Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Enamel Matrix Protein Amelotin on Biomineralization

Dental caries is one of the most common chronic diseases of people worldwide. Despite recent advances in oral health care and restorative dentistry, the problem of dental caries and erosion remains unresolved due to the lack of knowledge of the natural biomineralization process of tooth tissues. Dental enamel plays a crucial role in preventing the tooth from destruction. However, if damaged or lost, it cannot be regenerated. Understanding the molecular mechanisms behind formation of enamel would not only make restoration of the tissue possible, but would also provide new insights for optimum design of calcium phosphate based biomaterials for dental and orthopedic applications. Amelotin (AMTN) is a recently discovered protein that is primarily expressed during the maturation stage of enamel formation and is localized at the cell-mineral interface on the surface enamel layer. In vivo studies using transgenic mice suggest a direct regulatory function for AMTN in enamel biomineralization. The aim of this PhD project was to test this hypothesis using different in vitro model systems of mineralization. I first showed that recombinant human (rh) AMTN accelerates hydroxyapatite mineralization in a dose-dependent manner when dissolved in the mineralization SBF buffer. Inactivation of a conserved SSEEL motif resulted in significant reduction in the mineralizing ability of the full-length molecule. I also evaluated the importance of phosphorylation in mineralization by testing a synthetic peptide iii containing a short sequence of AMTN including phosphorylated SSEEL in the crystallization assay and showed that it promoted mineralization albeit to a lesser degree than rh-AMTN. Detailed characterization of secretory enamel matrix in overexpressor mice showed rapid and uncontrolled mineralization. I also tested the mineralizing ability of AMTN in an established osteoblast cell line and demonstrated that AMTN transfected or introduced in the culture media in the recombinant form both accelerate the formation of mineralized nodules. AMTN molecules embedded in collagen gel matrix were also able to mineralize the collagen material in the SBF buffer within a few hours. The findings of this PhD project provide solid evidence that AMTN is a promoter of hydroxyapatite mineralization and likely a key player in the establishment of surface enamel layer.
En route to a better integration and evaluation of social capacities in vocal artificial agents

In this talk, work about vocal artificial agent ongoing in the Vocal Interaction Group at LIA, University of Avignon, is presented. A focus is made on the research line aiming at endowing such interactive agents with human-like social abilities. After a short overview of the state-of-the-art in spoken dialogue systems a summary of recent efforts to improve systems' development through online learning using social signals is proposed. Then two examples of skills favoring human-like social interactions are presented: firstly a new turn-taking management scheme based on incremental processing and reinforcement learning, then automatic generation and usage optimisaton of humor traits. These studies converge in enabling to develop interactive systems which could foster studies in human sciences to better understand specificities of human social communication.
Emerging epidemic of drug-resistant tuberculosis in Europe, Russia, China, South America and Asia: current status and global perspectives

Purpose of review Drug resistance, particularly through multidrug-resistant tuberculosis (TB) and extensively drug-resistant TB strains, poses a real threat to TB control worldwide. Recent reports from the WHO and the International Union Against Tuberculosis and Lung Disease demonstrate that the emerging epidemic of drug-resistant TB is a global problem, although emphasis has been placed on several ‘hot spots’ because of lack of good global data. Recent findings The present article is aimed at reviewing the available information on drug-resistant TB with special focus on the features of the epidemic in Europe, Russia, Latin America, Asia and specifically China, and to discuss the global perspectives related to drug-resistant TB control and care. Summary Drug-resistant TB originates from different human errors, including misuse of anti-TB drugs and other reasons related to prescribers, patients and drug producers. Although there is an urgent need for new drugs, a sound public health approach is necessary for their introduction in clinical treatment settings to prevent/avoid creating additional resistance, as has already been observed for first and second-line anti-TB drugs in many settings.
Draft Genome Sequences of Klebsiella pneumoniae Clinical Type Strain ATCC 13883 and Three Multidrug-Resistant Clinical Isolates

ABSTRACT Klebsiella pneumoniae is a Gram-negative human pathogen capable of causing hospital-acquired infections with an increasing risk to human health. The total DNA from four clinically relevant strains was sequenced to >100× coverage, providing high-quality genome assemblies for K. pneumoniae strains ATCC 13883, KP4640, 101488, and 101712.
Incorporating Boosted Regression Trees into Ecological Latent Variable Models

