Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands

The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) beta2-microglobulin-deficient (beta2m-/-) RAG-2(-/-) H-2(b) mice specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, we identified a single weak agonist peptide variant V4L (L4) inducing phenotypic and functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/Kb was determined and refined to 2.1 A for comparison with the VSV8/Kb structure at similar resolution. Aside from changes on the p4 side chain of L4 and the resulting alteration of the exposed Kb Lys-66 side chain, these two structures are essentially identical. Hence, a given TCR recognizes subtle distinctions between highly related ligands, resulting in dramatically different selection outcomes. Based on these finding and the recent structural elucidation of the N15-VSV8/Kb complex, moreover, it appears that the germ-line Valpha repertoire contributes in a significant way to positive selection.     

Oral idarubicin pharmacokinetics--correlation of trough level with idarubicin area under curve

As part of a continuing program aimed at developing nonpolyglutamylatable inhibitors of dihydrofolate reductase that are less toxic and more specific in their action, we herein report the therapeutic efficacy and toxicity of gamma-methylene-10-deazaaminopterin (MDAM) in athymic nude mice bearing advanced human HCT-8 ileocecal xenografts and its antitumor activity in C57BL/6 x DBA/2 F1 (hereafter called B6D2F1) mice bearing P388 murine leukemia. For the xenograft study, MDAM was administered at the maximum tolerated dose by the following dose schedules: (a) 5-day continuous i.v. infusion at 1.0 mg/kg/day (schedule I); and (b) i.v. push, daily for 5 days at 50 mg/kg/day (schedule II). The maximum tolerated dose values for methotrexate (MTX) under these conditions were 0.2 and 1.0 mg/kg/day for schedule I and schedule II, respectively. MTX did not exhibit any significant antitumor activity in this model system by both schedules; however, MDAM induced complete responses of 13 and 25% and partial responses of 25 and 50% by schedules I and II, respectively. MDAM also exhibited antitumor activity significantly superior to that of MTX in the P388 tumor model. One of the enantiomers of MDAM, which possesses the natural configuration at the gamma-methyleneglutamate moiety (l-MDAM), has been shown to be a better inhibitor of human recombinant dihydrofolate reductase and H35 hepatoma cell growth than D,L-MDAM. L-MDAM inhibited the uptake of radiolabeled folinic acid to H35 hepatoma cells eight times more efficiently than MTX. The results indicate that the superior activity of MDAM relative to MTX may be partially due to a combination of enhanced transport to tumor cells and slower deactivation by aldehyde oxidase.     

T-cell epitope mapping by flow cytometry

From March 1994 to September 1996, 39 patients underwent stenting of the unprotected left main coronary artery because of high surgical risk. Stenting appeared to improve clinical outcome, but there was a significant mortality rate at long-term follow-up.     

Chemotherapy of alveolar echinococcosis with benzimidazoles. A prospective long-term study]

Hereditary bone dysplasia (HBD) is an extremely rare clinicopathological entity manifested by diaphyseal medullary stenosis and cortical bone thickening associated with a propensity for fractures affecting the long tubular bone. Malignant transformation has been reported to occur at an alarming frequency. The hereditary pattern appears to be autosomal dominant. In this paper we present the case of a 19-year-old man with hereditary bone dysplasia who was unaware of his underlying condition until he presented with malignant transformation arising in an area of bone infarct of the left tibia.     

Simple analysis and working equations for the solidification of cylinders and spheres

The analysis of solidification processes is complicated by a nonlinear boundary condition at the moving solid-liquid interface, and exact solutions are rare. Various attempts to predict the rate of solidification are available in the literature but most of the results seem to be of limited use for operation and design studies on metallurgical processes. In this article we present a physical model which can be solved analytically for the most commonly encountered boundary conditions; that is constant temperature at the cooling wall or finite heat transfer to the cooling fluid. The model is based on the assumption of a linear temperature profile in the solidified shell and a corresponding differential removal of internal energy. As a result one obtains a very simple expression for the soli-dification time as a function of the space variable and the pertinent system parameters. By comparison with numerical results the prediction error is shown to be less than 10 pet over a wide range of parameter combinations. In extreme situations, where a larger error may occur, equally accurate working equations can be generated by slightly modifying the basic results.     

Allgemeine Untersuchungsverfahren und Laboratoriumstechnik

Ohne Zusammenfassung     

Modifying instructional activities to promote desirable behavior: A conceptual and practical framework.

Summarizes a framework for conceptualizing and implementing a model to improve student behavior through individualized, assessment-based modifications of curricular activities. A summary of research documenting the influence of curricular variables is included, with particular focus on recent research on the assessment and utilization of student preferences. A practical model of functional assessment and curricular revision is presented, with examples to illustrate the process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

17Z-Tetracosenyl 1-glycerol ether from the spongesCinachyra alloclada andUlosa ruetzleri

The 1-glycerol ether of 17Z-tetracosenol has been identified as a major constituent of the dichloromethanesoluble extracts of two marine sponges,Cinachyra alloclada andUlosa ruetzleri. Spectral analysis and chemical degradations led to the assigned structure. Batyl alcohol was also found, in lesser quantities, inU. ruetzleri, but not inC. alloclada.     

Analysis of non-linear stress relaxation in polymeric glasses

Non-linear stress relaxation data were obtained for polycarbonate and polystyrene as a function of temperature, strain magnitude and thermal history. Data were analyzed according to the previously proposed free volume model to account for the shift of relaxation times with strain and thermal history. The result of the analysis is shown to be in close agreement with the tensile stress-strain data. The yield phenomenon is analyzed as a rate dependent strain-induced glass to rubber transition.