Conditional Spatial Quantile: Characterization and Nonparametric Estimation

Conditional quantiles are required in various economic, biomedical or industrial problems. Lack of objective basis for ordering multivariate observations is a major problem in extending the notion of quantiles or conditional quantiles (also called regression quantiles) in a multidimensional setting. We first recall some characterizations of the unconditional spatial quantiles and the corresponding estimators. Then, we consider the conditional case. In this work, we focus our study on the geometric (or spatial) notion of quantiles introduced by Chaudhuri (1992a, 1996). We generalize, in the conditional framework, the Theorem 2.1.2 of Chaudhuri (1996), and we present algorithms allowing the calculation of the unconditional and conditional spatial quantile estimators. Finally, these various concepts are illustrated using simulated data.Conditional Spatial Quantile, Contours, Kernel Estimators, Spatial Quantile

Numerical simulation of the force generated by a superelastic NiTi orthodontic archwire during tooth alignment phase: comparison between different constitutive models

International audienceNickel Titanium (NiTi) Superelastic (SE) Shape Memory Alloys (SMAs) are widely considered for applications that need high reversible strain or high recovery forces. In particular, the SE SMAs present a high interest for biomedical applications such as endodontic and orthodontic apparatus. They are available in a large variety of archwires exerting continuum forces to ensure the dental displacement. The purpose of this study is to report the clinical implications of NiTi SE wires for dental treatment in a given configuration. Three main constitutive models of the literature (Lagoudas and Boyd 1996 Int. J. Plast. 12 805–842, Auricchio and Petrini 2004 Int. J. Numer. Meth. Engng . 61 807–836 and Chemisky et al 2011 Mech. Mater . 68 361–376) are considered for the finite element (FE) numerical simulations of the SMA archwires response. Tensile tests had been carried out in order to identify the material parameters of these constitutive models. The FE numerical study allowed to predict the dental displacement and its corresponding orthodontic force level exerted by the wire in similar conditions to those in the oral environment. This work allows to predict the orthodontic generated load by a NiTi SE archwire with a 0.64 × 0.46 mm 2 rectangular cross section under prescribed thermomechanical conditions. The effect of the temperature and the alveolar bone stiffness on the orthodontic load level and the tooth displacement degree has been investigated. The performed numerical simulations demonstrate that the orthodontic load is sensitive to the displacement magnitude, to the tooth stiffness and to the temperature variations. The obtained forces applied continuously and at a constant level are within the acceptable orthodontic force level range. Some directives are therefore provided to help orthodontists to select the optimal archwire

Osmium uptake, distribution, and 187Os/188Os and 187Re/188Os compositions in Phaeophyceae macroalgae, Fucus vesiculosus: Implications for determining the 187Os/188Os composition of seawater

The osmium isotopic composition (187Os/188Os) of seawater reflects the balance of input from mantle-, continental- and anthropogenic-derived sources. This study utilizes the Phaeophyceae, Fucus vesiculosus, to analyse its Os abundance and uptake, as well as to assess if macroalgae records the Os isotope composition of the seawater in which it lives. The data demonstrates that Os is not located in one specific biological structure within macroalgae, but is found throughout the organism. Osmium uptake was measured by culturing F. vesiculosus non-fertile tips with different concentrations of Os with a known 187Os/188Os composition (∼0.16), which is significantly different from the background isotopic composition of local seawater (∼0.94). The Os abundance of cultured non-fertile tips show a positive correlation to the concentration of the Os doped seawater. Moreover, the 187Os/188Os composition of the seaweed equaled that of the culture medium, stongly confirming the possible use of macroalgae as a biological proxy for the Os isotopic composition of the seawater

Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases.

International audienceThe proliferation of the malaria-causing parasite Plasmodium falciparum within the erythrocyte is concomitant with massive phosphatidylcholine and phosphatidylethanolamine biosynthesis. Based on pharmacological and genetic data, de novo biosynthesis pathways of both phospholipids appear to be essential for parasite survival. The present study characterizes PfCK (P. falciparum choline kinase) and PfEK (P. falciparum ethanolamine kinase), which catalyse the first enzymatic steps of these essential metabolic pathways. Recombinant PfCK and PfEK were expressed as His6-tagged fusion proteins from overexpressing Escherichia coli strains, then purified to homogeneity and characterized. Using murine polyclonal antibodies against recombinant kinases, PfCK and PfEK were shown to be localized within the parasite cytoplasm. Protein expression levels increased during erythrocytic development. PfCK and PfEK appeared to be specific to their respective substrates and followed Michaelis-Menten kinetics. The Km value of PfCK for choline was 135.3+/-15.5 microM. PfCK was also able to phosphorylate ethanolamine with a very low affinity. PfEK was found to be an ethanolamine-specific kinase (Km=475.7+/-80.2 microM for ethanolamine). The quaternary ammonium compound hemicholinium-3 and an ethanolamine analogue, 2-amino-1-butanol, selectively inhibited PfCK or PfEK. In contrast, the bis-thiazolium compound T3, which was designed as a choline analogue and is currently in clinical trials for antimalarial treatment, affected PfCK and PfEK activities similarly. Inhibition exerted by T3 was competitive for both PfCK and PfEK and correlated with the impairment of cellular phosphatidylcholine biosynthesis. Comparative analyses of sequences and structures for both kinase types gave insights into their specific inhibition profiles and into the dual capacity of T3 to inhibit both PfCK and PfEK

MMP-2 and MMP-9 polymorphisms and preeclampsia risk in tunisian arabs : a case-control study

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case–control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women

The Phosphoarginine Phosphatase PtpB from Staphylococcus aureus Is Involved in Bacterial Stress Adaptation during Infection

Staphylococcus aureus continues to be a public health threat, especially in hospital settings. Studies aimed at deciphering the molecular and cellular mechanisms that underlie pathogenesis, host adaptation, and virulence are required to develop effective treatment strategies. Numerous host-pathogen interactions were found to be dependent on phosphatases-mediated regulation. This study focused on the analysis of the role of the low-molecular weight phosphatase PtpB, in particular, during infection. Deletion of ptpB in S. aureus strain SA564 significantly reduced the capacity of the mutant to withstand intracellular killing by THP-1 macrophages. When injected into normoglycemic C57BL/6 mice, the SA564 ∆ptpB mutant displayed markedly reduced bacterial loads in liver and kidney tissues in a murine S. aureus abscess model when compared to the wild type. We also observed that PtpB phosphatase-activity was sensitive to oxidative stress. Our quantitative transcript analyses revealed that PtpB affects the transcription of various genes involved in oxidative stress adaptation and infectivity. Thus, this study disclosed first insights into the physiological role of PtpB during host interaction allowing us to link phosphatase-dependent regulation to oxidative bacterial stress adaptation during infection

Influence of cell mechanics in embryonic bile duct lumen formation: insight from quantitative modeling

In biological and medical literature, alternative hypotheses for initial bile duct lumen formation during embryogenesis exist, which so far remained largely untested. Guided by the quantification of morphological features and expression of genes in developing bile ducts from embryonic mouse liver, these hypotheses were sharpened and data collected that permitted to develop a high resolution individual-based computational model to test the alternative hypotheses in silico. Simulations with this model suggest that successful bile duct lumen formation primarily requires the simultaneous contribution of directed cell division of cholangiocytes, local osmotic effects generated by salt excretion in the lumen, and temporally-controlled differentiation of hepatoblasts to cholangiocytes, with apical constriction of cholangiocytes only moderately affecting luminal size

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors