Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular characterization of a negative regulator of Streptococcus sobrinus surface protein antigen gene

Mutans streptococci have been shown to give rise to variants in terms of expression of surface protein antigens by repeated subculturing of the organisms, which in turn induces changes in colonial morphologies. A 2,850-bp upstream region of the gene (pag) for a surface protein antigen, PAg, of Streptococcus sobrinus MT3791 was determined. Analysis of the nucleotide sequence revealed the existence of three open reading frames (ORFs) located upstream of the pag gene. ORF1 extended from an undetermined further upstream sequence to the termination codon TAG lying 1,943 bp upstream of the pag gene. ORF2, consisting of 609 bp lying 1,689 bp upstream of the pag gene, encoded a protein of 23,347 Da and a protein of 22,792 Da. The synthesis of these proteins (protein antigen regulators) was demonstrated by using the in vitro T7 RNA polymerase/promoter system. ORF3, extending from 314 bp upstream of the pag gene to 712 bp upstream of the pag gene, encoded a protein of 14,802 Da. Disruption of chromosomal ORF2 of parent strain MT3791 by allelic exchange resulted in isogenic mutants, termed PAREm-1 and PAREm-2, that synthesized larger amounts of cell-free and cell-associated PAg than did the parent strain. RNA dot blot analysis demonstrated that expression of PAg-specific mRNA transcripts by mutants PAREm-1 and PAREm-2 was about 32-fold higher than that by strain 3791. Mutants PAREm-1 and PAREm-2 were found to be more hydrophobic than strain MT3791. Resting cells of these mutants attached in larger numbers to saliva-coated hydroxyapatite than did those of the parent strain. These results suggest that protein antigen regulator regulates the expression of PAg gene in a negative fashion, affecting the colonization of tooth surfaces by the organism. Thus, ORF2 is concluded to be a negative regulator gene of PAg synthesis and was designated par.
Nutritional factors in colorectal cancer risk: A case‐control study in majorca

The relationship between energy intake, selected nutrients and colorectal cancer was investigated in the population of Majorca, a Spanish island in the Mediterranean basin. A population‐based case‐control study using food frequency questionnaires was conducted during the period 1984‐1988 and included 286 cases of colorectal cancer, 295 population controls and 203 hospital controls. Food composition tables and ad‐hoc estimates of portion sizes were used to derive intake estimates of 29 nutrients and of total calories. Relative risks were calculated for quartiles of consumption of each specific nutrient after adjustment for total calorie intake. Colorectal cancer was found associated with dietary intake of total calories (RRs = 1.0, 1.6, 1.6, 2.6) and cholesterol (RRs = 1.0, 0.9, 1.7, 1.7) and a protective effect was associated with the intake of fibre from legumes (pulses) and folic acid. The associations and the trends were statistically significant. Among the main energy‐supplying nutrients, after adjustment for calories from other sources, increased risks were found for protein (RRs = 1.0, 1.1, 1.7, 2.5), notably animal protein, and carbohydrates (RRs = 1.0, 1.5, 1.4, 2.2), whereas no effects were found for increased consumption of lipids or saturated fats.
Inertial sensor location analysis in automatic balance assessment

This paper presents the study on the automatic computer-aided balance assessment system. The approach employs ambient assisted living architecture based on inertial sensors. The assessment relies on selected activities from the Berg Balance Scale test by means of the system supplied by a set of features extracted from the accelerometric signals. The feature space dimensionality reduction stage selects the feature vector for each activity and sensor combination using the Fisher's linear discriminant. The system is trained and evaluated using expert scoring of examinations involving 52 patients with different balance abilities. The investigation on the system performance with various sets of available sensors is presented and discussed.
Development of an Educational Spatial Game using an Augmented Reality Authoring Tool

Developing an augmented reality application is usually a task for expert programmers, but using appropriate resources a non-programmer can be successful in such intent. This paper discusses the development of an educational spatial game to be customized by non-programmers users and shows the used authoring tool, the development process of the game and its usability evaluation considering the augmented reality characteristics. Finally, we discuss the game authoring and the customization approach and point out directions to improve the tool and the game.
Pegylated-interferon alpha 2b and ribavirin for recurrent hepatitis C after liver transplantation: From a Canadian experience to recommendations for therapy.

