Prospects for spinel-stabilized, high-capacity lithium-ion battery cathodes

DOE PAGES

Croy, Jason R.; Park, Joong Sun; Shin, Youngho; ...

2016-10-13

Herein we report early results on efforts to optimize the electrochemical performance of a cathode composed of a lithium- and manganese-rich “layered-layered-spinel” material for lithium-ion battery applications. Pre-pilot scale synthesis leads to improved particle properties compared with lab-scale efforts, resulting in high capacities (≳200 mAh/g) and good energy densities (>700 Wh/kg) in tests with lithium-ion cells. Subsequent surface modifications give further improvements in rate capabilities and high-voltage stability. These results bode well for advances in the performance of this class of lithium- and manganese-rich cathode materials.

Engagement and Arousal: Optimism’s Effects During a Brief Stressor

PubMed Central

Nes, Lise Solberg; Segerstrom, Suzanne C.; Sephton, Sandra E.

2005-01-01

Optimism is usually associated with better psychological and physiological adjustment to stressors, but some contradictory findings exist. The purpose of this study was to investigate how optimism could result in negative immunological changes following difficult stressors. Because optimists are likely to see positive outcomes as attainable, they may invest greater effort to achieve their goals. It is proposed that such engagement would be more physiologically demanding when pursuing difficult goals. Participants (N = 54) worked on 11 difficult or insoluble anagrams. Optimism when combined with high self-awareness increased time spent working on the anagrams and skin conductance and salivary cortisol during the recovery period. The results support the notion that the increased engagement that arises from optimism may lead to short-term physiological costs. PMID:15574666

Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors.

PubMed

Ramachandran, Sreekanth A; Jadhavar, Pradeep S; Miglani, Sandeep K; Singh, Manvendra P; Kalane, Deepak P; Agarwal, Anil K; Sathe, Balaji D; Mukherjee, Kakoli; Gupta, Ashu; Haldar, Srijan; Raja, Mohd; Singh, Siddhartha; Pham, Son M; Chakravarty, Sarvajit; Quinn, Kevin; Belmar, Sebastian; Alfaro, Ivan E; Higgs, Christopher; Bernales, Sebastian; Herrera, Francisco J; Rai, Roopa

2017-05-15

Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design

PubMed Central

2012-01-01

PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for a structurally differentiated back-up candidate to PF-04691502, which is currently in phase I/II clinical trials for treating solid tumors, a lead optimization effort was carried out with a tricyclic imidazo[1,5]naphthyridine series. Integration of structure-based drug design and physical properties-based optimization yielded a potent and selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses the lead optimization for the tricyclic series, which both improved the in vitro potency and addressed a number of ADMET issues including high metabolic clearance mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor solubility. An empirical scaling tool was developed to predict human clearance from in vitro human liver S9 assay data for tricyclic derivatives that were AO substrates. PMID:24900568

Studies in Software Cost Model Behavior: Do We Really Understand Cost Model Performance?

NASA Technical Reports Server (NTRS)

Lum, Karen; Hihn, Jairus; Menzies, Tim

2006-01-01

While there exists extensive literature on software cost estimation techniques, industry practice continues to rely upon standard regression-based algorithms. These software effort models are typically calibrated or tuned to local conditions using local data. This paper cautions that current approaches to model calibration often produce sub-optimal models because of the large variance problem inherent in cost data and by including far more effort multipliers than the data supports. Building optimal models requires that a wider range of models be considered while correctly calibrating these models requires rejection rules that prune variables and records and use multiple criteria for evaluating model performance. The main contribution of this paper is to document a standard method that integrates formal model identification, estimation, and validation. It also documents what we call the large variance problem that is a leading cause of cost model brittleness or instability.

Strategy of arm movement control is determined by minimization of neural effort for joint coordination.

PubMed

Dounskaia, Natalia; Shimansky, Yury

2016-06-01

Optimality criteria underlying organization of arm movements are often validated by testing their ability to adequately predict hand trajectories. However, kinematic redundancy of the arm allows production of the same hand trajectory through different joint coordination patterns. We therefore consider movement optimality at the level of joint coordination patterns. A review of studies of multi-joint movement control suggests that a 'trailing' pattern of joint control is consistently observed during which a single ('leading') joint is rotated actively and interaction torque produced by this joint is the primary contributor to the motion of the other ('trailing') joints. A tendency to use the trailing pattern whenever the kinematic redundancy is sufficient and increased utilization of this pattern during skillful movements suggests optimality of the trailing pattern. The goal of this study is to determine the cost function minimization of which predicts the trailing pattern. We show that extensive experimental testing of many known cost functions cannot successfully explain optimality of the trailing pattern. We therefore propose a novel cost function that represents neural effort for joint coordination. That effort is quantified as the cost of neural information processing required for joint coordination. We show that a tendency to reduce this 'neurocomputational' cost predicts the trailing pattern and that the theoretically developed predictions fully agree with the experimental findings on control of multi-joint movements. Implications for future research of the suggested interpretation of the trailing joint control pattern and the theory of joint coordination underlying it are discussed.

B-Raf kinase inhibitors: hit enrichment through scaffold hopping.

PubMed

Gopalsamy, Ariamala; Shi, Mengxiao; Hu, Yongbo; Lee, Frederick; Feldberg, Larry; Frommer, Eileen; Kim, Steven; Collins, Karen; Wojciechowicz, Donald; Mallon, Robert

2010-04-15

In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. Copyright 2010 Elsevier Ltd. All rights reserved.

Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization.

PubMed

Kattar, Solomon D; Surdi, Laura M; Zabierek, Anna; Methot, Joey L; Middleton, Richard E; Hughes, Bethany; Szewczak, Alexander A; Dahlberg, William K; Kral, Astrid M; Ozerova, Nicole; Fleming, Judith C; Wang, Hongmei; Secrist, Paul; Harsch, Andreas; Hamill, Julie E; Cruz, Jonathan C; Kenific, Candia M; Chenard, Melissa; Miller, Thomas A; Berk, Scott C; Tempest, Paul

2009-02-15

The successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays. Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models.

Lead optimization mapper: automating free energy calculations for lead optimization.

PubMed

Liu, Shuai; Wu, Yujie; Lin, Teng; Abel, Robert; Redmann, Jonathan P; Summa, Christopher M; Jaber, Vivian R; Lim, Nathan M; Mobley, David L

2013-09-01

Alchemical free energy calculations hold increasing promise as an aid to drug discovery efforts. However, applications of these techniques in discovery projects have been relatively few, partly because of the difficulty of planning and setting up calculations. Here, we introduce lead optimization mapper, LOMAP, an automated algorithm to plan efficient relative free energy calculations between potential ligands within a substantial library of perhaps hundreds of compounds. In this approach, ligands are first grouped by structural similarity primarily based on the size of a (loosely defined) maximal common substructure, and then calculations are planned within and between sets of structurally related compounds. An emphasis is placed on ensuring that relative free energies can be obtained between any pair of compounds without combining the results of too many different relative free energy calculations (to avoid accumulation of error) and by providing some redundancy to allow for the possibility of error and consistency checking and provide some insight into when results can be expected to be unreliable. The algorithm is discussed in detail and a Python implementation, based on both Schrödinger's and OpenEye's APIs, has been made available freely under the BSD license.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

PubMed

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets

PubMed Central

Wasko, Michael J.; Pellegrene, Kendy A.; Madura, Jeffry D.; Surratt, Christopher K.

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for “growing” the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies. PMID:26441817

More efficient optimization of long-term water supply portfolios

NASA Astrophysics Data System (ADS)

Kirsch, Brian R.; Characklis, Gregory W.; Dillard, Karen E. M.; Kelley, C. T.

2009-03-01

The use of temporary transfers, such as options and leases, has grown as utilities attempt to meet increases in demand while reducing dependence on the expansion of costly infrastructure capacity (e.g., reservoirs). Earlier work has been done to construct optimal portfolios comprising firm capacity and transfers, using decision rules that determine the timing and volume of transfers. However, such work has only focused on the short-term (e.g., 1-year scenarios), which limits the utility of these planning efforts. Developing multiyear portfolios can lead to the exploration of a wider range of alternatives but also increases the computational burden. This work utilizes a coupled hydrologic-economic model to simulate the long-term performance of a city's water supply portfolio. This stochastic model is linked with an optimization search algorithm that is designed to handle the high-frequency, low-amplitude noise inherent in many simulations, particularly those involving expected values. This noise is detrimental to the accuracy and precision of the optimized solution and has traditionally been controlled by investing greater computational effort in the simulation. However, the increased computational effort can be substantial. This work describes the integration of a variance reduction technique (control variate method) within the simulation/optimization as a means of more efficiently identifying minimum cost portfolios. Random variation in model output (i.e., noise) is moderated using knowledge of random variations in stochastic input variables (e.g., reservoir inflows, demand), thereby reducing the computing time by 50% or more. Using these efficiency gains, water supply portfolios are evaluated over a 10-year period in order to assess their ability to reduce costs and adapt to demand growth, while still meeting reliability goals. As a part of the evaluation, several multiyear option contract structures are explored and compared.

Latency reversal and viral clearance to cure HIV-1

PubMed Central

Margolis, David M.; Garcia, J. Victor; Hazuda, Daria J.; Haynes, Barton F.

2016-01-01

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. PMID:27463679

Drug discovery for neglected tropical diseases at the Sandler Center.

PubMed

Robertson, Stephanie A; Renslo, Adam R

2011-08-01

The Sandler Center's approach to target-based drug discovery for neglected tropical diseases is to focus on parasite targets that are homologous to human targets being actively investigated in the pharmaceutical industry. In this way we attempt to use both the know-how and actual chemical matter from other drug-development efforts to jump start the discovery process for neglected tropical diseases. Our approach is akin to drug repurposing, except that we seek to repurpose leads rather than drugs. Medicinal chemistry can then be applied to optimize the leads specifically for the desired antiparasitic indication.

Drug discovery for neglected tropical diseases at the Sandler Center

PubMed Central

Robertson, Stephanie A; Renslo, Adam R

2011-01-01

The Sandler Center’s approach to target-based drug discovery for neglected tropical diseases is to focus on parasite targets that are homologous to human targets being actively investigated in the pharmaceutical industry. In this way we attempt to use both the know-how and actual chemical matter from other drug-development efforts to jump start the discovery process for neglected tropical diseases. Our approach is akin to drug repurposing, except that we seek to repurpose leads rather than drugs. Medicinal chemistry can then be applied to optimize the leads specifically for the desired antiparasitic indication. PMID:21859302

Transformational leadership in the local police in Spain: a leader-follower distance approach.

PubMed

Álvarez, Octavio; Lila, Marisol; Tomás, Inés; Castillo, Isabel

2014-01-01

Based on the transformational leadership theory (Bass, 1985), the aim of the present study was to analyze the differences in leadership styles according to the various leading ranks and the organizational follower-leader distance reported by a representative sample of 975 local police members (828 male and 147 female) from Valencian Community (Spain). Results showed differences by rank (p < .01), and by rank distance (p < .05). The general intendents showed the most optimal profile of leadership in all the variables examined (transformational-leadership behaviors, transactional-leadership behaviors, laissez-faire behaviors, satisfaction with the leader, extra effort by follower, and perceived leadership effectiveness). By contrast, the least optimal profiles were presented by intendents. Finally, the maximum distance (five ranks) generally yielded the most optimal profiles, whereas the 3-rank distance generally produced the least optimal profiles for all variables examined. Outcomes and practical implications for the workforce dimensioning are also discussed.

Modern drug discovery technologies: opportunities and challenges in lead discovery.

PubMed

Guido, Rafael V C; Oliva, Glaucius; Andricopulo, Adriano D

2011-12-01

The identification of promising hits and the generation of high quality leads are crucial steps in the early stages of drug discovery projects. The definition and assessment of both chemical and biological space have revitalized the screening process model and emphasized the importance of exploring the intrinsic complementary nature of classical and modern methods in drug research. In this context, the widespread use of combinatorial chemistry and sophisticated screening methods for the discovery of lead compounds has created a large demand for small organic molecules that act on specific drug targets. Modern drug discovery involves the employment of a wide variety of technologies and expertise in multidisciplinary research teams. The synergistic effects between experimental and computational approaches on the selection and optimization of bioactive compounds emphasize the importance of the integration of advanced technologies in drug discovery programs. These technologies (VS, HTS, SBDD, LBDD, QSAR, and so on) are complementary in the sense that they have mutual goals, thereby the combination of both empirical and in silico efforts is feasible at many different levels of lead optimization and new chemical entity (NCE) discovery. This paper provides a brief perspective on the evolution and use of key drug design technologies, highlighting opportunities and challenges.

Latency reversal and viral clearance to cure HIV-1.

PubMed

Margolis, David M; Garcia, J Victor; Hazuda, Daria J; Haynes, Barton F

2016-07-22

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication--a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. Copyright © 2016, American Association for the Advancement of Science.

Increasing the statistical significance of entanglement detection in experiments.

PubMed

Jungnitsch, Bastian; Niekamp, Sönke; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei

2010-05-28

Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise. Furthermore, we provide a way to develop entanglement tests with high statistical significance.

Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.

PubMed

Casale, Elena; Amboldi, Nadia; Brasca, Maria Gabriella; Caronni, Dannica; Colombo, Nicoletta; Dalvit, Claudio; Felder, Eduard R; Fogliatto, Gianpaolo; Galvani, Arturo; Isacchi, Antonella; Polucci, Paolo; Riceputi, Laura; Sola, Francesco; Visco, Carlo; Zuccotto, Fabio; Casuscelli, Francesco

2014-08-01

In the last decade the heat shock protein 90 (Hsp90) has emerged as a major therapeutic target and many efforts have been dedicated to the discovery of Hsp90 inhibitors as new potent anticancer agents. Here we report the identification of a novel class of Hsp90 inhibitors by means of a biophysical FAXS-NMR based screening of a library of fragments. The use of X-ray structure information combined with modeling studies enabled the fragment evolution of the initial triazoloquinazoline hit to a class of compounds with nanomolar potency and drug-like properties suited for further lead optimization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeting blood–brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery

PubMed Central

Ronaldson, Patrick T; Davis, Thomas P

2012-01-01

The blood–brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery. PMID:22468221

Pharmacology and Clinical Drug Candidates in Redox Medicine

PubMed Central

Casas, Ana I.; Maghzal, Ghassan J.; Seredenina, Tamara; Kaludercic, Nina; Robledinos-Anton, Natalia; Di Lisa, Fabio; Stocker, Roland; Ghezzi, Pietro; Jaquet, Vincent; Cuadrado, Antonio

2015-01-01

Abstract Significance: Oxidative stress is suggested to be a disease mechanism common to a wide range of disorders affecting human health. However, so far, the pharmacotherapeutic exploitation of this, for example, based on chemical scavenging of pro-oxidant molecules, has been unsuccessful. Recent Advances: An alternative emerging approach is to target the enzymatic sources of disease-relevant oxidative stress. Several such enzymes and isoforms have been identified and linked to different pathologies. For some targets, the respective pharmacology is quite advanced, that is, up to late-stage clinical development or even on the market; for others, drugs are already in clinical use, although not for indications based on oxidative stress, and repurposing seems to be a viable option. Critical Issues: For all other targets, reliable preclinical validation and drug ability are key factors for any translation into the clinic. In this study, specific pharmacological agents with optimal pharmacokinetic profiles are still lacking. Moreover, these enzymes also serve largely unknown physiological functions and their inhibition may lead to unwanted side effects. Future Directions: The current promising data based on new targets, drugs, and drug repurposing are mainly a result of academic efforts. With the availability of optimized compounds and coordinated efforts from academia and industry scientists, unambiguous validation and translation into proof-of-principle studies seem achievable in the very near future, possibly leading towards a new era of redox medicine. Antioxid. Redox Signal. 23, 1113–1129. PMID:26415051

Computer-Aided Drug Discovery Approaches against the Tropical Infectious Diseases Malaria, Tuberculosis, Trypanosomiasis, and Leishmaniasis.

PubMed

Njogu, Peter M; Guantai, Eric M; Pavadai, Elumalai; Chibale, Kelly

2016-01-08

Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases. The research efforts have involved increased application of computational technologies in mainstream drug discovery programs at the hit identification, hit-to-lead, and lead optimization stages. This review highlights various computer-aided drug discovery approaches that have been utilized in efforts to identify novel antimalarial, antitubercular, antitrypanosomal, and antileishmanial agents. The focus is largely on developments over the past 5 years (2010-2014).

Research in the design of high-performance reconfigurable systems

NASA Technical Reports Server (NTRS)

Mcewan, S. D.; Spry, A. J.

1985-01-01

Computer aided design and computer aided manufacturing have the potential for greatly reducing the cost and lead time in the development of VLSI components. This potential paves the way for the design and fabrication of a wide variety of economically feasible high level functional units. It was observed that current computer systems have only a limited capacity to absorb new VLSI component types other than memory, microprocessors, and a relatively small number of other parts. The first purpose is to explore a system design which is capable of effectively incorporating a considerable number of VLSI part types and will both increase the speed of computation and reduce the attendant programming effort. A second purpose is to explore design techniques for VLSI parts which when incorporated by such a system will result in speeds and costs which are optimal. The proposed work may lay the groundwork for future efforts in the extensive simulation and measurements of the system's cost effectiveness and lead to prototype development.

An optimized treatment for algorithmic differentiation of an important glaciological fixed-point problem

DOE PAGES

Goldberg, Daniel N.; Narayanan, Sri Hari Krishna; Hascoet, Laurent; ...

2016-05-20

We apply an optimized method to the adjoint generation of a time-evolving land ice model through algorithmic differentiation (AD). The optimization involves a special treatment of the fixed-point iteration required to solve the nonlinear stress balance, which differs from a straightforward application of AD software, and leads to smaller memory requirements and in some cases shorter computation times of the adjoint. The optimization is done via implementation of the algorithm of Christianson (1994) for reverse accumulation of fixed-point problems, with the AD tool OpenAD. For test problems, the optimized adjoint is shown to have far lower memory requirements, potentially enablingmore » larger problem sizes on memory-limited machines. In the case of the land ice model, implementation of the algorithm allows further optimization by having the adjoint model solve a sequence of linear systems with identical (as opposed to varying) matrices, greatly improving performance. Finally, the methods introduced here will be of value to other efforts applying AD tools to ice models, particularly ones which solve a hybrid shallow ice/shallow shelf approximation to the Stokes equations.« less

Current Incentives for Scientists Lead to Underpowered Studies with Erroneous Conclusions.

PubMed

Higginson, Andrew D; Munafò, Marcus R

2016-11-01

We can regard the wider incentive structures that operate across science, such as the priority given to novel findings, as an ecosystem within which scientists strive to maximise their fitness (i.e., publication record and career success). Here, we develop an optimality model that predicts the most rational research strategy, in terms of the proportion of research effort spent on seeking novel results rather than on confirmatory studies, and the amount of research effort per exploratory study. We show that, for parameter values derived from the scientific literature, researchers acting to maximise their fitness should spend most of their effort seeking novel results and conduct small studies that have only 10%-40% statistical power. As a result, half of the studies they publish will report erroneous conclusions. Current incentive structures are in conflict with maximising the scientific value of research; we suggest ways that the scientific ecosystem could be improved.

Current Incentives for Scientists Lead to Underpowered Studies with Erroneous Conclusions

PubMed Central

Higginson, Andrew D.; Munafò, Marcus R.

2016-01-01

We can regard the wider incentive structures that operate across science, such as the priority given to novel findings, as an ecosystem within which scientists strive to maximise their fitness (i.e., publication record and career success). Here, we develop an optimality model that predicts the most rational research strategy, in terms of the proportion of research effort spent on seeking novel results rather than on confirmatory studies, and the amount of research effort per exploratory study. We show that, for parameter values derived from the scientific literature, researchers acting to maximise their fitness should spend most of their effort seeking novel results and conduct small studies that have only 10%–40% statistical power. As a result, half of the studies they publish will report erroneous conclusions. Current incentive structures are in conflict with maximising the scientific value of research; we suggest ways that the scientific ecosystem could be improved. PMID:27832072

Enhancing ecosystem restoration efficiency through spatial and temporal coordination.

PubMed

Neeson, Thomas M; Ferris, Michael C; Diebel, Matthew W; Doran, Patrick J; O'Hanley, Jesse R; McIntyre, Peter B

2015-05-12

In many large ecosystems, conservation projects are selected by a diverse set of actors operating independently at spatial scales ranging from local to international. Although small-scale decision making can leverage local expert knowledge, it also may be an inefficient means of achieving large-scale objectives if piecemeal efforts are poorly coordinated. Here, we assess the value of coordinating efforts in both space and time to maximize the restoration of aquatic ecosystem connectivity. Habitat fragmentation is a leading driver of declining biodiversity and ecosystem services in rivers worldwide, and we simultaneously evaluate optimal barrier removal strategies for 661 tributary rivers of the Laurentian Great Lakes, which are fragmented by at least 6,692 dams and 232,068 road crossings. We find that coordinating barrier removals across the entire basin is nine times more efficient at reconnecting fish to headwater breeding grounds than optimizing independently for each watershed. Similarly, a one-time pulse of restoration investment is up to 10 times more efficient than annual allocations totaling the same amount. Despite widespread emphasis on dams as key barriers in river networks, improving road culvert passability is also essential for efficiently restoring connectivity to the Great Lakes. Our results highlight the dramatic economic and ecological advantages of coordinating efforts in both space and time during restoration of large ecosystems.

Enhancing ecosystem restoration efficiency through spatial and temporal coordination

PubMed Central

Neeson, Thomas M.; Ferris, Michael C.; Diebel, Matthew W.; Doran, Patrick J.; O’Hanley, Jesse R.; McIntyre, Peter B.

2015-01-01

In many large ecosystems, conservation projects are selected by a diverse set of actors operating independently at spatial scales ranging from local to international. Although small-scale decision making can leverage local expert knowledge, it also may be an inefficient means of achieving large-scale objectives if piecemeal efforts are poorly coordinated. Here, we assess the value of coordinating efforts in both space and time to maximize the restoration of aquatic ecosystem connectivity. Habitat fragmentation is a leading driver of declining biodiversity and ecosystem services in rivers worldwide, and we simultaneously evaluate optimal barrier removal strategies for 661 tributary rivers of the Laurentian Great Lakes, which are fragmented by at least 6,692 dams and 232,068 road crossings. We find that coordinating barrier removals across the entire basin is nine times more efficient at reconnecting fish to headwater breeding grounds than optimizing independently for each watershed. Similarly, a one-time pulse of restoration investment is up to 10 times more efficient than annual allocations totaling the same amount. Despite widespread emphasis on dams as key barriers in river networks, improving road culvert passability is also essential for efficiently restoring connectivity to the Great Lakes. Our results highlight the dramatic economic and ecological advantages of coordinating efforts in both space and time during restoration of large ecosystems. PMID:25918378

Sustainability is possible despite greed - Exploring the nexus between profitability and sustainability in common pool resource systems.

PubMed

Osten, Friedrich Burkhard von der; Kirley, Michael; Miller, Tim

2017-05-23

The sustainable use of common pool resources has become a significant global challenge. It is now widely accepted that specific mechanisms such as community-based management strategies, institutional responses such as resource privatization, information availability and emergent social norms can be used to constrain individual 'harvesting' to socially optimal levels. However, there is a paucity of research focused specifically on aligning profitability and sustainability goals. In this paper, an integrated mathematical model of a common pool resource game is developed to explore the nexus between the underlying costs and benefits of harvesting decisions and the sustainable level of a shared, dynamic resource. We derive optimal harvesting efforts analytically and then use numerical simulations to show that individuals in a group can learn to make harvesting decisions that lead to the globally optimal levels. Individual agents make their decision based on signals received and a trade-off between economic and ecological sustainability. When the balance is weighted towards profitability, acceptable economic and social outcomes emerge. However, if individual agents are solely driven by profit, the shared resource is depleted in the long run - sustainability is possible despite some greed, but too much will lead to over-exploitation.

Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design.

PubMed

Polizzotti, Brian D; Thomson, Lindsay M; O'Connell, Daniel W; McGowan, Francis X; Kheir, John N

2014-08-01

Tissue hypoxia is a final common pathway that leads to cellular injury and death in a number of critical illnesses. Intravenous injections of self-assembling, lipid-based oxygen microbubbles (LOMs) can be used to deliver oxygen gas, preventing organ injury and death from systemic hypoxemia. However, current formulations exhibit high polydispersity indices (which may lead to microvascular obstruction) and poor shelf-lives, limiting the translational capacity of LOMs. In this study, we report our efforts to optimize LOM formulations using a mixture response surface methodology (mRSM). We study the effect of changing excipient proportions (the independent variables) on microbubble diameter and product loss (the dependent variables). By using mRSM analysis, the experimental data were fit using a reduced Scheffé linear mixture model. We demonstrate that formulations manufactured from 1,2-distearoyl-sn-glycero-3-phosphocholine, corn syrup, and water produce micron-sized microbubbles with low polydispersity indices, and decreased product loss (relative to previously described formulations) when stored at room temperature over a 30-day period. Optimized LOMs were subsequently tested for their oxygen-releasing ability and found to have similar release kinetics as prior formulations. © 2014 Wiley Periodicals, Inc.

Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer

PubMed Central

Scholz, Arne; Lienau, Philip; Siemeister, Gerhard; Kosemund, Dirk; Bohlmann, Rolf; Briem, Hans; Terebesi, Ildiko; Meyer, Kirstin; Prelle, Katja; Denner, Karsten; Bömer, Ulf; Schäfer, Martina; Eis, Knut; Valencia, Ray; Ince, Stuart; von Nussbaum, Franz; Mumberg, Dominik; Ziegelbauer, Karl; Klebl, Bert; Choidas, Axel; Nussbaumer, Peter; Baumann, Matthias; Schultz‐Fademrecht, Carsten; Rühter, Gerd; Eickhoff, Jan; Brands, Michael

2017-01-01

Abstract Selective inhibition of exclusively transcription‐regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY‐958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited the best overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAY 1143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer. PMID:28961375

Design of optimal groundwater remediation systems under flexible environmental-standard constraints.

PubMed

Fan, Xing; He, Li; Lu, Hong-Wei; Li, Jing

2015-01-01

In developing optimal groundwater remediation strategies, limited effort has been exerted to solve the uncertainty in environmental quality standards. When such uncertainty is not considered, either over optimistic or over pessimistic optimization strategies may be developed, probably leading to the formulation of rigid remediation strategies. This study advances a mathematical programming modeling approach for optimizing groundwater remediation design. This approach not only prevents the formulation of over optimistic and over pessimistic optimization strategies but also provides a satisfaction level that indicates the degree to which the environmental quality standard is satisfied. Therefore the approach may be expected to be significantly more acknowledged by the decision maker than those who do not consider standard uncertainty. The proposed approach is applied to a petroleum-contaminated site in western Canada. Results from the case study show that (1) the peak benzene concentrations can always satisfy the environmental standard under the optimal strategy, (2) the pumping rates of all wells decrease under a relaxed standard or long-term remediation approach, (3) the pumping rates are less affected by environmental quality constraints under short-term remediation, and (4) increased flexible environmental standards have a reduced effect on the optimal remediation strategy.

Optimization of a New Cell-Based Fluorescence Assay for U.S. Army Global Malaria Surveillance Efforts in Support of the Warfighter

DTIC Science & Technology

2006-11-01

humans. Of these, Plasmodium falciparum is the most deadly. P . vivax, although it rarely causes death, is a constant annoyance and the leading...liver hepatocytes. Both P . vivax and P . falciparum have developed resistance to numerous antimalarial drugs, which has undermined the available...assay in our own laboratory. P . falciparum strains D6 and W2 were treated with a panel of known anti-malarial drugs and their respective IC50s were

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

PubMed

Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

2015-08-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

PubMed Central

Boyle, John; Czito, Brian; Willett, Christopher

2015-01-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

Scale-dependent feedbacks between patch size and plant reproduction in desert grassland

USGS Publications Warehouse

Svejcar, Lauren N.; Bestelmeyer, Brandon T.; Duniway, Michael C.; James, Darren K.

2015-01-01

Theoretical models suggest that scale-dependent feedbacks between plant reproductive success and plant patch size govern transitions from highly to sparsely vegetated states in drylands, yet there is scant empirical evidence for these mechanisms. Scale-dependent feedback models suggest that an optimal patch size exists for growth and reproduction of plants and that a threshold patch organization exists below which positive feedbacks between vegetation and resources can break down, leading to critical transitions. We examined the relationship between patch size and plant reproduction using an experiment in a Chihuahuan Desert grassland. We tested the hypothesis that reproductive effort and success of a dominant grass (Bouteloua eriopoda) would vary predictably with patch size. We found that focal plants in medium-sized patches featured higher rates of grass reproductive success than when plants occupied either large patch interiors or small patches. These patterns support the existence of scale-dependent feedbacks in Chihuahuan Desert grasslands and indicate an optimal patch size for reproductive effort and success in B. eriopoda. We discuss the implications of these results for detecting ecological thresholds in desert grasslands.

Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery

PubMed Central

Ekins, Sean; Freundlich, Joel S.; Choi, Inhee; Sarker, Malabika; Talcott, Carolyn

2010-01-01

We are witnessing the growing menace of both increasing cases of drug-sensitive and drug-resistant Mycobacterium tuberculosis strains and the challenge to produce the first new tuberculosis (TB) drug in well over 40 years. The TB community, having invested in extensive high-throughput screening efforts, is faced with the question of how to optimally leverage this data in order to move from a hit to a lead to a clinical candidate and potentially a new drug. Complementing this approach, yet conducted on a much smaller scale, cheminformatic techniques have been leveraged and are herein reviewed. We suggest these computational approaches should be more optimally integrated in a workflow with experimental approaches to accelerate TB drug discovery. PMID:21129975

Structure-Based Optimization of Arylamides as Inhibitors of Soluble Epoxide Hydrolase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldrup, Anne B.; Soleymanzadeh, Fariba; Taylor, Steven J.

2009-11-04

Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of an effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection. The screen identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat livermore » microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.« less

Lattice Boltzmann Simulation Optimization on Leading Multicore Platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Samuel; Carter, Jonathan; Oliker, Leonid

2008-02-01

We present an auto-tuning approach to optimize application performance on emerging multicore architectures. The methodology extends the idea of search-based performance optimizations, popular in linear algebra and FFT libraries, to application-specific computational kernels. Our work applies this strategy to a lattice Boltzmann application (LBMHD) that historically has made poor use of scalar microprocessors due to its complex data structures and memory access patterns. We explore one of the broadest sets of multicore architectures in the HPC literature, including the Intel Clovertown, AMD Opteron X2, Sun Niagara2, STI Cell, as well as the single core Intel Itanium2. Rather than hand-tuning LBMHDmore » for each system, we develop a code generator that allows us identify a highly optimized version for each platform, while amortizing the human programming effort. Results show that our auto-tuned LBMHD application achieves up to a 14x improvement compared with the original code. Additionally, we present detailed analysis of each optimization, which reveal surprising hardware bottlenecks and software challenges for future multicore systems and applications.« less

Lattice Boltzmann simulation optimization on leading multicore platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, S.; Carter, J.; Oliker, L.

2008-01-01

We present an auto-tuning approach to optimize application performance on emerging multicore architectures. The methodology extends the idea of searchbased performance optimizations, popular in linear algebra and FFT libraries, to application-specific computational kernels. Our work applies this strategy to a lattice Boltzmann application (LBMHD) that historically has made poor use of scalar microprocessors due to its complex data structures and memory access patterns. We explore one of the broadest sets of multicore architectures in the HPC literature, including the Intel Clovertown, AMD Opteron X2, Sun Niagara2, STI Cell, as well as the single core Intel Itanium2. Rather than hand-tuning LBMHDmore » for each system, we develop a code generator that allows us identify a highly optimized version for each platform, while amortizing the human programming effort. Results show that our autotuned LBMHD application achieves up to a 14 improvement compared with the original code. Additionally, we present detailed analysis of each optimization, which reveal surprising hardware bottlenecks and software challenges for future multicore systems and applications.« less

Optimization of an electromagnetic linear actuator using a network and a finite element model

NASA Astrophysics Data System (ADS)

Neubert, Holger; Kamusella, Alfred; Lienig, Jens

2011-03-01

Model based design optimization leads to robust solutions only if the statistical deviations of design, load and ambient parameters from nominal values are considered. We describe an optimization methodology that involves these deviations as stochastic variables for an exemplary electromagnetic actuator used to drive a Braille printer. A combined model simulates the dynamic behavior of the actuator and its non-linear load. It consists of a dynamic network model and a stationary magnetic finite element (FE) model. The network model utilizes lookup tables of the magnetic force and the flux linkage computed by the FE model. After a sensitivity analysis using design of experiment (DoE) methods and a nominal optimization based on gradient methods, a robust design optimization is performed. Selected design variables are involved in form of their density functions. In order to reduce the computational effort we use response surfaces instead of the combined system model obtained in all stochastic analysis steps. Thus, Monte-Carlo simulations can be applied. As a result we found an optimum system design meeting our requirements with regard to function and reliability.

Lessons Learned During Solutions of Multidisciplinary Design Optimization Problems

NASA Technical Reports Server (NTRS)

Patnaik, Suna N.; Coroneos, Rula M.; Hopkins, Dale A.; Lavelle, Thomas M.

2000-01-01

Optimization research at NASA Glenn Research Center has addressed the design of structures, aircraft and airbreathing propulsion engines. During solution of the multidisciplinary problems several issues were encountered. This paper lists four issues and discusses the strategies adapted for their resolution: (1) The optimization process can lead to an inefficient local solution. This deficiency was encountered during design of an engine component. The limitation was overcome through an augmentation of animation into optimization. (2) Optimum solutions obtained were infeasible for aircraft and air-breathing propulsion engine problems. Alleviation of this deficiency required a cascading of multiple algorithms. (3) Profile optimization of a beam produced an irregular shape. Engineering intuition restored the regular shape for the beam. (4) The solution obtained for a cylindrical shell by a subproblem strategy converged to a design that can be difficult to manufacture. Resolution of this issue remains a challenge. The issues and resolutions are illustrated through six problems: (1) design of an engine component, (2) synthesis of a subsonic aircraft, (3) operation optimization of a supersonic engine, (4) design of a wave-rotor-topping device, (5) profile optimization of a cantilever beam, and (6) design of a cvlindrical shell. The combined effort of designers and researchers can bring the optimization method from academia to industry.

Supersonic Aerodynamic Design Improvements of an Arrow-Wing HSCT Configuration Using Nonlinear Point Design Methods

NASA Technical Reports Server (NTRS)

Unger, Eric R.; Hager, James O.; Agrawal, Shreekant

1999-01-01

This paper is a discussion of the supersonic nonlinear point design optimization efforts at McDonnell Douglas Aerospace under the High-Speed Research (HSR) program. The baseline for these optimization efforts has been the M2.4-7A configuration which represents an arrow-wing technology for the High-Speed Civil Transport (HSCT). Optimization work on this configuration began in early 1994 and continued into 1996. Initial work focused on optimization of the wing camber and twist on a wing/body configuration and reductions of 3.5 drag counts (Euler) were realized. The next phase of the optimization effort included fuselage camber along with the wing and a drag reduction of 5.0 counts was achieved. Including the effects of the nacelles and diverters into the optimization problem became the next focus where a reduction of 6.6 counts (Euler W/B/N/D) was eventually realized. The final two phases of the effort included a large set of constraints designed to make the final optimized configuration more realistic and they were successful albeit with a loss of performance.

Discovery of pyridyl sulfonamide 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors for the treatment of metabolic disorders.

PubMed

Yoon, David S; Wu, Shung C; Seethala, Ramakrishna; Golla, Rajasree; Nayeem, Akbar; Everlof, John G; Gordon, David A; Hamann, Lawrence G; Robl, Jeffrey A

2014-11-01

A previous disclosure from this lab highlighted the discovery of pyridyl amides as potent 11β-HSD1 inhibitors. In order to build additional novelty and polarity into this chemotype, replacement of the hydrogen-bonding carbonyl (CO) pharmacophore with the bioisosteric sulfonyl (SO2) group was examined. Despite initial comparisons suggesting the corresponding sulfonamides exhibited weaker activity versus their carbonyl counterparts, further optimization was performed in an effort to identify various potent and unique leads for the program. Judicious incorporation of polar moieties resulted in the identification of compounds with enhanced potency and lipophilicity profiles, resulting in leads with superior aqueous solubility and liver microsomal stability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluating Thermodynamic Integration Performance of the New Amber Molecular Dynamics Package and Assess Potential Halogen Bonds of Enoyl-ACP Reductase (FabI) Benzimidazole Inhibitors

PubMed Central

Su, Pin-Chih; Johnson, Michael E.

2015-01-01

Thermodynamic integration (TI) can provide accurate binding free energy insights in a lead optimization program, but its high computational expense has limited its usage. In the effort of developing an efficient and accurate TI protocol for FabI inhibitors lead optimization program, we carefully compared TI with different Amber molecular dynamics (MD) engines (sander and pmemd), MD simulation lengths, the number of intermediate states and transformation steps, and the Lennard-Jones and Coulomb Softcore potentials parameters in the one-step TI, using eleven benzimidazole inhibitors in complex with Francisella tularensis enoyl acyl reductase (FtFabI). To our knowledge, this is the first study to extensively test the new AMBER MD engine, pmemd, on TI and compare the parameters of the Softcore potentials in the one-step TI in a protein-ligand binding system. The best performing model, the one-step pmemd TI, using 6 intermediate states and 1 ns MD simulations, provides better agreement with experimental results (RMSD = 0.52 kcal/mol) than the best performing implicit solvent method, QM/MM-GBSA from our previous study (RMSD = 3.00 kcal/mol), while maintaining similar efficiency. Briefly, we show the optimized TI protocol to be highly accurate and affordable for the FtFabI system. This approach can be implemented in a larger scale benzimidazole scaffold lead optimization against FtFabI. Lastly, the TI results here also provide structure-activity relationship insights, and suggest the para-halogen in benzimidazole compounds might form a weak halogen bond with FabI, which is a well-known halogen bond favoring enzyme. PMID:26666582

Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors.

PubMed

Su, Pin-Chih; Johnson, Michael E

2016-04-05

Thermodynamic integration (TI) can provide accurate binding free energy insights in a lead optimization program, but its high computational expense has limited its usage. In the effort of developing an efficient and accurate TI protocol for FabI inhibitors lead optimization program, we carefully compared TI with different Amber molecular dynamics (MD) engines (sander and pmemd), MD simulation lengths, the number of intermediate states and transformation steps, and the Lennard-Jones and Coulomb Softcore potentials parameters in the one-step TI, using eleven benzimidazole inhibitors in complex with Francisella tularensis enoyl acyl reductase (FtFabI). To our knowledge, this is the first study to extensively test the new AMBER MD engine, pmemd, on TI and compare the parameters of the Softcore potentials in the one-step TI in a protein-ligand binding system. The best performing model, the one-step pmemd TI, using 6 intermediate states and 1 ns MD simulations, provides better agreement with experimental results (RMSD = 0.52 kcal/mol) than the best performing implicit solvent method, QM/MM-GBSA from our previous study (RMSD = 3.00 kcal/mol), while maintaining similar efficiency. Briefly, we show the optimized TI protocol to be highly accurate and affordable for the FtFabI system. This approach can be implemented in a larger scale benzimidazole scaffold lead optimization against FtFabI. Lastly, the TI results here also provide structure-activity relationship insights, and suggest the parahalogen in benzimidazole compounds might form a weak halogen bond with FabI, which is a well-known halogen bond favoring enzyme. © 2015 Wiley Periodicals, Inc.

In Situ Passivation for Efficient PbS Quantum Dot Solar Cells by Precursor Engineering.

PubMed

Wang, Yongjie; Lu, Kunyuan; Han, Lu; Liu, Zeke; Shi, Guozheng; Fang, Honghua; Chen, Si; Wu, Tian; Yang, Fan; Gu, Mengfan; Zhou, Sijie; Ling, Xufeng; Tang, Xun; Zheng, Jiawei; Loi, Maria Antonietta; Ma, Wanli

2018-04-01

Current efforts on lead sulfide quantum dot (PbS QD) solar cells are mostly paid to the device architecture engineering and postsynthetic surface modification, while very rare work regarding the optimization of PbS synthesis is reported. Here, PbS QDs are successfully synthesized using PbO and PbAc 2  · 3H 2 O as the lead sources. QD solar cells based on PbAc-PbS have demonstrated a high power conversion efficiency (PCE) of 10.82% (and independently certificated values of 10.62%), which is significantly higher than the PCE of 9.39% for PbO-PbS QD based ones. For the first time, systematic investigations are carried out on the effect of lead precursor engineering on the device performance. It is revealed that acetate can act as an efficient capping ligands together with oleic acid, providing better surface coverage and replace some of the harmful hydroxyl (OH) ligands during the synthesis. Then the acetate on the surface can be exchanged by iodide and lead to desired passivation. This work demonstrates that the precursor engineering has great potential in performance improvement. It is also pointed out that the initial synthesis is an often neglected but critical stage and has abundant room for optimization to further improve the quality of the resultant QDs, leading to breakthrough efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Planning intensive care unit design using computer simulation modeling: optimizing integration of clinical, operational, and architectural requirements.

PubMed

OʼHara, Susan

2014-01-01

Nurses have increasingly been regarded as critical members of the planning team as architects recognize their knowledge and value. But the nurses' role as knowledge experts can be expanded to leading efforts to integrate the clinical, operational, and architectural expertise through simulation modeling. Simulation modeling allows for the optimal merge of multifactorial data to understand the current state of the intensive care unit and predict future states. Nurses can champion the simulation modeling process and reap the benefits of a cost-effective way to test new designs, processes, staffing models, and future programming trends prior to implementation. Simulation modeling is an evidence-based planning approach, a standard, for integrating the sciences with real client data, to offer solutions for improving patient care.

Stochastic Optimization For Water Resources Allocation

NASA Astrophysics Data System (ADS)

Yamout, G.; Hatfield, K.

2003-12-01

For more than 40 years, water resources allocation problems have been addressed using deterministic mathematical optimization. When data uncertainties exist, these methods could lead to solutions that are sub-optimal or even infeasible. While optimization models have been proposed for water resources decision-making under uncertainty, no attempts have been made to address the uncertainties in water allocation problems in an integrated approach. This paper presents an Integrated Dynamic, Multi-stage, Feedback-controlled, Linear, Stochastic, and Distributed parameter optimization approach to solve a problem of water resources allocation. It attempts to capture (1) the conflict caused by competing objectives, (2) environmental degradation produced by resource consumption, and finally (3) the uncertainty and risk generated by the inherently random nature of state and decision parameters involved in such a problem. A theoretical system is defined throughout its different elements. These elements consisting mainly of water resource components and end-users are described in terms of quantity, quality, and present and future associated risks and uncertainties. Models are identified, modified, and interfaced together to constitute an integrated water allocation optimization framework. This effort is a novel approach to confront the water allocation optimization problem while accounting for uncertainties associated with all its elements; thus resulting in a solution that correctly reflects the physical problem in hand.

Synthesis and Evaluation of N-phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators inhibiting Hepatitis B Virus (HBV).

PubMed

Vandyck, Koen; Rombouts, Geert; Stoops, Bart; Tahri, Abdellah; Vos, Ann; Verschueren, Wim; Wu, Yiming; Yang, Jingmei; Hou, Fuliang; Huang, Bing; Vergauwen, Karen; Dehertogh, Pascale; Berke, Jan-Martin; Raboisson, Pierre Jean Marie Bernard

2018-06-15

Small molecule induced Hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts towards the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice, resulted in a 2.77 log reduction of the HBV DNA viral load.

Financial advantages. Preventative measures ensure the health of your accounts receivable.

PubMed

Duda, Michelle

2009-11-01

Running a dental practice is no small task; from staying on the leading edge of new medical developments and products, to monitoring ever-changing dental insurance plans, to simply overseeing the fundamental day-to-day operations. But there is one area of your practice that can be streamlined to significantly improve your cash flow, minimize delinquencies and optimize fiscal operations. Your accounts receivable and collections can be economically and efficiently managed by a savvy combination of internal efforts and the partnership of a third party resource.

Mean-Field Games for Marriage

PubMed Central

Bauso, Dario; Dia, Ben Mansour; Djehiche, Boualem; Tembine, Hamidou; Tempone, Raul

2014-01-01

This article examines mean-field games for marriage. The results support the argument that optimizing the long-term well-being through effort and social feeling state distribution (mean-field) will help to stabilize marriage. However, if the cost of effort is very high, the couple fluctuates in a bad feeling state or the marriage breaks down. We then examine the influence of society on a couple using mean-field sentimental games. We show that, in mean-field equilibrium, the optimal effort is always higher than the one-shot optimal effort. We illustrate numerically the influence of the couple’s network on their feeling states and their well-being. PMID:24804835

Mean-field games for marriage.

PubMed

Bauso, Dario; Dia, Ben Mansour; Djehiche, Boualem; Tembine, Hamidou; Tempone, Raul

2014-01-01

This article examines mean-field games for marriage. The results support the argument that optimizing the long-term well-being through effort and social feeling state distribution (mean-field) will help to stabilize marriage. However, if the cost of effort is very high, the couple fluctuates in a bad feeling state or the marriage breaks down. We then examine the influence of society on a couple using mean-field sentimental games. We show that, in mean-field equilibrium, the optimal effort is always higher than the one-shot optimal effort. We illustrate numerically the influence of the couple's network on their feeling states and their well-being.

Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coteron, Jose M.; Marco, Maria; Esquivias, Jorge

2012-02-27

Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model,more » can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.« less

Docking ligands into flexible and solvated macromolecules. 7. Impact of protein flexibility and water molecules on docking-based virtual screening accuracy.

PubMed

Therrien, Eric; Weill, Nathanael; Tomberg, Anna; Corbeil, Christopher R; Lee, Devin; Moitessier, Nicolas

2014-11-24

The use of predictive computational methods in the drug discovery process is in a state of continual growth. Over the last two decades, an increasingly large number of docking tools have been developed to identify hits or optimize lead molecules through in-silico screening of chemical libraries to proteins. In recent years, the focus has been on implementing protein flexibility and water molecules. Our efforts led to the development of Fitted first reported in 2007 and further developed since then. In this study, we wished to evaluate the impact of protein flexibility and occurrence of water molecules on the accuracy of the Fitted docking program to discriminate active compounds from inactive compounds in virtual screening (VS) campaigns. For this purpose, a total of 171 proteins cocrystallized with small molecules representing 40 unique enzymes and receptors as well as sets of known ligands and decoys were selected from the Protein Data Bank (PDB) and the Directory of Useful Decoys (DUD), respectively. This study revealed that implementing displaceable crystallographic or computationally placed particle water molecules and protein flexibility can improve the enrichment in active compounds. In addition, an informed decision based on library diversity or research objectives (hit discovery vs lead optimization) on which implementation to use may lead to significant improvements.

Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.

PubMed

Curreli, Francesca; Belov, Dmitry S; Kwon, Young Do; Ramesh, Ranjith; Furimsky, Anna M; O'Loughlin, Kathleen; Byrge, Patricia C; Iyer, Lalitha V; Mirsalis, Jon C; Kurkin, Alexander V; Altieri, Andrea; Debnath, Asim K

2018-05-12

We are continuing our concerted effort to optimize our first lead entry antagonist, NBD-11021, which targets the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, to improve antiviral potency and ADMET properties. In this report, we present a structure-based approach that helped us to generate working hypotheses to modify further a recently reported advanced lead entry antagonist, NBD-14107, which showed significant improvement in antiviral potency when tested in a single-cycle assay against a large panel of Env-pseudotyped viruses. We report here the synthesis of twenty-nine new compounds and evaluation of their antiviral activity in a single-cycle and multi-cycle assay to derive a comprehensive structure-activity relationship (SAR). We have selected three inhibitors with the high selectivity index for testing against a large panel of 55 Env-pseudotyped viruses representing a diverse set of clinical isolates of different subtypes. The antiviral activity of one of these potent inhibitors, 55 (NBD-14189), against some clinical isolates was as low as 63 nM. We determined the sensitivity of CD4-binding site mutated-pseudoviruses to these inhibitors to confirm that they target HIV-1 gp120. Furthermore, we assessed their ADMET properties and compared them to the clinical candidate attachment inhibitor, BMS-626529. The ADMET data indicate that some of these new inhibitors have comparable ADMET properties to BMS-626529 and can be optimized further to potential clinical candidates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Competition or cooperation in transboundary fish stocks management: Insight from a dynamical model.

PubMed

Nguyen, Trong Hieu; Brochier, Timothée; Auger, Pierre; Trinh, Viet Duoc; Brehmer, Patrice

2018-06-14

An idealized system of a shared fish stock associated with different exclusive economic zones (EEZ) is modelled. Parameters were estimated for the case of the small pelagic fisheries shared between Southern Morocco, Mauritania and the Senegambia. Two models of fishing effort distribution were explored. The first one considers independent national fisheries in each EEZ, with a cost per unit of fishing effort that depends on local fishery policy. The second one considers the case of a fully cooperative fishery performed by an international fleet freely moving across the borders. Both models are based on a set of six ordinary differential equations describing the time evolution of the fish biomass and the fishing effort. We take advantage of the two time scales to obtain a reduced model governing the total fish biomass of the system and fishing efforts in each zone. At the fast equilibrium, the fish distribution follows the ideal free distribution according to the carrying capacity in each area. Different equilibria can be reached according to management choices. When fishing fleets are independent and national fishery policies are not harmonized, in the general case, competition leads after a few decades to a scenario where only one fishery remains sustainable. In the case of sub-regional agreement acting on the adjustment of cost per unit of fishing effort in each EEZ, we found that a large number of equilibria exists. In this last case the initial distribution of fishing effort strongly impact the optimal equilibrium that can be reached. Lastly, the country with the highest carrying capacity density may get less landings when collaborating with other countries than if it minimises its fishing costs. The second fully cooperative model shows that a single international fishing fleet moving freely in the fishing areas leads to a sustainable equilibrium. Such findings should foster regional fisheries organizations to get potential new ways for neighbouring fish stock management. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Design of alumina forming FeCrAl steels for lead or lead-bismuth cooled fast reactors

NASA Astrophysics Data System (ADS)

Lim, Jun; Hwang, Il Soon; Kim, Ji Hyun

2013-10-01

Iron-chromium-aluminum alloys containing 15-20 wt.% Cr and 4-6 wt.% Al have shown excellent corrosion resistance in the temperature range up to 600 °C or higher in liquid lead and lead-bismuth eutectic environments by the formation of protective Al2O3 layers. However, the higher Cr and Al concentrations in ferritic alloys could be problematic because of severe embrittlement in the manufacturing process as well as in service, caused by the formation of brittle phases. For this reason, efforts worldwide have so far mainly focused on the development of aluminizing surface treatments. However, aluminizing surface treatments have major disadvantages of cost, processing difficulties and reliability issues. In this study, a new FeCrAl alloy is proposed for structural materials in lead and lead-bismuth cooled nuclear applications. The alloy design relied on corrosion experiments in high temperature lead and lead-bismuth eutectic environments and computational thermodynamic calculations using the commercial software, JMatPro. The design of new alloys has focused on the optimization of Cr and Al levels for the formation of an external Al2O3 layer which can provide excellent oxidation and corrosion resistance in liquid lead alloys in the temperature range 300-600 °C while still retaining workable mechanical properties.

When Optimal Feedback Control Is Not Enough: Feedforward Strategies Are Required for Optimal Control with Active Sensing.

PubMed

Yeo, Sang-Hoon; Franklin, David W; Wolpert, Daniel M

2016-12-01

Movement planning is thought to be primarily determined by motor costs such as inaccuracy and effort. Solving for the optimal plan that minimizes these costs typically leads to specifying a time-varying feedback controller which both generates the movement and can optimally correct for errors that arise within a movement. However, the quality of the sensory feedback during a movement can depend substantially on the generated movement. We show that by incorporating such state-dependent sensory feedback, the optimal solution incorporates active sensing and is no longer a pure feedback process but includes a significant feedforward component. To examine whether people take into account such state-dependency in sensory feedback we asked people to make movements in which we controlled the reliability of sensory feedback. We made the visibility of the hand state-dependent, such that the visibility was proportional to the component of hand velocity in a particular direction. Subjects gradually adapted to such a sensory perturbation by making curved hand movements. In particular, they appeared to control the late visibility of the movement matching predictions of the optimal controller with state-dependent sensory noise. Our results show that trajectory planning is not only sensitive to motor costs but takes sensory costs into account and argues for optimal control of movement in which feedforward commands can play a significant role.

A reduced successive quadratic programming strategy for errors-in-variables estimation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tjoa, I.-B.; Biegler, L. T.; Carnegie-Mellon Univ.

Parameter estimation problems in process engineering represent a special class of nonlinear optimization problems, because the maximum likelihood structure of the objective function can be exploited. Within this class, the errors in variables method (EVM) is particularly interesting. Here we seek a weighted least-squares fit to the measurements with an underdetermined process model. Thus, both the number of variables and degrees of freedom available for optimization increase linearly with the number of data sets. Large optimization problems of this type can be particularly challenging and expensive to solve because, for general-purpose nonlinear programming (NLP) algorithms, the computational effort increases atmore » least quadratically with problem size. In this study we develop a tailored NLP strategy for EVM problems. The method is based on a reduced Hessian approach to successive quadratic programming (SQP), but with the decomposition performed separately for each data set. This leads to the elimination of all variables but the model parameters, which are determined by a QP coordination step. In this way the computational effort remains linear in the number of data sets. Moreover, unlike previous approaches to the EVM problem, global and superlinear properties of the SQP algorithm apply naturally. Also, the method directly incorporates inequality constraints on the model parameters (although not on the fitted variables). This approach is demonstrated on five example problems with up to 102 degrees of freedom. Compared to general-purpose NLP algorithms, large improvements in computational performance are observed.« less

Orbital Transfer Vehicle (OTV) engine study. Phase A: Extension

NASA Technical Reports Server (NTRS)

Sobin, A. J.

1980-01-01

The current Phase A-Extension of the OTV engine study program aims to provide additional expander and staged combustion cycle data that will lead to design definition of the OTV engine. The proposed program effort seeks to optimize the expander cycle engine concept (consistent with identified OTV engine requirements), investigate the feasibility of kitting the staged combustion cycle engine to provide extended thrust operation, and conduct in-depth analysis of development risk, crew safety, and reliability for both cycles. Additional tasks address the costing of a 10/K thrust expander cycle engine and support of OTV systems study contractors.

High resolution diffraction imaging of crystals grown in microgravity and closely related terrestrial crystals

NASA Technical Reports Server (NTRS)

Steiner, B.; Dobbyn, R.; Black, D.; Burdette, H.; Kuriyama, M.; Spal, R.; Vandenberg, L.; Fripp, A.; Simchick, R.; Lal, R.

1991-01-01

Irregularities found in three crystals grown in space, in four crystals grown entirely on the ground were examined and compared. Irregularities were observed in mercuric iodide, lead tin telluride, triglycine sulfate, and gallium arsenide by high resolution synchrotron x radiation diffraction imaging. Radiation detectors made from mercuric iodide crystals grown in microgravity were reported to perform far better than conventional detectors grown from the same material under full gravity. Effort is now underway to reproduce these 'space' crystals, optimize their properties, and extend comparable superiority to other types of materials.

Computational nuclear quantum many-body problem: The UNEDF project

NASA Astrophysics Data System (ADS)

Bogner, S.; Bulgac, A.; Carlson, J.; Engel, J.; Fann, G.; Furnstahl, R. J.; Gandolfi, S.; Hagen, G.; Horoi, M.; Johnson, C.; Kortelainen, M.; Lusk, E.; Maris, P.; Nam, H.; Navratil, P.; Nazarewicz, W.; Ng, E.; Nobre, G. P. A.; Ormand, E.; Papenbrock, T.; Pei, J.; Pieper, S. C.; Quaglioni, S.; Roche, K. J.; Sarich, J.; Schunck, N.; Sosonkina, M.; Terasaki, J.; Thompson, I.; Vary, J. P.; Wild, S. M.

2013-10-01

The UNEDF project was a large-scale collaborative effort that applied high-performance computing to the nuclear quantum many-body problem. The primary focus of the project was on constructing, validating, and applying an optimized nuclear energy density functional, which entailed a wide range of pioneering developments in microscopic nuclear structure and reactions, algorithms, high-performance computing, and uncertainty quantification. UNEDF demonstrated that close associations among nuclear physicists, mathematicians, and computer scientists can lead to novel physics outcomes built on algorithmic innovations and computational developments. This review showcases a wide range of UNEDF science results to illustrate this interplay.

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

PubMed

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Using a Geographic Information System to Improve Childhood Lead-Screening Efforts

PubMed Central

2013-01-01

The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure–risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts. PMID:23764346

Dynamic Resource Allocation in Disaster Response: Tradeoffs in Wildfire Suppression

PubMed Central

Petrovic, Nada; Alderson, David L.; Carlson, Jean M.

2012-01-01

Challenges associated with the allocation of limited resources to mitigate the impact of natural disasters inspire fundamentally new theoretical questions for dynamic decision making in coupled human and natural systems. Wildfires are one of several types of disaster phenomena, including oil spills and disease epidemics, where (1) the disaster evolves on the same timescale as the response effort, and (2) delays in response can lead to increased disaster severity and thus greater demand for resources. We introduce a minimal stochastic process to represent wildfire progression that nonetheless accurately captures the heavy tailed statistical distribution of fire sizes observed in nature. We then couple this model for fire spread to a series of response models that isolate fundamental tradeoffs both in the strength and timing of response and also in division of limited resources across multiple competing suppression efforts. Using this framework, we compute optimal strategies for decision making scenarios that arise in fire response policy. PMID:22514605

Discovery and SAR of Novel 2,3‐Dihydroimidazo[1,2‐c]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80‐6946)

PubMed Central

Hentemann, Martin F.; Rowley, R. Bruce; Bull, Cathy O.; Jenkins, Susan; Bullion, Ann M.; Johnson, Jeffrey; Redman, Anikó; Robbins, Arthur H.; Esler, William; Fracasso, R. Paul; Garrison, Timothy; Hamilton, Mark; Michels, Martin; Wood, Jill E.; Wilkie, Dean P.; Xiao, Hong; Levy, Joan; Stasik, Enrico; Liu, Ningshu; Schaefer, Martina; Brands, Michael

2016-01-01

Abstract The phosphoinositide 3‐kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or by the genetic mutation and amplification of key pathway components. A variety of PI3K isoforms play differential roles in cancers. As such, the development of PI3K inhibitors from novel compound classes should lead to differential pharmacological and pharmacokinetic profiles and allow exploration in various indications, combinations, and dosing regimens. A screening effort aimed at the identification of PI3Kγ inhibitors for the treatment of inflammatory diseases led to the discovery of the novel 2,3‐dihydroimidazo[1,2‐c]quinazoline class of PI3K inhibitors. A subsequent lead optimization program targeting cancer therapy focused on inhibition of PI3Kα and PI3Kβ. Herein, initial structure–activity relationship findings for this class and the optimization that led to the identification of copanlisib (BAY 80‐6946) as a clinical candidate for the treatment of solid and hematological tumors are described. PMID:27310202

Climate, bleaching and connectivity in the Coral Triangle.

NASA Astrophysics Data System (ADS)

Curchitser, E. N.; Kleypas, J. A.; Castruccio, F. S.; Drenkard, E.; Thompson, D. M.; Pinsky, M. L.

2016-12-01

The Coral Triangle (CT) is the apex of marine biodiversity and supports the livelihoods of millions of people. It is also one of the most threatened of all reef regions in the world. We present results from a series of high-resolution, numerical ocean models designed to address physical and ecological questions relevant to the region's coral communities. The hierarchy of models was designed to optimize the model performance in addressing questions ranging from the role of internal tides in larval connectivity to distinguishing the role of interannual variability from decadal trends in thermal stress leading to mass bleaching events. In this presentation we will show how combining ocean circulation with models of larval dispersal leads to new insights into the interplay of physics and ecology in this complex oceanographic region, which can ultimately be used to inform conservation efforts.

Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series - Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2.

PubMed

Muthukaman, Nagarajan; Deshmukh, Sanjay; Tambe, Macchindra; Pisal, Dnyandeo; Tondlekar, Shital; Shaikh, Mahamadhanif; Sarode, Neelam; Kattige, Vidya G; Sawant, Pooja; Pisat, Monali; Karande, Vikas; Honnegowda, Srinivasa; Kulkarni, Abhay; Behera, Dayanidhi; Jadhav, Satyawan B; Sangana, Ramchandra R; Gudi, Girish S; Khairatkar-Joshi, Neelima; Gharat, Laxmikant A

2018-04-15

In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED 50 : 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED 50 : 106 mg/kg). Copyright © 2018 Elsevier Ltd. All rights reserved.

Continuous Adaptive Population Reduction (CAPR) for Differential Evolution Optimization.

PubMed

Wong, Ieong; Liu, Wenjia; Ho, Chih-Ming; Ding, Xianting

2017-06-01

Differential evolution (DE) has been applied extensively in drug combination optimization studies in the past decade. It allows for identification of desired drug combinations with minimal experimental effort. This article proposes an adaptive population-sizing method for the DE algorithm. Our new method presents improvements in terms of efficiency and convergence over the original DE algorithm and constant stepwise population reduction-based DE algorithm, which would lead to a reduced number of cells and animals required to identify an optimal drug combination. The method continuously adjusts the reduction of the population size in accordance with the stage of the optimization process. Our adaptive scheme limits the population reduction to occur only at the exploitation stage. We believe that continuously adjusting for a more effective population size during the evolutionary process is the major reason for the significant improvement in the convergence speed of the DE algorithm. The performance of the method is evaluated through a set of unimodal and multimodal benchmark functions. In combining with self-adaptive schemes for mutation and crossover constants, this adaptive population reduction method can help shed light on the future direction of a completely parameter tune-free self-adaptive DE algorithm.

Dispositional Optimism

PubMed Central

Carver, Charles S.; Scheier, Michael F.

2014-01-01

Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. PMID:24630971

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longenecker, Kenton L.; Stamper, Geoffrey F.; Hajduk, Philip J.

In a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differsmore » dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target.« less

Active Control of Separation From the Flap of a Supercritical Airfoil

NASA Technical Reports Server (NTRS)

Melton, La Tunia Pack; Yao, Chung-Sheng; Seifert, Avi

2003-01-01

Active flow control in the form of periodic zero-mass-flux excitation was applied at several regions on the leading edge and trailing edge flaps of a simplified high-lift system t o delay flow separation. The NASA Energy Efficient Transport (EET) supercritical airfoil was equipped with a 15% chord simply hinged leading edge flap and a 25% chord simply hinged trailing edge flap. Detailed flow features were measured in an attempt to identify optimal actuator placement. The measurements included steady and unsteady model and tunnel wall pressures, wake surveys, arrays of surface hot-films, flow visualization, and particle image velocimetry (PIV). The current paper describes the application of active separation control at several locations on the deflected trailing edge flap. High frequency (F(+) approx.= 10) and low frequency amplitude modulation (F(+)AM approx.= 1) of the high frequency excitation were used for control. Preliminary efforts to combine leading and trailing edge flap excitations are also reported.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

PubMed

Dinges, Jurgen; Harris, Christopher M; Wallace, Grier A; Argiriadi, Maria A; Queeney, Kara L; Perron, Denise C; Dominguez, Eric; Kebede, Tegest; Desino, Kelly E; Patel, Hetal; Vasudevan, Anil

2016-05-01

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coordinating vendor-buyer decisions for imperfect quality items considering trade credit and fully backlogged shortages

NASA Astrophysics Data System (ADS)

Khanna, Aditi; Gautam, Prerna; Jaggi, Chandra K.

2016-03-01

Supply chain management has become a critical issue for modern business environments. In today's world of cooperative decision-making, individual decisions in order to reduce inventory costs may not lead to an overall optimal solution. Coordination is necessary among participants of supply chain to achieve better performance. There are legitimate and important efforts from the vendor to enhance the relation with buyer; one such effort is offering trade credit which has been a driver of growth and development of business between them. The cost of financing is a core consideration in effective financial management, in general and in context of business. Also, due to imperfect production a vendor may produce defective items which results in shortages. Motivated with these aspects, an integrated vendor-buyer inventory model is developed for imperfect quality items with allowable shortages; in which the vendor offers credit period to the buyer for payment. The objective is to minimize the total joint annual costs incurred by the vendor and the buyer by using integrated decision making approach. The expected total annual integrated cost is derived and a solution procedure is provided to find the optimal solution. Numerical analysis shows that the integrated model gives an impressive cost reduction, in comparison to independent decision policies by the vendor and the buyer.

The value of the wechsler intelligence scale for children-fourth edition digit span as an embedded measure of effort: an investigation into children with dual diagnoses.

PubMed

Loughan, Ashlee R; Perna, Robert; Hertza, Jeremy

2012-11-01

The Test of Memory Malingering (TOMM) is a measure of test-taking effort which has traditionally been utilized with adults, but which more recently has demonstrated utility with children. The purpose of this study was to investigate whether the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) Digit Span, commonly used in neuropsychological evaluations, can also be functional as an embedded measure by detecting effort in children with dual diagnoses; a population yet to be investigated. Participants (n = 51) who completed neuropsychological evaluations including the TOMM, WISC-IV, Wisconsin Card Sorting Test, Children's Memory Scale, and Delis-Kaplan Executive Function System were divided into two groups: Optimal Effort and Suboptimal Effort, based on their TOMM Trial 2 scores. Digit Span findings suggest a useful scaled score of ≤4 resulted in optimal cutoff scores, yielding specificity of 91% and sensitivity of 43%. This study supports previous research that the WISC-IV Digit Span has good utility in determining optimal effort, even in children with dual diagnosis or comorbidities.

Crash pulse optimization for occupant protection at various impact velocities.

PubMed

Ito, Daisuke; Yokoi, Yusuke; Mizuno, Koji

2015-01-01

Vehicle deceleration has a large influence on occupant kinematic behavior and injury risks in crashes, and the optimization of the vehicle crash pulse that mitigates occupant loadings has been the subject of substantial research. These optimization research efforts focused on only high-velocity impact in regulatory or new car assessment programs though vehicle collisions occur over a wide range of velocities. In this study, the vehicle crash pulse was optimized for various velocities with a genetic algorithm. Vehicle deceleration was optimized in a full-frontal rigid barrier crash with a simple spring-mass model that represents the vehicle-occupant interaction and a Hybrid III 50th percentile male multibody model. To examine whether the vehicle crash pulse optimized at the high impact velocity is useful for reducing occupant loading at all impact velocities less than the optimized velocity, the occupant deceleration was calculated at various velocities for the optimized crash pulse determined at a high speed. The optimized vehicle deceleration-deformation characteristics that are effective for various velocities were investigated with 2 approaches. The optimized vehicle crash pulse at a single impact velocity consists of a high initial impulse followed by zero deceleration and then constant deceleration in the final stage. The vehicle deceleration optimized with the Hybrid III model was comparable to that determined from the spring-mass model. The optimized vehicle deceleration-deformation characteristics determined at a high speed did not necessarily lead to an occupant deceleration reduction at a lower velocity. The maximum occupant deceleration at each velocity was normalized by the maximum deceleration determined in the single impact velocity optimization. The resulting vehicle deceleration-deformation characteristic was a square crash pulse. The objective function was defined as the number of injuries, which was the product of the number of collisions at the velocity and the probability of occupant injury. The optimized vehicle deceleration consisted of a high deceleration in the initial phase, a small deceleration in the middle phase, and then a high deceleration in the final phase. The optimized vehicle crash pulse at a single impact velocity is effective for reducing occupant deceleration in a crash at the specific impact velocity. However, the crash pulse does not necessarily lead to occupant deceleration reduction at a lower velocity. The optimized vehicle deceleration-deformation characteristics, which are effective for all impact velocities, depend on the weighting of the occupant injury measures at each impact velocity.

Rapid near-optimal aerospace plane trajectory generation and guidance

NASA Technical Reports Server (NTRS)

Calise, A. J.; Corban, J. E.; Markopoulos, N.

1991-01-01

Effort was directed toward the problems of the real time trajectory optimization and guidance law development for the National Aerospace Plane (NASP) applications. In particular, singular perturbation methods were used to develop guidance algorithms suitable for onboard, real time implementation. The progress made in this research effort is reported.

Statistical aspects of point count sampling

USGS Publications Warehouse

Barker, R.J.; Sauer, J.R.; Ralph, C.J.; Sauer, J.R.; Droege, S.

1995-01-01

The dominant feature of point counts is that they do not census birds, but instead provide incomplete counts of individuals present within a survey plot. Considering a simple model for point count sampling, we demon-strate that use of these incomplete counts can bias estimators and testing procedures, leading to inappropriate conclusions. A large portion of the variability in point counts is caused by the incomplete counting, and this within-count variation can be confounded with ecologically meaningful varia-tion. We recommend caution in the analysis of estimates obtained from point counts. Using; our model, we also consider optimal allocation of sampling effort. The critical step in the optimization process is in determining the goals of the study and methods that will be used to meet these goals. By explicitly defining the constraints on sampling and by estimating the relationship between precision and bias of estimators and time spent counting, we can predict the optimal time at a point for each of several monitoring goals. In general, time spent at a point will differ depending on the goals of the study.

Optimization of auxiliary basis sets for the LEDO expansion and a projection technique for LEDO-DFT.

PubMed

Götz, Andreas W; Kollmar, Christian; Hess, Bernd A

2005-09-01

We present a systematic procedure for the optimization of the expansion basis for the limited expansion of diatomic overlap density functional theory (LEDO-DFT) and report on optimized auxiliary orbitals for the Ahlrichs split valence plus polarization basis set (SVP) for the elements H, Li--F, and Na--Cl. A new method to deal with near-linear dependences in the LEDO expansion basis is introduced, which greatly reduces the computational effort of LEDO-DFT calculations. Numerical results for a test set of small molecules demonstrate the accuracy of electronic energies, structural parameters, dipole moments, and harmonic frequencies. For larger molecular systems the numerical errors introduced by the LEDO approximation can lead to an uncontrollable behavior of the self-consistent field (SCF) process. A projection technique suggested by Löwdin is presented in the framework of LEDO-DFT, which guarantees for SCF convergence. Numerical results on some critical test molecules suggest the general applicability of the auxiliary orbitals presented in combination with this projection technique. Timing results indicate that LEDO-DFT is competitive with conventional density fitting methods. (c) 2005 Wiley Periodicals, Inc.

Accounting for escape mortality in fisheries: implications for stock productivity and optimal management.

PubMed

Baker, Matthew R; Schindler, Daniel E; Essington, Timothy E; Hilborn, Ray

2014-01-01

Few studies have considered the management implications of mortality to target fish stocks caused by non-retention in commercial harvest gear (escape mortality). We demonstrate the magnitude of this previously unquantified source of mortality and its implications for the population dynamics of exploited stocks, biological metrics, stock productivity, and optimal management. Non-retention in commercial gillnet fisheries for Pacific salmon (Oncorhynchus spp.) is common and often leads to delayed mortality in spawning populations. This represents losses, not only to fishery harvest, but also in future recruitment to exploited stocks. We estimated incidence of non-retention in Alaskan gillnet fisheries for sockeye salmon (O. nerka) and found disentanglement injuries to be extensive and highly variable between years. Injuries related to non-retention were noted in all spawning populations, and incidence of injury ranged from 6% to 44% of escaped salmon across nine river systems over five years. We also demonstrate that non-retention rates strongly correlate with fishing effort. We applied maximum likelihood and Bayesian approaches to stock-recruitment analyses, discounting estimates of spawning salmon to account for fishery-related mortality in escaped fish. Discounting spawning stock estimates as a function of annual fishing effort improved model fits to historical stock-recruitment data in most modeled systems. This suggests the productivity of exploited stocks has been systematically underestimated. It also suggests that indices of fishing effort may be used to predict escape mortality and correct for losses. Our results illustrate how explicitly accounting for collateral effects of fishery extraction may improve estimates of productivity and better inform management metrics derived from estimates of stock-recruitment analyses.

Using SCOR as a Supply Chain Management Framework for Government Agency Contract Requirements

NASA Technical Reports Server (NTRS)

Paxton, Joe

2010-01-01

Enterprise Supply Chain Management consists of: Specifying suppliers to support inter-program and inter-agency efforts. Optimizing inventory levels and locations throughout the supply chain. Executing corrective actions to improve quality and lead time issues throughout the supply chain. Processing reported data to calculate and make visible supply chain performance (provide information for decisions and actions). Ensuring the right hardware and information is provided at the right time and in the right place. Monitoring the industrial base while developing, producing, operating and retiring a system. Seeing performance deep in the supply chain that could indicate issues affecting system availability and readiness.

Development of an improved high efficiency thin silicon solar cell

NASA Technical Reports Server (NTRS)

Lindmayer, J.

1978-01-01

Efforts were concerned with optimizing techniques for thinning silicon slices in NaOH etches, initial investigations of surface texturing, variation of furnace treatments to improve cell efficiency, initial efforts on optimization of gridline and cell sizes and Pilot Line fabrication of quantities of 2 cm x 2 cm 50 micron thick cells.

Interlead distance and left ventricular lead electrical delay predict reverse remodeling during cardiac resynchronization therapy.

PubMed

Merchant, Faisal M; Heist, E Kevin; Nandigam, K Veena; Mulligan, Lawrence J; Blendea, Dan; Riedl, Lindsay; McCarty, David; Orencole, Mary; Picard, Michael H; Ruskin, Jeremy N; Singh, Jagmeet P

2010-05-01

Both anatomic interlead separation and left ventricle lead electrical delay (LVLED) have been associated with outcomes following cardiac resynchronization therapy (CRT). However, the relationship between interlead distance and electrical delay in predicting CRT outcomes has not been defined. We studied 61 consecutive patients undergoing CRT for standard clinical indications. All patients underwent intraprocedural measurement of LVLED. Interlead distances in the horizontal (HD), vertical (VD), and direct (DD) dimensions were measured from postprocedure chest radiographs (CXR). Remodeling indices [percent change in left ventricle (LV) ejection fraction, end-diastolic, end-systolic dimensions] were assessed by transthoracic echocardiogram. There was a positive correlation between corrected LVLED and HD on lateral CXR (r = 0.361, P = 0.004) and a negative correlation between LVLED and VD on posteroanterior (PA) CXR (r =-0.281, P = 0.028). To account for this inverse relationship, we developed a composite anatomic distance (defined as: lateral HD-PA VD), which correlated most closely with LVLED (r = 0.404, P = 0.001). Follow-up was available for 48 patients. At a mean of 4.1 +/- 3.2 months, patients with optimal values for both corrected LVLED (>or=75%) and composite anatomic distance (>or=15 cm) demonstrated greater reverse LV remodeling than patients with either one or neither of these optimized values. We identified a significant correlation between LV-right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes.

Improving monoclonal antibody selection and engineering using measurements of colloidal protein interactions

PubMed Central

Geng, Steven B.; Cheung, Jason K.; Narasimhan, Chakravarthy; Shameem, Mohammed; Tessier, Peter M.

2014-01-01

A limitation of using monoclonal antibodies as therapeutic molecules is their propensity to associate with themselves and/or with other molecules via non-affinity (colloidal) interactions. This can lead to a variety of problems ranging from low solubility and high viscosity to off-target binding and fast antibody clearance. Measuring such colloidal interactions is challenging given that they are weak and potentially involve diverse target molecules. Nevertheless, assessing these weak interactions – especially during early antibody discovery and lead candidate optimization – is critical to preventing problems that can arise later in the development process. Here we review advances in developing and implementing sensitive methods for measuring antibody colloidal interactions as well as using these measurements for guiding antibody selection and engineering. These systematic efforts to minimize non-affinity interactions are expected to yield more effective and stable monoclonal antibodies for diverse therapeutic applications. PMID:25209466

In-silico guided discovery of novel CCR9 antagonists

NASA Astrophysics Data System (ADS)

Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

2018-03-01

Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

Machine-Learning Techniques Applied to Antibacterial Drug Discovery

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.

2014-01-01

The emergence of drug-resistant bacteria threatens to catapult humanity back to the pre-antibiotic era. Even now, multi-drug-resistant bacterial infections annually result in millions of hospital days, billions in healthcare costs, and, most importantly, tens of thousands of lives lost. As many pharmaceutical companies have abandoned antibiotic development in search of more lucrative therapeutics, academic researchers are uniquely positioned to fill the resulting vacuum. Traditional high-throughput screens and lead-optimization efforts are expensive and labor intensive. Computer-aided drug discovery techniques, which are cheaper and faster, can accelerate the identification of novel antibiotics in an academic setting, leading to improved hit rates and faster transitions to pre-clinical and clinical testing. The current review describes two machine-learning techniques, neural networks and decision trees, that have been used to identify experimentally validated antibiotics. We conclude by describing the future directions of this exciting field. PMID:25521642

Design Methods and Optimization for Morphing Aircraft

NASA Technical Reports Server (NTRS)

Crossley, William A.

2005-01-01

This report provides a summary of accomplishments made during this research effort. The major accomplishments are in three areas. The first is the use of a multiobjective optimization strategy to help identify potential morphing features that uses an existing aircraft sizing code to predict the weight, size and performance of several fixed-geometry aircraft that are Pareto-optimal based upon on two competing aircraft performance objectives. The second area has been titled morphing as an independent variable and formulates the sizing of a morphing aircraft as an optimization problem in which the amount of geometric morphing for various aircraft parameters are included as design variables. This second effort consumed most of the overall effort on the project. The third area involved a more detailed sizing study of a commercial transport aircraft that would incorporate a morphing wing to possibly enable transatlantic point-to-point passenger service.

Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery

PubMed Central

2011-01-01

The central nervous system (CNS) is the major area that is affected by aging. Alzheimer’s disease (AD), Parkinson’s disease (PD), brain cancer, and stroke are the CNS diseases that will cost trillions of dollars for their treatment. Achievement of appropriate blood–brain barrier (BBB) penetration is often considered a significant hurdle in the CNS drug discovery process. On the other hand, BBB penetration may be a liability for many of the non-CNS drug targets, and a clear understanding of the physicochemical and structural differences between CNS and non-CNS drugs may assist both research areas. Because of the numerous and challenging issues in CNS drug discovery and the low success rates, pharmaceutical companies are beginning to deprioritize their drug discovery efforts in the CNS arena. Prompted by these challenges and to aid in the design of high-quality, efficacious CNS compounds, we analyzed the physicochemical property and the chemical structural profiles of 317 CNS and 626 non-CNS oral drugs. The conclusions derived provide an ideal property profile for lead selection and the property modification strategy during the lead optimization process. A list of substructural units that may be useful for CNS drug design was also provided here. A classification tree was also developed to differentiate between CNS drugs and non-CNS oral drugs. The combined analysis provided the following guidelines for designing high-quality CNS drugs: (i) topological molecular polar surface area of <76 Å2 (25–60 Å2), (ii) at least one (one or two, including one aliphatic amine) nitrogen, (iii) fewer than seven (two to four) linear chains outside of rings, (iv) fewer than three (zero or one) polar hydrogen atoms, (v) volume of 740–970 Å3, (vi) solvent accessible surface area of 460–580 Å2, and (vii) positive QikProp parameter CNS. The ranges within parentheses may be used during lead optimization. One violation to this proposed profile may be acceptable. The chemoinformatics approaches for graphically analyzing multiple properties efficiently are presented. PMID:22267984

Winning and losing: an evolutionary approach to mood disorders and their therapy.

PubMed

Sloman, Leon; Sturman, Edward D; Price, John S

2011-06-01

To advance a new evolutionary model that examines the effects of winning and losing on mood and physiological variables. Previous studies have focused on the involuntary defeat strategy in de-escalating conflict. Here, we propose that there also exists an involuntary winning strategy (IWS) that is triggered by success and characterized by euphoria and increased self-confidence. It motivates efforts to challenge, and promotes reconciliation. Previous studies are presented, including data on student athletes, demonstrating the impact of winning and losing on mood. Winning is consistently shown to be related to physiological changes such as increased testosterone and serotonin levels in primates. It reliably leads to mood changes that serve to motivate winners to continue their competitive efforts. When the IWS functions optimally, success leads to success in an adaptive cycle. Over time, the initial differences between the winners and losers of agonistic encounters become magnified in a process known as difference amplification. As a result of assortative mating, the children of people who have entered into an adaptive cycle will inherit traits from both parents that will, in turn, give them an increased competitive advantage. In this manner, difference amplification could have accelerated human evolution by natural selection. Vignettes of clinical interventions are also used to illustrate therapeutic strategies designed to disrupt maladaptive cycles and promote adaptive behaviour.

The cost of model reference adaptive control - Analysis, experiments, and optimization

NASA Technical Reports Server (NTRS)

Messer, R. S.; Haftka, R. T.; Cudney, H. H.

1993-01-01

In this paper the performance of Model Reference Adaptive Control (MRAC) is studied in numerical simulations and verified experimentally with the objective of understanding how differences between the plant and the reference model affect the control effort. MRAC is applied analytically and experimentally to a single degree of freedom system and analytically to a MIMO system with controlled differences between the model and the plant. It is shown that the control effort is sensitive to differences between the plant and the reference model. The effects of increased damping in the reference model are considered, and it is shown that requiring the controller to provide increased damping actually decreases the required control effort when differences between the plant and reference model exist. This result is useful because one of the first attempts to counteract the increased control effort due to differences between the plant and reference model might be to require less damping, however, this would actually increase the control effort. Optimization of weighting matrices is shown to help reduce the increase in required control effort. However, it was found that eventually the optimization resulted in a design that required an extremely high sampling rate for successful realization.

Sulcal set optimization for cortical surface registration.

PubMed

Joshi, Anand A; Pantazis, Dimitrios; Li, Quanzheng; Damasio, Hanna; Shattuck, David W; Toga, Arthur W; Leahy, Richard M

2010-04-15

Flat mapping based cortical surface registration constrained by manually traced sulcal curves has been widely used for inter subject comparisons of neuroanatomical data. Even for an experienced neuroanatomist, manual sulcal tracing can be quite time consuming, with the cost increasing with the number of sulcal curves used for registration. We present a method for estimation of an optimal subset of size N(C) from N possible candidate sulcal curves that minimizes a mean squared error metric over all combinations of N(C) curves. The resulting procedure allows us to estimate a subset with a reduced number of curves to be traced as part of the registration procedure leading to optimal use of manual labeling effort for registration. To minimize the error metric we analyze the correlation structure of the errors in the sulcal curves by modeling them as a multivariate Gaussian distribution. For a given subset of sulci used as constraints in surface registration, the proposed model estimates registration error based on the correlation structure of the sulcal errors. The optimal subset of constraint curves consists of the N(C) sulci that jointly minimize the estimated error variance for the subset of unconstrained curves conditioned on the N(C) constraint curves. The optimal subsets of sulci are presented and the estimated and actual registration errors for these subsets are computed. Copyright 2009 Elsevier Inc. All rights reserved.

Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target

PubMed Central

Asiedu, Kingsley; Fitzpatrick, Christopher; Jannin, Jean

2014-01-01

Background Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million. Conclusions The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved. PMID:25254372

The importance of hydration thermodynamics in fragment-to-lead optimization.

PubMed

Ichihara, Osamu; Shimada, Yuzo; Yoshidome, Daisuke

2014-12-01

Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X-ray crystallographic data of published fragment-to-lead optimization studies from various therapeutically relevant targets were studied. The analysis reveals a distinct difference between the thermodynamic profile of water molecules displaced by fragment hits and those displaced by the corresponding optimized lead compounds. Specifically, fragment hits tend to displace water molecules with notably unfavorable excess entropies-configurationally constrained water molecules-relative to those displaced by the newly added moieties of the lead compound during the course of fragment-to-lead optimization. Herein we describe the details of this analysis with the goal of providing practical guidelines for exploiting thermodynamic signatures of binding site water molecules in the context of fragment-to-lead optimization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimal consensus algorithm integrated with obstacle avoidance

NASA Astrophysics Data System (ADS)

Wang, Jianan; Xin, Ming

2013-01-01

This article proposes a new consensus algorithm for the networked single-integrator systems in an obstacle-laden environment. A novel optimal control approach is utilised to achieve not only multi-agent consensus but also obstacle avoidance capability with minimised control efforts. Three cost functional components are defined to fulfil the respective tasks. In particular, an innovative nonquadratic obstacle avoidance cost function is constructed from an inverse optimal control perspective. The other two components are designed to ensure consensus and constrain the control effort. The asymptotic stability and optimality are proven. In addition, the distributed and analytical optimal control law only requires local information based on the communication topology to guarantee the proposed behaviours, rather than all agents' information. The consensus and obstacle avoidance are validated through simulations.

The Whole is Greater than the Sum of the Parts: Optimizing the Joint Science Return from LSST, Euclid and WFIRST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, B.; Spergel, D.; Connolly, A.

2015-02-02

The scientific opportunity offered by the combination of data from LSST, WFIRST and Euclid goes well beyond the science enabled by any one of the data sets alone. The range in wavelength, angular resolution and redshift coverage that these missions jointly span is remarkable. With major investments in LSST and WFIRST, and partnership with ESA in Euclid, the US has an outstanding scientific opportunity to carry out a combined analysis of these data sets. It is imperative for us to seize it and, together with our European colleagues, prepare for the defining cosmological pursuit of the 21st century. The mainmore » argument for conducting a single, high-quality reference co-analysis exercise and carefully documenting the results is the complexity and subtlety of systematics that define this co-analysis. Falling back on many small efforts by different teams in selected fields and for narrow goals will be inefficient, leading to significant duplication of effort.« less

Continuous Czochralski growth. Development of advanced Czochralski growth process to produce low cost 150 kg silicon ingots from a single crucible for technology readiness

NASA Technical Reports Server (NTRS)

1982-01-01

The improvement of growth rates using radiation shielding and investigation of the crucible melt interaction for improved yields were emphasized. Growth runs were performed from both 15 and 16 inch diameter crucibles, producing 30 and 37 kg ingots respectively. Efforts to increase the growth rate of 150 mm diameter ingots were limited by temperature instabilities believed to be caused by undesirable thermal convections in the larger melts. The radiation shield improved the growth rate somewhat, but the thermal instability was still evident, leading to nonround ingots and loss of dislocation-free structure. A 38 kg crystal was grown to demonstrate the feasibility of producing 150 kg with four growth cycles. After the grower construction phase, the Hamco microprocessor control system was interfaced to the growth facility, including the sensor for automatic control of seeding temperature, and the sensor for automatic shouldering. Efforts focused upon optimization of the seeding, necking, and shoulder growth automation programs.

TRU Waste Management Program. Cost/schedule optimization analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detamore, J.A.; Raudenbush, M.H.; Wolaver, R.W.

This Current Year Work Plan presents in detail a description of the activities to be performed by the Joint Integration Office Rockwell International (JIO/RI) during FY86. It breaks down the activities into two major work areas: Program Management and Program Analysis. Program Management is performed by the JIO/RI by providing technical planning and guidance for the development of advanced TRU waste management capabilities. This includes equipment/facility design, engineering, construction, and operations. These functions are integrated to allow transition from interim storage to final disposition. JIO/RI tasks include program requirements identification, long-range technical planning, budget development, program planning document preparation, taskmore » guidance development, task monitoring, task progress information gathering and reporting to DOE, interfacing with other agencies and DOE lead programs, integrating public involvement with program efforts, and preparation of reports for DOE detailing program status. Program Analysis is performed by the JIO/RI to support identification and assessment of alternatives, and development of long-term TRU waste program capabilities. These analyses include short-term analyses in response to DOE information requests, along with performing an RH Cost/Schedule Optimization report. Systems models will be developed, updated, and upgraded as needed to enhance JIO/RI's capability to evaluate the adequacy of program efforts in various fields. A TRU program data base will be maintained and updated to provide DOE with timely responses to inventory related questions.« less

Associations of Occupational Stressors, Perceived Organizational Support, and Psychological Capital with Work Engagement among Chinese Female Nurses.

PubMed

Wang, Xiaoxi; Liu, Li; Zou, Futing; Hao, Junhui; Wu, Hui

2017-01-01

This study aimed to explore the associations of occupational stressors (extrinsic effort, reward, and overcommitment), perceived organizational support (POS), and psychological capital (PsyCap) and its components (self-efficacy, hope, resilience, and optimism) with work engagement and the mediating roles of PsyCap and its components among Chinese female nurses within the framework of the job demands-resources (JD-R) model. A cross-sectional sample (1,330) completed the Utrecht Work Engagement Scale, Effort-Reward Imbalance Scale, Survey of POS, and PsyCap Questionnaire, and effective respondents were 1,016 (76.4%). Hierarchical regression analysis and Preacher and Hayes' asymptotic and resampling strategies were used. Extrinsic effort was negatively associated with vigor, dedication, and absorption, while POS, PsyCap, and hope were positively associated with them. Reward and overcommitment were positively associated with dedication and absorption. Optimism was positively associated with vigor and dedication. Optimism mediated the associations of extrinsic effort, reward, and POS with vigor and dedication. PsyCap and hope mediated the associations of POS with vigor, dedication, and absorption. There is a low level of work engagement among Chinese female nurses. Extrinsic effort could reduce work engagement, while reward, overcommitment, POS, PsyCap, hope, and optimism could enhance work engagement. Hospital managers should develop the PsyCap of female nurses through controlling occupational stressors and establishing supportive organizational climate to enhance their work engagement.

Associations of Occupational Stressors, Perceived Organizational Support, and Psychological Capital with Work Engagement among Chinese Female Nurses

PubMed Central

Wang, Xiaoxi; Zou, Futing; Hao, Junhui

2017-01-01

This study aimed to explore the associations of occupational stressors (extrinsic effort, reward, and overcommitment), perceived organizational support (POS), and psychological capital (PsyCap) and its components (self-efficacy, hope, resilience, and optimism) with work engagement and the mediating roles of PsyCap and its components among Chinese female nurses within the framework of the job demands-resources (JD-R) model. A cross-sectional sample (1,330) completed the Utrecht Work Engagement Scale, Effort-Reward Imbalance Scale, Survey of POS, and PsyCap Questionnaire, and effective respondents were 1,016 (76.4%). Hierarchical regression analysis and Preacher and Hayes' asymptotic and resampling strategies were used. Extrinsic effort was negatively associated with vigor, dedication, and absorption, while POS, PsyCap, and hope were positively associated with them. Reward and overcommitment were positively associated with dedication and absorption. Optimism was positively associated with vigor and dedication. Optimism mediated the associations of extrinsic effort, reward, and POS with vigor and dedication. PsyCap and hope mediated the associations of POS with vigor, dedication, and absorption. There is a low level of work engagement among Chinese female nurses. Extrinsic effort could reduce work engagement, while reward, overcommitment, POS, PsyCap, hope, and optimism could enhance work engagement. Hospital managers should develop the PsyCap of female nurses through controlling occupational stressors and establishing supportive organizational climate to enhance their work engagement. PMID:28168198

Space Synthetic Biology Project

NASA Technical Reports Server (NTRS)

Howard, David; Roman, Monsi; Mansell, James (Matt)

2015-01-01

Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the project in selecting the best approaches to the application of bioelectrochemical technologies to ECLS. Figure 1 shows results of simulation of charge transport in an experimental system. Figure 2 shows one of five conceptual designs for ECLS subsystems based on bioelectrochemical reactors. Also during the first 2 years, some work was undertaken to gather fundamental data (conductivities, overpotentials) relevant to the modeling efforts.

