Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma viremia in macaques infected with simian immunodeficiency virus: plasma viral load early in infection predicts survival

A reliable method for the quantitation of plasma viremia in nonhuman primates infected with simian immunodeficiency virus (SIV) and related viruses is described. This method is based on an established quantitative-competitive PCR format and includes a truncated control for internal assay calibration. Optimization of assay conditions has significantly improved amplification specificity, and interassay variability is comparable to that of commercially available assays for human immunodeficiency virus (HIV) quantitation. This procedure was used to monitor viral loads in a group of Macaca mulatta animals that were infected with SIVsmE660 for over 2 years. Highly diverse profiles of plasma viremia were observed among animals, and high viral loads were associated with more rapid disease progression. Spearman rank correlation analyses were done for survival versus three parameters of viral load: plasma viremia, p27 core antigen, and frequency of infected peripheral blood mononuclear cells. Plasma viremia had the strongest overall correlation and was significantly (P < 0.05 to P < 0.01) associated with survival at 10 of the 13 time points examined. Plasma viremia did not correlate with survival during the primary viremia phase; however, the strength of this correlation increased with time postinfection and, remarkably, viremia levels as early as week 6 postinfection were highly predictive (P < 0.01) of relative survival. These findings are consistent with the available clinical data concerning viral load correlates early in HIV infection, and they provide further support for the view that disease outcome in lentiviral infection may be largely determined by events that occur shortly after infection.
Disentangling Contagion Among Sovereign CDS Spreads During the European Debt Crisis

During the last crisis, developed economies' sovereign credit default swap (hereafter CDS) premia have gained in importance as a tool for approximating credit risk. In this paper, we fit a dynamic factor model to decompose the sovereign CDS spreads of ten OECD economies into three components: a common factor, a second factor driven by European peripheral countries and an idiosyncratic component. We use this decomposition to propose a novel methodology based on the real-time estimates of the model to characterize contagion among the ten series. Our procedure allows the country that triggers contagion in each period, which can be any peripheral economy, to be disentangled. According to our findings, since the onset of the sovereign debt crisis, contagion has played a non-negligible role in the European peripheral countries, which confirms the existence of significant financial linkages between these economies.
The dynein–tubulin motor powers active oscillations and amplification in the hearing organ of the mosquito

The design principles and specific proteins of the dynein–tubulin motor, which powers the flagella and cilia of eukaryotes, have been conserved throughout the evolution of life from algae to humans. Cilia and flagella can support both motile and sensory functions independently, or sometimes in parallel to each other. In this paper we show that this dual sensory–motile role of eukaryotic cilia is preserved in the most sensitive of all invertebrate hearing organs, the Johnston's organ of the mosquito. The Johnston's organ displays spontaneous oscillations, which have been identified as being a characteristic of amplification in the ears of mosquitoes and Drosophila. In the auditory organs of Drosophila and vertebrates, the molecular basis of amplification has been attributed to the gating and adaptation of the mechanoelectrical transducer channels themselves. On the basis of their temperature-dependence and sensitivity to colchicine, we attribute the molecular basis of spontaneous oscillations by the Johnston's organ of the mosquito Culex quinquefasciatus, to the dynein–tubulin motor of the ciliated sensillae. If, as has been claimed for insect and vertebrate hearing organs, spontaneous oscillations epitomize amplification, then in the mosquito ear, this process is independent of mechanotransduction.
Iterative free-energy optimization for recurrent neural networks (INFERNO)

The intra-parietal lobe coupled with the Basal Ganglia forms a working memory that demonstrates strong planning capabilities for generating robust yet flexible neuronal sequences. Neurocomputational models however, often fails to control long range neural synchrony in recurrent spiking networks due to spontaneous activity. As a novel framework based on the free-energy principle, we propose to see the problem of spikes’ synchrony as an optimization problem of the neurons sub-threshold activity for the generation of long neuronal chains. Using a stochastic gradient descent, a reinforcement signal (presumably dopaminergic) evaluates the quality of one input vector to move the recurrent neural network to a desired activity; depending on the error made, this input vector is strengthened to hill-climb the gradient or elicited to search for another solution. This vector can be learned then by one associative memory as a model of the basal-ganglia to control the recurrent neural network. Experiments on habit learning and on sequence retrieving demonstrate the capabilities of the dual system to generate very long and precise spatio-temporal sequences, above two hundred iterations. Its features are applied then to the sequential planning of arm movements. In line with neurobiological theories, we discuss its relevance for modeling the cortico-basal working memory to initiate flexible goal-directed neuronal chains of causation and its relation to novel architectures such as Deep Networks, Neural Turing Machines and the Free-Energy Principle.
Healing of prosthetic arterial grafts.

Numerous synthetic biomaterials have been developed as vascular substitutes. In vitro, ex vivo and in vivo studies have demonstrated that in animals, selected materials, i.e., Dacron and ePTFE (expanded polytetrafluoroethylene) grafts, are successfully incorporated in both the large and the small caliber host arteries through a process which is generally referred to as graft healing. Morphologically, this process consists of a series of complex events including fibrin deposition and degradation, monocyte-macrophage recruitment and flow-oriented cell-layer generation, this last event being the complete endothelialization of the arterial substitute. In contrast to experimental animals, the flow surface of synthetic vascular grafts remains unhealed in humans, particularly in the small caliber conduits. Healing in man consists of graft incorporation by the perigraft fibrous tissue response with a surface covered by more or less compacted, cross-linked fibrin. It is therefore obvious that: i) marked differences in graft healing exist between animals and man; and ii) the usual mechanisms of graft endothelialization are partially ineffective in man. In order to guarantee the patency of synthetic vascular grafts for human small artery bypass, new strategies and approaches have recently been attempted. In particular, the endothelial cell seeding approach has been successfully accomplished in animals and is being experimented in human clinical studies. The problems and results of this biological approach are outlined in this paper.
Optimal radiotherapy of tumour cells following exponential-quadratic survival curves and exponential repopulation kinetics.

A previous paper (Wheldon and Kirk, 1976) presented the mathematical derivation of optimal treatment schedules in radiotherapy, assuming a single-hit multi-target radiation survival curve (see Elkind and Whitmore, 1967) and exponential repopulation kinetics for tumour cells, and utilizing the Cumulative Radiation Effect (CRE) representation of radiation damage to normal connective tissue (Kirk et al., 1971). Recently, attention has been focused on cell survival curves which, contrary to the multi-target model, have non-zero initial slopes (Alper, 1975). Some evidence favours an exponential-quadratic survival curve with non-zero initial slope and continuously steepening slope as radiation dose increases (Neary, 1965; Sinclair, 1969; Kellerer and Rossi, 1971; Chadwick and Leenhouts, 1973; Douglas and Fowler, 1975).
Machine Translation for Twitter

We carried out a study in which we explored the feasibility of machine translation for Twitter for the language pair English and German. As a first step we created a small bilingual corpus of 1,000 tweets. Using this corpus we carried out an analysis of the linguistic features of tweets. We tested different strategies of domain adaptation and found that they improved translation performance. In our experiments we found large differences in performance due to the handling of unknown words. By using xml-markup we were able to reduce this difference. We also replaced special Twitter expressions with placeholders, which enabled us to learn more robust n-gram statistics from Twitter data. We carried out a small-scale human evaluation to balance our automatic scores. Finally, we tested strategies to enforce translation output of legal length. Generating n-best-lists of translation candidates and searching for legal tweets was found to be helpful, but ultimately too unreliable because there was no systematic way to determine the required value of n. We suggested a feature function based on character count as a potential solution.
Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study.

