Miracle-dz/UniFAR-FTUs huggingface dataset:
Erythropoietin in Friedreich ataxia

In Friedreich ataxia (FRDA), several candidate substances including erythropoietin (EPO) focus on increase in the amount of frataxin and aim to counteract the consequences of frataxin deficiency. Evidence for recombinant human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes from FRDA patients or control subjects which showed a dose‐dependent increase of frataxin after incubation with different erythropoietins. The mechanism by which EPO induces frataxin increase remains to be elucidated, but may involve post‐transcriptional and/or post‐translational modifications of frataxin or alterations in frataxin half‐life and metabolism. In vivo data on rHuEPO's ability to increase frataxin in FRDA patients is contradictory as studies on the effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and duration. Open‐label studies indicate for sustained frataxin increase, decrease of oxidative stress, and clinical improvement in FRDA patients after administration of rHuEPO. Two randomized controlled studies found acceptable safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures, however, such as frataxin up‐regulation and clinical efficacy were not met. This review will focus on (i) pre‐clinical work on erythropoietins in FRDA and (ii) clinical studies in FRDA patients exposed to erythropoietins.
Real time automated facial expression recognition app development on smart phones

Automated facial expression recognition (AFER) is a crucial technology to and a challenging task for human computer interaction. Previous methods of AFER have incorporated different features and classification methods and use basic testing approaches. In this paper, we employ the best feature descriptor for AFER by empirically evaluating the feature descriptors named the Facial Landmarks descriptor and the Center of Gravity descriptor. We examine each feature descriptor by considering one classification method, such as the Support Vector Machine (SVM) method, with three unique facial expression recognition (FER) datasets. In addition to test accuracies, we present confusion matrices of AFER. We also analyze the effect of using these feature and image resolutions on AFER performance. Our study indicates that the Facial Landmarks descriptor is the best choice to run AFER on mobile phones. The results of our study demonstrate that the proposed facial expression recognition on a mobile phone application is successful and provides up to 96.3% recognition accuracy.
Novel Mutations in a Tissue Culture-Adapted Hepatitis C Virus Strain Improve Infectious-Virus Stability and Markedly Enhance Infection Kinetics

ABSTRACT Hepatitis C virus (HCV) establishes persistent infections and leads to chronic liver disease. It only recently became possible to study the entire HCV life cycle due to the ability of a unique cloned patient isolate (JFH-1) to produce infectious particles in tissue culture. However, despite efficient RNA replication, yields of infectious virus particles remain modest. This presents a challenge for large-scale tissue culture efforts, such as inhibitor screening. Starting with a J6/JFH-1 chimeric virus, we used serial passaging to generate a virus with substantially enhanced infectivity and faster infection kinetics compared to the parental stock. The selected virus clone possessed seven novel amino acid mutations. We analyzed the contribution of individual mutations and identified three specific mutations, core K78E, NS2 W879R, and NS4B V1761L, which were necessary and sufficient for the adapted phenotype. These three mutations conferred a 100-fold increase in specific infectivity compared to the parental J6/JFH-1 virus, and media collected from cells infected with the adapted virus yielded infectious titers as high as 1 × 108 50% tissue culture infective doses (TCID50)/ml. Further analyses indicated that the adapted virus has longer infectious stability at 37°C than the wild type. Given that the adapted phenotype resulted from a combination of mutations in structural and nonstructural proteins, these data suggest that the improved viral titers are likely due to differences in virus particle assembly that result in significantly improved infectious particle stability. This adapted virus will facilitate further studies of the HCV life cycle, virus structure, and high-throughput drug screening.
Clopidogrel Response Variability: Impact of Genetic Polymorphism and Platelet Biomarkers for Predicting Adverse Outcomes Poststenting

The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C19*2 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events.
Caring Presence: Providing a Safe Space for Patients

Previously explored as separate phenomena, this phenomenological-hermeneutic study integrated caring and presence with the experience of caring presence described within the context of a shared nurse practitioner–patient relationship. The results suggest that caring presence is (1) mutual trust and sharing; (2) transcending connectedness; and (3) experience. Research related to caring presence within the nurse practitioner–patient relationship in the context of a managed care outpatient system provides another basis from which to develop nursing knowledge that guides practice within the boundaries of and barriers to care in the technologic world of healthcare.
N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3–[OCH2CH2]n–) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.
Probing Host Pathogen Cross-Talk by Transcriptional Profiling of Both Mycobacterium tuberculosis and Infected Human Dendritic Cells and Macrophages

Background Transcriptional profiling using microarrays provides a unique opportunity to decipher host pathogen cross-talk on the global level. Here, for the first time, we have been able to investigate gene expression changes in both Mycobacterium tuberculosis, a major human pathogen, and its human host cells, macrophages and dendritic cells. Methodology/Principal Findings In addition to common responses, we could identify eukaryotic and microbial transcriptional signatures that are specific to the cell type involved in the infection process. In particular M. tuberculosis shows a marked stress response when inside dendritic cells, which is in accordance with the low permissivity of these specialized phagocytes to the tubercle bacillus and to other pathogens. In contrast, the mycobacterial transcriptome inside macrophages reflects that of replicating bacteria. On the host cell side, differential responses to infection in macrophages and dendritic cells were identified in genes involved in oxidative stress, intracellular vesicle trafficking and phagosome acidification. Conclusions/Significance This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments.
Universal recovery from a decrease of quantum relative entropy

The data processing inequality states that the quantum relative entropy between two states ρ and σ can never increase by applying the same quantum channel N to both states. This inequality can be strengthened with a remainder term in the form of a distance between ρ and the closest recovered state (R∘N)(ρ), where R is a recovery map with the property that σ=(R∘N)(σ). We show the existence of an explicit recovery map that is universal in the sense that it depends only on σ and the quantum channel N to be reversed. This result gives an alternate, information-theoretic characterization of the conditions for approximate quantum error correction.
Implementation and Assessment of an Intervention to Debias Adolescents against Causal Illusions

Researchers have warned that causal illusions are at the root of many superstitious beliefs and fuel many people’s faith in pseudoscience, thus generating significant suffering in modern society. Therefore, it is critical that we understand the mechanisms by which these illusions develop and persist. A vast amount of research in psychology has investigated these mechanisms, but little work has been done on the extent to which it is possible to debias individuals against causal illusions. We present an intervention in which a sample of adolescents was introduced to the concept of experimental control, focusing on the need to consider the base rate of the outcome variable in order to determine if a causal relationship exists. The effectiveness of the intervention was measured using a standard contingency learning task that involved fake medicines that typically produce causal illusions. Half of the participants performed the contingency learning task before participating in the educational intervention (the control group), and the other half performed the task after they had completed the intervention (the experimental group). The participants in the experimental group made more realistic causal judgments than did those in the control group, which served as a baseline. To the best of our knowledge, this is the first evidence-based educational intervention that could be easily implemented to reduce causal illusions and the many problems associated with them, such as superstitions and belief in pseudoscience.
Probabilistic finite-state machines - part II

Probabilistic finite-state machines are used today in a variety of areas in pattern recognition or in fields to which pattern recognition is linked. In part I of this paper, we surveyed these objects and studied their properties. In this part, we study the relations between probabilistic finite-state automata and other well-known devices that generate strings like hidden Markov models and n-grams and provide theorems, algorithms, and properties that represent a current state of the art of these objects.
Multiple Views in Ensembles of Nearest Neighbor Classifiers

Multi-view classification is a machine learning methodology when patterns or objects of interest are represented by a set of dierent views (sets of features) rather than the union of all views. In this paper, multiple views are employed in ensembles of nearest neighbor classifiers where they demonstrate promising results in classifying a challenging data set of protein folds. In particular, up to 4.68% increase in accuracy can be achieved, compared to the best result in single-view classification, thus rendering ensembles of nearest neighbor classifiers employing multiple views an attractive research direction.
AN EVOLVING COMPACT JET IN THE BLACK HOLE X-RAY BINARY MAXI J1836−194

We report striking changes in the broadband spectrum of the compact jet of the black hole transient MAXI J1836−194 over state transitions during its discovery outburst in 2011. A fading of the optical–infrared (IR) flux occurred as the source entered the hard–intermediate state, followed by a brightening as it returned to the hard state. The optical–IR spectrum was consistent with a power law from optically thin synchrotron emission, except when the X-ray spectrum was softest. By fitting the radio to optical spectra with a broken power law, we constrain the frequency and flux of the optically thick/thin break in the jet synchrotron spectrum. The break gradually shifted to higher frequencies as the source hardened at X-ray energies, from ∼1011 to ∼4 × 1013 Hz. The radiative jet luminosity integrated over the spectrum appeared to be greatest when the source entered the hard state during the outburst decay (although this is dependent on the high-energy cooling break, which is not seen directly), even though the radio flux was fading at the time. The physical process responsible for suppressing and reactivating the jet (neither of which are instantaneous but occur on timescales of weeks) is uncertain, but could arise from the varying inner accretion disk radius regulating the fraction of accreting matter that is channeled into the jet. This provides an unprecedented insight into the connection between inflow and outflow, and has implications for the conditions required for jets to be produced, and hence their launching process.
Cloning and expression analysis of the ornithine decarboxylase gene (PbrODC) of the pathogenic fungus Paracoccidioides brasiliensis

We describe the isolation and sequencing of PbrODC, the gene encoding ornithine decarboxylase (ODC) in Paracoccidioides brasiliensis. The gene contains a single open reading frame made of 1413 bp with a single intron (72 bp), and encodes a 447 amino acid polypeptide with a predicted molecular weight of 50.0 kDa, an isoelectric point of 4.9 and a high similarity to other fungal ornithine decarboxylases. Functionality of the gene was demonstrated by transformation into a Saccharomyces cerevisiae odc null mutant. A phylogenetic tree generated with several fungal ODCs provided additional evidence to favour a taxonomic position for P. brasiliensis as an ascomycetous fungus, belonging to the order Onygenales. Expression of the PbrODC gene was determined by Northern analyses during growth of the mycelial and yeast forms, and through the temperature‐regulated dimorphic transition between these two extreme phases. Expression of PbrODC remained constant at all stages of the fungal growth, and did not correlate with a previously observed increase in the activity of ornithine decarboxylase at the onset of the budding process in both yeast growth and mycelium‐to‐yeast transition. Accordingly, post‐transcriptional regulation for the product of PbrODC is suggested. The PbrODC gene sequence is available at the GenBank database under Accession No. AF212867. Copyright © 2004 John Wiley & Sons, Ltd.
Frequency Modulation System and speech perception in the classroom: a systematic literature review.

PURPOSE This review aimed at presenting the benefits regarding the speech perception in noise shown by children who wear hearing aid devices and/or cochlear implants with the Frequency Modulation (FM) System at school. RESEARCH STRATEGY A bibliographic survey was conducted in an electronic database with standardized search until the year 2012, and a manual search was performed by using specific keywords. SELECTION CRITERIA For the selection and evaluation of the scientific studies chosen in the search, criteria were established covering the following aspects: type of study, participants, adopted intervention, and evaluation of results. DATA ANALYSIS The FM system was verified to improve speech perception and speech threshold in noise in all studies. RESULTS Regarding the performance as to type, the best results were obtained when children used the personal FM system, followed by the table and the sound field systems. CONCLUSION After extensive review of national and international literature, it was concluded that the studies indicate the need for further research concerning mainly the impact of the FM system on the school performance of children who have sensory devices coupled to the FM system. Findings in the literature with relation to the publications focused on speech perception in noise did not relate educational and auditory aspects.
Crumbs stabilises epithelial polarity during tissue remodelling

The apicobasal polarity of epithelia depends on the integrated activity of apical and basolateral proteins, and is essential for tissue integrity and body homeostasis. Yet these tissues are frequently on the move as they are sculpted by active morphogenetic cell rearrangements. How does cell polarity survive these stresses? We analyse this question in the renal tubules of Drosophila, a tissue that undergoes dramatic morphogenetic change as it develops. Here we show that, whereas the Bazooka and Scribble protein groups are required for the establishment of tubule cell polarity, the key apical determinant, Crumbs, is required for cell polarity in the tubules only from the time when morphogenetic movements start. Strikingly, if these movements are stalled, polarity persists in the absence of Crumbs. Similar rescue of the ectodermal phenotype of the crumbs mutant when germ-band extension is reduced suggests that Crumbs has a specific, conserved function in stabilising cell polarity during tissue remodelling rather than in its initial stabilisation. We also identify a requirement for the exocyst component Exo84 during tissue morphogenesis, which suggests that Crumbs-dependent stability of epithelial polarity is correlated with a requirement for membrane recycling and targeted vesicle delivery.
Resistance to Six Aminoglycosidic Aminocyclitol Antibiotics Among Enterococci: Prevalence, Evolution, and Relationship to Synergism with Penicillin

Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 μg/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of Streptococcus faecalis subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin.
The gamma-2-herpesvirus bovine herpesvirus 4 causes apoptotic infection in permissive cell lines.

Increasing evidence suggests that regulation of apoptosis in infected cells is associated with several viral infections. The gammaherpesvirus bovine herpesvirus 4 (BHV-4) has been shown to harbor genes with antiapoptotic potentialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by BHV-4 resulted in a cytopathic effect characterized by induction of apoptosis. This phenomenon was confirmed using different techniques to detect apoptosis and using different virus strains and cell targets. Apoptosis induced by BHV-4 was inhibited by (1) treatment with doses of heparin, which completely inhibited virus attachment and infectivity; (2) UV treatment, which completely abrogated infectivity; and (3) treatment with a dose of phosphonoacetic acid, which blocked virus replication. Virus-induced apoptosis was associated with a down-regulation of Bcl-2 expression and was reduced by Z-VAD-FMK, but not by Z-DEVD-FMK (caspase-3-specific) caspase inhibitors. Inhibition of apoptosis by Z-VAD-FMK treatment during infection did not modify virus yield. Therefore, despite the presence of antiapoptotic genes in its genoma, BHV-4 could complete its cycle of productive infection while inducing apoptosis of infected cells. This finding might have implications for the pathobiology of BHV-4 and other gammaherpesviruses in vivo.