Logistical constraints lead to an intermediate optimum in outbreak response vaccination

PubMed Central

Shea, Katriona; Ferrari, Matthew

2018-01-01

Dynamic models in disease ecology have historically evaluated vaccination strategies under the assumption that they are implemented homogeneously in space and time. However, this approach fails to formally account for operational and logistical constraints inherent in the distribution of vaccination to the population at risk. Thus, feedback between the dynamic processes of vaccine distribution and transmission might be overlooked. Here, we present a spatially explicit, stochastic Susceptible-Infected-Recovered-Vaccinated model that highlights the density-dependence and spatial constraints of various diffusive strategies of vaccination during an outbreak. The model integrates an agent-based process of disease spread with a partial differential process of vaccination deployment. We characterize the vaccination response in terms of a diffusion rate that describes the distribution of vaccination to the population at risk from a central location. This generates an explicit trade-off between slow diffusion, which concentrates effort near the central location, and fast diffusion, which spreads a fixed vaccination effort thinly over a large area. We use stochastic simulation to identify the optimum vaccination diffusion rate as a function of population density, interaction scale, transmissibility, and vaccine intensity. Our results show that, conditional on a timely response, the optimal strategy for minimizing outbreak size is to distribute vaccination resource at an intermediate rate: fast enough to outpace the epidemic, but slow enough to achieve local herd immunity. If the response is delayed, however, the optimal strategy for minimizing outbreak size changes to a rapidly diffusive distribution of vaccination effort. The latter may also result in significantly larger outbreaks, thus suggesting a benefit of allocating resources to timely outbreak detection and response. PMID:29791432

NEV supply chain coordination and sustainability considering sales effort and risk aversion under the CVaR criterion

PubMed Central

Xu, Xingzhong

2018-01-01

In a two-echelon new energy vehicle (NEV) supply chain consisting of a risk-neutral manufacturer and a risk-averse retailer, the coordination and sustainability problem is investigated. The risk-averse retailer, who makes sales effort and undertakes the incurred effort cost, decides the order quantity and sales effort level under the Conditional Value-at-Risk (CVaR) criterion. We derive the optimal centralized decisions of a vertically integrated supply chain where the retailer is owned by the manufacturer. Taking such a centralized case as the benchmark, we prove that the subsidy-sharing-based wholesale price (SS-WP) contract fails to coordinate the NEV supply chain under the decentralized case where the retailer makes decisions independently. Then we design a subsidy-sharing-based sales rebate/penalty (SS-SRP) contract and derive the contract parameters to achieve coordination. We evaluate the coordination efficiency of this contract and find that a well-designed SS-SRP contract can promote the NEV sales and lead to a Pareto-improving win-win situation for both the NEV manufacturer and retailer compared to the non-coordination case. A series of numerical experiments are carried out to compare the effects of significant parameters under the SS-WP and SS-SRP contract and provide additional observations and implications, including an indication of the necessary conditions to sustainably maintain the NEV supply chain. PMID:29912926

A Combinatorial Platform for the Optimization of Peptidomimetic Methyl-Lysine Reader Antagonists

NASA Astrophysics Data System (ADS)

Barnash, Kimberly D.

Post-translational modification of histone N-terminal tails mediates chromatin compaction and, consequently, DNA replication, transcription, and repair. While numerous post-translational modifications decorate histone tails, lysine methylation is an abundant mark important for both gene activation and repression. Methyl-lysine (Kme) readers function through binding mono-, di-, or trimethyl-lysine. Chemical intervention of Kme readers faces numerous challenges due to the broad surface-groove interactions between readers and their cognate histone peptides; yet, the increasing interest in understanding chromatin-modifying complexes suggests tractable lead compounds for Kme readers are critical for elucidating the mechanisms of chromatin dysregulation in disease states and validating the druggability of these domains and complexes. The successful discovery of a peptide-derived chemical probe, UNC3866, for the Polycomb repressive complex 1 (PRC1) chromodomain Kme readers has proven the potential for selective peptidomimetic inhibition of reader function. Unfortunately, the systematic modification of peptides-to-peptidomimetics is a costly and inefficient strategy for target-class hit discovery against Kme readers. Through the exploration of biased chemical space via combinatorial on-bead libraries, we have developed two concurrent methodologies for Kme reader chemical probe discovery. We employ biased peptide combinatorial libraries as a hit discovery strategy with subsequent optimization via iterative targeted libraries. Peptide-to-peptidomimetic optimization through targeted library design was applied based on structure-guided library design around the interaction of the endogenous peptide ligand with three target Kme readers. Efforts targeting the WD40 reader EED led to the discovery of the 3-mer peptidomimetic ligand UNC5115 while combinatorial repurposing of UNC3866 for off-target chromodomains resulted in the discovery of UNC4991, a CDYL/2-selective ligand, and UNC4848, a MPP8 and CDYL/2 ligand. Ultimately, our efforts demonstrate the generalizability of a peptidomimetic combinatorial platform for the optimization of Kme reader ligands in a target class manner.

The relationship of acquisition systems to automated stereo correlation.

USGS Publications Warehouse

Colvocoresses, A.P.

1983-01-01

Today a concerted effort is being made to expedite the mapping process through automated correlation of stereo data. Stereo correlation involves the comparison of radiance (brightness) signals or patterns recorded by sensors. Conventionally, two-dimensional area correlation is utilized but this is a rather slow and cumbersome procedure. Digital correlation can be performed in only one dimension where suitable signal patterns exist, and the one-dimensional mode is much faster. Electro-optical (EO) systems, suitable for space use, also have much greater flexibility than film systems. Thus, an EO space system can be designed which will optimize one-dimensional stereo correlation and lead toward the automation of topographic mapping.-from Author

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jane L.; Limburg, David; Graneto, Matthew J.

2012-05-29

In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t{sub 1/2} = 360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t{sub 1/2} = 34 h.

Design of an Electric Propulsion System for SCEPTOR

NASA Technical Reports Server (NTRS)

Dubois, Arthur; van der Geest, Martin; Bevirt, JoeBen; Clarke, Sean; Christie, Robert J.; Borer, Nicholas K.

2016-01-01

The rise of electric propulsion systems has pushed aircraft designers towards new and potentially transformative concepts. As part of this effort, NASA is leading the SCEPTOR program which aims at designing a fully electric distributed propulsion general aviation aircraft. This article highlights critical aspects of the design of SCEPTOR's propulsion system conceived at Joby Aviation in partnership with NASA, including motor electromagnetic design and optimization as well as cooling system integration. The motor is designed with a finite element based multi-objective optimization approach. This provides insight into important design tradeoffs such as mass versus efficiency, and enables a detailed quantitative comparison between different motor topologies. Secondly, a complete design and Computational Fluid Dynamics analysis of the air breathing cooling system is presented. The cooling system is fully integrated into the nacelle, contains little to no moving parts and only incurs a small drag penalty. Several concepts are considered and compared over a range of operating conditions. The study presents trade-offs between various parameters such as cooling efficiency, drag, mechanical simplicity and robustness.

Noise properties and task-based evaluation of diffraction-enhanced imaging

PubMed Central

Brankov, Jovan G.; Saiz-Herranz, Alejandro; Wernick, Miles N.

2014-01-01

Abstract. Diffraction-enhanced imaging (DEI) is an emerging x-ray imaging method that simultaneously yields x-ray attenuation and refraction images and holds great promise for soft-tissue imaging. The DEI has been mainly studied using synchrotron sources, but efforts have been made to transition the technology to more practical implementations using conventional x-ray sources. The main technical challenge of this transition lies in the relatively lower x-ray flux obtained from conventional sources, leading to photon-limited data contaminated by Poisson noise. Several issues that must be understood in order to design and optimize DEI imaging systems with respect to noise performance are addressed. Specifically, we: (a) develop equations describing the noise properties of DEI images, (b) derive the conditions under which the DEI algorithm is statistically optimal, (c) characterize the imaging performance that can be obtained as measured by task-based metrics, and (d) consider image-processing steps that may be employed to mitigate noise effects. PMID:26158056

COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

PubMed Central

Kapetanovic, I.M.

2008-01-01

It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

A holistic approach to movement education in sport and fitness: a systems based model.

PubMed

Polsgrove, Myles Jay

2012-01-01

The typical model used by movement professionals to enhance performance relies on the notion that a linear increase in load results in steady and progressive gains, whereby, the greater the effort, the greater the gains in performance. Traditional approaches to movement progression typically rely on the proper sequencing of extrinsically based activities to facilitate the individual in reaching performance objectives. However, physical rehabilitation or physical performance rarely progresses in such a linear fashion; instead they tend to evolve non-linearly and rather unpredictably. A dynamic system can be described as an entity that self-organizes into increasingly complex forms. Applying this view to the human body, practitioners could facilitate non-linear performance gains through a systems based programming approach. Utilizing a dynamic systems view, the Holistic Approach to Movement Education (HADME) is a model designed to optimize performance by accounting for non-linear and self-organizing traits associated with human movement. In this model, gains in performance occur through advancing individual perspectives and through optimizing sub-system performance. This inward shift of the focus of performance creates a sharper self-awareness and may lead to more optimal movements. Copyright © 2011 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

On June 16–17, 2015, the U.S. Department of Energy (DOE) convened the Optima Stakeholder Listening ay to share information on an emerging effort to concurrently investigate the optimization of fuels and vehicles. At the time of the stakeholder listening day, this effort was referred to as “Optima.” The revised name of the effort is Co-Optimization of Fuels & Engines (Co-Optima). The effort and the listening day will use the term “Co-Optima” hereafter in this report.Co-Optima officially began in FY 2016 and is a collaboration of the DOE Vehicle Technologies Office, Bioenergy Technologies Office, and the DOE national laboratories. In FYmore » 2015, DOE invited industry stakeholders to the listening day to obtain critical input on the opportunities and challenges of this effort. The meeting was held in Golden, Colorado, and hosted by the National Renewable Energy Laboratory.« less

INNOVATIVE METHODS FOR THE OPTIMIZATION OF GRAVITY STORM SEWER DESIGN

EPA Science Inventory

The purpose of this paper is to describe a new method for optimizing the design of urban storm sewer systems. Previous efforts to optimize gravity sewers have met with limited success because classical optimization methods require that the problem be well behaved, e.g. describ...

Coordination of the EMS system: an organizational theory approach.

PubMed

Narad, R A

1998-01-01

Emergency medical services (EMS) systems include autonomous organizations with high degrees of interdependence. The need to coordinate system participants has long been recognized but seldom achieved. This can be explained by organizational theory--specifically, the study of the relationships among organizations. Existing models identify the total system's functions, but fail to explain roles and relationships among the system's participants. Coordination among organizations is more difficult than coordination within an organization because of lack of an authority structure. The EMS system can be described as "a functionally interdependent system," consisting of multiple autonomous organizations with high degrees of interdependence in their technical functions. Communities have five potential management approaches, varying according to their aggressiveness. These are laissez-faire, where even voluntary coordination efforts are not tried; voluntary cooperation efforts, such as coordinating councils; external planning agencies without regulatory control; "framework organizations" with regulatory control over the system participants; and bureaucratization, placing the system participants within a single organizational hierarchy. The "multicratic organization" is a model for management of multiorganizational systems. A "system lead agency" plans joint activities and manages relationships among system participants in the way that the management of a uniorganization integrates departments. A lead agency is usually a unit of government or organized pursuant to government action, but a managed care organization can also fill this role. In extreme application of the model, the system is viewed as a framework and temporary modules are attached. Their interests are limited, as needed, to optimize the entire system. The lead agency sets policies affecting relationships of modules and policies crossing organizational boundaries.

Analysis of neighborhood behavior in lead optimization and array design.

PubMed

Papadatos, George; Cooper, Anthony W J; Kadirkamanathan, Visakan; Macdonald, Simon J F; McLay, Iain M; Pickett, Stephen D; Pritchard, John M; Willett, Peter; Gillet, Valerie J

2009-02-01

Neighborhood behavior describes the extent to which small structural changes defined by a molecular descriptor are likely to lead to small property changes. This study evaluates two methods for the quantification of neighborhood behavior: the optimal diagonal method of Patterson et al. and the optimality criterion method of Horvath and Jeandenans. The methods are evaluated using twelve different types of fingerprint (both 2D and 3D) with screening data derived from several lead optimization projects at GlaxoSmithKline. The principal focus of the work is the design of chemical arrays during lead optimization, and the study hence considers not only biological activity but also important drug properties such as metabolic stability, permeability, and lipophilicity. Evidence is provided to suggest that the optimality criterion method may provide a better quantitative description of neighborhood behavior than the optimal diagonal method.

Aerodynamic shape optimization using preconditioned conjugate gradient methods

NASA Technical Reports Server (NTRS)

Burgreen, Greg W.; Baysal, Oktay

1993-01-01

In an effort to further improve upon the latest advancements made in aerodynamic shape optimization procedures, a systematic study is performed to examine several current solution methodologies as applied to various aspects of the optimization procedure. It is demonstrated that preconditioned conjugate gradient-like methodologies dramatically decrease the computational efforts required for such procedures. The design problem investigated is the shape optimization of the upper and lower surfaces of an initially symmetric (NACA-012) airfoil in inviscid transonic flow and at zero degree angle-of-attack. The complete surface shape is represented using a Bezier-Bernstein polynomial. The present optimization method then automatically obtains supercritical airfoil shapes over a variety of freestream Mach numbers. Furthermore, the best optimization strategy examined resulted in a factor of 8 decrease in computational time as well as a factor of 4 decrease in memory over the most efficient strategies in current use.

Case study: technology initiative led to advanced lead optimization screening processes at Bristol-Myers Squibb, 2004-2009.

PubMed

Zhang, Litao; Cvijic, Mary Ellen; Lippy, Jonathan; Myslik, James; Brenner, Stephen L; Binnie, Alastair; Houston, John G

2012-07-01

In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimization screening support models across all therapeutic groups at BMS. Together, harnessing advanced screening technology platforms and expanding panel screening strategy led to a paradigm shift at BMS in supporting lead optimization screening capability. Parallel SAR and structure liability relationship (SLR) screening approaches were first and broadly introduced to empower more-rapid and -informed decisions about chemical synthesis strategy and to broaden options for identifying high-quality drug candidates during lead optimization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Minimal invasive epicardial lead implantation: optimizing cardiac resynchronization with a new mapping device for epicardial lead placement.

PubMed

Maessen, J G; Phelps, B; Dekker, A L A J; Dijkman, B

2004-05-01

To optimize resynchronization in biventricular pacing with epicardial leads, mapping to determine the best pacing site, is a prerequisite. A port access surgical mapping technique was developed that allowed multiple pace site selection and reproducible lead evaluation and implantation. Pressure-volume loops analysis was used for real time guidance in targeting epicardial lead placement. Even the smallest changes in lead position revealed significantly different functional results. Optimizing the pacing site with this technique allowed functional improvement up to 40% versus random pace site selection.

Integration of Rotor Aerodynamic Optimization with the Conceptual Design of a Large Civil Tiltrotor

NASA Technical Reports Server (NTRS)

Acree, C. W., Jr.

2010-01-01

Coupling of aeromechanics analysis with vehicle sizing is demonstrated with the CAMRAD II aeromechanics code and NDARC sizing code. The example is optimization of cruise tip speed with rotor/wing interference for the Large Civil Tiltrotor (LCTR2) concept design. Free-wake models were used for both rotors and the wing. This report is part of a NASA effort to develop an integrated analytical capability combining rotorcraft aeromechanics, structures, propulsion, mission analysis, and vehicle sizing. The present paper extends previous efforts by including rotor/wing interference explicitly in the rotor performance optimization and implicitly in the sizing.

Study of the Use of Time-Mean Vortices to Generate Lift for MAV Applications

DTIC Science & Technology

2011-05-31

microplate to in-plane resonance. Computational effort centers around optimization of a range of parameters (geometry, frequency, amplitude of oscillation, etc...issue involved. Towards this end, a suspended microplate was fabricated via MEMS technology and driven to in-plane resonance via Lorentz force...force to drive the suspended MEMS-based microplate to in-plane resonance. Computational effort centers around optimization of a range of parameters

Driver ASIC Environmental Testing and Performance Optimization for SpaceBased Active Mirrors

NASA Astrophysics Data System (ADS)

Mejia Prada, Camilo

Direct imaging of Earth-like planets requires techniques for light suppression, such as coronagraphs or nulling interferometers, in which deformable mirrors (DM) are a principal component. On ground-based systems, DMs are used to correct for turbulence in the Earth’s atmosphere in addition to static aberrations in the optics. For space-based observations, DMs are used to correct for static and quasi- static aberrations in the optical train. State-of-the-art, high-actuator count deformable mirrors suffer from external heavy and bulky electronics in which electrical connections are made through thousands of wires. We are instead developing Application Specific Integrated Circuits (ASICs) capable of direct integration with the DM in a single small package. This integrated ASIC-DM is ideal for space missions, where it offers significant reduction in mass, power and complexity, and performance compatible with high-contrast observations of exoplanets. We have successfully prototyped and tested a 32x32 format Switch-Mode (SM) ASIC which consumes only 2mW static power (total, not per-actuator). A number of constraints were imposed on key parameters of this ASIC design, including sub-picoamp levels of leakage across turned-off switches and from switch-to-substrate, control resolution of 0.04 mV, satisfactory rise/fall times, and a near-zero on-chip crosstalk over a useful range of operating temperatures. This driver ASIC technology is currently at TRL 4. This Supporting Technology proposal will further develop the ASIC technology to TRL 5 by carrying on environmental tests and further optimizing performance, with the end goal of making ASICs suitable for space-based deployment. The effort will be led by JPL, which has considerable expertise with DMs used in highcontrast imaging systems for exoplanet missions and in adaptive optic systems, and in design of DM driver electronics. Microscale, which developed the prototype of the ASICDM, will continue its development. We propose a three-part program to advance the device maturity. The effort will cover (1) radiation hardness, (2) thermal-vacuum environment tests, and (3) parameter performance optimization. We expect to implement the results in an optimized ASIC design for NASA's space applications, expanding the current state-of-the-art into radiation-hardened electronics robust enough for a space environment. This effort will fill technology gaps listed in the Exoplanet Exploration Program Technology Plan 2017 : “The challenge is believed to not be the mosaicking of 48×48 devices or 32×32 devices (to reach 128×128) but rather dealing with the enormous number of interconnects and their electronics.”. After the close of this effort, continued ASIC development is of course planned, leading to further improvement in parameters.

Maintenance service contract model for heavy equipment in mining industry using principal agent theory

NASA Astrophysics Data System (ADS)

Pakpahan, Eka K. A.; Iskandar, Bermawi P.

2015-12-01

Mining industry is characterized by a high operational revenue, and hence high availability of heavy equipment used in mining industry is a critical factor to ensure the revenue target. To maintain high avaliability of the heavy equipment, the equipment's owner hires an agent to perform maintenance action. Contract is then used to control the relationship between the two parties involved. The traditional contracts such as fixed price, cost plus or penalty based contract studied is unable to push agent's performance to exceed target, and this in turn would lead to a sub-optimal result (revenue). This research deals with designing maintenance contract compensation schemes. The scheme should induce agent to select the highest possible maintenance effort level, thereby pushing agent's performance and achieve maximum utility for both parties involved. Principal agent theory is used as a modeling approach due to its ability to simultaneously modeled owner and agent decision making process. Compensation schemes considered in this research includes fixed price, cost sharing and revenue sharing. The optimal decision is obtained using a numerical method. The results show that if both parties are risk neutral, then there are infinite combination of fixed price, cost sharing and revenue sharing produced the same optimal solution. The combination of fixed price and cost sharing contract results in the optimal solution when the agent is risk averse, while the optimal combination of fixed price and revenue sharing contract is obtained when agent is risk averse. When both parties are risk averse, the optimal compensation scheme is a combination of fixed price, cost sharing and revenue sharing.

A liquid metal-based structurally embedded vascular antenna: II. Multiobjective and parameterized design exploration

NASA Astrophysics Data System (ADS)

Hartl, D. J.; Frank, G. J.; Malak, R. J.; Baur, J. W.

2017-02-01

Research on the structurally embedded vascular antenna concept leverages past efforts on liquid metal (LM) reconfigurable electronics, microvascular composites, and structurally integrated and reconfigurable antennas. Such a concept has potential for reducing system weight or volume while simultaneously allowing in situ adjustment of resonant frequencies and/or changes in antenna directivity. This work considers a microvascular pattern embedded in a laminated composite and filled with LM. The conductive liquid provides radio frequency (RF) functionality while also allowing self-cooling. Models describing RF propagation and heat transfer, in addition to the structural effects of both the inclusion of channels and changes in temperature, were described in part 1 of this two-part work. In this part 2, the engineering models developed and demonstrated in part 1 toward the initial exploration of design trends are implemented into multiple optimization frameworks for more detailed design studies, one of which being novel and particularly applicable to this class of problem. The computational expense associated with the coupled multiphysical analysis of the structurally embedded LM transmitting antenna motivates the consideration of surrogate-based optimization methods. Both static and adaptive approaches are explored; it is shown that iteratively correcting the surrogate leads to more accurate optimized design predictions. The expected strong dependence of antenna performance on thermal environment motivates the consideration of a novel ‘parameterized’ optimization approach that simultaneously calculates whole families of optimal designs based on changes in design or operational variables generally beyond the control of the designer. The change in Pareto-optimal response with evolution in operating conditions is clearly demonstrated.

Space mapping method for the design of passive shields

NASA Astrophysics Data System (ADS)

Sergeant, Peter; Dupré, Luc; Melkebeek, Jan

2006-04-01

The aim of the paper is to find the optimal geometry of a passive shield for the reduction of the magnetic stray field of an axisymmetric induction heater. For the optimization, a space mapping algorithm is used that requires two models. The first is an accurate model with a high computational effort as it contains finite element models. The second is less accurate, but it has a low computational effort as it uses an analytical model: the shield is replaced by a number of mutually coupled coils. The currents in the shield are found by solving an electrical circuit. Space mapping combines both models to obtain the optimal passive shield fast and accurately. The presented optimization technique is compared with gradient, simplex, and genetic algorithms.

Co-Optimization of Fuels and Engines (Co-Optima) -- Introduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrell, John T; Wagner, Robert; Holladay, John

The Co-Optimization of Fuels and Engines (Co-Optima) initiative is a U.S. Department of Energy (DOE) effort funded by both the Vehicle and Bioenergy Technology Offices. The overall goal of the effort is to identify the combinations of fuel properties and engine characteristics that maximize efficiency, independent of production pathway or fuel composition, and accelerate commercialization of these technologies. Multiple research efforts are underway focused on both spark-ignition and compression-ignition strategies applicable across the entire light, medium, and heavy-duty fleet. A key objective of Co-Optima's research is to identify new blendstocks that enhance current petroleum blending components, increase blendstock diversity, andmore » provide refiners with increased flexibility to blend fuels with the key properties required to optimize advanced internal combustion engines. In addition to fuels and engines R&D, the initiative is guided by analyses assessing the near-term commercial feasibility of new blendstocks based on economics, environmental performance, compatibility, and large-scale production viability. This talk will provide an overview of the Co-Optima effort.« less

Back to the Future: Lessons Learned in Modern Target-based and Whole-Cell Lead Optimization of Antimalarials

PubMed Central

Chatterjee, Arnab K; Yeung, Bryan KS

2012-01-01

Antimalarial drug discovery has historically benefited from the whole-cell (phenotypic) screening approach to identify lead molecules in the search for new drugs. However over the past two decades there has been a shift in the pharmaceutical industry to move away from whole-cell screening to target-based approaches. As part of a Wellcome Trust and Medicines for Malaria Venture (MMV) funded consortium to discover new blood-stage antimalarials, we used both approaches to identify new antimalarial chemotypes, two of which have progressed beyond the lead optimization phase and display excellent in vivo efficacy in mice. These two advanced series were identified through a cell-based optimization devoid of target information and in this review we summarize the advantages of this approach versus a target-based optimization. Although the each lead optimization required slightly different medicinal chemistry strategies, we observed some common issues across the different the scaffolds which could be applied to other cell based lead optimization programs. PMID:22242845

Earth resources data analysis program, phase 3

NASA Technical Reports Server (NTRS)

1975-01-01

Tasks were performed in two areas: (1) systems analysis and (2) algorithmic development. The major effort in the systems analysis task was the development of a recommended approach to the monitoring of resource utilization data for the Large Area Crop Inventory Experiment (LACIE). Other efforts included participation in various studies concerning the LACIE Project Plan, the utility of the GE Image 100, and the specifications for a special purpose processor to be used in the LACIE. In the second task, the major effort was the development of improved algorithms for estimating proportions of unclassified remotely sensed data. Also, work was performed on optimal feature extraction and optimal feature extraction for proportion estimation.

Identification and prioritization of novel anti-Wolbachia chemotypes from screening a 10,000-compound diversity library

PubMed Central

Johnston, Kelly L.; Cook, Darren A. N.; Berry, Neil G.; David Hong, W.; Clare, Rachel H.; Goddard, Megan; Ford, Louise; Nixon, Gemma L.; O’Neill, Paul M.; Ward, Stephen A.; Taylor, Mark J.

2017-01-01

Lymphatic filariasis and onchocerciasis are two important neglected tropical diseases (NTDs) that cause severe disability. Control efforts are hindered by the lack of a safe macrofilaricidal drug. Targeting the Wolbachia bacterial endosymbionts in these parasites with doxycycline leads to a macrofilaricidal outcome, but protracted treatment regimens and contraindications restrict its widespread implementation. The Anti-Wolbachia consortium aims to develop improved anti-Wolbachia drugs to overcome these barriers. We describe the first screening of a large, diverse compound library against Wolbachia. This whole-organism screen, streamlined to reduce bottlenecks, produced a hit rate of 0.5%. Chemoinformatic analysis of the top 50 hits led to the identification of six structurally diverse chemotypes, the disclosure of which could offer interesting avenues of investigation to other researchers active in this field. An example of hit-to-lead optimization is described to further demonstrate the potential of developing these high-quality hit series as safe, efficacious, and selective anti-Wolbachia macrofilaricides. PMID:28959730

Using Aerospace Technology To Design Orthopedic Implants

NASA Technical Reports Server (NTRS)

Saravanos, D. A.; Mraz, P. J.; Davy, D. T.

1996-01-01

Technology originally developed to optimize designs of composite-material aerospace structural components used to develop method for optimizing designs of orthopedic implants. Development effort focused on designing knee implants, long-term goal to develop method for optimizing designs of orthopedic implants in general.

MouthLab: A Tricorder Concept Optimized for Rapid Medical Assessment.

PubMed

Fridman, Gene Y; Tang, Hai; Feller-Kopman, David; Hong, Yang

2015-09-01

The goal of rapid medical assessment (RMA) is to estimate the general health of a patient during an emergency room or a doctor's office visit, or even while the patient is at home. Currently the devices used during RMA are typically "all-in-one" vital signs monitors. They require time, effort and expertise to attach various sensors to the body. A device optimized for RMA should instead require little effort or expertise to operate and be able to rapidly obtain and consolidate as much information as possible. MouthLab is a battery powered hand-held device intended to acquire and evaluate many measurements such as non-invasive blood sugar, saliva and respiratory biochemistry. Our initial prototype acquires standard vital signs: pulse rate (PR), breathing rate (BR), temperature (T), blood oxygen saturation (SpO2), blood pressure (BP), and a three-lead electrocardiogram. In our clinical study we tested the device performance against the measurements obtained with a standard patient monitor. 52 people participated in the study. The measurement errors were as follows: PR: -1.7 ± 3.5 BPM, BR: 0.4 ± 2.4 BPM, T: -0.4 ± 1.24 °F, SpO2: -0.6 ± 1.7%. BP systolic: -1.8 ± 12 mmHg, BP diastolic: 0.6 ± 8 mmHg. We have shown that RMA can be easily performed non-invasively by patients with no prior training.

Analysis of LED arrangement in an array with respect to lens geometry

NASA Astrophysics Data System (ADS)

Ley, Peer-Phillip; Held, Marcel Philipp; Lachmayer, Roland

2018-02-01

Highly adaptive light sources such as LED arrays have been surpassing conventional light sources (halogen, xenon) for automotive applications. Individual LED arrangements within the array, high durability and low energy consumption of the LEDs are some of the reasons. With the introduction of Audi's Matrix beam system, efforts to increase the quantity of pixels were already underway and the stage was practically set for pixel light systems. Current efforts are focused towards the exploration of an optimal LED array density and the use of spatial light modulators. In both cases, one question remains - What arrangement of LEDs is the most suitable in terms of light output efficiency for a given lens geometry? The radiation characteristics of an LED usually shows a Lambertian pattern. Following from the definition of luminous efficacy, this characteristic property of LEDs has a decisive impact on the lens geometry in a given array. Due to the proportional correlation between the lens diameter and the distance of LEDs emission surface to the lens surface. Assuming a constant viewing angle an increase of the distance leads to an increase of the lens diameter. In this paper, two different approaches for an optimized LED array with regards to the LED arrangement will be presented. The introduced designs result from one imaging and one non-imaging optical system, which will be investigated. The paper is concluded with a comparative analysis of the LED array design as a function of the LED pitch and the luminous efficacy.

The Educational Kanban: promoting effective self-directed adult learning in medical education.

PubMed

Goldman, Stuart

2009-07-01

The author reviews the many forces that have driven contemporary medical education approaches to evaluation and places them in an adult learning theory context. After noting their strengths and limitations, the author looks to lessons learned from manufacturing on both efficacy and efficiency and explores how these can be applied to the process of trainee assessment in medical education.Building on this, the author describes the rationale for and development of the Educational Kanban (EK) at Children's Hospital Boston--specifically, how it was designed to integrate adult learning theory, Japanese manufacturing models, and educator observations into a unique form of teacher-student collaboration that allows for continuous improvement. It is a formative tool, built on the Accreditation Council for Graduate Medical Education's six core competencies, that guides educational efforts to optimize teaching and learning, promotes adult learner responsibility and efficacy, and takes advantage of the labor-intensive clinical educational setting. The author discusses how this model, which will be implemented in July 2009, will lead to training that is highly individualized, optimizes faculty and student educational efforts, and ultimately conserves faculty resources. A model EK is provided for general reference.The EK represents a novel approach to adult learning that will enhance educational effectiveness and efficiency and complement existing evaluative models. Described here in a specific graduate medical setting, it can readily be adapted and integrated into a wide range of undergraduate and graduate clinical educational environments.

Design of optimally normal minimum gain controllers by continuation method

NASA Technical Reports Server (NTRS)

Lim, K. B.; Juang, J.-N.; Kim, Z. C.

1989-01-01

A measure of the departure from normality is investigated for system robustness. An attractive feature of the normality index is its simplicity for pole placement designs. To allow a tradeoff between system robustness and control effort, a cost function consisting of the sum of a norm of weighted gain matrix and a normality index is minimized. First- and second-order necessary conditions for the constrained optimization problem are derived and solved by a Newton-Raphson algorithm imbedded into a one-parameter family of neighboring zero problems. The method presented allows the direct computation of optimal gains in terms of robustness and control effort for pole placement problems.

Betacaryophyllene - A phytocannabinoid as potential therapeutic modality for human sepsis?

PubMed

Meza, Angel; Lehmann, Christian

2018-01-01

Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radon, smoking, and lung cancer: the need to refocus radon control policy.

PubMed

Lantz, Paula M; Mendez, David; Philbert, Martin A

2013-03-01

Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy.

Expanding the definition of addiction: DSM-5 vs. ICD-11.

PubMed

Grant, Jon E; Chamberlain, Samuel R

2016-08-01

While considerable efforts have been made to understand the neurobiological basis of substance addiction, the potentially "addictive" qualities of repetitive behaviors, and whether such behaviors constitute "behavioral addictions," is relatively neglected. It has been suggested that some conditions, such as gambling disorder, compulsive stealing, compulsive buying, compulsive sexual behavior, and problem Internet use, have phenomenological and neurobiological parallels with substance use disorders. This review considers how the issue of "behavioral addictions" has been handled by latest revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD), leading to somewhat divergent approaches. We also consider key areas for future research in order to address optimal diagnostic classification and treatments for such repetitive, debilitating behaviors.

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα).

PubMed

Sabbah, Dima A; Saada, Musaab; Khalaf, Reema Abu; Bardaweel, Sanaa; Sweidan, Kamal; Al-Qirim, Tariq; Al-Zughier, Amani; Halim, Heba Abdel; Sheikha, Ghassan Abu

2015-08-15

The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.

PubMed

Cernak, Tim; Gesmundo, Nathan J; Dykstra, Kevin; Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; Vachal, Petr; Sperbeck, Donald; He, Shuwen; Murphy, Beth Ann; Sonatore, Lisa; Williams, Steven; Madeira, Maria; Verras, Andreas; Reiter, Maud; Lee, Claire Heechoon; Cuff, James; Sherer, Edward C; Kuethe, Jeffrey; Goble, Stephen; Perrotto, Nicholas; Pinto, Shirly; Shen, Dong-Ming; Nargund, Ravi; Balkovec, James; DeVita, Robert J; Dreher, Spencer D

2017-05-11

Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S N Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.

Optimal Dynamic Advertising Strategy Under Age-Specific Market Segmentation

NASA Astrophysics Data System (ADS)

Krastev, Vladimir

2011-12-01

We consider the model proposed by Faggian and Grosset for determining the advertising efforts and goodwill in the long run of a company under age segmentation of consumers. Reducing this model to optimal control sub problems we find the optimal advertising strategy and goodwill.

Linking state regulation, brain laterality, and self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults.

PubMed

Mohamed, Saleh M H; Börger, Norbert A; Geuze, Reint H; van der Meere, Jaap J

2016-10-01

Many clinical studies have shown that performance of subjects with attention-deficit/hyperactivity disorder (ADHD) is impaired when stimuli are presented at a slow rate compared to a medium or fast rate. According to the cognitive-energetic model, this finding may reflect difficulty in allocating sufficient effort to regulate the motor activation state. Other studies have shown that the left hemisphere is relatively responsible for keeping humans motivated, allocating sufficient effort to complete their tasks. This leads to a prediction that poor effort allocation might be associated with an affected left-hemisphere functioning in ADHD. So far, this prediction has not been directly tested, which is the aim of the present study. Seventy-seven adults with various scores on the Conners' Adult ADHD Rating Scale performed a lateralized lexical decision task in three conditions with stimuli presented in a fast, a medium, and a slow rate. The left-hemisphere functioning was measured in terms of visual field advantage (better performance for the right than for the left visual field). All subjects showed an increased right visual field advantage for word processing in the slow presentation rate of stimuli compared to the fast and the medium rate. Higher ADHD scores were related to a reduced right visual field advantage in the slow rate only. The present findings suggest that ADHD symptomatology is associated with less involvement of the left hemisphere when extra effort allocation is needed to optimize the low motor activation state.

Prediction of pilot-aircraft stability boundaries and performance contours

NASA Technical Reports Server (NTRS)

Stengel, R. F.; Broussard, J. R.

1977-01-01

Control-theoretic pilot models can provide important new insights regarding the stability and performance characteristics of the pilot-aircraft system. Optimal-control pilot models can be formed for a wide range of flight conditions, suggesting that the human pilot can maintain stability if he adapts his control strategy to the aircraft's changing dynamics. Of particular concern is the effect of sub-optimal pilot adaptation as an aircraft transitions from low to high angle-of-attack during rapid maneuvering, as the changes in aircraft stability and control response can be extreme. This paper examines the effects of optimal and sub-optimal effort during a typical 'high-g' maneuver, and it introduces the concept of minimum-control effort (MCE) adaptation. Limited experimental results tend to support the MCE adaptation concept.

Processing and plating helical metallic coils

NASA Technical Reports Server (NTRS)

1972-01-01

The results of research efforts to develop an optimized nickel cobalt coating suitable as a recording medium are outlined. The coating is to be used directly on a BeCu helical coil substrate of a helical coil NASA recorder. Specifically, efforts were made to: optimize the coating thickness; establish processes and techniques adaptable for the production of finalized plated helical coils; design and fabricate the equipment required for production and testing of the coils; and deliver finalized helical coils to NASA.

Development and application of optimum sensitivity analysis of structures

NASA Technical Reports Server (NTRS)

Barthelemy, J. F. M.; Hallauer, W. L., Jr.

1984-01-01

The research focused on developing an algorithm applying optimum sensitivity analysis for multilevel optimization. The research efforts have been devoted to assisting NASA Langley's Interdisciplinary Research Office (IRO) in the development of a mature methodology for a multilevel approach to the design of complex (large and multidisciplinary) engineering systems. An effort was undertaken to identify promising multilevel optimization algorithms. In the current reporting period, the computer program generating baseline single level solutions was completed and tested out.

Consciousness, endogenous generation of goals and homeostasis

NASA Astrophysics Data System (ADS)

Tsitolovsky, Lev E.

2015-08-01

Behaviour can be both unpredictable and goal directed, as animals act in correspondence with their motivation. Motivation arises when neurons in specific brain areas leave the state of homeostatic equilibrium and are injured. The basic goal of organisms and living cells is to maintain their life and their functional state is optimal if it does not lead to physiological damage. This can somehow be sensed by neurons and the occurrence of damage elicits homeostatic protection to recover excitability and the ability to produces spikes. It can be argued that the neuron's activity is guided on the scale of "damage-protection" and it behaves as an object possessing minimum awareness. The approach of death increases cellular efforts to operate. Thus, homeostasis may evidently produce both maintenance of life and will. The question is - how does homeostasis reach the optimum? We have no possibility of determining how the cell evaluates its own states, e.g. as "too little free energy" or in terms of "threat" to life. In any case, the approach of death increases cellular efforts to operate. For the outside observer, this is reminiscent of intentional action and a manifestation of will.

Modelling the effects of trade-offs between long and short-term objectives in fisheries management.

PubMed

Mardle, Simon; Pascoe, Sean

2002-05-01

Fisheries management is typically a complex problem, from both an environmental and political perspective. The main source of conflict occurs between the need for stock conservation and the need for fishing community well-being, which is typically measured by employment and income levels. For most fisheries, overexploitation of the stock requires a reduction in the level of fishing activity. While this may lead to long-term benefits (both conservation and economic), it also leads to a short-term reduction in employment and regional incomes. In regions which are heavily dependent on fisheries, short-term consequences of conservation efforts may be considerable. The relatively high degree of scientific uncertainty with respect to the status of the stocks and the relatively short lengths of political terms of office, generally give rise to the short-run view taking the highest priority when defining policy objectives. In this paper, a multi-objective model of the North Sea is developed that incorporates both long-term and short-term objectives. Optimal fleet sizes are estimated taking into consideration different preferences between the defined short-term and long-term objectives. The subsequent results from the model give the short-term and long-term equilibrium status of the fishery incorporating the effects of the short-term objectives. As would be expected, an optimal fleet from a short-term perspective is considerably larger than an optimal fleet from a long-run perspective. Conversely, stock sizes and sustainable yields are considerably lower in the long-term if a short-term perspective is used in setting management policies. The model results highlight what is essentially a principal-agent problem, with the objectives of the policy makers not necessarily reflecting the objectives of society as a whole.

Combining analysis with optimization at Langley Research Center. An evolutionary process

NASA Technical Reports Server (NTRS)

Rogers, J. L., Jr.

1982-01-01

The evolutionary process of combining analysis and optimization codes was traced with a view toward providing insight into the long term goal of developing the methodology for an integrated, multidisciplinary software system for the concurrent analysis and optimization of aerospace structures. It was traced along the lines of strength sizing, concurrent strength and flutter sizing, and general optimization to define a near-term goal for combining analysis and optimization codes. Development of a modular software system combining general-purpose, state-of-the-art, production-level analysis computer programs for structures, aerodynamics, and aeroelasticity with a state-of-the-art optimization program is required. Incorporation of a modular and flexible structural optimization software system into a state-of-the-art finite element analysis computer program will facilitate this effort. This effort results in the software system used that is controlled with a special-purpose language, communicates with a data management system, and is easily modified for adding new programs and capabilities. A 337 degree-of-freedom finite element model is used in verifying the accuracy of this system.

Quality effort decision in service supply chain with quality preference based on quantum game

NASA Astrophysics Data System (ADS)

Zhang, Cuihua; Xing, Peng; Wang, Jianwei

2015-04-01

Service quality preference behaviors of both members are considered in service supply chain (SSC) including a service integrator and a service provider with stochastic demand. Through analysis of service quality cost and revenue, the utility functions are established on service quality effort degree and service quality preference level in integrated and decentralized SSC. Nash equilibrium and quantum game are used to optimize the models. By comparing the different solutions, the optimal strategies are obtained in SSC with quality preference. Then some numerical examples are studied and the changing trend of service quality effort is further analyzed by the influence of the entanglement operator and quality preferences.

Lead optimization in the nondrug-like space.

PubMed

Zhao, Hongyu

2011-02-01

Drug-like space might be more densely populated with orally available compounds than the remaining chemical space, but lead optimization can still occur outside this space. Oral drug space is more dynamic than the relatively static drug-like space. As new targets emerge and optimization tools advance the oral drug space might expand. Lead optimization protocols are becoming more complex with greater optimization needs to be satisfied, which consequently could change the role of drug-likeness in the process. Whereas drug-like space should usually be explored preferentially, it can be easier to find oral drugs for certain targets in the nondrug-like space. Copyright © 2010 Elsevier Ltd. All rights reserved.

Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase.

PubMed

Zhang, Baofeng; D'Erasmo, Michael P; Murelli, Ryan P; Gallicchio, Emilio

2016-09-30

We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.

YAPPA: a Compiler-Based Parallelization Framework for Irregular Applications on MPSoCs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lovergine, Silvia; Tumeo, Antonino; Villa, Oreste

Modern embedded systems include hundreds of cores. Because of the difficulty in providing a fast, coherent memory architecture, these systems usually rely on non-coherent, non-uniform memory architectures with private memories for each core. However, programming these systems poses significant challenges. The developer must extract large amounts of parallelism, while orchestrating communication among cores to optimize application performance. These issues become even more significant with irregular applications, which present data sets difficult to partition, unpredictable memory accesses, unbalanced control flow and fine grained communication. Hand-optimizing every single aspect is hard and time-consuming, and it often does not lead to the expectedmore » performance. There is a growing gap between such complex and highly-parallel architectures and the high level languages used to describe the specification, which were designed for simpler systems and do not consider these new issues. In this paper we introduce YAPPA (Yet Another Parallel Programming Approach), a compilation framework for the automatic parallelization of irregular applications on modern MPSoCs based on LLVM. We start by considering an efficient parallel programming approach for irregular applications on distributed memory systems. We then propose a set of transformations that can reduce the development and optimization effort. The results of our initial prototype confirm the correctness of the proposed approach.« less

Optimization of a magnetic capture RT-LAMP assay for fast and real-time detection of potato virus Y and differentiation of N and O serotypes.

PubMed

Treder, Krzysztof; Chołuj, Joanna; Zacharzewska, Bogumiła; Babujee, Lavanya; Mielczarek, Mateusz; Burzyński, Adam; Rakotondrafara, Aurélie M

2018-02-01

Potato virus Y (PVY) infection has been a global challenge for potato production and the leading cause of downgrading and rejection of seed crops for certification. Accurate and timely diagnosis is a key for effective disease control. Here, we have optimized a reverse transcription loop-mediated amplification (RT-LAMP) assay to differentiate the PVY O and N serotypes. The RT-LAMP assay is based on isothermal autocyclic strand displacement during DNA synthesis. The high specificity of this method relies heavily on the primer sets designed for the amplification of the targeted regions. We designed specific primer sets targeting a region within the coat protein gene that contains nucleotide signatures typical for O and N coat protein types, and these primers differ in their annealing temperature. Combining this assay with total RNA extraction by magnetic capture, we have established a highly sensitive, simplified and shortened RT-LAMP procedure as an alternative to conventional nucleic acid assays for diagnosis. This optimized procedure for virus detection may be used as a preliminary test for identifying the viral serotype prior to investing time and effort in multiplex RT-PCR tests when a specific strain is needed.

Assessment of Cognitive Communications Interest Areas for NASA Needs and Benefits

NASA Technical Reports Server (NTRS)

Knoblock, Eric J.; Madanayake, Arjuna

2017-01-01

This effort provides a survey and assessment of various cognitive communications interest areas, including node-to-node link optimization, intelligent routing/networking, and learning algorithms, and is conducted primarily from the perspective of NASA space communications needs and benefits. Areas of consideration include optimization methods, learning algorithms, and candidate implementations/technologies. Assessments of current research efforts are provided with mention of areas for further investment. Other considerations, such as antenna technologies and cognitive radio platforms, are briefly provided as well.

A mathematical model of sentimental dynamics accounting for marital dissolution.

