88 research outputs found

    Alien Registration- Stiles, Ella V. (Fort Fairfield, Aroostook County)

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    https://digitalmaine.com/alien_docs/35699/thumbnail.jp

    Laser cooling of a magnetically guided ultra cold atom beam

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    We report on the transverse laser cooling of a magnetically guided beam of ultra cold chromium atoms. Radial compression by a tapering of the guide is employed to adiabatically heat the beam. Inside the tapered section heat is extracted from the atom beam by a two-dimensional optical molasses perpendicular to it, resulting in a significant increase of atomic phase space density. A magnetic offset field is applied to prevent optical pumping to untrapped states. Our results demonstrate that by a suitable choice of the magnetic offset field, the cooling beam intensity and detuning, atom losses and longitudinal heating can be avoided. Final temperatures below 65 microkelvin have been achieved, corresponding to an increase of phase space density in the guided beam by more than a factor of 30.Comment: 9 pages, 4 figure

    Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

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    Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

    Learning at the Interstices; Locating Practical Philosophies for Understanding Physical/virtual Inter-spaces

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    Virtual worlds are relatively recent developments, and so it is tempting to believe that they need to be understood through newly developed theories and philosophies. However, humans have long thought about the nature of reality and what it means to be “real.” This paper examines the three persistent philosophical concepts of Metaxis, Liminality and Space that have evolved across more than 2000 years of meditation, contemplation and reflection. Our particular focus here is on the nature of the interface between the virtual and the physical: at the interstices, and how the nature of transactions and transitions across those interfaces may impact upon learning. This may, at first, appear to be an esoteric pursuit, but we ground our arguments in primary and secondary data from research studies in higher education

    Responsible management: Engaging moral reflexive practice through threshold concepts

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    YesIn this conceptual paper we argue that, to date, principles of responsible management have not impacted practice as anticipated because of a disconnect between knowledge and practice. This disconnect means that an awareness of ethical concerns, by itself, does not help students take personal responsibility for their actions. We suggest that an abstract knowledge of principles has to be supplemented by an engaged understanding of the responsibility of managers and leaders to actively challenge irresponsible practices. We argue that a form of moral reflexive practice drawing on an understanding of threshold concepts is central to responsible management, and provides a gateway to transformative learning. Our conceptual argument leads to implications for management and professional education

    Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes

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    Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils.We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i 1 μM; F/F0 5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structureinduced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes

    Modeling CICR in rat ventricular myocytes: voltage clamp studies

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    <p>Abstract</p> <p>Background</p> <p>The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect <it>Ca</it><sup>2+ </sup>loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR <it>Ca</it><sup>2+ </sup>release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic <it>Ca</it><sup>2+ </sup>concentration ([<it>Ca</it><sup>2+</sup>]<it><sub>myo</sub></it>).</p> <p>Methods</p> <p>The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed <it>Ca</it><sup>2+ </sup>channels (trigger-channel and release-channel). It releases <it>Ca</it><sup>2+ </sup>flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[<it>Ca</it><sup>2+</sup>]<it><sub>myo</sub></it>.</p> <p>Results</p> <p>Our model reproduces measured VC data published by several laboratories, and generates graded <it>Ca</it><sup>2+ </sup>release at high <it>Ca</it><sup>2+ </sup>gain in a homeostatically-controlled environment where [<it>Ca</it><sup>2+</sup>]<it><sub>myo </sub></it>is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR <it>Ca</it><sup>2+ </sup>release, its activation by trigger <it>Ca</it><sup>2+</sup>, and its refractory characteristics mediated by the luminal SR <it>Ca</it><sup>2+ </sup>sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence <it>Ca</it><sup>2+ </sup>homeostasis.</p> <p>Conclusions</p> <p>We examine the role of the above <it>Ca</it><sup>2+ </sup>regulating mechanisms in handling various types of induced disturbances in <it>Ca</it><sup>2+ </sup>levels by quantifying cellular <it>Ca</it><sup>2+ </sup>balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.</p

    The physician's unique role in preventing violence: a neglected opportunity?

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    Love it when you speak foreign: A trans-national perspective on the professional development of doctoral supervisors in South Africa

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    Being a successful doctoral supervisor and adhering to international requirements and contexts involve important qualities. Being knowledgeable in disciplines and understanding different methodologies, being sensitive to cultural diversity and cultivating interpersonal relationships are examples. As doctoral candidates and their supervisors carry major responsibilities, doctoral quality and success are associated with several challenges. This paper explores some of these challenges and suggests that candidates and supervisors might contribute more substantially to new knowledge if international quality measures for theses and ‘doctorateness’ (or ‘doctoralness’) are considered. This explorative study reports descriptive and analytical findings from a project in South Africa whereby three senior academics from three countries collaborated and acted as facilitators of research and developmental efforts concerning doctoral education and the professional development of supervisors. Such efforts involved both supervisors and doctoral candidates – the latter whose views are seen as important to shape supervisors’ views of their own supervisory practices and standards for the doctorate. The paper outlines the processes and feedback from a series of developmental opportunities that were created and provides guidelines as to how trans-national efforts – particularly, but not exclusively, in the context of a developing country – can be used to promote doctoral education and supervisor professional development

    Doctorateness – An Elusive Concept?

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