Condensing of self-organizing groups
- Condensing phenomena for systems biology, ecology and sociology present in real life different complex behaviors. Based on local interaction between agents, we present another result of the Energy-based model presented by . We involve an additional condition providing the total condensing (also called consensus) of a discrete positive measure. Key words: Condensing; consensus; random move; self-organizing groups; collective intelligence; stochastic modeling. AMS Subject Classifications: 81T80; 93A30; 37M05; 68U20
Differentiation of the brain vasculature : the answer came blowing by the Wnt
Karl H. Plate
- Vascularization of the vertebrate brain takes place during embryonic development from a preformed perineural vascular plexus. As a consequence of the intimate contact with neuroectodermal cells the vessels, which are entering the brain exclusively via sprouting angiogenesis, acquire and maintain unique barrier properties known as the blood-brain barrier (BBB). The endothelial BBB depends upon the close association of endothelial cells with pericytes, astrocytes, neurons and microglia, which are summarized in the term neuro-vascular unit. Although it is known since decades that the CNS tissue provides the cues for BBB induction and differentiation in endothelial cells, the molecular mechanism remained obscure. Only recently, the canonical Wnt/beta-catenin pathway and the Wnt7a/7b growth factors have been implicated in brain angiogenesis on the one hand and in BBB induction on the other. This breakthrough in understanding the differentiation of the brain vasculature prompted us to review these findings embedded in the emerging concepts of Wnt signaling in the vasculature. In particular, interactions with other pathways that are crucial for vascular development such as VEGF, Notch, angiopoietins and Sonic hedgehog are discussed. Finally, we considered the potential role of the Wnt pathway in vascular brain pathologies in which BBB function is hampered, as for example in glioma, stroke and Alzheimer's disease.
Synchronization of dissipative dynamical systems driven by non-Gaussian Lévy noises
Peter E. Kloeden
- Dynamical systems driven by Gaussian noises have been considered extensively in modeling, simulation, and theory. However, complex systems in engineering and science are often subject to non-Gaussian fluctuations or uncertainties. A coupled dynamical system under a class of Lévy noises is considered. After discussing cocycle property, stationary orbits, and random attractors, a synchronization phenomenon is shown to occur, when the drift terms of the coupled system satisfy certain dissipativity and integrability conditions. The synchronization result implies that coupled dynamical systems share a dynamical feature in some asymptotic sense.
Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation
Kai D. Zacharowski
- Introduction: Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion in-jury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anes-thetic postconditioning with sevoflurane affect cerebral inflammatory response after cardio-pulmonary resuscitation. Methods: Thirty pigs (28 - 34kg) were subjected to cardiac arrest following temporary coro-nary artery occlusion. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to ei-ther normothermia at 38degreesC, hypothermia at 33degreesC or hypothermia at 33degreesC combined with se-voflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques. Results: Global cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/- 2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham control). Hypothermia was associated with a significant (P <0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also confirmed for IL-1beta on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects com-pared with hypothermia alone. Conclusions: Mild therapeutic hypothermia resulted in decreased expression of typical ce-rebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.
Identification and functional characterisation of Complement Regulator Acquiring Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4
Nathalie D. van Burgel
Tim J. Schuijt
Peter F. Zipfel
Alje P. van Dam
- Background: B. burgdorferi sensu lato (sl) is the etiological agent of Lyme borreliosis in humans. Spirochetes have adapted themselves to the human immune system in many distinct ways. One important immune escape mechanism for evading complement activation is the binding of complement regulators Factor H (CFH) or Factor H-like protein1 (FHL-1) to Complement Regulator-Acquiring Surface Proteins (CRASPs). Results: We demonstrate that B. garinii OspA serotype (ST4) PBi resist complement-mediated killing by binding of FHL-1. To identify the primary ligands of FHL-1 four CspA orthologs from B. garinii ST4 PBi were cloned and tested for binding to human CFH and FHL-1. Orthologs BGA66 and BGA71 were found to be able to bind both complement regulators but with different intensities. In addition, all CspA orthologs were tested for binding to mammalian and avian CFH. Distinct orthologs were able to bind to CFH of different animal origins. Conclusions: B. garinii ST4 PBi is able to evade complement killing and can bind FHL-1 to membrane expressed proteins. Recombinant proteins BGA66 can bind FHL-1 and human CFH, while BGA71 can bind only FHL-1. All recombinant CspA orthologs from B. garinii ST4 PBi can bind CFH from different animal origins. This partly explains the wide variety of animals that can be infected by B. garinii.
ADAM10 is expressed in human podocytes and found in urinary vesicles of patients with glomerular kidney diseases
Mohamed Sadek Abdel-Bakky
Ingeborg A. Hauser
Josef Martin Pfeilschifter
- Background: The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex. Methods: By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue. Results: We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases. Conclusions: The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient : a case report
Ignacio G. Bravo
Barbara S. Schnierle
- The human immunodeficiency virus type 1 (HIV-1) coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT). Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5)-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.