Important ecological phenomena are often observed indirectly. Consequently, probabilistic latent variable models provide an important tool, because they can include explicit models of the ecological phenomenon of interest and the process by which it is observed. However, existing latent variable methods rely on hand-formulated parametric models, which are expensive to design and require extensive preprocessing of the data. Nonparametric methods (such as regression trees) automate these decisions and produce highly accurate models. However, existing tree methods learn direct mappings from inputs to outputs — they cannot be applied to latent variable models. This paper describes a methodology for integrating nonparametric tree methods into probabilistic latent variable models by extending functional gradient boosting. The approach is presented in the context of occupancy-detection (OD) modeling, where the goal is to model the distribution of a species from imperfect detections. Experiments on 12 real and 3 synthetic bird species compare standard and tree-boosted OD models (latent variable models) with standard and tree-boosted logistic regression models (without latent structure). All methods perform similarly when predicting the observed variables, but the OD models learn better representations of the latent process. Most importantly, tree-boosted OD models learn the best latent representations when nonlinearities and interactions are present.
Horizontal Transmission of Mutans Streptococci in Children

It has not been established whether transmission of mutans streptococci occurs between unrelated children older than 4 years of age. The aim of the study was to investigate the possible transmission of mutans streptococci genotypes from child to child in kindergarten. We studied 96 children (ages 5–6 yrs) in three San Francisco Bay Area public schools. Mutans streptococci colonies from each child were isolated from selective culture on Mitis Salivarius Sucrose Bacitracin agar. We used arbitrary primed polymerase chain reactions to determine the mutans streptococci genotypes. Two children (not siblings) in each of the three schools (6%) shared an identical amplitype of S. mutans, unique to each pair. The 19 S. sobrinus amplitypes were found in 12 children, and all were unique to each child. The presence of matching genotypes of S. mutans demonstrates horizontal transmission of this species between unrelated children aged 5–6 years.
Extracellular UTP stimulates electrogenic bicarbonate secretion across CFTR knockout gallbladder epithelium.

The loss of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated transepithelial HCO(3)(-) secretion contributes to the pathogenesis of pancreatic and biliary disease in cystic fibrosis (CF) patients. Recent studies have investigated P2Y(2) nucleotide receptor agonists, e.g., UTP, as a means to bypass the CFTR defect by stimulating Ca(2+)-activated Cl(-) secretion. However, the value of this treatment in facilitating transepithelial HCO(3)(-) secretion is unknown. Gallbladder mucosae from CFTR knockout mice were used to isolate the Ca(2+)-dependent anion conductance during activation of luminal P2Y(2) receptors. In Ussing chamber studies, UTP stimulated a transient peak in short-circuit current (I(sc)) that declined to a stable plateau phase lasting 30-60 min. The plateau I(sc) after UTP was Cl(-) independent, HCO(3)(-) dependent, insensitive to bumetanide, and blocked by luminal DIDS. In pH stat studies, luminal UTP increased both I(sc) and serosal-to-mucosal HCO(3)(-) flux (J(s-->m)) during a 30-min period. Substitution of Cl(-) with gluconate in the luminal bath to inhibit Cl(-)/HCO(3)(-) exchange did not prevent the increase in J(s-->m) and I(sc) during UTP. In contrast, luminal DIDS completely inhibited UTP-stimulated increases in J(s-->m) and I(sc). We conclude that P2Y(2) receptor activation results in a sustained (30-60 min) increase in electrogenic HCO(3)(-) secretion that is mediated via an intracellular Ca(2+)-dependent anion conductance in CF gallbladder.
Uncertainty-Aware Household Appliance Scheduling Considering Dynamic Electricity Pricing in Smart Home

High quality demand side management has become indispensable in the smart grid infrastructure for enhanced energy reduction and system control. In this paper, a new demand side management technique, namely, a new energy efficient scheduling algorithm, is proposed to arrange the household appliances for operation such that the monetary expense of a customer is minimized based on the time-varying pricing model. The proposed algorithm takes into account the uncertainties in household appliance operation time and intermittent renewable generation. Moreover, it considers the variable frequency drive and capacity-limited energy storage. Our technique first uses the linear programming to efficiently compute a deterministic scheduling solution without considering uncertainties. To handle the uncertainties in household appliance operation time and energy consumption, a stochastic scheduling technique, which involves an energy consumption adaptation variable , is used to model the stochastic energy consumption patterns for various household appliances. To handle the intermittent behavior of the energy generated from the renewable resources, the offline static operation schedule is adapted to the runtime dynamic scheduling considering variations in renewable energy. The simulation results demonstrate the effectiveness of our approach. Compared to a traditional scheduling scheme which models typical household appliance operations in the traditional home scenario, the proposed deterministic linear programming based scheduling scheme achieves up to 45% monetary expense reduction, and the proposed stochastic design scheme achieves up to 41% monetary expense reduction. Compared to a worst case design where an appliance is assumed to consume the maximum amount of energy, the proposed stochastic design which considers the stochastic energy consumption patterns achieves up to 24% monetary expense reduction without violating the target trip rate of 0.5%. Furthermore, the proposed energy consumption scheduling algorithm can always generate the scheduling solution within 10 seconds, which is fast enough for household appliance applications.
Explorer Derivative processes for modelling metabolic fluxes