BACKGROUND Recurrent hepatitis C (HCV) after liver transplantation (LT) is often more aggressive and treatments tend to be less successful. Pegylated-interferon and ribavirin are the standard of care for the treatment of HCV; however, there is limited published experience of its use after LT. OBJECTIVE To report the results of pegylated-interferon alpha 2b (PEG-IFN) plus ribavirin for the treatment of recurrent HCV after LT and compare the results with published data. METHODS Thirteen patients with recurrent HCV were treated with PEG-IFN plus ribavirin. Liver biopsies demonstrated early-stage disease in eight patients and advanced fibrosis in five patients. The average starting dose of PEG-IFN was 0.91 microg/kg (range 0.5 microg/kg to 1.1 microg/kg) per week and ribavirin was started at 662 mg (range 0 mg to 1200 mg) per day. PEG-IFN treatment began an average of 24 months after LT (range six to 73 months). The dose of PEG-IFN was increased in four patients but only two reached 1.5 microg/kg. The ribavirin dose was increased in four, reduced in six and only seven patients reached a ribavirin dose greater than 10.6 mg/kg. RESULTS A sustained virological response was seen in four of 13 (30.7%) patients and in four of eight (50%) patients with early-stage disease compared with zero of five patients with advanced fibrosis (P=0.1). Cytopenias were common and therapy was poorly tolerated in four of five patients with advanced fibrosis, including acute cellular rejection in three, renal failure in two, liver decompensation in four and death in three. CONCLUSIONS Although a reasonable sustained virological response can be achieved with the use of PEG-IFN and ribavirin, the treatment is very poorly tolerated by patients with advanced-stage recurrent HCV. Treatment should be instituted before the development of significant fibrosis after LT.
Depression and anxiety disorders associated with headache frequency. The Nord‐Trøndelag Health Study

The aim of this large cross‐sectional population‐based study was to examine the association between migraine, non‐migrainous headache and headache frequency with depression, and anxiety disorders. From 1995 to 1997, all 92 566 inhabitants aged 20 years and above in Nord‐Trøndelag County in Norway were invited to participate in the Nord‐Trøndelag Health Study (‘Helseundersøkelsen i Nord‐Trøndelag’ = HUNT‐2). A total of 64 560 participated, whereof 51 383 subjects (80%) completed a headache questionnaire that was included. Of these 51 383 individuals, 47 257 (92%) completed the depression subscale items and 43 478 (85%), the anxiety subscale items of the Hospital Anxiety and Depression Scale (HADS). Associations were assessed in multivariate analyses, estimating prevalence odds ratios (OR) with 95% confidence intervals (CI). Depression and anxiety disorders as measured by HADS, were significantly associated with migraine (OR = 2.7, 95% CI 2.3–3.2; OR = 3.2, 95% CI 2.8–3.6) and non‐migrainous headache (OR = 2.2, 95% CI 2.0–2.5; OR = 2.7, 95% CI 2.4–3.0) when compared with headache‐free individuals. The association was stronger for anxiety disorders than for depression. The ORs for depression and anxiety disorders amongst both migraine and non‐migrainous sufferers increased with increasing headache frequency. Depression and anxiety disorders are associated with both migraine and non‐migrainous headache, and this association seems more dependent on headache frequency than diagnostic category.
Towards realistic string vacua from branes at singularities

We report on progress towards constructing string models incorporating both realistic D-brane matter content and moduli stabilisation with dynamical low-scale super- symmetry breaking. The general framework is that of local D-brane models embedded into the LARGE volume approach to moduli stabilisation. We review quiver theories on del Pezzo n (dPn) singularities including both D3 and D7 branes. We provide supersymmet- ric examples with three quark/lepton families and the gauge symmetries of the Standard, Left-Right Symmetric, Pati-Salam and Trinification models, without unwanted chiral ex- otics. We describe how the singularity structure leads to family symmetries governing the Yukawa couplings which may give mass hierarchies among the different generations. We outline how these models can be embedded into compact Calabi-Yau compactifications with LARGE volume moduli stabilisation, and state the minimal conditions for this to be possible. We study the general structure of soft supersymmetry breaking. At the singular- ity all leading order contributions to the soft terms (both gravity- and anomaly-mediation) vanish. We enumerate subleading contributions and estimate their magnitude. We also de- scribe model-independent physical implications of this scenario. These include the masses of anomalous and non-anomalous U(1)'s and the generic existence of a new hyperweak force under which leptons and/or quarks could be charged. We propose that such a gauge boson could be responsible for the ghost muon anomaly recently found at the Tevatron's CDF detector.
Cover times, blanket times, and majorizing measures

We exhibit a strong connection between cover times of graphs, Gaussian processes, and Talagrand's theory of majorizing measures. In particular, we show that the cover time of any graph G is equivalent, up to universal constants, to the square of the expected maximum of the Gaussian free field on G, scaled by the number of edges in G. This allows us to resolve a number of open questions. We give a deterministic polynomial-time algorithm that computes the cover time to within an O(1) factor for any graph, answering a question of Aldous and Fill (1994). We also positively resolve the blanket time conjectures of Winkler and Zuckerman (1996), showing that for any graph, the blanket and cover times are within an O(1) factor. The best previous approximation factor for both these problems was O((log log n)2) for n-vertex graphs, due to Kahn, Kim, Lovasz, and Vu (2000).
Links between infant temperament and neurophysiological measures of attention to happy and fearful faces.

BACKGROUND Developing control of attention helps infants to regulate their emotions, and individual differences in attention skills may shape how infants perceive and respond to their socio-emotional environments. This study examined whether the temperamental dimensions of self-regulation and negative emotionality relate to infants' attention skills and whether the emotional content of the attended stimulus affects this relation. METHODS Event-related potentials provided a neurophysiological index of attention (Nc) while 3 to 13-month-old infants viewed images of happy and fearful facial expressions. Temperament was measured via parent report using the Infant Behavior Questionnaire-Revised. RESULTS The peak latency of the Nc was slower for infants with lower regulatory capacity, independent of facial expression. The amplitude of the Nc over right fronto-central electrodes was related to both self-regulation and negative emotionality, but the effects differed by emotion: infants with better self-regulation had larger Nc responses to fearful faces, and infants scoring higher on negative emotionality had larger Nc responses to happy faces. These results are discussed in relation to the development of executive attention networks and their modulation by the amygdala.
Prediction of Human Drug-Drug Interactions from Time-Dependent Inactivation of CYP3A4 in Primary Hepatocytes Using a Population-Based Simulator

Time-dependent inactivation (TDI) of human cytochromes P450 3A4 (CYP3A4) is a major cause of clinical drug-drug interactions (DDIs). Human liver microsomes (HLM) are commonly used as an enzyme source for evaluating the inhibition of CYP3A4 by new chemical entities. The inhibition data can then be extrapolated to assess the risk of human DDIs. Using this approach, under- and overpredictions of in vivo DDIs have been observed. In the present study, human hepatocytes were used as an alternative to HLM. Hepatocytes incorporate the effects of other mechanisms of drug metabolism and disposition (i.e., phase II enzymes and transporters) that may modulate the effects of TDI on clinical DDIs. The in vitro potency (KI and kinact) of five known CYP3A4 TDI drugs (clarithromycin, diltiazem, erythromycin, verapamil, and troleandomycin) was determined in HLM (pooled, n = 20) and hepatocytes from two donors (D1 and D2), and the results were extrapolated to predict in vivo DDIs using a Simcyp population trial-based simulator. Compared with observed DDIs, the predictions derived from HLM appeared to be overestimated. The predictions based on TDI measured in hepatocytes were better correlated with the DDIs (n = 37) observed in vivo (R2 = 0.601 for D1 and 0.740 for D2) than those from HLM (R2 = 0.451). In addition, with the use of hepatocytes a greater proportion of the predictions were within a 2-fold range of the clinical DDIs compared with using HLM. These results suggest that DDI predictions from CYP3A4 TDI kinetics in hepatocytes could provide an alternative approach to balance HLM-based predictions that can sometimes substantially overestimate DDIs and possibly lead to erroneous conclusions about clinical risks.
Phosphosite Mapping of P-type Plasma Membrane H+-ATPase in Homologous and Heterologous Environments*

Background: Protein phosphorylation is an important posttranslational modification. Results: Both in planta and when expressed in yeast, the P-type proton pump is phosphorylated at multiple new positions at its terminal regulatory domains. Conclusion: Multiple methods for phosphopeptide enrichment are required for complete phosphosite mapping. Significance: This work provides a surprising example of functional conservation of protein kinase action between plants and yeast. Phosphorylation is an important posttranslational modification of proteins in living cells and primarily serves regulatory purposes. Several methods were employed for isolating phosphopeptides from proteolytically digested plasma membranes of Arabidopsis thaliana. After a mass spectrometric analysis of the resulting peptides we could identify 10 different phosphorylation sites in plasma membrane H+-ATPases AHA1, AHA2, AHA3, and AHA4/11, five of which have not been reported before, bringing the total number of phosphosites up to 11, which is substantially higher than reported so far for any other P-type ATPase. Phosphosites were almost exclusively (9 of 10) in the terminal regulatory domains of the pumps. The AHA2 isoform was subsequently expressed in the yeast Saccharomyces cerevisiae. The plant protein was phosphorylated at multiple sites in yeast, and surprisingly, seven of nine of the phosphosites identified in AHA2 were identical in the plant and fungal systems even though none of the target sequences in AHA2 show homology to proteins of the fungal host. These findings suggest an unexpected accessibility of the terminal regulatory domain of plasma membrane H+-ATPase to protein kinase action.
Early detection of lean blow out (LBO) via generalized D-Markov machine construction

