2,702 research outputs found

    Stochastic perturbation of sweeping process and a convergence result for an associated numerical scheme

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    Here we present well-posedness results for first order stochastic differential inclusions, more precisely for sweeping process with a stochastic perturbation. These results are provided in combining both deterministic sweeping process theory and methods concerning the reflection of a Brownian motion. In addition, we prove convergence results for a Euler scheme, discretizing theses stochastic differential inclusions.Comment: 30 page

    α-Hemolysin as a Candidate for a Vaccine for \u3cem\u3eStaphylococcus aureus\u3c/em\u3e in Bovine Mastitis

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    Staphylococcus aureus is a Gram-positive bacteria responsible for many types of infections. It is abundant in nature, even present on our own skin, usually harmless. However, it is the leading cause of infection in humans. S. aureus also harms animals, and in dairy cows, causes Bovine mastitis. This disease results in a decreased quality and quantity of milk, inflammation of the mammary glands, and can even be transmitted to humans.(1) Because of this, there are massive economic ramifications estimated at $629 million annually.(2) This study focuses on a virulent factor known as a-hemolysin (Hla) and cloning this into S. aureus bacteria to make a vaccine to treat bovine mastitis. This is a protein present on the cell membrane of S. aureus, known for its cytotoxic properties. To harm eukaryotic cells, research suggests that Hla has a close relationship with a eukaryotic cell receptor known as ADAM10. Normally, this receptor has a role in the development of the nervous system, and in precursor formation of the amyloid protein. When S. aureus is exposed to these cell receptors, a bridge is formed between the Hla protein of the bacteria and the surface receptor ADAM10. After the link is formed, the Hla protein drills a pore into the eukaryotic cell causing it to lyse. (3) This makes the Hla protein a great candidate for a vaccine, as if this interaction could be prevented, then harm would be reduced in the host cell

    Inactivation of Tor proteins affects the dynamics of endocytic proteins in early stage of endocytosis

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    Tor2 is an activator of the Rom2/Rho1 pathway that regulates α-factor internalization. Since the recruitment of endocytic proteins such as actin-binding proteins and the amphiphysins precedes the internalization of α-factor, we hypothesized that loss of Tor function leads to an alteration in the dynamics of the endocytic proteins. We report here that endocytic proteins, Abp1 and Rvs167, are less recruited to endocytic sites not only in tor2 but also tor1 mutants. Furthermore, we found that the endocytic proteins Rvs167 and Sjl2 are completely mistargeted to the cytoplasm in tor1Δtor2ts double mutant cells. We also demonstrate here that the efficiency of endocytic internalization or scission in all tor mutants was drastically decreased. In agreement with the Sjl2 mislocalization, we found that in tor1Δtor2ts double mutant cells, as well as other tor mutant cells, the overall PIP2 level was dramatically increased. Finally, the cell wall chitin content in tor2ts and tor1Δtor2ts mutant cells was also significantly increased. Taken together, both functional Tor proteins, Tor1 and Tor2, are essentially required for proper endocytic protein dynamics at the early stage of endocytosis

    Lineage-specific co-evolution of the Egf receptor/ligand signaling system

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    <p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand system contributes to many human malignancies. Consistent with such various tasks, the Egfr gene family has expanded during vertebrate evolution as a consequence of several rounds of whole genome duplication. Of particular interest is the effect of the fish-specific whole genome duplication (FSGD) on the ligand-receptor system, as it has supplied this largest group of vertebrates with additional opportunities for sub- and/or neofunctionalization in this signaling system.</p> <p>Results</p> <p>We identified the predicted components of the Egf receptor-ligand signaling system in teleost fishes (medaka, platyfish, stickleback, pufferfishes and zebrafish). We found two duplicated <it>egfr </it>genes, <it>egfra </it>and <it>egfrb</it>, in all available teleost genomes. Surprisingly only one copy for each of the seven Egfr ligands could be identified in most fishes, with zebrafish <it>hbegf </it>being the only exception. Special focus was put on medaka, for which we more closely investigated all Egf receptors and Egfr ligands. The different expression patterns of <it>egfra</it>, <it>egfrb </it>and their ligands in medaka tissues and embryo stages suggest differences in role and function. Preferential co-expression of different subsets of Egfr ligands corroborates the possible subfunctionalization and specialization of the two receptors in adult tissues. Bioinformatic analyses of the ligand-receptor interface between Egfr and its ligands show a very weak evolutionary conservation within this region. Using <it>in vitro </it>analyses of medaka Egfra, we could show that this receptor is only activated by medaka ligands, but not by human EGF. Altogether, our data suggest a lineage-specific Egfr/Egfr ligand co-evolution.</p> <p>Conclusions</p> <p>Our data indicate that medaka Egfr signaling occurs via its two copies, Egfra and Egfrb, each of them being preferentially coexpressed with different subsets of Egfr ligands. This fish-specific occurrence of Egf receptor specialization offers unique opportunities to study the functions of different Egf receptor-ligand combinations and their biological outputs in vertebrates. Furthermore, our results strongly support the use of homologous ligands in future studies, as sufficient cross-specificity is very unlikely for this ligand/receptor system.</p

