Computational structure‐based drug design: Predicting target flexibility

The role of molecular modeling in drug design has experienced a significant revamp in the last decade. The increase in computational resources and molecular models, along with software developments, is finally introducing a competitive advantage in early phases of drug discovery. Medium and small companies with strong focus on computational chemistry are being created, some of them having introduced important leads in drug design pipelines. An important source for this success is the extraordinary development of faster and more efficient techniques for describing flexibility in three‐dimensional structural molecular modeling. At different levels, from docking techniques to atomistic molecular dynamics, conformational sampling between receptor and drug results in improved predictions, such as screening enrichment, discovery of transient cavities, etc. In this review article we perform an extensive analysis of these modeling techniques, dividing them into high and low throughput, and emphasizing in their application to drug design studies. We finalize the review with a section describing our Monte Carlo method, PELE, recently highlighted as an outstanding advance in an international blind competition and industrial benchmarks.We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by a grant from the Spanish Government CTQ2016-79138-R.J.I. acknowledges support from SVP-2014-068797, awarded by the Spanish Government.Peer ReviewedPostprint (author's final draft

How Flexible Can Inflation Targeting Be and Still Work?

This paper takes up the issue of the flexibility of inflation targeting regimes, with the specific goal of determining whether the monetary policy of the Bank of England, which has a formal inflation target, has been any less flexible than that of the Federal Reserve, which does not have such a target. The empirical analysis uses the speed of inflation forecast convergence, estimated from professional forecastersÂ’ predictions at successive forecast horizons, to gauge the perceived flexibility of the central bankÂ’s response to macroeconomic shocks. Based on this criterion, there is no evidence to suggest that the Bank of EnglandÂ’s inflation target has compelled it to be more aggressive in pursuit of low inflation than the Federal Reserve.

Explosive cord

Device, jetcord, is metal-clad linear explosive of sufficient flexibility to allow forming into intricate shapes. Total effect is termed ''cutting'' with jetcord consistently ''cutting'' a target of greater thickness than can be penetrated. Applications include sheet metal working, pipe cutting and fire-fighting

Change & flexibility: the role of serviced office space in corporate real estate portfolios and office markets

With the increasing pace of change, organisations have sought new real estate solutions which provide greater flexibility. What appears to be required is not flexibility for all uses but appropriate flexibility for the volatile, risky and temporal part of a business. This is the essence of the idea behind the split between the core and periphery portfolio. The serviced office has emerged to fill the need for absolute flexibility. This market is very diverse in terms of the product, services and target market. It has grown and gained credibility with occupiers and more recently with the property investment market. Occupiers similarly use this space in a variety of ways. Some solely occupy serviced space while others use it to complement their more permanent space. It therefore appears that the market is fulfilling the role of providing periphery space for at least some of the occupiers. In all instances the key to this space is a focus on financial and tenurial flexibility which is not provided by other types of business space offered

Oxidation protection coatings for polymers

A polymeric substrate is coated with a metal oxide film to provide oxidation protection in low Earth orbital environments. The film contains about 4 volume percent polymer to provide flexibility. A coil of polymer material moves through an ion beam as it is fed between reels. The ion beam first cleans the polymer material surface and then sputters the film material from a target onto this surface

Fast H.264 intra prediction for network video processing

This letter proposes a fast parallel and deeply pipelined architecture for realtime H. 264 intra 4x4 prediction capable of handling up to 32 High Definition video streams (1920x1080 @ 30 fps) simultaneously, while offering high flexibility and consuming only a fraction of resources available on modern FPGA's. The design has been validated on target using a state of the art Altera Stratix IV FPGA

An SDN-based Approach For Defending Against Reflective DDoS Attacks

Distributed Reflective Denial of Service (DRDoS) attacks are an immanent threat to Internet services. The potential scale of such attacks became apparent in March 2018 when a memcached-based attack peaked at 1.7 Tbps. Novel services built upon UDP increase the need for automated mitigation mechanisms that react to attacks without prior knowledge of the actual application protocols used. With the flexibility that software-defined networks offer, we developed a new approach for defending against DRDoS attacks; it not only protects against arbitrary DRDoS attacks but is also transparent for the attack target and can be used without assistance of the target host operator. The approach provides a robust mitigation system which is protocol-agnostic and effective in the defense against DRDoS attacks

Assessment of Optimal Flexibility in Ensemble of Frequency Responsive Loads

Potential of electrical loads in providing grid ancillary services is often limited due to the uncertainties associated with the load behavior. A knowledge of the expected uncertainties with a load control program would invariably yield to better informed control policies, opening up the possibility of extracting the maximal load control potential without affecting grid operations. In the context of frequency responsive load control, a probabilistic uncertainty analysis framework is presented to quantify the expected error between the target and actual load response, under uncertainties in the load dynamics. A closed-form expression of an optimal demand flexibility, minimizing the expected error in actual and committed flexibility, is provided. Analytical results are validated through Monte Carlo simulations of ensembles of electric water heaters.Comment: IEEE International Conference on Smart Grid Communication