Miracle-dz/UniFAR-FTUs huggingface dataset:
New Aspects on the Structure of Neutrophil Extracellular Traps from Chronic Obstructive Pulmonary Disease and In Vitro Generation

Polymorphonuclear neutrophils have in recent years attracted new attention due to their ability to release neutrophil extracellular traps (NETs). These web-like extracellular structures deriving from nuclear chromatin have been depicted in ambiguous roles between antimicrobial defence and host tissue damage. NETs consist of DNA strands of varying thickness and are decorated with microbicidal and cytotoxic proteins. Their principal structure has in recent years been characterised at molecular and ultrastructural levels but many features that are of direct relevance to cytotoxicity are still incompletely understood. These include the extent of chromatin decondensation during NET formation and the relative amounts and spatial distribution of the microbicidal components within the NET. In the present work, we analyse the structure of NETs found in induced sputum of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD) using confocal laser microscopy and electron microscopy. In vitro induced NETs from human neutrophils serve for purposes of comparison and extended analysis of NET structure. Results demonstrate that COPD sputa are characterised by the pronounced presence of NETs and NETotic neutrophils. We provide new evidence that chromatin decondensation during NETosis is most extensive and generates substantial amounts of double-helix DNA in ‘beads-on-a-string’ conformation. New information is also presented on the abundance and location of neutrophil elastase (NE) and citrullinated histone H3 (citH3). NE occurs in high densities in nearly all non-fibrous constituents of the NETs while citH3 is much less abundant. We conclude from the results that (i) NETosis is an integral part of COPD pathology; this is relevant to all future research on the etiology and therapy of the disease; and that (ii) release of ‘beads-on-a-string’ DNA studded with non-citrullinated histones is a common feature of in vivo NETosis; this is of relevance to both the antimicrobial and the cytotoxic effects of NETs.
Catastrophic defects oriented testability analysis of a class AB amplifier

Process defects have been recognized as one of the major contributors to the yield loss in CMOS integrated circuits. Any test philosophy without taking into consideration the probable processing defects is likely to compromise the quality of the tested devices. Owing to the specification oriented testing, analog devices frequently suffer from quality and reliability related issues. However, defect oriented testability analysis can be utilized to improve the quality of test methods and reduce the test costs. Furthermore, this analysis can provide inputs to the designer to improve the design robustness against the likely process defects. This methodology has been demonstrated with an example of a class AB amplifier.
Model Checking Population Protocols

Population protocols are a model for parameterized systems in which a set of identical, anonymous, finite-state processes interact pairwise through rendezvous synchronization. In each step, the pair of interacting processes is chosen by a random scheduler. Angluin et al. (PODC 2004) studied population protocols as a distributed computation model. They characterized the computational power in the limit (semi-linear predicates) of a subclass of protocols (the well-specified ones). However, the modeling power of protocols go beyond computation of semi-linear predicates and they can be used to study a wide range of distributed protocols, such as asynchronous leader election or consensus, stochastic evolutionary processes, or chemical reaction networks. Correspondingly, one is interested in checking specifications on these protocols that go beyond the well-specified computation of predicates. In this paper, we characterize the decidability frontier for the model checking problem for population protocols against probabilistic linear-time specifications. We show that the model checking problem is decidable for qualitative objectives, but as hard as the reachability problem for Petri nets - a well-known hard problem without known elementary algorithms. On the other hand, model checking is undecidable for quantitative properties.
Is Efficiency Expensive

We study the simultaneous optimization of efficiency and revenue in pay-per-click keyword auctions in a Bayesian setting. Our main result is that the efficient keyword auction yields near-optimal revenue even under modest competition. In the process, we build on classical results in auction theory to prove that increasing the number of bidders by the number of slots outweighs the benefit of employing the optimal reserve price.
Relative Importance of T-Cell Subsets in Monocytotropic Ehrlichiosis: a Novel Effector Mechanism Involved in Ehrlichia-Induced Immunopathology in Murine Ehrlichiosis

