Sustained release of IL-1Ra from biodegradable microspheres prolongs its IL-1-neutralizing effects

A sustained delivery system for interleukin-1 receptor antagonist (IL-1Ra) may have great therapeutic and industrial potential due to the cytokine activity as an IL-1 inhibitor. Here, we investigated the capability of biodegradable polymeric microspheres to sustain the release and prolong the therapeutic efficacy of IL-1Ra. IL-1Ra was encapsulated within rapidly degrading poly(lactic/glycolic acid) PLGA RG502H microspheres, which showed a desirable release profile of IL-1Ra in vitro. Pharmacokinetic study in mice revealed elevated serum levels of the recombinant IL-1Ra (rIL-1Ra) for up to 8 days following subcutaneous injection of IL-1Ra microspheres. In comparison, the serum levels of rIL-1Ra following subcutaneous or intravenous bolus injection of the soluble cytokine decreased very rapidly; within 48 h no recombinant cytokine was detected in mice sera. The sustained delivery of rIL-1Ra for over two weeks was efficient in inhibiting IL-1ß-stimulated induction of serum IL-6. These results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-1Ra within PLGA RG502H microspheres.     

Serotonin receptors: subtypes, functional responses and therapeutic relevance

Recent, rapid progress in the molecular biology of serotonin (5-HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of the receptor protein, the Nomenclature Committee of the Serotonin Club has proposed the following classification and nomenclature: the main receptor types 5-HT1 to 5-HT4, recombinant receptors (e.g. 5-ht5 to 5-ht7) and 'orphan' receptors. The aim of the present review is to discuss the events leading to this classification, the criteria for and functional responses mediated by various 5-HT receptors, as well as the therapeutic possibilities with 5-HT ligands.     

Collusion set detection using graph clustering

Many mal-practices in stock market trading—e.g., circular trading and price manipulation—use the modus operandi of collusion. Informally, a set of traders is a candidate collusion set when they have “heavy trading” among themselves, as compared to their trading with others. We formalize the problem of detection of collusion sets, if any, in the given trading database. We show that naïve approaches are inefficient for real-life situations. We adapt and apply two well-known graph clustering algorithms for this problem. We also propose a new graph clustering algorithm, specifically tailored for detecting collusion sets. A novel feature of our approach is the use of Dempster–Schafer theory of evidence to combine the candidate collusion sets detected by individual algorithms. Treating individual experiments as evidence, this approach allows us to quantify the confidence (or belief) in the candidate collusion sets. We present detailed simulation experiments to demonstrate effectiveness of the proposed algorithms.     

An overhead and resource contention aware analytical model for overloaded Web servers

A Web server, when overloaded, shows a severe degradation of goodput initially, with the eventual settling of goodput as load increases further. Traditional performance models have failed to capture this behavior. In this paper, we propose an analytical model, which is a two-stage and layered queuing model of the Web server, which is able to reproduce this behavior. We do this by explicitly modelling the overhead processing, the user abandonment and retry behavior, and the contention for resources, for the FIFO and LIFO queuing disciplines. We show that LIFO provides better goodput in most overload situations. We compare our model predictions with experimental results from a test bed and find that our results match well with measurements.     

Transistors made in laser recrystallized polysilicon on insulator films

lpcvd polycrystalline silicon films were deposited on thermally oxidized silicon as well as onlpcvd silicon nitride deposited on silicon. Acw argon ion laser was used to recrystallize the polysilicon film into large grains (grain size from 5μm to 40μm). Boron was then implanted and standard N-channel silicon gate process and N-channel metal gate process were carried out to realisemosfets on this material. Channel mobilities upto 450 cm²/V-sec for electrons have been measured. This thin filmmosfet has a four-terminal structure with a top and a bottom gate and the influence of one gate on the drain current due to the other gate has been investigated. Comparison of theI _D v-V _D curves of the devices with physical models was found in good agreement.     

Influence of carrier-specific, thymus-derived cells on the immunologlobulin M antibody response to staphylococcal lipoteichoic acid

The immunoglobulin M antibody response to the lipoteichoic acid (LTA) of Staphylococcus aureus ATCC 6538P was examined by a procedure in which erythrocytes sensitized with periodate-activated LTA were used for the detection of immunoglobulin M-producing plaque-forming cells LTA-specific plaque-forming cells were first detected 2 days after immunization with heat-killed bacterial cells, and maximal numbers of plaque-forming cells, mostly of the immunoglobulin M class rather than the immunoblogulin G or immunoglobulin A class, were attained by day 4; specificity for LTA was affirmed by plaque inhibition tests. No plaque-forming cells were found in mice given isolated LTA over a 10,000-fold range of immunizing doses. Mice pretreated with a carrier known to activate thymus-derived helper lymphocytes produced a plaque-forming cell response to LTA only when immunized with LTA bound to the same carrier. This suggests that carrier-specific thymus-derived cells are needed to initiate an antibody response to poorly immunogenic LTA. Since an antibody response can be elicited in mice given heat-killed cells, other cell wall and/or cell membrane constituents may play an important role as immunologically active carriers for this antigen.