Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130

It has previously been reported that in resting T-lymphocytes the protein tyrosine kinase p59 constitutively co-precipitates with four phosphoproteins of 43, 55, 85, and 120 kDa, respectively. We have recently cloned the 55-kDa protein that was termed Src kinase-associated phosphoprotein of 55 kDa (SKAP55). Here we demonstrate that the recently characterized SH2-domain-containing leukocyte protein 76-associated phosphoprotein of 130 kDa (SLAP-130) is one of the components of the Fyn complex and that it also co-precipitates with SKAP55 in human T-cells. We establish that SKAP55 and SLAP-130 associate with each other when both molecules are co-expressed in COS cells. By co-transfection of truncated mutants of SKAP55 and SLAP-130 as well as by using the two-hybrid selection system, we further demonstrate that the association between SLAP-130 and SKAP55 is direct and involves the Src homology 3 domain of SKAP55 and the proline-rich sequence of SLAP-130.     

Ultrasound biomicroscopy in the diagnosis and management of anterior segment tumors

BACKGROUND: High-frequency ultrasound biomicroscopy has allowed eye care specialists to evaluate posterior extension of anterior segment tumors. This article evaluates the role of ultrasound biomicroscopy for the diagnosis and management of anterior segment tumors. METHODS: Fourteen patients with anterior segment tumors were selected for evaluation. Each patient underwent a complete clinical examination followed by slit-lamp photography and ultrasound biomicroscopy. RESULTS: Unlike standard ultrasonography of anterior segment tumors, high-frequency ultrasound biomicroscopy allowed quantitative measurements of tumor size, extension within and posterior to the iris, as well as differentiation of solid and cystic lesions. These characteristics were used to differentially diagnose anterior segment tumors and document the response of iridociliary body melanomas to radiotherapy. CONCLUSIONS: This study demonstrates how ultrasound biomicroscopy has become an effective and necessary procedure, used for both the diagnosis and management of anterior segment tumors.     

Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

Increased levels of intracellular calcium are not required for the formation of attaching and effacing lesions by enteropathogenic and enterohemorrhagic Escherichia coli

Elevated concentrations of intracellular calcium ([Ca]i) have been implicated as an important signalling event during attaching and effacing (A/E) lesion formation by enteropathogenic Escherichia coli (EPEC). The highly localized nature of the cytoskeletal and cell surface alterations occurring during A/E lesion formation suggests that there should be equally localized EPEC-induced signalling events. To analyze further the calcium responses to infection of HEp-2 cells by EPEC, we employed calcium-imaging fluorescence microscopy, which allows both temporal and spatial measurements of [Ca]i in live cells. Using this imaging technique, not only were we unable to detect any significant elevation in [Ca]i at sites of A/E EPEC adhesion, but, with several different classical EPEC and enterohemorrhagic E. coli (EHEC) strains and three different infection procedures, each of which resulted in extensive A/E bacterial adhesion, we were unable to detect any significant alterations in [Ca]i in infected cells compared to uninfected cells. In addition, chelation of intracellular free calcium with bis-(aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not, as previously reported, prevent A/E lesion formation. We conclude that increased [Ca]i are not required for A/E lesion formation by EPEC and EHEC.     

Reward revision and the average reward markov decision process

Summary We integrate two numerical procedures for solving the average reward Markov decision process (MDP), standard successive approximations and modified policy iteration with reward revision. Reward revision is the process of revising the reward structure of a second, more computationally desirable MDP so as to produce, in the limit, an optimality equation having a fixed point identical to that associated with the original MDP. A numerical study indicates that for MDP's having a non-sparse transition structure with a small number of relatively large entries per row, the addition of reward revision can have significant computational benefits.

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Zusammenfassung Zur Lösung Markovscher Entscheidungsprozesse (MDP) mit Durchschnitts-Kriterium werden zwei numerische Verfahren, nämlich sukzessive Approximation und modifizierte Politik-Iteration, mit einer Transformation, der sogenannten 'Reward-Revision, kombiniert. Bei dieser Transformation werden die Übergangswahrscheinlichkeiten so abgeändert (ausgedünnt), daß das neue Modell sich numerisch günstiger verhält. Dazu müssen die einstufigen Erträge so revidiert werden, daß die Optimalitäts-Gleichung des neuen Modells im Limes mit der des ursprünglichen übereinstimmt. Numerische Untersuchungen zeigen, daß für MDP mit stark besetzten Übergangsmatrizen, bei denen nur an wenigen Stellen je Zeile große Werte stehen, die Anwendung von 'Reward Revision zu wesentlichen Einsparungen an Rechenaufwand führen kann.

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Research supported by NSF Grant ECS-8319355     

Exploring single electrode reactions in polymer electrolyte fuel cells

Utilising a pseudo-reference electrode in polymer electrolyte fuel cells allows for the separation of anodic and cathodic contributions to the entire cell impedance. Modelling the impedance responses by using equivalent circuits inhibits the investigation of kinetic parameters of the basic electrochemical reactions, which take place at single electrode-electrolyte interfaces. Therefore, we evaluate single electrode impedance measurements by a kinetic model, which is based on specific reaction pathways, either for the oxygen reduction reaction (ORR) or the hydrogen oxidation reaction (HOR). As a consequence, it is possible to obtain kinetic parameters for the specific reaction of interest. Furthermore, the information gained from the single electrode impedance measurements and the kinetic model can give insight into single reactions steps. In particular, the ORR has to include a chemical step in the reaction pathway.     

An LMI approach to synthesis subject to almost asymptotic regulation constraints

A multi-objective controller synthesis problem is considered in which an output is to be regulated approximately by assuring a bound on the steady-state peak amplification in response to an infinite-energy disturbance, while also guaranteeing a desired level of performance measured in terms of the worst-case energy gain from a finite-energy input to a performance output. Relying on a characterization of the controllers with which almost asymptotic regulation is accomplished, the problem of guaranteeing the desired level of performance is reduced to solving a system of linear matrix inequalities subject to a set of linear equality constraints. Based on the solution of this system, a procedure is outlined for the construction of a suitable controller whose order is equal to the order of the plant plus the order of the exogenous system.