Debris flow susceptibility mapping at a regional scale along the National Road N7, Argentina

A first assessment of debris flow susceptibility at a large scale was performed along the National Road N7, Argentina. Numerous catchments are prone to debris flows and likely to endanger the road-users. A 1:50,000 susceptibility map was created. The use of a DEM (grid 30 m) associated to three complementary criteria (slope, contributing area, curvature) allowed the identification of potential source areas. The debris flow spreading was estimated using a process- and GISbased model (Flow-R) based on basic probabilistic and energy calculations. The best-fit values for the coefficient of friction and the mass-to-drag ratio of the PCM model were found to be ? = 0.02 and M/D = 180 and the resulting propagation on one of the calibration site was validated using the Coulomb friction model. The results are realistic and will be useful to determine which areas need to be prioritized for detailed studies.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract

Purpose: Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients. Methods: Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR. Results: We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5'UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5'UTR region. Conclusions: Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

The Candida albicans plasma membrane protein Rch1p, a member of the vertebrate SLC10 carrier family, is a novel regulator of cytosolic Ca(2+) homoeostasis.

Candida albicans RCH1 (regulator of Ca(2+) homoeostasis 1) encodes a protein of ten TM (transmembrane) domains, homologous with human SLC10A7 (solute carrier family 10 member 7), and Rch1p localizes in the plasma membrane. Deletion of RCH1 confers hypersensitivity to high concentrations of extracellular Ca(2+) and tolerance to azoles and Li(+), which phenocopies the deletion of CaPMC1 (C. albicans PMC1) encoding the vacuolar Ca(2+) pump. Additive to CaPMC1 mutation, lack of RCH1 alone shows an increase in Ca(2+) sensitivity, Ca(2+) uptake and cytosolic Ca(2+) level. The Ca(2+) hypersensitivity is abolished by cyclosporin A and magnesium. In addition, deletion of RCH1 elevates the expression of CaUTR2 (C. albicans UTR2), a downstream target of the Ca(2+)/calcineurin signalling. Mutational and functional analysis indicates that the Rch1p TM8 domain, but not the TM9 and TM10 domains, are required for its protein stability, cellular functions and subcellular localization. Therefore Rch1p is a novel regulator of cytosolic Ca(2+) homoeostasis, which expands the functional spectrum of the vertebrate SLC10 family.

Identification and characterization of the Arabidopsis PHO1 gene involved in phosphate loading to the xylem.

The Arabidopsis mutant pho1 is deficient in the transfer of Pi from root epidermal and cortical cells to the xylem. The PHO1 gene was identified by a map-based cloning strategy. The N-terminal half of PHO1 is mainly hydrophilic, whereas the C-terminal half has six potential membrane-spanning domains. PHO1 shows no homology with any characterized solute transporter, including the family of H(+)-Pi cotransporters identified in plants and fungi. PHO1 shows highest homology with the Rcm1 mammalian receptor for xenotropic murine leukemia retroviruses and with the Saccharomyces cerevisiae Syg1 protein involved in the mating pheromone signal transduction pathway. PHO1 is expressed predominantly in the roots and is upregulated weakly under Pi stress. Studies with PHO1 promoter-beta-glucuronidase constructs reveal predominant expression of the PHO1 promoter in the stelar cells of the root and the lower part of the hypocotyl. There also is beta-glucuronidase staining of endodermal cells that are adjacent to the protoxylem vessels. The Arabidopsis genome contains 10 additional genes showing homology with PHO1. Thus, PHO1 defines a novel class of proteins involved in ion transport in plants.

Transcriptome and membrane fatty acid analyses reveal different strategies for responding to permeating and non-permeating solutes in the bacterium Sphingomonas wittichii.

