Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR

The role of lipids in inflammasome activation remains underappreciated. The phospholipid, platelet-activating factor (PAF), exerts multiple physiological functions by binding to a G protein-coupled seven-transmembrane receptor (PAFR). PAF is associated with a number of inflammatory disorders, yet the molecular mechanism underlying its proinflammatory function remains to be fully elucidated. We show that multiple PAF isoforms and PAF-like lipids can activate the inflammasome, resulting in IL-1β and IL-18 maturation. This is dependent on NLRP3, ASC, caspase-1, and NEK7, but not on NLRC4, NLRP1, NLRP6, AIM2, caspase-11, or GSDMD. Inflammasome activation by PAF also requires potassium efflux and calcium influx but not lysosomal cathepsin or mitochondrial reactive oxygen species. PAF exacerbates peritonitis partly through inflammasome activation, but PAFR is dispensable for PAF-induced inflammasome activation in vivo or in vitro. These findings reveal that PAF represents a damage-associated signal that activates the canonical inflammasome independently of PAFR and provides an explanation for the ineffectiveness of PAFR antagonist in blocking PAF-mediated inflammation in the clinic

Comparing Bayesian models for multisensory cue combination without mandatory integration

Bayesian models of multisensory perception traditionally address the problem of estimating an underlying variable that is assumed to be the cause of the two sensory signals. The brain, however, has to solve a more general problem: it also has to establish which signals come from the same source and should be integrated, and which ones do not and should be segregated. In the last couple of years, a few models have been proposed to solve this problem in a Bayesian fashion. One of these has the strength that it formalizes the causal structure of sensory signals. We first compare these models on a formal level. Furthermore, we conduct a psychophysics experiment to test human performance in an auditory-visual spatial localization task in which integration is not mandatory. We find that the causal Bayesian inference model accounts for the data better than other models

Dysregulated Epstein-Barr virus infection in patients with CIDP

Ubiquitous viruses have frequently been proposed as a cause or trigger of chronic immune-mediated diseases. Infections are reported to be temporally associated with clinical exacerbations in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We examined immunological parameters of herpesvirus infections in untreated patients with CIDP compared to demographically matched controls. Patients with CIDP were uniformly seropositive for EBV-specific IgG and the disease was associated with a moderately enhanced IgG reactivity to EBV-encoded antigens expressed during both B cell transformation and productive viral replication. Moreover, cellular EBV copy numbers were 3-fold increased in patients with CIDP. In contrast, humoral immune responses to other herpesviruses (HCMV, HSV) as well as virus-specific IgM responses were unchanged in CIDP. These data indicate that host-pathogen interactions during chronic EBV infection are dysregulated in treatment-naïve patients with CIDP

Annual Report of the Municipal Officers of the Town of Turner Maine For the Year Ending Feb. 15 1920

\u3cp\u3eThis chapter addresses the problem of estimating the parameters of a Bayesian network from incomplete data. This is a hard problem, which for computational reasons cannot be effectively tackled by a full Bayesian approach. The work around is to search for the estimate with maximum posterior probability. This is usually done by selecting the highest posterior probability estimate among those found by multiple runs of Expectation-Maximization with distinct starting points. However, many local maxima characterize the posterior probability function, and several of them have similar high probability. We argue that high probability is necessary but not sufficient in order to obtain good estimates.We present an approach based on maximum entropy to address this problem and describe a simple and effective way to implement it. Experiments show that our approach produces significantly better estimates than the most commonly used method.\u3c/p\u3

The European register for specialists in clinical chemistry and laboratory medicine: guide to the register version 2-2003 and procedure for re-registration

The European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) opened a Register for European Chemists in 1997. The operation of the Register is undertaken by a Register Committee (EC4RC). During the last 5 years more than 1400 clinical chemists entered the register. In this article an update of the first Guide to the Register is given, based on the experience of 5 years of operation and the development of the discipline. The registration is valid for 5 years. In a second part the procedure and the conditions for re-registration are presented

Laserschweissgerechtes Konstruieren Beitraege zu innovativen Fertigungsverfahren

The research report starts with a presentation of research projects into laser beam welding, also addressing aircraft and spacecraft construction. This is followed by a presentation of the general principles of methodological design of laser welded joints as well as a description of the status and development trends in laser welding. A manual for designers provides guidelines for design to meet the requirements of laser welding. (orig.)Im vorliegenden Forschungsbericht werden zunaechst Forschungsvorhaben zum Laserstrahlschweissen dargestellt. Dabei wird auch auf den Flugzeug- und Raumflugkoerperbau eingegangen. Danach werden die allgemeinen Grundlagen des methodischen Konstruierens von Laserschweissverbindungen vorgestellt sowie Stand und Entwicklungstendenzen des Laserschweissens beschrieben. Ein Handbuch fuer Konstrukteure liefert Richtlinien zum laserschweissgerechten Gestalten. Abschliessend wird ueber industrielle Anwendungen berichtet. (orig.)Available from TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The practice of clinical chemistry in the European Union.

The European Communities Confederation of Clinical Chemistry has been actively engaged in raising the level of clinical chemistry in the European Union. Closer contacts between the national societies for clinical chemistry have resulted in more comparable programs for postgraduate training of clinical chemists, closer similarity of contents and practice of the profession in the different countries, and the official registration of professionals. This article reviews some of the characteristics of professional organisation, practice, and regulation in the fifteen European Union countries. Many similarities appear. In half of the countries microbiology, blood-banking and transfusion medicine fall within the domain of clinical chemistry. The minimum number of years for training (university and postgraduate) is eight, but in practice this will extend to 10 or more years. Official regulation of the profession by law exists in a minority of countries. Continuing education and re-registration have not been officially instituted yet in any country, but these issues will be the next steps forward. In those countries that prepare themselves for entering the European Union, training and practice of clinical chemistry are moving towards the common standards of the European Communities Confederation of Clinical Chemistry