PubMed

Rey, José-Manuel

2010-03-31

Marital dissolution is ubiquitous in western societies. It poses major scientific and sociological problems both in theoretical and therapeutic terms. Scholars and therapists agree on the existence of a sort of second law of thermodynamics for sentimental relationships. Effort is required to sustain them. Love is not enough. Building on a simple version of the second law we use optimal control theory as a novel approach to model sentimental dynamics. Our analysis is consistent with sociological data. We show that, when both partners have similar emotional attributes, there is an optimal effort policy yielding a durable happy union. This policy is prey to structural destabilization resulting from a combination of two factors: there is an effort gap because the optimal policy always entails discomfort and there is a tendency to lower effort to non-sustaining levels due to the instability of the dynamics. These mathematical facts implied by the model unveil an underlying mechanism that may explain couple disruption in real scenarios. Within this framework the apparent paradox that a union consistently planned to last forever will probably break up is explained as a mechanistic consequence of the second law.

Space Transfer Vehicle Concepts and Requirements Study. Volume 2, Book 2: System and Program Requirements Trade Studies

NASA Technical Reports Server (NTRS)

Weber, Gary A.

1991-01-01

During the 90-day study, support was provided to NASA in defining a point-of-departure space transfer vehicle (STV). The resulting STV concept was performance optimized with a two-stage LTV/LEV configuration. Appendix A reports on the effort during this period of the study. From the end of the 90-day study until the March Interim Review, effort was placed on optimizing the two-stage vehicle approach identified in the 90-day effort. After the March Interim Review, the effort was expanded to perform a full architectural trade study with the intent of developing a decision database to support STV system decisions in response to changing SEI infrastructure concepts. Several of the architecture trade studies were combined in a System Architecture Trade Study. In addition to this trade, system optimization/definition trades and analyses were completed and some special topics were addressed. Program- and system-level trade study and analyses methodologies and results are presented in this section. Trades and analyses covered in this section are: (1) a system architecture trade study; (2) evolution; (3) safety and abort considerations; (4) STV as a launch vehicle upper stage; and (5) optimum crew and cargo split.

A Mathematical Model of Sentimental Dynamics Accounting for Marital Dissolution

PubMed Central

Rey, José-Manuel

2010-01-01

Background Marital dissolution is ubiquitous in western societies. It poses major scientific and sociological problems both in theoretical and therapeutic terms. Scholars and therapists agree on the existence of a sort of second law of thermodynamics for sentimental relationships. Effort is required to sustain them. Love is not enough. Methodology/Principal Findings Building on a simple version of the second law we use optimal control theory as a novel approach to model sentimental dynamics. Our analysis is consistent with sociological data. We show that, when both partners have similar emotional attributes, there is an optimal effort policy yielding a durable happy union. This policy is prey to structural destabilization resulting from a combination of two factors: there is an effort gap because the optimal policy always entails discomfort and there is a tendency to lower effort to non-sustaining levels due to the instability of the dynamics. Conclusions/Significance These mathematical facts implied by the model unveil an underlying mechanism that may explain couple disruption in real scenarios. Within this framework the apparent paradox that a union consistently planned to last forever will probably break up is explained as a mechanistic consequence of the second law. PMID:20360987

Multiple control strategies for prevention of avian influenza pandemic.

PubMed

Ullah, Roman; Zaman, Gul; Islam, Saeed

2014-01-01

We present the prevention of avian influenza pandemic by adjusting multiple control functions in the human-to-human transmittable avian influenza model. First we show the existence of the optimal control problem; then by using both analytical and numerical techniques, we investigate the cost-effective control effects for the prevention of transmission of disease. To do this, we use three control functions, the effort to reduce the number of contacts with human infected with mutant avian influenza, the antiviral treatment of infected individuals, and the effort to reduce the number of infected birds. We completely characterized the optimal control and compute numerical solution of the optimality system by using an iterative method.

A policy iteration approach to online optimal control of continuous-time constrained-input systems.

PubMed

Modares, Hamidreza; Naghibi Sistani, Mohammad-Bagher; Lewis, Frank L

2013-09-01

This paper is an effort towards developing an online learning algorithm to find the optimal control solution for continuous-time (CT) systems subject to input constraints. The proposed method is based on the policy iteration (PI) technique which has recently evolved as a major technique for solving optimal control problems. Although a number of online PI algorithms have been developed for CT systems, none of them take into account the input constraints caused by actuator saturation. In practice, however, ignoring these constraints leads to performance degradation or even system instability. In this paper, to deal with the input constraints, a suitable nonquadratic functional is employed to encode the constraints into the optimization formulation. Then, the proposed PI algorithm is implemented on an actor-critic structure to solve the Hamilton-Jacobi-Bellman (HJB) equation associated with this nonquadratic cost functional in an online fashion. That is, two coupled neural network (NN) approximators, namely an actor and a critic are tuned online and simultaneously for approximating the associated HJB solution and computing the optimal control policy. The critic is used to evaluate the cost associated with the current policy, while the actor is used to find an improved policy based on information provided by the critic. Convergence to a close approximation of the HJB solution as well as stability of the proposed feedback control law are shown. Simulation results of the proposed method on a nonlinear CT system illustrate the effectiveness of the proposed approach. Copyright © 2013 ISA. All rights reserved.

An agenda for 21st century neurodevelopmental medicine: lessons from autism.

PubMed

Klin, A; Jones, W

2018-03-01

The future of neurodevelopmental medicine has the potential of situating child neurology at the forefront of a broad-based public health effort to optimize neurodevelopmental outcomes of children born with high-prevalence and diverse genetic, pre- and peri-natal, and environmental burdens compromising early brain development and leading to lifetime disabilities. Building on advancements in developmental social neuroscience and in implementation science, this shift is already occurring in the case of emblematic neurodevelopmental disorders such as autism. Capitalizing on early neuroplasticity and on quantification of trajectories of social-communicative development, new technologies are emerging for high-throughput and cost-effective diagnosis and for community-viable delivery of powerful treatments, in seamless integration across previously fragmented systems of healthcare delivery. These solutions could be deployed in the case of other groups of children at greater risk for autism and communication delays, such as those born extremely premature or with congenital heart disease. The galvanizing concept in this aspirational future is a public health focus on promoting optimal conditions for early brain development, not unlike current campaigns promoting pre-natal care, nutrition or vaccination.

Adjoint sensitivity analysis of a tumor growth model and its application to spatiotemporal radiotherapy optimization.

PubMed

Fujarewicz, Krzysztof; Lakomiec, Krzysztof

2016-12-01

We investigate a spatial model of growth of a tumor and its sensitivity to radiotherapy. It is assumed that the radiation dose may vary in time and space, like in intensity modulated radiotherapy (IMRT). The change of the final state of the tumor depends on local differences in the radiation dose and varies with the time and the place of these local changes. This leads to the concept of a tumor's spatiotemporal sensitivity to radiation, which is a function of time and space. We show how adjoint sensitivity analysis may be applied to calculate the spatiotemporal sensitivity of the finite difference scheme resulting from the partial differential equation describing the tumor growth. We demonstrate results of this approach to the tumor proliferation, invasion and response to radiotherapy (PIRT) model and we compare the accuracy and the computational effort of the method to the simple forward finite difference sensitivity analysis. Furthermore, we use the spatiotemporal sensitivity during the gradient-based optimization of the spatiotemporal radiation protocol and present results for different parameters of the model.

Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.

PubMed

Siegel, Dustin; Hui, Hon C; Doerffler, Edward; Clarke, Michael O; Chun, Kwon; Zhang, Lijun; Neville, Sean; Carra, Ernest; Lew, Willard; Ross, Bruce; Wang, Queenie; Wolfe, Lydia; Jordan, Robert; Soloveva, Veronica; Knox, John; Perry, Jason; Perron, Michel; Stray, Kirsten M; Barauskas, Ona; Feng, Joy Y; Xu, Yili; Lee, Gary; Rheingold, Arnold L; Ray, Adrian S; Bannister, Roy; Strickley, Robert; Swaminathan, Swami; Lee, William A; Bavari, Sina; Cihlar, Tomas; Lo, Michael K; Warren, Travis K; Mackman, Richard L

2017-03-09

The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC 50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.

Optimal harvesting policy of predator-prey model with free fishing and reserve zones

NASA Astrophysics Data System (ADS)

Toaha, Syamsuddin; Rustam

2017-03-01

The present paper deals with an optimal harvesting of predator-prey model in an ecosystem that consists of two zones, namely the free fishing and prohibited zones. The dynamics of prey population in the ecosystem can migrate from the free fishing to the prohibited zone and vice versa. The predator and prey populations in the free fishing zone are then harvested with constant efforts. The existence of the interior equilibrium point is analyzed and its stability is determined using Routh-Hurwitz stability test. The stable interior equilibrium point is then related to the problem of maximum profit and the problem of present value of net revenue. We follow the Pontryagin's maximal principle to get the optimal harvesting policy of the present value of the net revenue. From the analysis, we found a critical point of the efforts that makes maximum profit. There also exists certain conditions of the efforts that makes the present value of net revenue becomes maximal. In addition, the interior equilibrium point is locally asymptotically stable which means that the optimal harvesting is reached and the unharvested prey, harvested prey, and harvested predator populations remain sustainable. Numerical examples are given to verify the analytical results.

Cyberinfrastructure for Atmospheric Discovery

NASA Astrophysics Data System (ADS)

Wilhelmson, R.; Moore, C. W.

2004-12-01

Each year across the United States, floods, tornadoes, hail, strong winds, lightning, hurricanes, and winter storms cause hundreds of deaths, routinely disrupt transportation and commerce, and result in billions of dollars in annual economic losses . MEAD and LEAD are two recent efforts aimed at developing the cyberinfrastructure for studying and forecasting these events through collection, integration, and analysis of observational data coupled with numerical simulation, data mining, and visualization. MEAD (Modeling Environment for Atmospheric Discovery) has been funded for two years as an NCSA (National Center for Supercomputing Applications) Alliance Expedition. The goal of this expedition has been the development/adaptation of cyberinfrastructure that will enable research simulations, datamining, machine learning and visualization of hurricanes and storms utilizing the high performance computing environments including the TeraGrid. Portal grid and web infrastructure are being tested that will enable launching of hundreds of individual WRF (Weather Research and Forecasting) simulations. In a similar way, multiple Regional Ocean Modeling System (ROMS) or WRF/ROMS simulations can be carried out. Metadata and the resulting large volumes of data will then be made available for further study and for educational purposes using analysis, mining, and visualization services. Initial coupling of the ROMS and WRF codes has been completed and parallel I/O is being implemented for these models. Management of these activities (services) are being enabled through Grid workflow technologies (e.g. OGCE). LEAD (Linked Environments for Atmospheric Discovery) is a recently funded 5-year, large NSF ITR grant that involves 9 institutions who are developing a comprehensive national cyberinfrastructure in mesoscale meteorology, particularly one that can interoperate with others being developed. LEAD is addressing the fundamental information technology (IT) research challenges needed to create an integrated, scalable for identifying, accessing, preparing, assimilating, predicting, managing, analyzing, mining, and visualizing a broad array of meteorological data and model output, independent of format and physical location. A transforming element of LEAD is Workflow Orchestration for On-Demand, Real-Time, Dynamically-Adaptive Systems (WOORDS), which allows the use of analysis tools, forecast models, and data repositories as dynamically adaptive, on-demand, Grid-enabled systems that can a) change configuration rapidly and automatically in response to weather; b) continually be steered by new data; c) respond to decision-driven inputs from users; d) initiate other processes automatically; and e) steer remote observing technologies to optimize data collection for the problem at hand. Although LEAD efforts are primiarly directed at mesoscale meteorology, the IT services being developed has general applicability to other geoscience and environmental science. Integration of traditional and new data sources is a crucial component in LEAD for data analysis and assimilation, for integration of (ensemble mining) of data from sets of simulations, and for comparing results to observational data. As part of the integration effort, LEAD is creating a myLEAD metadata catalog service: a personal metacatalog that extends the Globus MCS system and is built on top of the OGSA-DAI system developed at the National e-Science Center in Edinburgh, Scotland.

Development of an adaptive hp-version finite element method for computational optimal control

NASA Technical Reports Server (NTRS)

Hodges, Dewey H.; Warner, Michael S.

1994-01-01

In this research effort, the usefulness of hp-version finite elements and adaptive solution-refinement techniques in generating numerical solutions to optimal control problems has been investigated. Under NAG-939, a general FORTRAN code was developed which approximated solutions to optimal control problems with control constraints and state constraints. Within that methodology, to get high-order accuracy in solutions, the finite element mesh would have to be refined repeatedly through bisection of the entire mesh in a given phase. In the current research effort, the order of the shape functions in each element has been made a variable, giving more flexibility in error reduction and smoothing. Similarly, individual elements can each be subdivided into many pieces, depending on the local error indicator, while other parts of the mesh remain coarsely discretized. The problem remains to reduce and smooth the error while still keeping computational effort reasonable enough to calculate time histories in a short enough time for on-board applications.

Optimal Computing Budget Allocation for Particle Swarm Optimization in Stochastic Optimization.

PubMed

Zhang, Si; Xu, Jie; Lee, Loo Hay; Chew, Ek Peng; Wong, Wai Peng; Chen, Chun-Hung

2017-04-01

Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort.

Optimal Computing Budget Allocation for Particle Swarm Optimization in Stochastic Optimization

PubMed Central

Zhang, Si; Xu, Jie; Lee, Loo Hay; Chew, Ek Peng; Chen, Chun-Hung

2017-01-01

Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort. PMID:29170617

Barriers to optimal diabetes care in Trinidad and Tobago: a health care Professionals' perspective.

PubMed

Roopnarinesingh, Nira; Brennan, Nancyellen; Khan, Claude; Ladenson, Paul W; Hill-Briggs, Felicia; Kalyani, Rita Rastogi

2015-09-19

The republic of Trinidad and Tobago (T&T) is a middle income country with a comparatively high prevalence of diabetes mellitus (DM) compared to others in the Caribbean. To date, there have been no studies on health care professionals' (HCP) perspectives regarding the barriers to achieving optimal care of patients with DM in this country and few previous studies in the Caribbean, yet such perspectives are imperative to develop strategies that reduce the global burden of this disease. An electronic invitation was sent to prospective HCP in T&T inviting them to attend a symposium on DM and cardiovascular disease. A total of 198 HCP participants attended of whom approximately 100 participants completed an Audience Response Survey at the completion of the conference. The Audience Response Survey included questions regarding access to resources, need for prevention and education, and coordination of care for to diabetes care in T&T. Responses were analyzed in aggregate. The 198 HCP participants attending the symposium included mostly nurses (40 %) and physicians (43 %). The most common specialty indicated by the 198 HCP participants was Internal and Family Medicine (28 %), followed by Anesthesiology (7 %), Emergency Medicine (6 %), Endocrinology and Diabetes (5 %) and Cardiology (3 %). Among the ~100 HCP who completed the Audience Response Survey, multiple barriers to achieving optimal care of patients with diabetes were reported such as: limited access to blood testing (75 %), ophthalmological evaluations (96 %), ECGs (69 %), and cardiac stress tests (92 %); inadequate time to screen and evaluate DM complications (95 %); poor access to consultants for referral of difficult cases (77 %); and lack of provider education regarding cardiovascular complications of DM (57 %). HCP agreed that nurses could potentially be considered to have a more active role in the care and prevention of cardiovascular disease and diabetes through leading patient education efforts (98 %), screening patients for complications (91 %), coordinating care efforts (99 %) and educating family members (98 %). The HCP in our study reported significant barriers to achieving optimal diabetes care in T&T. In the future, such barriers to care will need to be addressed in order to respond to the projected growth of diabetes in developing countries both within the Caribbean and globally.

Conduction and Narrow Escape in Dense, Disordered, Particulate-based Heterogeneous Materials

NASA Astrophysics Data System (ADS)

Lechman, Jeremy

For optimal and reliable performance, many technological devices rely on complex, disordered heterogeneous or composite materials and their associated manufacturing processes. Examples include many powder and particulate-based materials found in phyrotechnic devices for car airbags, electrodes in energy storage devices, and various advanced composite materials. Due to their technological importance and complex structure, these materials have been the subject of much research in a number of fields. Moreover, the advent of new manufacturing techniques based on powder bed and particulate process routes, the potential of functional nano-structured materials, and the additional recognition of persistent shortcomings in predicting reliable performance of high consequence applications; leading to ballooning costs of fielding and maintaining advanced technologies, should motivate renewed efforts in understanding, predicting and controlling these materials' fabrication and behavior. Our particular effort seeks to understand the link between the top-down control presented in specific non-equilibrium processes routes (i.e., manufacturing processes) and the variability and uncertainty of the end product performance. Our ultimate aim is to quantify the variability inherent in these constrained dynamical or random processes and to use it to optimize and predict resulting material properties/performance and to inform component design with precise margins. In fact, this raises a set of deep and broad-ranging issues that have been recognized and as touching the core of a major research challenge at Sandia National Laboratories. In this talk, we will give an overview of recent efforts to address aspects of this vision. In particular the case of conductive properties of packed particulate materials will be highlighted. Combining a number of existing approaches we will discuss new insights and potential directions for further development toward the stated goal. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a Lockheed-Martin Company, for the U. S. Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.

Final Report: Pilot Region-Based Optimization Program for Fund-Lead Sites, EPA Region III

EPA Pesticide Factsheets

This report describes a pilot study for a Region-based optimization program, implemented by a Regional Optimization Evaluation Team (ROET) that was conducted in U.S. EPA Region III at Fund-lead sites with pump-and-treat (P&T) systems.

Lead poisoning in precious metals refinery assayers: a failure to notify workers at high risk.

PubMed

Kern, D G

1994-05-01

Lead poisoning in a precious metals refinery fire assayer and a routine OSHA inspection prompted an investigation of the index facility, a survey of the industry, and efforts to notify assayers of this previously unrecognized hazard. Air and blood samples were obtained at the index facility. Management personnel from all fire assay laboratories in Rhode Island and southern Massachusetts were interviewed. The industry's trade association, OSHA, NIOSH, trade unions, and the media were asked to assist in a nationwide notification effort. Assayers at the index facility had excessive exposures to lead due to an age-old, lead-based assaying method that remains the industry gold standard. Blood lead levels of the three assayers (mean 61.3 micrograms/dl, range 48-86 micrograms/dl) were considerably higher than those of 16 other refinery workers (mean 27.4 micrograms/dl, range 13-49 micrograms/dl). The industry survey revealed inadequate knowledge of both the lead hazard and the applicability of the OSHA lead standard. Notification efforts failed in large part due to economic obstacles. The notification of workers at high risk of lead exposure and the eradication of occupational lead poisoning will require greater attention to economic forces.

Optimal Prediction in the Retina and Natural Motion Statistics

NASA Astrophysics Data System (ADS)

Salisbury, Jared M.; Palmer, Stephanie E.

2016-03-01

Almost all behaviors involve making predictions. Whether an organism is trying to catch prey, avoid predators, or simply move through a complex environment, the organism uses the data it collects through its senses to guide its actions by extracting from these data information about the future state of the world. A key aspect of the prediction problem is that not all features of the past sensory input have predictive power, and representing all features of the external sensory world is prohibitively costly both due to space and metabolic constraints. This leads to the hypothesis that neural systems are optimized for prediction. Here we describe theoretical and computational efforts to define and quantify the efficient representation of the predictive information by the brain. Another important feature of the prediction problem is that the physics of the world is diverse enough to contain a wide range of possible statistical ensembles, yet not all inputs are probable. Thus, the brain might not be a generalized predictive machine; it might have evolved to specifically solve the prediction problems most common in the natural environment. This paper summarizes recent results on predictive coding and optimal predictive information in the retina and suggests approaches for quantifying prediction in response to natural motion. Basic statistics of natural movies reveal that general patterns of spatiotemporal correlation are present across a wide range of scenes, though individual differences in motion type may be important for optimal processing of motion in a given ecological niche.

Velocity field measurements in the wake of a propeller model

NASA Astrophysics Data System (ADS)

Mukund, R.; Kumar, A. Chandan

2016-10-01

Turboprop configurations are being revisited for the modern-day regional transport aircrafts for their fuel efficiency. The use of laminar flow wings is an effort in this direction. One way to further improve their efficiency is by optimizing the flow over the wing in the propeller wake. Previous studies have focused on improving the gross aerodynamic characteristics of the wing. It is known that the propeller slipstream causes early transition of the boundary layer on the wing. However, an optimized design of the propeller and wing combination could delay this transition and decrease the skin friction drag. Such a wing design would require the detailed knowledge of the development of the slipstream in isolated conditions. There are very few studies in the literature addressing the requirements of transport aircraft having six-bladed propeller and cruising at a high propeller advance ratio. Low-speed wind tunnel experiments have been conducted on a powered propeller model in isolated conditions, measuring the velocity field in the vertical plane behind the propeller using two-component hot-wire anemometry. The data obtained clearly resolved the mean velocity, the turbulence, the ensemble phase averages and the structure and development of the tip vortex. The turbulence in the slipstream showed that transition could be close to the leading edge of the wing, making it a fine case for optimization. The development of the wake with distance shows some interesting flow features, and the data are valuable for flow computation and optimization.

The efficacy of using inventory data to develop optimal diameter increment models

Treesearch

Don C. Bragg

2002-01-01

Most optimal tree diameter growth models have arisen through either the conceptualization of physiological processes or the adaptation of empirical increment models. However, surprisingly little effort has been invested in the melding of these approaches even though it is possible to develop theoretically sound, computationally efficient optimal tree growth models...

Experimental and Numerical Optimization of a High-Lift System to Improve Low-Speed Performance, Stability, and Control of an Arrow-Wing Supersonic Transport

NASA Technical Reports Server (NTRS)

Hahne, David E.; Glaab, Louis J.

1999-01-01

An investigation was performed to evaluate leading-and trailing-edge flap deflections for optimal aerodynamic performance of a High-Speed Civil Transport concept during takeoff and approach-to-landing conditions. The configuration used for this study was designed by the Douglas Aircraft Company during the 1970's. A 0.1-scale model of this configuration was tested in the Langley 30- by 60-Foot Tunnel with both the original leading-edge flap system and a new leading-edge flap system, which was designed with modem computational flow analysis and optimization tools. Leading-and trailing-edge flap deflections were generated for the original and modified leading-edge flap systems with the computational flow analysis and optimization tools. Although wind tunnel data indicated improvements in aerodynamic performance for the analytically derived flap deflections for both leading-edge flap systems, perturbations of the analytically derived leading-edge flap deflections yielded significant additional improvements in aerodynamic performance. In addition to the aerodynamic performance optimization testing, stability and control data were also obtained. An evaluation of the crosswind landing capability of the aircraft configuration revealed that insufficient lateral control existed as a result of high levels of lateral stability. Deflection of the leading-and trailing-edge flaps improved the crosswind landing capability of the vehicle considerably; however, additional improvements are required.

Engineering microorganisms for improving polyhydroxyalkanoate biosynthesis.

PubMed

Chen, Guo-Qiang; Jiang, Xiao-Ran

2017-11-20

Biosynthesis of polyhydroxyalkanoates (PHA) has been studied since the 1920s. The biosynthesis pathways have been well understood and various attempts have been made to improve the PHA biosynthesis efficiency. Recent progresses have been focused on systematic improvements on PHA biosynthesis including changing growth pattern for rapid proliferation, engineering to enlarge cell sizes for more PHA accumulation space, reprogramming the PHA synthesis pathways using optimized RBS and promoter, redirecting metabolic flux to PHA synthesis using CRISPR/Cas9 tools, and very importantly, the employment of non-traditional host such as halophiles for reduced complexity on PHA production. All of the efforts should lead to ultrahigh PHA accumulation, controllable PHA compositions and molecular weights, open and continuous PHA production with gravity separation processes, resulting in competitive PHA production cost. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing performance in complex team environments.

PubMed

Whitmore, Jeffrey N

2005-07-01

This paper provides a brief introduction to team performance assessment. It highlights some critical aspects leading to the successful measurement of team performance in realistic console operations; discusses the idea of process and outcome measures; presents two types of team data collection systems; and provides an example of team performance assessment. Team performance assessment is a complicated endeavor relative to assessing individual performance. Assessing team performance necessitates a clear understanding of each operator's task, both at the individual and team level, and requires planning for efficient data capture and analysis. Though team performance assessment requires considerable effort, the results can be very worthwhile. Most tasks performed in Command and Control environments are team tasks, and understanding this type of performance is becoming increasingly important to the evaluation of mission success and for overall system optimization.

Radon, Smoking, and Lung Cancer: The Need to Refocus Radon Control Policy

PubMed Central

Mendez, David; Philbert, Martin A.

2013-01-01

Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy. PMID:23327258

Electroporating Fields Target Oxidatively Damaged Areas in the Cell Membrane

PubMed Central

Vernier, P. Thomas; Levine, Zachary A.; Wu, Yu-Hsuan; Joubert, Vanessa; Ziegler, Matthew J.; Mir, Lluis M.; Tieleman, D. Peter

2009-01-01

Reversible electropermeabilization (electroporation) is widely used to facilitate the introduction of genetic material and pharmaceutical agents into living cells. Although considerable knowledge has been gained from the study of real and simulated model membranes in electric fields, efforts to optimize electroporation protocols are limited by a lack of detailed understanding of the molecular basis for the electropermeabilization of the complex biomolecular assembly that forms the plasma membrane. We show here, with results from both molecular dynamics simulations and experiments with living cells, that the oxidation of membrane components enhances the susceptibility of the membrane to electropermeabilization. Manipulation of the level of oxidative stress in cell suspensions and in tissues may lead to more efficient permeabilization procedures in the laboratory and in clinical applications such as electrochemotherapy and electrotransfection-mediated gene therapy. PMID:19956595

Latest experience in design of piezoelectric-driven fine-steering mirrors

NASA Astrophysics Data System (ADS)

Marth, Harry; Donat, Michael; Pohlhammer, Charles F.

1992-01-01

The European Space Organization (ESO) requested Physik Instrumente (PI) to develop a system to compensate for atmospherically induced image jitter in astronomical telescopes. The product, designated S-380 by PI, is a sophisticated adaptive optic system using closed loop piezoelectric actuators and momentum compensation to significantly improve telescope resolution during long integrations by correcting for image jitter in real time. Optimizing the design of this system involved solving several interdependent problems, including: (1) selection of the motion system, (2) arrangement of the pivot points and actuators, (3) momentum compensation, and (4) selection of the sensor system. This paper presents the trade-offs leading to final design of the S-380 system, some supporting technical analysis and ongoing efforts at PI to provide fast tilting platforms for larger mirrors.

Performance Evaluation of the NASA GTX RBCC Flowpath

NASA Technical Reports Server (NTRS)

Thomas, Scott R.; Palac, Donald T.; Trefny, Charles J.; Roche, Joseph M.

2001-01-01

The NASA Glenn Research Center serves as NASAs lead center for aeropropulsion. Several programs are underway to explore revolutionary airbreathing propulsion systems in response to the challenge of reducing the cost of space transportation. Concepts being investigated include rocket-based combined cycle (RBCC), pulse detonation wave, and turbine-based combined cycle (TBCC) engines. The GTX concept is a vertical launched, horizontal landing, single stage to orbit (SSTO) vehicle utilizing RBCC engines. The propulsion pod has a nearly half-axisymmetric flowpath that incorporates a rocket and ram-scramjet. The engine system operates from lift-off up to above Mach 10, at which point the airbreathing engine flowpath is closed off, and the rocket alone powers the vehicle to orbit. The paper presents an overview of the research efforts supporting the development of this RBCC propulsion system. The experimental efforts of this program consist of a series of test rigs. Each rig is focused on development and optimization of the flowpath over a specific operating mode of the engine. These rigs collectively establish propulsion system performance over all modes of operation, therefore, covering the entire speed range. Computational Fluid Mechanics (CFD) analysis is an important element of the GTX propulsion system development and validation. These efforts guide experiments and flowpath design, provide insight into experimental data, and extend results to conditions and scales not achievable in ground test facilities. Some examples of important CFD results are presented.

Structural Design for a Neptune Aerocapture Mission

NASA Technical Reports Server (NTRS)

Dyke, R. Eric; Hrinda, Glenn A.

2004-01-01

A multi-center study was conducted in 2003 to assess the feasibility of and technology requirements for using aerocapture to insert a scientific platform into orbit around Neptune. The aerocapture technique offers a potential method of greatly reducing orbiter mass and thus total spacecraft launch mass by minimizing the required propulsion system mass. This study involved the collaborative efforts of personnel from Langley Research Center (LaRC), Johnson Space Flight Center (JSFC), Marshall Space Flight Center (MSFC), Ames Research Center (ARC), and the Jet Propulsion Laboratory (JPL). One aspect of this effort was the structural design of the full spacecraft configuration, including the ellipsled aerocapture orbiter and the in-space solar electric propulsion (SEP) module/cruise stage. This paper will discuss the functional and structural requirements for each of these components, some of the design trades leading to the final configuration, the loading environments, and the analysis methods used to ensure structural integrity. It will also highlight the design and structural challenges faced while trying to integrate all the mission requirements. Component sizes, materials, construction methods and analytical results, including masses and natural frequencies, will be presented, showing the feasibility of the resulting design for use in a Neptune aerocapture mission. Lastly, results of a post-study structural mass optimization effort on the ellipsled will be discussed, showing potential mass savings and their influence on structural strength and stiffness

An optimal control strategies using vaccination and fogging in dengue fever transmission model

NASA Astrophysics Data System (ADS)

Fitria, Irma; Winarni, Pancahayani, Sigit; Subchan

2017-08-01

This paper discussed regarding a model and an optimal control problem of dengue fever transmission. We classified the model as human and vector (mosquito) population classes. For the human population, there are three subclasses, such as susceptible, infected, and resistant classes. Then, for the vector population, we divided it into wiggler, susceptible, and infected vector classes. Thus, the model consists of six dynamic equations. To minimize the number of dengue fever cases, we designed two optimal control variables in the model, the giving of fogging and vaccination. The objective function of this optimal control problem is to minimize the number of infected human population, the number of vector, and the cost of the controlling efforts. By giving the fogging optimally, the number of vector can be minimized. In this case, we considered the giving of vaccination as a control variable because it is one of the efforts that are being developed to reduce the spreading of dengue fever. We used Pontryagin Minimum Principle to solve the optimal control problem. Furthermore, the numerical simulation results are given to show the effect of the optimal control strategies in order to minimize the epidemic of dengue fever.

A Unit-Problem Investigation of Blunt Leading-Edge Separation Motivated by AVT-161 SACCON Research

NASA Technical Reports Server (NTRS)

Luckring, James M.; Boelens, Okko J.

2011-01-01

A research effort has been initiated to examine in more detail some of the challenging flow fields discovered from analysis of the SACCON configuration aerodynamics. This particular effort is oriented toward a diamond wing investigation specifically designed to isolate blunt leading-edge separation phenomena relevant to the SACCON investigations of the present workshop. The approach taken to design this new effort is reviewed along with the current status of the program.

78 FR 53237 - Establishment of Area Navigation (RNAV) Routes; Washington, DC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

... ``Optimization of Airspace and Procedures in a Metroplex (OAPM)'' effort in that this rule did not include T.... The new routes support the Washington, DC Optimization of Airspace and Procedures in a Metroplex (OAPM...

Modeling Global Ocean Biogeochemistry With Physical Data Assimilation: A Pragmatic Solution to the Equatorial Instability

NASA Astrophysics Data System (ADS)

Park, Jong-Yeon; Stock, Charles A.; Yang, Xiaosong; Dunne, John P.; Rosati, Anthony; John, Jasmin; Zhang, Shaoqing

2018-03-01

Reliable estimates of historical and current biogeochemistry are essential for understanding past ecosystem variability and predicting future changes. Efforts to translate improved physical ocean state estimates into improved biogeochemical estimates, however, are hindered by high biogeochemical sensitivity to transient momentum imbalances that arise during physical data assimilation. Most notably, the breakdown of geostrophic constraints on data assimilation in equatorial regions can lead to spurious upwelling, resulting in excessive equatorial productivity and biogeochemical fluxes. This hampers efforts to understand and predict the biogeochemical consequences of El Niño and La Niña. We develop a strategy to robustly integrate an ocean biogeochemical model with an ensemble coupled-climate data assimilation system used for seasonal to decadal global climate prediction. Addressing spurious vertical velocities requires two steps. First, we find that tightening constraints on atmospheric data assimilation maintains a better equatorial wind stress and pressure gradient balance. This reduces spurious vertical velocities, but those remaining still produce substantial biogeochemical biases. The remainder is addressed by imposing stricter fidelity to model dynamics over data constraints near the equator. We determine an optimal choice of model-data weights that removed spurious biogeochemical signals while benefitting from off-equatorial constraints that still substantially improve equatorial physical ocean simulations. Compared to the unconstrained control run, the optimally constrained model reduces equatorial biogeochemical biases and markedly improves the equatorial subsurface nitrate concentrations and hypoxic area. The pragmatic approach described herein offers a means of advancing earth system prediction in parallel with continued data assimilation advances aimed at fully considering equatorial data constraints.

Coordination of a supply chain with consumer return under vendor-managed consignment inventory and stochastic demand

NASA Astrophysics Data System (ADS)

Wu, Zhihui; Chen, Dongyan; Yu, Hui

2016-07-01

In this paper, the problem of the coordination policy is investigated for vendor-managed consignment inventory supply chain subject to consumer return. Here, the market demand is assumed to be affected by promotional effort and consumer return policy. The optimal consignment inventory and the optimal promotional effort level are proposed under the decentralized and centralized decisions. Based on the optimal decision conditions, the markdown allowance-promotional cost-sharing contract is investigated to coordinate the supply chain. Subsequently, the comparison between the two extreme policies shows that full-refund policy dominates the no-return policy when the returning cost and the positive effect of return policy are satisfied certain conditions. Finally, a numerical example is provided to illustrate the impacts of consumer return policy on the coordination contract and optimal profit as well as the effectiveness of the proposed supply chain decision.

Sustainability and optimal control of an exploited prey predator system through provision of alternative food to predator.

PubMed

Kar, T K; Ghosh, Bapan

2012-08-01

In the present paper, we develop a simple two species prey-predator model in which the predator is partially coupled with alternative prey. The aim is to study the consequences of providing additional food to the predator as well as the effects of harvesting efforts applied to both the species. It is observed that the provision of alternative food to predator is not always beneficial to the system. A complete picture of the long run dynamics of the system is discussed based on the effort pair as control parameters. Optimal augmentations of prey and predator biomass at final time have been investigated by optimal control theory. Also the short and large time effects of the application of optimal control have been discussed. Finally, some numerical illustrations are given to verify our analytical results with the help of different sets of parameters. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Analysis of a Fishery Model with two competing prey species in the presence of a predator species for Optimal Harvesting

NASA Astrophysics Data System (ADS)

Sutimin; Khabibah, Siti; Munawwaroh, Dita Anis

2018-02-01

A harvesting fishery model is proposed to analyze the effects of the presence of red devil fish population, as a predator in an ecosystem. In this paper, we consider an ecological model of three species by taking into account two competing species and presence of a predator (red devil), the third species, which incorporates the harvesting efforts of each fish species. The stability of the dynamical system is discussed and the existence of biological and bionomic equilibrium is examined. The optimal harvest policy is studied and the solution is derived in the equilibrium case applying Pontryagin's maximal principle. The simulation results is presented to simulate the dynamical behavior of the model and show that the optimal equilibrium solution is globally asymptotically stable. The results show that the optimal harvesting effort is obtained regarding to bionomic and biological equilibrium.

Revenue Share between Layers and Investment Incentive for ISP in the Internet Market

NASA Astrophysics Data System (ADS)

Unno, Masaru; Xu, Hua

In this paper, we consider a revenue-sharing and network investment problem between an Internet service provider (ISP) and a content provider (CP) by applying the dynamic agency theory. We formulate the problem as the principal-agent problem where the ISP is the principal and the CP is the agent. The principal-agent problem is transformed to a stochastic optimal control problem in which the objectives of ISP are to find an optimal revenue-sharing strategy and a network investment strategy, and to advise an incentive compatible effort level to the CP. The sufficient conditions for the existence of the optimal revenue-sharing strategy, the optimal investment strategy and the incentive compatible effort to the CP are obtained. A numerical example is solved to show the existence of such strategies. The practical implications of the results obtained in the paper will also be discussed.

Utilization of in vitro Caco-2 permeability and liver microsomal half-life screens in discovering BMS-488043, a novel HIV-1 attachment inhibitor with improved pharmacokinetic properties.

PubMed

Yang, Zheng; Zadjura, Lisa M; Marino, Anthony M; D'Arienzo, Celia J; Malinowski, Jacek; Gesenberg, Christoph; Lin, Pin-Fang; Colonno, Richard J; Wang, Tao; Kadow, John F; Meanwell, Nicholas A; Hansel, Steven B

2010-04-01

Optimizing pharmacokinetic properties to improve oral exposure is a common theme in modern drug discovery. In the present work, in vitro Caco-2 permeability and microsomal half-life screens were utilized in an effort to guide the structure-activity relationship in order to improve the pharmacokinetic properties of novel HIV-1 attachment inhibitors. The relevance of the in vitro screens to in vivo pharmacokinetic properties was first demonstrated with a number of program compounds at the early stage of lead optimization. The Caco-2 permeability, tested at 200 microM, was quantitatively predictive of in vivo oral absorption, with complete absorption occurring at a Caco-2 permeability of 100 nm/s or higher. The liver microsomal half-life screen, conducted at 1 microM substrate concentration, can readily differentiate low-, intermediate-, and high-clearance compounds in rats, with a nearly 1:1 correlation in 12 out of 13 program compounds tested. Among the >100 compounds evaluated, BMS-488043 emerged as a lead, exhibiting a Caco-2 permeability of 178 nm/s and a microsomal half-life predictive of a low clearance (4 mL/min/kg) in humans. These in vitro characteristics translated well to the in vivo setting. The oral bioavailability of BMS-488043 in rats, dogs, and monkeys was 90%, 57%, and 60%, respectively. The clearance was low in all three species tested, with a terminal half-life ranging from 2.4 to 4.7 h. Furthermore, the oral exposure of BMS-488043 was significantly improved (6- to 12-fold in rats and monkeys) compared to the prototype compound BMS-378806 that had a suboptimal Caco-2 permeability (51 nm/s) and microsomal half-life. More importantly, the improvements in preclinical pharmacokinetics translated well to humans, leading to a >15-fold increase in the human oral exposure of BMS-488043 than BMS-378806 and enabling a clinical proof-of-concept for this novel class of anti-HIV agents. The current studies demonstrated the valuable role of in vitro ADME screens in improving oral pharmacokinetics at the lead optimization stage. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

A novel glycogen synthase kinase-3 inhibitor optimized for acute myeloid leukemia differentiation activity

PubMed Central

Stetson, Lindsay; Ignatz-Hoover, James; Moreton, Stephen; Chakrabarti, Amit; Xia, Zhiqiang; Karan, Goutam; de Lima, Marcos; Agrawal, Mukesh K; Wald, David N

2016-01-01

Standard therapies used for the treatment of Acute Myeloid Leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, Acute Promyelocytic Leukemia (APL), can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has previously been identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared to other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared to other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML. PMID:27196775

Structural optimization of mangiferin binding to cancer molecular targets: a guide for synthetic derivatization.

PubMed

Taiwo, Bamigboye J; Olubiyi, Olujide O; van Heerden, Fanie R

2018-03-20

Nigerian medicinal plants have been demonstrated to be veritable source of lead compounds for drug discovery efforts. One such example is mangiferin. Mangiferin was originally isolated from the Nigerian plant Ceiba pentandra (Mombacaceae), after which its structure was elucidated with the aid of spectroscopy. Mangiferin, a xanthone glycoside, has also been reported in certain other plant families including Gentianaceae and Anacardiaceae. In certain other climes and different parts of the world, folkloric and traditional medicine has extensively employed Mangifera indica (another source of mangiferin) in treating different diseases. For many of such cultural uses carefully designed experimental investigations have been conducted confirming mangiferin's efficacies in those different pathologies which have included but not limited to cytotoxic as well as chemopreventive properties in selected cancer cell lines. In this study, computational techniques were employed to profile the interaction of the xanthone glycoside at the atomistic level against nine selected molecular targets with clinical relevance in tumorigenesis. In attempt to investigate the potential of the mangiferin structure as a viable starting point for synthetic exploration of mangiferin-based analogs, extensive structural modifications were performed. By analyzing the resulting structure-energetic pattern, critical points capable of improving mangiferin interaction with the profiled targets were identified. The outcome of this study provides both direction and impetus for synthetic derivitization of the mangiferin molecule into novel optimized inhibitors for anticancer lead development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Space biology initiative program definition review. Trade study 1: Automation costs versus crew utilization

NASA Technical Reports Server (NTRS)

Jackson, L. Neal; Crenshaw, John, Sr.; Hambright, R. N.; Nedungadi, A.; Mcfayden, G. M.; Tsuchida, M. S.

1989-01-01

A significant emphasis upon automation within the Space Biology Initiative hardware appears justified in order to conserve crew labor and crew training effort. Two generic forms of automation were identified: automation of data and information handling and decision making, and the automation of material handling, transfer, and processing. The use of automatic data acquisition, expert systems, robots, and machine vision will increase the volume of experiments and quality of results. The automation described may also influence efforts to miniaturize and modularize the large array of SBI hardware identified to date. The cost and benefit model developed appears to be a useful guideline for SBI equipment specifiers and designers. Additional refinements would enhance the validity of the model. Two NASA automation pilot programs, 'The Principal Investigator in a Box' and 'Rack Mounted Robots' were investigated and found to be quite appropriate for adaptation to the SBI program. There are other in-house NASA efforts that provide technology that may be appropriate for the SBI program. Important data is believed to exist in advanced medical labs throughout the U.S., Japan, and Europe. The information and data processing in medical analysis equipment is highly automated and future trends reveal continued progress in this area. However, automation of material handling and processing has progressed in a limited manner because the medical labs are not affected by the power and space constraints that Space Station medical equipment is faced with. Therefore, NASA's major emphasis in automation will require a lead effort in the automation of material handling to achieve optimal crew utilization.

Experimental optimization of the FireFly 600 photovoltaic off-grid system.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyson, William Earl; Orozco, Ron; Ralph, Mark E.

2003-10-01

A comprehensive evaluation and experimental optimization of the FireFly{trademark} 600 off-grid photovoltaic system manufactured by Energia Total, Ltd. was conducted at Sandia National Laboratories in May and June of 2001. This evaluation was conducted at the request of the manufacturer and addressed performance of individual system components, overall system functionality and performance, safety concerns, and compliance with applicable codes and standards. A primary goal of the effort was to identify areas for improvement in performance, reliability, and safety. New system test procedures were developed during the effort.

Gas flow parameters in laser cutting of wood- nozzle design

Treesearch

Kali Mukherjee; Tom Grendzwell; Parwaiz A.A. Khan; Charles McMillin

1990-01-01

The Automated Lumber Processing System (ALPS) is an ongoing team research effort to optimize the yield of parts in a furniture rough mill. The process is designed to couple aspects of computer vision, computer optimization of yield, and laser cutting. This research is focused on optimizing laser wood cutting. Laser machining of lumber has the advantage over...

Optimizing Wartime Materiel Delivery: An Overview of DoD containerization. Volume 3. Annotated Bibliography

DOT National Transportation Integrated Search

1988-10-01

This annotated bibliography, Volume III of the study entitled, Optimizing Wartime Materiel Delivery: An overview of DOD Containerization Efforts, documents studies related to containerization. Several objectives of the study were defined. These inclu...

Measuring collections effort improves cash performance.

PubMed

Shutts, Joe

2009-09-01

Having a satisfied work force can lead to an improved collections effort. Hiring the right people and training them ensures employee engagement. Measuring collections effort and offering incentives is key to revenue cycle success.

Joint contact forces can be reduced by improving joint moment symmetry in below-knee amputee gait simulations.

PubMed

Koelewijn, Anne D; van den Bogert, Antonie J

2016-09-01

Despite having a fully functional knee and hip in both legs, asymmetries in joint moments of the knee and hip are often seen in gait of persons with a unilateral transtibial amputation (TTA), possibly resulting in excessive joint loading. We hypothesize that persons with a TTA can walk with more symmetric joint moments at the cost of increased effort or abnormal kinematics. The hypothesis was tested using predictive simulations of gait. Open loop controls of one gait cycle were found by solving an optimization problem that minimizes a combination of walking effort and tracking error in joint angles, ground reaction force and gait cycle duration. A second objective was added to penalize joint moment asymmetry, creating a multi-objective optimization problem. A Pareto front was constructed by changing the weights of the objectives and three solutions were analyzed to study the effect of increasing joint moment symmetry. When the optimization placed more weight on moment symmetry, walking effort increased and kinematics became less normal, confirming the hypothesis. TTA gait improved with a moderate increase in joint moment symmetry. At a small cost of effort and abnormal kinematics, the peak hip extension moment in the intact leg was decreased significantly, and so was the joint contact force in the knee and hip. Additional symmetry required a significant increase in walking effort and the joint contact forces in both hips became significantly higher than in able-bodied gait. Copyright © 2016 Elsevier B.V. All rights reserved.

A new multiresponse optimization approach in combination with a D-Optimal experimental design for the determination of biogenic amines in fish by HPLC-FLD.