ABSTRACT: BACKGROUND: Sphingomonas wittichii strain RW1 can completely oxidize dibenzo-p-dioxins and dibenzofurans, which are persistent contaminants of soils and sediments. For successful application in soil bioremediation systems, strain RW1 must cope with fluctuations in water availability, or water potential. Thus far, however, little is known about the adaptive strategies used by Sphingomonas bacteria to respond to changes in water potential. To improve our understanding, strain RW1 was perturbed with either the cell-permeating solute sodium chloride or the non-permeating solute polyethylene glycol with a molecular weight of 8000 (PEG8000). These solutes are assumed to simulate the solute and matric components of the total water potential, respectively. The responses to these perturbations were then assessed and compared using a combination of growth assays, transcriptome profiling, and membrane fatty acid analyses. RESULTS: Under conditions producing a similar decrease in water potential but without effect on growth rate, there was only a limited shared response to perturbation with sodium chloride or PEG8000. This shared response included the increased expression of genes involved with trehalose and exopolysaccharide biosynthesis and the reduced expression of genes involved with flagella biosynthesis. Mostly, the responses to perturbation with sodium chloride or PEG8000 were very different. Only sodium chloride triggered the increased expression of two ECF-type RNA polymerase sigma factors and the differential expression of many genes involved with outer membrane and amino acid metabolism. In contrast, only PEG8000 triggered the increased expression of a heat shock-type RNA polymerase sigma factor along with many genes involved with protein turnover and repair. Membrane fatty acid analyses further corroborated these differences. The degree of saturation of membrane fatty acids increased after perturbation with sodium chloride but had the opposite effect and decreased after perturbation with PEG8000. CONCLUSIONS: A combination of growth assays, transcriptome profiling, and membrane fatty acid analyses revealed that permeating and non-permeating solutes trigger different adaptive responses in strain RW1, suggesting these solutes affect cells in fundamentally different ways. Future work is now needed that connects these responses with the responses observed in more realistic scenarios of soil desiccation.

The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review).

During the last 2 years, several novel genes that encode glucose transporter-like proteins have been identified and characterized. Because of their sequence similarity with GLUT1, these genes appear to belong to the family of solute carriers 2A (SLC2A, protein symbol GLUT). Sequence comparisons of all 13 family members allow the definition of characteristic sugar/polyol transporter signatures: (1) the presence of 12 membrane-spanning helices, (2) seven conserved glycine residues in the helices, (3) several basic and acidic residues at the intracellular surface of the proteins, (4) two conserved tryptophan residues, and (5) two conserved tyrosine residues. On the basis of sequence similarities and characteristic elements, the extended GLUT family can be divided into three subfamilies, namely class I (the previously known glucose transporters GLUT1-4), class II (the previously known fructose transporter GLUT5, the GLUT7, GLUT9 and GLUT11), and class III (GLUT6, 8, 10, 12, and the myo-inositol transporter HMIT1). Functional characteristics have been reported for some of the novel GLUTs. Like GLUT1-4, they exhibit a tissue/cell-specific expression (GLUT6, leukocytes, brain; GLUT8, testis, blastocysts, brain, muscle, adipocytes; GLUT9, liver, kidney; GLUT10, liver, pancreas; GLUT11, heart, skeletal muscle). GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intra-cellular compartments by dileucine motifs in a dynamin dependent manner. Sugar transport has been reported for GLUT6, 8, and 11; HMIT1 has been shown to be a H+/myo-inositol co-transporter. Thus, the members of the extended GLUT family exhibit a surprisingly diverse substrate specificity, and the definition of sequence elements determining this substrate specificity will require a full functional characterization of all members.

Inferring transport characteristics in a fractured rock aquifer by combining single-hole ground-penetrating radar reflection monitoring and tracer test data

Investigations of solute transport in fractured rock aquifers often rely on tracer test data acquired at a limited number of observation points. Such data do not, by themselves, allow detailed assessments of the spreading of the injected tracer plume. To better understand the transport behavior in a granitic aquifer, we combine tracer test data with single-hole ground-penetrating radar (GPR) reflection monitoring data. Five successful tracer tests were performed under various experimental conditions between two boreholes 6 m apart. For each experiment, saline tracer was injected into a previously identified packed-off transmissive fracture while repeatedly acquiring single-hole GPR reflection profiles together with electrical conductivity logs in the pumping borehole. By analyzing depth-migrated GPR difference images together with tracer breakthrough curves and associated simplified flow and transport modeling, we estimate (1) the number, the connectivity, and the geometry of fractures that contribute to tracer transport, (2) the velocity and the mass of tracer that was carried along each flow path, and (3) the effective transport parameters of the identified flow paths. We find a qualitative agreement when comparing the time evolution of GPR reflectivity strengths at strategic locations in the formation with those arising from simulated transport. The discrepancies are on the same order as those between observed and simulated breakthrough curves at the outflow locations. The rather subtle and repeatable GPR signals provide useful and complementary information to tracer test data acquired at the outflow locations and may help us to characterize transport phenomena in fractured rock aquifers.

Concomitant administration of intravenous drugs in the ICU: evaluation of physico-chemical compatibilities

Background and objective: Patients in the ICU often get many intravenous (iv) drugs at the same time. Even with three-lumen central venous catheters, the administration of more than one drug in the same iv line (IVL) is frequently necessary. The objective of this study was to observe how nurses managed to administer these many medications and to evaluate the proportion of two-drugs associations (TDA) that are compatible or not, based on known compatibility data. Design: Observational prospective study over 4 consecutive months. All patients receiving simultaneously more than one drugs in the same IVL (Y-site injection or mixed in the same container) were included. For each patient, all iv drugs were recorded, as well as concentration, infusion solution, location on the IVL system, time, rate and duration of administration. For each association of two or more drugs, compatibility of each drug was checked with each other. Compatibilities between these pairs of drugs were assessed using published data (mainly Trissel LA. Handbook on Injectable Drugs and Trissel's Tables of Physical Compatibility) and visual tests performed in our quality control laboratory. Setting: 34 beds university hospital adult ICU. Main outcome measures: Percentage of compatibilities and incompatibilities between drugs administered in the same IVL. Results: We observed 1,913 associations of drugs administered together in the same IVL, 783 implying only two drugs. The average number of drugs per IVL was 3.1 ± 0.8 (range: 2-9). 83.2% of the drugs were given by continuous infusion, 14.3% by intermittent infusion and 2.5% in bolus. The associations observed allowed to form 8,421 pairs of drugs (71.7% drug-drug and 28.3% drug-solute). According to literature data, 80.2% of the association were considered as compatible and 4.4% incompatible. 15.4% were not interpretable because of different conditions between local practices and those described in the literature (drug concentration, solute, etc.) or because of a lack of data. After laboratory tests performed on the most used drugs (furosemide, KH2PO4, morphine HCl, etc.), the proportion of compatible TDA raised to 85.7%, the incompatible stayed at 4.6% and only 9.7% remain unknown or not interpretable. Conclusions: Nurses managed the administration of iv medications quite well, as only less than 5% of observed TDA were considered as incompatible. But the 10% of TDA with unavailable compatibility data should have been avoided too, since the consequences of their concomitant administration cannot be predictable. For practical reasons, drugs were analysed only by pairs, which constitutes the main limit of this work. The average number of drugs in the same association being three, laboratory tests are currently performed to evaluate some of the most observed three-drugs associations.

Biomechanical analysis of alpine skiers performing giant slalom turns

Over the past few years, technological breakthroughs have helpedcompetitive sports to attain new levels. Training techniques, athletes' management and methods to analyse specific technique and performancehave sharpened, leading to performance improvement. Alpine skiing is not different. The objective of the present work was to study the technique of highy skilled alpine skiers performing giant slalom, in order to determine the quantity of energy that can be produced by skiers to increase their speed. To reach this goal, several tools have been developed to allow field testing on ski slopes; a multi cameras system, a wireless synchronization system, an aerodynamic drag model and force plateforms have especially been designed and built. The analyses performed using the different tools highlighted the possibility for several athletes to increase their energy by approximately 1.5 % using muscular work. Nevertheless, the athletes were in average not able to use their muscular work in an efficient way. By offering functional tools such as drift analysis using combined data from GPS and inertial sensors, or trajectory analysis based on tracking morphological points, this research makes possible the analysis of alpine skiers technique and performance in real training conditions. The author wishes for this work to be used as a basis for continued knowledge and understanding of alpine skiing technique. - Le sport de compétition bénéficie depuis quelques années des progrès technologiques apportés par la science. Les techniques d'entraînement, le suivi des athlètes et les méthodes d'analyse deviennent plus pointus, induisant une nette amélioration des performances. Le ski alpin ne dérogeant pas à cette règle, l'objectif de ce travail était d'analyser la technique de skieurs de haut niveau en slalom géant afin de déterminer la quantité d'énergie fournie par les skieurs pour augmenter leur vitesse. Pour ce faire, il a été nécessaire de developer différents outils d'analyse adaptés aux contraintes inhérentes aux tests sur les pistes de skis; un système multi caméras, un système de synchronisation, un modèle aérodynamique et des plateformes de force ont notamment été développés. Les analyses effectuées grâce à ces différents outils ont montré qu'il était possible pour certains skieur d'augmenter leur énergie d'environ 1.5 % grâce au travail musculaire. Cependant, les athlètes n'ont en moyenne pas réussi à utiliser leur travail musculaire de manière efficace. Ce projet a également rendu possible des analyses adaptées aux conditions d'entraînement des skieurs en proposant des outils fonctionnels tels que l'analyse du drift grâce à des capteurs inertiels et GPS, ainsi que l'analyse simplifiée de trajectoires grâce au suivi de points morphologiques. L'auteur espère que ce travail servira de base pour approfondir les connaissances de la technique en ski alpin.

