Nonlinear Dynamical Equation for Irreversible, Steepest-Entropy-Ascent Relaxation to Stable Equilibrium

We discuss the structure and main features of the nonlinear evolution equation proposed by this author as the fundamental dynamical law within the framework of Quantum Thermodynamics. The nonlinear equation generates a dynamical group providing a unique deterministic description of irreversible, conservative relaxation towards equilibrium from any non-equilibrium state, and satisfies a very restrictive stability requirement equivalent to Hatsopoulos-Keenan statement of the second law of thermodynamics. Here, we emphasize its mathematical structure and its applicability also within other contexts, such as Classical and Quantum Statistical Mechanics, and Information Theory.Comment: Proceedings of the Conference "Quantum Theory: Reconsideration of Foundations - 4", Vaxjo, Sweden, June 11-16, 200

Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis

Objectives The DETECT algorithm has been developed to identify SSc patients at risk for pulmonary arterial hypertension (PAH) yielding high sensitivity but low specificity, and positive predictive value. We tested whether cardiopulmonary exercise testing (CPET) could improve the performance of the DETECT screening strategy. Methods Consecutive SSc patients over a 30-month period were screened with the DETECT algorithm and positive subjects were referred for CPET before the execution of right-heart catheterization. The predictive performance of CPET on top of DETECT was evaluated and internally validated via bootstrap replicates. Results Out of 314 patients, 96 satisfied the DETECT application criteria and 54 were positive. PAH was ascertained in 17 (31.5%) and pre-capillary pulmonary hypertension in 23 (42.6%) patients. Within CPET variables, the slope of the minute ventilation to carbon dioxide production relationship (VE/VCO2 slope) had the best performance to predict PAH at right-heart catheterization [median (interquartile range) of specificity 0.778 (0.714\u20130.846), positive predictive value 0.636 (0.556\u20130.750)]; exploratory analysis on pre-capillary yielded a specificity of 0.714 (0.636\u20130.8) and positive predictive value of 0.714 (0.636\u20130.8). Conclusion In association with the DETECT algorithm, CPET may be considered as a useful tool in the workup of SSc-related pulmonary hypertension. The sequential determination of the VE/VCO2 slope in DETECT-positive subjects may reduce the number of unnecessary invasive procedures without any loss in the capability to capture PAH. This strategy had also a remarkable performance in highlighting the presence of pre-capillary pulmonary hypertension

Spatial Molecular and Cellular Determinants of STAT3 Activation in Liver Fibrosis Progression in Non-alcoholic Fatty Liver Disease

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice. METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and transcriptomic changes in fibrotic NAFLD livers.Results: pSTAT3 scores in non-hepatocyte areas progressively increased with fibrosis severity (r = 0.53, CONCLUSION: Increased understanding of the spatial dependence of STAT3 signaling in NASH and liver fibrosis progression could lead to novel targeted treatment approaches. IMPACT AND IMPLICATIONS: Advanced liver fibrosis is the main determinant of mortality in patients with NASH. This study showed using liver biopsies from 133 patients with NAFLD, that STAT3 activation in non-hepatocyte areas is strongly associated with fibrosis severity, inflammation, and progression to NASH. STAT3 activation was enriched in hepatic progenitor cells (HPCs) and sinusoidal endothelial cells (SECs), as determined by innovative technologies interrogating the spatial distribution of pSTAT3. Finally, STAT3 inhibition in mice resulted in reduced liver fibrosis and depletion of HPCs, suggesting that STAT3 activation in HPCs contributes to their expansion and fibrogenesis in NAFLD

Development of FTK architecture: a fast hardware track trigger for the ATLAS detector

The Fast Tracker (FTK) is a proposed upgrade to the ATLAS trigger system that will operate at full Level-1 output rates and provide high quality tracks reconstructed over the entire detector by the start of processing in Level-2. FTK solves the combinatorial challenge inherent to tracking by exploiting the massive parallelism of Associative Memories (AM) that can compare inner detector hits to millions of pre-calculated patterns simultaneously. The tracking problem within matched patterns is further simplified by using pre-computed linearized fitting constants and leveraging fast DSP's in modern commercial FPGA's. Overall, FTK is able to compute the helix parameters for all tracks in an event and apply quality cuts in approximately one millisecond. By employing a pipelined architecture, FTK is able to continuously operate at Level-1 rates without deadtime. The system design is defined and studied using ATLAS full simulation. Reconstruction quality is evaluated for single muon events with zero pileup, as well as WH events at the LHC design luminosity. FTK results are compared with the tracking capability of an offline algorithm.Comment: To be published in the proceedings of DPF-2009, Detroit, MI, July 2009, eConf C09072

The Evolution of FTK, a Real-Time Tracker for Hadron Collider Experiments

We describe the architecture evolution of the highly-parallel dedicated processor FTK, which is driven by the simulation of LHC events at high luminosity (1034 cm-2 s-1). FTK is able to provide precise on-line track reconstruction for future hadronic collider experiments. The processor, organized in a two-tiered pipelined architecture, execute very fast algorithms based on the use of a large bank of pre-stored patterns of trajectory points (first tier) in combination with full resolution track fitting to refine pattern recognition and to determine off-line quality track parameters. We describe here how the high luminosity simulation results have produced a new organization of the hardware inside the FTK processor core.Comment: 11th ICATPP conferenc

Pierce the ear and stab the spleen

Splenic abscess is a rare but extremely dangerous condition generally spreading from a local, or systemic, focus of infection. We present the case of a young immunocompetent female admitted with sepsis and multiple splenic abscesses. The patient had a recent left ear piercing on the tragus complicated by an ear infection. The presence of a solitary parotid abscess, the absence of other infectious foci on computed tomography scan, the negativity of blood cultures and the absence of endocarditis vegetations led us to think that the most likely culprit was a hematogenous dissemination from the left tragus. The patient was successfully treated with intravenous antibiotics. There had been no need of splenectomy or any other procedure. This rather unique case underscores that splenic abscess should be suspected when a long-lasting fever and pain in the left hypochondrium are present, even when an apparently innocuous invasive procedure, such as a body piercing, is performed

Wehrl information entropy and phase distributions of Schrodinger cat and cat-like states

The Wehrl information entropy and its phase density, the so-called Wehrl phase distribution, are applied to describe Schr\"odinger cat and cat-like (kitten) states. The advantages of the Wehrl phase distribution over the Wehrl entropy in a description of the superposition principle are presented. The entropic measures are compared with a conventional phase distribution from the Husimi Q-function. Compact-form formulae for the entropic measures are found for superpositions of well-separated states. Examples of Schr\"odinger cats (including even, odd and Yurke-Stoler coherent states), as well as the cat-like states generated in Kerr medium are analyzed in detail. It is shown that, in contrast to the Wehrl entropy, the Wehrl phase distribution properly distinguishes between different superpositions of unequally-weighted states in respect to their number and phase-space configuration.Comment: 10 pages, 4 figure

Cellular and Molecular Mechanisms of Liver Fibrosis in Patients with NAFLD

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3+ T cells compared to CD68+ macrophages. While the number of CD68+ macrophages increased with fibrosis severity, the increase in CD3+ T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3+CD45R0+ memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3+CD45RO+FOXP3+CD8- and CD3+CD45RO-FOXP3+CD8- regulatory T cells. A specific increase in the density of CD68+CD11b+ Kupffer cells with liver fibrosis progression was also observed

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches