265 research outputs found

    Study of V/STOL aircraft implementation. Volume 2: Appendices

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    An analysis of V/STOL aircraft implementation and utilization is presented. The subjects discussed are: (1) short haul air transportation requirements, (2) available aircraft technology, (3) aircraft production requirements, (4) airport requirements, (5) roles and responsibilities, and (6) cost and funding

    Competition for Graphene: Graphynes with Direction-Dependent Dirac Cones

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    The existence of Dirac cones in the band structure of two-dimensional materials accompanied by unprecedented electronic properties is considered to be a unique feature of graphene related to its hexagonal symmetry. Here, we present other two-dimensional carbon materials, graphynes, that also possess Dirac cones according to first-principles electronic structure calculations. One of these materials, 6,6,12-graphyne, does not have hexagonal symmetry and features two self-doped nonequivalent distorted Dirac cones suggesting electronic properties even more amazing than that of graphene

    Genetic susceptibility to burnout in a Swedish twin cohort

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    Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout

    Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma

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    Abstract Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. Here, we demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Selective targeting of multiple myeloma cell lines through CBP/EP300 bromodomain inhibition is the result of direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4, which is essential for the viability of myeloma cells, and the concomitant repression of the IRF4 target gene c-MYC. Ectopic expression of either IRF4 or MYC antagonizes the phenotypic and transcriptional effects of CBP/EP300 bromodomain inhibition, highlighting the IRF4/MYC axis as a key component of its mechanism of action. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network

    High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart

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    Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following ÎČ-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 Όm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart

    Person-Specific Non-shared Environmental Influences in Intra-individual Variability : A Preliminary Case of Daily School Feelings in Monozygotic Twins

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    Most behavioural genetic studies focus on genetic and environmental influences on inter-individual phenotypic differences at the population level. The growing collection of intensive longitudinal data in social and behavioural science offers a unique opportunity to examine genetic and environmental influences on intra-individual phenotypic variability at the individual level. The current study introduces a novel idiographic approach and one novel method to investigate genetic and environmental influences on intra-individual variability by a simple empirical demonstration. Person-specific non-shared environmental influences on intra-individual variability of daily school feelings were estimated using time series data from twenty-one pairs of monozygotic twins (age = 10 years, 16 female pairs) over two consecutive weeks. Results showed substantial inter-individual heterogeneity in person-specific non-shared environmental influences. The current study represents a first step in investigating environmental influences on intra-individual variability with an idiographic approach, and provides implications for future behavioural genetic studies to examine developmental processes from a microscopic angle
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