Pure Parsimony Xor Haplotyping

The haplotype resolution from xor-genotype data has been recently formulated as a new model for genetic studies. The xor-genotype data is a cheaply obtainable type of data distinguishing heterozygous from homozygous sites without identifying the homozygous alleles. In this paper we propose a formulation based on a well-known model used in haplotype inference: pure parsimony. We exhibit exact solutions of the problem by providing polynomial time algorithms for some restricted cases and a fixed-parameter algorithm for the general case. These results are based on some interesting combinatorial properties of a graph representation of the solutions. Furthermore, we show that the problem has a polynomial time k-approximation, where k is the maximum number of xor-genotypes containing a given SNP. Finally, we propose a heuristic and produce an experimental analysis showing that it scales to real-world large instances taken from the HapMap project

Normalized solutions of mass supercritical Schr\"odinger equations with potential

This paper is concerned with the existence of normalized solutions of the nonlinear Schr\"odinger equation $$-\Delta u+V(x)u+\lambda u = |u|^{p-2}u \qquad\text{in $\mathbb{R}^N$}$$ in the mass supercritical and Sobolev subcritical case $2+\frac{4}{N}<p<2^*$. We prove the existence of a solution $(u,\lambda)\in H^1(\mathbb{R}^N)\times\mathbb{R}^+$ with prescribed $L^2$-norm $\|u\|_2=\rho$ under various conditions on the potential $V:\mathbb{R}^N\to\mathbb{R}$, positive and vanishing at infinity, including potentials with singularities. The proof is based on a new min-max argument.Comment: 24 page

Effect of annealing temperature on microstructure and high-temperature tensile behaviour of Ti-6242S alloy produced by Laser Powder Bed Fusion

This work is focussed at investigating the properties of additive manufactured Ti-6242S, a Ti alloy with excellent mechanical strength and stability up to 550 °C. Special attention is given to the effect of different heat treatment routes on microstructure and high-temperature mechanical behaviour of the Ti-6242S alloy produced by Laser Powder Bed Fusion. Annealing was performed in the α/β field (at 940 °C, 960 °C, 980 °C) or above the β transus (at 1050 °C). Annealing step was followed by Ar gas cooling and ageing at 595 °C. The as-built material exhibits high strength and anisotropic behaviour, showing lower fracture elongation in the direction parallel to the build platform. Heat treatments are responsible for a reduction of material strength but an increase in fracture elongation. Tensile tests at high temperature show that the best heat treatment for applications up to 300 °C is the annealing at 940 °C followed by Ar cooling and ageing. For applications at higher temperatures (namely 550 °C, 750 °C) the annealing step should be performed above the β transus temperature, at 1050 °C, to achieve the best tensile properties

Complexity Insights of the Minimum Duplication Problem

International audienceThe Minimum Duplication problem is a well-known problem in phylogenetics and comparative genomics. Given a set of gene trees, the Minimum Duplication problem asks for a species tree that induces the minimum number of gene duplications in the input gene trees. Recently, a variant of the Minimum Duplication problem, called Minimum Duplication Bi-partite, has been introduced, where the goal is to find all pre-duplications, that is duplications that in the evolution precede the first speciation with respect to a species tree. In this paper, we investigate the complexity of both Minimum Duplication and Minimum Duplication Bipartite. First of all, we prove that the Minimum Duplication problem is APX-hard, even when the input consists of five uniquely leaf-labelled gene trees (improving upon known results on the complexity of the problem). Then, we show that the Minimum Duplication Bipartite problem can be solved efficiently with a randomized algorithm when the input gene trees have bounded depth. An extended abstract of this paper appeared in SOFSEM 2012

Asymmetry in sleep spindles and motor outcome in infants with unilateral brain injury

