Miracle-dz/UniFAR-FTUs huggingface dataset:
Consensus perspectives on prophylactic therapy for haemophilia: summary statement

Summary. Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long‐term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality‐of‐life assessment instruments, and cost‐benefit analyses.
Collection of user judgments on spoken dialog system with crowdsourcing

This paper presents an initial attempt at the use of crowd-sourcing for collection of user judgments on spoken dialog systems (SDSs). This is implemented on Amazon Mechanical Turk (MTurk), where a Requester can design a human intelligence task (HIT) to be performed by a large number of Workers efficiently and cost-effectively. We describe a design methodology for two types of HITs - the first targets at fast rating of a large number of dialogs regarding some dimensions of the SDS's performance and the second aims to assess the reliability of Workers on MTurk through the variability in ratings across different Workers. A set of approval rules are also designed to control the quality of ratings from MTurk. At the end of the collection work, user judgments for about 8,000 dialogs rated by around 700Workers are collected in 45 days. We observe reasonable consistency between the manual MTurk ratings and an automatic categorization of dialogs in terms of task completion, which partially verifies the reliability of the approved ratings from MTurk. From the second type of HITs, we also observe moderate inter-rater agreement for ratings in task completion which provides support for the utilization of MTurk as a judgments collection platform. Further research on the exploration of SDS evaluation models could be developed based on the collected corpus.
FIBONACCI-HORNER DECOMPOSITION OF THE MATRIX EXPONENTIAL AND THE FUNDAMENTAL SYSTEM OF SOLUTIONS ∗

This paper concerns the Fibonacci-Horner decomposition of the matrix powers A n and the matrix exponential etA (A ∈ M (r;C), t ∈ R), which is derived fromthe com binatorial properties of the generalized Fibonacci sequences in the algebra of square matrices. More precisely, etA is expressed in a natural way in the so-called Fibonacci-Horner basis with the aid of the dynamical solution of the associated ordinary differential equation. Two simple processes for computing the dynamical solution and the fundamental system of solutions are given. The connection to Verde- Star's approach is discussed. Moreover, an extension to the computation of f (A), where f is an analytic function is initiated. Finally, some illustrative examples are presented.
A time-domain fourth-order-convergent numerical algorithm to integrate black hole perturbations in the extreme-mass-ratio limit

We obtain a fourth-order accurate numerical algorithm to integrate the Zerilli and Regge–Wheeler wave equations, describing perturbations of non-rotating black holes, with source terms due to an orbiting particle. Those source terms contain Dirac's delta and its first derivative. We also re-derive the source of the Zerilli and Regge–Wheeler equations for more convenient definitions of the waveforms that allow direct metric reconstruction (in the Regge–Wheeler gauge).
Variation in Mitochondrial DNA of Vietnamese Pigs: Relationships with Asian Domestic Pigs and Ryukyu Wild Boars

Abstract Mitochondrial DNA (mtDNA) sequences (574 bp) of 30 Vietnamese pigs (large and small) were examined and compared with those of 61 haplotypes from wild boars and domestic pigs from various locations in Asia. The large Vietnamese pigs had genetic links to Ryukyu wild boars in southern Japan. The small Vietnamese pigs were closely related to other East Asian domestic pigs. These results indicate that Vietnamese pigs are genetically diverse and may be descendents of wild and domestic pigs from other regions of Asia.
CLINICAL TRIAL ON DIFFERENT ADJUVANT TREATMENT IN UNIPOLAR DEPRESSION

Depressive disorders are considered to be clinical entities frequently seen in medical practice, causing a very high level of disease burden and are expected to show a rising trend during the coming 20 years. Simptoms of depressive episode in both recurrent depressive disorder and bipolar affective disorder are similar. Despite of theese similarities, recent studies show that depressive episode who appears in both disorders, is different regarding etiology, course and adjacent neurochemical processes. The therapeutic plan used for the treatment of depression usually combines an antidepressant with a benzodiazepine. The current study investigates the therapeutic efficiency of clonazepam versus diazepam in association with paroxetine used to treat the depressive episode – Major Depressive Disorder.
Cardiac Workup of Ischemic Stroke