    SuPAR correlates with mortality and clinical severity in patients with necrotizing soft-tissue infections:results from a prospective, observational cohort study

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    Abstract Necrotizing soft tissue infections (NSTI) have a 90-day mortality rate of 18–22%. Tools are needed for estimating the prognosis and severity of NSTI upon admission. We evaluated soluble urokinase-type plasminogen activator receptor (suPAR) levels at admission as a prognostic marker of NSTI severity and mortality. In a prospective, observational cohort study, suPAR was measured in 200 NSTI patients. We compared admission suPAR levels in survivors and non-survivors, patients with septic shock and non-shock, amputation and non-amputation, correlations with Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA) score. Admission suPAR levels were higher in septic shock vs. non-septic shock patients (9.2 vs. 5.8 ng/mL, p-value < 0.001) and non-survivors vs. survivors (11 vs. 6.1 ng/mL, p-value < 0.001) and correlated with SAPS II (r = 0.52, p < 0.001) and SOFA score (r = 0.64, p < 0.001). Elevated suPAR upon admission was associated with 90-day mortality (log-rank test p < 0.001), however not after adjustment for age, sex, and SOFA score. The AUC for suPAR and 90-day mortality was 0.77. We found that suPAR is a promising candidate for prognosis and severity in patients with NSTI

    On the reduced sensitivity of the Atlantic overturning to Greenland ice sheet melting in projections: a multi-model assessment

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    Large uncertainties exist concerning the impact of Greenland ice sheet melting on the Atlantic meridional overturning circulation (AMOC) in the future, partly due to different sensitivity of the AMOC to freshwater input in the North Atlantic among climate models. Here we analyse five projections from different coupled ocean–atmosphere models with an additional 0.1 Sv (1 Sv = 10 6 m3/s) of freshwater released around Greenland between 2050 and 2089. We find on average a further weakening of the AMOC at 26°N of 1.1 ± 0.6 Sv representing a 27 ± 14% supplementary weakening in 2080–2089, as compared to the weakening relative to 2006–2015 due to the effect of the external forcing only. This weakening is lower than what has been found with the same ensemble of models in an identical experimen - tal set-up but under recent historical climate conditions. This lower sensitivity in a warmer world is explained by two main factors. First, a tendency of decoupling is detected between the surface and the deep ocean caused by an increased thermal stratification in the North Atlantic under the effect of global warming. This induces a shoaling of ocean deep ventilation through convection hence ventilating only intermediate levels. The second important effect concerns the so-called Canary Current freshwater leakage; a process by which additionally released fresh water in the North Atlantic leaks along the Canary Current and escapes the convection zones towards the subtropical area. This leakage is increasing in a warming climate, which is a consequence of decreasing gyres asymmetry due to changes in Ekman rumping. We suggest that these modifications are related with the northward shift of the jet stream in a warmer world. For these two reasons the AMOC is less susceptible to freshwater perturbations (near the deep water formation sides) in the North Atlantic as compared to the recent historical climate conditions. Finally, we propose a bilinear model that accounts for the two former processes to give a conceptual explanation about the decreasing AMOC sensitivity due to freshwater input. Within the limit of this bilinear model, we find that 62 ± 8% of the reduction in sensitivity is related with the changes in gyre asymmetry and freshwater leakage and 38 ± 8% is due to the reduction in deep ocean ventilation associated with the increased stratification in the North Atlantic

    Characterization of THB1, a Chlamydomonas reinhardtii truncated hemoglobin: linkage to nitrogen metabolism and identification of lysine as the distal heme ligand