PubMed

Herrero, A; Sanllorente, S; Reguera, C; Ortiz, M C; Sarabia, L A

2016-11-16

A new strategy to approach multiresponse optimization in conjunction to a D-optimal design for simultaneously optimizing a large number of experimental factors is proposed. The procedure is applied to the determination of biogenic amines (histamine, putrescine, cadaverine, tyramine, tryptamine, 2-phenylethylamine, spermine and spermidine) in swordfish by HPLC-FLD after extraction with an acid and subsequent derivatization with dansyl chloride. Firstly, the extraction from a solid matrix and the derivatization of the extract are optimized. Ten experimental factors involved in both stages are studied, seven of them at two levels and the remaining at three levels; the use of a D-optimal design leads to optimize the ten experimental variables, significantly reducing by a factor of 67 the experimental effort needed but guaranteeing the quality of the estimates. A model with 19 coefficients, which includes those corresponding to the main effects and two possible interactions, is fitted to the peak area of each amine. Then, the validated models are used to predict the response (peak area) of the 3456 experiments of the complete factorial design. The variability among peak areas ranges from 13.5 for 2-phenylethylamine to 122.5 for spermine, which shows, to a certain extent, the high and different effect of the pretreatment on the responses. Then the percentiles are calculated from the peak areas of each amine. As the experimental conditions are in conflict, the optimal solution for the multiresponse optimization is chosen from among those which have all the responses greater than a certain percentile for all the amines. The developed procedure reaches decision limits down to 2.5 μg L -1 for cadaverine or 497 μg L -1 for histamine in solvent and 0.07 mg kg -1 and 14.81 mg kg -1 in fish (probability of false positive equal to 0.05), respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

[Trance(s)--music and more].

PubMed

Stahl, Ziva; Grotto, Itamar; Moran, Dany; Ginsberg, Avidor

2013-12-01

The recent amendment, of the Israeli regulation for nutrition labeling on the packaged food label, as published in the government registry, mandates the labeling of trans fatty acids. The relationship between the types of fatty acids and the risk of developing heart disease is well known and has been researched for many years. As part of efforts of the health authorities around the world and in Israel to reduce morbidity and mortality from chronic diseases, the authorities act to reduce consumption of trans fatty acids and saturated fatty acids. This article reviews the major changes that have taken place in reducing the consumption of trans fatty acids in recent years. This includes the evidence which pointed to the negative effects of their use, the Latest recommendations of several leading health leading organization regarding optimal consumption of fats in particular and regarding nutrition in general. It also entails trends in the world food industry towards the reduction in trans fatty acids use, and policies countries are implementing in order to reduce the world's consumption of trans fatty acids, including the updating of nutritional labeling regulations in Israel.

New Instruments for Studying the Impacts of Science Teacher Professional Development

ERIC Educational Resources Information Center

Trygstad, Peggy J.; Banilower, Eric R.; Smith, P. Sean; Nelson, Courtney L.

2014-01-01

The logic model that implicitly drives most professional development (PD) efforts asserts that PD leads to changes in teacher knowledge and beliefs, which leads to improved classroom practice, and ultimately, better student outcomes. However, efforts to study the impacts of PD programs are often hampered by the scarcity of high-quality…

IMPROVING THE ENVIRONMENTAL PERFORMANCE OF CHEMICAL PROCESSES THROUGH THE USE OF INFORMATION TECHNOLOGY

EPA Science Inventory

Efforts are currently underway at the USEPA to develop information technology applications to improve the environmental performance of the chemical process industry. These efforts include the use of genetic algorithms to optimize different process options for minimal environmenta...

Integrated multidisciplinary design optimization of rotorcraft

NASA Technical Reports Server (NTRS)

Adelman, Howard M.; Mantay, Wayne R.

1989-01-01

The NASA/Army research plan for developing the logic elements for helicopter rotor design optimization by integrating appropriate disciplines and accounting for important interactions among the disciplines is discussed. The paper describes the optimization formulation in terms of the objective function, design variables, and constraints. The analysis aspects are discussed, and an initial effort at defining the interdisciplinary coupling is summarized. Results are presented on the achievements made in the rotor aerodynamic performance optimization for minimum hover horsepower, rotor dynamic optimization for vibration reduction, rotor structural optimization for minimum weight, and integrated aerodynamic load/dynamics optimization for minimum vibration and weight.

The road to heaven is paved with effort: Perceived effort amplifies moral judgment.

PubMed

Bigman, Yochanan E; Tamir, Maya

2016-12-01

If good intentions pave the road to hell, what paves the road to heaven? We propose that moral judgments are based, in part, on the degree of effort exerted in performing the immoral or moral act. Because effort can serve as an index of goal importance, greater effort in performing immoral acts would lead to more negative judgments, whereas greater effort in performing moral acts would lead to more positive judgments. In support of these ideas, we found that perceived effort intensified judgments of both immoral (Studies 1-2) and moral (Studies 2-7) agents. The effect of effort on judgment was independent of the outcome (Study 3) and of perceptions of the outcome extremity (Study 6). Furthermore, the effect of effort on judgment was mediated by perceived goal importance (Studies 4-6), even when controlling for perceived intentions (Studies 5-6). Finally, we demonstrate that perceived effort can influence actual behavior, such as the assignment of monetary rewards (Study 7). We discuss the possible implications of effort as a causal motivational factor in moral judgment and social retribution. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Lead optimization attrition analysis (LOAA): a novel and general methodology for medicinal chemistry.

PubMed

Munson, Mark; Lieberman, Harvey; Tserlin, Elina; Rocnik, Jennifer; Ge, Jie; Fitzgerald, Maria; Patel, Vinod; Garcia-Echeverria, Carlos

2015-08-01

Herein, we report a novel and general method, lead optimization attrition analysis (LOAA), to benchmark two distinct small-molecule lead series using a relatively unbiased, simple technique and commercially available software. We illustrate this approach with data collected during lead optimization of two independent oncology programs as a case study. Easily generated graphics and attrition curves enabled us to calibrate progress and support go/no go decisions on each program. We believe that this data-driven technique could be used broadly by medicinal chemists and management to guide strategic decisions during drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries.

PubMed

Alecu, I M; Zheng, Jingjing; Zhao, Yan; Truhlar, Donald G

2010-09-14

Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Optimizing water depth for wetland-dependent wildlife could increase wetland restoration success, water efficiency, and water security

USGS Publications Warehouse

Nadeau, Christopher P.; Conway, Courtney J.

2015-01-01

Securing water for wetland restoration efforts will be increasingly difficult as human populations demand more water and climate change alters the hydrologic cycle. Minimizing water use at a restoration site could help justify water use to competing users, thereby increasing future water security. Moreover, optimizing water depth for focal species will increase habitat quality and the probability that the restoration is successful. We developed and validated spatial habitat models to optimize water depth within wetland restoration projects along the lower Colorado River intended to benefit California black rails (Laterallus jamaicensis coturniculus). We observed a 358% increase in the number of black rails detected in the year after manipulating water depth to maximize the amount of predicted black rail habitat in two wetlands. The number of black rail detections in our restoration sites was similar to those at our reference site. Implementing the optimal water depth in each wetland decreased water use while simultaneously increasing habitat suitability for the focal species. Our results also provide experimental confirmation of past descriptive accounts of black rail habitat preferences and provide explicit water depth recommendations for future wetland restoration efforts for this species of conservation concern; maintain surface water depths between saturated soil and 100 mm. Efforts to optimize water depth in restored wetlands around the world would likely increase the success of wetland restorations for the focal species while simultaneously minimizing and justifying water use.

Influence of optimized leading-edge deflection and geometric anhedral on the low-speed aerodynamic characteristics of a low-aspect-ratio highly swept arrow-wing configuration. [langley 7 by 10 foot tunnel

NASA Technical Reports Server (NTRS)

Coe, P. L., Jr.; Huffman, J. K.

1979-01-01

An investigation conducted in the Langley 7 by 10 foot tunnel to determine the influence of an optimized leading-edge deflection on the low speed aerodynamic performance of a configuration with a low aspect ratio, highly swept wing. The sensitivity of the lateral stability derivative to geometric anhedral was also studied. The optimized leading edge deflection was developed by aligning the leading edge with the incoming flow along the entire span. Owing to spanwise variation of unwash, the resulting optimized leading edge was a smooth, continuously warped surface for which the deflection varied from 16 deg at the side of body to 50 deg at the wing tip. For the particular configuration studied, levels of leading-edge suction on the order of 90 percent were achieved. The results of tests conducted to determine the sensitivity of the lateral stability derivative to geometric anhedral indicate values which are in reasonable agreement with estimates provided by simple vortex-lattice theories.

Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study.

PubMed

Nakai, Ryuichiro; Salisbury, Cleo M; Rosen, Hugh; Cravatt, Benjamin F

2009-02-01

High-throughput screening (HTS) has become an integral part of academic and industrial efforts aimed at developing new chemical probes and drugs. These screens typically generate several 'hits', or lead active compounds, that must be prioritized for follow-up medicinal chemistry studies. Among primary considerations for ranking lead compounds is selectivity for the intended target, especially among mechanistically related proteins. Here, we show how the chemical proteomic technology activity-based protein profiling (ABPP) can serve as a universal assay to rank HTS hits based on their selectivity across many members of an enzyme superfamily. As a case study, four metalloproteinase-13 (MMP13) inhibitors of similar potency originating from a publically supported HTS and reported in PubChem were tested by ABPP for selectivity against a panel of 27 diverse metalloproteases. The inhibitors could be readily separated into two groups: (1) those that were active against several metalloproteases and (2) those that showed high selectivity for MMP13. The latter set of inhibitors was thereby designated as more suitable for future medicinal chemistry optimization. We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes.

Neoclassic drug discovery: the case for lead generation using phenotypic and functional approaches.

PubMed

Lee, Jonathan A; Berg, Ellen L

2013-12-01

Innovation and new molecular entity production by the pharmaceutical industry has been below expectations. Surprisingly, more first-in-class small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) between 1999 and 2008 were identified by functional phenotypic lead generation strategies reminiscent of pre-genomics pharmacology than contemporary molecular targeted strategies that encompass the vast majority of lead generation efforts. This observation, in conjunction with the difficulty in validating molecular targets for drug discovery, has diminished the impact of the "genomics revolution" and has led to a growing grassroots movement and now broader trend in pharma to reconsider the use of modern physiology-based or phenotypic drug discovery (PDD) strategies. This "From the Guest Editors" column provides an introduction and overview of the two-part special issues of Journal of Biomolecular Screening on PDD. Terminology and the business case for use of PDD are defined. Key issues such as assay performance, chemical optimization, target identification, and challenges to the organization and implementation of PDD are discussed. Possible solutions for these challenges and a new neoclassic vision for PDD that combines phenotypic and functional approaches with technology innovations resulting from the genomics-driven era of target-based drug discovery (TDD) are also described. Finally, an overview of the manuscripts in this special edition is provided.

Recycling of Zinc- and Lead-Bearing Residues with Pyrolysis Gas

NASA Astrophysics Data System (ADS)

Pichler, C.; Antrekowitsch, J.

2015-09-01

Efforts in the metallurgical industry for an approximation to the zero waste concept has led to many different investigations. Together with the greenhouse effect, CO2 emissions have caused additional costs for different process steps in the industry. For this reason, alternative carbon carriers have been sought, and charcoal was found to be an ideal substitute, due to its CO2 neutrality. In order to use it in the metallurgical industry, an optimization of the charcoal production through a carbonization process must be carried out. Beside the charcoal, pyrolysis gas also occurs during the heating of wood or agricultural wastes under the exclusion of air. Because of combustible compounds in this gas, it is possible to use it as a reduction agent instead of fossil carbon carriers. Together with the idea of preventing landfilling of metallurgical by-products, an investigation was carried out to treat zinc- and lead-containing materials. For this issue a special process concept was designed and developed. The main aspect was to recycle the zinc- and lead-containing Waelz slag, which results from the processing of steel mill dusts, in a vertical retort. Two different sizes of facilities were constructed to perform the reaction system of the solid Waelz slag with the gaseous reduction agent of pyrolysis gas.

Magnetic Suspension Technology Development

NASA Technical Reports Server (NTRS)

Britcher, Colin

1998-01-01

This Cooperative Agreement, intended to support focused research efforts in the area of magnetic suspension systems, was initiated between NASA Langley Research Center (LaRC) and Old Dominion University (ODU) starting January 1, 1997. The original proposal called for a three-year effort, but funding for the second year proved to be unavailable, leading to termination of the agreement following a 5-month no-cost extension. This report covers work completed during the entire 17-month period of the award. This research built on work that had taken place over recent years involving both NASA LARC and the Principal Investigator (PI). The research was of a rather fundamental nature, although specific applications were kept in mind at all times, such as wind tunnel Magnetic Suspension and Balance Systems (MSBS), space payload pointing and vibration isolation systems, magnetic bearings for unconventional applications, magnetically levitated ground transportation and electromagnetic launch systems. Fundamental work was undertaken in areas such as the development of optimized magnetic configurations, analysis and modelling of eddy current effects, control strategies for magnetically levitated wind tunnel models and system calibration procedures. Despite the termination of this Cooperative Agreement, several aspects of the research work are currently continuing with alternative forms of support.

Improving Employees' Safety Awareness in Healthcare Organizations Using the DMAIC Quality Improvement Approach.

PubMed

Momani, Amer; Hirzallah, Muʼath; Mumani, Ahmad

Occupational injuries and illnesses in healthcare can cause great human suffering, incur high cost, and have an adverse impact on the quality of patient care. One of the most effective solutions for addressing health and safety issues and improving decisions at the point of care rests in raising employees' safety awareness to recognize, avoid, or respond to potential problems before they arise. In this article, the DMAIC Six Sigma model (Define, Measure, Analyze, Improve, Control) is used as a systematic program to measure, improve, and sustain employees' safety awareness in healthcare organizations. We report on a case study using the model, which was implemented and validated at a local hospital. First, the occupational health and safety knowledge that each job requires was identified. Next, the degree of competence of jobholders to meet these requirements was assessed. Based on the assessment, different awareness-raising efforts were proposed and implemented. The results showed significant improvement in the overall safety awareness compliance assessed: from 74.2% to 84.4% (p < .001) after the intervention. The proposed model ensures that the organization's awareness-raising efforts serve its actual needs and produce optimized and sustained results that eventually lead to safer healthcare service.

Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction

PubMed Central

Lancaster, Jenessa; Lorenz, Romy; Leech, Rob; Cole, James H.

2018-01-01

Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalization to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimizing resampling parameters using Bayesian optimization. Using data on N = 2003 healthy individuals (aged 16–90 years) we trained support vector machines to (i) distinguish between young (<22 years) and old (>50 years) brains (classification) and (ii) predict chronological age (regression). We also evaluated generalisability of the age-regression model to an independent dataset (CamCAN, N = 648, aged 18–88 years). Bayesian optimization was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values. When distinguishing between young and old brains a classification accuracy of 88.1% was achieved, (optimal voxel size = 11.5 mm3, smoothing kernel = 2.3 mm). For predicting chronological age, a mean absolute error (MAE) of 5.08 years was achieved, (optimal voxel size = 3.73 mm3, smoothing kernel = 3.68 mm). This was compared to performance using default values of 1.5 mm3 and 4mm respectively, resulting in MAE = 5.48 years, though this 7.3% improvement was not statistically significant. When assessing generalisability, best performance was achieved when applying the entire Bayesian optimization framework to the new dataset, out-performing the parameters optimized for the initial training dataset. Our study outlines the proof-of-principle that neuroimaging models for brain-age prediction can use Bayesian optimization to derive case-specific pre-processing parameters. Our results suggest that different pre-processing parameters are selected when optimization is conducted in specific contexts. This potentially motivates use of optimization techniques at many different points during the experimental process, which may improve statistical sensitivity and reduce opportunities for experimenter-led bias. PMID:29483870

Connecting synthetic chemistry decisions to cell and genome biology using small-molecule phenotypic profiling

PubMed Central

Wagner, Bridget K.; Clemons, Paul A.

2009-01-01

Discovering small-molecule modulators for thousands of gene products requires multiple stages of biological testing, specificity evaluation, and chemical optimization. Many cellular profiling methods, including cellular sensitivity, gene-expression, and cellular imaging, have emerged as methods to assess the functional consequences of biological perturbations. Cellular profiling methods applied to small-molecule science provide opportunities to use complex phenotypic information to prioritize and optimize small-molecule structures simultaneously against multiple biological endpoints. As throughput increases and cost decreases for such technologies, we see an emerging paradigm of using more information earlier in probe- and drug-discovery efforts. Moreover, increasing access to public datasets makes possible the construction of “virtual” profiles of small-molecule performance, even when multiplexed measurements were not performed or when multidimensional profiling was not the original intent. We review some key conceptual advances in small-molecule phenotypic profiling, emphasizing connections to other information, such as protein-binding measurements, genetic perturbations, and cell states. We argue that to maximally leverage these measurements in probe and drug discovery requires a fundamental connection to synthetic chemistry, allowing the consequences of synthetic decisions to be described in terms of changes in small-molecule profiles. Mining such data in the context of chemical structure and synthesis strategies can inform decisions about chemistry procurement and library development, leading to optimal small-molecule screening collections. PMID:19825513

Evaluation of the role of risk perception in stakeholder engagement to prevent lead exposure in an urban setting.

PubMed

Harclerode, Melissa A; Lal, Pankaj; Vedwan, Neeraj; Wolde, Bernabas; Miller, Michael E

2016-12-15

Stakeholder engagement is a vital sustainable remediation practice for obtaining useful feedback and identifying societal needs. Evaluating and integrating risk perception of stakeholders into remediation and outreach efforts allows for greater insight, increases the likelihood of success and ultimately, benefits the community by protecting its members from environmental hazards. In this study, we identified risk perception factors that influenced residents' level of concern for mitigating their exposure to elevated concentrations of lead in household paint and historic fill material. Risk perception factors were assessed by an in-person survey conducted in public green spaces. The analysis of survey participants' responses indicated that their perception of risk to exposed lead was mostly influenced by the presence of hazardous materials in close proximity to their residence, the ability to address pollution, and awareness, interest, and individual accountability in mitigating environmental risks. Responses also revealed that residents considered risk of lead and soil pollution as less menacing than the presence of more immediate and perceptible risks posed by factors such as air and water pollution. In addition, the community seemed to exhibit "optimism bias" and did not identify itself at high risk to susceptible and immediate hazards, including lead exposure. This lack of concern over lead exposure created a significant obstacle to community participation in state-led education and outreach programs. By integrating risk perception analysis and increasing stakeholder engagement, we can bring more attention to this issue, educate the public about the threat of lead pollution, and efficiently use financial resources to implement a more sustainable solution. Copyright © 2016. Published by Elsevier Ltd.

Manufacture of TATB and TNT from Biosynthesized Phloroglucinols

DTIC Science & Technology

2010-07-01

the microbial synthesis of mono-O-methylphloroglucinols, phloroglucinol O-methyl transferase (POMT) from Rosa chinensis var. spontanea has been...successfully de novo synthesized in codon-optimized form for expression in E. coli, which is the host currently used for microbial synthesis of...efforts had been made in both strain development and optimizing fermentation conditions for microbial phloroglucinol synthesis . Under optimized resin

Linear-Quadratic-Gaussian Regulator Developed for a Magnetic Bearing

NASA Technical Reports Server (NTRS)

Choi, Benjamin B.

2002-01-01

Linear-Quadratic-Gaussian (LQG) control is a modern state-space technique for designing optimal dynamic regulators. It enables us to trade off regulation performance and control effort, and to take into account process and measurement noise. The Structural Mechanics and Dynamics Branch at the NASA Glenn Research Center has developed an LQG control for a fault-tolerant magnetic bearing suspension rig to optimize system performance and to reduce the sensor and processing noise. The LQG regulator consists of an optimal state-feedback gain and a Kalman state estimator. The first design step is to seek a state-feedback law that minimizes the cost function of regulation performance, which is measured by a quadratic performance criterion with user-specified weighting matrices, and to define the tradeoff between regulation performance and control effort. The next design step is to derive a state estimator using a Kalman filter because the optimal state feedback cannot be implemented without full state measurement. Since the Kalman filter is an optimal estimator when dealing with Gaussian white noise, it minimizes the asymptotic covariance of the estimation error.

An Atmospheric General Circulation Model with Chemistry for the CRAY T3E: Design, Performance Optimization and Coupling to an Ocean Model

NASA Technical Reports Server (NTRS)

Farrara, John D.; Drummond, Leroy A.; Mechoso, Carlos R.; Spahr, Joseph A.

1998-01-01

The design, implementation and performance optimization on the CRAY T3E of an atmospheric general circulation model (AGCM) which includes the transport of, and chemical reactions among, an arbitrary number of constituents is reviewed. The parallel implementation is based on a two-dimensional (longitude and latitude) data domain decomposition. Initial optimization efforts centered on minimizing the impact of substantial static and weakly-dynamic load imbalances among processors through load redistribution schemes. Recent optimization efforts have centered on single-node optimization. Strategies employed include loop unrolling, both manually and through the compiler, the use of an optimized assembler-code library for special function calls, and restructuring of parts of the code to improve data locality. Data exchanges and synchronizations involved in coupling different data-distributed models can account for a significant fraction of the running time. Therefore, the required scattering and gathering of data must be optimized. In systems such as the T3E, there is much more aggregate bandwidth in the total system than in any particular processor. This suggests a distributed design. The design and implementation of a such distributed 'Data Broker' as a means to efficiently couple the components of our climate system model is described.

On the use of controls for subsonic transport performance improvement: Overview and future directions

NASA Technical Reports Server (NTRS)

Gilyard, Glenn; Espana, Martin

1994-01-01

Increasing competition among airline manufacturers and operators has highlighted the issue of aircraft efficiency. Fewer aircraft orders have led to an all-out efficiency improvement effort among the manufacturers to maintain if not increase their share of the shrinking number of aircraft sales. Aircraft efficiency is important in airline profitability and is key if fuel prices increase from their current low. In a continuing effort to improve aircraft efficiency and develop an optimal performance technology base, NASA Dryden Flight Research Center developed and flight tested an adaptive performance seeking control system to optimize the quasi-steady-state performance of the F-15 aircraft. The demonstrated technology is equally applicable to transport aircraft although with less improvement. NASA Dryden, in transitioning this technology to transport aircraft, is specifically exploring the feasibility of applying adaptive optimal control techniques to performance optimization of redundant control effectors. A simulation evaluation of a preliminary control law optimizes wing-aileron camber for minimum net aircraft drag. Two submodes are evaluated: one to minimize fuel and the other to maximize velocity. This paper covers the status of performance optimization of the current fleet of subsonic transports. Available integrated controls technologies are reviewed to define approaches using active controls. A candidate control law for adaptive performance optimization is presented along with examples of algorithm operation.

Prognostic benefit of optimum left ventricular lead position in cardiac resynchronization therapy: follow-up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy).

PubMed

Kydd, Anna C; Khan, Fakhar Z; Watson, William D; Pugh, Peter J; Virdee, Munmohan S; Dutka, David P

2014-06-01

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Automated Design of Complex Dynamic Systems

PubMed Central

Hermans, Michiel; Schrauwen, Benjamin; Bienstman, Peter; Dambre, Joni

2014-01-01

Several fields of study are concerned with uniting the concept of computation with that of the design of physical systems. For example, a recent trend in robotics is to design robots in such a way that they require a minimal control effort. Another example is found in the domain of photonics, where recent efforts try to benefit directly from the complex nonlinear dynamics to achieve more efficient signal processing. The underlying goal of these and similar research efforts is to internalize a large part of the necessary computations within the physical system itself by exploiting its inherent non-linear dynamics. This, however, often requires the optimization of large numbers of system parameters, related to both the system's structure as well as its material properties. In addition, many of these parameters are subject to fabrication variability or to variations through time. In this paper we apply a machine learning algorithm to optimize physical dynamic systems. We show that such algorithms, which are normally applied on abstract computational entities, can be extended to the field of differential equations and used to optimize an associated set of parameters which determine their behavior. We show that machine learning training methodologies are highly useful in designing robust systems, and we provide a set of both simple and complex examples using models of physical dynamical systems. Interestingly, the derived optimization method is intimately related to direct collocation a method known in the field of optimal control. Our work suggests that the application domains of both machine learning and optimal control have a largely unexplored overlapping area which envelopes a novel design methodology of smart and highly complex physical systems. PMID:24497969

Louisiana: a model for advancing regional e-Research through cyberinfrastructure.

PubMed

Katz, Daniel S; Allen, Gabrielle; Cortez, Ricardo; Cruz-Neira, Carolina; Gottumukkala, Raju; Greenwood, Zeno D; Guice, Les; Jha, Shantenu; Kolluru, Ramesh; Kosar, Tevfik; Leger, Lonnie; Liu, Honggao; McMahon, Charlie; Nabrzyski, Jarek; Rodriguez-Milla, Bety; Seidel, Ed; Speyrer, Greg; Stubblefield, Michael; Voss, Brian; Whittenburg, Scott

2009-06-28

Louisiana researchers and universities are leading a concentrated, collaborative effort to advance statewide e-Research through a new cyberinfrastructure: computing systems, data storage systems, advanced instruments and data repositories, visualization environments and people, all linked together by software programs and high-performance networks. This effort has led to a set of interlinked projects that have started making a significant difference in the state, and has created an environment that encourages increased collaboration, leading to new e-Research. This paper describes the overall effort, the new projects and environment and the results to date.

[Computational chemistry in structure-based drug design].

PubMed

Cao, Ran; Li, Wei; Sun, Han-Zi; Zhou, Yu; Huang, Niu

2013-07-01

Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.

Dissemination and implementation sciences in pharmacy: A call to action for professional organizations.

PubMed

Seaton, Terry L

There is a substantial gap between the generation of new knowledge and its widespread incorporation into routine clinical practice, including the medication use process. Principles of dissemination and implementation sciences, if fully embraced by clinicians and researchers, have the potential of improving healthcare effectiveness, efficiency, quality, and safety. This commentary is a call to action for member-driven professional organizations in pharmacy to serve their members and the profession by proactively and strategically leading efforts to develop pharmacist's abilities to incorporate principles of dissemination and implementation sciences into their practice. Additionally, these organizations should provide meaningful support for dissemination and implementation research that hastens the adoption, promotes intervention fidelity, and demonstrates the scaling and sustaining of evidence-based practices to optimize patient care delivery and medication therapy outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Commentary: Increasing the Connectivity Between Implementation Science and Public Health: Advancing Methodology, Evidence Integration, and Sustainability.

PubMed

Chambers, David A

2018-04-01

Gaps remain between the outcomes of biomedical research and their application within clinical and community settings. The field of implementation science, also referred to as dissemination and implementation research, is intended to improve the adoption, uptake, and sustainability of evidence-based health interventions. The articles in this volume's symposium on implementation science and public health identify important directions in the effort to maximize the impact of research on public and population health. Leading researchers present reviews of the use of quasi-experimental designs in implementation science, the movement toward enhancing evidence-based public health, and intervention sustainability. Each article presents lessons learned from prior research and recommendations for the next generation of studies. Collectively, the symposium offers a road map for future implementation science that seeks to optimize public health.

Introduction and a Quick Look at MUESR, the Magnetic Structure and mUon Embedding Site Refinement Suite

NASA Astrophysics Data System (ADS)

Bonfà, Pietro; Onuorah, Ifeanyi John; De Renzi, Roberto

The estimation of the magnetic field generated at a given point by magnetic dipoles is an undergraduate exercise. However, under certain approximation, this is all that is needed to evaluate the local field at the muon site once the interstitial position of the muon in the unit cell is known. The development of an application to specifically solve this problem may therefore seem an excessive effort. At the same time, the lack of a general solution leads to the development of small ad hoc codes that are generally rewritten or re-adapted for different experiments and are poorly optimized. This and other motivations led to the development of MuESR, a python+C tool to perform dipolar field simulations. In this manuscript we will describe the tool, its features and its development strategies.

Cerebro-rhino orbital mucormycosis: an update.

PubMed

Wali, Upender; Balkhair, Abdullah; Al-Mujaini, Abdullah

2012-04-01

Mucormycosis is an uncommon fungal infection which can lead to fulminant necrotizing infection under optimal host condition. Fungi have the ability to invade blood vessels and can affect different parts of the body. The most common, though the most aggressive, form is cerebro-rhino-orbital mucormycosis that occurs in debilitated patients, in conjunction with sinus or para-sinus involvement. Due to increased number of newly diagnosed cases of mucormycosis world-wide resulting from uncontrolled metabolic conditions, this paper intends to widen the reader's scope and knowledge about the nature of the disease and its multicomplexity that require a collaborative effort for careful management. Patients who are at risks both at the onset of the disease and during its management have been identified in the paper. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Noninvasive, automatic optimization strategy in cardiac resynchronization therapy.

PubMed

Reumann, Matthias; Osswald, Brigitte; Doessel, Olaf

2007-07-01

Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.

Waste management as an effort to improve urban area cleanliness and community income (journal review)

NASA Astrophysics Data System (ADS)

Kinantan, Bag; Rahim Matondang, A.; Hidayati, Juliza

2018-02-01

The problem of urban waste has reached a point of concern. Population and economic growth are thought to be the cause of increasing the waste generation. The major problem related to this condition is the increasing of waste production which is not balance with the increase of its management capacity. Based on the Law Number 18 of 2008 that waste management starts from the source by applying the 3R approach (Reduction, Reuse, Recycle). This regulation provides a way which expect the waste management can be better, so that, the level of waste service can be improved and load on landfills (TPA) can be reduced.The cost of garbage collection and transport are 85% of the total waste management cost, so if this is optimized, it will optimize the system as a whole. Subsequent research focuses on how to optimize the garbage collection and transport sub-systems by finding the shortest route of transportation to the landfill by developing a Vehicle Routing Problem (VRP) model. The development of an urban area leads to the preparation of the best route is no longer an optimal solution. The complexity of the waste problem is not only related to the technical matters, but also the social and economic problems of the community. So, it is necessary to develop a model of waste management which does not only pay attention to the technical aspects, but also the social and economic. Waste is expected to be no longer a burden, but can also be utilized economically to increase community income.

Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery.

PubMed

Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J

2018-01-01

GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

A Framework for Widespread Replication of a Highly Spatially Resolved Childhood Lead Exposure Risk Model

PubMed Central

Kim, Dohyeong; Galeano, M. Alicia Overstreet; Hull, Andrew; Miranda, Marie Lynn

2008-01-01

Background Preventive approaches to childhood lead poisoning are critical for addressing this longstanding environmental health concern. Moreover, increasing evidence of cognitive effects of blood lead levels < 10 μg/dL highlights the need for improved exposure prevention interventions. Objectives Geographic information system–based childhood lead exposure risk models, especially if executed at highly resolved spatial scales, can help identify children most at risk of lead exposure, as well as prioritize and direct housing and health-protective intervention programs. However, developing highly resolved spatial data requires labor-and time-intensive geocoding and analytical processes. In this study we evaluated the benefit of increased effort spent geocoding in terms of improved performance of lead exposure risk models. Methods We constructed three childhood lead exposure risk models based on established methods but using different levels of geocoded data from blood lead surveillance, county tax assessors, and the 2000 U.S. Census for 18 counties in North Carolina. We used the results to predict lead exposure risk levels mapped at the individual tax parcel unit. Results The models performed well enough to identify high-risk areas for targeted intervention, even with a relatively low level of effort on geocoding. Conclusions This study demonstrates the feasibility of widespread replication of highly spatially resolved childhood lead exposure risk models. The models guide resource-constrained local health and housing departments and community-based organizations on how best to expend their efforts in preventing and mitigating lead exposure risk in their communities. PMID:19079729

OPTIMIZATION OF DECENTRALIZED BMP CONTROLS IN URBAN AREAS

EPA Science Inventory

This paper will present an overview of a recently completed project for the US EPA entitled, Optimization of Urban Wet-weather Flow Control Systems. The focus of this effort is on techniques that are suitable for evaluating decentralized BMP controls. The four major components ...

OPTIMIZATION OF DECENTRALIZED BMP CONTROLS IN URBAN AREAS

EPA Science Inventory

This paper will present an overview of a recently completed project for the US EPA entitled Optimization of Urban Wet-weather Flow Control Systems. The focus of this effort is on techniques that are suitable for evaluating decentralized BMP controls. The four major components o...

Vacuum Pump System Optimization Saves Energy at a Dairy Farm

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

In 1998, S&S Dairy optimized the vacuum pumping system at their dairy farm in Modesto, California. In an effort to reduce energy costs, S&S Dairy evaluated their vacuum pumping system to determine if efficiency gains and energy savings were possible.

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

PubMed Central

Montaner, Luis J.

2017-01-01

Abstract Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. PMID:28520969

Targeting the Tumor Microenvironment with Immunotherapy for Genitourinary Malignancies.

PubMed

Marciscano, Ariel E; Madan, Ravi A

2018-03-08

Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis. Despite this success, many patients fail to respond to immune checkpoint inhibitors and progression/relapse remains common. Furthermore, modest clinical activity has been observed with ICIs as a monotherapy in advanced PCa. As such, novel treatment approaches are warranted and improved biomarkers for patient selection and treatment response are desperately needed. Future efforts should focus on exploring synergistic and rational combinations that safely and effectively boost response rates and survival in genitourinary malignancies. Specific areas of interest include (1) evaluating the optimal sequencing, disease burden, and timing of immuno-oncology agents with other anti-cancer therapeutics and (2) validating novel biomarkers of response to immunotherapy to optimize patient selection and to identify individuals most likely to benefit from immunotherapy across the heterogenous spectrum of genitourinary malignancies.

Monitoring/Verification using DMS: TATP Example

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephan Weeks, Kevin Kyle, Manuel Manard

Field-rugged and field-programmable differential mobility spectrometry (DMS) networks provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. CBE sensor motes used in conjunction with automated fast gas chromatography with DMS detection (GC/DMS) verification instrumentation integrated into situational operations-management systems can be readily deployed and optimized for changing application scenarios. The feasibility of developing selective DMS motes for a “smart dust” sampling approach with guided, highly selective, fast GC/DMS verification analysis is a compelling approach to minimize or prevent the illegal use of explosives or chemical and biologicalmore » materials. DMS is currently one of the foremost emerging technologies for field separation and detection of gas-phase chemical species. This is due to trace-level detection limits, high selectivity, and small size. Fast GC is the leading field analytical method for gas phase separation of chemical species in complex mixtures. Low-thermal-mass GC columns have led to compact, low-power field systems capable of complete analyses in 15–300 seconds. A collaborative effort optimized a handheld, fast GC/DMS, equipped with a non-rad ionization source, for peroxide-based explosive measurements.« less

Competition among Li+, Na+, K+ and Rb+ Monovalent Ions for DNA in Molecular Dynamics Simulations using the Additive CHARMM36 and Drude Polarizable Force Fields

PubMed Central

Savelyev, Alexey; MacKerell, Alexander D.

2015-01-01

In the present study we report on interactions of and competition between monovalent ions for two DNA sequences in MD simulations. Efforts included the development and validation of parameters for interactions among the first-group monovalent cations, Li+, Na+, K+ and Rb+, and DNA in the Drude polarizable and additive CHARMM36 force fields (FF). The optimization process targeted gas-phase QM interaction energies of various model compounds with ions and osmotic pressures of bulk electrolyte solutions of chemically relevant ions. The optimized ionic parameters are validated against counterion condensation theory and buffer exchange-atomic emission spectroscopy measurements providing quantitative data on the competitive association of different monovalent ions with DNA. Comparison between experimental and MD simulation results demonstrates that, compared to the additive CHARMM36 model, the Drude FF provides an improved description of the general features of the ionic atmosphere around DNA and leads to closer agreement with experiment on the ionic competition within the ion atmosphere. Results indicate the importance of extended simulation systems on the order of 25 Å beyond the DNA surface to obtain proper convergence of ion distributions. PMID:25751286

Burial Duration and Frequency Influences Resilience of Differing Propagule Types in a Subtidal Seagrass, Posidonia australis

PubMed Central

2016-01-01

Sedimentation that leads to periodic, and often prolonged, burial events is becoming more common on the world’s coastlines as human populations expand and create urbanised marine environments. Different seagrass species react differently to sediment burial but many species in the southern hemisphere are yet to be examined. How seagrasses react to burial has restoration implications. There is a need to critically assess seagrass transplant propagule responses to periodic (pulse) and prolonged (press) burial events before selecting the most appropriate species, transplant propagule, and transplant site. In my study, mesocosm experiments, coupled with field measurements were used to assess how sexual (seedlings) and vegetative (sprigs) propagules of Posidonia australis responded to pulse and press burial events. Seedlings were highly susceptible to burial (both pulse and press), with no survival at the end of the experimental period. In contrast, rhizome growth in vegetative propagules was stimulated by pulse burial, although press burial events resulted in mortality. The implication for Posidonia australis restoration efforts in areas where burial is periodic, was that vegetative propagules are optimal transplant units, in comparison to seedlings. Press burial however, renders a transplant site sub-optimal for both seedling and sprig transplants. PMID:27526020

On sequential data assimilation for scalar macroscopic traffic flow models

NASA Astrophysics Data System (ADS)

Blandin, Sébastien; Couque, Adrien; Bayen, Alexandre; Work, Daniel

2012-09-01

We consider the problem of sequential data assimilation for transportation networks using optimal filtering with a scalar macroscopic traffic flow model. Properties of the distribution of the uncertainty on the true state related to the specific nonlinearity and non-differentiability inherent to macroscopic traffic flow models are investigated, derived analytically and analyzed. We show that nonlinear dynamics, by creating discontinuities in the traffic state, affect the performances of classical filters and in particular that the distribution of the uncertainty on the traffic state at shock waves is a mixture distribution. The non-differentiability of traffic dynamics around stationary shock waves is also proved and the resulting optimality loss of the estimates is quantified numerically. The properties of the estimates are explicitly studied for the Godunov scheme (and thus the Cell-Transmission Model), leading to specific conclusions about their use in the context of filtering, which is a significant contribution of this article. Analytical proofs and numerical tests are introduced to support the results presented. A Java implementation of the classical filters used in this work is available on-line at http://traffic.berkeley.edu for facilitating further efforts on this topic and fostering reproducible research.

Monitoring/Verification Using DMS: TATP Example

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kevin Kyle; Stephan Weeks

Field-rugged and field-programmable differential mobility spectrometry (DMS) networks provide highly selective, universal monitoring of vapors and aerosols at detectable levels from persons or areas involved with illicit chemical/biological/explosives (CBE) production. CBE sensor motes used in conjunction with automated fast gas chromatography with DMS detection (GC/DMS) verification instrumentation integrated into situational operationsmanagement systems can be readily deployed and optimized for changing application scenarios. The feasibility of developing selective DMS motes for a “smart dust” sampling approach with guided, highly selective, fast GC/DMS verification analysis is a compelling approach to minimize or prevent the illegal use of explosives or chemical and biologicalmore » materials. DMS is currently one of the foremost emerging technologies for field separation and detection of gas-phase chemical species. This is due to trace-level detection limits, high selectivity, and small size. GC is the leading analytical method for the separation of chemical species in complex mixtures. Low-thermal-mass GC columns have led to compact, low-power field systems capable of complete analyses in 15–300 seconds. A collaborative effort optimized a handheld, fast GC/DMS, equipped with a non-rad ionization source, for peroxide-based explosive measurements.« less

Hiring at Risk: Time to Ensure Hiring Really Is the Most Important Thing We Do

ERIC Educational Resources Information Center

Hughes, Thomas Ross

2014-01-01

This article focuses on the necessity of providing foundational preparatory training for those who are charged with leading teacher hiring efforts at the K-12 level. The essential question proposed within the article is: Why are the very educators tasked with directly leading K-12 staff selection and retention efforts far more likely to be…

Bioprocessing automation in cell therapy manufacturing: Outcomes of special interest group automation workshop.

PubMed

Ball, Oliver; Robinson, Sarah; Bure, Kim; Brindley, David A; Mccall, David

2018-04-01

Phacilitate held a Special Interest Group workshop event in Edinburgh, UK, in May 2017. The event brought together leading stakeholders in the cell therapy bioprocessing field to identify present and future challenges and propose potential solutions to automation in cell therapy bioprocessing. Here, we review and summarize discussions from the event. Deep biological understanding of a product, its mechanism of action and indication pathogenesis underpin many factors relating to bioprocessing and automation. To fully exploit the opportunities of bioprocess automation, therapeutics developers must closely consider whether an automation strategy is applicable, how to design an 'automatable' bioprocess and how to implement process modifications with minimal disruption. Major decisions around bioprocess automation strategy should involve all relevant stakeholders; communication between technical and business strategy decision-makers is of particular importance. Developers should leverage automation to implement in-process testing, in turn applicable to process optimization, quality assurance (QA)/ quality control (QC), batch failure control, adaptive manufacturing and regulatory demands, but a lack of precedent and technical opportunities can complicate such efforts. Sparse standardization across product characterization, hardware components and software platforms is perceived to complicate efforts to implement automation. The use of advanced algorithmic approaches such as machine learning may have application to bioprocess and supply chain optimization. Automation can substantially de-risk the wider supply chain, including tracking and traceability, cryopreservation and thawing and logistics. The regulatory implications of automation are currently unclear because few hardware options exist and novel solutions require case-by-case validation, but automation can present attractive regulatory incentives. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Structural Analysis of DFG-in and DFG-out Dual Src-Abl Inhibitors Sharing a Common Vinyl Purine Template

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng

2010-09-30

Bcr-Abl is the oncogenic protein tyrosine kinase responsible for chronic myeloid leukemia (CML). Treatment of the disease with imatinib (Gleevec) often results in drug resistance via kinase mutations at the advanced phases of the disease, which has necessitated the development of new mutation-resistant inhibitors, notably against the T315I gatekeeper mutation. As part of our efforts to discover such mutation resistant Abl inhibitors, we have focused on optimizing purine template kinase inhibitors, leading to the discovery of potent DFG-in and DFG-out series of Abl inhibitors that are also potent Src inhibitors. Here we present crystal structures of Abl bound by twomore » such inhibitors, based on a common N9-arenyl purine, and that represent both DFG-in and -out binding modes. In each structure the purine template is bound deeply in the adenine pocket and the novel vinyl linker forms a non-classical hydrogen bond to the gatekeeper residue, Thr315. Specific template substitutions promote either a DFG-in or -out binding mode, with the kinase binding site adjusting to optimize molecular recognition. Bcr-Abl T315I mutant kinase is resistant to all currently marketed Abl inhibitors, and is the focus of intense drug discovery efforts. Notably, our DFG-out inhibitor, AP24163, exhibits modest activity against this mutant, illustrating that this kinase mutant can be inhibited by DFG-out class inhibitors. Furthermore our DFG-out inhibitor exhibits dual Src-Abl activity, absent from the prototypical DFG-out inhibitor, imatinib as well as its analog, nilotinib. The data presented here provides structural guidance for the further design of novel potent DFG-out class inhibitors against Src, Abl and Abl T315I mutant kinases.« less

An efficient approach for the assembly of mass and stiffness matrices of structures with modifications

NASA Astrophysics Data System (ADS)

Wagner, Andreas; Spelsberg-Korspeter, Gottfried

2013-09-01

The finite element method is one of the most common tools for the comprehensive analysis of structures with applications reaching from static, often nonlinear stress-strain, to transient dynamic analyses. For single calculations the expense to generate an appropriate mesh is often insignificant compared to the analysis time even for complex geometries and therefore negligible. However, this is not the case for certain other applications, most notably structural optimization procedures, where the (re-)meshing effort is very important with respect to the total runtime of the procedure. Thus it is desirable to find methods to efficiently generate mass and stiffness matrices allowing to reduce this effort, especially for structures with modifications of minor complexity, e.g. panels with cutouts. Therefore, a modeling approach referred to as Energy Modification Method is proposed in this paper. The underlying idea is to model and discretize the basis structure, e.g. a plate, and the modifications, e.g. holes, separately. The discretized energy expressions of the modifications are then subtracted from (or added to) the energy expressions of the basis structure and the coordinates are related to each other by kinematical constraints leading to the mass and stiffness matrices of the complete structure. This approach will be demonstrated by two simple examples, a rod with varying material properties and a rectangular plate with a rectangular or circular hole, using a finite element discretization as basis. Convergence studies of the method based on the latter example follow demonstrating the rapid convergence and efficiency of the method. Finally, the Energy Modification Method is successfully used in the structural optimization of a circular plate with holes, with the objective to split all its double eigenfrequencies.

Position of the American Dietetic Association and Dietitians of Canada: nutrition and women's health.

PubMed

2004-06-01

It is the position of the American Dietetic Association (ADA) and Dietitians of Canada (DC) that women have specific nutritional needs and vulnerabilities and, as such, are at unique risk for various nutrition-related diseases and conditions. Therefore, the ADA and the DC strongly support research, health promotion activities, health services, and advocacy efforts that will enable women to adopt desirable nutrition practices for optimal health. Women are at risk for numerous chronic diseases and conditions that affect the duration and quality of their lives. Although women's health-related issues are multifaceted, nutrition has been shown to influence significantly the risk of chronic disease and to assist in maintaining optimal health status. Dietetics professionals strongly support research, health promotion activities, health services, and advocacy efforts that will enable women to adopt desirable nutrition practices for optimal health.

Ethical Issues in Using Children's Blood Lead Levels as a Remedial Action Objective

PubMed Central

Evans, Emily Lorraine

2011-01-01

The Environmental Protection Agency measures the success or failure of Superfund site remediation efforts against remedial action objectives (RAOs). RAOs are frequently based on environmental contaminant concentrations, but with lead exposure, blood lead levels from the population at risk are often used. Although childhood lead screening is an important public health tool, an RAO based on child blood lead levels raises ethical concerns: public health efforts that are more reactive than preventive, a blood lead standard (10 μg/dL) that may not be fully protective, the use of a measure whose validity and reliability may be easily compromised, and exacerbation of environmental injustice and systematic disadvantages. The example of Bunker Hill mine, Kellogg, Idaho, allowed an examination of these ethical concerns. PMID:21836120

Ant colony system algorithm for the optimization of beer fermentation control.