Motivation: One of the challenging questions in modelling biological systems is to characterize the functional forms of the processes that control and orchestrate molecular and cellular phenotypes. Recently proposed methods for the analysis of metabolic pathways, for example, dynamic flux estimation, can only provide estimates of the underlying fluxes at discrete time points but fail to capture the complete temporal behaviour. To describe the dynamic variation of the fluxes, we additionally require the assumption of specific functional forms that can capture the temporal behaviour. However, it also remains unclear how to address the noise which might be present in experimentally measured metabolite concentrations. Results: Here we propose a novel approach to modelling metabolic fluxes: derivative processes that are based on multiple-output Gaussian processes (MGPs), which are a flexible non-parametric Bayesian modelling technique. The main advantages that follow from MGPs approach include the natural non-parametric representation of the fluxes and ability to impute the missing data in between the measurements. Our derivative process approach allows us to model changes in metabolite derivative concentrations and to characterize the temporal behaviour of metabolic fluxes from time course data. Because the derivative of a Gaussian process is itself a Gaussian process, we can readily link metabolite concentrations to metabolic fluxes and vice versa. Here we discuss how this can be implemented in an MGP framework and illustrate its application to simple models, including nitrogen metabolism in Escherichia coli. Availability and implementation: R code is available from the authors upon request. Contact: j.norkunaite@imperial.ac. uk; m.stumpf@imperial.ac. uk Supplementary information: Supplementary data are available at Bioinformatics online. Received on October 20, 2013; revised on December 28, 2013; accepted on January 26, 2014
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.
Kinetics and mechanisms of heterogeneous reaction of NO 2 on CaCO 3 surfaces under dry and wet conditions

Abstract. With increasing NO2 concentration in the troposphere, the importance of NO2 reaction with mineral dust in the atmosphere needs to be evaluated. Until now, little is known about the reaction of NO2 with CaCO3. In this study, the heterogeneous reaction of NO2 on the surface of CaCO3 particles was investigated at 296 K and NO2 concentrations between 4.58×1015 molecules cm−3 to 1.68×1016 molecules cm−3, using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) combined with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), under wet and dry conditions. Nitrate formation was observed under both conditions, while nitrite was observed under wet conditions, indicating the reaction of NO2 on the CaCO3 surface produced nitrate and probably nitrous acid (HONO). Relative humidity (RH) influences both the initial uptake coefficient and the reaction mechanism. At low RH, surface −OH is formed through dissociation of the surface adsorbed water via oxygen vacancy, thus determining the reaction order. As RH increases, water starts to condense on the surface and the gas-liquid reaction of NO2 with the condensed water begins. With high enough RH (>52% in our experiment), the gas-liquid reaction of NO2 with condensed water becomes dominant, forming HNO3 and HONO. The initial uptake coefficient γ0 was determined to be (4.25±1.18)×10−9 under dry conditions and up to (6.56±0.34)×10−8 under wet conditions. These results suggest that the reaction of NO2 on CaCO3 particle is unable to compete with that of HNO3 in the atmosphere. Further studies at lower NO2 concentrations and with a more accurate assessment of the surface area for calculating the uptake coefficient of the reaction of NO2 on CaCO3 particle and to examine its importance as a source of HONO in the atmosphere are needed.
Instructions for use Title Irreversible damage to auditory system functions caused byperinatal hypothyroidism in rats

We examined the effect of perinatal hypothyroidism on auditory function in rats using a prepulse inhibition paradigm. Pregnant rats were treated with the antithyroid drug methimazole (1-methyl-2-mercaptoimidazole) from gestational day 15 to postnatal day 21 via drinking water at concentrations (w/v) of 0 (control), 0.002 (low dose), or 0.02% (high dose). Rats from methimazole-treated mothers were tested at ages 1, 6, and 12 months using techniques to examine prepulse inhibition and startle response. The startle stimulus consisted of 40 ms of white noise at 115 dB, whereas the prepulse, which preceded the startle stimulus by 30 ms, consisted of 20 ms of white noise at 75, 85, or 95 dB. When the prepulse intensity was 75 or 85 dB, the high-dose group showed decreased prepulse inhibition percentages compared with the control and low-dose groups. The reduced percentages of prepulse inhibition did not return to control levels over the 12-month study period. In contrast, no differences in prepulse inhibition were observed among the three dose groups when prepulse intensity was 95 dB. Moreover, the high-dose group displayed excessive reaction to auditory startle stimuli compared with the other groups. Reductions in plasma free thyroxine and body weight gain were observed in the high-dose group. We conclude that perinatal hypothyroidism results in irreversible damage to auditory function in rats.
A complete Verilog-A Gate-All-Around junctionless MOSFET model

In this paper, we present the results of the implementation of a complete DC and AC Gate-All-Around (GAA) long-channel junctionless MOSFET model in Verilog-A code, which will be further used in commercial circuit simulators. The model in Verilog-A is integrated in the SmartSpice circuit simulator and tested in a CMOS inverter. Both p-channel and n-channel device models are validated. Also, the results are compared with data from 3D numerical simulations, showing a very good agreement in all transistors' operation regimes.
A Quantitative Analysis of Hedge Fund Style and Performance

In this analysis we identify dynamic hedge fund strategies quantitatively pursuing a Principal Component Analysis following Fung & Hsieh (1997). We extract five dominant hedge fund strategies each representing similar investment styles and analyse the performance of each strategy by employing a multi-factor model comprising both market indices and passive option strategies along the lines of Agerwal & Naik (2000). We find that that such passive option strategies play an important role in explaining hedge fund returns. Moreover we show that the majority of the five homogenous strategies show neutral performance, but this result turns out to be sensitive to any potential survivorship biases.
Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome.

BACKGROUND Marfan syndrome (MFS) is an underrecognized heritable connective tissue disorder resulting from mutations in the gene for fibrillin-1 (FBN1). Affected patients are at risk for aortic dissection and/or severe ocular and orthopedic problems. The diagnosis is primarily based on a set of well-defined clinical criteria (Ghent nosology). The age-related nature of some clinical manifestations and variable phenotypic expression may hinder the diagnosis, particularly in children. Molecular analysis may be helpful to identify at-risk individuals early and start prophylactic medical treatment. FBN1 mutations have also been reported in patients with Marfan-related conditions, but it is unknown what proportion of all FBN1 mutation carriers they represent. METHODS We reviewed the clinical and molecular data of 171 consecutive patients referred for FBN1 analysis because either MFS was diagnosed or they had signs suggestive of MFS. We compared the incidence of mutations in patients who fulfilled the clinical diagnostic criteria for MFS with those who did not. RESULTS Diagnostic criteria for MFS were fulfilled in 94 patients, 62 (66%) of whom had an FBN1 mutation. A significantly higher incidence of ectopia lentis was found in the patients with MFS with an FBN1 mutation vs those without (P=.04). Among the 77 patients who did not meet the criteria, an FBN1 mutation was found in 9 patients (12%). No correlation was found between the severity of the phenotype and the position and nature of the FBN1 mutation. CONCLUSIONS This study showed a significant difference in the number of FBN1 mutations between patients fulfilling and those not fulfilling the diagnostic criteria for MFS, which seems to be a good predictor of the presence of an FBN1 mutation. A comprehensive clinical evaluation is mandatory before establishing a definitive diagnosis. An FBN1 mutation analysis is helpful to identify individuals at high risk for MFS who need careful follow-up, particularly in families displaying phenotypic variability and in children.
Fibronectin‐binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin α5β1

The ability of Staphylococcus aureus to invade mammalian cells may explain its capacity to colonize mucosa and to persist in tissues after bacteraemia. To date, the underlying molecular mechanisms of cellular invasion by S. aureus are unknown, despite its high prevalence and difficulties in treatment. Here, we show cellular invasion as a novel function for an S. aureus adhesin, previously implicated solely in attachment. S. aureus, but not S. epidermidis, invaded epithelial 293 cells in a temperature‐ and F‐actin‐dependent manner. Formaldehyde‐fixed and live bacteria were equally invasive, suggesting that no active bacterial process was involved. All clinical S. aureus isolates analysed, but only a subset of laboratory strains, were invasive. Fibronectin‐binding proteins (FnBPs) acted as S. aureus invasins, because: (i) FnBP deletion mutants of invasive laboratory strains lost invasiveness; (ii) expression of FnBPs in non‐invasive strains conferred invasiveness; and (iii) the soluble isolated fibronectin‐binding domain of FnBP (D1–D4) completely blocked invasion. Integrin α5β1 served as host cell receptor, which interacted with staphylococcal FnBPs through cellular or soluble fibronectin. FnBP‐deficient mutants lost invasiveness for epithelial cells, endothelial cells and fibroblasts. Thus, fibronectin‐dependent bridging between S. aureus FnBPs and host cell integrin α5β1 is a conserved mechanism for S. aureus invasion of human cells. This may prove useful in developing new therapeutic and vaccine strategies for S. aureus infections.