1,536 research outputs found

    Stone-Wales Transformation Paths in Fullerene C60

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    The mechanisms of formation of a metastable defect isomer of fullerene C60 due to the Stone-Wales transformation are theoretically studied. It is demonstrated that the paths of the "dynamic" Stone-Wales transformation at a high sufficient for overcoming potential barriers) temperature can differ from the two "adiabatic" transformation paths discussed in the literature. This behavior is due to the presence of a great near-flat segment of the potential-energy surface in the neighborhood of metastable states. Besides, the sequence of rupture and formation of interatomic bonds is other than that in the case of the adiabatictransformation.Comment: 10 pages, 6 figure

    Lessons learnt, and still to learn, in first in human stem cell trials

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    Developing cellular therapies is not straightforward. This Perspective summarizes the experience of a group of academic stem cell investigators working in different clinical areas and aims to share insight into what we wished we knew before starting. These include (1) choosing the stem cell line and assessing the genome of both the starting and final product, (2) familiarity with GMP manufacturing, reagent validation, and supply chain management, (3) product delivery issues and the additional regulatory challenges, (4) the relationship between clinical trial design and preclinical studies, and (5) the market approval requirements, pathways, and partnerships needed

    Instantaneous Normal Mode Analysis of Supercooled Water

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    We use the instantaneous normal mode approach to provide a description of the local curvature of the potential energy surface of a model for water. We focus on the region of the phase diagram in which the dynamics may be described by the mode-coupling theory. We find, surprisingly, that the diffusion constant depends mainly on the fraction of directions in configuration space connecting different local minima, supporting the conjecture that the dynamics are controlled by the geometric properties of configuration space. Furthermore, we find an unexpected relation between the number of basins accessed in equilibrium and the connectivity between them.Comment: 5 pages, 4 figure

    Knockout of ERK5 causes multiple defects in placental and embryonic development

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    BACKGROUD: ERK5 is a member of the mitogen activated protein kinase family activated by certain mitogenic or stressful stimuli in cells, but whose physiological role is largely unclear. RESULTS: To help determine the function of ERK5 we have used gene targeting to inactivate this gene in mice. Here we report that ERK5 knockout mice die at approximately E10.5. In situ hybridisation for ERK5, and its upstream activator MKK5, showed strong expression in the head and trunk of the embryo at this stage of development. Between E9.5 and E10.5, multiple developmental problems are seen in the ERK5-/- embryos, including an increase in apoptosis in the cephalic mesenchyme tissue, abnormalities in the hind gut, as well as problems in vascular remodelling, cardiac development and placental defects. CONCLUSION: Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival

    Ischaemic preconditioning improves proteasomal activity and increases the degradation of Ī“PKC during reperfusion

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    The response of the myocardium to an ischaemic insult is regulated by two highly homologous protein kinase C (PKC) isozymes, delta and epsilon PKC. Here, we determined the spatial and temporal relationships between these two isozymes in the context of ischaemia/reperfusion (I/R) and ischaemic preconditioning (IPC) to better understand their roles in cardioprotection. Using an ex vivo rat model of myocardial infarction, we found that short bouts of ischaemia and reperfusion prior to the prolonged ischaemic event (IPC) diminished delta PKC translocation by 3.8-fold and increased epsilon PKC accumulation at mitochondria by 16-fold during reperfusion. In addition, total cellular levels of delta PKC decreased by 60 +/- 2.7% in response to IPC, whereas the levels of epsilon PKC did not significantly change. Prolonged ischaemia induced a 48 +/- 11% decline in the ATP-dependent proteasomal activity and increased the accumulation of misfolded proteins during reperfusion by 192 +/- 32%; both of these events were completely prevented by IPC. Pharmacological inhibition of the proteasome or selective inhibition of epsilon PKC during IPC restored delta PKC levels at the mitochondria while decreasing epsilon PKC levels, resulting in a loss of IPC-induced protection from I/R. Importantly, increased myocardial injury was the result, in part, of restoring a delta PKC-mediated I/R pro-apoptotic phenotype by decreasing pro-survival signalling and increasing cytochrome c release into the cytosol. Taken together, our findings indicate that IPC prevents I/R injury at reperfusion by protecting ATP-dependent 26S proteasomal function. This decreases the accumulation of the pro-apoptotic kinase, delta PKC, at cardiac mitochondria, resulting in the accumulation of the pro-survival kinase, epsilon PKC.NIH[AA11147]Oklahoma Center for Advancement of Science and Technology[HR05-171S
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