Modulated dispersion explains changes in arrhythmia vulnerability during premature stimulation of the heart

BACKGROUND: Previously, we have shown that a premature stimulus can significantly modulate spatial gradients of ventricular repolarization (ie, modulated dispersion), which result from heterogeneous electrophysiological properties between cells. The role modulated dispersion may play in determining electrical instability in the heart is unknown. METHODS AND RESULTS: To determine if premature stimulus-induced changes in repolarization are a mechanism that governs susceptibility to cardiac arrhythmias, optical action potentials were recorded simultaneously from 128 ventricular sites (1 cm2) in 8 Langendorff-perfused guinea pig hearts. After baseline pacing (S1), a single premature stimulus (S2) was introduced over a range of S1S2 coupling intervals. Arrhythmia vulnerability after each premature stimulus was determined by measurement of a modified ventricular fibrillation threshold (VFT) during the T wave of each S2 beat (ie, S2-VFT). As the S1S2 interval was shortened to an intermediate value, spatial gradients of repolarization and vulnerability to fibrillation decreased by 51+/-9% (mean+/-SEM) and 73+/-45%, respectively, compared with baseline levels. As the S1S2 interval was further shortened, repolarization gradients increased above baseline levels by 54+/-30%, which was paralleled by a corresponding increase (37+/-8%) in vulnerability. CONCLUSIONS: These data demonstrate that modulation of repolarization gradients by a single premature stimulus significantly influences vulnerability to ventricular fibrillation. This may represent a novel mechanism for the formation of arrhythmogenic substrates during premature stimulation of the heart.     

Crystal structure of human uroporphyrinogen decarboxylase

Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by decarboxylating the four acetate side chains of the substrate. This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT). We have determined the crystal structure of recombinant human URO-D at 1.60 A resolution. The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. Many conserved residues cluster at this cleft, including the invariant side chains of Arg37, Arg41 and His339, which probably function in substrate binding, and Asp86, Tyr164 and Ser219, which may function in either binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers.     

Short-term and long-term cytokine release by mouse bone marrow mast cells and the differentiated KU-812 cell line are inhibited by brefeldin A

Mast cells and basophils produce a wide range of cytokines, including large amounts of both IL-6 and granulocyte-macrophage CSF (GM-CSF). However, the route by which cytokines are secreted is poorly understood. In the current study, we used two inhibitors of vesicular transport, brefeldin A and monensin, to examine the routes of secretion of IL-6 and GM-CSF in the differentiated KU812 human cell line and cultured mouse bone marrow mast cells (mBMMC). Studies of cytokine production over 6 to 24 h demonstrated that IL-6 and GM-CSF release from both cell types were inhibited by brefeldin A (BFA) following activation with calcium ionophore, A23187. Monensin had similar inhibitory effects to that of BFA on the initial and ongoing IL-6 release from KU812 cells. In contrast, the amount of each cytokine remaining within the cells was significantly enhanced. Similar results were obtained following IgE-mediated activation of mBMMC. BFA significantly inhibited both the constitutive secretion of IL-6 and the immediate ionophore-induced increase in IL-6 release from KU812 cells at 20 min postactivation. However, treatment with these agents did not alter the release of histamine and beta-hexaminidase from either mBMMC or KU812 cells. These studies suggest that both the initial 20-min release of IL-6 and secretion of IL-6 and GM-CSF over up to 24 h by mBMMC and differentiated KU-812 cells occur predominately through a vesicular transport-dependent mechanism, and that little, if any, IL-6 and GM-CSF is released through degranulation.     

A 110-MHz/1-Mb synchronous TagRAM

A 4-way set associative TagRAM with 1.189-Mb capacity has been developed which can handle a secondary cache system of up to 16 Mbytes. A 9-ns cycle operation and clock to D_out of 4.7 ns are achieved by use of circuit techniques such as a pipelined decoding scheme, a single PMOS load BiCMOS main decoder, a BiCMOS sense-amplifying comparator, doubly placed self-timed write circuits, and highly linear VCO for a PLL. The device is successfully implemented with 0.7-μm double polysilicon double-metal BiCMOS technology     

Abnormal gallium-67 skull uptake: a sign of peripheral marrow activation in HIV-positive patients with disseminated mycobacterioses

The purpose of this study was to investigate the significance of abnormal 67Ga-citrate skull uptake in AIDS patients with mycobacterioses. METHODS: Gallium-67 scans of 39 HIV-positive patients who have been diagnosed with mycobacterioses were analyzed; the scans of 15 consecutive HIV-positive patients without mycobacterioses were also reviewed as a control group. The skull was chosen to assess bone marrow uptake because of the absence of overlapping structures. RESULTS: Twenty-nine of 39 (74%) patients with mycobacterial infections had disseminated disease. Gallium-67 uptake in the skull was visualized in 24 of these 29 patients (82%). One of the patients without disseminated disease and one patient in the control group (n = 15) showed skull uptake. CONCLUSION: Abnormal 67Ga skull uptake appears to be a sensitive (82%) and specific (82%) indicator of disseminated mycobacterial infection in HIV-positive patients.     

EVALUATION OF SIC MATRIX COMPOSITES FOR HIGH TEMPERATURE APPLICATIONS

SiC matrix composite components have been fabricated by infiltrating and overcoating fiber preforms of graphite, alumina, and SiC via chemical vapor deposition (CVD). The degree of CVD densification could be controlled to yield vacuum tight components as well as porous open mesh structures where only the fiber was coated. These components have been fabricated in a wide variety of shapes including baskets, tubes and corrugated panels. The CVD process has been successfully scaled up to produce panels 80 cm by 80 cm. The morphology, chemistry, and geometry of the fiber was found to have a significant effect on the deposition process. Thus, process conditions had to be modified based on the fiber being infiltrated. These components were subjected to 1400 C temperature treatments including operation in gas-fired furnaces. After 2000 hours of testing in a gas-fired furnace at 1300 C, the SiC composite tubes have remained intact and un cracked. This suggests that the monolithic SiC coating is the controlling material and not the fibers. Hence, in light-load applications these structures still have useful lifetimes.     

Affect and the motivational foundations of social capital.

Social capital is a resource that includes the willingness of members of society to cooperate with each other, even when it is not in their own individual material self-interests to do so, or enforce beneficial social norms, even when this is materially costly for the enforcer. Evidence from economic choice experiments suggests that affect may play an important role in the individual-level decision process that generates these behavioral tendencies. Negative affective responses to uncooperative behavior can lead to a breakdown in social capital, if there is no option to punish. Given a punishment option, however, individuals discipline uncooperative types, even though it is materially costly to do so. This can completely counteract the tendency for social capital to decline in repeated interactions. Positive affect, triggered by punishing uncooperative types, appears to play a role in generating this socially beneficial willingness to sanction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)