99 research outputs found

    Self-similarity and novel sample-length-dependence of conductance in quasiperiodic lateral magnetic superlattices

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    We study the transport of electrons in a Fibonacci magnetic superlattice produced on a two-dimensional electron gas modulated by parallel magnetic field stripes arranged in a Fibonacci sequence. Both the transmission coefficient and conductance exhibit self-similarity and the six-circle property. The presence of extended states yields a finite conductivity at infinite length, that may be detected as an abrupt change in the conductance as the Fermi energy is varied, much as a metal-insulator transition. This is a unique feature of transport in this new kind of structure, arising from its inherent two-dimensional nature.Comment: 9 pages, 5 figures, revtex, important revisions made. to be published in Phys. Rev.

    Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations

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    Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection

    A patient-derived explant (PDE) model of hormone-dependent cancer

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    Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica L. Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur, Peter D. Sutherland, Clive E. Hoffmann, Claus G. Roehrborn, Leonard G. Gomella, Jason S. Carroll, Stephen N. Birrell, Karen E. Knudsen, Ganesh V. Raj, Lisa M. Butler, Wayne D. Tille

    Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces cerevisiae

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    In pressProtein kinase C is apparently involved in the control of many cellular systems: the cell wall integrity pathway, the synthesis of ribosomes, the appropriated reallocation of transcription factors under specific stress conditions and also the regulation of N-glycosylation activity. All these observations suggest the existence of additional targets not yet identified. In the context of the control of carbon metabolism, previous data demonstrated that Pkc1 p might play a central role in the control of cellular growth and metabolism in yeast. In particular, it has been suggested that it might be involved in the derepression of genes under glucose-repression by driving an appropriated subcellular localization of transcriptional factors, such as Mig1 p. In this work, we show that pkc1∆ mutant is unable to grow on glycerol because it cannot perform the derepression of GUT1 gene that encodes for glycerol kinase. Additionally, active transport is also partially affected. Using this phenotype, we were able to isolate a new pkc1∆ revertant. We also isolated two transformants identified as the nuclear exportin Msn5 and the histone deacetylase Hos2 extragenic suppressors of this mutation. Based on these results, we postulate that Pkc1 p may be involved in the control of the cellular localization and/or regulation of the activity of nuclear proteins implicated in gene expression.Fundação Universidade Federal de Ouro Preto (FUFOP). Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) - CBS-1875/95. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 300998/89-9 to R.L.B., 301255/01-6 to L.G.F

    EG-Wettbewerbspolitik: Ein Rueckblick und Ausblick

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    SIGLEBibliothek Weltwirtschaft Kiel YY 11742 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

    No evidence for presence of maternal mitochondrial DNA in the sperm of Mytilus galloprovincialis males

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    Species of the mussel family Mytilidae have a special mitochondrial DNA (mtDNA) transmission system, known as doubly uniparental inheritance (DUI), which consists of a maternally inherited (F) and a paternally inherited (M) mitochondrial genome. Females are normally homoplasmic for the F genome and males are heteroplasmic mosaics, with their somatic tissues dominated by the maternal and their gonads dominated by the paternal genome. Several studies have indicated that the maternal genome may often be present in the male germ line. Here we report the results from the examination of mtDNA in pure sperm from more than 30 males of Mytilus galloprovincialis. In all cases, except one, we detected only the M genome. In the sperm of one male, we detected a paternal genome with an F-like primary sequence that was different from the sequence of the maternal genome in the animal's somatic tissues. We conclude that the male germ line is protected against invasion by the maternal genome. This is important because fidelity of gamete-specific transmission of the two mitochondrial genomes is a basic requirement for the stability of DUI
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