also about data collection in official competitions. Examples of force patterns give an idea of peak forces and impulse during different vault groups (handspring, Kasamatsu)

Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

Tertiary lymphoid organs (TLOs) emerge in tissues in response to non-resolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs) in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE(−/−) mice. ATLOs are structured into T cell areas harboring conventional dendritic cells and monocyte-derived DCs; B cell follicles containing follicular dendritic cells within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV) neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4(+) and CD8(+) effector T cells, natural and induced CD4(+) T regulatory (nTregs; iTregs) cells as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses toward atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease

Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice

<p>Abstract</p> <p>Background</p> <p>In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation, and alleviated cognitive deficits. Furthermore, ADAM10 overexpression increased the cortical synaptogenesis. These results suggest that upregulation of ADAM10 in the brain has beneficial effects on AD pathology.</p> <p>Results</p> <p>To assess the influence of ADAM10 on the gene expression profile in the brain, we performed a microarray analysis using RNA isolated from brains of five months old mice overexpressing either the α-secretase ADAM10, or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, in ADAM10 transgenic mice 355 genes, and in dnADAM10 mice 143 genes were found to be differentially expressed. A higher number of genes was differentially regulated in double-transgenic mouse strains additionally expressing the human APP_[V717I]mutant.</p> <p>Overexpression of proteolytically active ADAM10 affected several physiological pathways, such as cell communication, nervous system development, neuron projection as well as synaptic transmission. Although ADAM10 has been implicated in Notch and β-catenin signaling, no significant changes in the respective target genes were observed in adult ADAM10 transgenic mice.</p> <p>Real-time RT-PCR confirmed a downregulation of genes coding for the inflammation-associated proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression. Overexpression of the dominant-negative form dnADAM10 led to a significant increase in the expression of the fatty acid-binding protein Fabp7, which also has been found in higher amounts in brains of Down syndrome patients.</p> <p>Conclusion</p> <p>In general, there was only a moderate alteration of gene expression in ADAM10 overexpressing mice. Genes coding for pro-inflammatory or pro-apoptotic proteins were not over-represented among differentially regulated genes. Even a decrease of inflammation markers was observed. These results are further supportive for the strategy to treat AD by increasing the α-secretase activity.</p

Datengenerierung in Automationsgeräten, Datenintegration und Visualisierung in CPS-Leitständen

Der durchgängige Einsatz von ETHERNET-Technologien in der Industrie ermöglicht den Durchgriff auf Daten von der (Werks-)Leitebene bis in die Feldebene (Aktoren und Sensoren). Die Realisierung dieser Funktionen bedarf struktureller und funktioneller Festlegungen und Normative, an die Entwickler und Nutzer zu binden sind. Die konzipierten und umgesetzten Daten-Erfassungs-, -Übertragungs- und -Visualisierungskonzepte konnten in ihrer Funktionsfähigkeit demonstratorhaft nachgewiesen werden. Eine Anpassung auf weitere Technologien ist möglich und im Zuge der Weiterentwicklung in Richtung Vermarktbarkeit vorgesehen

Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions

Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors

Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs