Our objective was to test the hypothesis that acute exposure of human skin vasculature to nicotine may have deleterious effects on endothelial function. Vasoconstriction and vasorelaxation in ...isolated perfused human skin flaps (approximately 8 x 18 cm) derived from dermolipectomy specimens were assessed by studying changes in skin perfusion pressure measured by a pressure transducer, and skin perfusion was assessed by a dermofluorometry technique (n = 4 or 5). It was observed that nicotine (10(-7) M) amplified (P < 0.05) the norepinephrine (NE)-induced concentration-dependent (10(-7)-10(-5) M) increase in skin vasoconstriction compared with the control. This amplification effect of nicotine in NE-induced skin vasoconstriction was not blocked by the nicotine-receptor antagonist hexamethonium (10(-6) M) or the cyclooxygenase inhibitor indomethacin (10(-5) M). It was also observed that ACh and nitroglycerin (NTG) elicited a concentration-dependent (10(-8)-10(-5) M) vasorelaxation in skin flaps preconstricted with 8 x 10(-7) M of NE. The vasorelaxation induced by ACh was attenuated (P < 0.05) in the presence of nicotine (10(-7) M) compared with the control. However, skin vasorelaxation induced by NTG was not affected by nicotine (10(-7) M). ACh and NTG are known to induce endothelium-dependent and -independent vasorelaxation, respectively. The present findings were interpreted to indicate that acute exposure of human skin vasculature to nicotine was associated with 1) amplification of NE-induced skin vasoconstriction and 2) impairment of endothelium-dependent skin vasorelaxation. Cyclooxygenase products and nicotine receptors blocked by hexamethonium were not involved in the amplification of NE-induced skin vasoconstriction by nicotine. These findings may provide further insight into the pathogenesis of skin vasospasm in skin flap surgery and skin ischemic disease associated with cigarette smoking or use of smokeless tobacco.
The fibrillins and latent transforming growth factor binding proteins (LTBPs) form a superfamily of extracellular matrix (ECM) proteins characterized by the presence of a unique domain, the ...8-cysteine transforming growth factor beta (TGFβ) binding domain. These proteins are involved in the structure of the extracellular matrix and controlling the bioavailability of TGFβ family members. Genes encoding these proteins show differential expression in mesenchymal cell types which synthesize the extracellular matrix. We have investigated the promoter regions of the seven gene family members using the FANTOM5 CAGE database for human. While the protein and nucleotide sequences show considerable sequence similarity, the promoter regions were quite diverse. Most genes had a single predominant transcription start site region but LTBP1 and LTBP4 had two regions initiating different transcripts. Most of the family members were expressed in a range of mesenchymal and other cell types, often associated with use of alternative promoters or transcription start sites within a promoter in different cell types. FBN3 was the lowest expressed gene, and was found only in embryonic and fetal tissues. The different promoters for one gene were more similar to each other in expression than to promoters of the other family members. Notably expression of all 22 LTBP2 promoters was tightly correlated and quite distinct from all other family members. We located candidate enhancer regions likely to be involved in expression of the genes. Each gene was associated with a unique subset of transcription factors across multiple promoters although several motifs including MAZ, SP1, GTF2I and KLF4 showed overrepresentation across the gene family. FBN1 and FBN2, which had similar expression patterns, were regulated by different transcription factors. This study highlights the role of alternative transcription start sites in regulating the tissue specificity of closely related genes and suggests that this important class of extracellular matrix proteins is subject to subtle regulatory variations that explain the differential roles of members of this gene family.
•We examine expression, promoter use and enhancers for the fibrillin/LTBP gene family.•Promoter switching was observed for most family members.•Multiple enhancers were identified for all family members.•Family members overlapped in tissue specificity with some unique expression patterns.•A degree of redundancy among family members is possible.
An overview is presented of the state-of-the-art of computational tools, data and models developed for neutronics and activation analyses of the IFMIF neutron source. Significant progress has been ...achieved in making available computational tools for simulating the d-Li neutron (and photon) source term with the McDeLicious Monte Carlo code and associated d+6,7Li cross-section data, in generating neutronics Monte Carlo geometry models by the McCad conversion software, and in providing the interface programme MCDO to enable coupled 3D Monte Carlo and discrete ordinates shielding calculations. In the field of nuclear data for IFMIF, a major milestone has been achieved with the launching of the FENDL-3 research project co-ordinated by the IAEA. Another major achievement is the production of the European Activation File, version EAF-2007, which has the neutron energy range extended to the needs of IFMIF and also provides calculated data libraries for deuteron and proton induced activation reactions.
The University of Alabama's Graduate Geropsychology Education (GGE) program was conceived and implemented in the years before the design of the Pike's Peak Model (PPM) of geropsychology training. The ...GGE program provides a unique opportunity to evaluate the PPM, and this paper outlines the GGE program in the framework of the model. Three primary goals defined the GGE program: recruitment and retention of students in the geropsychology program, a doctoral-level interdisciplinary class, and a set of clinical rotations in urban and rural sites. Outcomes were promising, indicating that geropsychology students were able to provide services with positive outcomes to underserved older adults in primary care settings and in a legal clinic, students from several disciplines rated the course very highly, and psychology students indicated that they were likely to continue in the field of geriatric care. Participating students have gone on to careers in geropsychology. Findings from this program support the design of the PPM and provide support for broader implementation of similar training programs.
Abstract Background The Millennium Development Goals (MDGs) have prompted an expansion in approaches to deriving health metrics to measure progress towards their achievement. Accurate measurements ...should take into account the high degrees of spatial heterogeneity in health risks across countries, prompting the development of sophisticated cartographic techniques for mapping and modelling risks. Conversion of these risks to relevant population-based metrics requires equally detailed information on the spatial distribution and attributes of the denominator populations. However, spatial information on age and sex composition are lacking, prompting many health metric studies to overlook the substantial demographic variations that exist subnationally and to merely apply national-level adjustments. Methods Here, we describe the development of high-resolution age and sex structured spatial population datasets for Africa, Asia, and Latin America in 2000–15, built from millions of measurements mapped to more than 200 000 subnational units, and originating from censuses, census microdata, and household surveys. Findings We analysed the substantial variations seen within countries, by settlement type, and across the continents for key MDG indicator groups, focusing on children under 5 and women of childbearing age, and found that substantial differences in various MDG-related health and development indicators can result through using only national-level statistics compared with accounting for subnational variation. Interpretation Progress towards meeting the MDGs will be measured through national-level indicators that mask substantial inequalities and heterogeneities across nations. Cartographic approaches are providing opportunities for quantitative assessments of these inequalities and the targeting of interventions, but demographic spatial datasets to support such efforts remain reliant on coarse and outdated input data for accurately locating risk groups. We have shown here that sufficient data exist to map the distribution of key vulnerable groups, and that doing so has substantial impacts on health metrics. Further details and data are available through the project websites: www.afripop.org , www.asiapop.org , and www.ameripop.org. Funding AJT acknowledges funding support from the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health , and is also supported by grants from NIH/NIAID ( U19AI089674 ) and the Bill & Melinda Gates Foundation ( #49446 and #1032350 ).
Small‐molecule solar cells are demonstrated using Pt and Pd tetraphenylbenzoporphyrin as donor materials. High efficiencies are achieved, and the effects of triplet excited state diffusion are ...studied. The solubility of these molecules allows for the fabrication of solution processed solar cells with relatively high performance.
Lymphangiogenesis plays a crucial role during development, in cancer metastasis and in inflammation. Activation of VEGFR-3 (also known as FLT4) by VEGF-C is one of the main drivers of ...lymphangiogenesis, but the transcriptional events downstream of VEGFR-3 activation are largely unknown. Recently, we identified a wave of immediate early transcription factors that are upregulated in human lymphatic endothelial cells (LECs) within the first 30 to 80 min after VEGFR-3 activation. Expression of these transcription factors must be regulated by additional pre-existing transcription factors that are rapidly activated by VEGFR-3 signaling. Using transcription factor activity analysis, we identified the homeobox transcription factor HOXD10 to be specifically activated at early time points after VEGFR-3 stimulation, and to regulate expression of immediate early transcription factors, including NR4A1. Gain- and loss-of-function studies revealed that HOXD10 is involved in LECs migration and formation of cord-like structures. Furthermore, HOXD10 regulates expression of VE-cadherin, claudin-5 and NOS3 (also known as e-NOS), and promotes lymphatic endothelial permeability. Taken together, these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability.
Cascade Organic Solar Cells Schlenker, Cody W; Barlier, Vincent S; Chin, Stephanie W ...
Chemistry of materials,
09/2011, Letnik:
23, Številka:
18
Journal Article
Recenzirano
We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: ...glass/indium-tin-oxide/donor cascade/C60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl-tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (V oc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and J sc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene–C60 solar cells (FF = 0.54 ± 0.02 and J sc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor–acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer.
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