ABSTRACT Infection with gram-negative monocytotropic Ehrlichia strains results in a fatal toxic shock-like syndrome characterized by a decreased number of Ehrlichia-specific CD4+ Th1 cells, the expansion of tumor necrosis factor alpha (TNF-α)-producing CD8+ T cells, and the systemic overproduction of interleukin-10 (IL-10) and TNF-α. Here, we investigated the role of CD4+ and CD8+ T cells in immunity to Ehrlichia and the pathogenesis of fatal ehrlichiosis caused by infection with low- and high-dose (103 and 105 bacterial genomes/mouse, respectively) ehrlichial inocula. The CD4+ T-cell-deficient mice showed exacerbated susceptibility to a lethal high- or low-dose infection and harbored higher bacterial numbers than did wild-type (WT) mice. Interestingly, the CD8+ T-cell-deficient mice were resistant to a low dose but succumbed to a high dose of Ehrlichia. The absence of CD8+ T cells abrogated TNF-α and IL-10 production, reduced tissue injury and bacterial burden, restored splenic CD4+ T-cell numbers, and increased the frequency of Ehrlichia-specific CD4+ Th1 cells in comparison to infected WT mice. Although fatal disease is perforin independent, our data suggested that perforin played a critical role in controlling bacterial burden and mediating liver injury. Similar to WT mice, mortality of infected perforin-deficient mice was associated with CD4+ T-cell apoptosis and a high serum concentration of IL-10. Depletion of IL-10 restored the number of CD4+ and CD8+ T cells in infected WT mice. Our data demonstrate a novel mechanism of immunopathology in which CD8+ T cells mediate Ehrlichia-induced toxic shock, which is associated with IL-10 overproduction and CD4+ T-cell apoptosis.
A labile transcriptional repressor modulates endotoxin tolerance

Tolerance to bacterial lipopolysaccharide (LPS, endotoxin) is an adaptive cellular process whereby exposure to endotoxin induces a subsequent hyporesponsive state characterized by decreased levels of LPS-induced cytokine mRNA and protein. We demonstrate, in a human promonocytic cell line, THP-1, that endotoxin tolerance is manifested by decreased LPS-induced interleukin 1 beta (IL-1 beta) transcription. Inhibition of protein synthesis reverses the tolerant phenotype by inducing transcription of IL-1 beta in the absence of a second stimulus. These results indicate that a labile protein contributes to the endotoxin-tolerant phenotype, and that this factor acts in a dominant repressive manner to inhibit the activity of existing transcription factors. We provide further data that cellular expression of I kappa B-alpha correlates with downregulated IL-1 beta gene expression during endotoxin tolerance, implicating I kappa B-alpha as a potential candidate for the labile repressor identified herein.
Prognostic Significance of Ultrasound Myocardial Tissue Characterization in Patients With Cardiac Amyloidosis

Background—Cycle-dependent variation of myocardial integrated backscatter (CV-IB) is an objective measurement that may detect myocardial abnormalities. However, no data exist about the prognostic value of CV-IB in primary cardiac amyloidosis. Methods and Results—We prospectively examined 208 consecutive biopsy-proven patients with primary amyloidosis. The magnitude of CV-IB was analyzed at the interventricular septum and left ventricular (LV) posterior wall and its prognostic value was compared with standard Doppler measurements with to the Tei index (isovolumic contraction time plus isovolumic relaxation time divided by ejection time). One hundred thirty-three patients had cardiac involvement (mean LV thickness > 12 mm). Forty-one patients (20%) (32 cardiac deaths) died during a mean follow-up of period of 307±156 days. Univariate analysis showed that the CV-IB at the LV posterior wall was the best predictor of cardiac death (P <0.0001) and all-cause death (P < 0.0001). The Tei index did not identify patients at risk of death. Multivariate analysis showed that CV-IB at the LV posterior wall was the only independent predictor of both cardiac and overall deaths. Conclusions—Among patients with cardiac amyloidosis, CV-IB at the LV posterior wall is a powerful predictor of clinical outcome and is superior to standard echocardiographic/Doppler flow indexes.
Investing in Mutual Funds: Does it Pay to Be a Sinner or a Saint in Times of Crisis?

We investigate the performance of US socially responsible funds that employ different stock selection criteria: religious, social and ‘irresponsible’ criteria. Performance is evaluated over different market regimes using a Markov-switching conditional CAPM model that defines different states of the market endogenously. The ‘irresponsible’ fund outperforms in low volatility regimes, but underperforms in high volatility regimes. Furthermore, the risk of the ‘irresponsible’ fund is higher in low volatility regimes and lower in high volatility regimes. Socially responsible funds do not adjust risk according to market conditions. These findings suggest that socially responsible companies might provide better investments during periods of crisis.
A projected Lagrange-d'Alembert principle for forced nonsmooth mechanics and optimal control