Alterations of the 5'untranslated region of SLC16A12 lead to age-related cataract.

PURPOSE. Knowledge of genetic factors predisposing to age-related cataract is very limited. The aim of this study was to identify DNA sequences that either lead to or predispose for this disease. METHODS. The candidate gene SLC16A12, which encodes a solute carrier of the monocarboxylate transporter family, was sequenced in 484 patients with cataract (134 with juvenile cataract, 350 with age-related cataract) and 190 control subjects. Expression studies included luciferase reporter assay and RT-PCR experiments. RESULTS. One patient with age-related cataract showed a novel heterozygous mutation (c.-17A>G) in the 5'untranslated region (5'UTR). This mutation is in cis with the minor G-allele of the single nucleotide polymorphism (SNP) rs3740030 (c.-42T/G), also within the 5'UTR. Using a luciferase reporter assay system, a construct with the patient's haplotype caused a significant upregulation of luciferase activity. In comparison, the SNP G-allele alone promoted less activity, but that amount was still significantly higher than the amount of the common T-allele. Analysis of SLC16A12 transcripts in surrogate tissue demonstrated striking allele-specific differences causing 5'UTR heterogeneity with respect to sequence and quantity. These differences in gene expression were mirrored in an allele-specific predisposition to age-related cataract, as determined in a Swiss population (odds ratio approximately 2.2; confidence intervals, 1.23-4.3). CONCLUSIONS. The monocarboxylate transporter SLC16A12 may contribute to age-related cataract. Sequences within the 5'UTR modulate translational efficiency with pathogenic consequences.

Gravity-driven slug motion in capillary tubes

The velocity of a liquid slug falling in a capillary tube is lower than predicted for Poiseuille flow due to presence of menisci, whose shapes are determined by the complex interplay of capillary, viscous, and gravitational forces. Due to the presence of menisci, a capillary pressure proportional to surface curvature acts on the slug and streamlines are bent close to the interface, resulting in enhanced viscous dissipation at the wedges. To determine the origin of drag-force increase relative to Poiseuille flow, we compute the force resultant acting on the slug by integrating Navier-Stokes equations over the liquid volume. Invoking relationships from differential geometry we demonstrate that the additional drag is due to viscous forces only and that no capillary drag of hydrodynamic origin exists (i.e., due to hydrodynamic deformation of the interface). Requiring that the force resultant is zero, we derive scaling laws for the steady velocity in the limit of small capillary numbers by estimating the leading order viscous dissipation in the different regions of the slug (i.e., the unperturbed Poiseuille-like bulk, the static menisci close to the tube axis and the dynamic regions close to the contact lines). Considering both partial and complete wetting, we find that the relationship between dimensionless velocity and weight is, in general, nonlinear. Whereas the relationship obtained for complete-wetting conditions is found in agreement with the experimental data of Bico and Quere [J. Bico and D. Quere, J. Colloid Interface Sci. 243, 262 (2001)], the scaling law under partial-wetting conditions is validated by numerical simulations performed with the Volume of Fluid method. The simulated steady velocities agree with the behavior predicted by the theoretical scaling laws in presence and in absence of static contact angle hysteresis. The numerical simulations suggest that wedge-flow dissipation alone cannot account for the entire additional drag and that the non-Poiseuille dissipation in the static menisci (not considered in previous studies) has to be considered for large contact angles.

Identification of HMX1 target genes: a predictive promoter model approach.

PURPOSE: A homozygous mutation in the H6 family homeobox 1 (HMX1) gene is responsible for a new oculoauricular defect leading to eye and auricular developmental abnormalities as well as early retinal degeneration (MIM 612109). However, the HMX1 pathway remains poorly understood, and in the first approach to better understand the pathway's function, we sought to identify the target genes. METHODS: We developed a predictive promoter model (PPM) approach using a comparative transcriptomic analysis in the retina at P15 of a mouse model lacking functional Hmx1 (dmbo mouse) and its respective wild-type. This PPM was based on the hypothesis that HMX1 binding site (HMX1-BS) clusters should be more represented in promoters of HMX1 target genes. The most differentially expressed genes in the microarray experiment that contained HMX1-BS clusters were used to generate the PPM, which was then statistically validated. Finally, we developed two genome-wide target prediction methods: one that focused on conserving PPM features in human and mouse and one that was based on the co-occurrence of HMX1-BS pairs fitting the PPM, in human or in mouse, independently. RESULTS: The PPM construction revealed that sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) (Sgcg), teashirt zinc finger homeobox 2 (Tshz2), and solute carrier family 6 (neurotransmitter transporter, glycine) (Slc6a9) genes represented Hmx1 targets in the mouse retina at P15. Moreover, the genome-wide target prediction revealed that mouse genes belonging to the retinal axon guidance pathway were targeted by Hmx1. Expression of these three genes was experimentally validated using a quantitative reverse transcription PCR approach. The inhibitory activity of Hmx1 on Sgcg, as well as protein tyrosine phosphatase, receptor type, O (Ptpro) and Sema3f, two targets identified by the PPM, were validated with luciferase assay. CONCLUSIONS: Gene expression analysis between wild-type and dmbo mice allowed us to develop a PPM that identified the first target genes of Hmx1.

Stochastic inversion of tracer test and electrical geophysical data to estimate hydraulic conductivities.

Quantifying the spatial configuration of hydraulic conductivity (K) in heterogeneous geological environments is essential for accurate predictions of contaminant transport, but is difficult because of the inherent limitations in resolution and coverage associated with traditional hydrological measurements. To address this issue, we consider crosshole and surface-based electrical resistivity geophysical measurements, collected in time during a saline tracer experiment. We use a Bayesian Markov-chain-Monte-Carlo (McMC) methodology to jointly invert the dynamic resistivity data, together with borehole tracer concentration data, to generate multiple posterior realizations of K that are consistent with all available information. We do this within a coupled inversion framework, whereby the geophysical and hydrological forward models are linked through an uncertain relationship between electrical resistivity and concentration. To minimize computational expense, a facies-based subsurface parameterization is developed. The Bayesian-McMC methodology allows us to explore the potential benefits of including the geophysical data into the inverse problem by examining their effect on our ability to identify fast flowpaths in the subsurface, and their impact on hydrological prediction uncertainty. Using a complex, geostatistically generated, two-dimensional numerical example representative of a fluvial environment, we demonstrate that flow model calibration is improved and prediction error is decreased when the electrical resistivity data are included. The worth of the geophysical data is found to be greatest for long spatial correlation lengths of subsurface heterogeneity with respect to wellbore separation, where flow and transport are largely controlled by highly connected flowpaths.

Accuracy of indirect estimation of power output from uphill performance in cycling.

PURPOSE: To use measurement by cycling power meters (Pmes) to evaluate the accuracy of commonly used models for estimating uphill cycling power (Pest). Experiments were designed to explore the influence of wind speed and steepness of climb on accuracy of Pest. The authors hypothesized that the random error in Pest would be largely influenced by the windy conditions, the bias would be diminished in steeper climbs, and windy conditions would induce larger bias in Pest. METHODS: Sixteen well-trained cyclists performed 15 uphill-cycling trials (range: length 1.3-6.3 km, slope 4.4-10.7%) in a random order. Trials included different riding position in a group (lead or follow) and different wind speeds. Pmes was quantified using a power meter, and Pest was calculated with a methodology used by journalists reporting on the Tour de France. RESULTS: Overall, the difference between Pmes and Pest was -0.95% (95%CI: -10.4%, +8.5%) for all trials and 0.24% (-6.1%, +6.6%) in conditions without wind (<2 m/s). The relationship between percent slope and the error between Pest and Pmes were considered trivial. CONCLUSIONS: Aerodynamic drag (affected by wind velocity and orientation, frontal area, drafting, and speed) is the most confounding factor. The mean estimated values are close to the power-output values measured by power meters, but the random error is between ±6% and ±10%. Moreover, at the power outputs (>400 W) produced by professional riders, this error is likely to be higher. This observation calls into question the validity of releasing individual values without reporting the range of random errors.