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    The nuclear genome of the model organism Chlamydomonas reinhardtii contains genes for a dozen hemoglobins of the truncated lineage. Of those, THB1 is known to be expressed, but the product and its function have not yet been characterized. We present mutagenesis, optical, and nuclear magnetic resonance data for the recombinant protein and show that at pH near neutral in the absence of added ligand, THB1 coordinates the heme iron with the canonical proximal histidine and a distal lysine. In the cyanomet state, THB1 is structurally similar to other known truncated hemoglobins, particularly the heme domain of Chlamydomonas eugametos LI637, a light-induced chloroplastic hemoglobin. Recombinant THB1 is capable of binding nitric oxide (NO(*)) in either the ferric or ferrous state and has efficient NO(*) dioxygenase activity. By using different C. reinhardtii strains and growth conditions, we demonstrate that the expression of THB1 is under the control of the NIT2 regulatory gene and that the hemoglobin is linked to the nitrogen assimilation pathway

    SCORODOPHLONE A, A NOVEL ALKYLSULFONE FROM THE SEEDS OF SCORODOPHLOEUS ZENKERI. HARMS

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    A novel alkylsulfone, scorodophlone A 1, from the seeds of Scorodophloeus zenkeri Harms, has been assigned the structure 6-(methylsulfonyl)-1,2,3-dithiazinan-4-one on the basis of its spectroscopic properties. The known compounds &alpha;-sophoradiol (12-oleanene-3&beta;,22&alpha;-diol), lupeol and sitosterol were also obtained. KEY WORDS: Scorodophloeus zenkeri, Caesalpiniaceae, Scorodophlone A, Pentacyclic triterpene, Phytosterol Bull. Chem. Soc. Ethiop. 2006, 20(1), 173-176

    Potential Melting of Extrasolar Planets by Tidal Dissipation

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    Tidal heating on Io due to its finite eccentricity was predicted to drive surface volcanic activity, which was subsequently confirmed by the Voyager\textit{Voyager} spacecrafts. Although the volcanic activity in Io is more complex, in theory volcanism can be driven by runaway melting in which the tidal heating increases as the mantle thickness decreases. We show that this runaway melting mechanism is generic for a composite planetary body with liquid core and solid mantle, provided that (i) the mantle rigidity, ÎŒ\mu, is comparable to the central pressure, i.e. ÎŒ/(ρgRP)≳0.1\mu/ (\rho g R_{\rm P})\gtrsim0.1 for a body with density ρ\rho, surface gravitational acceleration gg, and radius RPR_{\rm P}, (ii) the surface is not molten, (iii) tides deposit sufficient energy, and (iv) the planet has nonzero eccentricity. We calculate the approximate liquid core radius as a function of ÎŒ/(ρgRP)\mu/ (\rho g R_{\rm P}), and find that more than 90%90\% of the core will melt due to this runaway for ÎŒ/(ρgRP)≳1\mu/ (\rho g R_{\rm P})\gtrsim1. From all currently confirmed exoplanets, we find that the terrestrial planets in the L98-59 system are the most promising candidates for sustaining active volcanism. However, uncertainties regarding the quality factors and the details of tidal heating and cooling mechanisms prohibit definitive claims of volcanism on any of these planets. We generate synthetic transmission spectra of these planets assuming Venus-like atmospheric compositions with an additional 5, 50, and 98%98\% SO2_2 component, which is a tracer of volcanic activity. We find a ≳3σ\gtrsim 3 \sigma preference for a model with SO2_2 with 5-10 transits with JWST\textit{JWST} for L98-59bcd.Comment: 16 pages, 8 Figures, accepted for publication in Ap

    ModÚle géométrique de frottement entre matériaux composites

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    Dans cette Ă©tude, on propose un modĂšle gĂ©omĂ©trique de frottement sous faible charge normale entre deux matĂ©riaux composites. Le contact est prĂ©sentĂ© comme une multitude de microcontacts dont la nature peut ĂȘtre de trois types : fibre-fibre, fibre-matrice ou matrice-matrice. La force de frottement interfaciale est la somme des forces locales de frottement en ces microcontacts. Le calcul montre que le coefficient de frottement hybride ne dĂ©pend pas de l'orientation de fibres mais seulement de leur fraction surfacique. Ce modĂšle est testĂ© expĂ©rimentalement
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