Staphylococcal Enterotoxins

Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious diseases. These diseases include food poisoning and toxic shock syndrome, which are caused by exotoxins produced by S. aureus. Of the more than 20 Staphylococcal enterotoxins, SEA and SEB are the best characterized and are also regarded as superantigens because of their ability to bind to class II MHC molecules on antigen presenting cells and stimulate large populations of T cells that share variable regions on the β chain of the T cell receptor. The result of this massive T cell activation is a cytokine bolus leading to an acute toxic shock. These proteins are highly resistant to denaturation, which allows them to remain intact in contaminated food and trigger disease outbreaks. A recognized problem is the emergence of multi-drug resistant strains of S. aureus and these are a concern in the clinical setting as they are a common cause of antibiotic-associated diarrhea in hospitalized patients. In this review, we provide an overview of the current understanding of these proteins

Engineering Soluble, High Affinity Receptor Antagonists for Bacterial Exotoxins

212 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006.Chapter four describes the engineering of murine Vbeta8.2 for picomolar affinity to staphylococcal enterotoxin B (SEB). As the known contact regions had already been heavily mutagenized, additional engineering of the Vbeta was performed through extension of the CDR1 loop. Soluble forms of the high-affinity Vbeta regions were tested for their ability to inhibit SEB-mediated T cell cytotoxicity in vitro. As the affinity of the Vbeta regions increased, the amount of protein needed to neutralize 50% of the toxin activity correspondingly decreased. These Vbeta regions were also tested in various rabbit models of toxic shock by Patrick Schlievert, and were remarkably effective at protecting rabbits from the lethal effects of the toxin.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Concorso di idee “Proposte per Roma-Una nuova sistemazione del Campidoglio”, II premio

Progetto di sistemazione del Campidoglio: realizzazione di una piazza attrezzata in sostituzione della salita delle Tre Pile; realizzazione di un bastione attrezzato per collegamenti verticali meccanici; pargheggio sotterraneo; organizzazione della pavimentazione e dei giardini in via di Villa Caffarelli. Individuazione diun percorso museale continuo interno-esterno

Reactor options for disposition of excess weapon plutonium: Selection criteria and decision process for assessment

DOE is currently considering a wide range of alternatives for disposition of excess weapon plutonium, including using plutonium in mixed oxide fuel for light water reactors (LWRs). Lawrence Livermore National Laboratory (LLNL) has been tasked to assist DOE in its efforts to develop a decision process and criteria for evaluating the technologies and reactor designs that have been proposed for the fission disposition alternative. This report outlines an approach for establishing such a decision process and selection criteria. The approach includes the capability to address multiple, sometimes conflicting, objectives, and to incorporate the impact of uncertainty. The approach has a firm theoretical foundation and similar approaches have been used successfully by private industry, DOE, and other government agencies to support and document complex, high impact technology choice decisions. Because of their similarity and relatively simple technology, this report focuses on three light water reactors studied in Phase 1 of the DOE Plutonium Disposition Study. The decision process can be extended to allow evaluation of other reactor technologies and disposition options such as direct disposal and retrievable storage

Multi-objective optimization of turbocharger turbines for low carbon vehicles using meanline and neural network models

Due to slow turnover of the global vehicle parc internal combustion engines will remain a primary means of motive power for decades, so the automotive industry must continue to improve engine thermal efficiency to reduce emissions, since savings will be compounded over the long lifetime of millions of vehicles. Turbochargers are a proven efficiency technology (most new vehicles are turbocharged) but are not optimally designed for real-world driving. The aim of this study was to develop a framework to optimize turbocharger turbine design for competing customer objectives: minimizing fuel consumption (and thus emissions) over a representative drive cycle, while minimizing transient response time. This is achieved by coupling engine cycle, turbine meanline, and neural network inertia models within a genetic algorithm-based optimizer, allowing aerodynamic and inertia changes to be accurately reflected in drive cycle fuel consumption and transient performance. Exercising the framework for the average new passenger car across a drive cycle representing the Worldwide harmonized Light vehicles Test Procedure reveals the trade-off between competing objectives and a turbine design that maintains transient response while minimizing fuel consumption due to a 3 percentage-point improvement in turbine peak efficiency, validated by experiment. This optimization framework is fast to execute, requiring only eight turbine geometric parameters, making it a commercially viable procedure that can refine existing or optimize tailor-made turbines for any turbocharged application (whether gasoline, diesel, or alternatively fuelled), but if applied to turbocharged gasoline cars in the EU would lead to lifetime savings of 290,000 tonnes per production year, and millions of tonnes if deployed worldwide

Experimental Modeling of Necrotizing Enterocolitis in Human Infant Intestinal Enteroids

Background: Experimental model systems are of paramount importance in advancing our understanding of human disease. Methods There are several limitations when using a single cell culture to recapitulate the findings in a complex organism and results often vary between species, when proxy animal models are studied. Results Human enteroids have allowed for study of human disease in complex multicellular culture systems. Here we present the novel use of human infant enteroids generated from premature infant intestine to study necrotizing enterocolitis (NEC), which is a devastating intestinal disorder that affects our most vulnerable pediatric population. Conclusions We demonstrate that NEC can be induced in premature human enteroids as supported by corresponding alterations in inflammation, apoptosis, tight junction expression, and permeability by treatment with lipopolysaccharide