PubMed

Xiao, Jie; Zhou, Ze-Kui; Zhang, Guang-Xin

2004-12-01

Beer fermentation is a dynamic process that must be guided along a temperature profile to obtain the desired results. Ant colony system algorithm was applied to optimize the kinetic model of this process. During a fixed period of fermentation time, a series of different temperature profiles of the mixture were constructed. An optimal one was chosen at last. Optimal temperature profile maximized the final ethanol production and minimized the byproducts concentration and spoilage risk. The satisfactory results obtained did not require much computation effort.

Genetic algorithm optimization of transcutaneous energy transmission systems for implantable ventricular assist devices.

PubMed

Byron, Kelly; Bluvshtein, Vlad; Lucke, Lori

2013-01-01

Transcutaneous energy transmission systems (TETS) wirelessly transmit power through the skin. TETS is particularly desirable for ventricular assist devices (VAD), which currently require cables through the skin to power the implanted pump. Optimizing the inductive link of the TET system is a multi-parameter problem. Most current techniques to optimize the design simplify the problem by combining parameters leading to sub-optimal solutions. In this paper we present an optimization method using a genetic algorithm to handle a larger set of parameters, which leads to a more optimal design. Using this approach, we were able to increase efficiency while also reducing power variability in a prototype, compared to a traditional manual design method.

Improved high operating temperature MCT MWIR modules

NASA Astrophysics Data System (ADS)

Lutz, H.; Breiter, R.; Figgemeier, H.; Schallenberg, T.; Schirmacher, W.; Wollrab, R.

2014-06-01

High operating temperature (HOT) IR-detectors are a key factor to size, weight and power (SWaP) reduced IR-systems. Such systems are essential to provide infantrymen with low-weight handheld systems with increased battery lifetimes or most compact clip-on weapon sights in combination with high electro-optical performance offered by cooled IR-technology. AIM's MCT standard n-on-p technology with vacancy doping has been optimized over many years resulting in MWIR-detectors with excellent electro-optical performance up to operating temperatures of ~120K. In the last years the effort has been intensified to improve this standard technology by introducing extrinsic doping with Gold as an acceptor. As a consequence the dark current could considerably be suppressed and allows for operation at ~140K with good e/o performance. More detailed investigations showed that limitation for HOT > 140K is explained by consequences from rising dark current rather than from defective pixel level. Recently, several crucial parameters were identified showing great promise for further optimization of HOT-performance. Among those, p-type concentration could successfully be reduced from the mid 1016 / cm3 to the lower 1015/ cm3 range. Since AIM is one of the leading manufacturers of split linear cryocoolers, an increase in operating temperature will directly lead to IR-modules with improved SWaP characteristics by making use of the miniature members of its SX cooler family with single piston and balancer technology. The paper will present recent progress in the development of HOT MWIR-detector arrays at AIM and show electro-optical performance data in comparison to focal plane arrays produced in the standard technology.

Synchronic interval Gaussian mixed-integer programming for air quality management.

PubMed

Cheng, Guanhui; Huang, Guohe Gordon; Dong, Cong

2015-12-15

To reveal the synchronism of interval uncertainties, the tradeoff between system optimality and security, the discreteness of facility-expansion options, the uncertainty of pollutant dispersion processes, and the seasonality of wind features in air quality management (AQM) systems, a synchronic interval Gaussian mixed-integer programming (SIGMIP) approach is proposed in this study. A robust interval Gaussian dispersion model is developed for approaching the pollutant dispersion process under interval uncertainties and seasonal variations. The reflection of synchronic effects of interval uncertainties in the programming objective is enabled through introducing interval functions. The proposition of constraint violation degrees helps quantify the tradeoff between system optimality and constraint violation under interval uncertainties. The overall optimality of system profits of an SIGMIP model is achieved based on the definition of an integrally optimal solution. Integer variables in the SIGMIP model are resolved by the existing cutting-plane method. Combining these efforts leads to an effective algorithm for the SIGMIP model. An application to an AQM problem in a region in Shandong Province, China, reveals that the proposed SIGMIP model can facilitate identifying the desired scheme for AQM. The enhancement of the robustness of optimization exercises may be helpful for increasing the reliability of suggested schemes for AQM under these complexities. The interrelated tradeoffs among control measures, emission sources, flow processes, receptors, influencing factors, and economic and environmental goals are effectively balanced. Interests of many stakeholders are reasonably coordinated. The harmony between economic development and air quality control is enabled. Results also indicate that the constraint violation degree is effective at reflecting the compromise relationship between constraint-violation risks and system optimality under interval uncertainties. This can help decision makers mitigate potential risks, e.g. insufficiency of pollutant treatment capabilities, exceedance of air quality standards, deficiency of pollution control fund, or imbalance of economic or environmental stress, in the process of guiding AQM. Copyright © 2015 Elsevier B.V. All rights reserved.

A Pareto frontier intersection-based approach for efficient multiobjective optimization of competing concept alternatives

NASA Astrophysics Data System (ADS)

Rousis, Damon A.

The expected growth of civil aviation over the next twenty years places significant emphasis on revolutionary technology development aimed at mitigating the environmental impact of commercial aircraft. As the number of technology alternatives grows along with model complexity, current methods for Pareto finding and multiobjective optimization quickly become computationally infeasible. Coupled with the large uncertainty in the early stages of design, optimal designs are sought while avoiding the computational burden of excessive function calls when a single design change or technology assumption could alter the results. This motivates the need for a robust and efficient evaluation methodology for quantitative assessment of competing concepts. This research presents a novel approach that combines Bayesian adaptive sampling with surrogate-based optimization to efficiently place designs near Pareto frontier intersections of competing concepts. Efficiency is increased over sequential multiobjective optimization by focusing computational resources specifically on the location in the design space where optimality shifts between concepts. At the intersection of Pareto frontiers, the selection decisions are most sensitive to preferences place on the objectives, and small perturbations can lead to vastly different final designs. These concepts are incorporated into an evaluation methodology that ultimately reduces the number of failed cases, infeasible designs, and Pareto dominated solutions across all concepts. A set of algebraic samples along with a truss design problem are presented as canonical examples for the proposed approach. The methodology is applied to the design of ultra-high bypass ratio turbofans to guide NASA's technology development efforts for future aircraft. Geared-drive and variable geometry bypass nozzle concepts are explored as enablers for increased bypass ratio and potential alternatives over traditional configurations. The method is shown to improve sampling efficiency and provide clusters of feasible designs that motivate a shift towards revolutionary technologies that reduce fuel burn, emissions, and noise on future aircraft.

Louisiana: a model for advancing regional e-Research through cyberinfrastructure

PubMed Central

Katz, Daniel S.; Allen, Gabrielle; Cortez, Ricardo; Cruz-Neira, Carolina; Gottumukkala, Raju; Greenwood, Zeno D.; Guice, Les; Jha, Shantenu; Kolluru, Ramesh; Kosar, Tevfik; Leger, Lonnie; Liu, Honggao; McMahon, Charlie; Nabrzyski, Jarek; Rodriguez-Milla, Bety; Seidel, Ed; Speyrer, Greg; Stubblefield, Michael; Voss, Brian; Whittenburg, Scott

2009-01-01

Louisiana researchers and universities are leading a concentrated, collaborative effort to advance statewide e-Research through a new cyberinfrastructure: computing systems, data storage systems, advanced instruments and data repositories, visualization environments and people, all linked together by software programs and high-performance networks. This effort has led to a set of interlinked projects that have started making a significant difference in the state, and has created an environment that encourages increased collaboration, leading to new e-Research. This paper describes the overall effort, the new projects and environment and the results to date. PMID:19451102

Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions.

PubMed

Jarrar, Mu'taman; Abdul Rahman, Hamzah; Don, Mohammad Sobri

2015-10-20

Demand for health care service has significantly increased, while the quality of healthcare and patient safety has become national and international priorities. This paper aims to identify the gaps and the current initiatives for optimizing the quality of care and patient safety in Malaysia. Review of the current literature. Highly cited articles were used as the basis to retrieve and review the current initiatives for optimizing the quality of care and patient safety. The country health plan of Ministry of Health (MOH) Malaysia and the MOH Malaysia Annual Reports were reviewed. The MOH has set four strategies for optimizing quality and sustaining quality of life. The 10th Malaysia Health Plan promotes the theme "1 Care for 1 Malaysia" in order to sustain the quality of care. Despite of these efforts, the total number of complaints received by the medico-legal section of the MOH Malaysia is increasing. The current global initiatives indicted that quality performance generally belong to three main categories: patient; staffing; and working environment related factors. There is no single intervention for optimizing quality of care to maintain patient safety. Multidimensional efforts and interventions are recommended in order to optimize the quality of care and patient safety in Malaysia.

Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions

PubMed Central

Jarrar, Mu’taman; Rahman, Hamzah Abdul; Don, Mohammad Sobri

2016-01-01

Background and Objective: Demand for health care service has significantly increased, while the quality of healthcare and patient safety has become national and international priorities. This paper aims to identify the gaps and the current initiatives for optimizing the quality of care and patient safety in Malaysia. Design: Review of the current literature. Highly cited articles were used as the basis to retrieve and review the current initiatives for optimizing the quality of care and patient safety. The country health plan of Ministry of Health (MOH) Malaysia and the MOH Malaysia Annual Reports were reviewed. Results: The MOH has set four strategies for optimizing quality and sustaining quality of life. The 10th Malaysia Health Plan promotes the theme “1 Care for 1 Malaysia” in order to sustain the quality of care. Despite of these efforts, the total number of complaints received by the medico-legal section of the MOH Malaysia is increasing. The current global initiatives indicted that quality performance generally belong to three main categories: patient; staffing; and working environment related factors. Conclusions: There is no single intervention for optimizing quality of care to maintain patient safety. Multidimensional efforts and interventions are recommended in order to optimize the quality of care and patient safety in Malaysia. PMID:26755459

Tool Support for Software Lookup Table Optimization

DOE PAGES

Wilcox, Chris; Strout, Michelle Mills; Bieman, James M.

2011-01-01

A number of scientific applications are performance-limited by expressions that repeatedly call costly elementary functions. Lookup table (LUT) optimization accelerates the evaluation of such functions by reusing previously computed results. LUT methods can speed up applications that tolerate an approximation of function results, thereby achieving a high level of fuzzy reuse. One problem with LUT optimization is the difficulty of controlling the tradeoff between performance and accuracy. The current practice of manual LUT optimization adds programming effort by requiring extensive experimentation to make this tradeoff, and such hand tuning can obfuscate algorithms. In this paper we describe a methodology andmore » tool implementation to improve the application of software LUT optimization. Our Mesa tool implements source-to-source transformations for C or C++ code to automate the tedious and error-prone aspects of LUT generation such as domain profiling, error analysis, and code generation. We evaluate Mesa with five scientific applications. Our results show a performance improvement of 3.0× and 6.9× for two molecular biology algorithms, 1.4× for a molecular dynamics program, 2.1× to 2.8× for a neural network application, and 4.6× for a hydrology calculation. We find that Mesa enables LUT optimization with more control over accuracy and less effort than manual approaches.« less

Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy.

PubMed

Rose, Carl H; Faksh, Arij; Traynor, Kyle D; Cabrera, Daniel; Arendt, Katherine W; Brost, Brian C

2015-11-01

Although perimortem delivery has been recorded in the medical literature for millennia, the procedural intent has evolved to the current fetocentric approach, predicating timing of delivery following maternal cardiopulmonary arrest to optimize neonatal outcome. We suggest a call to action to reinforce the concept that if the uterus is palpable at or above the umbilicus, preparations for delivery should be made simultaneous with initiation of maternal resuscitative efforts; if maternal condition is not rapidly reversible, hysterotomy with delivery should be performed regardless of fetal viability or elapsed time since arrest. Cognizant of the difficulty in determining precise timing of arrest in clinical practice, if fetal status is already compromised further delay while attempting to assess fetal heart rate, locating optimal surgical equipment, or transporting to an operating room will result in unnecessary worsening of both maternal and fetal condition. Even if intrauterine demise has already occurred, maternal resuscitative efforts will typically be markedly improved following delivery with uterine decompression. Consequently we suggest that perimortem cesarean delivery be renamed "resuscitative hysterotomy" to reflect the mutual optimization of resuscitation efforts that would potentially provide earlier and more substantial benefit to both mother and baby. Copyright © 2015 Elsevier Inc. All rights reserved.

Joint location, inventory, and preservation decisions for non-instantaneous deterioration items under delay in payments

NASA Astrophysics Data System (ADS)

Tsao, Yu-Chung

2016-02-01

This study models a joint location, inventory and preservation decision-making problem for non-instantaneous deteriorating items under delay in payments. An outside supplier provides a credit period to the wholesaler which has a distribution system with distribution centres (DCs). The non-instantaneous deteriorating means no deterioration occurs in the earlier stage, which is very useful for items such as fresh food and fruits. This paper also considers that the deteriorating rate will decrease and the reservation cost will increase as the preservation effort increases. Therefore, how much preservation effort should be made is a crucial decision. The objective of this paper is to determine the optimal locations and number of DCs, the optimal replenishment cycle time at DCs, and the optimal preservation effort simultaneously such that the total network profit is maximised. The problem is formulated as piecewise nonlinear functions and has three different cases. Algorithms based on piecewise nonlinear optimisation are provided to solve the joint location and inventory problem for all cases. Computational analysis illustrates the solution procedures and the impacts of the related parameters on decisions and profits. The results of this study can serve as references for business managers or administrators.

Optimizing Wartime Materiel Delivery: An Overview of DoD containerization. Volume 2. Framework for Action to Address DoD Containerization Issues

DOT National Transportation Integrated Search

1988-10-01

This second volume of the study entitled, Optimizing Wartime Materiel Delivery: An Overview of DOD Containerization Efforts, -outlines a framework for action to address containerization issues identified in Volume I. The objectives of the study inclu...

Topology optimization of two-dimensional elastic wave barriers

NASA Astrophysics Data System (ADS)

Van hoorickx, C.; Sigmund, O.; Schevenels, M.; Lazarov, B. S.; Lombaert, G.

2016-08-01

Topology optimization is a method that optimally distributes material in a given design domain. In this paper, topology optimization is used to design two-dimensional wave barriers embedded in an elastic halfspace. First, harmonic vibration sources are considered, and stiffened material is inserted into a design domain situated between the source and the receiver to minimize wave transmission. At low frequencies, the stiffened material reflects and guides waves away from the surface. At high frequencies, destructive interference is obtained that leads to high values of the insertion loss. To handle harmonic sources at a frequency in a given range, a uniform reduction of the response over a frequency range is pursued. The minimal insertion loss over the frequency range of interest is maximized. The resulting design contains features at depth leading to a reduction of the insertion loss at the lowest frequencies and features close to the surface leading to a reduction at the highest frequencies. For broadband sources, the average insertion loss in a frequency range is optimized. This leads to designs that especially reduce the response at high frequencies. The designs optimized for the frequency averaged insertion loss are found to be sensitive to geometric imperfections. In order to obtain a robust design, a worst case approach is followed.

"When the going gets tough, the tough get going": Motivation towards closure and effort investment in the performance of cognitive tasks.

PubMed

Sankaran, Sindhuja; Szumowska, Ewa; Kossowska, Małgorzata

2017-01-01

Previous studies have demonstrated that the need for closure (NFC), which refers to an individual's aversion toward uncertainty and the desire to quickly reduce it, leads to reluctance to invest effort in judgments and decision making. However, we argue that NFC may lead to either an increase or a decrease in effort depending on the availability of easy vs. difficult means to achieve closure and perceived importance of the task goal. We found that when closure could be achieved via both less and more demanding means, NFC was associated with decreased effort unless the task was perceived as important (Study 1). However, when attaining closure was possible via demanding means only, NFC was associated with increased effort, regardless of the task importance (Study 2). Moreover, NFC was related to choosing a more instrumental strategy for the goal of closure, even if this strategy required effort (Study 3). The results are discussed in the light of cognitive energetics theory.

Energy-saving management modelling and optimization for lead-acid battery formation process

NASA Astrophysics Data System (ADS)

Wang, T.; Chen, Z.; Xu, J. Y.; Wang, F. Y.; Liu, H. M.

2017-11-01

In this context, a typical lead-acid battery producing process is introduced. Based on the formation process, an efficiency management method is proposed. An optimization model with the objective to minimize the formation electricity cost in a single period is established. This optimization model considers several related constraints, together with two influencing factors including the transformation efficiency of IGBT charge-and-discharge machine and the time-of-use price. An example simulation is shown using PSO algorithm to solve this mathematic model, and the proposed optimization strategy is proved to be effective and learnable for energy-saving and efficiency optimization in battery producing industries.

Aerodynamic optimization studies on advanced architecture computers

NASA Technical Reports Server (NTRS)

Chawla, Kalpana

1995-01-01

The approach to carrying out multi-discipline aerospace design studies in the future, especially in massively parallel computing environments, comprises of choosing (1) suitable solvers to compute solutions to equations characterizing a discipline, and (2) efficient optimization methods. In addition, for aerodynamic optimization problems, (3) smart methodologies must be selected to modify the surface shape. In this research effort, a 'direct' optimization method is implemented on the Cray C-90 to improve aerodynamic design. It is coupled with an existing implicit Navier-Stokes solver, OVERFLOW, to compute flow solutions. The optimization method is chosen such that it can accomodate multi-discipline optimization in future computations. In the work , however, only single discipline aerodynamic optimization will be included.

Missed, Misused, or Mismanaged: Improving Early Detection Systems to Optimize Child Outcomes

ERIC Educational Resources Information Center

Macy, Marisa; Marks, Kevin; Towle, Alexander

2014-01-01

Early detection efforts have been shown to vary greatly in practice, and there is a general lack of systematic accountability built into monitoring early detection effort impact. This article reviews current early detection practices and the drawbacks of these practices, with particular attention given to prevalent issues of mismeasurement,…

Predicting costs of alien species surveillance across varying transportation networks

Treesearch

Laura Blackburn; Rebecca Epanchin-Niell; Alexandra Thompson; Andrew Liebhold; Jacqueline Beggs

2017-01-01

Efforts to detect and eradicate invading populations before they establish are a critical component of national biosecurity programmes. An essential element for maximizing the efficiency of these efforts is the balancing of expenditures on surveillance (e.g. trapping) versus treatment (e.g. eradication). Identifying the optimal allocation of resources towards...

Using FAA's SAGE model to conduct global inventories and to assess route-specific variability in aviation fuel burn, emissions and costs

DOT National Transportation Integrated Search

2006-09-30

The focus on optimizing aircraft fuel efficiency : as well as interest in assessing aviation : emissions inventories to measure the efficacy of : efforts to limit or reduce aviation emissions : worldwide has spurred a number of efforts in : the U.S. ...

Debiasing comparative optimism and increasing worry for health outcomes.

PubMed

Rose, Jason P

2012-11-01

Comparative optimism - feeling at less personal risk for negative outcomes than one's peers - has been linked to reduced prevention efforts. This study examined a novel debiasing technique aimed at simultaneously reducing both indirectly and directly measured comparative optimism. Before providing direct comparative estimates, participants provided absolute self and peer estimates in a joint format (same computer screen) or a separate format (different computer screens). Relative to the separate format condition, participants in the joint format condition showed (1) lower comparative optimism in absolute/indirect measures, (2) lower direct comparative optimism, and (3) heightened worry. Implications for risk perception screening are discussed.

Structural Optimization in automotive design

NASA Technical Reports Server (NTRS)

Bennett, J. A.; Botkin, M. E.

1984-01-01

Although mathematical structural optimization has been an active research area for twenty years, there has been relatively little penetration into the design process. Experience indicates that often this is due to the traditional layout-analysis design process. In many cases, optimization efforts have been outgrowths of analysis groups which are themselves appendages to the traditional design process. As a result, optimization is often introduced into the design process too late to have a significant effect because many potential design variables have already been fixed. A series of examples are given to indicate how structural optimization has been effectively integrated into the design process.

Chemistry challenges in lead optimization: silicon isosteres in drug discovery.

PubMed

Showell, Graham A; Mills, John S

2003-06-15

During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and a sub-optimal intellectual property (IP) position. The pharmaceutical industry has an ongoing need for new, safe medicines with a genuine biomedical benefit, a clean IP position and commercial viability. Inherent drug-like properties and chemical tractability are also essential for the smooth development of such agents. The introduction of bioisosteres, to improve the properties of a molecule and obtain new classes of compounds without prior art in the patent literature, is a key strategy used by medicinal chemists during the lead optimization process. Sila-substitution (C/Si exchange) of existing drugs is an approach to search for new drug-like candidates that have beneficial biological properties and a clear IP position. Some of the fundamental differences between carbon and silicon can lead to marked alterations in the physicochemical and biological properties of the silicon-containing analogues and the resulting benefits can be exploited in the drug design process.

Evolving Roles For Teaching Assistants In Introductory Courses

NASA Astrophysics Data System (ADS)

Dunbar, R. W.; Egger, A. E.; Schwartz, J. K.

2008-12-01

As we bring new research-based learning approaches, curricular innovations, and student engagement practices into the introductory science classroom, expectations of teaching assistants (TAs) should have, and have, changed. Similarly, the 21st century teaching assistant has different expectations of us. Maintaining relevance in this context means bringing TAs into an integrated teaching team that supports effective learning for students and provides structured professional development opportunities for TAs. A number of support efforts on our campus, with counterparts at many other universities, seek to optimize the instructional impact of faculty and teaching assistants, thus opening the door to enhanced student engagement (e.g. the quality of effort students put forth, their persistence in science and/or engineering courses, and their perception of scientific relevance in everyday life). Among these efforts, School of Earth Sciences course development TAs work 1:1 in advance of the term with introductory course faculty to design exercises and course materials that meet clearly articulated student learning goals or pedagogical challenges. Throughout the process, TAs are mentored by the faculty as well as science pedagogy experts. Initially funded by a major teaching award, the School is now moving to institutionalize this successful program which has broadened the definition of the TA role. Another area of optimization, reflecting Shulman's concept of pedagogical content knowledge, is our campus mandate that TA development take place within a departmental, as well as general, context. Both Chemistry and Physics expect introductory course TAs to lead interactive, guided-inquiry or tutorial-style sections. Integrating these sections with lecture and positively reinforcing course goals requires TA buy-in and a set of pedagogical facilitation skills cultivated through course-specific training and active mentoring while teaching. To better support the mentoring process in these and other departments, the MinT (Mentors in Teaching) program provides resources and a learning community for advanced graduate students who mentor TAs. There is clearly more to do, but we have come a long way from sink or swim toward an enriched infrastructure of support for teaching and learning in the introductory science classroom.

Energy-Water Microgrid Case Study at the University of Arizona's BioSphere 2

NASA Astrophysics Data System (ADS)

Daw, J.; Macknick, J.; Kandt, A.; Giraldez, J.

2016-12-01

Microgrids can provide reliable and cost-effective energy services in a variety of conditions and locations. To date, there has been minimal effort invested in developing energy-water microgrids that demonstrate the feasibility and leverage the synergies associated with designing and operating renewable energy and water systems in a coordinated framework. Water and wastewater treatment equipment can be operated in ways to provide ancillary services to the electrical grid and renewable energy can be utilized to power water-related infrastructure, but the potential for co-managed systems has not yet been quantified or fully characterized. Co-management and optimization of energy and water resources could lead to improved reliability and economic operating conditions. Energy-water microgrids could be a promising solution to improve energy and water resource management for islands, rural communities, distributed generation, Defense operations, and many parts of the world lacking critical infrastructure.The National Renewable Energy Laboratory (NREL) and the University of Arizona have been jointly researching energy-water microgrid opportunities through an effort at the university's BioSphere 2 (B2) Earth systems science research facility. B2 is an ideal case study for an energy-water microgrid test site, given its size, its unique mission and operations, the existence and criticality of water and energy infrastructure, and its ability to operate connected-to or disconnected-from the local electrical grid. Moreover, the B2 is a premier facility for undertaking agricultural research, providing an excellent opportunity to evaluate connections and tradeoffs in the food-energy-water nexus. The research effort at B2 identified the technical potential and associated benefits of an energy-water microgrid through the evaluation of energy ancillary services and peak load reductions and quantified the potential for B2 water-related loads to be utilized and modified to provide grid services in the context of an optimized energy-water microgrid. The foundational work performed at B2 also serves a model that can be built upon for identifying relevant energy-water microgrid data, analytical requirements, and operational challenges associated with development of future energy-water microgrids.

IAF 15 Draft Paper

NASA Technical Reports Server (NTRS)

Menkin, Evgeny; Juillerat, Robert

2015-01-01

With the International Space Station Program transition from assembly to utilization, focus has been placed on the optimization of essential resources. This includes resources both resupplied from the ground and also resources produced by the ISS. In an effort to improve the use of two of these, the ISS Engineering teams, led by the ISS Program Systems Engineering and Integration Office, undertook an effort to modify the techniques use to perform several key on-orbit events. The primary purposes of this endeavor was to make the ISS more efficient in the use of the Russian-supplied fuel for the propulsive attitude control system and also to minimize the impacts to available ISS power due to the positioning of the ISS solar arrays. Because the ISS solar arrays are sensitive to several factors that are present when propulsive attitude control is used, they must be operated in a manner to protect them from damage. This results in periods of time where the arrays must be positioned, rather than autonomously tracking the sun, resulting in negative impacts to power generated by the solar arrays and consumed by both the ISS core systems and payload customers. A reduction in the number and extent of the events each year that require the ISS to use propulsive attitude control simultaneously accomplishes both these goals. Each instance where the ISS solar arrays normal sun tracking mode must be interrupted represent a need for some level of powerdown of equipment. As the magnitude of payload power requirements increases, and the efficiency of the ISS solar arrays decreases, these powerdowns caused by array positioning, will likely become more significant and could begin to negatively impact the payload operations. Through efforts such as this, the total number of events each year that require positioning of the arrays to unfavorable positions for power generation, in order to protect them against other constraints, are reduced. Optimization of propulsive events and transitioning some of them to non-propulsive CMG control significantly reduces propellant usage on the ISS leading to the reduction of the propellant delivery requirement. This results in move available upmass that can be used for delivering critical dry cargo, additional water, air, crew supplies and science experiments.

Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

PubMed

Cournia, Zoe; Allen, Bryce; Sherman, Woody

2017-12-26

Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives, using a combination of retrospective literature examples and prospective studies from drug discovery projects. This work is intended to provide a contemporary overview of the scientific, technical, and practical issues associated with running relative binding free energy simulations, with a focus on real-world drug discovery applications. We offer guidelines for improving the accuracy of RBFE simulations, especially for challenging cases, and emphasize unresolved issues that could be improved by further research in the field.

Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists.

PubMed

Szabó, György; Kiss, Róbert; Páyer-Lengyel, Dóra; Vukics, Krisztina; Szikra, Judit; Baki, Andrea; Molnár, László; Fischer, János; Keseru, György M

2009-07-01

Hit-to-lead optimization of a novel series of N-alkyl-N-[2-oxo-2-(4-aryl-4H-pyrrolo[1,2-a]quinoxaline-5-yl)-ethyl]-carboxylic acid amides, derived from a high throughput screening (HTS) hit, are described. Subsequent optimization led to identification of in vitro potent cannabinoid 1 receptor (CB1R) antagonists representing a new class of compounds in this area.

No Cost – Low Cost Compressed Air System Optimization in Industry

NASA Astrophysics Data System (ADS)

Dharma, A.; Budiarsa, N.; Watiniasih, N.; Antara, N. G.

2018-04-01

Energy conservation is a systematic, integrated of effort, in order to preserve energy sources and improve energy utilization efficiency. Utilization of energy in efficient manner without reducing the energy usage it must. Energy conservation efforts are applied at all stages of utilization, from utilization of energy resources to final, using efficient technology, and cultivating an energy-efficient lifestyle. The most common way is to promote energy efficiency in the industry on end use and overcome barriers to achieve such efficiency by using system energy optimization programs. The facts show that energy saving efforts in the process usually only focus on replacing tools and not an overall system improvement effort. In this research, a framework of sustainable energy reduction work in companies that have or have not implemented energy management system (EnMS) will be conducted a systematic technical approach in evaluating accurately a compressed-air system and potential optimization through observation, measurement and verification environmental conditions and processes, then processing the physical quantities of systems such as air flow, pressure and electrical power energy at any given time measured using comparative analysis methods in this industry, to provide the potential savings of energy saving is greater than the component approach, with no cost to the lowest cost (no cost - low cost). The process of evaluating energy utilization and energy saving opportunities will provide recommendations for increasing efficiency in the industry and reducing CO2 emissions and improving environmental quality.

Optimal charges in lead progression: a structure-based neuraminidase case study.

PubMed

Armstrong, Kathryn A; Tidor, Bruce; Cheng, Alan C

2006-04-20

Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive intermolecular interaction component. To investigate whether knowledge of the ligand optimal charge distribution can facilitate more intuitive design of electrostatic interactions, we took a series of small-molecule influenza neuraminidase inhibitors with known protein cocrystal structures and calculated the difference between the optimal and actual charge distributions. This difference from the electrostatic optimum correlates with the calculated electrostatic contribution to binding (r(2) = 0.94) despite small changes in binding modes caused by chemical substitutions, suggesting that the optimal charge distribution is a useful design goal. Furthermore, detailed suggestions for chemical modification generated by this approach are in many cases consistent with observed improvements in binding affinity, and the method appears to be useful despite discrete chemical constraints. Taken together, these results suggest that charge optimization is useful in facilitating generation of compound ideas in lead optimization. Our results also provide insight into design of neuraminidase inhibitors.

Public-Private Partnerships in Lead Discovery: Overview and Case Studies.

PubMed

Gottwald, Matthias; Becker, Andreas; Bahr, Inke; Mueller-Fahrnow, Anke

2016-09-01

The pharmaceutical industry is faced with significant challenges in its efforts to discover new drugs that address unmet medical needs. Safety concerns and lack of efficacy are the two main technical reasons for attrition. Improved early research tools including predictive in silico, in vitro, and in vivo models, as well as a deeper understanding of the disease biology, therefore have the potential to improve success rates. The combination of internal activities with external collaborations in line with the interests and needs of all partners is a successful approach to foster innovation and to meet the challenges. Collaboration can take place in different ways, depending on the requirements of the participants. In this review, the value of public-private partnership approaches will be discussed, using examples from the Innovative Medicines Initiative (IMI). These examples describe consortia approaches to develop tools and processes for improving target identification and validation, as well as lead identification and optimization. The project "Kinetics for Drug Discovery" (K4DD), focusing on the adoption of drug-target binding kinetics analysis in the drug discovery decision-making process, is described in more detail. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel communication mechanism based on node potential multi-path routing

NASA Astrophysics Data System (ADS)

Bu, Youjun; Zhang, Chuanhao; Jiang, YiMing; Zhang, Zhen

2016-10-01

With the network scales rapidly and new network applications emerge frequently, bandwidth supply for today's Internet could not catch up with the rapid increasing requirements. Unfortunately, irrational using of network sources makes things worse. Actual network deploys single-next-hop optimization paths for data transmission, but such "best effort" model leads to the imbalance use of network resources and usually leads to local congestion. On the other hand Multi-path routing can use the aggregation bandwidth of multi paths efficiently and improve the robustness of network, security, load balancing and quality of service. As a result, multi-path has attracted much attention in the routing and switching research fields and many important ideas and solutions have been proposed. This paper focuses on implementing the parallel transmission of multi next-hop data, balancing the network traffic and reducing the congestion. It aimed at exploring the key technologies of the multi-path communication network, which could provide a feasible academic support for subsequent applications of multi-path communication networking. It proposed a novel multi-path algorithm based on node potential in the network. And the algorithm can fully use of the network link resource and effectively balance network link resource utilization.

Unmanned Aerial Vehicle Systems for Disaster Relief: Tornado Alley

NASA Technical Reports Server (NTRS)

DeBusk, Wesley M.

2009-01-01

Unmanned aerial vehicle systems are currently in limited use for public service missions worldwide. Development of civil unmanned technology in the United States currently lags behind military unmanned technology development in part because of unresolved regulatory and technological issues. Civil unmanned aerial vehicle systems have potential to augment disaster relief and emergency response efforts. Optimal design of aerial systems for such applications will lead to unmanned vehicles which provide maximum potentiality for relief and emergency response while accounting for public safety concerns and regulatory requirements. A case study is presented that demonstrates application of a civil unmanned system to a disaster relief mission with the intent on saving lives. The concept utilizes unmanned aircraft to obtain advanced warning and damage assessments for tornados and severe thunderstorms. Overview of a tornado watch mission architecture as well as commentary on risk, cost, need for, and design tradeoffs for unmanned aerial systems are provided.

Tunneled Mesoporous Carbon Nanofibers with Embedded ZnO Nanoparticles for Ultrafast Lithium Storage.

PubMed

An, Geon-Hyoung; Lee, Do-Young; Ahn, Hyo-Jin

2017-04-12

Carbon and metal oxide composites have received considerable attention as anode materials for Li-ion batteries (LIBs) owing to their excellent cycling stability and high specific capacity based on the chemical and physical stability of carbon and the high theoretical specific capacity of metal oxides. However, efforts to obtain ultrafast cycling stability in carbon and metal oxide composites at high current density for practical applications still face important challenges because of the longer Li-ion diffusion pathway, which leads to poor ultrafast performance during cycling. Here, tunneled mesoporous carbon nanofibers with embedded ZnO nanoparticles (TMCNF/ZnO) are synthesized by electrospinning, carbonization, and postcalcination. The optimized TMCNF/ZnO shows improved electrochemical performance, delivering outstanding ultrafast cycling stability, indicating a higher specific capacity than previously reported ZnO-based anode materials in LIBs. Therefore, the unique architecture of TMCNF/ZnO has potential for use as an anode material in ultrafast LIBs.

Optimal stabilization of Boolean networks through collective influence

NASA Astrophysics Data System (ADS)

Wang, Jiannan; Pei, Sen; Wei, Wei; Feng, Xiangnan; Zheng, Zhiming

2018-03-01

Boolean networks have attracted much attention due to their wide applications in describing dynamics of biological systems. During past decades, much effort has been invested in unveiling how network structure and update rules affect the stability of Boolean networks. In this paper, we aim to identify and control a minimal set of influential nodes that is capable of stabilizing an unstable Boolean network. For locally treelike Boolean networks with biased truth tables, we propose a greedy algorithm to identify influential nodes in Boolean networks by minimizing the largest eigenvalue of a modified nonbacktracking matrix. We test the performance of the proposed collective influence algorithm on four different networks. Results show that the collective influence algorithm can stabilize each network with a smaller set of nodes compared with other heuristic algorithms. Our work provides a new insight into the mechanism that determines the stability of Boolean networks, which may find applications in identifying virulence genes that lead to serious diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joel E. Kostka

This project represented a joint effort between Oak Ridge National Laboratory (ORNL), the University of Tennessee (UT), and Florida State University (FSU). ORNL served as the lead in-stitution with Dr. A.V. Palumbo responsible for project coordination, integration, and deliver-ables. In situ uranium bioremediation is focused on biostimulating indigenous microorganisms through a combination of pH neutralization and the addition of large amounts of electron donor. Successful biostimulation of U(VI) reduction has been demonstrated in the field and in the laboratory. However, little data is available on the dynamics of microbial populations capable of U(VI) reduction, and the differences in the microbialmore » community dynamics between proposed electron donors have not been explored. In order to elucidate the potential mechanisms of U(VI) reduction for optimization of bioremediation strategies, structure-function relationships of microbial populations were investigated in microcosms of subsurface materials cocontaminated with radionuclides and nitrate from the Oak Ridge Field Research Center (ORFRC), Oak Ridge, Tennessee.« less

Versatile and declarative dynamic programming using pair algebras.

PubMed

Steffen, Peter; Giegerich, Robert

2005-09-12

Dynamic programming is a widely used programming technique in bioinformatics. In sharp contrast to the simplicity of textbook examples, implementing a dynamic programming algorithm for a novel and non-trivial application is a tedious and error prone task. The algebraic dynamic programming approach seeks to alleviate this situation by clearly separating the dynamic programming recurrences and scoring schemes. Based on this programming style, we introduce a generic product operation of scoring schemes. This leads to a remarkable variety of applications, allowing us to achieve optimizations under multiple objective functions, alternative solutions and backtracing, holistic search space analysis, ambiguity checking, and more, without additional programming effort. We demonstrate the method on several applications for RNA secondary structure prediction. The product operation as introduced here adds a significant amount of flexibility to dynamic programming. It provides a versatile testbed for the development of new algorithmic ideas, which can immediately be put to practice.

Computing Properties of Hadrons, Nuclei and Nuclear Matter from Quantum Chromodynamics (LQCD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Negele, John W.

Building on the success of two preceding generations of Scientific Discovery through Advanced Computing (SciDAC) projects, this grant supported the MIT component (P.I. John Negele) of a multi-institutional SciDAC-3 project that also included Brookhaven National Laboratory, the lead laboratory with P. I. Frithjof Karsch serving as Project Director, Thomas Jefferson National Accelerator Facility with P. I. David Richards serving as Co-director, University of Washington with P. I. Martin Savage, University of North Carolina with P. I. Rob Fowler, and College of William and Mary with P. I. Andreas Stathopoulos. Nationally, this multi-institutional project coordinated the software development effort that themore » nuclear physics lattice QCD community needs to ensure that lattice calculations can make optimal use of forthcoming leadership-class and dedicated hardware, including that at the national laboratories, and to exploit future computational resources in the Exascale era.« less

Innovations in adolescent reproductive and sexual health education in Santiago de Chile: effects of physician leadership and direct service.

PubMed

Grizzard, Tarayn; González, Electra; Sandoval, Jorge; Molina, Ramiro

2004-01-01

Reproductive and sexual health (RSH) education is a key component of most family planning programs around the world and is particularly important for adolescents, for whom parenthood is more likely to have difficult or dangerous health outcomes. A lack of comprehensive RSH education targeted at adolescents may augment the poor outcomes associated with early pregnancy by creating barriers to optimal care. This article discusses the creation of the Centro de Medicina Reproductiva y Desarrollo Integral de la Adolescencia clinic, a comprehensive adolescent reproductive health center in Santiago de Chile, and its RSH education programs. In particular, the role of the physician in originating and leading the RSH education efforts, the controversy associated with RSH education in Chile, and the effects of comprehensive RHS education on the local and regional adolescent populations are discussed.

5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors.

PubMed

Ai, Teng; Wilson, Daniel J; More, Swati S; Xie, Jiashu; Chen, Liqiang

2016-04-14

Derived from our previously reported human sirtuin 2 (SIRT2) inhibitors that were based on a 5-aminonaphthalen-1-yloxy nicotinamide core structure, 5-((3-amidobenzyl)oxy)nicotinamides offered excellent activity against SIRT2 and high isozyme selectivity over SIRT1 and SIRT3. Selected compounds also exhibited generally favorable in vitro absorption, distribution, metabolism, and excretion properties. Kinetic studies revealed that a representative SIRT2 inhibitor acted competitively against both NAD(+) and the peptide substrate, an inhibitory modality that was supported by our computational study. More importantly, two selected compounds exhibited significant protection against α-synuclein aggregation-induced cytotoxicity in SH-SY5Y cells. Therefore, 5-((3-amidobenzyl)oxy)nicotinamides represent a new class of SIRT2 inhibitors that are attractive candidates for further lead optimization in our continued effort to explore selective inhibition of SIRT2 as a potential therapy for Parkinson's disease.

Toward Personalized Targeted Therapeutics: An Overview.

PubMed

Weathers, Shiao-Pei S; Gilbert, Mark R

2017-04-01

In neuro-oncology, there has been a movement towards personalized medicine, or tailoring treatment to the individual patient. Ideally, tumor and patient evaluations would lead to the selection of the best treatment (based on tumor characterization) and the right dosing schedule (based on patient characterization). The recent advances in the molecular analysis of glioblastoma have created optimism that personalized targeted therapy is within reach. Although our understanding of the molecular complexity of glioblastoma has increased over the years, the path to developing effective targeted therapeutic strategies is wrought with many challenges, as described in this review. These challenges include disease heterogeneity, clinical and genomic patient variability, limited number of effective treatments, clinical trial inefficiency, drug delivery, and clinical trial support and accrual. To confront these challenges, it will be imperative to devise innovative and adaptive clinical trials in order to accelerate our efforts in improving the outcomes for our patients who have been in desperate need.

Conducting interdisciplinary research to promote healthy and safe employment in health care: promises and pitfalls.

PubMed

Slatin, Craig; Galizzi, Monica; Melillo, Karen Devereaux; Mawn, Barbara

2004-01-01

Due to the complexity of human health, emphasis is increasingly being placed on the need for and conduct of multidisciplinary and/or interdisciplinary health research. Yet many academic and research organizations--and the discipline-specific associations and journals--may not yet be prepared to adopt changes necessary to optimally support interdisciplinary work. This article presents an ongoing interdisciplinary research project's efforts to investigate mechanisms and pathways that lead to occupational health disparities among healthcare workers. It describes the promises and pitfalls encountered during the research,and outlines effective strategies that emerged as a result. Lessons learned include: conflict resolution regarding theoretical and methodological differences; establishing a sense of intellectual ownership of the research, as well as guidelines for multiple authorship; and development and utilization of protocols, communication systems, and tools. This experience suggests a need for the establishment of supportive structures and processes to promote successful interdisciplinary research.

SPITFIRE-1

NASA Technical Reports Server (NTRS)

Ryntz, Edward F.

1995-01-01

The purpose of this effort is to develop low-cost rapid forming superplastic aluminum that will be evaluated in pilot production trials for automotive SPF components. The alloy development study conducted under SPITFIRE-1 showed that the addition of CU or Mn to the base 5083 aluminum alloy refined the grain size, leading to enhanced superplastic properties. In SPITFIRE-2, these alloy variants will be further refined and studied to meet the target properties established earlier in the program. Mechanical properties, component forming and post-forming properties will be evaluated. Also, the alloy production process, including thermomechanical processing (TMP) optimization to reduce production cost, will be investigated during SPITFIRE-2. After identifying preferred compositions and production processing, the most promising alloy will be manufactured into production coils for verification during SPITFIRE-3. Components will be produced from these coils in SPITFIRE-4, and the process and component performance will be assessed.

Conducting interdisciplinary research to promote healthy and safe employment in health care: promises and pitfalls.

PubMed Central

Slatin, Craig; Galizzi, Monica; Melillo, Karen Devereaux; Mawn, Barbara

2004-01-01

Due to the complexity of human health, emphasis is increasingly being placed on the need for and conduct of multidisciplinary and/or interdisciplinary health research. Yet many academic and research organizations--and the discipline-specific associations and journals--may not yet be prepared to adopt changes necessary to optimally support interdisciplinary work. This article presents an ongoing interdisciplinary research project's efforts to investigate mechanisms and pathways that lead to occupational health disparities among healthcare workers. It describes the promises and pitfalls encountered during the research,and outlines effective strategies that emerged as a result. Lessons learned include: conflict resolution regarding theoretical and methodological differences; establishing a sense of intellectual ownership of the research, as well as guidelines for multiple authorship; and development and utilization of protocols, communication systems, and tools. This experience suggests a need for the establishment of supportive structures and processes to promote successful interdisciplinary research. PMID:15147650

Creating targeted initial populations for genetic product searches in heterogeneous markets

NASA Astrophysics Data System (ADS)

Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph

2014-12-01

Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.

Ab Initio and Monte Carlo Approaches For the MagnetocaloricEffect in Co- and In-Doped Ni-Mn-Ga Heusler Alloys

NASA Astrophysics Data System (ADS)

Sokolovskiy, Vladimir; Grünebohm, Anna; Buchelnikov, Vasiliy; Entel, Peter

2014-09-01

This special issue collects contributions from the participants of the "Information in Dynamical Systems and Complex Systems" workshop, which cover a wide range of important problems and new approaches that lie in the intersection of information theory and dynamical systems. The contributions include theoretical characterization and understanding of the different types of information flow and causality in general stochastic processes, inference and identification of coupling structure and parameters of system dynamics, rigorous coarse-grain modeling of network dynamical systems, and exact statistical testing of fundamental information-theoretic quantities such as the mutual information. The collective efforts reported herein reflect a modern perspective of the intimate connection between dynamical systems and information flow, leading to the promise of better understanding and modeling of natural complex systems and better/optimal design of engineering systems.

Comparing the force ripple during asynchronous and conventional stimulation.

PubMed

Downey, Ryan J; Tate, Mark; Kawai, Hiroyuki; Dixon, Warren E

2014-10-01

Asynchronous stimulation has been shown to reduce fatigue during electrical stimulation; however, it may also exhibit a force ripple. We quantified the ripple during asynchronous and conventional single-channel transcutaneous stimulation across a range of stimulation frequencies. The ripple was measured during 5 asynchronous stimulation protocols, 2 conventional stimulation protocols, and 3 volitional contractions in 12 healthy individuals. Conventional 40 Hz and asynchronous 16 Hz stimulation were found to induce contractions that were as smooth as volitional contractions. Asynchronous 8, 10, and 12 Hz stimulation induced contractions with significant ripple. Lower stimulation frequencies can reduce fatigue; however, they may also lead to increased ripple. Future efforts should study the relationship between force ripple and the smoothness of the evoked movements in addition to the relationship between stimulation frequency and NMES-induced fatigue to elucidate an optimal stimulation frequency for asynchronous stimulation. © 2014 Wiley Periodicals, Inc.