Aim To determine whether interhemispheric difference in sleep spindles in infants with perinatal unilateral brain injury could link to a pathological network reorganization that underpins the development of unilateral cerebral palsy (CP). Method This was a multicentre retrospective study of 40 infants (19 females, 21 males) with unilateral brain injury. Sleep spindles were detected and quantified with an automated algorithm from electroencephalograph records performed at 2 months to 5 months of age. The clinical outcomes after 18 months were compared to spindle power asymmetry (SPA) between hemispheres in different brain regions. Results We found a significantly increased SPA in infants who later developed unilateral CP (n=13, with the most robust interhemispheric difference seen in the central spindles. The best individual-level prediction of unilateral CP was seen in the centro-occipital spindles with an overall accuracy of 93%. An empiric cut-off level for SPA at 0.65 gave a positive predictive value of 100% and a negative predictive value of 93% for later development of unilateral CP. Interpretation Our data suggest that automated analysis of interhemispheric SPA provides a potential biomarker of unilateral CP at a very early age. This holds promise for guiding the early diagnostic process in infants with a perinatally identified brain injury.Peer reviewe

The Synthesis of Kynurenic Acid in Mammals: An Updated Kynurenine Aminotransferase Structural KATalogue

Kynurenic acid (KYNA) is a bioactive compound that is produced along the kynurenine pathway (KP) during tryptophan degradation. In a few decades, KYNA shifted from being regarded a poorly characterized by-product of the KP to being considered a main player in many aspects of mammalian physiology, including the control of glutamatergic and cholinergic synaptic transmission, and the coordination of immunomodulation. The renewed attention being paid to the study of KYNA homeostasis is justified by the discovery of selective and potent inhibitors of kynurenine aminotransferase II, which is considered the main enzyme responsible for KYNA synthesis in the mammalian brain. Since abnormally high KYNA levels in the central nervous system have been associated with schizophrenia and cognitive impairment, these inhibitors promise the development of novel anti-psychotic and pro-cognitive drugs. Here, we summarize the currently available structural information on human and rodent kynurenine aminotransferases (KATs) as the result of global efforts aimed at describing the full complement of mammalian isozymes. These studies highlight peculiar features of KATs that can be exploited for the development of isozyme-specific inhibitors. Together with the optimization of biochemical assays to measure individual KAT activities in complex samples, this wealth of knowledge will continue to foster the identification and rational design of brain penetrant small molecules to attenuate KYNA synthesis, i.e., molecules capable of lowering KYNA levels without exposing the brain to the harmful withdrawal of KYNA-dependent neuroprotective actions

Concurrent and predictive validity of the infant motor profile in infants at risk of neurodevelopmental disorders

BACKGROUND: Preterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl's General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD.METHODS: 86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3months corrected age (CA) using the GMA and at 5months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18months.RESULTS: Results confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman's rho 0.76; p&lt;.001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p&lt;.001) and proves to be the strongest predictor of NDD (p&lt;.001). The comparison of areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%).CONCLUSIONS: Early motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment.TRIAL REGISTRATION: NCT01990183 and NCT03234959 (clinicaltrials.gov)

Directional enhancement of refractive index and tunable wettability of polymeric coatings due to preferential dispersion of colloidal TiO2 nanorods towards their surface

Abstract We demonstrate the fabrication of nanocomposite coatings, of organic-capped colloidal TiO 2 nanorods dispersed into a poly(methyl methacrylate) matrix, with rising value of refractive index from the bottom to the top layers, and UV-induced surface wettability alteration, in a reversible manner. This behaviour is attributable to preferential dispersion of the TiO 2 nanoparticles towards the superficial layers of the coatings. Above a critical TiO 2 loading, the nanorods at the surface form aggregates deteriorating the optical and the surface properties of the nanocomposites. The optimal conditions for nanocomposite films preparation in terms of optimized nanorods dispersion, optical clarity, and surface smoothness are determined

Therapeutic strategies to prevent the recurrence of nasal polyps after surgical treatment: an update and in vitro study on growth inhibition of fibroblasts

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence