Cerebral microbleeds and cognitive decline in a hemodialysis patient: Case report and review of literature

Cerebral microbleeds (CMBs) are small hemosiderin deposits indicative of prior cerebral microscopic hemorrhage and previously thought to be clinically silent. Recent population‐based cross‐sectional studies and prospective longitudinal cohort studies have revealed association between CMB and cognitive dysfunction. In the general population, CMBs are associated with age, hypertension, and cerebral amyloid angiopathy. In the chronic kidney disease (CKD) population, diminished estimated glomerular filtration rate has been found to be an independent risk factor for CMB, raising the possibility that a uremic milieu may predispose to microbleeds. In the end‐stage renal disease (ESRD) population on hemodialysis, the incidence of microbleeds is significantly higher compared with a control group without history of CKD or stroke. We present an ESRD patient on chronic hemodialysis with a history of gradual cognitive decline and progressive CMBs. Through this case and literature review, we illustrate the need to develop detection and prediction models to treat this frequent development in ESRD patients.     

Supply-side hurdles in Internet B2C e-commerce: an empirical investigation

Given Hong Kong's special circumstances of small physical size, advanced infrastructure, and low shopping cost, a survey is designed under which supply-side problems in Internet business-to-consumer (B2C) e-commerce are indirectly revealed by responses on the demand side. Difficulties arising from the reluctance to answer questionnaires on the part of e-firms wary about trade and innovation secrets and their small number at the outset are thereby overcome. Survey data on demand-side obstacle factors in the form of perceived low e-shopping comparability, e-shopping inconvenience, e-transaction insecurity, and poor Internet privacy, together with orientation toward social interaction and low awareness on the part of consumers, translate into information on notionally matching supply-side hurdles. Regression analysis and hypothesis testing indicate statistical significance for the above hurdle factors in terms of impact on individual unwillingness to shop online. These results add to the inductive basis for future research into a general demand-supply theory of Internet B2C e-commerce and offer an empirically-grounded position against which the effects of later supply-side changes can be evaluated. Useful information also follows for engineer-managers seeking to compare marginal improvements in supply-side problems, particularly in the form of estimated substitution ratios.     

A 1-V 10.7-MHz switched-opamp bandpass /spl Sigma//spl Delta/ modulator using double-sampling finite-gain-compensation technique

A 1 V switched-capacitor (SC) bandpass sigma-delta (/spl Sigma//spl Delta/) modulator is realized using a high-speed switched-opamp (SO) technique with a sampling frequency of up to 50 MHz, which is improved ten times more than prior 1 V SO designs and comparable to the performance of the state-of-the-art SC circuits that operate at much higher supply voltages. On the system level, a fast-settling double-sampling SC biquadratic filter architecture is proposed to achieve high-speed operation. A low-voltage double-sampling finite-gain-compensation technique is employed to realize a high-resolution /spl Sigma//spl Delta/ modulator using only low-DC-gain opamps to maximize the speed and to reduce power dissipation. On the circuit level, a fast-switching methodology is proposed for the design of the switchable opamps to achieve a switching frequency up to 50 MHz. Implemented in a 0.35-/spl mu/m CMOS process (V/sub TP/=0.82 V and V/sub TN/=0.65 V) and at 1 V supply, the modulator achieves a measured peak signal-to-noise-and-distortion ratio (SNDR) of 42.3 dB at 10.7 MHz with a signal bandwidth of 200 kHz, while dissipating 12 mW and occupying a chip area of 1.3 mm/sup 2/.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

A high-linearity 100-element diode grid mixer

Grid-mixer arrays can achieve high linearity and dynamic range through quasi-optical power combining. We present a 100-element single-ended diode grid mixer operating at 2.45 GHz. Each element incorporates two diodes in series. We measure an input third-order intercept of 11 W (40.5 dBm), and output third-order intercept of 3.4 W (35.4 dBm), and an associated conversion loss of 5.1 dB. The power-handling capability of the array is 100 times larger than that of a microstrip mixer using a single element. The local oscillator (LO) drive requirement for the entire array is 1.4 W (31.6 dBm). The angular dependence of the array's IF power is also presented and is in agreement with theory     

Solution of Helmholtz equation by Trefftz method

The application of the Trefftz method for calculating wave forces on offshore structures is presented. Indirect and direct formulations using complete and non-singular systems of Trefftz functions for the Helmholtz equation are posed in this paper. An effective technique using different interpolation functions for the velocity potential and wave force are suggested to improve the computational accuracy of the wave force. The numerical examples show that the present method is highly efficient and accurate.     