Capital adequacy regulation of financial conglomerates in the European Union
Y. Emilie Yoo
- Over the past few decades, changes in market conditions such as globalisation and deregulation of financial markets as well as product innovation and technical advancements have induced financial institutions to expand their business activities beyond their traditional boundaries and to engage in cross-sectoral operations. As combining different sectoral businesses offers opportunities for operational synergies and diversification benefits, financial groups comprising banks, insurance undertakings and/or investment firms, usually referred to as financial conglomerates, have rapidly emerged, providing a wide range of services and products in distinct financial sectors and oftentimes in different geographic locations. In the European Union (EU), financial conglomerates have become part of the biggest and most active financial market participants in recent years. Financial conglomerates generally pose new problems for financial authorities as they can raise new risks and exacerbate existing ones. In particular, their cross-sectoral business activities can involve prudentially substantial risks such as the risk of regulatory arbitrage and contagion risk arising from intra-group transactions. Moreover, the generally large size of financial conglomerates as well as the high complexity and interconnectedness of their corporate structures and risk exposures can entail substantial systemic risk and can therefore threaten the stability of the financial system as a whole. Until a few years ago, there was no supervisory framework in place which addressed a financial conglomerate in its entirety as a group. Instead, each group entity within a financial conglomerate was subject to the supervisory rules of its pertinent sector only. Such silo supervisory approach had the drawback of not taking account of risks which arise or aggravate at the group level. It also failed to consider how the risks from different business lines within the group interrelate with each other and affect the group as a whole. In order to address this lack of group-wide prudential supervision of financial conglomerates, the European legislator adopted the Financial Conglomerates Directive 2002/87/EC8 (‘FCD’) on 16 December 2002. The FCD was transposed into national law in the member states of the EU (‘Member States’) by 11 August 2004 for application to financial years beginning on 1 January 2005 and after. The FCD primarily aims at supplementing the existing sectoral directives to address the additional risks of concentration, contagion and complexity presented by financial conglomerates. It therefore provides for a supervisory framework which is applicable in addition to the sectoral supervision. Most importantly, the FCD has introduced additional capital requirements at the conglomerate level so as to prevent the multiple use of the same capital by different group entities. This paper seeks to examine to what extent the FCD provides for an adequate capital regulation of financial conglomerates in the EU while taking into account the underlying sectoral capital requirements and the inherent risks associated with financial conglomerates. In Part 1, the definition and the basic corporate models of financial conglomerates will be presented (I), followed by an illustration of the core motives behind the phenomenon of financial conglomeration (II) and an overview of the development of the supervision over financial conglomerates in the EU (III). Part 2 begins with a brief elaboration on the role of regulatory capital (I) and gives a general overview of the EU capital requirements applicable to banks and insurance undertakings respectively. A delineation of the commonalities and differences of the banking and the insurance capital requirements will be provided (II). It continues to further examine the need for a group-wide capital regulation of financial conglomerates and analyses the adequacy of the FCD capital requirements. In this context, the technical advice rendered by the Joint Committee on Financial Conglomerates (JCFC) as well as the currently ongoing legislative reforms at the EU level will be discussed (III). The paper finally closes with a conclusion and an outlook on remaining open issues (IV).
Cuff overinflation and endotracheal tube obstruction : case report and experimental study
Martin G. Mack
- Background: Initiated by a clinical case of critical endotracheal tube (ETT) obstruction, we aimed to determine factors that potentially contribute to the development of endotracheal tube obstruction by its inflated cuff. Prehospital climate and storage conditions were simulated. Methods: Five different disposable ETTs (6.0, 7.0, and 8.0 mm inner diameter) were exposed to ambient outside temperature for 13 months. In addition, every second of these tubes was mechanically stressed by clamping its cuffed end between the covers of a metal emergency case for 10 min. Then, all tubes were heated up to normal body temperature, placed within the cock of a syringe, followed by stepwise inflation of their cuffs to pressures of 3 kPa and >=12 kPa, respectively. The inner lumen of the ETT was checked with the naked eye for any obstruction caused by the external cuff pressure. Results: Neither in tubes that were exposed to ambient temperature (range: -12°C to +44°C) nor in those that were also clamped, visible obstruction by inflated cuffs was detected at any of the two cuff pressure levels. Conclusions: We could not demonstrate a critical obstruction of an ETT by its inflated cuff, neither when the cuff was over-inflated to a pressure of 12 kPa or higher, nor in ETTs that had been exposed to unfavorable storage conditions and significant mechanical stress.
Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry
Taane Gregrory Clark
Alistair T. Pagnamenta
Erik J. Mulder
Ruud B. Minderaa
Anthony J. Bailey
Anthony P. Monaco
- Background: Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods: In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Results: Significant results were found for LRRN3 and LRRTM3 (P< 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Conclusions: Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.