403 research outputs found

    On the origin of thermal string gas

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    We investigate decaying D-branes as the origin of the thermal string gas of string gas cosmology. We consider initial configurations of low-dimensional branes and argue that they can time evolve to thermal string gas. We find that there is a range in the weak string coupling and fast brane decay time regimes, where the initial configuration could drive the evolution of the dilaton to values, where exactly three spacelike directions grow large.Comment: 16 pages, 4 figures, v2: references adde

    Joy without demands: Hospital clowns in the world of ailing children

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    The aim of the present study was to achieve, using an affect theory approach (Tomkins, 1962; 1963; 1991), a deeper theoretical understanding of the psychological significance of hospital clowns' work in caring for ailing children viewed from a care-giver perspective. The methodological approach was qualitative and based on 20 interviews with healthcare staff: 3 men and 17 women. The result showed how the staff emphasized a psychological quality of care alongside the physical quality of care. The hospital clowns' “unexpected possibility” provided a safe area for recovery, for both the children and the staff. The theoretical interpretation showed the presence of the affects surprise/startle, interest/excitement, and enjoyment/joy as well as specifically how “joy without demands” often had a lingering effect in the form of vitality. Joy without demands is discussed in relation to psychological theory with emphasis on: a confirmation of the body's possibilities, a magical attachment, a chance to transcend boundaries, and a non-demanding situation

    Discovery of Small Molecules Targeting the Synergy of Cardiac Transcription Factors GATA4 and NKX2-5

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    Transcription factors are pivotal regulators of gene transcription, and many diseases are associated with the deregulation of transcriptional networks. In the heart, the transcription factors GATA4 and NKX2-5 are required for cardiogenesis. GATA4 and NKX2-5 interact physically, and the activation of GATA4, in cooperation with NKX2-5, is essential for stretch-induced cardiomyocyte hypertrophy. Here, we report the identification of four small molecule families that either inhibit or enhance the GATA4-NKX2-5 transcriptional synergy. A fragment-based screening, reporter gene assay, and pharmacophore search were utilized for the small molecule screening, identification, and optimization. The compounds modulated the hypertrophic agonist-induced cardiac gene expression. The most potent hit compound, N-[4-(diethylamino)phenyl]-5-methyl-3-phenylisoxazole-4-carboxamide (3, IC50 = 3 mu M), exhibited no activity on the protein kinases involved in the regulation of GATA4 phosphorylation. The identified and chemically and biologically characterized active compound, and its derivatives may provide a novel class of small molecules for modulating heart regeneration.Peer reviewe

    Magical attachment: Children in magical relations with hospital clowns

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    The aim of the present study was to achieve a theoretical understanding of several different-age children's experiences of magic relations with hospital clowns in the context of medical care, and to do so using psychological theory and a child perspective. The method used was qualitative and focused on nine children. The results showed that age was important to consider in better understanding how the children experienced the relation with the hospital clowns, how they described the magical aspects of the encounter and how they viewed the importance of clown encounters to their own well-being. The present theoretical interpretation characterized the encounter with hospital clowns as a magical safe area, an intermediate area between fantasy and reality. The discussion presented a line of reasoning concerning a magical attachment between the child and the hospital clowns, stating that this attachment: a) comprised a temporary relation; b) gave anonymity; c) entailed reversed roles; and d) created an emotional experience of boundary-transcending opportunities

    Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

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    Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding
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