Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Island TnSmu2 of Streptococcus mutans Harbors a Nonribosomal Peptide Synthetase-Polyketide Synthase Gene Cluster Responsible for the Biosynthesis of Pigments Involved in Oxygen and H2O2 Tolerance

ABSTRACT The oral biofilm community consists of >800 microbial species, among which Streptococcus mutans is considered a primary pathogen for dental caries. The genomic island TnSmu2 of S. mutans comprises >2% of the genome. In this study, we demonstrate that TnSmu2 harbors a gene cluster encoding nonribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and accessory proteins and regulators involved in nonribosomal peptide (NRP) and polyketide (PK) biosynthesis. Interestingly, the sequences of these genes and their genomic organizations and locations are highly divergent among different S. mutans strains, yet each TnSmu2 region encodes NRPS/PKS and accessory proteins. Mutagenesis of the structural genes and putative regulatory genes in strains UA159, UA140, and MT4653 resulted in colonies that were devoid of their yellow pigmentation (for strains UA140 and MT4653). In addition, these mutant strains also displayed retarded growth under aerobic conditions and in the presence of H2O2. High-performance liquid chromatography profiling of cell surface extracts identified unique peaks that were missing in the mutant strains, and partial characterization of the purified product from UA159 demonstrated that it is indeed a hybrid NRP/PK, as predicted. A genomic survey of 94 clinical S. mutans isolates suggests that the TnSmu2 gene cluster may be more prevalent than previously recognized.
Particle rearrangement during liquid phase sintering of Cu–20Zn and Cu–10Sn–10Pb prepared from prealloyed powder

It would be useful to be able to produce brass and bronze components made from prealloyed powders by supersolidus liquid phase sintering. The microstructures obtained in such alloys are sensitive to constituent alloying elements and small change in sintering temperature. Although the formation of liquid during sintering is potentially attractive for densification, the effects of gravity on the liquid phase can result in graded densification. Evaporation of alloying elements and their solubility in the base metal also affect the extent to which heterogeneous cross-sections are obtained. The aim of the present study was to examine the effect of alloying and sintering temperature on the mode of particle rearrangement, and consequently on graded densification, by microstructural and fractographic analysis. Comparing the fracture morphology from top to bottom of the fracture surface is also helpful in developing a model to describe the phenomena during sintering of similar alloys.
Modelling and Forecasting Multivariate Realized Volatility

This paper proposes a methodology for modelling time series of realized covariance matrices in order to forecast multivariate risks. The approach allows for flexible dynamic dependence patterns and guarantees positive definiteness of the resulting forecasts without imposing parameter restrictions. We provide an empirical application of the model, in which we show by means of stochastic dominance tests that the returns from an optimal portfolio based on the model’s forecasts second-order dominate returns of portfolios optimized on the basis of traditional MGARCH models. This result implies that any risk-averse investor, regardless of the type of utility function, would be better-off using our model.
Human Endogenous Retrovirus-K(II) Envelope Induction Protects Neurons during HIV/AIDS

Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and physiological circumstances. HERV-K has been implicated in the pathogenesis of several diseases although the functional consequences of its expression remain unknown. Human immunodeficiency virus (HIV) infection causes neuroinflammation with neuronal damage and death. Herein, we investigated HERV-K(II)/(HML-2) envelope (Env) expression and its actions in the brain during HIV/AIDS. HERV-K(II) Env expression was assessed in healthy brain tissues, autopsied HIV HIV− infected (HIV+) and uninfected (HIV−) brains and in neural cell cultures by real time RT-PCR, massively parallel (deep) sequencing, immunoblotting and immunohistochemistry. Neuronal and neural stem cells expressing HERV-K(II) Env were analyzed in assays of host responses including cellular viability, immune responses and neurobehavioral outcomes. Deep sequencing of human brain transcriptomes disclosed that RNA sequences encoded by HERV-K were among the most abundant HERV sequences detected in human brain. Comparison of different cell types revealed that HERV-K(II) env RNA abundance was highest in cultured human neurons but was suppressed by epidermal growth factor exposure. HERV-K(II) Env immunoreactivity was increased in the cerebral cortex from persons with HIV/AIDS, principally localized in neurons. Human neuronal cells transfected with HERV-K(II) Env exhibited increased NGF and BDNF expression. Expression of HERV-K(II) Env in neuronal cells increased cellular viability and prevented neurotoxicity mediated by HIV-1 Vpr. Intracerebral delivery of HERV-K(II) Env expressed by neural stem cells suppressed TNF-α expression and microglial activation while also improving neurobehavioral deficits in vpr/RAG1−/− mice. HERV-K(II) Env was highly expressed in human neurons, especially during HIV/AIDS, but in addition exerted neuroprotective effects. These findings imply that HERV gene products might exert adaptive effects in circumstances of pathophysiological stress, perhaps underlying the conservation of HERVs within the human genome.
THE ECOLOGY AND GENETICS OF FITNESS IN CHLAMYDOMONAS. VIII. THE DYNAMICS OF ADAPTATION TO NOVEL ENVIRONMENTS AFTER A SINGLE EPISODE OF SEX

