Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug safety evaluation of dronedarone in atrial fibrillation

Introduction: Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Areas covered: Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). Expert opinion: The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 – 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.
The sheep as a model for coronary artery bypass surgery

The sheep is considered to be a suitable model for cardiovascular surgery because of its ease of handling, size, and vascular anatomy which bears close resemblance to the human. Several difficulties, however, have limited the use of the sheep for such a purpose—mainly the high infection rate resulting from median sternotomy incision and its susceptibility to intractable ventricular fibrillation (VF) with the slightest manipulation of the heart, and even the risk of short periods of myocardial ischaemia. We have used the sheep model extensively to perform coronary artery bypass surgery and were successful in overcoming these difficulties. Fifty-seven adult female sheep were used to test a new anastomotic device for the creation of a sutureless connection between venous and arterial grafts and the coronary arteries. The study required full access to the heart and great vessels and mobilization of one of the internal mammary arteries. Changing to the left lateral thoracotomy (LLT) approach solved the initial fatal problems of postoperative infected median sternotomy incisions. Aggressive prophylactic treatment with anti-arrhythmic drugs, maintenance of normothermia and myocardial preconditioning rendered the heart much less vulnerable to manipulations and ischaemia. These measures have reduced the mortality rate from 45% to 0% (P <0.0001). With specific operative techniques and pharmaceutical interventions, the sheep can be effectively and safely used as a model for coronary artery surgery.
ACOUSTIC SIGNALS AND STRIDULATORY APPARATUS IN COPEIS INCERTUS SAY (COLEOPTERA SCARABAEIDAE: COPRINAE),

El presente trabajo trata sobre la emisión sonora y el aparato estridulador de los adultos de Coprís incertusSsy y forma parte de los análisis comparativos sobre los mecanismos de comunicación en escarabajos (Coleóptera). las características anatómicas fueron estudiadas desde el punto de vista morfofuncionai a través de la observación de ios movimientos estridulatorios en ejemplares vivos y el análisis de la estructura del aparato estridulador mediante el microscopio electrónico de barrido. El aparato estridulador está compuesto de una pars stridens y un plectrum, el sonido es producido cuando el plecirum raspa contra la pars siridens, debido al movimiento telescópico de los segmentos abdominales contra los élitros. los sonidos de protesta y molestia fueron registrados y analizados para obtener mediciones de tiempo y frecuencia. los sonidos son típicamente emitidos en largas secuencias, de acuerdo con la estructura y morfología del aparato estridulador; los sonidos consisten en series de pulsos cuya proporción de pulsos es modulada, pero con variaciones relativamente uniformes. Cada emisión consiste de dos subunidades ("chírp" disilábico), caracterizado por pulsos con una fase opuesta, ios cuales son producidos durante la extensión hacía arriba del abdomen y su subsecuente retorno a la posición de reposo. la primera subunidad es altamente constante mientras que la última es larga y no siempre se produce, con una proporción de pulsos bajo y más variable, a veces terminando con pulsos bien espaciados. Todos los sonidos analizados son homogéneos en relación con su estructura acústica. Con relación a las diferencias sexuales, los parámetros de tiempo son relativamente homogéneos entre los machos y las hembras, mientras que la proporción de pulsos es significativamente más baja en los machos.
Mitochondrial disturbances in HIV pregnancies

Background:Mitochondrial consequences from foetal exposure to HIV infection and antiretrovirals could be further investigated. Objective:The main objective of this study was to evaluate maternofoetal mitochondrial disturbances in HIV infection and antiretroviral administration in human pregnancies as the aetiopathogenic basis of suboptimal perinatal-clinical features. Design:Cross-sectional, prospective, observational, exploratory and controlled study. Methods:Clinical/epidemiological data of 35 HIV-infected pregnant women and 17 controls were collected. Mitochondrial DNA (mtDNA) and RNA (mtRNA) content (real time-PCR), enzymatic activities and content (spectrophotometry) were measured in leucocytes. Genetic-functional, maternofoetal and molecular-clinical correlations were assessed. Results:Birth weight was lower in infants from HIV-infected mothers compared with controls. MtDNA values were slightly decreased in HIV cases, although not reaching statistical significance. MtRNA values were lower in HIV-infected mothers. Similarly, binary complex II+III enzymatic activity decreased to 50% in both HIV-infected mothers (44.45 ± 3.77%) and their infants (48.79 ± 3.41%) (P = 0.001 and P < 0.001). Global CI+III+IV enzymatic activity was lower in HIV-infected mothers and infants (90.43 ± 2.39% and 51.16 ± 9.30%) (P < 0.005 and P < 0.05). MtDNA content correlated with function in mothers and infants. Maternofoetal parameters correlated at genetic and functional levels. Conclusion:HAART toxicity caused mitochondrial damage in HIV-infected pregnant women and their newborns, being present at a genetic and functional level with a maternofoetal correlation.
Solar influences on spatial patterns of Eurasian winter temperature and atmospheric general circulation anomalies

Solar influences on spatial patterns of Eurasian winter climate and possible mechanisms are investigated based on a multiple linear regression method and multisource observational and reanalysis data. Robust and significant solar signals are detected in Eurasian surface air temperature (SAT), and strong solar activity evidently warms most area of the continent. The spatial pattern of sea level pressure (SLP) responses to solar activity is similar but not identical to that of the North Atlantic Oscillation (NAO). Compared to the NAO, geographic distribution of solar‐induced SLP anomalies shifts eastward, with significantly enhanced influences over northern Eurasia. Relatively weaker solar signals were also found in mid‐to‐upper troposphere. The spatial pattern of 500 hPa geopotential anomalies resembles a negative Scandinavia teleconnection pattern, and the 200 hPa subtropical jet is weakened, while zonal wind at high latitudes is enhanced due to strong solar activity. The anomalous zonal circulations can be attributed to the “top‐down” mechanism. During high solar activity winters, an enhanced stratospheric zonal wind anomaly propagates downward, causing zonal wind anomalies in the troposphere. However, the “bottom‐up” mechanisms may provide more reasonable explanations of the distinct solar influences on Eurasian climate. Solar‐induced strong warm advection in lower atmosphere tends to increase SAT but decrease SLP, resulting in enhanced solar influences over northern Eurasia. Meanwhile, change in the land‐ocean thermal contrast (LOTC) could also amplify the circulation anomaly. Inhomogeneous surface heating caused by anomalous solar activity modifies LOTC, which probably enhances the solar‐induced circulation patterns. Such a positive feedback may potentially strengthen the solar influences.
On Using Approximate Finite Differences in Matrix-Free Newton-Krylov Methods

A Newton-Krylov method is an implementation of Newton's method in which a Krylov subspace method is used to solve approximately the linear systems that characterize steps of Newton's method. Newton-Krylov methods are often implemented in “matrix-free” form, in which the Jacobian-vector products required by the Krylov solver are approximated by finite differences. Here we consider using approximate function values in these finite differences. We first formulate a finite-difference Arnoldi process that uses approximate function values. We then outline a Newton-Krylov method that uses an implementation of the GMRES or Arnoldi method based on this process, and we develop a local convergence analysis for it, giving sufficient conditions on the approximate function values for desirable local convergence properties to hold. We conclude with numerical experiments involving particular function-value approximations suitable for nonlinear diffusion problems. For this case, conditions are given for meeting the convergence assumptions for both lagging and linearizing the nonlinearity in the function evaluation.
Aberrant reinnervation of facial musculature in a subhuman primate

A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zy-gomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.
Sample size formulas for estimating intraclass correlation coefficients with precision and assurance

The number of subjects required to estimate the intraclass correlation coefficient in a reliability study has usually been determined on the basis of the expected width of a confidence interval. However, this approach fails to explicitly consider the probability of achieving the desired interval width and may thus provide sample sizes that are too small to have adequate chance of achieving the desired precision. In this paper, we present a method that explicitly incorporates a prespecified probability of achieving the prespecified width or lower limit of a confidence interval. The resultant closed‐form formulas are shown to be very accurate. Copyright © 2012 John Wiley & Sons, Ltd.
Year‐Round In Situ Measurements of Arctic Low‐Level Clouds: Microphysical Properties and Their Relationships With Aerosols

Two years of continuous in situ measurements of Arctic low‐level clouds have been made at the Mount Zeppelin Observatory (78°56′N, 11°53′E), in Ny‐Ålesund, Spitsbergen. The monthly median value of the cloud particle number concentration (Nc) showed a clear seasonal variation: Its maximum appeared in May–July (65 ± 8 cm−3), and it remained low between October and March (8 ± 7 cm−3). At temperatures warmer than 0 °C, a clear correlation was found between the hourly Nc values and the number concentrations of aerosols with dry diameters larger than 70 nm (N70), which are proxies for cloud condensation nuclei (CCN). When clouds were detected at temperatures colder than 0 °C, some of the data followed the summertime Nc to N70 relationship, while other data showed systematically lower Nc values. The lidar‐derived depolarization ratios suggested that the former (CCN‐controlled) and latter (CCN‐uncontrolled) data generally corresponded to clouds consisting of supercooled water droplets and those containing ice particles, respectively. The CCN‐controlled data persistently appeared throughout the year at Zeppelin. The aerosol‐cloud interaction index (ACI = dlnNc/(3dlnN70)) for the CCN‐controlled data showed high sensitivities to aerosols both in the summer (clean air) and winter–spring (Arctic haze) seasons (0.22 ± 0.03 and 0.25 ± 0.02, respectively). The air parcel model calculations generally reproduced these values. The threshold diameters of aerosol activation (Dact), which account for the Nc of the CCN‐controlled data, were as low as 30–50 nm when N70 was less than 30 cm−3, suggesting that new particle formation can affect Arctic cloud microphysics.
Measuring Sample Quality with Diffusions

Standard Markov chain Monte Carlo diagnostics, like effective sample size, are ineffective for biased sampling procedures that sacrifice asymptotic correctness for computational speed. Recent work addresses this issue for a class of strongly log-concave target distributions by constructing a computable discrepancy measure based on Stein's method that provably determines convergence to the target. We generalize this approach to cover any target with a fast-coupling Ito diffusion by bounding the derivatives of Stein equation solutions in terms of Markov process coupling times. As example applications, we develop computable and convergence-determining diffusion Stein discrepancies for log-concave, heavy-tailed, and multimodal targets and use these quality measures to select the hyperparameters of biased samplers, compare random and deterministic quadrature rules, and quantify bias-variance tradeoffs in approximate Markov chain Monte Carlo. Our explicit multivariate Stein factor bounds may be of independent interest.
The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media*

Detailed knowledge of the rates, equilibria, and mechanism of biochemical reactions has traditionally been acquired through experiments conducted on solutions containing low concentrations (less than about 1 mg/ml) of total protein, nucleic acid, and/or polysaccharide together with buffer salts, low molecular weight substrates, and cofactors as required. In con-trast, biochemical reactions in living systems take place in media containing substantially greater total concentrations (50–400 mg/ml) of macromolecules that may be present in solution and/or in indefinitely large arrays (e.g. cytoskeletal fibers) (1, 2). Because no single macromolecular species may be present at high concentration, but all species taken together occupy a significant fraction of the volume of the medium, such media are referred to as “crowded” (3) and/or “confining” (4) rather than “concentrated,” depending upon whether the macrosolutes are soluble and/or structured. Fig. 1 provides a sche-matic illustration of crowding and confinement in eukaryotic cytoplasm. In such media, nonspecific interactions between macrosolutes contribute significantly to the total free energy of the medium. High concentrations of “background” macromolecules that do not participate directly in a particular test reaction have been observed to induce order-of-magnitude or greater changes in the rates and equilibria of numerous test reactions (see below). To properly assess the physiological role of a particular reaction or set of reactions characterized in vitro, it is important to consider the possible influence of crowding and/or confinement upon the reaction in its physiological milieu.
Vector Compaction Using Dynamic Markov Models

Evaluation of power dissipation is a critical step in the design of today’s ICs. Power disssipation is strongly input pattern dependent and hence, to obtain accurate power values, one must simulate the circuit with a large number of input vectors that typify the application data. The goal of this paper is to present an effective and robust technique for compacting a large sequence of input vectors into a much smaller input sequence so as to reduce the circuit/ gate level simulation time by orders of magnitude and mantain the accuracy of the power estimates. In particular, this paper introduces and characterizes a family of dynamic Markov trees that can model complex spatiotemporal correlations which occur during power estimation both in combinational and sequential circuits. This new framework is very effective and flexible: the Markov model itself is derived through a one-pass traversal of the initial sequence and it can be used after that with any available simulator to derive power consumption. As the results demonstrate, large compaction ratios of 1-2 orders of magnitude can be obtained without significant loss (less than 3% on average) in the accuracy of power estimates.
A Reliability Impact and Assessment of Distributed Generation Integration to Distribution System

The main purpose of this paper is to study the reliability due to the employment of distributed generations (DG) integrated to distribution system. The system under this study is from Provincial Electricity Authority (PEA) that is a part of Thailand’s distribution system. Data of geographic information systems (GIS) including the distance of distribution line and location of load that are parameter of PEA is simulated using digital simulation and electrical network calculation program (DIgSILENT) to analyze the impact of reliability with the installing DG into the distribution system. The system average interruption frequency index (SAIFI), the system average interruption duration index (SAIDI) and interruption cost are assessed as index of reliability by comparing the SAIFI, SAIDI, and interruption cost between the base case (no DG) and the case that DG connected to the distribution system. The results can be summarized by focusing on location of DG, the capacity of DG, the size of load, and the distance of load which are factors able to impact to SAIFI, SAIDI, and interruption cost.
Psychophysical and physiological responses to lifting symmetrical and asymmetrical loads symmetrically and asymmetrically.

Eighteen adult males (mean age 22·6 years, weight 78·6kg and height 176·6cm) participated in a study designed to investigate the effects of symmetrical and asymmetrical lifting on the maximum acceptable weight of lift and the resulting physiological cost. Each subject performed sixty different lifting tasks involving two lifting heights, three lifting frequencies and five containers. For each lifting task, the load was lifted either symmetrically (sagittal lifting) or asymmetrically (turning 90° while continuing to lift). The heart rate and oxygen uptake of the individuals at the maximum acceptable weight of lift were measured. At the end of the experiment, subjects also verbally indicated their preference for symmetrical and asymmetrical lifting. When lifting asymmetrically, subjects accepted approximately 8·5% less weight. There was, however, no difference in the physiological costs when lifting symmetrically or asymmetrically. Lifting asymmetrical loads also resulted in lower maximum acceptable weights.
Depletion of Spleen Macrophages Delays AA Amyloid Development: A Study Performed in the Rapid Mouse Model of AA Amyloidosis

AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM), marginal zone macrophages (MZM), metallophilic marginal zone macrophages (MMZM). MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.
Harmonic forms on manifolds with edges

Let (X, g) be a compact Riemannian stratified space with simple edge singularity. Thus a neighbourhood of the singular stratum is a bundle of truncated cones over a lower dimensional compact smooth manifold. We calculate the various polynomially weighted de Rham cohomology spaces of X, as well as the associated spaces of harmonic forms. In the unweighted case, this is closely related to recent work of Cheeger and Dai [5]. Because the metric g is incomplete, this requires a consideration of the various choices of ideal boundary conditions at the singular set. We also calculate the space of L2 harmonic forms for any complete edge metric on the regular part of X.
Periadventitial fat releases a vascular relaxing factor

Virtually all blood vessels are surrounded by adventitial fat. Adipocytes produce a host of vasoactive substances that may influence vascular contraction. We tested whether or not perivascular adipose tissue modulates contraction of aortic ring preparations. We studied aortic rings surrounded by periadventitial adipose tissue from adult Sprague‐Dawley rats. At a maximum concentration of 300 nM angiotensin II, 6.5 μM serotonin, and 5 μM phenyleph‐rine, the contractile response of intact rings was 95%, 80%, and 30% lower than that of vessels without periadventitial fat. The anticontractile effect of periad‐ventitial fat was reduced by inhibition of ATP‐dependent K+ channels with glibenclamide (3 μM) and by the tyrosine kinase inhibitor genistein (10 μM). Blocking NOS, cyclo‐oxygenase, cytochrome P450, or adenosine receptors did not restore the vascular response in intact vessels. The anticontractile effect of perivascular fat was present in Zucker fa/fa rats, suggesting that leptin receptors were not responsible. Transferring the bath solution from intact vessels, isolated periadventitial tissue, and cultured rat adipocytes to precontracted vessels lacking periadventitial fat resulted in a rapid relaxation. We suggest that perivascular adventitial adipose tissue releases a transferable adventitium‐derived relaxing factor that acts by tyrosine kinase‐dependent activation of K+ channels in vascular smooth muscle cells. —Löhn, M. , Dubrovska, G. , Lauterbach, B. , Luft, F. C. , Gollasch, M. , Sharma, A. M. Periadventitial fat releases a vascular relaxing factor. FASEB J. 16, 1057–1063 (2002)