3,081 research outputs found
Small-molecule inhibitors of myosin proteins
No full textAdvances in screening and computational methods have enhanced recent efforts to discover/design small-molecule protein inhibitors. One attractive target for inhibition is the myosin family of motor proteins. Myosins function in a wide variety of cellular processes, from intracellular trafficking to cell motility, and are implicated in several human diseases (e.g., cancer, hypertrophic cardiomyopathy, deafness and many neurological disorders). Potent and selective myosin inhibitors are, therefore, not only a tool for understanding myosin function, but are also a resource for developing treatments for diseases involving myosin dysfunction or overactivity. This review will provide a brief overview of the characteristics and scientific/therapeutic applications of the presently identified small-molecule myosin inhibitors before discussing the future of myosin inhibitor and activator desig
Benthic assemblage composition on subtidal reefs along a latitudinal gradient in Western Australia
No full textAt regional scales, the distribution of species and the structure of assemblages vary with latitude within many marine and terrestrial systems. The oligotrophic coastal waters of Western Australia (WA) support highly speciose and endemic assemblages, yet spatial patterns in benthic structure are currently poorly known. We examined benthic assemblage composition along a latitudinal gradient of 28.5–33.5°S and a depth gradient of 14–62 m, on subtidal reefs in warm-temperate WA. We surveyed benthos using a remotely triggered digital stills camera. In total, we sampled macroalgae and sessile invertebrates at 201 sites spread across four locations. Percent cover of coarse taxonomic groups and dominant species was estimated from over 2000 photoquadrat samples. We recorded significant differences in benthic assemblage composition between locations, and along depth gradients within each location. However, the magnitude of change with depth was not consistent between locations, and shifts in assemblage composition along the depth gradients were not as pronounced as expected. The percent cover of all dominant benthic groupings differed between locations, and several key taxa, such as the kelp Scytothalia dorycarpa, brown foliose macroalgae, hard corals and sponges, changed predictably along the latitudinal gradient. Our study adopted a coarse taxonomic, but assemblage-wide, approach to describing macrobenthic assemblages, and clear differences between locations and depths were detected. The surveys have provided baseline data on broad scale ecosystem structure against which to detect future ecological change
Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-dependent autophagosome maturation and fusion with the lysosome
No full textAutophagy targets pathogens, damaged organelles and protein aggregates for lysosomal degradation. These ubiquitylated cargoes are recognized by specific autophagy receptors, which recruit LC3-positive membranes to form autophagosomes. Subsequently, autophagosomes fuse with endosomes and lysosomes, thus facilitating degradation of their content; however, the machinery that targets and mediates fusion of these organelles with autophagosomes remains to be established. Here we demonstrate that myosin VI, in concert with its adaptor proteins NDP52, optineurin, T6BP and Tom1, plays a crucial role in autophagy. We identify Tom1 as a myosin VI binding partner on endosomes, and demonstrate that loss of myosin VI and Tom1 reduces autophagosomal delivery of endocytic cargo and causes a block in autophagosome-lysosome fusion. We propose that myosin VI delivers endosomal membranes containing Tom1 to autophagosomes by docking to NDP52, T6BP and optineurin, thereby promoting autophagosome maturation and thus driving fusion with lysosomes
Approximating the value function for optimal experimentation
No full textIn the economics literature, there are two dominant approaches for solving models with optimal experimentation (also called active learning). The first approach is based on the value function and the second on an approximation method. In principle the value function approach is the preferred method. However, it suffers from the curse of dimensionality and is only applicable to small problems with a limited number of policy variables. The approximation method allows for a computationally larger class of models, but may produce results that deviate from the optimal solution. Our simulations indicate that when the effects of learning are limited, the differences may be small. However, when there is sufficient scope for learning, the value function solution seems more aggressive in the use of the policy variable
Design metrics for evaluating the propulsive efficiency of future ships
No full textThere is an increasing need for the ship design process to take account of environmental issues such as the emission of greenhouse gases and the likely extension of a carbon dioxide charging mechanism to international shipping. These issues, together with the need for economic viability, provide further incentives to improve the efficiency of propulsion of ships. The main components of powering are firstly reviewed. Individual components and other power saving devices are identified which should contribute to improvements in the overall efficiency of propulsion. Suitable design metrics and procedures, taking into account economic and environmental factors, are recommended for the design of future ships
Brief note: some observations on oscillating tangential forces and wear in general plane contacts
No full textFor general plane contact of elastically similar materials, including cases where there are multiple regions of contact, general properties of the partial slip solution for conditions of constant normal force and monotonically increasing shearing force have been found recently by the first author. An extension is given here to cover the unloading and cyclic loading cases. Further, it is shown that, if the tangential load varies between two fixed limits, the region of stick does not change, even if relative microslip causes wear, changing continuously the profile of the indenter. The contact area will change, but wear will not enter the original region of adhesion. The theoretical limit to which wear will eventually, asymptotically proceed is established, viz. almost complete contact over what is the initial stick zone, although it may, in practice, take a long time to reach this state
Macroalgae and temperate rocky reefs
No full textThomas Wernberg, Alex Campbell, Melinda A. Coleman, Sean D. Connell, Gary A. Kendrick, Pippa J. Moore, Bayden D. Russell, Daniel A. Smale, Peter D. Steinber
The description of Kabarda by D.A. Milutin in the context of the cauсasus version of russian orien-talism foundation
No full textThe paper pertains to the analysis of a manuscript authored by D.A. Milutin in the first half of the 19th century, regarding the region of Kabarda. This manuscript, hitherto unpublished in academic circles, has been the subject of our examination. Our endeavor was to uncover the utilization of orientalist clichés by the manuscript's author, in order to depict both the geographical delineations of this ethno-political entity and the ethnography, livelihood, societal structure, and customary legal norms of its inhabitants. A remarkable parallel can be observed between certain aspects of the manuscript and the ideas propounded by E. Said in his discourse on European Orientalism. The researcher drew a comparison between the political framework and traditions of the Kabardian people and those prevalent in Europe. Moreover, the researcher romanticized the region's historical past, employing the conceptof "reverse human progress," along with other typical methodologies embraced by Orientalist thinkers of that era. Concomitantly, D.A. Milutin provided detailed descriptions of the political, social, and everyday existence in Kabarda, thereby endowing the manuscript with an intrinsic value as an original historical and cultural resource for contemporary scholars. It is concluded that, similar to numerous analogous texts produced by Orientalist scholars, the significance of D.A. Milutin's man-uscript lies not in its political arguments concerning the military and economic dominion of the Russian Empire over the Caucasian peoples, or the imperative to extend colonial governance to these ethnic territorie
Expected optimal feedback with Time-Varying Parameters
No full textIn this paper we derive the closed loop form of the Expected Optimal Feedback rule, sometimes called passive learning stochastic control, with time varying parameters. As such this paper extends the work of Kendrick (1981,2002, Chapter 6) where parameters are assumed to vary randomly around a known constant mean. Furthermore, we show that the cautionary myopic rule in Beck and Wieland (2002) model, a test bed for comparing various stochastic optimizations approaches, can be cast into this framework and can be treated as a special case of this solution
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