Commercial biotechnology processing on International Space Station

NASA Astrophysics Data System (ADS)

Deuser, Mark S.; Vellinger, John C.; Hardin, Juanita R.; Lewis, Marian L.

1998-01-01

Commercial biotechnology processing in space has the potential to eventually exceed the $35 billion annual worldwide market generated by the current satellite communications industry (Parone 1997). The International Space Station provides the opportunity to conduct long-term, crew-tended biotechnology research in microgravity to establish the foundation for this new commercial biotechnology market. Industry, government, and academia are collaborating to establish the infrastructure needed to catalyze this biotechnology revolution that could eventually lead to production of medical and pharmaceutical products in space. The biotechnology program discussed herein is evidence of this collaborative effort, with industry involvement from Space Hardware Optimization Technology, Inc., government participation through the NASA Commercial Space program, and academic guidance from the Consortium for Materials Development in Space at the University of Alabama in Huntsville. Blending the strengths and resources of each collaborator creates a strong partnership, that offers enormous research and commercial opportunities.

Discovery of novel drugs for promising targets.

PubMed

Martell, Robert E; Brooks, David G; Wang, Yan; Wilcoxen, Keith

2013-09-01

Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging. The goal of this study was to provide a road map to navigate drug discovery. Review general steps for drug discovery and provide illustrating references. A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed. Drug discovery is a complex process that has significantly evolved in recent years. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Sheet metals characterization using the virtual fields method

NASA Astrophysics Data System (ADS)

Marek, Aleksander; Davis, Frances M.; Pierron, Fabrice

2018-05-01

In this work, a characterisation method involving a deep-notched specimen subjected to a tensile loading is introduced. This specimen leads to heterogeneous states of stress and strain, the latter being measured using a stereo DIC system (MatchID). This heterogeneity enables the identification of multiple material parameters in a single test. In order to identify material parameters from the DIC data, an inverse method called the Virtual Fields Method is employed. The method combined with recently developed sensitivity-based virtual fields allows to optimally locate areas in the test where information about each material parameter is encoded, improving accuracy of the identification over the traditional user-defined virtual fields. It is shown that a single test performed at 45° to the rolling direction is sufficient to obtain all anisotropic plastic parameters, thus reducing experimental effort involved in characterisation. The paper presents the methodology and some numerical validation.

An Ounce of Prevention Beats a Pound of Cure: Resourcing the State Department to Defend the Nation

DTIC Science & Technology

2010-04-01

17 The DOS lacks the resources to lead USG efforts .....................................................25 Summary...failing states 5) The DOS lacks the resources to lead USG efforts After compelling the reader to accept these five arguments, a disparity in US foreign...world‟s most powerful nation. The nation-states in which these terrorists operate lack the ability to monitor or disrupt the operations of these

Recognizable or Not: Towards Image Semantic Quality Assessment for Compression

NASA Astrophysics Data System (ADS)

Liu, Dong; Wang, Dandan; Li, Houqiang

2017-12-01

Traditionally, image compression was optimized for the pixel-wise fidelity or the perceptual quality of the compressed images given a bit-rate budget. But recently, compressed images are more and more utilized for automatic semantic analysis tasks such as recognition and retrieval. For these tasks, we argue that the optimization target of compression is no longer perceptual quality, but the utility of the compressed images in the given automatic semantic analysis task. Accordingly, we propose to evaluate the quality of the compressed images neither at pixel level nor at perceptual level, but at semantic level. In this paper, we make preliminary efforts towards image semantic quality assessment (ISQA), focusing on the task of optical character recognition (OCR) from compressed images. We propose a full-reference ISQA measure by comparing the features extracted from text regions of original and compressed images. We then propose to integrate the ISQA measure into an image compression scheme. Experimental results show that our proposed ISQA measure is much better than PSNR and SSIM in evaluating the semantic quality of compressed images; accordingly, adopting our ISQA measure to optimize compression for OCR leads to significant bit-rate saving compared to using PSNR or SSIM. Moreover, we perform subjective test about text recognition from compressed images, and observe that our ISQA measure has high consistency with subjective recognizability. Our work explores new dimensions in image quality assessment, and demonstrates promising direction to achieve higher compression ratio for specific semantic analysis tasks.

When to stop managing or surveying cryptic threatened species

PubMed Central

Chadès, Iadine; McDonald-Madden, Eve; McCarthy, Michael A.; Wintle, Brendan; Linkie, Matthew; Possingham, Hugh P.

2008-01-01

Threatened species become increasingly difficult to detect as their populations decline. Managers of such cryptic threatened species face several dilemmas: if they are not sure the species is present, should they continue to manage for that species or invest the limited resources in surveying? We find optimal solutions to this problem using a Partially Observable Markov Decision Process and rules of thumb derived from an analytical approximation. We discover that managing a protected area for a cryptic threatened species can be optimal even if we are not sure the species is present. The more threatened and valuable the species is, relative to the costs of management, the more likely we are to manage this species without determining its continued persistence by using surveys. If a species remains unseen, our belief in the persistence of the species declines to a point where the optimal strategy is to shift resources from saving the species to surveying for it. Finally, when surveys lead to a sufficiently low belief that the species is extant, we surrender resources to other conservation actions. We illustrate our findings with a case study using parameters based on the critically endangered Sumatran tiger (Panthera tigris sumatrae), and we generate rules of thumb on how to allocate conservation effort for any cryptic species. Using Partially Observable Markov Decision Processes in conservation science, we determine the conditions under which it is better to abandon management for that species because our belief that it continues to exist is too low. PMID:18779594

When to stop managing or surveying cryptic threatened species.

PubMed

Chadès, Iadine; McDonald-Madden, Eve; McCarthy, Michael A; Wintle, Brendan; Linkie, Matthew; Possingham, Hugh P

2008-09-16

Threatened species become increasingly difficult to detect as their populations decline. Managers of such cryptic threatened species face several dilemmas: if they are not sure the species is present, should they continue to manage for that species or invest the limited resources in surveying? We find optimal solutions to this problem using a Partially Observable Markov Decision Process and rules of thumb derived from an analytical approximation. We discover that managing a protected area for a cryptic threatened species can be optimal even if we are not sure the species is present. The more threatened and valuable the species is, relative to the costs of management, the more likely we are to manage this species without determining its continued persistence by using surveys. If a species remains unseen, our belief in the persistence of the species declines to a point where the optimal strategy is to shift resources from saving the species to surveying for it. Finally, when surveys lead to a sufficiently low belief that the species is extant, we surrender resources to other conservation actions. We illustrate our findings with a case study using parameters based on the critically endangered Sumatran tiger (Panthera tigris sumatrae), and we generate rules of thumb on how to allocate conservation effort for any cryptic species. Using Partially Observable Markov Decision Processes in conservation science, we determine the conditions under which it is better to abandon management for that species because our belief that it continues to exist is too low.

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library.

PubMed

Sipos, Anna; Pató, János; Székely, Rita; Hartkoorn, Ruben C; Kékesi, László; Őrfi, László; Szántai-Kis, Csaba; Mikušová, Katarína; Svetlíková, Zuzana; Korduláková, Jana; Nagaraja, Valakunja; Godbole, Adwait Anand; Bush, Natassja; Collin, Frédéric; Maxwell, Anthony; Cole, Stewart T; Kéri, György

2015-06-01

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 μM and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays. Copyright © 2015 Elsevier Ltd. All rights reserved.

Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity.

PubMed

Šmelcerović, Andrija; Tomović, Katarina; Šmelcerović, Žaklina; Petronijević, Živomir; Kocić, Gordana; Tomašič, Tihomir; Jakopin, Žiga; Anderluh, Marko

2017-07-28

Xanthine oxidase (XO), a versatile metalloflavoprotein enzyme, catalyzes the oxidative hydroxylation of hypoxanthine and xanthine to uric acid in purine catabolism while simultaneously producing reactive oxygen species. Both lead to the gout-causing hyperuricemia and oxidative damage of the tissues where overactivity of XO is present. Over the past years, significant progress and efforts towards the discovery and development of new XO inhibitors have been made and we believe that not only experts in the field, but also general readership would benefit from a review that addresses this topic. Accordingly, the aim of this article was to overview and select the most potent recently reported XO inhibitors and to compare their structures, mechanisms of action, potency and effectiveness of their inhibitory activity, in silico calculated physico-chemical properties as well as predicted pharmacokinetics and toxicity. Derivatives of imidazole, 1,3-thiazole and pyrimidine proved to be more potent than febuxostat while also displaying/possessing favorable predicted physico-chemical, pharmacokinetic and toxicological properties. Although being structurally similar to febuxostat, these optimized inhibitors bear some structural freshness and could be adopted as hits for hit-to-lead development and further evaluation by in vivo studies towards novel drug candidates, and represent valuable model structures for design of novel XO inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bales, Benjamin B; Barrett, Richard F

In almost all modern scientific applications, developers achieve the greatest performance gains by tuning algorithms, communication systems, and memory access patterns, while leaving low level instruction optimizations to the compiler. Given the increasingly varied and complicated x86 architectures, the value of these optimizations is unclear, and, due to time and complexity constraints, it is difficult for many programmers to experiment with them. In this report we explore the potential gains of these 'last mile' optimization efforts on an AMD Barcelona processor, providing readers with relevant information so that they can decide whether investment in the presented optimizations is worthwhile.

Optimal harvesting of a stochastic delay logistic model with Lévy jumps

NASA Astrophysics Data System (ADS)

Qiu, Hong; Deng, Wenmin

2016-10-01

The optimal harvesting problem of a stochastic time delay logistic model with Lévy jumps is considered in this article. We first show that the model has a unique global positive solution and discuss the uniform boundedness of its pth moment with harvesting. Then we prove that the system is globally attractive and asymptotically stable in distribution under our assumptions. Furthermore, we obtain the existence of the optimal harvesting effort by the ergodic method, and then we give the explicit expression of the optimal harvesting policy and maximum yield.

Bionomic Exploitation of a Ratio-Dependent Predator-Prey System

ERIC Educational Resources Information Center

Maiti, Alakes; Patra, Bibek; Samanta, G. P.

2008-01-01

The present article deals with the problem of combined harvesting of a Michaelis-Menten-type ratio-dependent predator-prey system. The problem of determining the optimal harvest policy is solved by invoking Pontryagin's Maximum Principle. Dynamic optimization of the harvest policy is studied by taking the combined harvest effort as a dynamic…

Linking Temporal-Optimization and Spatial-Simulation Models for Forest Planning

Treesearch

Larry A. Leefers; Eric J. Gustafson; Phillip Freeman

2003-01-01

Increasingly, resource management agencies and researchers have turned their analysis and modeling efforts towards spatial and temporal information. This is driven by the need to address wildlife concerns, landscape issues, and social/economic questions. Historically, the USDA Forest Service has used optimization models (i.e., FORPLAN and Spectrum) for timber harvest...

Impact of a Flexible Evaluation System on Effort and Timing of Study

ERIC Educational Resources Information Center

Pacharn, Parunchana; Bay, Darlene; Felton, Sandra

2012-01-01

This paper examines results of a flexible grading system that allows each student to influence the weight allocated to each performance measure. We construct a stylized model to determine students' optimal responses. Our analytical model predicts different optimal strategies for students with varying academic abilities: a frontloading strategy for…

77 FR 64997 - Advisory Committee on Childhood Lead Poisoning Prevention

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... Committee on Childhood Lead Poisoning Prevention In accordance with section 10(a)(2) of the Federal Advisory... implications for childhood lead poisoning prevention efforts. The committee also reviews and reports regularly on childhood lead poisoning prevention practices and recommends improvements in national childhood...

Optimal patch code design via device characterization

NASA Astrophysics Data System (ADS)

Wu, Wencheng; Dalal, Edul N.

2012-01-01

In many color measurement applications, such as those for color calibration and profiling, "patch code" has been used successfully for job identification and automation to reduce operator errors. A patch code is similar to a barcode, but is intended primarily for use in measurement devices that cannot read barcodes due to limited spatial resolution, such as spectrophotometers. There is an inherent tradeoff between decoding robustness and the number of code levels available for encoding. Previous methods have attempted to address this tradeoff, but those solutions have been sub-optimal. In this paper, we propose a method to design optimal patch codes via device characterization. The tradeoff between decoding robustness and the number of available code levels is optimized in terms of printing and measurement efforts, and decoding robustness against noises from the printing and measurement devices. Effort is drastically reduced relative to previous methods because print-and-measure is minimized through modeling and the use of existing printer profiles. Decoding robustness is improved by distributing the code levels in CIE Lab space rather than in CMYK space.

Childhood lead poisoning: the torturous path from science to policy

PubMed Central

Bellinger, David C.; Bellinger, Andrew M.

2006-01-01

The long history of lead poisoning provides many lessons about the process by which scientific knowledge is translated into public health policy. In the United States, lead was added to paint and to gasoline in enormous quantities long after medical evidence clearly showed that excessive lead exposure caused considerable morbidity in the population. This article discusses some of the factors that contributed to the slow pace of efforts to address this problem, including the ubiquity and magnitude of lead exposure during much of the twentieth century, which produced a distorted notion about the blood lead level that can be considered “normal”; the prevailing model of disease during this period, notably the novelty of the concept of subclinical disease; the fact that childhood lead poisoning affected mostly families that were politically and economically disenfranchised, fostering a “blame the victim” attitude; and that controlling lead exposure would have impeded efforts to achieve other desirable goals, illustrating the role that value trade-offs often play in policy decisions. PMID:16585952

Advances in Quantum Trajectory Approaches to Dynamics

NASA Astrophysics Data System (ADS)

Askar, Attila

2001-03-01

The quantum fluid dynamics (QFD) formulation is based on the separation of the amplitude and phase of the complex wave function in Schrodinger's equation. The approach leads to conservation laws for an equivalent "gas continuum". The Lagrangian [1] representation corresponds to following the particles of the fluid continuum, i. e. calculating "quantum trajectories". The Eulerian [2] representation on the other hand, amounts to observing the dynamics of the gas continuum at the points of a fixed coordinate frame. The combination of several factors leads to a most encouraging computational efficiency. QFD enables the numerical analysis to deal with near monotonic amplitude and phase functions. The Lagrangian description concentrates the computation effort to regions of highest probability as an optimal adaptive grid. The Eulerian representation allows the study of multi-coordinate problems as a set of one-dimensional problems within an alternating direction methodology. An explicit time integrator limits the increase in computational effort with the number of discrete points to linear. Discretization of the space via local finite elements [1,2] and global radial functions [3] will be discussed. Applications include wave packets in four-dimensional quadratic potentials and two coordinate photo-dissociation problems for NOCl and NO2. [1] "Quantum fluid dynamics (QFD) in the Lagrangian representation with applications to photo-dissociation problems", F. Sales, A. Askar and H. A. Rabitz, J. Chem. Phys. 11, 2423 (1999) [2] "Multidimensional wave-packet dynamics within the fluid dynamical formulation of the Schrodinger equation", B. Dey, A. Askar and H. A. Rabitz, J. Chem. Phys. 109, 8770 (1998) [3] "Solution of the quantum fluid dynamics equations with radial basis function interpolation", Xu-Guang Hu, Tak-San Ho, H. A. Rabitz and A. Askar, Phys. Rev. E. 61, 5967 (2000)

Educating and training industrial ecologists for the 1990s.

PubMed

Troxell, D E

1992-02-01

For industrial ecology to become a reality and flourish, many talents must be integrated into a single system. Basically, there are four types of technologists who must be brought together to create a system: (i) technical specialists-those that can take the state of knowledge to the state of the art and eventually to the state of practice; (ii) technical "generalists"-those that can integrate diverse technologies into a comprehensive solution; (iii) technical managers-those that can lead technical efforts to an optimal solution (these people must have management skills in their area); and (iv) program managers-those that can understand and merge the overall efforts of technology, business, schedule, and finance. The initial questions for industrial ecology in the 1990s are: Do these people presently exist in industry? What will be needed to bring new people (recent graduates) into the field of industrial ecology? For this decade, the people who will develop and lead the concept of industrial ecology are presently in industry. However, certainly few, if any, today understand the concept of industrial ecology as a system issue. Training will be needed for these practitioners of the 1990s so that the overall goal and the mechanism for achieving industrial ecology are understood. A three-tiered approach is presented to define the education/training needed, to conduct training on an industry basis, and then to initiate the training to be done within a corporation. The three tiers propose the use of universities, professional societies, and industry groups. Having universities participate in the training of the 1990s industrial ecologists will give universities insight to the development of industrial ecology, and access to industry needs so that curriculum can be initiated to educate the industrial ecologists of the future.

Data management for interdisciplinary field experiments: OTTER project support

NASA Technical Reports Server (NTRS)

Angelici, Gary; Popovici, Lidia; Skiles, J. W.

1993-01-01

The ability of investigators of an interdisciplinary science project to properly manage the data that are collected during the experiment is critical to the effective conduct of science. When the project becomes large, possibly including several scenes of large-format remotely sensed imagery shared by many investigators requiring several services, the data management effort can involve extensive staff and computerized data inventories. The OTTER (Oregon Transect Ecosystem Research) project was supported by the PLDS (Pilot Land Data System) with several data management services, such as data inventory, certification, and publication. After a brief description of these services, experiences in providing them are compared with earlier data management efforts and some conclusions regarding data management in support of interdisciplinary science are discussed. In addition to providing these services, a major goal of this data management capability was to adopt characteristics of a pro-active attitude, such as flexibility and responsiveness, believed to be crucial for the effective conduct of active, interdisciplinary science. These are also itemized and compared with previous data management support activities. Identifying and improving these services and characteristics can lead to the design and implementation of optimal data management support capabilities, which can result in higher quality science and data products from future interdisciplinary field experiments.

Transitioning Lessons Learned and Assets of the Global Polio Eradication Initiative to Global and Regional Measles and Rubella Elimination.

PubMed

Kretsinger, Katrina; Strebel, Peter; Kezaala, Robert; Goodson, James L

2017-07-01

The Global Polio Eradication Initiative has built an extensive infrastructure with capabilities and resources that should be transitioned to measles and rubella elimination efforts. Measles continues to be a major cause of child mortality globally, and rubella continues to be the leading infectious cause of birth defects. Measles and rubella eradication is feasible and cost saving. The obvious similarities in strategies between polio elimination and measles and rubella elimination include the use of an extensive surveillance and laboratory network, outbreak preparedness and response, extensive communications and social mobilization networks, and the need for periodic supplementary immunization activities. Polio staff and resources are already connected with those of measles and rubella, and transitioning existing capabilities to measles and rubella elimination efforts allows for optimized use of resources and the best opportunity to incorporate important lessons learned from polio eradication, and polio resources are concentrated in the countries with the highest burden of measles and rubella. Measles and rubella elimination strategies rely heavily on achieving and maintaining high vaccination coverage through the routine immunization activity infrastructure, thus creating synergies with immunization systems approaches, in what is termed a "diagonal approach." © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

National Institute of Allergy and Infectious Diseases workshop report: "Chlamydia vaccines: The way forward".

PubMed

Zhong, Guangming; Brunham, Robert C; de la Maza, Luis M; Darville, Toni; Deal, Carolyn

2017-10-31

Chlamydia trachomatis (Ct), an intracellular pathogen, is the most common bacterial sexually transmitted infection. In addition to acute cervicitis and urethritis, Ct can lead to serious sequelae of significant public health burden including pelvic inflammatory disease (PID) and infertility. Ct control efforts have not resulted in desired outcomes such as reduced incidence and reinfection, and this highlights the need for the development of an effective Ct vaccine. To this end, NIAID organized a workshop to consider the current status of Ct vaccine research and address critical questions in Ct vaccine design and clinical testing. Topics included the goal(s) of a vaccine and the feasibility of achieving these goals, animal models of infection including mouse and nonhuman primate (NHP) models, and correlates of protection to guide vaccine design. Decades of research have provided both whole cell-based and subunit vaccine candidates for development. At least one is currently in clinical development and efforts now need to be directed toward further development of the most attractive candidates. Overall, the discussions and presentations from the workshop highlighted optimism about the current status of Ct vaccine research and detailed the remaining gaps and questions needed to move vaccines forward. Copyright © 2017 Elsevier Ltd. All rights reserved.

A simplified simulation model for a HPDC die with conformal cooling channels

NASA Astrophysics Data System (ADS)

Frings, Markus; Behr, Marek; Elgeti, Stefanie

2017-10-01

In general, the cooling phase of the high-pressure die casting process is based on complex physical phenomena: so-lidification of molten material; heat exchange between cast part, die and cooling fluid; turbulent flow inside the cooling channels that needs to be considered when computing the heat flux; interdependency of properties and temperature of the cooling liquid. Intuitively understanding and analyzing all of these effects when designing HPDC dies is not feasible. A remedy that has become available is numerical design, based for example on shape optimization methods. However, current computing power is not sufficient to perform optimization while at the same time fully resolving all physical phenomena. But since in HPDC suitable objective functions very often lead to integral values, e.g., average die temperature, this paper identifies possible simplifications in the modeling of the cooling phase. As a consequence, the computational effort is reduced to an acceptable level. A further aspect that arises in the context of shape optimization is the evaluation of shape gradients. The challenge here is to allow for large shape deformations without remeshing. In our approach, the cooling channels are described by their center lines. The flow profile of the cooling fluid is then estimated based on experimental data found in literature for turbulent pipe flows. In combination, the heat flux throughout cavity, die, and cooling channel can be described by one single advection-diffusion equation on a fixed mesh. The parameters in the equation are adjusted based on the position of cavity and cooling channel. Both results contribute towards a computationally efficient, yet accurate method, which can be employed within the frame of shape optimization of cooling channels in HPDC dies.

Genetic algorithm in the structural design of Cooke triplet lenses

NASA Astrophysics Data System (ADS)

Hazra, Lakshminarayan; Banerjee, Saswatee

1999-08-01

This paper is in tune with our efforts to develop a systematic method for multicomponent lens design. Our aim is to find a suitable starting point in the final configuration space, so that popular local search methods like damped least squares (DLS) may directly lead to a useful solution. For 'ab initio' design problems, a thin lens layout specifying the powers of the individual components and the intercomponent separations are worked out analytically. Requirements of central aberration targets for the individual components in order to satisfy the prespecified primary aberration targets for the overall system are then determined by nonlinear optimization. The next step involves structural design of the individual components by optimization techniques. This general method may be adapted for the design of triplets and their derivatives. However, for the thin lens design of a Cooke triplet composed of three airspaced singlets, the two steps of optimization mentioned above may be combined into a single optimization procedure. The optimum configuration for each of the single set, catering to the required Gaussian specification and primary aberration targets for the Cooke triplet, are determined by an application of genetic algorithm (GA). Our implementation of this algorithm is based on simulations of some complex tools of natural evolution, like selection, crossover and mutation. Our version of GA may or may not converge to a unique optimum, depending on some of the algorithm specific parameter values. With our algorithm, practically useful solutions are always available, although convergence to a global optimum can not be guaranteed. This is perfectly in keeping with our need to allow 'floating' of aberration targets in the subproblem level. Some numerical results dealing with our preliminary investigations on this problem are presented.

Molecular basis of the potential of vitamin D to prevent cancer.

PubMed

Ingraham, Betty A; Bragdon, Beth; Nohe, Anja

2008-01-01

To review current research findings in cell biology, epidemiology, preclinical, and clinical trials on the protective effects of vitamin D against the development of cancers of the breast, colon, prostate, lung, and ovary. Current recommendations for optimal vitamin D status, the movement towards revision of standards, and reflections on healthy exposure to sunlight are also reviewed. Search methodology: A literature search was conducted in April and updated in September 2007. The Medline and Web of Knowledge databases were searched for primary and review articles published between 1970 and 2007, using the search terms 'vitamin D', 'calcitriol', 'cancer', 'chemoprevention', 'nuclear receptor', 'vitamin D receptor', 'apoptosis', 'cell cycle', 'epidemiology', and 'cell adhesion molecule'. Articles that focused on epidemiological, preclinical, and clinical evidence for vitamin D's effects were selected and additional articles were obtained from reference lists of the retrieved articles. An increasing body of research supports the hypothesis that the active form of vitamin D has significant, protective effects against the development of cancer. Epidemiological studies show an inverse association between sun exposure, serum levels of 25(OH)D, and intakes of vitamin D and risk of developing and/or surviving cancer. The protective effects of vitamin D result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. A significant number of individuals have serum vitamin D levels lower than what appears to protect against cancer, and the research community is currently revising the guidelines for optimal health. This will lead to improved public health policies and to reduced risk of cancer. Research strongly supports the view that efforts to improve vitamin D status would have significant protective effects against the development of cancer. The clinical research community is currently revising recommendations for optimal serum levels and for sensible levels of sun exposure, to levels greater than previously thought. Currently, most experts in the field believe that intakes of between 1000 and 4000 IU will lead to a more healthy level of serum 25(OH)D, at approximately 75 nmol/L that will offer significant protection effects against cancers of the breast, colon, prostate, ovary, lungs, and pancreas. The first randomized trial has shown significant protection against breast cancer, and other clinical trials will follow and ultimately lead to improved public health policies and significantly fewer cancers.

Quality improvement in hospitals: how much does it reduce healthcare costs?

PubMed

Jones, S B

1995-01-01

The philosophy of W.E. Deming suggests that continuous quality improvement efforts, when properly applied, ultimately will lead to financial dividends and will help ensure business longevity. Reducing hospital charges can be exciting for the participants and can provide an impetus for expanding quality improvement efforts. Americans, however, tend to demand almost instant gratification and have limited patience for longer-term results. This factor, coupled with minimal knowledge of actual operational costs and inaccurate charge accounting systems, may lead hospital managers to misinterpret the potential net long-term effects of their quality improvement efforts. In the approaching environment of capitated reimbursement, such mistakes may have serious consequences.

Improving the Selection, Classification, and Utilization of Army Enlisted Personnel: Annual Report, 1987 Fiscal Year

DTIC Science & Technology

1989-10-01

unles so designated by other authrized documena. ’V FOREWORD This document is a descrition of the research effort of the fifth year (Fiscal Year 1987...criterion measures. This part of the effort included the design of job performance measures for the noncommissioned officers in their second tour who were...phase. In Chapter 2 the Project A analysis group reports on their efforts to use the Concurrent Validation sample results to design optimal ASVAB

EMR based telegeriatric system.

PubMed

Pallawala, P M; Lun, K C

2001-05-01

As medical services improve due to new technologies and breakthroughs, it has lead to an increasingly aging population. There has been much discussion and debate on how to solve various aspects such as psychological, socioeconomic and medical problems related to aging. Our effort is to implement a feasible telegeriatric medical service with the use of the state of the art technology to deliver medical services efficiently to remote sites where elderly homes are based. Telegeriatric system will lead to rapid decision-making in the presence of acute or subacute emergencies. This triage will also lead to a reduction of unnecessary admission. It will enable the doctors who visit these elderly homes on a once-a-week basis to improve their geriatric management skills by communication with geriatric specialist. Nursing skills in geriatric care will also benefit from this system. Integrated EMR service will be indispensable in the face of emergency admissions to hospitals. Evolution of EMR database would lead to future research in telegeriatrics and will help to identify the areas where telegeriatrics can be optimally used. This system is based on current web browsing technology and broadband communication. EMR web based server is developed using Java Technology. EMR database was developed using Microsoft SQL server. Both are based at the Medical Informatics Programme, National University of Singapore. Two elderly homes situated in the periphery of Singapore and a leading government hospital in geriatric care has been chosen for the project. These three institutions and National University of Singapore are connected via ADSL protocol, which support high bandwidth, which is necessary for high quality videoconferencing. Each time a patient needs a teleconsultation, a nurse or doctor in the remote site sends the history to the EMR server. EMR server forwards the request to the Alexandra Hospital for consultation. Geriatrics specialists at Alexandra Hospital carry out teleward rounds twice weekly and on demand basis. Following the implementation of the system, a trial run has been done. This shows a high degree of coordination and cooperation between remote site and the Alexandra Hospital Also the patient compliance is very high and they prefer teleconsultation. Initial results show that telegeriatric system has definite advantages in managing geriatric patients at a remote site. As the system evolves, further research will show the areas where telegeriatrics can be used optimally.

MO-DE-204-02: Optimization of the Patient CT Dose in Europe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsapaki, V.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Early Reading Proficiency. Leading Indicator Spotlight

ERIC Educational Resources Information Center

Musen, Lindsey

2010-01-01

In "Beyond Test Scores: Leading Indicators for Education," Foley and colleagues (2008) define leading indicators as those that "provide early signals of progress toward academic achievement" (p. 1) and stress that educators "need leading indicators to help them see the direction their efforts are going in and to take…

Dynamic optimization of chemical processes using ant colony framework.

PubMed

Rajesh, J; Gupta, K; Kusumakar, H S; Jayaraman, V K; Kulkarni, B D

2001-11-01

Ant colony framework is illustrated by considering dynamic optimization of six important bench marking examples. This new computational tool is simple to implement and can tackle problems with state as well as terminal constraints in a straightforward fashion. It requires fewer grid points to reach the global optimum at relatively very low computational effort. The examples with varying degree of complexities, analyzed here, illustrate its potential for solving a large class of process optimization problems in chemical engineering.

A temporal-spatial postprocessing model for probabilistic run-off forecast. With a case study from Ulla-Førre with five catchments and ten lead times

NASA Astrophysics Data System (ADS)

Engeland, K.; Steinsland, I.

2012-04-01

This work is driven by the needs of next generation short term optimization methodology for hydro power production. Stochastic optimization are about to be introduced; i.e. optimizing when available resources (water) and utility (prices) are uncertain. In this paper we focus on the available resources, i.e. water, where uncertainty mainly comes from uncertainty in future runoff. When optimizing a water system all catchments and several lead times have to be considered simultaneously. Depending on the system of hydropower reservoirs, it might be a set of headwater catchments, a system of upstream /downstream reservoirs where water used from one catchment /dam arrives in a lower catchment maybe days later, or a combination of both. The aim of this paper is therefore to construct a simultaneous probabilistic forecast for several catchments and lead times, i.e. to provide a predictive distribution for the forecasts. Stochastic optimization methods need samples/ensembles of run-off forecasts as input. Hence, it should also be possible to sample from our probabilistic forecast. A post-processing approach is taken, and an error model based on Box- Cox transformation, power transform and a temporal-spatial copula model is used. It accounts for both between catchment and between lead time dependencies. In operational use it is strait forward to sample run-off ensembles from this models that inherits the catchment and lead time dependencies. The methodology is tested and demonstrated in the Ulla-Førre river system, and simultaneous probabilistic forecasts for five catchments and ten lead times are constructed. The methodology has enough flexibility to model operationally important features in this case study such as hetroscadasety, lead-time varying temporal dependency and lead-time varying inter-catchment dependency. Our model is evaluated using CRPS for marginal predictive distributions and energy score for joint predictive distribution. It is tested against deterministic run-off forecast, climatology forecast and a persistent forecast, and is found to be the better probabilistic forecast for lead time grater then two. From an operational point of view the results are interesting as the between catchment dependency gets stronger with longer lead-times.

Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm.

PubMed

Pickett, Stephen D; Green, Darren V S; Hunt, David L; Pardoe, David A; Hughes, Ian

2011-01-13

Traditional lead optimization projects involve long synthesis and testing cycles, favoring extensive structure-activity relationship (SAR) analysis and molecular design steps, in an attempt to limit the number of cycles that a project must run to optimize a development candidate. Microfluidic-based chemistry and biology platforms, with cycle times of minutes rather than weeks, lend themselves to unattended autonomous operation. The bottleneck in the lead optimization process is therefore shifted from synthesis or test to SAR analysis and design. As such, the way is open to an algorithm-directed process, without the need for detailed user data analysis. Here, we present results of two synthesis and screening experiments, undertaken using traditional methodology, to validate a genetic algorithm optimization process for future application to a microfluidic system. The algorithm has several novel features that are important for the intended application. For example, it is robust to missing data and can suggest compounds for retest to ensure reliability of optimization. The algorithm is first validated on a retrospective analysis of an in-house library embedded in a larger virtual array of presumed inactive compounds. In a second, prospective experiment with MMP-12 as the target protein, 140 compounds are submitted for synthesis over 10 cycles of optimization. Comparison is made to the results from the full combinatorial library that was synthesized manually and tested independently. The results show that compounds selected by the algorithm are heavily biased toward the more active regions of the library, while the algorithm is robust to both missing data (compounds where synthesis failed) and inactive compounds. This publication places the full combinatorial library and biological data into the public domain with the intention of advancing research into algorithm-directed lead optimization methods.

Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm

PubMed Central

2010-01-01

Traditional lead optimization projects involve long synthesis and testing cycles, favoring extensive structure−activity relationship (SAR) analysis and molecular design steps, in an attempt to limit the number of cycles that a project must run to optimize a development candidate. Microfluidic-based chemistry and biology platforms, with cycle times of minutes rather than weeks, lend themselves to unattended autonomous operation. The bottleneck in the lead optimization process is therefore shifted from synthesis or test to SAR analysis and design. As such, the way is open to an algorithm-directed process, without the need for detailed user data analysis. Here, we present results of two synthesis and screening experiments, undertaken using traditional methodology, to validate a genetic algorithm optimization process for future application to a microfluidic system. The algorithm has several novel features that are important for the intended application. For example, it is robust to missing data and can suggest compounds for retest to ensure reliability of optimization. The algorithm is first validated on a retrospective analysis of an in-house library embedded in a larger virtual array of presumed inactive compounds. In a second, prospective experiment with MMP-12 as the target protein, 140 compounds are submitted for synthesis over 10 cycles of optimization. Comparison is made to the results from the full combinatorial library that was synthesized manually and tested independently. The results show that compounds selected by the algorithm are heavily biased toward the more active regions of the library, while the algorithm is robust to both missing data (compounds where synthesis failed) and inactive compounds. This publication places the full combinatorial library and biological data into the public domain with the intention of advancing research into algorithm-directed lead optimization methods. PMID:24900251

Engineering another class of anti-tubercular lead: Hit to lead optimization of an intriguing class of gyrase ATPase inhibitors.

PubMed

Jeankumar, Variam Ullas; Reshma, Rudraraju Srilakshmi; Vats, Rahul; Janupally, Renuka; Saxena, Shalini; Yogeeswari, Perumal; Sriram, Dharmarajan

2016-10-21

A structure based medium throughput virtual screening campaign of BITS-Pilani in house chemical library to identify novel binders of Mycobacterium tuberculosis gyrase ATPase domain led to the discovery of a quinoline scaffold. Further medicinal chemistry explorations on the right hand core of the early hit, engendered a potent lead demonstrating superior efficacy both in the enzyme and whole cell screening assay. The binding affinity shown at the enzyme level was further corroborated by biophysical characterization techniques. Early pharmacokinetic evaluation of the optimized analogue was encouraging and provides interesting potential for further optimization. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Outsourcing lead optimization: the eye of the storm.

PubMed

Clark, David E

2011-02-01

This article is the third in a series examining the evolution of the market for outsourced lead optimization services and covers developments from late 2006 to the present. Following an analysis of the significant events that have impacted the marketplace in recent years, a brief survey of the growing number of companies offering lead optimization services is presented. Subsequently, three notable trends that can be perceived in this highly dynamic field are discussed: the continuing rise of outsourcing companies in Asia and Eastern Europe, the increase in deals with not-for-profit organizations and, finally, the emergence of a variety of business models under which outsourced work is conducted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Next Generation Wind Turbine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheraghi, S. Hossein; Madden, Frank

The goal of this collaborative effort between Western New England University's College of Engineering and FloDesign Wind Turbine (FDWT) Corporation to wok on a novel areodynamic concept that could potentially lead to the next generation of wind turbines. Analytical studies and early scale model tests of FDWT's Mixer/Ejector Wind Turbine (MEWT) concept, which exploits jet-age advanced fluid dynamics, indicate that the concept has the potential to significantly reduce the cost of electricity over conventional Horizontal Axis Wind Turbines while reducing land usage. This project involved the design, fabrication, and wind tunnel testing of components of MEWT to provide the researchmore » and engineering data necessary to validate the design iterations and optimize system performance. Based on these tests, a scale model prototype called Briza was designed, fabricated, installed and tested on a portable tower to investigate and improve the design system in real world conditions. The results of these scale prototype efforts were very promising and have contributed significantly to FDWT's ongoing development of a product scale wind turbine for deployment in multiple locations around the U.S. This research was mutually beneficial to Western New England University, FDWT, and the DOE by utilizing over 30 student interns and a number of faculty in all efforts. It brought real-world wind turbine experience into the classroom to further enhance the Green Engineering Program at WNEU. It also provided on-the-job training to many students, improving their future employment opportunities, while also providing valuable information to further advance FDWT's mixer-ejector wind turbine technology, creating opportunities for future project innovation and job creation.« less

The pig genome project has plenty to squeal about.

PubMed

Fan, B; Gorbach, D M; Rothschild, M F

2011-01-01

Significant progress on pig genetics and genomics research has been witnessed in recent years due to the integration of advanced molecular biology techniques, bioinformatics and computational biology, and the collaborative efforts of researchers in the swine genomics community. Progress on expanding the linkage map has slowed down, but the efforts have created a higher-resolution physical map integrating the clone map and BAC end sequence. The number of QTL mapped is still growing and most of the updated QTL mapping results are available through PigQTLdb. Additionally, expression studies using high-throughput microarrays and other gene expression techniques have made significant advancements. The number of identified non-coding RNAs is rapidly increasing and their exact regulatory functions are being explored. A publishable draft (build 10) of the swine genome sequence was available for the pig genomics community by the end of December 2010. Build 9 of the porcine genome is currently available with Ensembl annotation; manual annotation is ongoing. These drafts provide useful tools for such endeavors as comparative genomics and SNP scans for fine QTL mapping. A recent community-wide effort to create a 60K porcine SNP chip has greatly facilitated whole-genome association analyses, haplotype block construction and linkage disequilibrium mapping, which can contribute to whole-genome selection. The future 'systems biology' that integrates and optimizes the information from all research levels can enhance the pig community's understanding of the full complexity of the porcine genome. These recent technological advances and where they may lead are reviewed. Copyright © 2011 S. Karger AG, Basel.

Site Protection Efforts at the AURA Observatory in Chile

NASA Astrophysics Data System (ADS)

Smith, R. Chris; Smith, Malcolm G.; Sanhueza, Pedro

2015-08-01

The AURA Observatory (AURA-O) was the first of the major international observatories to be established in northern Chile to exploit the optimal astronomical conditions available there. The site was originally established in 1962 to host the Cerro Tololo Inter-American Observatory (CTIO). It now hosts more than 20 operational telescopes, including some of the leading U.S. and international astronomical facilities in the southern hemisphere, such as the Blanco 4m telescope on Cerro Tololo and the Gemini-South and SOAR telescopes on Cerro Pachón. Construction of the next generation facility, the Large Synoptic Survey Telescope (LSST), has recently begun on Cerro Pachón, while additional smaller telescopes continue to be added to the complement on Cerro Tololo.While the site has become a major platform for international astronomical facilities over the last 50 years, development in the region has led to an ever-increasing threat of light pollution around the site. AURA-O has worked closely with local, regional, and national authorities and institutions (in particular with the Chilean Ministries of Environment and Foreign Relations) in an effort to protect the site so that future generations of telescopes, as well as future generations of Chileans, can benefit from the dark skies in the region. We will summarize our efforts over the past 15 years to highlight the importance of dark sky protection through education and public outreach as well as through more recent promotion of IDA certifications in the region and support for the World Heritage initiatives described by others in this conference.

Human factors aspects of lightplane safety.

DOT National Transportation Integrated Search

1963-12-01

This paper attempts to relate aircraft accident investigation and aeromedical research efforts for the purpose of clarifying research needs. Such efforts ultimately can lead to a reduction on lightplane accidents, injuries, and fatalities. Recent sta...

Development of Long-Pulse Heating and Current Drive Actuators and Operational Techniques Compatible with a High-Z Divertor and First Wall

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Guiding

Accurate measurement of the edge electron density profile is essential to optimizing antenna coupling and assessment of impurity contamination in studying long-pulse plasma heating and current drive in fusion devices. Measurement of the edge density profile has been demonstrated on the US fusion devices such as C-Mod, DIII-D, and TFTR amongst many devices, and has been used for RF loading and impurity modeling calculations for many years. University of Science and Technology of China (USTC) has recently installed a density profile reflectometer system on the EAST fusion device at the Institute of Plasma Physics, Chinese Academy of Sciences in Chinamore » based on the University of California Los Angeles (UCLA)-designed reflectometer system on the DIII-D fusion device at General Atomics Company in San Diego, California. UCLA has been working with USTC to optimize the existing microwave antenna, waveguide system, microwave electronics, and data analysis to produce reliable edge density profiles. During the past budget year, progress has been made in all three major areas: effort to achieve reliable system operations under various EAST operational conditions, effort to optimize system performance, and effort to provide quality density profiles into EAST’s database routinely.« less

Optimization of a Small Tropomyosin-related Kinase B (TrkB) Agonist 7,8-Dihydroxyflavone Active in Mouse Models of Depression

PubMed Central

Liu, Xia; Chan, Chi-Bun; Qi, Qi; Xiao, Ge; Luo, Hongbo R.; He, Xiaolin; Ye, Keqiang

2012-01-01

Structure-activity relationship study shows that the catechol group in 7,8-dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for the agonistic activity. To improve the poor pharmacokinetic profiles intrinsic to catechol-containing molecules and elevate the agonistic effect of the lead compound, we initiated the lead optimization campaign by synthesizing various bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4′-(pyrrolidin-1-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses the enhanced TrkB stimulatory activity. Chronic oral administration of this compound significantly reduces the immobility in forced swim test and tail suspension test, two classical antidepressant behavioral animal models, which is accompanied by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET studies demonstrate that this compound possesses the improved features compared to the previous lead compound. Hence, this optimized compound may act as a promising lead candidate for in-depth drug development for treating various neurological disorders including depression. PMID:22984948

Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.

PubMed

Gilson, Paul R; Tan, Cyrus; Jarman, Kate E; Lowes, Kym N; Curtis, Joan M; Nguyen, William; Di Rago, Adrian E; Bullen, Hayley E; Prinz, Boris; Duffy, Sandra; Baell, Jonathan B; Hutton, Craig A; Jousset Subroux, Helene; Crabb, Brendan S; Avery, Vicky M; Cowman, Alan F; Sleebs, Brad E

2017-02-09

Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites comparable to the known antimalarials, chloroquine and mefloquine. During the optimization process, we defined the functionality necessary for activity and improved in vitro metabolism and solubility. The resultant lead compounds possess potent activity against a multidrug resistant strain of P. falciparum and arrest parasites at the ring phase of the asexual stage and also gametocytogensis. Finally, we show that the lead compounds are orally efficacious in a 4 day murine model of malaria disease burden.

Predictive Cache Modeling and Analysis

DTIC Science & Technology

2011-11-01

metaheuristic /bin-packing algorithm to optimize task placement based on task communication characterization. Our previous work on task allocation showed...Cache Miss Minimization Technology To efficiently explore combinations and discover nearly-optimal task-assignment algorithms , we extended to our...it was possible to use our algorithmic techniques to decrease network bandwidth consumption by ~25%. In this effort, we adapted these existing

Creating Optimal Learning Environments through Invitational Education: An Alternative to Control Oriented School Reform

ERIC Educational Resources Information Center

Fretz, Joan R.

2015-01-01

Understanding what motivates people to put forth effort, persevere in the face of obstacles, and choose their behaviors is key to creating an optimal learning environment--the type of school that policy makers desire, but are unknowingly sabotaging (Dweck, 2000). Many motivation and self-concept theories provide important insight with regard to…

Factors in the intestinal absorption of oral cholecystopaques.

PubMed

Amberg, J R; Thompson, W M; Golberger, L; Williamson, S; Alexander, R; Bates, M

1980-01-01

Interest in the pharmacokinetics of cholecystopaques initially centered on transport from blood to bile. The data obtained in this effort have been valuable and have shown that the maximal iodine concentration achievable in the bile is quite similar for all of the currently available compounds. This concentration is, of course, dose dependent. the transport of contrast material from the bowel to the blood has been shown to be quite variable. Considerable progress was made in understanding this. The tremendous differences in absorption of iopanoic acid depending upon the pH of the administered solution was an initial revelation. The development of the concept that there is a water layer through which the cholecystopaque must pass before reaching the lipid membrane of the intestinal cell has added clarity to understanding the difference in absorption between water-soluble and water-insoluble cholecystopaques. A complete knowledge of what might enhance or inhibit absorption is not known. There is beginning to be an understanding of how intestinal dose relates to plasma levels. This should lead to an optimal dose-timing scheme for each cholecystopaque. The basic assumption is that the highest iodine concentration in the gallbladder leads to the most accurate cholecystography. If this is true, the gallbladder needs to be offered bile at the maximum concentrations during the period preceding filming. To accomplish this, the appropriate plasma level necessary for maximum excretion is needed. Experimental data suggest that our current clinical methods in regard to dose and dose timing need revision to optimize cholecystography. This revision needs to take place with a careful look at toxicity. Accepting the present premise that oral cholecystography can be improved, perhaps without a significant increase in morbidity, a fundamental question to be asked is: is it worth it?

Strategic Plan for the Elimination of Childhood Lead Poisoning.

ERIC Educational Resources Information Center

Binder, Sue; Falk, Henry

This document describes an agenda for the first 5 years of a comprehensive effort to eliminate childhood lead poisoning. In 1984, between 3 and 4 million children were estimated to have blood lead levels high enough to adversely affect intelligence and behavior. Lead in the home environment, especially lead-based paint, is the major source of lead…

Optimality study of a gust alleviation system for light wing-loading STOL aircraft

NASA Technical Reports Server (NTRS)

Komoda, M.

