A new technique for on-line and off-line high speed computation

A novel technique for both online and offline computation is presented. With this technique, a reconstruction analysis in elementary particle physics, otherwise prohibitively long, has been accomplished. It will be used online in an upcoming Fermilab experiment to reconstruct more than 100000 events per second and to trigger on the basis of that information. The technique delivers 40 gigaoperations per second, has a bandwidth on the order of gigabytes per second, and has a modest cost. An overview of the program, details of the system, and performance measurements are presented     

The role of transmembrane domain 2 in cation transport by the Na-K-Cl cotransporter

The human and shark Na-K-Cl cotransporters (NKCC), although 74% identical in amino acid sequence, exhibit marked differences in ion transport and bumetanide binding. We have utilized shark-human chimeras of NKCC1 to search for regions that confer the kinetic differences. Two chimeras (hs3.1 and its reverse sh3.1) with a junction point located at the beginning of the third transmembrane domain were examined after stable transfection in HEK-293 cells. Each carried out bumetanide-sensitive 86Rb influx with cation affinities intermediate between shark and human cotransporters. In conjunction with the previous finding that the N and C termini are not responsible for differences in ion transport, the current observations identify the second transmembrane domain as playing an important role. Site-specific mutagenesis of two pairs of residues in this domain revealed that one pair is indeed involved in the difference in Na affinity, and a second pair is involved in the difference in Rb affinity. Substitution of the same residues with corresponding residues from NKCC2 or the Na-Cl cotransporter resulted in cation affinity changes, consistent with the hypothesis that alternative splicing of transmembrane domain 2 endows different versions of NKCC2 with unique kinetic behaviors. None of the changes in transmembrane domain 2 was found to substantially affect Km(Cl), demonstrating that the affinity difference for Cl is specified by the region beyond predicted transmembrane domain 3. Finally, unlike Cl, bumetanide binding was strongly affected by shark-human replacement of transmembrane domain 2, indicating that the bumetanide-binding site is not the same as the Cl-binding site.     

Locating eating pathology within an empirical diagnostic taxonomy: Evidence from a community-based sample.

Existing structural models of psychopathology need to be expanded to include additional diagnostic constructs beyond mood, anxiety, substance use, and antisocial behavior disorders. The goal of this study was to locate eating disorders within a hierarchical structural model of psychopathology that is anchored by broad Internalizing and Externalizing factors. Participants were female adolescent twins (N = 1,434) from the Minnesota Twin Family Study. The authors compared the fit of 4 models in which eating disorders (a) defined their own diagnostic class, (b) represented a subclass within Internalizing, (c) formed a subclass within Externalizing, and (d) were allowed to cross-load on both Internalizing and Externalizing. In the best fitting model, eating disorders formed a subfactor within Internalizing. These findings underscore the value of developing more comprehensive empirically based models of psychopathology to increase researchers' understanding of diverse mental disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The clinical utility of personality subtypes in patients with anorexia nervosa.

Objective: Elucidation of clinically relevant subtypes has been proposed as a means of advancing treatment research, but classifying anorexia nervosa (AN) patients into restricting and binge-eating/purging types has demonstrated limited predictive validity. This study aimed to evaluate whether an approach to classifying eating disorder patients on the basis of comorbid personality psychopathology has utility in predicting treatment response and readmission in patients with AN. Method: Data were collected from 154 AN patients (M [SD] age = 25.6[9.4] years; 95.5% female; 96.8% Caucasian) at admission, discharge, and 3 months postdischarge from intensive treatment. Latent profile analysis of personality traits assessed at admission was performed to classify participants into personality subtypes, which were then used to predict outcomes at discharge and risk of readmission. Results: The best fitting model identified 3 personality subtypes (undercontrolled, overcontrolled, low psychopathology) that contributed significantly to multivariate models predicting study outcomes. Undercontrolled patients were more likely to have a poor outcome at discharge than overcontrolled (OR = 3.56, p = .01) and low psychopathology patients (OR = 11.23, p     

Noninvasive Fluid Property Measurements Using Acoustic Methods

The properties of a fluid are normally determined using invasive methods. These methods may lead to possibly contaminating or consuming the sample. When only very small amounts of a valuable sample exist, noninvasive measurement methods are preferred. The properties of fluids can then be used to deduce additional properties based on known relationships. In one case, the surface tension of a fluid may be used to determine the concentration of a fluid. We describe a measurement technique involving excitation of the surface of the fluid and the measurement of its response. An acoustic wave is used to both excite and monitor the surface of the liquid. This technique is used to determine the concentration of DMSO and water in solution, and the result determines the amount of fluid needed to deliver an accurate amount of solute in solution.     

A dominant-negative transgene defines a role for p56lck in thymopoiesis

The lymphocyte-specific protein tyrosine kinase p56lck participates in T cell signaling through functional interactions with components of the T cell antigen receptor complex and the interleukin-2 receptor. Additional insight into the function of p56lck has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56lckR273). Mice bearing the lckR273 transgene manifested a severe defect in the production of virtually all T lymphocytes. Those exceptional CD3+ cells that escaped the effects of the lckR273 transgene were confined primarily to the T cell subset that expresses gamma/delta T cell receptors. Remarkably, construction of a dose-response curve for the effects of the lckR273 transgene revealed that developmental arrest of thymocytes occurred at a discrete stage in the normal T cell maturation pathway, corresponding to a point at which thymoblasts ordinarily begin a series of mitotic divisions that result in expansion and maturation. These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts.     

CD8 inhibits signal transduction through the T cell receptor in CD4-CD8- thymocytes from T cell receptor transgenic mice reconstituted with a transgenic CD8 alpha molecule

T cell repertoire selection processes involve intracellular signaling events generated through the TCR. The CD4 and CD8 coreceptor molecules can act as positive regulators of TCR signal transduction during these developmental processes. In this report, we have used TCR transgenic mice to determine whether TCR signaling can be modulated by the CD8 coreceptor molecule. These mice express on the majority of their T cells a TCR specific for the male (H-Y) Ag presented by the H-2Db MHC class I molecule. We show that CD4-CD8-, but not CD4-CD8+, thymocytes expressing the H-Y TCR responded with high intracellular calcium fluxes to TCR/CD3 stimulation without extensive receptor cross-linking. To examine the effects of CD8 expression on intracellular signaling responses in the CD4-CD8- cells, the H-Y TCR transgenic mice were mated with transgenic mice that constitutively expressed the CD8 alpha molecule on all T cells. The expression of the CD8 alpha alpha homodimer in the CD4-CD8-thymocytes led to impaired intracellular calcium responses and less efficient protein tyrosine phosphorylation of substrates after TCR engagement. In male H-2b H-Y transgenic mice, the majority of thymocytes have been deleted with the surviving cells expressing a high density of the transgenic TCR and exhibiting either a CD4-CD8- or CD4-CD8lo phenotype. It has been postulated that these cells escaped deletion by down-regulating the CD8 molecule. In the H-Y TCR/CD8 alpha double transgenic male mice, the CD4-CD8lo cells were completely eliminated as a result of CD8 alpha expression. However, the CD4-CD8- T cells were not deleted despite normal levels of the CD8 alpha transgene expression. These results suggest that the CD4-CD8- thymocytes may not be susceptible to the same deletional mechanisms as other thymocytes expressing TCR-alpha beta.