13,142 research outputs found
The grounding argument against non-reductive moral realism
The supervenience argument against non-reductive moral realism threatens to rule out the existence of irreducibly normative properties by establishing that for every normative property there is a corresponding non-normative property that is necessarily co-extensive with it. This chapter identifies a hyperintensional analogue of the supervenience argument that threatens non-reductionism even within a hyperintensional setting by establishing that for every normative property there is a corresponding non-normative property that has the very same grounds and is, accordingly, hyperintensionally equivalent. It is then argued that non-reductionism can nevertheless be salvaged by distinguishing the different grounding relations that are involved in grounding the normative property and the corresponding non-normative property. Non-reductionist versions of moral realism thus turn out to be committed to there being irreducibly different grounding relations.</p
Chromogranin A in the pancreatic islet
Chromogranin A (CGA) is the major soluble protein within secretory vesicles of chromaffin cells. A polyclonal antiserum was raised against bovine CGA and characterized in two-dimensional immunoblots. Cellular and subcellular distribution of CGA in bovine pancreatic islet was investigated by immunocytochemistry. At the light microscopic level, CGA-like immunoreactivity was found in the same cells that react with antibodies against insulin, glucagon, and somatostatin. A minority of cells containing pancreatic polypeptide also showed faint immunostaining. At the ultrastructural level (protein A-gold technique), CGA-like immunoreactivity was confined exclusively to the secretory vesicles. Whereas the hormones were localized mainly in the central part of the secretory vesicles, CGA was present predominantly in the periphery. These findings indicate that a CGA-like protein is a regular constituent of the matrix of secretory vesicles in pancreatic endocrine cells
Serotonylation: serotonin signaling and epigenetics
Serotonylation, the covalent linkage of serotonin to proteins has been discovered more than 60 years ago but only recently the mechanisms and first functions have been elucidated. It has been found that transglutaminases (TG) such as TG2 and the blood coagulation factor XIIIa are the enzymes which catalyze the linkage of serotonin and other monoamines to distinct glutamine (Gln) residues of target proteins. The first target proteins, small G-proteins and extracellular matrix constituents, were found in platelets and are pivotally involved in platelet aggregation and the formation of thrombi. The serotonylation of the same proteins is also involved in insulin secretion and in the proliferation of pulmonary vascular smooth muscle cells and thereby in the pathogenesis of pulmonary arterial hypertension (PAH). Recently histones have been described as targets of serotonylation opening the area of transcriptional control to this posttranslational protein modification. Future studies will certainly reveal further target proteins, signaling pathways, cellular processes, and diseases, in which serotonylation or, more general, monoaminylation is important
Characterization of hormone and protein release from alpha-toxin- permeabilized chromaffin cells in primary culture
Addition of Staphylococcus aureus alpha-toxin to adult bovine chromaffin cells maintained in primary culture causes permeabilization of cell membrane as shown by the release of intracellular 86Rb+. The alpha-toxin does not provoke a spontaneous release of either catecholamines or chromogranin A, a protein marker of the secretory granule, showing the integrity of the secretory vesicle membrane. However the addition of micromolar free Ca2+ concentration induced the co-release of noradrenaline and chromogranin A. In alpha-toxin-treated cells, the released chromogranin A could not be sedimented and lactate dehydrogenase was still associated within cells, which provides direct evidence that secretory product is liberated by exocytosis. By contrast, permeabilization of cells with digitonin caused a Ca2+- dependent but also a Ca2+-independent release of secretory product, a dramatic loss of lactate dehydrogenase, as well as release of secretory product in a sedimentable form. Ca2+-dependent exocytosis from alpha- toxin-permeabilized cells required Mg2+-ATP and did not occur in the presence of other nucleotides. Thus alpha-toxin is a convenient tool to permeabilize chromaffin cells, and has the advantage of keeping intracellular structures, specifically the exocytotic machinery, intact
Swords and Plowshares
Cactus, chaos and caudillos: this awkwardly alliterative phrase unfortunately characterizes the views of many North Americans towards their neighbors south of the Rio Grande
Design and control of kinematically redundant robots for maximizing failure-tolerant workspaces
2021 Spring.Includes bibliographical references.Kinematically redundant robots have extra degrees of freedom so that they can tolerate a joint failure and still complete an assigned task. Previous work has defined the "failure-tolerant workspace" as the workspace that is guaranteed to be reachable both before and after an arbitrary locked-joint failure. One mechanism for maximizing this workspace is to employ optimal artificial joint limits prior to a failure. This dissertation presents two techniques for determining these optimal artificial joint limits. The first technique is based on the gradient ascent method. The proposed technique is able to deal with the discontinuities of the gradient that are due to changes in the boundaries of the failure tolerant workspace. This technique is illustrated using two examples of three degree-of-freedom planar serial robots. The first example is an equal link length robot where the optimal artificial joint limits are computed exactly. In the second example, both the link lengths and artificial joint limits are determined, resulting in a robot design that has more than twice the failure-tolerant area of previously published locally optimal designs. The second technique presented in this dissertation is a novel hybrid technique for estimating the failure-tolerant workspace size for robots of arbitrary kinematic structure and any number of degrees of freedom performing tasks in a 6D workspace. The method presented combines an algorithm for computing self-motion manifold ranges to estimate workspace envelopes and Monte-Carlo integration to estimate orientation volumes to create a computationally efficient algorithm. This algorithm is then combined with the coordinate ascent optimization technique to determine optimal artificial joint limits that maximize the size of the failure-tolerant workspace of a given robot. This approach is illustrated on multiple examples of robots that perform tasks in 3D planar and 6D spatial workspaces
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