Abstract According to classical evolutionary theory, sexual recombination can generate the variation necessary to adapt to changing environments and thereby confer an evolutionary advantage of sexual over asexual reproduction. Using the green alga, Chlamydomonas reinhardtii, we investigated the effect of a single sexual episode on adaptation of heterotrophic growth on different carbon sources. In an initial mixture of isolates, sex was induced and the resulting offspring constituted the sexual populations, along with any unmated vegetative cells; the unmated mixture of isolates represented the asexual populations. Mean and variance in division rates (i.e., fitness) were measured four times during approximately 50 generations of vegetative growth in the dark on all possible combinations of four carbon sources. Consistent with effects of recombination of epistatic genes in linkage disequilibrium, sexual populations initially had a higher variance in fitness, but their mean fitness was lower than that of asexual populations, possibly due to recombinational load. Subsequently, fitness of sexual populations exceeded that of asexual ones, but finally they regained parity in both mean and variance of fitness. Although recombination was not more effective on more complex substrates, these results generally support the idea that sex can accelerate adaptation to novel environments. Corresponding Editor: T. Kawecki
Integrated Regulation of the Type III Secretion System and Other Virulence Determinants in Ralstonia solanacearum

In many plant and animal bacterial pathogens, the Type III secretion system (TTSS) that directly translocates effector proteins into the eukaryotic host cells is essential for the development of disease. In all species studied, the transcription of the TTSS and most of its effector substrates is tightly regulated by a succession of consecutively activated regulators. However, the whole genetic programme driven by these regulatory cascades is still unknown, especially in bacterial plant pathogens. Here, we have characterised the programme triggered by HrpG, a host-responsive regulator of the TTSS activation cascade in the plant pathogen Ralstonia solanacearum. We show through genome-wide expression analysis that, in addition to the TTSS, HrpG controls the expression of a previously undescribed TTSS-independent pathway that includes a number of other virulence determinants and genes likely involved in adaptation to life in the host. Functional studies revealed that this second pathway co-ordinates the bacterial production of plant cell wall-degrading enzymes, exopolysaccharide, and the phytohormones ethylene and auxin. We provide experimental evidence that these activities contribute to pathogenicity. We also show that the ethylene produced by R. solanacearum is able to modulate the expression of host genes and can therefore interfere with the signalling of plant defence responses. These results provide a new, integrated view of plant bacterial pathogenicity, where a common regulator activates synchronously upon infection the TTSS, other virulence determinants and a number of adaptive functions, which act co-operatively to cause disease.
Populations of p53 codon 270 CGT to TGT mutant cells in SKH‐1 mouse skin tumors induced by simulated solar light

