Rockfall Hazard Analysis at Small Scale: A Numerical Study for the Estimation of Representative Slope Parameters

The identification of rockfall-affected areas depends on a large number of stochastic variables influencing both triggering and propagation phases. Therefore, rockfall hazard assessment presents huge uncertainties linked to the various scales of analysis. At the small scale (e.g. valley scale), a quick evaluation of rockfall hazard zones is generally required in order to highlight the most critical situations where more detailed analyses should be carried out. The Cone Method (Jaboyedoff and Labiouse 2011), recently implemented in the QPROTO plugin for QGIS, allows to reach this goal with simplified geometrical considerations. In a 3D analysis, the energy line angle and the lateral spreading angle α define a cone of propagation whose apex is located in the rockfall source point. The most significant issue in using the plugin is the evaluation of these angles, which must be defined by the users to consider all the rockfall dissipative processes included in the energy line method (Evans and Hungr 1993). In this paper a study concerning the influence of slope properties (forest coverage and slope inclination) and block characteristics (shape and volume) is proposed, in order to provide to the users of the plugin a preliminary dataset of calibrated angles

mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate

Non-syndromic cleft lip with or without cleft palate (NSCLP), the most common human craniofacial malformation, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological, and epigenetic findings. Epigenetic variations associated with NSCLP have been identified; however, functional investigation has been limited. Here, we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a region in mir152 that is frequently hypomethylated in NSCLP cohorts (21–26%), leading to mir152 overexpression. mir152 overexpression in human neural crest cells led to downregulation of spliceosomal, ribosomal, and adherens junction genes. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial cartilage impairment. Also, we suggest that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogous palatal alterations. We therefore propose that mir152 hypomethylation, potentially induced by hypoxia in early development, is a novel and frequent predisposing factor to NSCLP

Pulmonary contusion in a collegiate diver: a case report

Abstract Introduction Pulmonary contusions typically occur after high-energy trauma and have rarely been reported as occurring during participation in sports. This is the first reported case of a pulmonary contusion occurring in a sport other than football. Case Presentation A 19-year-old Caucasian man impacted the water awkwardly after diving off a one-meter springboard. He complained of chest discomfort and produced immediate hemoptysis. Computed tomography confirmed the diagnosis of pulmonary contusion. The athlete recovered without complications and returned to activity one week after injury. Conclusion Immediate hemoptysis following blunt chest trauma during sports activity may indicate an underlying pulmonary contusion. No specific guidelines exist for return to athletic competition following pulmonary contusion, but a progressive return to activities once symptoms resolve appears to be a reasonable approach.</p

Magnetothermodynamics of BPS baby skyrmions

The magnetothermodynamics of skyrmion type matter described by the gauged BPS baby Skyrme model at zero temperature is investigated. We prove that the BPS property of the model is preserved also for boundary conditions corresponding to an asymptotically constant magnetic field. The BPS bound and the corresponding BPS equations saturating the bound are found. Further, we show that one may introduce pressure in the gauged model by a redefinition of the superpotential. Interestingly, this is related to non-extremal type solutions in the so-called fake supersymmetry method. Finally, we compute the equation of state of magnetized BSP baby skyrmions inserted into an external constant magnetic field $H$ and under external pressure $P$, i.e., $V=V(P,H)$, where $V$ is the "volume" (area) occupied by the skyrmions. We show that the BPS baby skyrmions form a ferromagnetic medium.Comment: Latex, 39 pages, 14 figures. v2: New results and references added, physical interpretation partly change

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. © 2014 Ezzatizadeh et al.This article has been made available through the Brunel Open Access Publishing Fund

Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model

The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem

HIV-2 Integrase Variation in Integrase Inhibitor-Naïve Adults in Senegal, West Africa

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients

The Minimal Scale Invariant Extension of the Standard Model

We perform a systematic analysis of an extension of the Standard Model that includes a complex singlet scalar field and is scale invariant at the tree level. We call such a model the Minimal Scale Invariant extension of the Standard Model (MSISM). The tree-level scale invariance of the model is explicitly broken by quantum corrections, which can trigger electroweak symmetry breaking and potentially provide a mechanism for solving the gauge hierarchy problem. Even though the scale invariant Standard Model is not a realistic scenario, the addition of a complex singlet scalar field may result in a perturbative and phenomenologically viable theory. We present a complete classification of the flat directions which may occur in the classical scalar potential of the MSISM. After calculating the one-loop effective potential of the MSISM, we investigate a number of representative scenarios and determine their scalar boson mass spectra, as well as their perturbatively allowed parameter space compatible with electroweak precision data. We discuss the phenomenological implications of these scenarios, in particular, whether they realize explicit or spontaneous CP violation, neutrino masses or provide dark matter candidates. In particular, we find a new minimal scale-invariant model of maximal spontaneous CP violation which can stay perturbative up to Planck-mass energy scales, without introducing an unnaturally large hierarchy in the scalar-potential couplings.Comment: 71 pages, 34 eps figures, numerical error corrected, clarifying comments adde

Successful Surgical Treatment of a Spontaneous Rupture of the Esophagus Diagnosed Two Days after Onset

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient's general state was stable and there was no evidence of clinical sepsis