Stroke is the leading cause of disability in developed countries and the third cause of mortality. Up to 15-30% of ischemic strokes are caused by cardiac sources of emboli being associated with poor prognosis and high index of fatal recurrence. In order to establish an adequate preventive strategy it is crucial to identify the cause of the embolism. After a complete diagnostic workup up to 30% of strokes remain with an undetermined cause, and most of them are attributed to an embolic mechanism suggesting a cardiac origin. There is no consensus in the extent and optimal approach of cardiac workup of ischemic stroke. Clinical features along with brain imaging and the study of the cerebral vessels with ultrasonography or MRI/CT based angiography can identify other causes or lead to think about a possible cardioembolic origin. Atrial fibrillation is the most common cause of cardioembolic stroke. Identification of occult atrial fibrillation is essential. Baseline ECG, serial ECG(’s), cardiac monitoring during the first 48 hours, and Holter monitoring have detection rates varying from 4 to 8% each separately. Extended cardiac monitoring with event loop recorders has shown higher rates of detection of paroxysmal atrial fibrillation. Cardiac imaging with echocardiography is necessary to identify structural sources of emboli. There is insufficient data to determine which is the optimal approach. Transthoracic echocardiography has an acceptable diagnostic yield in patients with heart disease but transesophageal echocardiography has a higher diagnostic yield and is necessary if no cardiac sources have been identified in patients with cryptogenic stroke with embolic mechanism.
Comparison of Invasive and Non-Invasive Tests Diagnosis and Monitoring of Helicobacter Pylori Infection in Children

Background: There are few reports which the tests used for diagnosing Helicobacter pylori infection and monitoring its eradication in children. Study Aims: Prospective evaluation of invasive (gastric histology, rapid urease test [RUT]) and non-invasive (stool antigen [FemtoLab H. pylori], urea breath test [UBT]) tests in the diagnosis of H. pylori infection and post-treatment eradication in children and adolescents. Methods: Ninety-two patients (50 male, 42 female) referred for upper gastrointestinal endoscopy were prospectively enrolled. UBT was performed and stool specimens collected for monoclonal enzyme immunoassay for H. pylori antigen (FemtoLab) 1 to 4 days before endoscopy. H. pylori in gastric biopsies was evaluated by RUT and staining with hematoxylin-eosin and giemsa. Eradication therapy was given to children with abdominal pain and H. pylori gastritis. FemtoLab H. pylori and UBT were repeated 6 weeks after the end of triple therapy. Results: Histology identified H. pylori in 49 of 92 (53%) subjects. Concordance between histology and RUT was found in 78 of 92 children. FemtoLab H. pylori was positive in 41 of 78 (52.6%) children with sensitivity, specificity, positive and negative predictive values of 97.5%, 94.7%, 95.1% and 97.3%, respectively. For UBT, these values were 100%, 96.9%, 97.5% and 100%, respectively. Twenty-six of 36 patients who received triple therapy returned for eradication evaluation. Tests for H. pylori antigen in stool were positive in 10 of 26 and for UBT in 11 of 26. Conclusion: Stool antigen (FemtoLab) and UBT were equally effective in diagnosing and confirming eradication of H. pylori infection in children.
Sex, Age, and Cognitive Correlates of Asymmetries in Thickness of the Cortical Mantle Across the Life Span

We assessed the correlations of age, sex, and cognitive performance with measures of asymmetry in cortical thickness on high-resolution MRIs in 215 healthy human children and adults, 7–59 years of age. A left > right asymmetry in thickness of the cortical mantle was present throughout the entire lateral, dorsal, and mesial surfaces of the frontal lobe, extending into primary sensory, superior parietal, and anterior superior temporal cortices. A right > left asymmetry was present in the lateral, mesial, and dorsal surfaces of the posterior temporal, parietal, and occipital cortices, as well as in the entire inferior surface of the brain. An exaggerated left > right asymmetry was detected in females in anterior brain regions, and an exaggerated right > left asymmetry was detected in males in the orbitofrontal, inferior parietal, and inferior occipital cortices. Weaker moderating effects of sex were scattered along the mesial surface of the brain. Age significantly moderated asymmetry measures in the inferior sensorimotor, inferior parietal, posterior temporal, and inferior occipital cortices. The age × asymmetry interaction derived from a steeper decline in cortical thickness with age in the right hemisphere than in the left on the lateral surface, whereas it derived from a steeper decline with age in the left hemisphere than in the right on the mesial surface. Finally, measures of performance on working memory and vocabulary tasks improved with increasing magnitudes of normal asymmetries in regions thought to support these cognitive capacities.
Experimental Study of Flow Through Geotextiles

Filtration flows through various geotextiles are experimentally studied using a laser Doppler velocimetry technique. Comparisons are presented of the hydraulic behavior of needle-punched and heat-bonded geotextiles, and some influences of fabric damage and flow regimes are demonstrated to characterize geotextile efficiency.
Gαolf Levels Are Regulated by Receptor Usage and Control Dopamine and Adenosine Action in the Striatum