Optimal transfer trees and distinguishing trees for testing observable nondeterministic finite-state machines

The fault-state detection approach for blackbox testing consists of two phases. The first is to bring the system under test (SUT) from its initial state to a targeted state t and the second is to check various specified properties of the SUT at t. This paper investigates the first phase for testing systems specified as observable nondeterministic finite-state machines with probabilistic and weighted transitions. This phase involves two steps. The first step transfers the SUT to some state t' and the second step identifies whether t' is indeed the targeted state t or not. State transfer is achieved by moving the SUT along one of the paths of a transfer tree (TT) and state identification is realized by using diagnosis trees (DT). A theoretical foundation for the existence and characterization of TT and DT with minimum weighted height or minimum average weight is presented. Algorithms for their computation are proposed.     

Effects of serotonin and the serotonin blocker metergoline on meal patterns and macronutrient selection

Serotonin [5-hydroxytryptamine(5-HT)] in the paraventricular nucleus (PVN) of rats has a suppressive effect on feeding behavior and causes a selective decrease in carbohydrate ingestion, specifically at the onset of the natural (dark) feeding period. Studies conducted here provide further evidence for this phenomena, showing a similar dose-related decrease in carbohydrate ingestion at dark onset after PVN injection of 5-HT or of the agonists, d-norfenfluramine or fluoxetine, which act through endogenous 5-HT. To further characterize the effects of this indoleamine on the macrostructure of feeding, a computer-automated data acquisition system was used to analyze macronutrient feeding patterns in freely feeding animals maintained on the pure diets of protein, carbohydrate, and fat. Results indicate that PVN administration of 5-HT at dark onset decreases intake of the carbohydrate nutrient by decreasing meal size, feeding time, and feeding rate for this nutrient and increasing the satiating effect of carbohydrate. These effects, which occur specifically during the first meal after injection, are opposite those seen after peripheral administration of the 5-HT receptor antagonist, metergoline. This drug stimulates feeding through a selective increase in carbohydrate intake, characterized by an increase in meal size, percent composition, and feeding time for this nutrient and a decrease in the satiety ratio for carbohydrate. These results implicate the serotonergic system in the termination of carbohydrate-rich meals that are prevalent during the early hours of the natural feeding cycle.     

ATP-Dependent inhibition of Ca2+-activated K+ channels in vascular smooth muscle cells by neuropeptide Y

Neuropeptide Y(NPY) inhibits Ca2+-activated K+ channels reversibly in vascular smooth muscle cells from the rat tail artery. NPY (200 microM) had no effect in the absence of intracellular adenosine 5'-triphosphate (ATP) and when the metabolic poison cyanide-M-chlorophenyl hydrozone (10 microM) was included in the intracellular pipette solution. NPY was also not effective when ATP was substituted by the non-hydrolysable ATP analogue adenosine 5'-[beta gamma-methylene]-triphosphate (AMP-PCP). NPY inhibited Ca2+-activated K+ channel activity when ATP was replaced by adenosine 5'-O-(3-thiotriphosphate) (ATP [gamma-S]) and the inhibition was not readily reversed upon washing. Protein kinase inhibitor (1 microM), a specific inhibitor of adenosine 3', 5'-cyclic monophosphate-dependent protein kinase, had no significant effect on the inhibitory action of NPY. The effect of NPY on single-channel activity was inhibited by the tyrosine kinase inhibitor genistein (10 microM) but not by daidzein, an inactive analogue of genistein. These observations suggest that the inhibition by NPY of Ca2+-activated K+ channels is mediated by ATP-dependent phosphorylation. The inhibitory effect of NPY was antagonized by the tyrosine kinase inhibitor genistein.