626 research outputs found

    Modification of the standard model for the lanthanides

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    We show that incorporation of strong electron correlations into the Kohn-Sham scheme of band structure calculations leads to a modification of the standard model of the lanthanides and that this procedure removes the existing discrepancy between theory and experiment concerning the ground state properties. Within the picture suggested, part of the upper Hubbard ff-band is occupied due to conduction band-ff-mixing interaction (that is renormalized due to correlations) and this contributes to the cohesive energy of the crystal. The lower Hubbard band has zero width and describes fermionic excitations in the shell of localized ff-s. Fully self-consistent calculations (with respect to both charge density and many-electron population numbers of the ff-shell) of the equilibrium volume V0V_0 and the bulk modulus of selected lanthanides have been performed and a good agreement is obtained.Comment: 1 fi

    Antimalarial 4(1H)-pyridones bind to the Qisite of cytochromebc1

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    Cytochrome bc1 is a proven drug target in the prevention and treatment of malaria. The rise in drug-resistant strains of Plasmodium falciparum, the organism responsible for malaria, has generated a global effort in designing new classes of drugs. Much of the design/redesign work on overcoming this resistance has been focused on compounds that are presumed to bind the Qo site (one of two potential binding sites within cytochrome bc1) using the known crystal structure of this large membrane-bound macromolecular complex via in silico modeling. Cocrystallization of the cytochrome bc1 complex with the 4(1H)-pyridone class of inhibitors, GSK932121 and GW844520, that have been shown to be potent antimalarial agents in vivo, revealed that these inhibitors do not bind at the Qo site but bind at the Qi site. The discovery that these compounds bind at the Qi site may provide a molecular explanation for the cardiotoxicity and eventual failure of GSK932121 in phase-1 clinical trial and highlight the need for direct experimental observation of a compound bound to a target site before chemical optimization and development for clinical trials. The binding of the 4(1H)-pyridone class of inhibitors to Qi also explains the ability of this class to overcome parasite Qo-based atovaquone resistance and provides critical structural information for future design of new selective compounds with improved safety profiles

    Status of the Super-B factory Design

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    The SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single-collision luminosity) and a storage-ring collider (high repetition rate), bringing together all accelerator physics aspects to make a very high luminosity of 1036^{36} cm2^{-2} sec1^{-1}. This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the Υ\Upsilon(4S) resonance. The present design is based on extremely low emittance beams colliding at a large Piwinski angle to allow very low βy\beta_y^\star without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and allowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal polarization of the electron beam at the Interaction Point. Optimized for best colliding-beam performance, the facility may also provide high-brightness photon beams for synchrotron radiation applications

    Baseline Design of the SuperB Factory Injection System

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    TUPPR088International audienceThe injection complex of the SuperB, B-factory project of INFN consists of a polarized electron gun, a positron production system, electron and positron linac sections, a positron damping ring and the transfer lines connecting these systems and the collider main rings. To keep the ultra high luminosity nearly constant, continuous injection of 4 GeV electrons and 7 GeV positrons in both Low Energy Ring (LER) and High Energy Ring (HER) is necessary. In this paper we describe the baseline design and the beam dynamics studies performed to evaluate the system performance

    Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

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    Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis

    Vitis vinifera subsp. sylvestris and sativa; so far, so close: a 20 SSR based comparison of the two taxa

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    In Vitis vinifera L., the hypothesis of secondary domestication center, located along the wild progenitor distribution areas, is suggestive and credible even if up to now close parentage relationships between domestic (Vitis vinifera L. subsp. sativa (DC.) Hegi) and wild (Vitis vinifera L. subsp. sylvestris (Gmel.) Hegi) grapevines have not been detected, possibly due to century long separation of the two subspecies. The aim of this work was to verify the possibility of tracing a flow between the two compartments basing on molecular data and thanks to the availability of a huge dataset comprising 645 wild and more than 1400 cultivated samples. Twenty SSR loci were used to describe and genotype both sylvestris and sativa compartments. The sylvestris samples were all collected in the frame of a three year census in Italy and are representative of the Italian distribution range from north to south. The cultivated sativa accessions mainly (1231 samples) belong to the Vassal (INRA-Montpellier) collection, while the remaining (200) were selected in the frame of the Italian grapevine germplasm. Results highlighted a high level of genetic diversity for both wild and cultivated groups. STRUCTURE analysis clearly evidenced the separation of the two compartments and no first or second degree relationships were evidenced between the two subspecies