The p53 codon 270 CGT to TGT mutation was investigated as a biomarker of sunlight‐induced mutagenesis and carcinogenesis. The relationship between tumor development and abundance of this hotspot mutation was analyzed in mouse skin tumors induced by chronic exposure to simulated solar light (SSL). The 24 tumors analyzed had similar growth kinetics, with an average doubling time of ∼16.4 d. Levels of the p53 codon 270 mutation were quantified in the 24 mouse skin tumors using allele‐specific competitive blocker‐polymerase chain reaction (ACB‐PCR). All tumors contained measurable amounts of the mutation. The p53 codon 270 CGT to TGT mutant fraction (MF) ranged from 2.29 × 10−3 to 9.42 × 10−2, with 3.26 × 10−2 as the median. These p53 MF measurements are lower than expected for an initiating mutation involved in the development of tumors of monoclonal origin. There was no evidence of a correlation between p53 codon 270 MF and either tumor area or an estimate of tumor cell number. Thus, the data do not support the idea that p53 mutation accumulates linearly during tumor development. To investigate how p53 mutation was distributed within tumors, 19 needle biopsies from seven different tumors were analyzed by ACB‐PCR. This analysis demonstrated that p53 codon 270 mutation is heterogeneously distributed within tumors. The long‐term goal of this research is to combine morphological and p53 MF measurements from tissues corresponding to the various stages of tumor development, in order to derive mathematical models relating the p53 codon 270 mutation to the development of SSL‐induced skin tumors. Published 2008 Wiley‐Liss, Inc.
Enhancing the Emergency Department Approach to Pediatric Sexual Assault Care: Implementation of a Pediatric Sexual Assault Response Team Program

Objectives The objectives of this study were to describe the experience of a novel pediatric sexual assault response team (SART) program in the first 3 years of implementation and compare patient characteristics, evaluation, and treatment among subpopulations of patients. Methods This was a retrospective chart review of a consecutive sample of patients evaluated at a pediatric emergency department (ED) who met institutional criteria for a SART evaluation. Associations of evaluation and treatment with sex, menarchal status, and presence of injuries were measured using logistic regression. Results One hundred eighty-four patients met criteria for SART evaluation, of whom 87.5% were female; mean age was 10.1 (SD, 4.6) years. The majority of patients underwent forensic evidence collection (89.1%), which varied by menarchal status among girls (P < 0.01), but not by sex. Evidence of acute anogenital injury on physical examination was found in 20.6% of patients. As per the Centers for Disease Control and Prevention guidelines for acute sexual assault evaluations in pediatric patients, menarchal girls were more likely to undergo testing for sexually transmitted infections and pregnancy (P < 0.01) and to be offered pregnancy, sexually transmitted infection, and HIV prophylaxis (P < 0.01). Conclusions In an effort to improve quality and consistency of acute sexual assault examinations in a pediatric ED, development of a SART program supported the majority of eligible patients undergoing forensic evidence collection. Furthermore, a substantial number of patients had evidence of injury on examination. These findings underscore the importance of having properly trained personnel to support ED care for pediatric victims of acute sexual assault.
Association of Glutathione-S-Transferase (GSTM1 and GSTT1) and FTO Gene Polymorphisms with Type 2 Diabetes Mellitus Cases in Northern India

Abstract Type 2 diabetes mellitus (T2DM) is growing in an epidemic manner across the world and India has the world’s largest number of diabetic subjects. The present study was carried out to investigate the association of glutathione-S-transferase (GSTM1, GSTT1) and fat mass and obesity associated (FTO) gene polymorphisms with T2DM patients and controls, and its role in increasing the susceptibility to T2DM. A total of 198 subjects (101 T2DM patients and 97 controls) participated in this study. GSTM1, GSTT1 and FTO gene polymorphisms in the patients and controls were evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). We observed significant association of GSTM1 positive (p = 0.046) and GSTM1 null (p = 0.046) genotypes with T2DM, while no significant association was found with the FTO gene polymorphism in our study. It seems that the GSTM1 gene polymorphism can be a predictive marker for early identification of a population at risk of T2DM. The potential role of GST and FTO gene polymorphisms as a marker of susceptibility to T2DM needs further studies in a larger number of patients.
Assessing the short-term outcomes of a community-based intervention for overweight and obese children: The MEND 5-7 programme

