Local coherence and deflation of the low quark modes in lattice QCD

The spontaneous breaking of chiral symmetry in QCD is known to be linked to a non-zero density of eigenvalues of the massless Dirac operator near the origin. Numerical studies of two-flavour QCD now suggest that the low quark modes are locally coherent to a certain extent. As a consequence, the modes can be simultaneously deflated, using local projectors, with a total computational effort proportional to the lattice volume (rather than its square). Deflation has potentially many uses in lattice QCD. The technique is here worked out for the case of quark propagator calculations, where large speed-up factors and a flat scaling behaviour with respect to the quark mass are achieved.Comment: Plain TeX, 23 pages, 4 figures included; minor text modifications; version published in JHE

Fluorescence resonance energy transfer sensors for quantitative monitoring of pentose and disaccharide accumulation in bacteria

<p>Abstract</p> <p>Background</p> <p>Engineering microorganisms to improve metabolite flux requires detailed knowledge of the concentrations and flux rates of metabolites and metabolic intermediates <it>in vivo</it>. Fluorescence resonance energy transfer sensors represent a promising technology for measuring metabolite levels and corresponding rate changes in live cells. These sensors have been applied successfully in mammalian and plant cells but potentially could also be used to monitor steady-state levels of metabolites in microorganisms using fluorimetric assays. Sensors for hexose and pentose carbohydrates could help in the development of fermentative microorganisms, for example, for biofuels applications. Arabinose is one of the carbohydrates to be monitored during biofuels production from lignocellulose, while maltose is an important degradation product of starch that is relevant for starch-derived biofuels production.</p> <p>Results</p> <p>An <it>Escherichia coli </it>expression vector compatible with phage λ recombination technology was constructed to facilitate sensor construction and was used to generate a novel fluorescence resonance energy transfer sensor for arabinose. In parallel, a strategy for improving the sensor signal was applied to construct an improved maltose sensor. Both sensors were expressed in the cytosol of <it>E. coli </it>and sugar accumulation was monitored using a simple fluorimetric assay of <it>E. coli </it>cultures in microtiter plates. In the case of both nanosensors, the addition of the respective ligand led to concentration-dependent fluorescence resonance energy transfer responses allowing quantitative analysis of the intracellular sugar levels at given extracellular supply levels as well as accumulation rates.</p> <p>Conclusion</p> <p>The nanosensor destination vector combined with the optimization strategy for sensor responses should help to accelerate the development of metabolite sensors. The new carbohydrate fluorescence resonance energy transfer sensors can be used for <it>in vivo </it>monitoring of sugar levels in prokaryotes, demonstrating the potential of such sensors as reporter tools in the development of metabolically engineered microbial strains or for real-time monitoring of intracellular metabolite during fermentation.</p

SESAM and TXL Results for Wilson Action--A Status Report

Results from two studies of full QCD with two flavours of dynamical Wilson fermions are presented. At beta=5.6, the region 0.83 > m_pi/m_rho > 0.56 at m_pia > 0.23 L^{-1} is explored. The SESAM collaboration has generated ensembles of about 200 statistically independent configurations on a 16^3 x 32-lattice at three different kappa-values and is entering the final phase of data analysis. The TXL simulation on a 24^3 x 40-lattice at two kappa-values has reached half statistics and data analysis has started recently, hence most results presented here are preliminary. The focus of this report is fourfold: we demonstrate that algorithmic improvements like fast Krylov solvers and parallel preconditioning recently introduced can be put into practise in full QCD simulations, we present encouraging observations as to the critical dynamics of the Hybrid Monte Carlo algorithm in the approach to the chiral limit, we mention signal improvements of noisy estimator techniques for disconnected diagrams to the pi-N sigma term, and we report on SESAM's results for light hadron spectrum, light quark masses, and heavy quarkonia.Comment: 24 pages, tex + postscript figures, to appear in Proceedings of Int. Workshop "Lattice QCD on Parallel Computers", University of Tsukuba, Japa

Nanosensor Detection of an Immunoregulatory Tryptophan Influx/Kynurenine Efflux Cycle

Mammalian cells rely on cellular uptake of the essential amino acid tryptophan. Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation, indoleamine 2,3-dioxygenase (IDO), e.g., in cancer and inflammation, is thought to suppress the immune response via T cell starvation. Additionally, the excreted tryptophan catabolites (kynurenines) induce apoptosis of lymphocytes. Whereas tryptophan transport systems have been identified, the molecular nature of kynurenine export remains unknown. To measure cytosolic tryptophan steady-state levels and flux in real time, we developed genetically encoded fluorescence resonance energy transfer nanosensors (FLIPW). The transport properties detected by FLIPW in KB cells, a human oral cancer cell line, and COS-7 cells implicate LAT1, a transporter that is present in proliferative tissues like cancer, in tryptophan uptake. Importantly, we found that this transport system mediates tryptophan/kynurenine exchange. The tryptophan influx/kynurenine efflux cycle couples tryptophan starvation to elevation of kynurenine serum levels, providing a two-pronged induction of apoptosis in neighboring cells. The strict coupling protects cells that overproduce IDO from kynurenine accumulation. Consequently, this mechanism may contribute to immunosuppression involved in autoimmunity and tumor immune escape

Coronary Artery Surgery Study (CASS): Comparability of 10 year survival in randomized and randomizable patients

AbstractThe Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction.Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison.Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis ≥70% and an ejection fraction < 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction < 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p < 0.05).After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial

Critical Dynamics of the Hybrid Monte Carlo Algorithm

We investigate the critical dynamics of the Hybrid Monte Carlo algorithm approaching the chiral limit of standard Wilson fermions. Our observations are based on time series of lengths O(5000) for a variety of observables. The lattice sizes are 16^3 x 32 and 24^3 x 40. We work at beta=5.6, and kappa=0.156, 0.157, 0.1575, 0.158, with 0.83 > m_pi/m_rho > 0.55. We find surprisingly small integrated autocorrelation times for local and extended observables. The dynamical critical exponent $z$ of the exponential autocorrelation time is compatible with 2. We estimate the total computational effort to scale between V^2 and V^2.25 towards the chiral limit.Comment: 3 pages, Latex with espcrc2.sty and postscript figures, Talk given at Lattice 9

Análise da estrutura da glutamina sintetase por microscopia de força atômica: primeiros resultados.

bitstream/CNPDIA/9905/1/PA19_97.pd

Somatosensory function and cortical unit activity in cats with only dorsal column fibers

Cats received lesions that transected the entire thoracic cord except for partial sparing of the dorsal columns. The cats were required to discriminate the side on which they were touched, the size of simultaneously presented discs, or the direction their fur was stroked to obtain food reward. All cats found by anatomical and/or electrophysiological criteria to have any functional continuity in the dorsal columns were able to master the first of these tasks; some responded above chance on the second. Performance was at chance on blank trials, and cats with complete cord transection failed to discriminate. Lesioned cats did not orient or otherwise react to any nonrewarded stimulus below the level of the lesion. A total of 532 units were recorded under light barbiturate anesthesia from the hind paw projection near the tip of the ansate sulcus in these and other similarly prepared cats. Three-fourths of the units found before and acutely after the cord lesions were made were driven by hind limb stimulation. Only 27% of the units recorded 10 or more days afterwards could be driven. Of these driven units, 15 (38%) responded to foreleg stimulation, 13 exclusively so. No such units were found in intact or acutely lesioned cats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46547/1/221_2004_Article_BF00237693.pd

Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin

Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour