209 research outputs found
Coagulation systems of invertebrates and vertebrates and their roles in innate immunity: The same side of two coins?
No full textTorsten G. Loof, Otto Schmidt, Heiko Herwald, Ulrich Theopol
by Dendritic Cells
No full textStreptococcus pyogenes is one of the most frequent human pathogens. Recent studies have identified dendritic cells (DCs) as important contributors to host defense against S. pyogenes. The objective of this study was to identify the receptors involved in immune recognition of S. pyogenes by DCs. To determine whether Toll-like receptors (TLRs) were involved in DC sensing of S. pyogenes, we evaluated the response of bone marrow-derived DCs obtained from mice deficient in MyD88, an adapter molecule used by almost all TLRs, following S. pyogenes stimulation. Despite the fact that MyD88(-/-) DCs did not differ from wild-type DCs in the ability to internalize and kill S. pyogenes, the up-regulation of maturation markers, such as CD40, CD80, and CD86, and the production of inflammatory cytokines, such as interleukin-12 (IL-12), IL-6, and tumor necrosis factor alpha, were dramatically impaired in S. pyogenes-stimulated MyD88(-/-) DCs. These results suggest that signaling through TLRs is the principal pathway by which DCs sense S. pyogenes and become activated. Surprisingly, DCs deficient in signaling through each of the TLRs reported as potential receptors for gram-positive cell components, such as TLR1, TLR2, TLR4, TLR9, and TLR2/6, were not impaired in the secretion of proinflammatory cytokines and the up-regulation of costimulatory molecules after S. pyogenes stimulation. In conclusion, our results exclude a major involvement of a single TLR or the heterodimer TLR2/6 in S. pyogenes sensing by DCs and argue for a multimodal recognition in which a combination of several different TLR-mediated signals is essential for a rapid and effective response to the pathogen
Möglichkeiten der Strukturierung von Hedgefondsportfolios
No full textThe year 2000 started the evolution of the German market for Structured Products with incorporated Hedge Fund exposures. This paper provides an extensive commentary on this fast growing segment. Our analysis suggests that the market for existing products is affected by significant heterogeneity. This heterogeneity relates to amongst others the underlying product and cost structure, the performance and the investment style. The diversity and flexibility that enables the investor to acquire a tailor-made and portfolio-optimized asset allocation, has proven to remain attractive, despite the events of recent years. A new investment act ('Investmentmodernisierungsgesetz') was implemented in Germany in 2004. This means that direct investments in (Fund of) Hedge Funds now compete against Structured Products. However our analysis concludes that these product groups coexist. One reason is the innovation power of financial engineers who continuously create new structured products with specific features. --Hedgefonds,Structured Products,Index Certificates,Constant Proportion Portfolio Insurance,Indizes
The role of coagulation/fibrinolysis during Streptococcus pyogenes infection
No full textThe hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit
On the cost of delayed currency fixing announcements
No full textIn Foreign Exchange Markets vanilla and barrier options are traded frequently. The market standard is a cutoff time of 10:00 a.m. in New York for the strike of vanillas and a knock-out event based on a continuously observed barrier in the inter bank market. However, many clients, particularly from Italy, prefer the cutoff and knock-out event to be based on the fixing published by the European Central Bank on the Reuters Page ECB37. These barrier options are called discretely monitored barrier options. While these options can be priced in several models by various techniques, the ECB source of the fixing causes two problems. First of all, it is not tradable, and secondly it is published with a delay of about 10 - 20 minutes. We examine here the effect of these problems on the hedge of those options and consequently suggest a cost based on the additional uncertainty encountered. --exotic options,currency fixings
Aberrant Inflammatory Response to Streptococcus pyogenes in Mice Lacking Myeloid Differentiation Factor 88.
No full textSeveral in vitro studies have emphasized the importance of toll-like receptor/myeloid differentiation factor 88 (MyD88) signaling in the inflammatory response to Streptococcus pyogenes. Since the extent of inflammation has been implicated in the severity of streptococcal diseases, we have examined here the role of toll-like receptor/MyD88 signaling in the pathophysiology of experimental S. pyogenes infection. To this end, we compared the response of MyD88-knockout (MyD88(-/-)) after subcutaneous inoculation with S. pyogenes with that of C57BL/6 mice. Our results show that MyD88(-/-) mice harbored significantly more bacteria in the organs and succumbed to infection much earlier than C57BL/6 animals. Absence of MyD88 resulted in diminished production of inflammatory cytokines such as interleukin-12, interferon-gamma, and tumor necrosis factor-alpha as well as chemoattractants such as monocyte chemotactic protein-1 (MCP-1) and Keratinocyte-derived chemokine (KC), and hampered recruitment of effector cells involved in bacterial clearance (macrophages and neutrophils) to the infection site. Furthermore, MyD88(-/-) but not C57BL/6 mice exhibited a massive infiltration of eosinophils in infected organs, which can be explained by an impaired production of the regulatory chemokines, gamma interferon-induced monokine (MIG/CXCL9) and interferon-induced protein 10 (IP-10/CXCL10), which can inhibit transmigration of eosinophils. Our results indicate that MyD88 signaling targets effector cells to the site of streptococcal infection and prevents extravasation of cells that can induce tissue damage. Therefore, MyD88 signaling may be important for shaping the quality of the inflammatory response elicited during infection to ensure optimal effector functions
Interest rate convexity and the volatility smile
No full textWhen pricing the convexity effect in irregular interest rate derivatives such as, e.g., Libor-in-arrears or CMS, one often ignores the volatility smile, which is quite pronounced in the interest rate options market. This note solves the problem of convexity by replicating the irregular interest flow or option with liquidly traded options with different strikes thereby taking into account the volatility smile. This idea is known among practitioners for pricing CMS caps. We approach the problem on a more general scale and apply the result to various examples. --interest rate options,volatility smile,convexity,,option replication
A case for money in the ECB monetary policy strategy
No full textOne major outcome of the review of the ECBs two pillar monetary policy strategy, which was published on 8 May 2003, has been the de facto downgrading of the hitherto prominent role assigned to the stock of money. According to the authors judgement, however, there is a strong theoretical and empirical rationale for the ECB monetary policy to pay close attention to the information content of money in the form of M3. However, the authors argue the ECB should make use of the so-called price gap or real money gap concept rather than the reference value as the latter runs the risk of giving misleading policy recommendations and compromising the indicator quality of the stock of money. Making use of M3 seems all the more rational as currently no better inflation indicator appears to exist in providing inflation forecasts in the euro area. --P-star,real money gap,excess liquidity,ECB
Spatial attention related SEP amplitude modulations covary with BOLD signal in S1-a simultaneous EEG-fMRI study
No full textRecent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1. © The Author 2008. Published by Oxford University Press. All rights reserved
Central bank independence : a critical view
No full textWhile expansive literature on central bank independence contains some criticisms to the independent central bank quasi-paradigm, few critical analyses have been undertaken in the years between Friedman (1962) and Posen (1994). The author extends Posen's analysis to developing countries, discussing more broadly and systematically the reasons why merely instituting an independent central bank may not bring about its professed benefits, especially in developing countries. The author argues that widely reported empirical tests that are purported to support the central bank independence proposition are plagued by potential problems of simultaneity, reverse causality, missing variables, and measurement errors. Yet one can not make positive recommendations about institutional arrangements for central banks if causality relations are not well established. Institutions are shaped by a country's record of and preferences for inflation and may have little influence on them. The author also argues that the purported benefits of an independent central bank may be eroded by conflicts between fiscal and monetary policy and by inherent problems of central bank institutional design (especially mechanisms for board appointments, public accountability, and budgetary control). If these institutional problems are not solved, problems of dynamic inconsistency traditionally associated with monetary policy are not eliminated,but merely transformed. The author suggests that the benefits of central bank independence are less likely obtained in less developed countries with shallow financial markets. Accordingly, central bank independence should be granted at a later stage in a country's financial sector development. If a less developed country seeks to establish a low-inflation path, it should concentrate on instituting financial policy reforms (such as liberalization and privatization) that bolster opposition to inflation rather than easily reversible and practically meaningless changes in legal and institutional structures. This will better ensure the sustainability -- and hence the credibility -- of the government's anti-inflation stance. Fiscal policy is often at the root of macroeconomic disturbances in developing countries. Fiscal policy is more deserving of special protection from politics because of fiscal dominance over monetary policy and its greater vulnerability to private interests. The author suggests that the solution might be to make fiscal policy less susceptible to political pressures by creating an independent fiscal board. Tying the fiscal hands of government may seem a far-fetched idea. But would it not make more sense to force discipline on fiscal policy directly rather than indirectly through monetary policy?Economic Theory&Research,National Governance,Banks&Banking Reform,Economic Stabilization,Macroeconomic Management
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