493 research outputs found

    A comparison between pulsed and CW laser annealing for solar cell applications

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    The application of laser processing in solar cell fabrication is considered. Specific emphasis is placed on a process developed for the fabrication of a 16.6% silicon solar cell using pulsed laser processing. Results are presented which compare pulsed laser annealing with CW laser annealing in solar cell fabrication

    Avidity maturation of memory CD8 T cells is limited by self-antigen expression

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    Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. We developed a system that revealed a population of self-specific CD8 T cells within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)-expressing transgenic mice with recombinant viruses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T cells able to respond to secondary infection. However, whereas the avidity of memory cells in normal mice increased dramatically with repeated immunizations, avidity maturation was limited for self-specific CD8 T cells. Despite decreased avidity, such memory cells afforded protection against infection, but did not induce overt autoimmunity. Further, up-regulation of self-antigen expression in dendritic cells using an inducible system promoted programmed death-1 expression, but not clonal expansion of preexisting memory cells. Thus, the self-reactive T cell repertoire is controlled by overlapping mechanisms influenced by antigen dose

    Cell-selective Knockout and 3D Confocal Image Analysis Reveals Separate Roles for Astrocyte- and Endothelial-derived CCL2 in Neuroinflammation

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    Background Expression of chemokine CCL2 in the normal central nervous system (CNS) is nearly undetectable, but is significantly upregulated and drives neuroinflammation during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis which is considered a contributing factor in the human disease. As astrocytes and brain microvascular endothelial cells (BMEC) forming the blood–brain barrier (BBB) are sources of CCL2 in EAE and other neuroinflammatory conditions, it is unclear if one or both CCL2 pools are critical to disease and by what mechanism(s). Methods Mice with selective CCL2 gene knockout (KO) in astrocytes (Astro KO) or endothelial cells (Endo KO) were used to evaluate the respective contributions of these sources to neuroinflammation, i.e., clinical disease progression, BBB damage, and parenchymal leukocyte invasion in a myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced EAE model. High-resolution 3-dimensional (3D) immunofluorescence confocal microscopy and colloidal gold immuno-electron microscopy were employed to confirm sites of CCL2 expression, and 3D immunofluorescence confocal microscopy utilized to assess inflammatory responses along the CNS microvasculature. Results Cell-selective loss of CCL2 immunoreactivity was demonstrated in the respective KO mice. Compared to wild-type (WT) mice, Astro KO mice showed reduced EAE severity but similar onset, while Endo KO mice displayed near normal severity but significantly delayed onset. Neither of the KO mice showed deficits in T cell proliferation, or IL-17 and IFN-γ production, following MOG35-55 exposure in vitro, or altered MOG-major histocompatibility complex class II tetramer binding. 3D confocal imaging further revealed distinct actions of the two CCL2 pools in the CNS. Astro KOs lacked the CNS leukocyte penetration and disrupted immunostaining of CLN-5 at the BBB seen during early EAE in WT mice, while Endo KOs uniquely displayed leukocytes stalled in the microvascular lumen. Conclusions These results point to astrocyte and endothelial pools of CCL2 each regulating different stages of neuroinflammation in EAE, and carry implications for drug delivery in neuroinflammatory disease

    CD4+ T Cell Regulation of CD25 Expression Controls Development of Short-Lived Effector CD8+ T Cells in Primary and Secondary Responses

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    Both CD4(+) T cell help and IL-2 have been postulated to program activated CD8(+) T cells for memory cell development. However, the linkage between these two signals has not been well elucidated. Here we have studied effector and memory CD8(+) T cell differentiation following infection with three pathogens (Listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both CD4(+) T cells and IL-2 signaling. We found that expression of CD25 on antigen-specific CD8(+) T cells peaked 3-4 days after initial priming and was dependent on CD4(+) T cell help, likely through a CD28:CD80/86 mediated pathway. CD4(+) T cell or CD25-deficiency led to normal early effector CD8(+) T cell differentiation, but a subsequent lack of accumulation of CD8(+) T cells resulting in overall decreased memory cell generation. Interestingly, in both primary and recall responses KLRG1(high) CD127(low) short-lived effector cells were drastically diminished in the absence of IL-2 signaling, although memory precursors remained intact. In contrast to previous reports, upon secondary antigen encounter CD25-deficient CD8(+) T cells were capable of undergoing robust expansion, but short-lived effector development was again impaired. Thus, these results demonstrated that CD4(+) T cell help and IL-2 signaling were linked via CD25 up-regulation, which controls the expansion and differentiation of antigen-specific effector CD8(+) T cells, rather than programming memory cell traits

    Ocean change within shoreline communities: from biomechanics to behaviour and beyond

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    Humans are changing the physical properties of Earth. In marine systems, elevated carbon dioxide concentrations are driving notable shifts in temperature and seawater chemistry. Here, we consider consequences of such perturbations for organism biomechanics and linkages amongst species within communities.In particular,we examine case examples of altered morphologies and material properties, disrupted consumer–prey behaviours, and the potential for modulated positive (i.e. facilitative) interactions amongst taxa, as incurred through increasing ocean acidity and rising temperatures. We focus on intertidal rocky shores of temperate seas as model systems, acknowledging the longstanding role of these communities in deciphering ecological principles. Our survey illustrates the broad capacity for biomechanical and behavioural shifts in organisms to influence the ecology of a transforming worl

    Diversity of Francisella Species in Environmental Samples from Martha’s Vineyard, Massachusetts

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    We determined whether Francisella spp. are present in water, sediment, and soil from an active tularemia natural focus on Martha’s Vineyard, Massachusetts, during a multiyear outbreak of pneumonic tularemia. Environmental samples were tested by polymerase chain reaction (PCR) targeting Francisella species 16S rRNA gene and succinate dehydrogenase A (sdhA) sequences; evidence of the agent of tularemia was sought by amplification of Francisella tularensis-specific sequences for the insertion element ISFTu2, 17-kDa protein gene tul4, and the 43-kDa outer membrane protein gene fopA. Evidence of F. tularensis subsp. tularensis, the causative agent of the human infections in this outbreak, was not detected from environmental samples despite its active transmission among ticks and animals in the sampling site. Francisella philomiragia was frequently detected from a brackish-water pond using Francisella species PCR targets, and subsequently F. philomiragia was isolated from an individual brackish-water sample. Distinct Francisella sp. sequences that are closely related to F. tularensis and Francisella novicida were detected from samples collected from the brackish-water pond. We conclude that diverse Francisella spp. are present in the environment where human cases of pneumonic tularemia occur

    Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age.

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    The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain

    Metapopulation structure for perpetuation of Francisella tularensis tularensis

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    <p>Abstract</p> <p>Background</p> <p>Outbreaks of Type A tularemia due to <it>Francisella tularensis tularensis </it>are typically sporadic and unstable, greatly hindering identification of the determinants of perpetuation and human risk. Martha's Vineyard, Massachusetts has experienced an outbreak of Type A tularemia which has persisted for 9 years. This unique situation has allowed us to conduct long-term eco-epidemiologic studies there. Our hypothesis is that the agent of Type A tularemia is perpetuated as a metapopulation, with many small isolated natural foci of transmission. During times of increased transmission, the foci would merge and a larger scale epizootic would occur, with greater likelihood that humans become exposed.</p> <p>Methods</p> <p>We sampled questing dog ticks from two natural foci on the island and tested them for tularemia DNA. We determined whether the force of transmission differed between the two foci. In addition, we examined the population structure of <it>F. tularensis </it>from ticks by variable number tandem repeat (VNTR) analysis, which allowed estimates of diversity, linkage disequilibrium, and eBURST analysis.</p> <p>Results</p> <p>The prevalence of tularemia DNA in ticks from our two field sites was markedly different: one site was stable over the course of the study yielding as many as 5.6% positive ticks. In contrast, infected ticks from the comparison site markedly increased in prevalence, from 0.4% in 2003 to 3.9% in 2006. Using 4 VNTR loci, we documented 75 different haplotypes (diversity = 0.91). eBURST analysis indicates that the stable site was essentially clonal, but the comparison site contained multiple unrelated lineages. The general bacterial population is evolving clonally (multilocus disequilibrium) and the bacteria in the two sites are reproductively isolated.</p> <p>Conclusion</p> <p>Even within an isolated island, tularemia natural foci that are no more than 15 km apart are uniquely segregated. One of our sites has stable transmission and the other is emergent. The population structure at the stable site is that of a clonal complex of circulating bacteria, whereas the emerging focus is likely to be derived from multiple founders. We conclude that the agent of tularemia may perpetuate in small stable natural foci and that new foci emerge as a result of spillover from such stable sites.</p

    Proximity induced metal/insulator transition in YBa2Cu3O7/La2/3Ca1/3MnO3Y Ba_2 Cu_3 O_7 / La_{2/3} Ca_{1/3} Mn O_3 superlattices

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    The far-infrared dielectric response of superlattices (SL) composed of superconducting YBa2_{2}Cu3_{3}O7_{7} (YBCO) and ferromagnetic La0.67_{0.67}% Ca0.33_{0.33}MnO3_{3} (LCMO) has been investigated by ellipsometry. A drastic decrease of the free carrier response is observed which involves an unusually large length scale of dcrit^{crit}\approx 20 nm in YBCO and dcrit^{crit}\approx 10 nm in LCMO. A corresponding suppression of metallicity is not observed in SLs where LCMO is replaced by the paramagnetic metal LaNiO3_{3}. Our data suggest that either a long range charge transfer from the YBCO to the LCMO layers or alternatively a strong coupling of the charge carriers to the different and competitive kind of magnetic correlations in the LCMO and YBCO layers are at the heart of the observed metal/insulator transition. The low free carrier response observed in the far-infrared dielectric response of the magnetic superconductor RuSr2_{2}GdCu2_{2}O8_{8} is possibly related to this effect

    Optical properties of MgH2 measured in situ in a novel gas cell for ellipsometry/spectrophotometry

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    The dielectric properties of alpha-MgH2 are investigated in the photon energy range between 1 and 6.5 eV. For this purpose, a novel sample configuration and experimental setup are developed that allow both optical transmission and ellipsometric measurements of a transparent thin film in equilibrium with hydrogen. We show that alpha-MgH2 is a transparent, colour neutral insulator with a band gap of 5.6 +/- 0.1 eV. It has an intrinsic transparency of about 80% over the whole visible spectrum. The dielectric function found in this work confirms very recent band structure calculations using the GW approximation by Alford and Chou [J.A. Alford and M.Y. Chou (unpublished)]. As Pd is used as a cap layer we report also the optical properties of PdHx thin films.Comment: REVTeX4, 15 pages, 12 figures, 5 table
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