The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets. 相似文献
Journal of Communications Technology and Electronics - Abstract—The article presents a rigorous numerical solution, using the Wiener–Hopf method, to the problem of plane wave... 相似文献
The proliferating need for sustainability intervention in food grain transportation planning is anchoring the attention of researchers in the interests of stakeholders and environment at large. Uncertainty associated with food grain supply further intensifies the problem steering the need for designing robust, cost-efficient and sustainable models. In line with this, this paper aims to develop a robust and sustainable intermodal transportation model to facilitate single type of food grain commodity shipments while considering procurement uncertainty, greenhouse gas emissions, and intentional hub disruption. The problem is designed as a mixed integer non-linear robust optimisation model on a hub and spoke network for evaluating near optimal shipment quantity, route selection and hub location decisions. The robust optimisation approach considers minimisation of total relative regret associated with total cost subject to several real-time constraints. A version of Particle Swarm Optimisation with Differential Evolution is proposed to tackle the resulting NP-hard problem. The model is tested with two other state-of the art meta-heuristics for small, medium, and large datasets subject to different procurement scenarios inspired from real time food grain operations in Indian context. Finally, the solution is evaluated with respect to total cost, model and solution robustness for all instances. 相似文献
Surface integrity characterization of manufactured component is very important as it significantly affects the in-service performance of the component. Till now, surface integrity was evaluated using conventional measurement technique like microhardness tester, X-ray diffraction, optical microscopy and surface roughness tester. But, this technique being laboratory based cannot be used for in-service monitoring of the surface integrity. The present study focuses on the characterization of surface integrity upon electric discharge machined sample using non-destructive magnetic Barkhausen noise technique. Electric discharge machining was performed in die-sinking mode on die steel using copper–tungsten electrode (negative polarity). Experiment was performed by selecting different levels of peak current, gap voltage and pulse on time. Surface integrity characteristics like microhardness change, residual stress, microstructural alteration and surface roughness were analysed using microhardness tester, X-ray diffraction, optical microscopy and surface roughness tester, respectively, and were then correlated with magnetic parameter like root mean square value and peak value obtained from Barkhausen noise signal. The results show a good correlation between magnetic parameter (RMS and Peak value) of Barkhausen noise with the microhardness and surface roughness of the machined sample.
Photonic Network Communications - Optical packet switching is a prominent technology proposing not only a reduction in the energy consumption by the elimination of numerous... 相似文献