This paper extends the projected Hamilton's principle (PHP) formulation of nonsmooth mechanics to include systems with nonconservative forcing according to a projected Lagrange-d'Alembert principle (PLdAP). As seen with the conservative PHP, the PLdAP treats mechanical systems on the whole of their configuration space, captures nonsmooth behaviors using a projection mapping onto the system's feasible space, and offers additional smoothness (relative to classical approaches) in the space of solution curves. Examining implications of the PLdAP for fully actuated optimal control problems, we prove that to identify optimal feasible trajectories it is sufficient to find unconstrained trajectories according to an alternate set of optimality conditions. Focusing on the control problem expressed in the unconstrained space, we approximate optimal solutions with a path planning method that dynamically adds and removes impacts during optimization. The method is demonstrated in determining an optimal policy for a forced particle subject to a nonlinear unilateral constraint.
AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 μU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.
Increasing Trends of Leptospirosis in Northern India: A Clinico-Epidemiological Study

Background Leptospirosis, a zoonosis associated with potentially fatal consequences, has long been a grossly underreported disease in India. There is no accurate estimate of the problem of leptospirosis in non-endemic areas such as north India. Methods/Principal Findings In order to understand the clinical spectrum and risk factors associated with leptospirosis, we carried out a retrospective study in patients with acute febrile illness in north India over the last 5 years (January 2004 to December 2008). There was increased incidence of leptospirosis (11.7% in 2004 to 20.5% in 2008) as diagnosed by IgM ELISA and microscopic agglutination titer in paired acute and convalescent sera. The disease showed a peak during the rainy season (August and September). We followed up 86 cases of leptospirosis regarding their epidemiological pattern, clinical features, laboratory parameters, complications, therapy, and outcome. Mean age of patients was 32.6 years (2.5 years to 78 years) and males (57%) outnumbered females (43%). Infestation of dwellings with rats (53.7%), working in farm lands (44.2%), and contact with animals (62.1%) were commonly observed epidemiological risk factors. Outdoor workers including farmers (32.6%), labourers (11.6%), para-military personnel (2.3%), and sweepers (1.2%) were commonly affected. Modified Faine's criteria could diagnose 76 cases (88.3%). Renal failure (60.5%), respiratory failure (20.9%), the neuroleptospirosis (11.6%), and disseminated intravascular coagulation (DIC) (11.6%) were the commonest complications. Five patients died, giving a case fatality rate of 5.9%. Conclusions/Significance There has been a rapid rise in the incidence of leptospirosis in north India. Severe complications such as renal failure, respiratory failure, neuroleptospirosis, and DIC are being seen with increasing frequency. Increased awareness among physicians, and early diagnosis and treatment, may reduce mortality due to leptospirosis.
Heading recovery from optic flow: comparing performance of humans and computational models

Human observers can perceive their direction of heading with a precision of about a degree. Several computational models of the processes underpinning the perception of heading have been proposed. In the present study we set out to assess which of four candidate models best captured human performance; the four models we selected reflected key differences in terms of approach and methods to modelling optic flow processing to recover movement parameters. We first generated a performance profile for human observers by measuring how performance changed as we systematically manipulated both the quantity (number of dots in the stimulus per frame) and quality (amount of 2D directional noise) of the flow field information. We then generated comparable performance profiles for the four candidate models. Models varied markedly in terms of both their performance and similarity to human data. To formally assess the match between the models and human performance we regressed the output of each of the four models against human performance data. We were able to rule out two models that produced very different performance profiles to human observers. The remaining two shared some similarities with human performance profiles in terms of the magnitude and pattern of thresholds. However none of the models tested could capture all aspect of the human data.
Risks and Benefits of Anticoagulation in Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry

Background—Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC. Methods and Results—We analyzed OAC use among 10 098 patients with AF from 174 community-based outpatient practices enrolled in 2010–2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS2), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS2 scores, from 53% for CHADS2=0 to 80% for CHADS2≥2 (P<0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 (P<0.001). A significant interaction existed between ATRIA and CHADS2 scores (P=0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS2 stroke risk had a smaller impact on use of OAC. Conclusions—In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.
Experimental human exposure to carbon monoxide.