In the striatum, dopamine D1 and adenosine A2A receptors stimulate the production of cAMP, which is involved in neuromodulation and long-lasting changes in gene expression and synaptic function. Positive coupling of receptors to adenylyl cyclase can be mediated through the ubiquitous GTP-binding protein GαS subunit or through the olfactory isoform, Gαolf, which predominates in the striatum. In this study, using double in situ hybridization, we show that virtually all striatal efferent neurons, identified by the expression of preproenkephalin A, substance P, or D1 receptor mRNA, contained high amounts of Gαolf mRNA and undetectable levels of Gαs mRNA. In contrast, the large cholinergic interneurons contained both Gαolf and Gαstranscripts. To assess the functional relationship between dopamine or adenosine receptors and G-proteins, we examined G-protein levels in the striatum of D1 and A2A receptor knock-out mice. A selective increase in Gαolf protein was observed in these animals, without change in mRNA levels. Conversely, Gαolf levels were decreased in animals lacking a functional dopamine transporter. These results indicate that Gαolf protein levels are regulated through D1and A2A receptor usage. To determine the functional consequences of changes in Gαolf levels, we used heterozygous Gαolf knock-out mice, which possess half of the normal Gαolf levels. In these animals, the locomotor effects of amphetamine and caffeine, two psychostimulant drugs that affect dopamine and adenosine signaling, respectively, were markedly reduced. Together, these results identify Gαolf as a critical and regulated component of both dopamine and adenosine signaling.
Absorption, first-pass metabolism, and disposition of itraconazole in rats.

This study examined the pharmacokinetic disposition, oral absorption and hepatic extraction of itraconazole and its active metabolite, hydroxyitraconazole, in rats. After i.v. injection, serum itraconazole concentrations decreased biexponentially, with an average terminal elimination half-life, volume of distribution and systemic clearance of 4.9 h, 6.0 l/kg and 14.2 ml/min/kg, respectively. When given orally, its absorption was low, with a mean absolute bioavailability of 16.6%. The metabolite to parent drug area under the curve (AUC) ratio was higher after oral administration compared with i.v. injection (mean ratio, 2.7 vs. 0.9). The hepatic drug extraction ratio determined after femoral and portal vein administration averaged 18.5%. When hydroxyitraconazole was injected i.v. , the elimination half-life, volume of distribution and systemic clearance of itraconazole averaged 10.0 h, 2.4 l/kg and 3.4 ml/min/kg, respectively. The fraction of the systemically available itraconazole that was metabolized to hydroxyitraconazole was 21.0% and 76.0% after i.v. and oral administration, respectively. In summary, this study is the first reporting the hepatic extraction of itraconazole and the i.v. disposition characteristics of hydroxyitraconazole in rats. Itraconazole is a drug with a low hepatic extraction ratio and its systemic clearance appears to be largely accounted for by hepatic metabolism.
Asymmetric k-center is log* n-hard to approximate

In the ASYMMETRIC <i>k</i>-CENTER problem, the input is an integer <i>k</i> and a complete digraph over <i>n</i> points together with a distance function obeying the directed triangle inequality. The goal is to choose a set of <i>k</i> points to serve as centers and to assign all the points to the centers, so that the maximum distance of any point from its center is as small as possible.We show that the ASYMMETRIC <i>k</i>-CENTER problem is hard to approximate up to a factor of log<sup>*</sup><i>n</i>−<i>O</i>(1) unless <b>NP</b> ⊆ <b>DTIME</b>(<i>n</i><sup>log log</sup> <i>n</i>). Since an <i>O</i>(log<sup>*</sup><i>n</i>)-approximation algorithm is known for this problem, this resolves the asymptotic approximability of ASYMMETRIC <i>k</i>-CENTER. This is the first natural problem whose approximability threshold does not polynomially relate to the known approximation classes. We also resolve the approximability threshold of the metric (symmetric) <i>k</i>-Center problem with costs.
Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo

The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence is provided that the NPXY structural motif within the beta 3 subunit, comprising residues 744-747, is essential for cell morphological and migratory responses mediated by integrin alpha v beta 3 in vitro and in vivo. Transfection of CS-1 melanoma cells with a cDNA encoding the wild-type integrin beta 3 subunit, results in de novo alpha v beta 3 expression and cell attachment, spreading, and migration on vitronectin. CS-1 cells expressing alpha v beta 3 with mutations that disrupt the NPXY sequence interact with soluble vitronectin or an RGD peptide, yet fail to attach, spread, or migrate on immobilized ligand. The biological consequences of these observations are underscored by the finding that CS-1 cells expressing wild-type alpha v beta 3 acquire the capacity to form spontaneous pulmonary metastases in the chick embryo when grown on the chorioallantoic membrane. However, migration-deficient CS-1 cells expressing alpha v beta 3 with mutations in the NPXY sequence lose this ability to metastasize. These findings demonstrate that the NPXY motif within the integrin beta 3 cytoplasmic tail is essential for alpha v beta 3-dependent post-ligand binding events involved in cell migration and the metastatic phenotype of melanoma cells.
Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum–Infected Erythrocytes

The malaria parasite mines actin from the membrane skeleton of its erythrocyte host to generate a cytoskeletal structure. The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host-derived actin cytoskeleton within the cytoplasm of wild-type red blood cells that connected the Maurer’s clefts with the host cell membrane and to which transport vesicles were attached. The actin cytoskeleton and the Maurer’s clefts were aberrant in erythrocytes containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.
MC1R, ASIP, TYR, and TYRP1 gene variants in a population‐based series of multiple primary melanomas

Allelic variants of the low‐penetrance melanoma gene MC1R increase the risk of both melanoma and non‐melanoma skin cancer. Common variants of the genes ASIP, TYR, and TYRP1, which regulate the melanogenic pathway, have also been shown to associate with melanoma. In this population‐based study, we investigated SNPs of MC1R, ASIP, TYR, and TYRP1 as risk factors for development of multiple primary melanomas (MPM) in 388 Norwegian cases. The MPM patients had a significantly higher likelihood of carrying any MC1R variant than the control group of 420 blood donors [86.8 vs. 78.3%, OR = 1.73, and confidence intervals (CI) 1.18–2.52]. When MC1R variants were analyzed individually, Asp84Glu and Arg151Cys were significantly more frequent among the MPM cases than among the controls (OR = 5.77, CI 1.97–16.90, and OR = 1.80, CI 1.36–2.37, respectively). In addition, there was an allele dose‐dependent increase in MPM risk for carriers of red hair color (RHC) MC1R variants. The AH haplotype of ASIP was also a significant risk factor for MPM development (OR = 1.72 and CI 1.12–2.49), whereas no association was observed for previously reported risk variants of the TYR and TYRP1 genes. In summary, by using a population‐based material of high‐risk melanoma cases, we demonstrate a significant effect of both MC1R RHC variants and an ASIP haplotype, but could not replicate an association with postulated risk SNPs of TYR and TYRP1. © 2012 Wiley Periodicals, Inc.
Solving Ill-Posed Linear Systems with GMRES and a Singular Preconditioner

Almost singular linear systems arise in discrete ill-posed problems. Either because of the intrinsic structure of the problem or because of preconditioning, the spectrum of the coefficient matrix is often characterized by a sizable gap between a large group of numerically zero eigenvalues and the rest of the spectrum. Correspondingly, the right-hand side has leading eigencomponents associated with the eigenvalues away from zero. In this paper the effect of this setting in the convergence of the generalized minimal residual (GMRES) method is considered. It is shown that in the initial phase of the iterative algorithm, the residual components corresponding to the large eigenvalues are reduced in norm, and these can be monitored without extra computation. The analysis is supported by numerical experiments. In particular, ill-posed Cauchy problems for partial differential equations with variable coefficients are considered, where the preconditioner is a fast, low-rank solver for the corresponding problem with.
Modeling the Winter–to–Summer Transition of Prokaryotic and Viral Abundance in the Arctic Ocean

One of the challenges in oceanography is to understand the influence of environmental factors on the abundances of prokaryotes and viruses. Generally, conventional statistical methods resolve trends well, but more complex relationships are difficult to explore. In such cases, Artificial Neural Networks (ANNs) offer an alternative way for data analysis. Here, we developed ANN-based models of prokaryotic and viral abundances in the Arctic Ocean. The models were used to identify the best predictors for prokaryotic and viral abundances including cytometrically-distinguishable populations of prokaryotes (high and low nucleic acid cells) and viruses (high- and low-fluorescent viruses) among salinity, temperature, depth, day length, and the concentration of Chlorophyll-a. The best performing ANNs to model the abundances of high and low nucleic acid cells used temperature and Chl-a as input parameters, while the abundances of high- and low-fluorescent viruses used depth, Chl-a, and day length as input parameters. Decreasing viral abundance with increasing depth and decreasing system productivity was captured well by the ANNs. Despite identifying the same predictors for the two populations of prokaryotes and viruses, respectively, the structure of the best performing ANNs differed between high and low nucleic acid cells and between high- and low-fluorescent viruses. Also, the two prokaryotic and viral groups responded differently to changes in the predictor parameters; hence, the cytometric distinction between these populations is ecologically relevant. The models imply that temperature is the main factor explaining most of the variation in the abundances of high nucleic acid cells and total prokaryotes and that the mechanisms governing the reaction to changes in the environment are distinctly different among the prokaryotic and viral populations.
Molecular Evolution in the Drosophila melanogaster Species Subgroup: Frequent Parameter Fluctuations on the Timescale of Molecular Divergence

Although mutation, genetic drift, and natural selection are well established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood. DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree. In this study, we compare patterns of codon usage and protein evolution in 22 genes (>11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup. We assign changes to eight lineages using a maximum-likelihood approach to infer ancestral states. Uncertainty in ancestral reconstructions is taken into account, at least to some extent, by weighting reconstructions by their posterior probabilities. Four of the eight lineages show potentially genomewide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage. Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites. Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages. The magnitude of forces governing silent, intron, and protein evolution appears to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup.