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
Debittered trub (brewing waste) is an important source of protein source (70.26%). Trub and whey protein were used for 5% protein enrichment of ice cream frozen by liquid nitrogen. Three formulations were elaborated: ice cream standard (ICS), ice cream with whey protein (ICW) and ice cream with trub (ICT). Chemical composition, rheological properties, texture, overrun, melting rate, scanning electron microscopy and a sensorial test were performed. Results showed that ICT presented a higher viscosity, obtained on the upward curve up to 6.76 Pa s−1, consistency index (22.96 (Pa s−1)n), hysteresis area (140.40 mPa s−1) and hardness (31113.33 g) but a lower melting rate (0.38 g min−1), overrun (13.92%) and sensorial acceptability than the other formulations. The addition of trub debittered for protein enrichment improved ice cream properties and demonstrated that it could be used as a food ingredient. 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
The Fourth Industrial Revolution – also known as Industry 4.0 (i4.0) – comprises the digitalisation of the industrial sector. This paper uses the theoretical lens of supply chain innovation (SCI) to investigate the implications of i4.0 on supply chain management. For these purposes, the method of structured content analysis is applied to more than 200 use cases of i4.0-enabled SCI introduced by both established and startup companies. i4.0-enabled SCI manifests along three dimensions: process, technology, and business architecture. The key findings of this study can be summarised as follows: first, i4.0-enabled SCI extends the initial focus on productivity improvements in SC processes towards scalability and flexibility. Second, extant i4.0 solutions rely mostly on analytics and smart things while omitting smart people technology and the human-centric approach associated with the i4.0 paradigm. Third, established companies adopt i4.0 merely to sustain their existing business architectures while startup companies radically change their operating models, relying heavily on data analytics and the platform economy. Consequently, established companies pursue a problem-driven, engineering-based approach to SCI while startup companies follow an ‘asset-light’, business-driven approach. Lastly, there are two distinct approaches to digitalising operational SC processes: platform-based crowdsourcing of standard processes and on-demand provision of customised services. 相似文献
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
Nano Research - Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally... 相似文献
Reconstructing gene regulatory networks (GRNs) plays an important role in identifying the complicated regulatory relationships, uncovering regulatory patterns in cells, and gaining a systematic view for biological processes. In order to reconstruct large-scale GRNs accurately, in this paper, we first use fuzzy cognitive maps (FCMs), which are a kind of cognition fuzzy influence graphs based on fuzzy logic and neural networks, to model GRNs. Then, a novel hybrid method is proposed to reconstruct GRNs from time series expression profiles using memetic algorithm (MA) combined with neural network (NN), which is labeled as MANNFCM-GRN. In MANNFCM-GRN, the MA is used to determine regulatory connections in GRNs and the NN is used to determine the interaction strength of the regulatory connections. In the experiments, the performance of MANNFCM-GRN is validated on both synthetic data and the benchmark dataset DREAM3 and DREAM4. The experimental results demonstrate the efficacy of MANNFCM-GRN and show that MANNFCM-GRN can reconstruct GRNs with high accuracy without expert knowledge. The comparison with existing algorithms also shows that MANNFCM-GRN outperforms ant colony optimization, non-linear Hebbian learning, and real-coded genetic algorithms.
World Wide Web - The wide spread use of positioning and photographing devices gives rise to a deluge of traffic trajectory data (e.g., vehicle passage records and taxi trajectory data), with each... 相似文献