Human volunteers were exposed to carbon monoxide at concentrations of < 1, 25, 50, 100, 200, 500, and 1,000 ppm for periods of one-half to 24 hours. No untoward effects were observed in sedentary males exposed to 100 ppm for eight hours. Exposures producing carboxyhemoglobin saturations greater than 15% to 20% resulted in delayed headaches, changes in the visual evoked response, and impairment of manual coordination.
Behavioral/systems/cognitive Selective Attention Modulates Face-specific Induced Gamma Oscillations Recorded from Ventral Occipitotemporal Cortex Eeg Studies from Subdural Electrodes Have Demonstrated a Face-specific Event-related Potential (face-n200) Recorded from Human Ventral Occipitotemporal Co

an initial obligatory response to faces. This result stands in striking contrast to results of neuroimaging studies that have demonstrated strong task sensitivity of the fusiform hemodynamic response evoked by faces, and thus has created a paradox in the face perception literature. We recorded field potentials directly from the cortical surface of 16 patients while they selectively attended to faces or houses. Here we report that face-specific gamma activity recorded at face-N200 sites is strongly modulated by selective attention, while face-N200 is not. Our results reconcile prior electrophysiological and hemodynamic studies of face perception, and suggest that attentional modulation of the face response follows an initial phase that is largely insensitive to attention.
Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial Cells

Objective—Monocyte proinflammatory activity has been demonstrated in obesity, insulin resistance, and type 2 diabetes, metabolic conditions that are frequently associated with elevated levels of nonesterified fatty acids (NEFA). We therefore tested the hypothesis that NEFA may induce monocyte inflammation. Methods and Results—Monocytes exposed to NEFA for 2 days demonstrated a dose-related increase in intracellular reactive oxygen species (ROS) formation and adhesion to endothelial cells. All of these effects were inhibited by the coaddition of antioxidants such as glutathione or butylated hydroxytoluene, by inhibition of ROS generation by NADPH oxidase inhibitors, and by inhibition of protein kinase C, a recognized stimulator of NAPDH oxidase. Monocytes exposed to NEFA also demonstrated a significant increase in CD11b message expression. Stimulation of monocyte adhesion to endothelial cells by NEFA was inhibited by addition of neutralizing antibodies to either CD11b or CD18. Finally, surface expression of CD11b increased significantly on monocytes as measured by flow cytometry, after their incubation with NEFA. Conclusion—These studies indicate that elevated concentrations of NEFA may enhance integrin facilitated monocyte adhesion to endothelial cells and these effects appear mediated, in part, through activation of NADPH oxidase and oxidative stress.
Source Estimate for the 1960 Chile Earthquake From Joint Inversion of Geodetic and Transoceanic Tsunami Data

The slip distribution of the 1960 Chile earthquake was estimated using geodetic data, local tsunami data, and newly usable transoceanic tsunami data. The large slips triggered a significant tsunami which was recorded by the tide gauges around the Pacific Ocean. We performed a two‐step inversion to estimate the slip distribution. In the first step, we jointly inverted the tsunami waveforms and local geodetic data to recover the ground and seafloor vertical displacement. The transoceanic tsunami data could not be used for waveform inversions until the wave phase and arrival time discrepancies were recently reconciled by improving the long‐wave theory with the phase correction method. The random arrival time discrepancy due to inaccurate local bathymetry and/or instrumental problems was considered by the optimal time alignment. In the second step, we estimated the slip distribution on the plate interface by inverting the vertical displacement obtained in the first step. Checkerboard tests showed that our method and data can resolve displacement at a spatial resolution of at least ~100 km but cannot estimate the rupture velocity. The result for actual data shows a rupture extended about 800 km with a width of about 150 km and three asperities. The large slips are concentrated in the offshore shallow plate interface. Our results indicate that the central and south patches contribute to the large coastal elevation changes at southern source area and high tsunami waves at far field. The estimated moment ranges 1.3–1.9 × 1023 Nm (Mw 9.3–9.4) for rake angles of 90–140°.
Spectral Methods for Numerical Relativity

Equations arising in general relativity are usually too complicated to be solved analytically and one must rely on numerical methods to solve sets of coupled partial differential equations. Among the possible choices, this paper focuses on a class called spectral methods in which, typically, the various functions are expanded in sets of orthogonal polynomials or functions. First, a theoretical introduction of spectral expansion is given with a particular emphasis on the fast convergence of the spectral approximation. We then present different approaches to solving partial differential equations, first limiting ourselves to the one-dimensional case, with one or more domains. Generalization to more dimensions is then discussed. In particular, the case of time evolutions is carefully studied and the stability of such evolutions investigated. We then present results obtained by various groups in the field of general relativity by means of spectral methods. Work, which does not involve explicit time-evolutions, is discussed, going from rapidly-rotating strange stars to the computation of black-hole-binary initial data. Finally, the evolution of various systems of astrophysical interest are presented, from supernovae core collapse to black-hole-binary mergers.