55 research outputs found

    Therapeutic Effect of a Novel Oxazolidinone, DA-7867, in BALB/c Mice Infected with Nocardia brasiliensis

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    Actinomycetoma is an infectious disease of tropical and subtropical regions produced by actinobacteria of the genera Nocardia, Streptomyces, and Actinomadura. Therapeutic alternatives are scarce and include trimethoprim-sulfamethoxazole, diaminodiphenylsulfone, amoxicillin-clavulanate, imipenem, and amikacin. Oxazolidinones are a new class of antimicrobials with a completely different cellular target; the first compound in the market, linezolid, was introduced in the year 2000. It is active against many species of Nocardia and other aerobic actinomycetes; however, the long-term application in human subjects produces side effects including peripheral neuropathy and mielossupression. Therefore, it is important to screen other oxazolidinones with higher activity and less toxicity. In the present work, we tested DA-7867, a new oxazolidinone, in an experimental mouse model. The drug is active in vivo and decreases the production of lesions using only one dose a day in contrast to linezolid, which needs to be injected three times a day. Although it was tested on N. brasiliensis, it can possibly be active (once it is accepted for its use in humans) against Actinomadura spp and Streptomyces spp, which are frequently found in places of Africa and India where actinomycetoma is also an important consult in dermatology

    DNA glycosylases: in DNA repair and beyond

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    The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

    Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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    Peer reviewe

    Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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    Peer reviewe

    Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

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    Peer reviewe

    Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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    Search for narrow resonances and quantum black holes in inclusive and b-tagged dijet mass spectra from pp collisions at √s=7 TeV

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    This is the pre-print version of the Article. The official published version of the Article can be accessed from the links below - Copyright @ 2013 Springer-Verlag.A search for narrow resonances and quantum black holes is performed in inclusive and b-tagged dijet mass spectra measured with the CMS detector at the LHC. The data set corresponds to 5 fb−1 of integrated luminosity collected in pp collisions at √s=7 TeV. No narrow resonances or quantum black holes are observed. Model-independent upper limits at the 95% confidence level are obtained on the product of the cross section, branching fraction into dijets, and acceptance for three scenarios: decay into quark-quark, quark-gluon, and gluon-gluon pairs. Specific lower limits are set on the mass of string resonances (4.31 TeV), excited quarks (3.32 TeV), axigluons and colorons (3.36 TeV), scalar color-octet resonances (2.07 TeV), E6 diquarks (3.75 TeV), and on the masses of W′ (1.92 TeV) and Z′ (1.47 TeV) bosons. The limits on the minimum mass of quantum black holes range from 4 to 5.3 TeV. In addition, b-quark tagging is applied to the two leading jets and upper limits are set on the production of narrow dijet resonances in a model-independent fashion as a function of the branching fraction to b-jet pairs.This study is supported by the BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBr (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)
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