CONTEXT Obesity induces low-grade inflammation that may promote the development of insulin resistance. IL-1 is one of the key inflammatory factors. OBJECTIVE The objective of the study was to demonstrate improvement of insulin sensitivity by blocking IL-1. DESIGN This was a randomized, double-blind, crossover study. SETTING The study was based on ambulatory care. PARTICIPANTS Participants included nondiabetic, obese subjects with the metabolic syndrome. INTERVENTION Intervention included 150 mg anakinra sc once daily or matching placebo for 4 wk. MAIN OUTCOME MEASURE Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. RESULTS A total of 13 of 19 subjects completed the study. Although anakinra treatment resulted in a significantly lower level of inflammation illustrated by a reduction in circulating C-reactive protein concentrations and leukocyte numbers, insulin sensitivity was not significantly different after anakinra treatment (2.8 × 10(-2) ± 0.5 × 10(-2)) compared with placebo treatment (2.4 × 10(-2) ± 0.3 × 10(-2) μmol/kg(-1) · min(-1) · pmol(-1), P = 0.15). Adipose tissue examination, performed to analyze local effects of IL-1 receptor antagonist, showed an increased influx of macrophages after treatment with anakinra most likely due to an injection site reaction caused by the vehicle (0.28 ± 0.05 vs. 0.11 ± 0.01 macrophages per adipocyte, P = 0.005). The differences in individual subject insulin sensitivity after anakinra as compared with placebo between subjects were negatively correlated with macrophage infiltration into the adipose tissue (r(2) = 0.46, P = 0.01). The disposition index increased significantly after anakinra treatment (P = 0.04), reflecting an improvement in β-cell function. CONCLUSIONS Our results suggest that anakinra does not improve insulin sensitivity in obese, insulin-resistant, nondiabetic subjects.
Studies of the processing of the protease which initiates degradation of small, acid-soluble proteins during germination of spores of Bacillus species

Three mutant forms of the protease (GPR) that initiates degradation of small, acid-soluble spore proteins (SASP) during germination of spores of Bacillus species have been generated. In one variant (GPR delta), the putative pro sequence removed in conversion of the GPR zymogen (termed P46) to the active enzyme (termed P41) was deleted. GPR delta was expressed in both Escherichia coli and Bacillus subtilis as a polypeptide of 41 kDa (P41) which was active both in vivo and in vitro. The other two variants had changes in the sequence around the site where the pro sequence is removed, making this sequence even more like that recognized and cleaved by GPR in its SASP substrates. One of these variants (GPRS) was synthesized as P46S in both B. subtilis and E. coli, but P46S was processed to P41S earlier in B. subtilis sporulation than was wild-type P46. The second variant (GPREI) was made as P46EI but underwent extremely rapid processing to P41EI in both E. coli and B. subtilis. Expression of elevated (> 100-fold) levels of GPR delta or GPREI blocked sporulation at the time of synthesis of glucose dehydrogenase. Expression of elevated levels of GPRS or low levels (< 20% of the wild-type level) of GPR delta or GPREI did not retard sporulation, but the SASP level in the resultant spores was greatly reduced. Prolonged incubation of P41 delta, P41EI, or wild-type P41, either in vivo or with purified proteins in vitro, resulted in a second self-cleavage event generating a 39-kDa polypeptide termed P39. The sequence in the P(41)-->P(39) cleavage site was also quite similar to that recognized and cleaved by GPR in SASP. Together, these results strongly support a model in which activation of GPR during sporulation by conversion of P(46) to P(41) is a self-processing event triggered by a change in the spore core environment (i.e., dehydration) which precludes attack of the active P(41) on its SASP substrates. However, in the first minutes of spore germination, rapid spore core hydration allows rapid attack of active GPR on SASP.
Comparison of NucliSens and Roche Monitor Assays for Quantitation of Levels of Human Immunodeficiency Virus Type 1 RNA in Plasma

ABSTRACT We compared the performance of Organon Teknika’s NucliSens and Roche Diagnostic Systems’ Monitor quantitative human immunodeficiency type 1 RNA assays. Both had similar linearity and sensitivity over most of the dynamic range of the assays, although the Monitor assay was superior at the low range of RNA values while the NucliSens assay was more consistent at higher RNA values. NucliSens generally showed less interassay variability.
A Framework for Learning Predictive Structures from Multiple Tasks and Unlabeled Data

One of the most important issues in machine learning is whether one can improve the performance of a supervised learning algorithm by including unlabeled data. Methods that use both labeled and unlabeled data are generally referred to as semi-supervised learning. Although a number of such methods are proposed, at the current stage, we still don't have a complete understanding of their effectiveness. This paper investigates a closely related problem, which leads to a novel approach to semi-supervised learning. Specifically we consider learning predictive structures on hypothesis spaces (that is, what kind of classifiers have good predictive power) from multiple learning tasks. We present a general framework in which the structural learning problem can be formulated and analyzed theoretically, and relate it to learning with unlabeled data. Under this framework, algorithms for structural learning will be proposed, and computational issues will be investigated. Experiments will be given to demonstrate the effectiveness of the proposed algorithms in the semi-supervised learning setting.
Expression of the Oxytocin and V1a Vasopressin Receptors in Human Myometrium in Differing Physiologic States and following Misoprostol Administration

Objective: To assess relative expression levels of mRNA for the oxytocin receptor (OTR) and the V1a vasopressin receptor (V1aR) in human myometrium in various physiologic states and to determine if misoprostol exposure affects the expression of mRNA for these receptors. Study Design: Using semiquantitative reverse transcription-polymerase chain reaction, we analyzed myometrial samples from 37 women (10 menopausal, 10 nongravid premenopausal, 10 gravidae, 7 premenopausal misoprostol-treated nongravid women) for the specific expression of mRNA messages for OTR and V1aR. The presence of the OTR and V1aR protein was confirmed by immunohistochemistry. Results: We found that the expression of OTR was significantly higher in gravid compared to premenopausal nongravid (p < 0.0001), misoprostol-treated (p < 0.001) and menopausal myometrium (p < 0.0001). Differences in V1aR expression were not statistically significant among the four study groups. Conclusion: The expression of OTR mRNA in myometrium is markedly increased during late gestation. V1aR expression is present in all physiologic states, and does not appear to be altered by the presence or absence of labor. Misoprostol administration does not appear to have an effect on OTR and V1aR mRNA receptor expression.
A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents.

OBJECTIVE Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy. METHOD A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10-17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels. RESULTS Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of insulin sensitivity, decreased in treated subjects. Overt diabetes was diagnosed in two subjects before treatment (elevated baseline fasting glucose and insulin values) and in two placebo-treated subjects (one at week 12 and the other after study completion). One subject taking placebo developed impaired fasting glucose. Placebo treatment was associated with the need to perform oral glucose tolerance testing upon study completion, by which three additional subjects were identified with impaired glucose tolerance. No serious adverse events resulted from metformin treatment. CONCLUSIONS Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals.
Changing Taste by Targeting the Ion Channel TRPM5~!2009-12-02~!2010-02-22~!2010-07-26~!

The taste system has evolved to make nutritious foods attractive and toxic substances aversive so as to achieve a maximal health benefit for the organism. However, evolution has not kept up with changes in human diet and lifestyle, including the development of life-saving, but bitter tasting pharmaceuticals, and the over abundance of high calorie, sweet tasting, food. The recent identification of molecular components of the taste system promises to pave the way for the rational design of flavor modifiers that enhance sweetness without caloric consequences or reduce the bitterness of prescription drugs, thereby improving human health. One such molecule is the ion channel TRPM5, which is expressed in taste receptor and other chemosensory cells and is required for bitter and sweet taste sensations. Knowledge of the structure, function and tissue localization of TRPM5 provides a basis for developing pharmacological screens for small molecule taste modifiers.
Confabulation, Memory Deficits, and Frontal Dysfunction

This paper explores potential cognitive deficits underlying confabulation of patient, G.S. , following an anterior communication artery aneurysm. G.S. 's performance on tasks assessing memory for temporal duration, temporal order, and speaker identification is examined as is his recollection of autobiographical events. We compare G.S. with three nonconfabulating patients matched with him for age, education, and neuropsychological measures of memory and frontal deficits and with three age- and education-matched control subjects. Like frontal control patients, G.S. underestimated temporal durations and showed poor source monitoring (speaker identification). In addition, G.S. showed an even more pronounced deficit in recall of autobiographical memories and relatively more detailed reports of laboratory-induced memories for imagined events. We suggest that this configuration of deficits rather than any single factor accounts for G.S. 's tendency to confabulate.
Cost-Effectiveness Analysis of Diagnostic Options for Pneumocystis Pneumonia (PCP)

Background Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. Methods and Findings We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77–90% of patients at $26–51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68–90% of patients at costs of $189–232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options. Conclusions For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.