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We describe an interactive, multi-phase color-based image retrieval system which is capable of identifying query objects specified by the user in an image in the presence of significant, interfering backgrounds. The system uses a split and merge histogram peak detection technique, efficient indexing and a color neighborhood graph-based refinement phase for removing false matches. The method is fast and has low storage overhead. Good retrieval results are obtained with multi-colored query objects even when they occur in arbitrary sizes, rotations and locations in the database images. The overall scheme is flexible so that one or more phases could be used for retrieval depending on the precision desired. The experimental results on a database of advertisement images highlights the capabilities of the system.

This report documents an Icosystem contract that was awarded under the IARPA Proactive Intelligence (PAINT) program to develop the capability to rapidly generate simulation models. This work was to address a need in the Intelligence Community to predict unanticipated consequences that emerge from complex situations. Fast Interactive Modeling and Strategy Design (FASTIMS) was the proposed integrated framework for this rapid development of simulation models. Using FASTIMS, an analyst would have been able to create a model, perform validation and calibration interactively (either alone or in a group setting), discover key indicators, quantify uncertainty, and identify data needs and design and test strategies. Due to budget constraints, this effort was terminated at an early stage so the final result was not realized. This report details the preparations for the work and the steps that were taken during the short duration of the contract.

Link to YouTube version:  https://www.youtube.com/watch?v=bL2NHrfdbIs Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios.   Ottoman Fast Industrial Strategy! AoE III Is a fast industrial strategy possible?!? I would love to hear your guys thoughts! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Ottoman Fast Industrial Strategy! AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

The key to fast Poisson solving in an extended domain is nonlocal residual error dispersal. The fastest, most stable iterations are obtained when 'most' of the nonconstant-coefficient elliptic operator can be inverted implicitly . Although local inversion approaches (ICCG, SOR, etc.) are workable, there are good incentives to seek computationally inexpensive nonlocal techniques whose worst case convergence is expected to be far better than for local inverse techniques. This note presents one such approach for a useful class of variable coefficient problems. (Author)

Link to YouTube version:  https://www.youtube.com/watch?v=Jhi_PShTNlk Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios .   Fast Revolution Strategy?!? AoE III Finally! A true 1v1 attempt at the Fast Revolution! Let me know your thoughts below! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Fast Revolution Strategy?!? AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

This article is from Nucleic Acids Research , volume 41 . Abstract Recombineering in bacteria is a powerful technique for genome reconstruction, but until now, it was not generally applicable for development of small-molecule producers because of the inconspicuous phenotype of most compounds of biotechnological relevance. Here, we establish recombineering for Corynebacterium glutamicum using RecT of prophage Rac and combine this with our recently developed nanosensor technology, which enables the detection and isolation of productive mutants at the single-cell level via fluorescence-activated cell sorting (FACS). We call this new technology RecFACS, which we use for genomic site-directed saturation mutagenesis without relying on pre-constructed libraries to directly isolate l-lysine-producing cells. A mixture of 19 different oligonucleotides was used targeting codon 81 in murE of the wild-type, at a locus where one single mutation is known to cause l-lysine production. Using RecFACS, productive mutants were screened and isolated. Sequencing revealed 12 different amino acid exchanges in the targeted murE codon, which caused different l-lysine production titers. Apart from introducing a rapid genome construction technology for C. glutamicum, the present work demonstrates that RecFACS is suitable to simply create producers as well as genetic diversity in one single step, thus establishing a new general concept in synthetic biology.

Flash Talk - Fast Follower Strategy Mike Brown, Director, Defense Innovation Unit Panel: Mike Brown, Director, Defense Innovation Unit Chris Lynch, Co-Founder and CEO, Rebellion Defense Teresa Shea, Vice President, Cyber Offense and Defense Experts, Raytheon Intelligence and Space Moderator: Nancy Youssef, National Security Correspondent, The Wall Street Journal ​

The purpose of this case study was to examine the efficacy of a developing technique that has been coined by this author as a Mental Wellness Fast. Therefore, this paper has been written for therapists who utilize spirituality and/or religion into their practice. The technique is geared to assist clients with healing poor inner dialogues and it provides methods that could be utilized by providing spiritual guidance. Thus, this technique could be implemented by various religious denominations. There is a discussion of the counseling premise for implementing a Mental Wellness Fast, and it explores how the technique is grounded in Cognitive Behavior Therapy, Person-Centered Therapy, and a belief in a monotheistic God. Two case examples are explored and implications are discussed with implementing this type of strategy for counseling services. The results indicate that there was improvement with how these women approached life after implementing a mental wellness fast. In conclusion, this is a developing technique that would need to be implemented in a larger research study. Most important, it offers a method for future research. It is recommended that therapists create innovative strategies that promotes mental wellness and utilizes a client's belief system as a source of strength to heal negative perceptions and/or inner dialogues, which can then help clients become more productive.

Includes bibliographical references (p. 231-239) and index

The online learning of deep neural networks is an interesting problem of machine learning because, for example, major IT companies want to manage the information of the massive data uploaded on the web daily, and this technology can contribute to the next generation of lifelong learning. We aim to train deep models from new data that consists of new classes, distributions, and tasks at minimal computational cost, which we call online deep learning. Unfortunately, deep neural network learning through classical online and incremental methods does not work well in both theory and practice. In this paper, we introduce dual memory architectures for online incremental deep learning. The proposed architecture consists of deep representation learners and fast learnable shallow kernel networks, both of which synergize to track the information of new data. During the training phase, we use various online, incremental ensemble, and transfer learning techniques in order to achieve lower error of the architecture. On the MNIST, CIFAR-10, and ImageNet image recognition tasks, the proposed dual memory architectures performs much better than the classical online and incremental ensemble algorithm, and their accuracies are similar to that of the batch learner.

Big data or fast data? 🚀 Ellie Najewicz breaks down their key differences, exploring how they shape AI, automation, and real-time analytics. Learn about data architectures, maturity models, and how to align your strategy for scalable, AI-driven success!

Islam is always promoted over other religions in Britain, to such an extent that some people believe it to be part of a sinister plan. https://nhsmuslimnetwork.co.uk/nhsramadanchallenge

Today's Episode: How To Increase Your Revenue In Most Profitable Services....Fast Season # 2 Ep 154 of Business Growth School for service providers Welcome to daily 5-minute Business Growth lessons for service providers. Are you a Dentist, Realtor, Lawyer, Accountant, Plumber, Consultant or Contractor....If you provide services locally than this podcast is for you. Here we share strategies, tricks, techniques on how to generate leads, grow your revenue and sales. Join us every day for 5 minutes and take away strategies which you can apply in your business.

Gulp is a card game that originated with Mormon missionaries in Brazil. 

In this paper we present a parallelization strategy on distributed memory systems for the Fast Kinetic Scheme --- a semi-Lagrangian scheme developed in [J. Comput. Phys., Vol. 255, 2013, pp 680-698] for solving kinetic equations. The original algorithm was proposed for the BGK approximation of the collision kernel. In this work we deal with its extension to the full Boltzmann equation in six dimensions, where the collision operator is resolved by means of fast spectral method. We present close to ideal scalability of the proposed algorithm on tera- and peta-scale systems.

Includes bibiographical references and index

Link to YouTube version:  https://www.youtube.com/watch?v=Jw9mKBNb3mw Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios.   Russia Fast Fortress Strategy! AoE III This was hilarious! I totally recommend it if you can pull it off! The Russian's need a second strategy with their strelets, and here it is. Let me know your thoughts below! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Russia Fast Fortress Strategy! AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

Link to YouTube version:  https://www.youtube.com/watch?v=Jw9mKBNb3mw Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios.   Russia Fast Fortress Strategy! AoE III This was hilarious! I totally recommend it if you can pull it off! The Russian's need a second strategy with their strelets, and here it is. Let me know your thoughts below! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Russia Fast Fortress Strategy! AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

Link to YouTube version:  https://www.youtube.com/watch?v=Jw9mKBNb3mw Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios.   Russia Fast Fortress Strategy! AoE III This was hilarious! I totally recommend it if you can pull it off! The Russian's need a second strategy with their strelets, and here it is. Let me know your thoughts below! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Russia Fast Fortress Strategy! AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

Link to YouTube version:  https://www.youtube.com/watch?v=Jw9mKBNb3mw Video created by SamuraiRevolution .  Rights to the gameplay footage belongs to Microsoft Studios.   Russia Fast Fortress Strategy! AoE III This was hilarious! I totally recommend it if you can pull it off! The Russian's need a second strategy with their strelets, and here it is. Let me know your thoughts below! AGE OF EMPIRES III FOR UNDER $12! https://www.g2a.com/r/age-of-empires-... Follow me on Twitter for channel updates: https://twitter.com/SamuraiRev Follow me on steam: SamuraiRevolution Age of Empires III © Microsoft Corporation. Russia Fast Fortress Strategy! AoE III was created under Microsoft's "Game Content Usage Rules" using assets from Age of Empires III, and it is not endorsed by or affiliated with Microsoft. Link is below: http://www.xbox.com/en-us/developers/...

Want to dominate Google search in 2025? In this video, I’ll walk you through a step-by-step SEO strategy that’s working right now — from keyword research to content optimization and link building. ✅ What You’ll Learn: How to find high-traffic, low-competition keywords On-page SEO tips to make your content rank Link building strategies that actually work Tools & resources to speed up your SEO process

On the eve of the Sears Classic 500, legendary NASCAR coach Dan Amon shares his strategy for driving really fast in circles. More coverage at: http://www.onion.com

This paper concerns a fast, one-step iterative technique of imaging extended perfectly conducting cracks with Dirichlet boundary condition. In order to reconstruct the shape of cracks from scattered field data measured at the boundary, we introduce a topological derivative-based electromagnetic imaging function operated at several nonzero frequencies. The properties of the imaging function are carefully analyzed for the configurations of both symmetric and non-symmetric incident field directions. This analysis explains why the application of incident fields with symmetric direction operated at multiple frequencies guarantees a successful reconstruction. Various numerical simulations with noise-corrupted data are conducted to assess the performance, effectiveness, robustness, and limitations of the proposed technique.

The COVID-19 pandemic caught the world by surprise and raised many questions. One of the questions is whether infectious diseases indeed drive fast life history (LH) as the extent research suggests. This paper challenges this assumption and raises a different perspective. We argue that infectious diseases are not linearly related with LH strategies, but depending on the severity of the diseases, manifest either as intrinsic or extrinsic risks in enacting either slower or faster LH strategies and the related behavior.

This article is from BMC Research Notes , volume 4 . Abstract Background: Gene targeting by homologous recombination using recombinant adeno-associated virus (rAAV) is becoming a useful tool for basic research and therapeutic applications due to the remarkably high targeting frequency of rAAV virus vectors. However, the screening for the pure gene-targeted and random-integration-free primary cell clones is difficult since the cells have a limited proliferation capacity and often cannot be grown to produce sufficient DNA for non-PCR based analysis. This hampers the applications of this technology. Findings: In this study, we have developed an improved PCR screening method, which can be used for fast screening of clones with unwanted random integration (RI) of the rAAV genome. This improved screening method includes four PCRs: a PCR for the selection gene (e.g. Neo-PCR), a PCR for targeted gene knockout (e.g. BRCA1-KO-PCR), and two generalized PCRs for random integration of the rAAV genome (5'-AAV-RI-PCR, and 3'-AAV-RI-PCR). We have shown that this screening method greatly facilitates the procedure of screening for BRCA1 (BReast CAncer susceptibility gene 1) targeted cell clones, eliminating cell clones with both BRCA1 knockout and random integration of the rAAV genome. Conclusions: This screening method has facilitated the screening of correct gene-targeted cells. As the AAV-RI-PCRs are generalized PCRs, this method can also be applied for screening of rAAV-mediated targeting of other genes.

This article is from BMC Research Notes , volume 4 . Abstract Background: Gene targeting by homologous recombination using recombinant adeno-associated virus (rAAV) is becoming a useful tool for basic research and therapeutic applications due to the remarkably high targeting frequency of rAAV virus vectors. However, the screening for the pure gene-targeted and random-integration-free primary cell clones is difficult since the cells have a limited proliferation capacity and often cannot be grown to produce sufficient DNA for non-PCR based analysis. This hampers the applications of this technology. Findings: In this study, we have developed an improved PCR screening method, which can be used for fast screening of clones with unwanted random integration (RI) of the rAAV genome. This improved screening method includes four PCRs: a PCR for the selection gene (e.g. Neo-PCR), a PCR for targeted gene knockout (e.g. BRCA1-KO-PCR), and two generalized PCRs for random integration of the rAAV genome (5'-AAV-RI-PCR, and 3'-AAV-RI-PCR). We have shown that this screening method greatly facilitates the procedure of screening for BRCA1 (BReast CAncer susceptibility gene 1) targeted cell clones, eliminating cell clones with both BRCA1 knockout and random integration of the rAAV genome. Conclusions: This screening method has facilitated the screening of correct gene-targeted cells. As the AAV-RI-PCRs are generalized PCRs, this method can also be applied for screening of rAAV-mediated targeting of other genes.

This article is from BMC Research Notes , volume 4 . Abstract Background: Gene targeting by homologous recombination using recombinant adeno-associated virus (rAAV) is becoming a useful tool for basic research and therapeutic applications due to the remarkably high targeting frequency of rAAV virus vectors. However, the screening for the pure gene-targeted and random-integration-free primary cell clones is difficult since the cells have a limited proliferation capacity and often cannot be grown to produce sufficient DNA for non-PCR based analysis. This hampers the applications of this technology. Findings: In this study, we have developed an improved PCR screening method, which can be used for fast screening of clones with unwanted random integration (RI) of the rAAV genome. This improved screening method includes four PCRs: a PCR for the selection gene (e.g. Neo-PCR), a PCR for targeted gene knockout (e.g. BRCA1-KO-PCR), and two generalized PCRs for random integration of the rAAV genome (5'-AAV-RI-PCR, and 3'-AAV-RI-PCR). We have shown that this screening method greatly facilitates the procedure of screening for BRCA1 (BReast CAncer susceptibility gene 1) targeted cell clones, eliminating cell clones with both BRCA1 knockout and random integration of the rAAV genome. Conclusions: This screening method has facilitated the screening of correct gene-targeted cells. As the AAV-RI-PCRs are generalized PCRs, this method can also be applied for screening of rAAV-mediated targeting of other genes.

The purpose of this study is to examine the relationship between Sales Promotion Strategies and Organizational Success of Fast-Food Firms in Rivers State. This study adopted the descriptive survey research design with a causal type of investigation. The fifty-nine registered fast-food firms in Rivers State as enlisted in (Rivers State Yellow Pages, 2013 - 2014) constituted the population. The study adopted 59 fast food firms as its sample. However, 2 top management staff (Operations Manager and Marketing Manager) of each of the 59 registered fast-food firms were sampled bringing the sample element to 118 respondents. Of the 118 copies of questionnaire administered, 86 copies were retrieved and used for the analysis. The Spearman Rank Order Correlation was used for the analysis and aided with the use of Statistical Package for Social Sciences version 23.0. The study found a significant relationship between the dimensions of Sales Promotion Strategies and the measures of Organizational Success. The study therefore concludes that Sales Promotion is a Strategy for Organizational Success. The study recommends that management of fast-food firms in Rivers State should ensure the use of premium, coupon and loyalty card as strategies in order to stimulate organizational success.

We present a new type of search strategy designed specifically to find continuously emitting gravitational wave sources in known binary systems based on the incoherent sum of frequency modulated binary signal sidebands. The search pipeline can be divided into three stages: the first is a wide bandwidth, F-statistic search demodulated for sky position. This is followed by a fast second stage in which areas in frequency space are identified as signal candidates through the frequency domain convolution of the F-statistic with an approximate signal template. For this second stage only precise information on the orbit period and approximate information on the orbital semi-major axis are required apriori. For the final stage we propose a fully coherent Markov chain monte carlo based follow up search on the frequency subspace defined by the candidates identified by the second stage. This search is particularly suited to the low-mass X-ray binaries, for which orbital period and sky position are typically well known and additional orbital parameters and neutron star spin frequency are not. We note that for the accreting X-ray millisecond pulsars, for which spin frequency and orbital parameters are well known, the second stage can be omitted and the fully coherent search stage can be performed. We describe the search pipeline with respect to its application to a simplified phase model and derive the corresponding sensitivity of the search.

Talk of exit strategy premature? Can we trust numbers? What's happening in Prisons? Care workers dying, Trump vs WHO and more 00:00 Lockdown Exit Strategy 03:03 Testing 04:23: What's happening in Prisons? 05:12: Shielding at risk groups 08:04 Economy 10:01 Keir Starmer 13:32 German Response Vs British Response 14:35 Can we trust the Death toll? 16:27 Do Not Resuscitate *Adults with Autism, a child with cancer and disabled patients 17:11 Heathcare workers dying 17:43 COVID-19 disproportionately effecting BAME communities and men 19:27 Trump vs World Health Organisation 21:41 Looking back at my own Coronavirus journey Join the Future of Journalism: http://www.patreon.com/doubledownnews Support DDN: https://www.paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=TLXUE9P9GA9ZC&source=url

The recently initiated Arecibo Legacy Fast ALFA (ALFALFA) survey aims to map 7000 square degrees of the high galactic latitude sky visible from Arecibo, providing a HI line spectral database covering the redshift range between -1600 km/s and 18,000 km/s with 5 km/s resolution. Exploiting Arecibo's large collecting area and small beam size, ALFALFA is specifically designed to probe the faint end of the HI mass function in the local universe and will provide a census of HI in the surveyed sky area to faint flux limits, making it especially useful in synergy with wide area surveys conducted at other wavelengths. ALFALFA will also provide the basis for studies of the dynamics of galaxies within the Local and nearby superclusters, will allow measurement of the HI diameter function, and enable a first wide-area blind search for local HI tidal features, HI absorbers at z < 0.06 and OH megamasers in the redshift range 0.16 < z < 0.25. Although completion of the survey will require some five years, public access to the ALFALFA data and data products will be provided in a timely manner, thus allowing its application for studies beyond those targeted by the ALFALFA collaboration. ALFALFA adopts a two-pass, minimum intrusion, drift scan observing technique which samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference. Survey simulations, which take into account large scale structure in the mass distribution and incorporate experience with the ALFA system gained from tests conducted during its commissioning phase, suggest that ALFALFA will detect on the order of 20,000 extragalactic HI line sources out to z=0.06, including several hundred with HI masses of less than 10^{7.5} msun.

Cost effectiveness is a major concern when implementing low impact development (LID) practices for urban stormwater management (USWM). To optimize LID layout, an efficient and more reliable method, namely, the Marginal-Cost-based Greedy Strategy (MCGS) was developed based on the economic law of increasing marginal costs (MCs) and the stepwise minimization of MCs. To verify its broad applicability, MCGS was applied in three case studies in China with different system settings and environmental goals. Both Cases I and II were watershed-scale studies in Suzhou City urban districts, but in Case II, the impact of future uncertainties (i.e., climate change, urban expansion, and LID performance degradation) on USWM system performance was considered. Case III was a block-scale study of the Xixian New District (a pilot “Sponge City” in China), which involved a rainwater pipe network and a complicated environmental goal. Compared with the extensively used but complicated NSGA-II, the MCGS performed better in terms of yielding more converged performance trade-offs, providing more choices for city planners, and requiring much less computational resources in all three cases. Meanwhile, MCGS established an optimal pathway for multi-stage LID layout planning. The success of MCGS indicated that the MC of a LID practice determined its favorability in an USWM system.

This article is from PLoS ONE , volume 9 . Abstract The purpose of this study was to determine both the independent and additive effects of prior heavy-intensity exercise and pacing strategies on the VO2 kinetics and performance during high-intensity exercise. Fourteen endurance cyclists (VO2max  = 62.8±8.5 mL.kg−1.min−1) volunteered to participate in the present study with the following protocols: 1) incremental test to determine lactate threshold and VO2max; 2) four maximal constant-load tests to estimate critical power; 3) six bouts of exercise, using a fast-start (FS), even-start (ES) or slow-start (SS) pacing strategy, with and without a preceding heavy-intensity exercise session (i.e., 90% critical power). In all conditions, the subjects completed an all-out sprint during the final 60 s of the test as a measure of the performance. For the control condition, the mean response time was significantly shorter (p

Includes bibliographical references (p. 273-280) and index

This paper discusses about the photovoltaic (PV) system novel non-iterative maximum power point tracking algorithm with faster converging speed under varying solar irradiation level. PV system is a scattered renewable energy resource and a safe environmental energy source. However, the PV power oscillates around MPP value due to the fluctuations of temperature and insolation effects, leading to nonlinear maximum power tracking issues. For each change in atmospheric condition, output of the PV system changes necessitating the need to search for new maximum power conditions. An efficient maximum power point tracking (MPPT) device that improves the power transmitting efficiency along with a suitable high frequency direct current (DC) to DC power converter device are required for efficient operation. Finally, a comparison is made between existing MPPT algorithms and proposed novel non-iterative MPPT algorithm. The proposed MPPT system show that the overall tracking speed of the proposed MPPT is 5.6 times, 3.8 times faster than perturb and observe (P&O) method and INC method respectively. During the variation of irradiance, the power loss is reduced by 18.84% and 11.29% in comparison with P&O and INC method. The proposed method also minimizes the steady state oscillations.

In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4. Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1{\mu}second-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4. Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1{\mu}second-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

'FAST TRACK STRATEGY (25-Jul-2002)' from the Parliament Digital Library

'Fast track strategy for Railways (12-Aug-2002)' from the RS Debates Digital Library

A variable annuity contract with Guaranteed Minimum Withdrawal Benefit (GMWB) promises to return the entire initial investment through cash withdrawals during the policy life plus the remaining account balance at maturity, regardless of the portfolio performance. Under the optimal withdrawal strategy of a policyholder, the pricing of variable annuities with GMWB becomes an optimal stochastic control problem. So far in the literature these contracts have only been evaluated by solving partial differential equations (PDE) using the finite difference method. The well-known Least-Squares or similar Monte Carlo methods cannot be applied to pricing these contracts because the paths of the underlying wealth process are affected by optimal cash withdrawals (control variables) and thus cannot be simulated forward in time. In this paper we present a very efficient new algorithm for pricing these contracts in the case when transition density of the underlying asset between withdrawal dates or its moments are known. This algorithm relies on computing the expected contract value through a high order Gauss-Hermite quadrature applied on a cubic spline interpolation. Numerical results from the new algorithm for a series of GMWB contract are then presented, in comparison with results using the finite difference method solving corresponding PDE. The comparison demonstrates that the new algorithm produces results in very close agreement with those of the finite difference method, but at the same time it is significantly faster; virtually instant results on a standard desktop PC.