1,533 research outputs found

    Mindfulness and spirituality: Therapeutic perspectives

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    Social aspects that relate to beliefs and spirituality are subjects of the soul and mind, material to be studied out of the materialistic world. They transcend the body and nest in the experiences of the soul. Nonetheless, taught by mindfulness, a practice that stems from eastern spirituality the religious and/or the spiritual are experiences lived through the body. We conducted a pilot cross-sectional study to test the hypothesis that mindfulness correlates with spiritual beliefs. The results provide insight on the potential impact of mindfulness interventions in patients that value spirituality and metacognitive beliefs in the psychotherapeutic process. These preliminary findings provide a potential insight into the possible mechanisms underlying the application of mindfulness in psychotherapy

    In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

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    A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C–F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.National Institutes of Health (U.S.) (GM46059)National Science Foundation (U.S.) (Predoctoral Fellowship 2010094243)Amgen Inc

    Nuclear variants of bone morphogenetic proteins

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    <p>Abstract</p> <p>Background</p> <p>Bone morphogenetic proteins (BMPs) contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts.</p> <p>Results</p> <p>In all three proteins, a bipartite nuclear localization signal (NLS) was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5) containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle.</p> <p>Conclusions</p> <p>The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.</p

    A proof by graphical construction of the no-pumping theorem of stochastic pumps

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    A stochastic pump is a Markov model of a mesoscopic system evolving under the control of externally varied parameters. In the model, the system makes random transitions among a network of states. For such models, a "no-pumping theorem" has been obtained, which identifies minimal conditions for generating directed motion or currents. We provide a derivation of this result using a simple graphical construction on the network of states

    Inhibition of transforming growth factor-β restores endothelial thromboresistance in vein grafts

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    BackgroundThrombosis is a major cause of the early failure of vein grafts (VGs) implanted during peripheral and coronary arterial bypass surgeries. Endothelial expression of thrombomodulin (TM), a key constituent of the protein C anticoagulant pathway, is markedly suppressed in VGs after implantation and contributes to local thrombus formation. While stretch-induced paracrine release of transforming growth factor-β (TGF-β) is known to negatively regulate TM expression in heart tissue, its role in regulating TM expression in VGs remains unknown.MethodsChanges in relative mRNA expression of major TGF-β isoforms were measured by quantitative polymerase chain reaction (qPCR) in cultured human saphenous vein smooth muscle cells (HSVSMCs) subjected to cyclic stretch. To determine the effects of paracrine release of TGF-β on endothelial TM mRNA expression, human saphenous vein endothelial cells (HSVECs) were co-cultured with stretched HSVSMCs in the presence of 1D11, a pan-neutralizing TGF-β antibody, or 13C4, an isotype-control antibody. Groups of rabbits were then administered 1D11 or 13C4 and underwent interpositional grafting of jugular vein segments into the carotid circulation. The effect of TGF-β inhibition on TM gene expression was measured by qPCR; protein C activating capacity and local thrombus formation were measured by in situ chromogenic substrate assays; and VG remodeling was assessed by digital morphometry.ResultsCyclic stretch induced TGF-β1 expression in HSVSMCs by 1.9 ± 0.2-fold (P < .001) without significant change in the expressions of TGF-β2 and TGF-β3. Paracrine release of TGF-β1 by stretched HSVSMCs inhibited TM expression in stationary HSVECs placed in co-culture by 57 ± 12% (P = .03), an effect that was abolished in the presence of 1D11. Similarly, TGF-β1 was the predominant isoform induced in rabbit VGs 7 days after implantation (3.5 ± 0.4-fold induction; P < .001). TGF-β1 protein expression localized predominantly to the developing neointima and coincided with marked suppression of endothelial TM expression (16% ± 2% of vein controls; P < .03), a reduction in situ activated protein C (APC)-generating capacity (53% ± 9% of vein controls; P = .001) and increased local thrombus formation (3.7 ± 0.8-fold increase over vein controls; P < .01). External stenting of VGs to limit vessel distension significantly reduced TGF-β1 induction and TM downregulation. Systemic administration of 1D11 also effectively prevented TM downregulation, preserved APC-generating capacity, and reduced local thrombus in rabbit VGs without observable effect on neointima formation and other morphometric parameters 6 weeks after implantation.ConclusionTM downregulation in VGs is mediated by paracrine release of TGF-β1 caused by pressure-induced vessel stretch. Systemic administration of an anti-TGF-β antibody effectively prevented TM downregulation and preserved local thromboresistance without negative effect on VG remodeling.Clinical RelevanceVein grafts (VGs) are commonly used conduits for coronary and peripheral arterial bypass surgeries. Thrombosis is a major cause of early VG failure. Trombomodulin (TM), a key component of the anticoagulant protein C pathway, is downregulated early after VG implantation and facilitates local thrombus formation. We found that paracrine release of transforming growth factor-β1 (TGF-β1), caused by pressure-induced stretch, was a potent negative regulator of TM in rabbit VGs. Administration of a neutralizing anti-TGF-β antibody effectively prevented TM downregulation and reduced local thrombus generation without adversely affecting long-term VG remodeling. This may represent a novel strategy to improve patency in patients undergoing arterial bypass procedures

    Dangerous work: The gendered nature of bullying in the context of higher education

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    This paper discusses results from a research project which set out to investigate gender differences in the nature and experience of bullying within the higher education sector. Gender differences emerged in the form and perception of bullying as well as in target response. Results also indicate that, irrespective of gender, bullies can capture and subvert organizational structures and procedures (official hierarchies, mentoring systems, probationary reviews) to further their abuse of the target and to conceal aggressive intent. These outcomes are discussed in relation to gendered assumptions behind management practices and in relation to the masculinist ethic that underpins many higher education management initiatives. Overall, results indicate that bullying cannot be divorced from gender and that such behaviour needs to be seen in a gendered context

    Quantum Theory and Time Asymmetry

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    The relation between quantum measurement and thermodynamically irreversible processes is investigated. The reduction of the state vector is fundamentally asymmetric in time and shows an observer-relatedness which may explain the double interpretation of the state vector as a representation of physical states as well as of information about them. The concept of relevance being used in all statistical theories of irreversible thermodynamics is shown to be based on the same observer-relatedness. Quantum theories of irreversible processes implicitly use an objectivized process of state vector reduction. The conditions for the reduction are discussed, and I speculate that the final (subjective) observer system might even be carried by a spacetime point.Comment: Latex version of a paper published in 1979 (with minor revisions), 18 page
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