2,105 research outputs found

    Sur quelques crustacés néo-calédoniens de profondeur

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    AIS Council White Paper: Tools and Techniques for AIS Strategic Planning

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    AIS went through and will continue to undergo evolution and revolution as it grows. This article analyzes the current state of AIS and concludes that it is in, or approaching, a crisis of priorities. Planning is the recommended path for solving this crisis. Four planning methods are proposed: stakeholder analysis, service matrix analysis, missions matrix analysis, and a four-year budget cycle

    A fixed point theorem for L 1 spaces

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    We prove a fixed point theorem for a family of Banach spaces including notably L 1 and its non-commutative analogues. Several applications are given, e.g. the optimal solution to the "derivation problem” studied since the 1960

    Fermi Velocity Spectrum and Incipient Magnetism in TiBe2

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    We address the origin of the incipient magnetism in TiBe2_2 through precise first principles calculations, which overestimate the ferromagnetic tendency and therefore require correction to account for spin fluctuations. TiBe2_2 has sharp fine structure in its electronic density of states, with a van Hove singularity only 3 meV above the Fermi level. Similarly to the isovalent weak ferromagnet ZrZn2_2, it is flat bands along the K-W-U lines of hexagonal face of the fcc Brillouin zone make the system prone to magnetism, and more so if electrons are added. We find that the Moriya BB coefficient (multiplying ωq\frac{\omega}{q} in the fluctuation susceptibility Δχ(q,ω)\Delta \chi(q,\omega)) is divergent when the velocity vanishes at a point on the Fermi surface, which is very close (3 meV) to occurring in TiBe2_2. In exploring how the FM instability (the qq=0 Stoner enhancement is S60S\approx 60) might be suppressed by fluctuations in TiBe2_2, we calculate that the Moriya A coefficient (of q2q^2) is negative, so qq=0 is not the primary instability. Explicit calculation of χo(q)\chi_o(q) shows that its maximum occurs at the X point (1,0,0)2πa(1,0,0)\frac{2\pi}{a}; TiBe2_2 is thus an incipient {\it anti}ferromagnet rather than ferromagnet as has been supposed. We further show that simple temperature smearing of the peak accounts for most of the temperature dependence of the susceptibility, which previously had been attributed to local moments (via a Curie-Weiss fit), and that energy dependence of the density of states also strongly affects the magnetic field variation of χ\chi

    Statistical inference of the generation probability of T-cell receptors from sequence repertoires

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    Stochastic rearrangement of germline DNA by VDJ recombination is at the origin of immune system diversity. This process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Since any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on non-productive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our distribution predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.Comment: 20 pages, including Appendi

    The Ptk2-Pma1 pathway enhances tolerance to terbinafine in Trichophyton rubrum.

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    The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae. Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes

    On the distortion of twin building lattices

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    We show that twin building lattices are undistorted in their ambient group; equivalently, the orbit map of the lattice to the product of the associated twin buildings is a quasi-isometric embedding. As a consequence, we provide an estimate of the quasi-flat rank of these lattices, which implies that there are infinitely many quasi-isometry classes of finitely presented simple groups. In an appendix, we describe how non-distortion of lattices is related to the integrability of the structural cocycle

    Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point Mutations in the Squalene Epoxidase Gene.

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    Terbinafine is one of the allylamine antifungal agents whose target is squalene epoxidase (SQLE). This agent has been extensively used in the therapy of dermatophyte infections. The incidence of patients with tinea pedis or unguium tolerant to terbinafine treatment prompted us to screen the terbinafine resistance of all javax.xml.bind.JAXBElement@dc06fb4 clinical isolates from the laboratory of the Centre Hospitalier Universitaire Vaudois collected over a 3-year period and to identify their mechanism of resistance. Among 2,056 tested isolates, 17 (≈1%) showed reduced terbinafine susceptibility, and all of these were found to harbor javax.xml.bind.JAXBElement@374d721c gene alleles with different single point mutations, leading to single amino acid substitutions at one of four positions (Leu javax.xml.bind.JAXBElement@4655f570 , Phe javax.xml.bind.JAXBElement@112b804a , Phe javax.xml.bind.JAXBElement@1f18e014 , and His javax.xml.bind.JAXBElement@4319ac79 ) of the SQLE protein. Point mutations leading to the corresponding amino acid substitutions were introduced into the endogenous javax.xml.bind.JAXBElement@2a0e3f1f gene of a terbinafine-sensitive javax.xml.bind.JAXBElement@67eac3c4 (formerly javax.xml.bind.JAXBElement@3f2a876d ) strain. All of the generated javax.xml.bind.JAXBElement@315e9e95 transformants expressing mutated SQLE proteins exhibited obvious terbinafine-resistant phenotypes compared to the phenotypes of the parent strain and of transformants expressing wild-type SQLE proteins. Nearly identical phenotypes were also observed in javax.xml.bind.JAXBElement@6af3a966 transformants expressing mutant forms of javax.xml.bind.JAXBElement@5bb6b31f SQLE proteins. Considering that the genome size of dermatophytes is about 22 Mb, the frequency of terbinafine-resistant clinical isolates was strikingly high. Increased exposure to antifungal drugs could favor the generation of resistant strains

    Effect of Copper Doping on Charge Ordering in La 1/3 Ca 2/3 Mn 1 - y Cu y O 3 (0 ≤ y ≤ 0.07)

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    Electron microscope studies have shown that the presence of copper suppresses the formation of a regular superstructure, which is characteristic of the undoped starting compound, beginning already from low concentrations (y=0.01). Differential scanning calorimetry revealed a substantial decrease in the transition entropy at the onset of charge ordering in copper-doped samples as compared to the starting compound. Doping with copper destroys long-range charge-orbital ordering and retains apparently only short-range orderyesBelgorod State Universit
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