This paper develops a method for early detection of lean-blow-out (LBO) in combustion systems by extracting low-dimensional features from chemiluminescence time series of optical sensor data. In the proposed method, symbol strings are generated by partitioning the (finite-length) time series to construct a special class of probabilistic finite state automata (PFSA), called D-Markov machines. These PFSA have a deterministic algebraic structure and their states are represented by symbol blocks of length D or less. The states of D-Markov machines are constructed in two steps: (i) state splitting, i.e., the states are split based on their information contents, and (ii) state merging, i.e., two or more states (of possibly different lengths) are merged together to form a new state without any significant loss of their embedded information. The modeling complexity (i.e., the number of states) of a D-Markov machine is observed to be drastically reduced as the combustion system approaches LBO. The prediction of LBO is posed as a pattern classification problem based on different ranges of equivalence ratio of the flame. It is shown that, over a wide range of air-fuel premixing, a generalized D-Markov machine (i.e., with D > 1) performs better than a D-Markov machine with D = 1 as a predictor of LBO.
Simpson's Paradox and the implications for medical trials

This paper describes Simpson's paradox, and explains its serious implications for randomised control trials. In particular, we show that for any number of variables we can simulate the result of a controlled trial which uniformly points to one conclusion (such as 'drug is effective') for every possible combination of the variable states, but when a previously unobserved confounding variable is included every possible combination of the variables state points to the opposite conclusion ('drug is not effective'). In other words no matter how many variables are considered, and no matter how 'conclusive' the result, one cannot conclude the result is truly 'valid' since there is theoretically an unobserved confounding variable that could completely reverse the result.
Current Controller Based on Reduced Order Generalized Integrators for Distributed Generation Systems

This paper presents a current controller based on a stationary reference frame implementation of an integrator in the synchronous reference frame [called here reduced order generalized integrator (ROGI)], suitable for three-phase distributed generation systems. The proposed controller is compared with the traditional second-order generalized integrator (SOGI)-based current controller. It is confirmed that, in normal operation conditions, both controllers have similar performance, requiring the ROGI-based controller much less computational burden than the SOGI counterpart. The proposed controller injects sinusoidal currents synchronized with the grid voltage, without requiring any dedicated synchronization algorithm. Three different current injection strategies are realizable with the same controller structure: balanced current injection, constant instantaneous active power injection, and maximum instantaneous active power injection. A state-variable-based control methodology in the discrete-time domain is presented. It ensures the stability and performance of the closed-loop system, even for high-order controllers and large digital signal processor processing delay. Moreover, it is confirmed that the proposed controller works satisfactorily even on faulty grid conditions.
The RAB5‐GEF Function of RIN1 Regulates Multiple Steps During Listeria monocytogenes Infection

Listeria monocytogenes is a food‐borne pathogenic bacterium that invades intestinal epithelial cells through a phagocytic pathway that relies on the activation of host cell RAB5 GTPases. Listeria monocytogenes must subsequently inhibit RAB5, however, in order to escape lysosome‐mediated destruction. Relatively little is known about upstream RAB5 regulators during L. monocytogenes entry and phagosome escape processes in epithelial cells. Here we identify RIN1, a RAS effector and RAB5‐directed guanine nucleotide exchange factor (GEF), as a host cell factor in L. monocytogenes infection. RIN1 is rapidly engaged following L. monocytogenes infection and is required for efficient invasion of intestinal epithelial cells. RIN1‐mediated RAB5 activation later facilitates the fusion of phagosomes with lysosomes, promoting clearance of bacteria from the host cell. These results suggest that RIN1 is a host cell regulator that performs counterbalancing functions during early and late stages of L. monocytogenes infection, ultimately favoring pathogen clearance.
Complex Visual Hallucinations in Macular Degeneration

A previously healthy elderly patient with a recent onset of macular degeneration presented for evaluation of elaborate complex visual hallucinations. The patient's psychiatric evaluation and level of cognitive functioning were normal. A diagnosis of organic hallucinosis secondary to macular degeneration was made, and the hallucinations ceased with increased sensory stimulation in the hospital. Numerous diagnoses were considered and are discussed, including Charles Bonnet hallucinations and peduncular hallucinosis.
Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial

Purpose To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Methods Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. Results A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, −0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 (p = 0.530) and the carryover effect was not significant (p = 0.283). Conclusions Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.