    Proposal for taking data with the KLOE-2 detector at the DAΦ\PhiNE collider upgraded in energy

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    This document reviews the physics program of the KLOE-2 detector at DAΦ\PhiNE upgraded in energy and provides a simple solution to run the collider above the ϕ\phi-peak (up to 2, possibly 2.5 GeV). It is shown how a precise measurement of the multihadronic cross section in the energy region up to 2 (possibly 2.5) GeV would have a major impact on the tests of the Standard Model through a precise determination of the anomalous magnetic moment of the muon and the effective fine-structure constant at the MZM_Z scale. With a luminosity of about 103210^{32}cm2^{-2}s1^{-1}, DAΦ\PhiNE upgraded in energy can perform a scan in the region from 1 to 2.5 GeV in one year by collecting an integrated luminosity of 20 pb1^{-1} (corresponding to a few days of data taking) for single point, assuming an energy step of 25 MeV. A few years of data taking in this region would provide important tests of QCD and effective theories by γγ\gamma\gamma physics with open thresholds for pseudo-scalar (like the η\eta'), scalar (f0,f0f_0,f'_0, etc...) and axial-vector (a1a_1, etc...) mesons; vector-mesons spectroscopy and baryon form factors; tests of CVC and searches for exotics. In the final part of the document a technical solution for the energy upgrade of DAΦ\PhiNE is proposed.Comment: 19 pages, 8 figure

    SuperB: next-generation e+e- B-factory collider

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    International audienceThe SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single- collision luminosity) and a storage-ring collider (high rep- etition rate), bringing together all accelerator physics as- pects to make a very high luminosity of 10^36 cm^−2 sec^−1 . This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the Υ(4S) resonance. The present design is based on ex- tremely low emittance beams colliding at a large Piwin- ski angle to allow very low β⋆y without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and al- lowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal po- larization of the electron beam at the Interaction Point. Op- timized for best colliding-beam performance, the facility may also provide high-brightness photon beams for syn- chrotron radiation applications

    Vitis vinifera subsp. sylvestris and sativa; so far, so close: a 20 SSR based comparison of the two taxa

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    In Vitis vinifera L., the hypothesis of secondary domestication center, located along the wild progenitor distribution areas, is suggestive and credible even if up to now close parentage relationships between domestic (Vitis vinifera L. subsp. sativa (DC.) Hegi) and wild (Vitis vinifera L. subsp. sylvestris (Gmel.) Hegi) grapevines have not been detected, possibly due to century long separation of the two subspecies. The aim of this work was to verify the possibility of tracing a flow between the two compartments basing on molecular data and thanks to the availability of a huge dataset comprising 645 wild and more than 1400 cultivated samples. Twenty SSR loci were used to describe and genotype both sylvestris and sativa compartments. The sylvestris samples were all collected in the frame of a three year census in Italy and are representative of the Italian distribution range from north to south. The cultivated sativa accessions mainly (1231 samples) belong to the Vassal (INRA-Montpellier) collection, while the remaining (200) were selected in the frame of the Italian grapevine germplasm. Results highlighted a high level of genetic diversity for both wild and cultivated groups. STRUCTURE analysis clearly evidenced the separation of the two compartments and no first or second degree relationships were evidenced between the two subspecies

    Ca2+ monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor

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    Calcium (Ca2+)-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (300?nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca2+ level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca2+ signaling in P. falciparum and is applicable for drug screening.We are grateful to Japanese Red Cross Blood Society for providing human RBC and plasma. We also thank Tanaka R, Ogoshi (Sakura) M and Matsumoto N for technical assistance and Templeton TJ for critical reading. This study was conducted at the Joint Usage / Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan. KP was a Tokyo Biochemical Research Foundation (TBRF, http://www.tokyobrf.or.jp) post-doctoral fellow and PEF was a Japanese Society of Promotion Sciences (JSPS) post-doctoral fellow. This work was supported in part by the TBRF (K.P.), JSPS (P.E.F.), Takeda Science Foundation (K.Y.), Grants-in-Aids for Scientific Research 24590509 (K.Y.), 22390079 (O.K.), and for Scientific Research on Innovative Areas 23117008 (O.K.), MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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