Objective The aim of this study was to report outcomes of the UK service level delivery of MEND (Mind,Exercise,Nutrition.Do it! ) 5-7, a multicomponent, community-based, healthy lifestyle intervention designed for overweight and obese children aged 5–7 years and their families. Design Repeated measures. Setting Community venues at 37 locations across the UK. Participants 440 overweight or obese children (42% boys; mean age 6.1 years; body mass index (BMI) z-score 2.86) and their parents/carers participated in the intervention. Intervention MEND 5-7 is a 10-week, family-based, child weight-management intervention consisting of weekly group sessions. It includes positive parenting, active play, nutrition education and behaviour change strategies. The intervention is designed to be scalable and delivered by a range of health and social care professionals. Primary and secondary outcome measures The primary outcome was BMI z-score. Secondary outcome measures included BMI, waist circumference, waist circumference z-score, children's psychological symptoms, parenting self-efficacy, physical activity and sedentary behaviours and the proportion of parents and children eating five or more portions of fruit and vegetables. Results 274 (62%) children were measured preintervention and post-intervention (baseline; 10-weeks). Post-intervention, mean BMI and waist circumference decreased by 0.5 kg/m2 and 0.9 cm, while z-scores decreased by 0.20 and 0.20, respectively (p<0.0001). Improvements were found in children's psychological symptoms (−1.6 units, p<0.0001), parent self-efficacy (p<0.0001), physical activity (+2.9 h/week, p<0.01), sedentary activities (−4.1 h/week, p<0.0001) and the proportion of parents and children eating five or more portions of fruit and vegetables per day (both p<0.0001). Attendance at the 10 sessions was 73% with a 70% retention rate. Conclusions Participation in the MEND 5-7 programme was associated with beneficial changes in physical, behavioural and psychological outcomes for children with complete sets of measurement data, when implemented in UK community settings under service level conditions. Further investigation is warranted to establish if these findings are replicable under controlled conditions.
Equalization-Enhanced Phase Noise in Stokes-Vector Direct Detection Systems

In this work, we provide both numerical and experimental investigations of equalization-enhanced phase noise (EEPN) in Stokes-vector direct detection (SV-DD) systems. We show that the influence of EEPN cannot be neglected in high symbol rate SV-DD systems after transmission over several hundred kilometers of fibers when electronic chromatic dispersion compensation and lasers with linewidths of the order of Megahertz are employed. Simulation results are presented to evaluate the dependence of EEPN effects on laser linewidth, transmission distance, and symbol rate. Experiments are then conducted in a 56-Gbaud 16-quadrature amplitude modulation (QAM) SV-DD system to demonstrate the EEPN-induced performance degradation after 320-km transmission over standard single mode fiber (SSMF).
Hysterosalpingo-contrast sonography: is possible to quantify the therapeutic effect of a diagnostic test?

Objective To evaluate the effect of hysterosalpingo-contrast sonography (HyCoSy) on natural conception in the infertile patient. Methods We conducted a prospective observational study recruiting 180 patients admitted to Infertility Center of Ferrara University from January 2010 to February 2012. The essential inclusion criteria was the couple's desire to perform only diagnostic evaluation on infertility causes and to wait for natural conception before proceeding with further management. Couples were investigated with hormonal profile, semen analysis and HyCoSy. Expected time for spontaneous pregnancy was 180 days from HyCoSy. First datation sonography of pregnancy was used calculating time elapsed from HyCoSy at conception. Results Forty patients (22.2%) obtained spontaneous pregnancy within 6 months after HyCoSy. The mean of "conception time" was 75 days. The pregnancy rate was significantly higher in the first 30 days (45%) compared to other the months of observation (p<0.0005). Multiple linear regression analysis showed that maternal age and sterility duration proved independent variables in detecting the "conception time" after HyCoSy (t=3.742, p=0.001, t=2.371, p=0.02, respectively). Conclusion A possible beneficial effect of HyCoSy is feasible especially in the days following its execution. This temporal correlation supports its therapeutic use.
Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage.

BACKGROUND AND PURPOSE Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only. METHODS We used an isotope dilution technique to estimate the magnitude and time course of sympathoadrenal activation in 18 subarachnoid patients. RESULTS Compared with 2 different control groups, the patients with subarachnoid hemorrhage exhibited an approximately 3-fold increase in total-body norepinephrine spillover into plasma within 48 hours after insult (3.2+/-0.3 and 4.2+/-0.7 versus 10.2+/-1.4 nmol/L; P<0.05 versus both). This sympathetic activation persisted throughout the 7- to 10-day examination period and was normalized at the 6-month follow-up visit. CONCLUSIONS The present study has established that massive sympathetic nervous activation occurs in patients after subarachnoid hemorrhage. This overactivation may relate to the well-known cardiac complications described in subarachnoid hemorrhage.
Mathematical modeling of biofilm structure with a hybrid differential-discrete cellular automaton approach.

A hybrid differential-discrete mathematical model has been used to simulate biofilm structures (surface shape, roughness, porosity) as a result of microbial growth in different environmental conditions. In this study, quantitative two- and three-dimensional models were evaluated by introducing statistical measures to characterize the complete biofilm structure, both the surface structure and volume structure. The surface enlargement, coefficient of roughness, fractal dimension of surface, biofilm compactness, and solids hold-up were found to be good measures of biofilm structure complexity. Among many possible factors affecting the biofilm structure, the influence of biomass growth in relation to the diffusive substrate transport was investigated. Porous biofilms, with many channels and voids between the "finger-like" or "mushroom" outgrowth, were obtained in a substrate-transport-limited regime. Conversely, compact and dense biofilms occurred in systems limited by the biomass growth rate and not by the substrate transfer rate. The surface complexity measures (enlargement, roughness, fractal dimension) all increased with increased transport limitation, whereas the volume measures (compactness, solid hold-up) decreased, showing the change from a compact and dense to a highly porous and open biofilm.
Functional observer design for retarded system with interval time-varying delays

ABSTRACT Functional observers are the key solution to numerous practical estimation problems, wherein full-order observers cannot be applied. This paper studies the novel problem of minimum-order functional observer design for time-delay systems with interval time-varying state delays. Moreover, unlike the majority of the existing papers on this topic, which consider either small or unknown delay rates, the delay derivative is assumed to possess an upper bound not limited to be less than one. A new augmented Lyapunov–Krasovskii functional with triple integral terms is employed to derive less conservative delay-dependent sufficient conditions for the stability of the closed-loop observer dynamics, which are expressed in terms of linear matrix inequalities. In addition, contemporary techniques such as Wirtinger-based single- and double-integral inequalities, delay splitting scheme, reciprocally convex approach and convex combination technique, along with the descriptor transformation, are adopted in constructing the new stability criterion that is exploited for obtaining the observer parameters. A genetic-algorithm-based searching schema is proposed to optimally tune a number of weighting parameters in the observer design procedure. Numerical examples and simulation results are demonstrated to confirm the effectiveness and the superiority of the proposed observer design algorithm.
Synergistic Effects of Streptococcal Glucosyltransferases on Adhesive Biofilm Formation

Glucosyltransferases (GTF)-I and GTF-SI of Streptococcus mutans synthesize water-insoluble and both water-soluble and -insoluble glucans, respectively, and play essential roles in the sucrose-dependent adhesion of the organism to tooth surfaces. To examine the interactions of different GTFs on artificial biofilm formed by S. mutans and other oral streptococci, we generated GTF-I- and GTF-SI-hyperproducing isogenic mutant strains. Transformant B42-21, which hyperexpressed GTF-SI, exhibited firm adhesion in the presence of sucrose, whereas transformant B42-10, which hyperexpressed GTF-I, failed to exhibit firm adhesion. Furthermore, co-culture of transformant B42-21 with water-soluble glucan-synthesizing Streptococcus sanguinis yielded firm adhesion, while the addition of dextran T10 to B42-21 growing culture had no effect on adhesion. These findings suggest that GTF-SI has a strong effect on sucrose-dependent adhesion and is essential for biofilm formation on smooth surfaces, in cooperation with water-soluble glucans synthesized de novo by oral streptococci that inherently lack cell adhesion ability.