Co-capping studies reveal CD8/TCR interactions after capping CD8 beta polypeptides and intracellular associations of CD8 with p56(lck)

A reaction-diffusion model was developed to predict the fate of nitric oxide (NO) released by cells of the immune system. The model was used to analyze data obtained previously using macrophages attached to microcarrier beads suspended in a stirred vessel. Activated macrophages synthesize NO, which is oxidized in the culture medium by molecular oxygen and superoxide (O2-, also released by the cells), yielding mainly nitrite (NO2-) and nitrate (NO3-) as the respective end products. In the analysis the reactor was divided into a "stagnant film" with position-dependent concentrations adjacent to a representative carrier bead and a well-mixed bulk solution. It was found that the concentration of NO was relatively uniform in the film. In contrast, essentially all of the O2- was calculated to be consumed within approximately 2 microm of the cell surfaces, due to its reaction with NO to yield peroxynitrite. The decomposition of peroxynitrite caused its concentration to fall to nearly zero over a distance of approximately 30 microm from the cells. Although the film regions (which had an effective thickness of 63 microm) comprised just 2% of the reactor volume and were predicted to account for only 6% of the NO2- formation under control conditions, they were calculated to be responsible for 99% of the NO3- formation. Superoxide dismutase in the medium (at 3.2 microM) was predicted to lower the ratio of NO3- to NO2- formation rates from near unity to <0.5, in reasonable agreement with the data. The NO3-/NO2- ratio was predicted to vary exponentially with the ratio of O2- to NO release rates from the cells. Recently reported reactions involving CO2 and bicarbonate were found to have important effects on the concentrations of peroxynitrite and nitrous anhydride, two of the compounds that have been implicated in NO cytotoxicity and mutagenesis.     

Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence

Surgical treatment of refractory epilepsy in childhood and adolescence has been shown to be effective in reducing the seizure frequency. This paper examines the question: "Does this result in a better socioeconomic outcome in later years?" Patients who underwent a surgical procedure for the treatment of their medically refractory epilepsy at our hospital, had more than 2-years' follow-up, and were less than 18 years old at time of survey were included. From a retrospective chart review, age at onset and at surgery, duration of seizures prior to surgery, years of follow-up, type of surgery, and neurological status were obtained. From a telephone survey, seizure frequency after surgery, marital, financial and driving status, level of education, and employment status were ascertained. Sixty-four patients in our epileptic surgical series meet entry criteria. Significantly higher levels of education, employment status and independence were found in patients with a class I Engel outcome compared to other Engel outcomes.     

Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology

We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups.     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Stability of linear discrete switched systems with delays based on average dwell time method

This paper deals with the problem of exponential stability for a class of linear discrete switched systems with constant delays.The switched systems consist of stable and unstable subsystems.Based on the average dwell time method, some switching signals will be found to guarantee exponential stability of these systems.The explicit state decay estimation is also given in the form of the solutions of linear matrix inequalities(LMIs).An example relating to networked control systems(NCSs) illustrates the effect...     

A graph-based approach for assessing storm-induced coastal changes

Hurricanes and tropical storms are severe threats to coastal properties, settlements, and infrastructure. Airborne light detection and ranging (lidar) surveys conducted before and after storm events allow detailed analysis of coastal geomorphologic and sediment volumetric changes and have been proved very useful in the study of coastal changes. Traditionally, most studies use the pixel-based differencing method to quantify the spatial extent and magnitude of coastal changes based on sequential lidar surveys. This research presents a graph theory-based approach and associated software tools for representing and quantifying storm-induced damages to buildings, beaches and sand dunes, coastal vegetation canopy, and infrastructure. Generation of elevation difference grids, construction of local contour trees, and derivation of semantic properties are key components of the new algorithm for change object detection and extraction. An ontology and taxonomy are proposed to classify change objects into different types of coastal damages in terms of their semantic properties. This method has been successfully applied to assess damages of Hurricane Ike to the Bolivar Peninsula on the Texas Gulf Coast based on pre- and post-storm airborne lidar data and colour infrared aerial photographs.     

The development of multiple reaction monitoring assays for liver-derived plasma proteins

There is wide interpatient variability in toxicity to chemotherapeutic drugs and a lack of routine clinical tests for prospectively identifying patients at risk of developing toxicity from chemotherapy. An empirically driven MS strategy has been developed to monitor liver-derived plasma proteins as potential biomarkers of early toxicity. Multiple reaction monitoring (MRM) has been used to assess 46 candidate peptides from 18 liver-derived proteins. Following an iterative process of assay design, optimisation and assessment we selected 29 MRM assays (median CV 4.6%, range 1.2-11.6%) and monitored changes in levels of plasma proteins from a small number of colorectal cancer (CRC) patients undergoing chemotherapy. We demonstrated MRM assay robustness, and show that patients undergo minor elevation in plasma proteins when profiled on Day 3 of the chemotherapeutic regime. The MRM assays were in general agreement with 2-D DIGE-based quantitation from the same patient samples. The data supports the application of MRM-based methods as facile, highly reproducible, medium-throughput techniques that warrant expanded investigation for clinical utility in identifying patients at risk of developing chemotoxicity.     

On the self-erasing nature of errors of prediction.

82 female undergraduates were assigned to 1 of 4 experimental groups—predict-request, information-request, predict only, and request only—in which requested tasks involved writing a counterattitudinal essay or singing over the telephone. In 3 experiments, Ss overpredicted the degree to which their behavior would be socially desirable and these errors of prediction proved to be self-erasing. Having mispredicted a given behavior, Ss were likely to have these predictions confirmed in later behavior, indicating that prediction of a behavioral sequence evokes a specific cognitive representation of that sequence which is subsequently accessed. Results demonstrate the strong effects on behavior of engaging in prebehavioral cognitive work. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diagnosis and treatment of aortic valve stenosis

The present review has attempted to summarize the classic symptoms and signs of aortic valve stenosis, especially in an adult. It is emphasized that all the classic signs rarely are present and their absence may mislead an unwary clinician. The diagnostic help provided by noninvasive tests, including echocardiography and phonocardiography, has been emphasized. A need for cardiac catheterization and angiography in most patients prior to corrective surgery is stressed. The natural history of the disease without operative intervention is dim and a significant risk of sudden death exists. The current surgical approach with immediate and long-term results is summarized. Finally, attention has been drawn to the special clinical circumstances when the aortic valve stenosis provides a strinkingly different clinical picture. We cannot find a better way to end this review than by quoting a warning note given by Thomas Lewis in 1920: "It is the faint cry of an anguished and fast failing muscle, which, when it comes, all should strain to hear, for it is not long repeated. A few months, a few years at most, and the end comes."