1976-01-01

An analytical study was made of an optimal gust alleviation system that employs a vertical gust sensor mounted forward of an aircraft's center of gravity. Frequency domain optimization techniques were employed to synthesize the optimal filters that process the corrective signals to the flaps and elevator actuators. Special attention was given to evaluating the effectiveness of lead time, that is, the time by which relative wind sensor information should lead the actual encounter of the gust. The resulting filter is expressed as an implicit function of the prescribed control cost. A numerical example for a light wing loading STOL aircraft is included in which the optimal trade-off between performance and control cost is systematically studied.

Finding the optimal shape of the leading-and-trailing car of a high-speed train using design-by-morphing

NASA Astrophysics Data System (ADS)

Oh, Sahuck; Jiang, Chung-Hsiang; Jiang, Chiyu; Marcus, Philip S.

2017-10-01

We present a new, general design method, called design-by-morphing for an object whose performance is determined by its shape due to hydrodynamic, aerodynamic, structural, or thermal requirements. To illustrate the method, we design a new leading-and-trailing car of a train by morphing existing, baseline leading-and-trailing cars to minimize the drag. In design-by-morphing, the morphing is done by representing the shapes with polygonal meshes and spectrally with a truncated series of spherical harmonics. The optimal design is found by computing the optimal weights of each of the baseline shapes so that the morphed shape has minimum drag. As a result of optimization, we found that with only two baseline trains that mimic current high-speed trains with low drag that the drag of the optimal train is reduced by 8.04% with respect to the baseline train with the smaller drag. When we repeat the optimization by adding a third baseline train that under-performs compared to the other baseline train, the drag of the new optimal train is reduced by 13.46% . This finding shows that bad examples of design are as useful as good examples in determining an optimal design. We show that design-by-morphing can be extended to many engineering problems in which the performance of an object depends on its shape.

Finding the optimal shape of the leading-and-trailing car of a high-speed train using design-by-morphing

NASA Astrophysics Data System (ADS)

Oh, Sahuck; Jiang, Chung-Hsiang; Jiang, Chiyu; Marcus, Philip S.

2018-07-01

We present a new, general design method, called design-by-morphing for an object whose performance is determined by its shape due to hydrodynamic, aerodynamic, structural, or thermal requirements. To illustrate the method, we design a new leading-and-trailing car of a train by morphing existing, baseline leading-and-trailing cars to minimize the drag. In design-by-morphing, the morphing is done by representing the shapes with polygonal meshes and spectrally with a truncated series of spherical harmonics. The optimal design is found by computing the optimal weights of each of the baseline shapes so that the morphed shape has minimum drag. As a result of optimization, we found that with only two baseline trains that mimic current high-speed trains with low drag that the drag of the optimal train is reduced by 8.04% with respect to the baseline train with the smaller drag. When we repeat the optimization by adding a third baseline train that under-performs compared to the other baseline train, the drag of the new optimal train is reduced by 13.46%. This finding shows that bad examples of design are as useful as good examples in determining an optimal design. We show that design-by-morphing can be extended to many engineering problems in which the performance of an object depends on its shape.

Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry.

PubMed

Planatscher, Hannes; Supper, Jochen; Poetz, Oliver; Stoll, Dieter; Joos, Thomas; Templin, Markus F; Zell, Andreas

2010-06-25

Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency. We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties. For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.

Type 2 diabetes: epidemiologic trends, evolving pathogenetic [corrected] concepts, and recent changes in therapeutic approach.

PubMed

Rizvi, Ali A

2004-11-01

The prevalence of type 2 diabetes has assumed epidemic dimensions. Children are now vulnerable to a disease that was once the exclusive domain of adulthood. Increased body weight and sedentary behavior accelerate insulin resistance and beta-cell dysfunction, leading to the clinical manifestation of hyperglycemia. Other cardiovascular risk factors tend to cluster in this milieu, setting the stage for vastly increased macrovascular morbidity. Many more people have impaired glucose tolerance ('prediabetes'). They are not only at risk for frank diabetes but also for the recently recognized entity of 'metabolic syndrome,' which is further characterized by hypertension, dyslipidemia, and central adiposity. A multifactorial approach addressing these aspects in addition to intensive glycemic control is the most efficacious therapy, optimally achieved through a team effort comprising the clinician, diabetes nurse, dietitian, and other professionals. Early use of oral-agent combinations is gaining favor. Insulin is best utilized in a basal-bolus fashion to manage both fasting and postprandial glycemia, delivered with multiple-dose injections or continuously via the pump. In hospitalized patients, good diabetic control reduces mortality. Finally, recent trials show that optimal weight maintenance and regular exercise can prevent or delay type 2 diabetes. Such information can serve as the foundation for large-scale preventive endeavors at the community level.

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.

PubMed

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2017-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo . However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa , which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo .

Optimizing the chances of success in the search for epigenetic biomarkers: Embracing genetic variation.

PubMed

Philibert, Robert; Glatt, Stephen J

2017-09-01

The emphasis on clinical translation in biomedical research continues to grow. This focus has been particularly notable in those investigators using epigenetic approaches to decipher the biology of complex behavioral disorders. As a result of these efforts, reproducible findings for several disorders, such as smoking, have been generated, giving rise to hopes that biomarkers for other behavioral illnesses would be forthcoming. Unfortunately, that biomedical cornucopia has not yet materialized. In this editorial, we review progress to date and discuss barriers to generating epigenetic biomarkers for complex behavioral disorders. We highlight the need to incorporate information on genetic variation and develop more powerful bioinformatics tools in order to optimize the likelihood of success. We emphasize that searches should focus on clearly defined, readily distinguishable behavioral constructs and suggest that some well-intentioned methods, such as correction for cellular heterogeneity, may actually impede the identification of clinically relevant biomarkers in peripheral blood. Finally, we describe how the understanding created by the development of these biomarkers may lead to more valid animal models of neuropsychiatric illness. We conclude that the prospects for epigenetic biomarkers for complex disorders are bright, but emphasize that the journey to the clinical implementation of these findings will be a slow, iterative process. © 2017 Wiley Periodicals, Inc.

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics

PubMed Central

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2018-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo. However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa, which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo. PMID:29375551

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir.

PubMed

Riley, James L; Montaner, Luis J

2017-03-15

Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Optimal control of the orientation and alignment of an asymmetric-top molecule with terahertz and laser pulses

NASA Astrophysics Data System (ADS)

Coudert, L. H.

2018-03-01

Quantum optimal control theory is applied to determine numerically the terahertz and nonresonant laser pulses leading, respectively, to the highest degree of orientation and alignment of the asymmetric-top H2S molecule. The optimized terahertz pulses retrieved for temperatures of zero and 50 K lead after 50 ps to an orientation with ⟨ΦZx⟩ = 0.959 73 and ⟨⟨ΦZx⟩⟩ = 0.742 30, respectively. For the zero temperature, the orientation is close to its maximum theoretical value; for the higher temperature, it is below the maximum theoretical value. The mechanism by which the terahertz pulse populates high lying rotational levels is elucidated. The 5 ps long optimized laser pulse calculated for a zero temperature leads to an alignment with ⟨ΦZy 2 ⟩ =0.944 16 and consists of several kick pulses with a duration of ≈0.1 ps. It is found that the timing of these kick pulses is such that it leads to an increase of the rotational energy of the molecule. The optimized laser pulse retrieved for a temperature of 20 K is 6 ps long and yields a lower alignment with ⟨⟨ΦZy 2 ⟩ ⟩ =0.717 20 .

Growth hormone-insulin-like growth factor-1 and inflammatory response to a single exercise bout in children and adolescents.

PubMed

Nemet, Dan; Eliakim, Alon

2010-01-01

Physical activity plays an important role in tissue anabolism, growth and development, but the mechanisms that link patterns of exercise with tissue anabolism are not completely understood. The effectiveness of physical training depends on the training load and on the individual ability to tolerate it, and an imbalance between the two may lead to under or over-training. Therefore, many efforts have been made to find objective parameters to quantify the balance between training load and the athlete's tolerance. One of the unique features of exercise is that it leads to a simultaneous increase of antagonistic mediators. On the one hand, exercise stimulates anabolic components of the growth hormone (GH) → IGF-1 (insulin-like growth factor-1) axis. On the other hand, exercise elevates catabolic pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α). This emphasizes probably the importance of optimal adaptation to exercise in particularly during adolescence. The very fine balance between the anabolic and inflammatory/catabolic response to exercise will determine the effectiveness of exercise training and the health consequences of exercise. If the anabolic response is stronger, exercise will probably lead ultimately to increased muscle mass and improved fitness. A greater catabolic response, in particularly if persists for long duration, may lead to overtraining. Therefore, changes in the anabolic-catabolic hormonal balance and in circulating inflammatory cytokines can be used by adolescent athletes and/or their coaches to gauge the training intensity in individual and team sports. Copyright © 2010 S. Karger AG, Basel.

The Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug Targets

PubMed Central

Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

2015-01-01

The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal. PMID:25635061

How to achieve benefit from mission-oriented research: lessons from the U.S. Department of Agriculture and the Naval Research Laboratory

NASA Astrophysics Data System (ADS)

Logar, N. J.

2006-12-01

Does the research performed by government mission agencies contribute to improved decision-making? Climate research within the U.S. Department of Agriculture (USDA) has the stated goal of providing "optimal benefit" to decision makers on all levels, and the meteorology division of Department of Defense's Naval Research Laboratory promises research directed towards application. Assuming that research can lead to benefit for decision makers with minimal guidance can lead to irrelevance, wasted effort, and missed opportunities. Moving beyond the assumption leads to critical consideration of processes creating climate and meteorological science. I report the results of contextual mapping, of research on decision processes, and of interviews with agency scientists and users of science to evaluate their science regimes. In the case of the USDA scientists do target stakeholders through formal and informal mechanisms, but much of the science does not find use due to institutional constraints, political considerations, and disciplinary inertia. The research results will provide options for closing these policy gaps, such as higher-level stakeholder interaction and better representation of diverse interests. I apply the economic concept of supply and demand to describe where supply of science provides decision support that matches user demand, and where science policies might miss opportunities or mischaracterize research as useful to a specific user. This analysis leads to increased understanding of how factors such as the definition of scientific problems, hierarchies in science decision-making structures, quality control mechanisms beyond peer review, distribution of participants in the knowledge production enterprise, and social accountability guide the process of producing useful information.

Advanced methods of structural and trajectory analysis for transport aircraft

NASA Technical Reports Server (NTRS)

Ardema, Mark D.

1995-01-01

This report summarizes the efforts in two areas: (1) development of advanced methods of structural weight estimation, and (2) development of advanced methods of trajectory optimization. The majority of the effort was spent in the structural weight area. A draft of 'Analytical Fuselage and Wing Weight Estimation of Transport Aircraft', resulting from this research, is included as an appendix.

A Tale of Three Cities: Piloting a Measure of Effort and Comfort Levels within Town-Gown Relationships

ERIC Educational Resources Information Center

Gavazzi, Stephen M.; Fox, Michael

2015-01-01

This article extends the argument that scholarship on marriages and families provides invaluable insights into town-gown relationships. First, a four-square matrix constructed from the twin dimensions of effort and comfort levels is used to describe a typology of campus and community associations. Next the construction of the Optimal College Town…

A model for the optimization of the detection and eradication of isolated gypsy moth colonies

Treesearch

Tiffany L. Bogich; Andrew Liebhold; Katriona Shea

2007-01-01

Biological invasions of pest species pose a threat to the stability of ecosystems, both natural and managed (Liebhold et al. 1995, Shogren and Tschirhart 2005). Considerable effort is expended by national and local governments on excluding alien species via detection and eradication of invading populations, but these efforts are not necessarily designed in the most...

Demographics of reintroduced populations: estimation, modeling, and decision analysis

USGS Publications Warehouse

Converse, Sarah J.; Moore, Clinton T.; Armstrong, Doug P.

2013-01-01

Reintroduction can be necessary for recovering populations of threatened species. However, the success of reintroduction efforts has been poorer than many biologists and managers would hope. To increase the benefits gained from reintroduction, management decision making should be couched within formal decision-analytic frameworks. Decision analysis is a structured process for informing decision making that recognizes that all decisions have a set of components—objectives, alternative management actions, predictive models, and optimization methods—that can be decomposed, analyzed, and recomposed to facilitate optimal, transparent decisions. Because the outcome of interest in reintroduction efforts is typically population viability or related metrics, models used in decision analysis efforts for reintroductions will need to include population models. In this special section of the Journal of Wildlife Management, we highlight examples of the construction and use of models for informing management decisions in reintroduced populations. In this introductory contribution, we review concepts in decision analysis, population modeling for analysis of decisions in reintroduction settings, and future directions. Increased use of formal decision analysis, including adaptive management, has great potential to inform reintroduction efforts. Adopting these practices will require close collaboration among managers, decision analysts, population modelers, and field biologists.

Correction method for stripe nonuniformity.

PubMed

Qian, Weixian; Chen, Qian; Gu, Guohua; Guan, Zhiqiang

2010-04-01

Stripe nonuniformity is very typical in line infrared focal plane arrays (IR-FPA) and uncooled staring IR-FPA. In this paper, the mechanism of the stripe nonuniformity is analyzed, and the gray-scale co-occurrence matrix theory and optimization theory are studied. Through these efforts, the stripe nonuniformity correction problem is translated into the optimization problem. The goal of the optimization is to find the minimal energy of the image's line gradient. After solving the constrained nonlinear optimization equation, the parameters of the stripe nonuniformity correction are obtained and the stripe nonuniformity correction is achieved. The experiments indicate that this algorithm is effective and efficient.

Further efforts in optimizing nonlinear optical molecules

NASA Astrophysics Data System (ADS)

Dirk, Carl W.; Caballero, Noel; Tan, Alarice; Kuzyk, Mark G.; Cheng, Lap-Tak A.; Katz, Howard E.; Shilling, Marcia; King, Lori A.

1993-02-01

We summarize some of our past work in the field on optimizing molecules for second order and third order nonlinear optical applications. We also present some previously unpublished results suggesting a particular optimization of the popular cyano- and nitrovinyl acceptor groups. In addition we provide some new quadratic electro-optic results which serve to further verify our choice of a restricted three-level model suitable for optimizing third order nonlinearities in molecules. Finally we present a new squarylium dye with a large third order optical nonlinearity (-9.5 X 10-34 cm7/esu2; EFISH (gamma) at 1906 nm).

Composite fuselage crown panel manufacturing technology

NASA Technical Reports Server (NTRS)

Willden, Kurtis; Metschan, S.; Grant, C.; Brown, T.

1992-01-01

Commercial fuselage structures contain significant challenges in attempting to save manufacturing costs with advanced composite technology. Assembly issues, material costs, and fabrication of elements with complex geometry are each expected to drive the cost of composite fuselage structures. Boeing's efforts under the NASA ACT program have pursued key technologies for low-cost, large crown panel fabrication. An intricate bond panel design and manufacturing concepts were selected based on the efforts of the Design Build Team (DBT). The manufacturing processes selected for the intricate bond design include multiple large panel fabrication with the Advanced Tow Placement (ATP) process, innovative cure tooling concepts, resin transfer molding of long fuselage frames, and utilization of low-cost material forms. The process optimization for final design/manufacturing configuration included factory simulations and hardware demonstrations. These efforts and other optimization tasks were instrumental in reducing cost by 18 percent and weight by 45 percent relative to an aluminum baseline. The qualitative and quantitative results of the manufacturing demonstrations were used to assess manufacturing risks and technology readiness.

Evaluation of Frameworks for HSCT Design Optimization

NASA Technical Reports Server (NTRS)

Krishnan, Ramki

1998-01-01

This report is an evaluation of engineering frameworks that could be used to augment, supplement, or replace the existing FIDO 3.5 (Framework for Interdisciplinary Design and Optimization Version 3.5) framework. The report begins with the motivation for this effort, followed by a description of an "ideal" multidisciplinary design and optimization (MDO) framework. The discussion then turns to how each candidate framework stacks up against this ideal. This report ends with recommendations as to the "best" frameworks that should be down-selected for detailed review.

The Preventive Control of a Dengue Disease Using Pontryagin Minimum Principal

NASA Astrophysics Data System (ADS)

Ratna Sari, Eminugroho; Insani, Nur; Lestari, Dwi

2017-06-01

Behaviour analysis for host-vector model without control of dengue disease is based on the value of basic reproduction number obtained using next generation matrices. Furthermore, the model is further developed involving a preventive control to minimize the contact between host and vector. The purpose is to obtain an optimal preventive strategy with minimal cost. The Pontryagin Minimum Principal is used to find the optimal control analytically. The derived optimality model is then solved numerically to investigate control effort to reduce infected class.

Use of High Fidelity Methods in Multidisciplinary Optimization-A Preliminary Survey

NASA Technical Reports Server (NTRS)

Guruswamy, Guru P.; Kwak, Dochan (Technical Monitor)

2002-01-01

Multidisciplinary optimization is a key element of design process. To date multidiscipline optimization methods that use low fidelity methods are well advanced. Optimization methods based on simple linear aerodynamic equations and plate structural equations have been applied to complex aerospace configurations. However, use of high fidelity methods such as the Euler/ Navier-Stokes for fluids and 3-D (three dimensional) finite elements for structures has begun recently. As an activity of Multidiscipline Design Optimization Technical Committee (MDO TC) of AIAA (American Institute of Aeronautics and Astronautics), an effort was initiated to assess the status of the use of high fidelity methods in multidisciplinary optimization. Contributions were solicited through the members MDO TC committee. This paper provides a summary of that survey.

[Parameters optimization and cleaning efficiency evaluation of attrition scrubbing remediation of Pb-contaminated soil].

PubMed

Yang, Wen; Huang, Jin-lou; Peng, Hui-qing; Li, Si-tuo

2013-09-01

Attrition scrubbing was used to remediate lead contaminated-site soil, and the main purpose was to remove fine particles and lead contaminants from the surface of sand. The optimal parameters of attrition scrubbing were determined by orthogonal experiment, and three soil samples with different lead concentration were subjected to attrition scrubbing experiments. The results showed that the optimal scrubbing parameters were: a solid ratio of 70% dry matter, a temperature of 25 degrees C, an attrition time of 30 min, and an attrition speed of 1200 r x min(-1). Before attrition scrubbing, the screening and analysis of soil showed that in all three soil samples, lead was mainly enriched on sand and fine particles, and the distribution of lead was highly correlated to the organic matter. After attrition scrubbing, the washing efficiency of the original state lead contaminated sand soil in triplicates was 67.61%, 31.71% and 41.01%, respectively, which indicates that attrition scrubbing can remove part of the fine soil and lead contaminants from the surface of sand, to accomplish the purpose of pollutants enrichment. Scanning electron microscopy (SEM) analysis showed that the sand surface became smooth after attrition scrubbing. The results above show that attrition scrubbing has a good washing effect for the remediation of lead contaminated sand soil.

A Primer on Population Health Management and Its Perioperative Application.

PubMed

Boudreaux, Arthur M; Vetter, Thomas R

2016-07-01

The movement toward value-based payment models, driven by governmental policies, federal statutes, and market forces, is propelling the importance of effectively managing the health of populations to the forefront in the United States and other developed countries. However, for many anesthesiologists, population health management is a new or even foreign concept. A primer on population health management and its potential perioperative application is thus presented here. Although it certainly continues to evolve, population health management can be broadly defined as the specific policies, programs, and interventions directed at optimizing population health. The Population Health Alliance has created a particularly cogent conceptual framework and interconnected and very useful population health process model, which together identify the key components of population health and its management. Population health management provides a useful rationale for patients, providers, payers, and policymakers to move collectively away from the traditional system of individual, siloed providers to a more integrated, coordinated, team-based approach, thus creating a holistic view of the patient population. The goal of population health management is to keep the targeted patient population as healthy as possible, thus minimizing the need for costly interventions such as emergency department visits, acute hospitalizations, laboratory testing and imaging, and diagnostic and therapeutic procedures. Population health management strategies are increasingly more important to leaders of health care systems as the health of populations for which they care, especially in a strong cost risk-sharing environment, must be optimized. Most population health management efforts rely on a patient-centric team approach, coordination of care, effective communication, robust outcomes data analysis, and continuous quality improvement. Anesthesiologists have an opportunity to help lead these efforts in concert with their surgical and nursing colleagues. The Triple Aim of Healthcare includes (1) improving the patient experience of care (including quality and satisfaction); (2) improving the health of populations; and (3) reducing per-capita costs of care. The Perioperative Surgical Home essentially seeks to transform perioperative care by achieving the Triple Aim, including improving the health of the surgical population. Many health care delivery systems and many clinicians (including anesthesiologists) are just beginning their population health management journeys. However, by doing so, they are preparing to navigate a much greater risk-sharing landscape, where these efforts can create greater financial stability by preventing major financial loss. Anesthesiologists can and should be leaders in this effort to add value by improving the comprehensive continuum of care of our patients.

Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors.

PubMed

Kuhnert, Maren; Köster, Helene; Bartholomäus, Ruben; Park, Ah Young; Shahim, Amir; Heine, Andreas; Steuber, Holger; Klebe, Gerhard; Diederich, Wibke E

2015-02-23

Successful lead optimization in structure-based drug discovery depends on the correct deduction and interpretation of the underlying structure-activity relationships (SAR) to facilitate efficient decision-making on the next candidates to be synthesized. Consequently, the question arises, how frequently a binding mode (re)-validation is required, to ensure not to be misled by invalid assumptions on the binding geometry. We present an example in which minor chemical modifications within one inhibitor series lead to surprisingly different binding modes. X-ray structure determination of eight inhibitors derived from one core scaffold resulted in four different binding modes in the aspartic protease endothiapepsin, a well-established surrogate for e.g. renin and β-secretase. In addition, we suggest an empirical metrics that might serve as an indicator during lead optimization to qualify compounds as candidates for structural revalidation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimal Inspection of Imports to Prevent Invasive Pest Introduction.

PubMed

Chen, Cuicui; Epanchin-Niell, Rebecca S; Haight, Robert G

2018-03-01

The United States imports more than 1 billion live plants annually-an important and growing pathway for introduction of damaging nonnative invertebrates and pathogens. Inspection of imports is one safeguard for reducing pest introductions, but capacity constraints limit inspection effort. We develop an optimal sampling strategy to minimize the costs of pest introductions from trade by posing inspection as an acceptance sampling problem that incorporates key features of the decision context, including (i) simultaneous inspection of many heterogeneous lots, (ii) a lot-specific sampling effort, (iii) a budget constraint that limits total inspection effort, (iv) inspection error, and (v) an objective of minimizing cost from accepted defective units. We derive a formula for expected number of accepted infested units (expected slippage) given lot size, sample size, infestation rate, and detection rate, and we formulate and analyze the inspector's optimization problem of allocating a sampling budget among incoming lots to minimize the cost of slippage. We conduct an empirical analysis of live plant inspection, including estimation of plant infestation rates from historical data, and find that inspections optimally target the largest lots with the highest plant infestation rates, leaving some lots unsampled. We also consider that USDA-APHIS, which administers inspections, may want to continue inspecting all lots at a baseline level; we find that allocating any additional capacity, beyond a comprehensive baseline inspection, to the largest lots with the highest infestation rates allows inspectors to meet the dual goals of minimizing the costs of slippage and maintaining baseline sampling without substantial compromise. © 2017 Society for Risk Analysis.

Development of an hp-version finite element method for computational optimal control

NASA Technical Reports Server (NTRS)

Hodges, Dewey H.; Warner, Michael S.

1993-01-01

The purpose of this research effort was to begin the study of the application of hp-version finite elements to the numerical solution of optimal control problems. Under NAG-939, the hybrid MACSYMA/FORTRAN code GENCODE was developed which utilized h-version finite elements to successfully approximate solutions to a wide class of optimal control problems. In that code the means for improvement of the solution was the refinement of the time-discretization mesh. With the extension to hp-version finite elements, the degrees of freedom include both nodal values and extra interior values associated with the unknown states, co-states, and controls, the number of which depends on the order of the shape functions in each element. One possible drawback is the increased computational effort within each element required in implementing hp-version finite elements. We are trying to determine whether this computational effort is sufficiently offset by the reduction in the number of time elements used and improved Newton-Raphson convergence so as to be useful in solving optimal control problems in real time. Because certain of the element interior unknowns can be eliminated at the element level by solving a small set of nonlinear algebraic equations in which the nodal values are taken as given, the scheme may turn out to be especially powerful in a parallel computing environment. A different processor could be assigned to each element. The number of processors, strictly speaking, is not required to be any larger than the number of sub-regions which are free of discontinuities of any kind.

All-in-one model for designing optimal water distribution pipe networks

NASA Astrophysics Data System (ADS)

Aklog, Dagnachew; Hosoi, Yoshihiko

2017-05-01

This paper discusses the development of an easy-to-use, all-in-one model for designing optimal water distribution networks. The model combines different optimization techniques into a single package in which a user can easily choose what optimizer to use and compare the results of different optimizers to gain confidence in the performances of the models. At present, three optimization techniques are included in the model: linear programming (LP), genetic algorithm (GA) and a heuristic one-by-one reduction method (OBORM) that was previously developed by the authors. The optimizers were tested on a number of benchmark problems and performed very well in terms of finding optimal or near-optimal solutions with a reasonable computation effort. The results indicate that the model effectively addresses the issues of complexity and limited performance trust associated with previous models and can thus be used for practical purposes.

A case study on topology optimized design for additive manufacturing

NASA Astrophysics Data System (ADS)

Gebisa, A. W.; Lemu, H. G.

2017-12-01

Topology optimization is an optimization method that employs mathematical tools to optimize material distribution in a part to be designed. Earlier developments of topology optimization considered conventional manufacturing techniques that have limitations in producing complex geometries. This has hindered the topology optimization efforts not to fully be realized. With the emergence of additive manufacturing (AM) technologies, the technology that builds a part layer upon a layer directly from three dimensional (3D) model data of the part, however, producing complex shape geometry is no longer an issue. Realization of topology optimization through AM provides full design freedom for the design engineers. The article focuses on topologically optimized design approach for additive manufacturing with a case study on lightweight design of jet engine bracket. The study result shows that topology optimization is a powerful design technique to reduce the weight of a product while maintaining the design requirements if additive manufacturing is considered.

Site Optimization Tracker: Crossley Farm Superfund Site, Hereford and Washington Townships, Berks County, Pennsylvania

EPA Pesticide Factsheets

Pilot Region-Based Optimization Program for Fund-Lead Sites in EPA Region 3. Site Optimization Tracking information for Crossley Farm Superfund Site, Hereford and Washington Townships, Berks County, Pennsylvania.

Joint global optimization of tomographic data based on particle swarm optimization and decision theory

NASA Astrophysics Data System (ADS)

Paasche, H.; Tronicke, J.

2012-04-01

In many near surface geophysical applications multiple tomographic data sets are routinely acquired to explore subsurface structures and parameters. Linking the model generation process of multi-method geophysical data sets can significantly reduce ambiguities in geophysical data analysis and model interpretation. Most geophysical inversion approaches rely on local search optimization methods used to find an optimal model in the vicinity of a user-given starting model. The final solution may critically depend on the initial model. Alternatively, global optimization (GO) methods have been used to invert geophysical data. They explore the solution space in more detail and determine the optimal model independently from the starting model. Additionally, they can be used to find sets of optimal models allowing a further analysis of model parameter uncertainties. Here we employ particle swarm optimization (PSO) to realize the global optimization of tomographic data. PSO is an emergent methods based on swarm intelligence characterized by fast and robust convergence towards optimal solutions. The fundamental principle of PSO is inspired by nature, since the algorithm mimics the behavior of a flock of birds searching food in a search space. In PSO, a number of particles cruise a multi-dimensional solution space striving to find optimal model solutions explaining the acquired data. The particles communicate their positions and success and direct their movement according to the position of the currently most successful particle of the swarm. The success of a particle, i.e. the quality of the currently found model by a particle, must be uniquely quantifiable to identify the swarm leader. When jointly inverting disparate data sets, the optimization solution has to satisfy multiple optimization objectives, at least one for each data set. Unique determination of the most successful particle currently leading the swarm is not possible. Instead, only statements about the Pareto optimality of the found solutions can be made. Identification of the leading particle traditionally requires a costly combination of ranking and niching techniques. In our approach, we use a decision rule under uncertainty to identify the currently leading particle of the swarm. In doing so, we consider the different objectives of our optimization problem as competing agents with partially conflicting interests. Analysis of the maximin fitness function allows for robust and cheap identification of the currently leading particle. The final optimization result comprises a set of possible models spread along the Pareto front. For convex Pareto fronts, solution density is expected to be maximal in the region ideally compromising all objectives, i.e. the region of highest curvature.

International Implications of Lead Poisoning in School Aged Children

ERIC Educational Resources Information Center

Schultz, Susan M.

2016-01-01

The United States and the World Health Organization have worked to decrease lead exposure in children, but despite these efforts lead poisoning continues to exist in industrialized and developing countries. Prevention is the only way to preclude the health, academic and behavioral problems that occur due to the effects of lead. Public awareness…

Using College Admission Test Scores to Clarify High School Placement. Leading Indicator Spotlight

ERIC Educational Resources Information Center

Flug, Susanna

2010-01-01

In "Beyond Test Scores: Leading Indicators for Education," Foley and colleagues (2008) define leading indicators as those that "provide early signals of progress toward academic achievement" (p. 1) and stress that educators "need leading indicators to help them see the direction their efforts are going in and to take…

Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates.

PubMed

Braggio, Simone; Montanari, Dino; Rossi, Tino; Ratti, Emiliangelo

2010-07-01

As a result of their wide acceptance and conceptual simplicity, drug-like concepts are having a major influence on the drug discovery process, particularly in the selection of the 'optimal' absorption, distribution, metabolism, excretion and toxicity and physicochemical parameters space. While they have an undisputable value when assessing the potential of lead series or in evaluating inherent risk of a portfolio of drug candidates, they result much less useful in weighing up compounds for the selection of the best potential clinical candidate. We introduce the concept of drug efficiency as a new tool both to guide the drug discovery program teams during the lead optimization phase and to better assess the developability potential of a drug candidate.

Optimized Algorithms for Prediction Within Robotic Tele-Operative Interfaces

NASA Technical Reports Server (NTRS)

Martin, Rodney A.; Wheeler, Kevin R.; Allan, Mark B.; SunSpiral, Vytas

2010-01-01

Robonaut, the humanoid robot developed at the Dexterous Robotics Labo ratory at NASA Johnson Space Center serves as a testbed for human-rob ot collaboration research and development efforts. One of the recent efforts investigates how adjustable autonomy can provide for a safe a nd more effective completion of manipulation-based tasks. A predictiv e algorithm developed in previous work was deployed as part of a soft ware interface that can be used for long-distance tele-operation. In this work, Hidden Markov Models (HMM?s) were trained on data recorded during tele-operation of basic tasks. In this paper we provide the d etails of this algorithm, how to improve upon the methods via optimization, and also present viable alternatives to the original algorithmi c approach. We show that all of the algorithms presented can be optim ized to meet the specifications of the metrics shown as being useful for measuring the performance of the predictive methods. 1

Techniques development for whale migration tracking

NASA Technical Reports Server (NTRS)

Goodman, R. M.; Norris, K. S.; Gibson, R. J.; Gentry, R.; Dougherty, E.; Hobbs, L.

1973-01-01

Effort leading to the completion of development and fabrication of expansible whale harnesses and whale-carried instrument pods is described, along with details of the gear. Early preparative effort for a January-February 1974 field expedition is reported.

NASA-DoD Lower Process Temperature Lead-Free Solder Project Overview

NASA Technical Reports Server (NTRS)

Kessel, Kurt R.

2014-01-01

This project is a follow-on effort to the Joint Council on Aging AircraftJoint Group on Pollution Prevention (JCAAJG-PP) Pb-free Solder Project and NASA-DoD Lead-Free Electronics Project which were the first projects to test the reliability of Pb-free solder joints against the requirements of the aerospace and military community. This effort would continue to build on the results from the JCAAJG-PP Lead-Free Solder Project and NASA-DoD Lead-Free Electronics Project while focusing on a particular failure mechanism currently plaguing Pb-free assemblies, pad cratering.The NASA-DoD Lead-Free Electronics Project confirmed that pad cratering is one of the dominant failure modes that occur in various board level reliability tests, especially under dynamic loading. Pad Cratering is a latent defect that may occur during assembly, rework, and post assembly handling and testing.

Library design practices for success in lead generation with small molecule libraries.

PubMed

Goodnow, R A; Guba, W; Haap, W

2003-11-01

The generation of novel structures amenable to rapid and efficient lead optimization comprises an emerging strategy for success in modern drug discovery. Small molecule libraries of sufficient size and diversity to increase the chances of discovery of novel structures make the high throughput synthesis approach the method of choice for lead generation. Despite an industry trend for smaller, more focused libraries, the need to generate novel lead structures makes larger libraries a necessary strategy. For libraries of a several thousand or more members, solid phase synthesis approaches are the most suitable. While the technology and chemistry necessary for small molecule library synthesis continue to advance, success in lead generation requires rigorous consideration in the library design process to ensure the synthesis of molecules possessing the proper characteristics for subsequent lead optimization. Without proper selection of library templates and building blocks, solid phase synthesis methods often generate molecules which are too heavy, too lipophilic and too complex to be useful for lead optimization. The appropriate filtering of virtual library designs with multiple computational tools allows the generation of information-rich libraries within a drug-like molecular property space. An understanding of the hit-to-lead process provides a practical guide to molecular design characteristics. Examples of leads generated from library approaches also provide a benchmarking of successes as well as aspects for continued development of library design practices.

Advances on the constitutive characterization of composites via multiaxial robotic testing and design optimization

Treesearch

John G. Michopoulos; John Hermanson; Athanasios Iliopoulos

2014-01-01

The research areas of mutiaxial robotic testing and design optimization have been recently utilized for the purpose of data-driven constitutive characterization of anisotropic material systems. This effort has been enabled by both the progress in the areas of computers and information in engineering as well as the progress in computational automation. Although our...

Time optimal control of a jet engine using a quasi-Hermite interpolation model. M.S. Thesis

NASA Technical Reports Server (NTRS)

Comiskey, J. G.

1979-01-01

This work made preliminary efforts to generate nonlinear numerical models of a two-spooled turbofan jet engine, and subject these models to a known method of generating global, nonlinear, time optimal control laws. The models were derived numerically, directly from empirical data, as a first step in developing an automatic modelling procedure.

For Better and for Worse: Understanding Optimal Campus-Community Relationships through the Lens of Marriage

ERIC Educational Resources Information Center

Gavazzi, Stephen M.

2015-01-01

Borrowing from marital research literature, a four-square matrix constructed from the twin dimensions of effort and comfort levels is used to describe a typology of campus and community associations. Results from a study using the Optimal College Town Assessment to measure community member perceptions on town-gown relationships are presented next,…

Finite Energy and Bounded Actuator Attacks on Cyber-Physical Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Djouadi, Seddik M; Melin, Alexander M; Ferragut, Erik M

As control system networks are being connected to enterprise level networks for remote monitoring, operation, and system-wide performance optimization, these same connections are providing vulnerabilities that can be exploited by malicious actors for attack, financial gain, and theft of intellectual property. Much effort in cyber-physical system (CPS) protection has focused on protecting the borders of the system through traditional information security techniques. Less effort has been applied to the protection of cyber-physical systems from intelligent attacks launched after an attacker has defeated the information security protections to gain access to the control system. In this paper, attacks on actuator signalsmore » are analyzed from a system theoretic context. The threat surface is classified into finite energy and bounded attacks. These two broad classes encompass a large range of potential attacks. The effect of theses attacks on a linear quadratic (LQ) control are analyzed, and the optimal actuator attacks for both finite and infinite horizon LQ control are derived, therefore the worst case attack signals are obtained. The closed-loop system under the optimal attack signals is given and a numerical example illustrating the effect of an optimal bounded attack is provided.« less

Dissociable contributions of dorsal and ventral striatal regions on a rodent cost/benefit decision-making task requiring cognitive effort.

PubMed

Silveira, Mason M; Tremblay, Melanie; Winstanley, Catharine A

2018-04-24

Cognitive effort is a ubiquitous process, yet surprisingly little is known about the brain mechanisms responsible for evaluating it. Here, we utilize the rat Cognitive Effort Task (rCET) to probe the striatum's role in deciding between options that vary in the amount of cognitive effort required for success. In the rCET, animals choose to perform either an easy trial, in which the attentional demand is low but the potential reward is small, or a difficult trial which is more attentionally demanding but can yield twice the sugar pellets. Twenty-six male Long Evans rats were trained on the rCET and the effects of pharmacologically inactivating the dorsomedial striatum (DMS) and core region of the nucleus accumbens were determined. Temporary inactivation of the DMS decreased all animals' choice of the high-effort, high-reward option, impaired attentional accuracy, and robustly increased premature responding without impairing general indices of motor ability. The DMS therefore appears necessary for the integration of cognitive signals required for optimal performance. In stark contrast, following temporary inactivation of the ventral striatum, subjects were fundamentally unable to perform the task, as reflected by a drastic decrease in the number of trials initiated and an increase in omitted responses. Together, these data suggest the striatum is likely part of a larger cortico-limbic-striatal network whose function is to optimize decisions requiring cognitive effort costs, at least in the attentional domain, and that striatal subregions have dissociable roles in the adjudication and application of this form of cognitive effort. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computational wing optimization and comparisons with experiment for a semi-span wing model

NASA Technical Reports Server (NTRS)

Waggoner, E. G.; Haney, H. P.; Ballhaus, W. F.

1978-01-01

A computational wing optimization procedure was developed and verified by an experimental investigation of a semi-span variable camber wing model in the NASA Ames Research Center 14 foot transonic wind tunnel. The Bailey-Ballhaus transonic potential flow analysis and Woodward-Carmichael linear theory codes were linked to Vanderplaats constrained minimization routine to optimize model configurations at several subsonic and transonic design points. The 35 deg swept wing is characterized by multi-segmented leading and trailing edge flaps whose hinge lines are swept relative to the leading and trailing edges of the wing. By varying deflection angles of the flap segments, camber and twist distribution can be optimized for different design conditions. Results indicate that numerical optimization can be both an effective and efficient design tool. The optimized configurations had as good or better lift to drag ratios at the design points as the best designs previously tested during an extensive parametric study.

Concern for Others Leads to Vicarious Optimism

PubMed Central

Kappes, Andreas; Faber, Nadira S.; Kahane, Guy; Savulescu, Julian; Crockett, Molly J.

2018-01-01

An optimistic learning bias leads people to update their beliefs in response to better-than-expected good news but neglect worse-than-expected bad news. Because evidence suggests that this bias arises from self-concern, we hypothesized that a similar bias may affect beliefs about other people’s futures, to the extent that people care about others. Here, we demonstrated the phenomenon of vicarious optimism and showed that it arises from concern for others. Participants predicted the likelihood of unpleasant future events that could happen to either themselves or others. In addition to showing an optimistic learning bias for events affecting themselves, people showed vicarious optimism when learning about events affecting friends and strangers. Vicarious optimism for strangers correlated with generosity toward strangers, and experimentally increasing concern for strangers amplified vicarious optimism for them. These findings suggest that concern for others can bias beliefs about their future welfare and that optimism in learning is not restricted to oneself. PMID:29381448

Concern for Others Leads to Vicarious Optimism.

PubMed

Kappes, Andreas; Faber, Nadira S; Kahane, Guy; Savulescu, Julian; Crockett, Molly J

2018-03-01

An optimistic learning bias leads people to update their beliefs in response to better-than-expected good news but neglect worse-than-expected bad news. Because evidence suggests that this bias arises from self-concern, we hypothesized that a similar bias may affect beliefs about other people's futures, to the extent that people care about others. Here, we demonstrated the phenomenon of vicarious optimism and showed that it arises from concern for others. Participants predicted the likelihood of unpleasant future events that could happen to either themselves or others. In addition to showing an optimistic learning bias for events affecting themselves, people showed vicarious optimism when learning about events affecting friends and strangers. Vicarious optimism for strangers correlated with generosity toward strangers, and experimentally increasing concern for strangers amplified vicarious optimism for them. These findings suggest that concern for others can bias beliefs about their future welfare and that optimism in learning is not restricted to oneself.

Optimization principles and the figure of merit for triboelectric generators.

PubMed

Peng, Jun; Kang, Stephen Dongmin; Snyder, G Jeffrey

2017-12-01

Energy harvesting with triboelectric nanogenerators is a burgeoning field, with a growing portfolio of creative application schemes attracting much interest. Although power generation capabilities and its optimization are one of the most important subjects, a satisfactory elemental model that illustrates the basic principles and sets the optimization guideline remains elusive. We use a simple model to clarify how the energy generation mechanism is electrostatic induction but with a time-varying character that makes the optimal matching for power generation more restrictive. By combining multiple parameters into dimensionless variables, we pinpoint the optimum condition with only two independent parameters, leading to predictions of the maximum limit of power density, which allows us to derive the triboelectric material and device figure of merit. We reveal the importance of optimizing device capacitance, not only load resistance, and minimizing the impact of parasitic capacitance. Optimized capacitances can lead to an overall increase in power density of more than 10 times.

Advances in hypersonic vehicle synthesis with application to studies of advanced thermal protection system

NASA Technical Reports Server (NTRS)

Ardema, Mark D.

1995-01-01

This report summarizes the work entitled 'Advances in Hypersonic Vehicle Synthesis with Application to Studies of Advanced Thermal Protection Systems.' The effort was in two areas: (1) development of advanced methods of trajectory and propulsion system optimization; and (2) development of advanced methods of structural weight estimation. The majority of the effort was spent in the trajectory area.

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

PubMed

Yoshida, Takeshi; Roldan, Rollin; Beraldo, Marcelo A; Torsani, Vinicius; Gomes, Susimeire; De Santis, Roberta R; Costa, Eduardo L V; Tucci, Mauro R; Lima, Raul G; Kavanagh, Brian P; Amato, Marcelo B P

2016-08-01

We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. Crossover design. University animal research laboratory. Anesthetized landrace pigs. Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.

EPA Science Matters Newsletter: Effort to Cut Children’s Lead Exposure Continues

EPA Pesticide Factsheets

Read more about the Agency’s Integrated Science Assessment for Lead in June 2013. It presents an evaluation and synthesis of the latest and most relevant scientific knowledge to help determine the potential health effects of lead in ambient air

ISS-Crystal Growth of Photorefractive Materials (BSO): Critical Design Issues for Optimized Data Extraction from Space Experiments

NASA Technical Reports Server (NTRS)

Hyers, Robert W.; Motakef, S.; Witt, A. F.; Wuensch, B.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Realization of the full potential of photorefractive materials in device technology is seriously impeded by our inability to achieve controlled formation of critical defects during single crystal growth and by difficulties in meeting the required degree of compositional uniformity on a micro-scale over macroscopic dimensions. The exact nature and origin of the critical defects which control photorefractivity could not as yet be identified because of gravitational interference. There exists, however, strong evidence that the density of defect formation and their spatial distribution are adversely affected by gravitational interference which precludes the establishment of quantifiable and controllable heat and mass transfer conditions during crystal growth. The current, NASA sponsored research at MIT is directed at establishing a basis for the development of a comprehensive approach to the optimization of property control during melt growth of photorefractive materials, making use of the m-g environment, provided in the International Space Station. The objectives to be pursued in m-g research on photorefractive BSO (Bi12SiO20) are: (a) identification of the x-level(s) responsible for photorefractivity in undoped BSO; (b) development of approaches leading to the control of x-level formation at uniform spatial distribution; (c) development of doping and processing procedures for optimization of the critical, application specific parameters, spectral response, sensitivity, response time and matrix stability. The presentation will focus on: the rationale for the justification of the space experiment, ground-based development efforts, design considerations for the space experiments, strategic plan of the space experiments, and approaches to the quantitative analysis of the space experiments.

Energy transfer between a passing vortex ring and a flexible plate in an ideal quiescent fluid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, JiaCheng; Peterson, Sean D., E-mail: peterson@mme.uwaterloo.ca; Porfiri, Maurizio

Recent advancements in highly deformable smart materials have lead to increasing interest in small-scale energy harvesting research for powering low consumption electronic devices. One such recent experimental study by Goushcha et al. explored energy harvesting from a passing vortex ring by a cantilevered smart material plate oriented parallel to and offset from the path of the ring in an otherwise quiescent fluid. The present study focuses on modeling this experimental study using potential flow to facilitate optimization of the energy extraction from the passing ring to raise the energy harvesting potential of the device. The problem is modeled in two-dimensionsmore » with the vortex ring represented as a pair of counter-rotating free vortices. Vortex pair parameters are determined to match the convection speed of the ring in the experiments, as well as the imposed pressure loading on the plate. The plate is approximated as a Kirchhoff-Love plate and represented as a finite length vortex sheet in the fluid domain. The analytical model matches experimental measurements, including the tip displacement, the integrated force along the entire plate length as a function of vortex ring position, and the pressure along the plate. The potential flow solution is employed in a parametric study of the governing dimensionless parameters in an effort to guide the selection of plate properties for optimal energy harvesting performance. Results of the study indicate an optimal set of plate properties for a given vortex ring configuration, in which the time-scale of vortex advection matches that of the plate vibration.« less

Lead poisoning in United States-bound refugee children: Thailand-Burma border, 2009.

PubMed

Mitchell, Tarissa; Jentes, Emily; Ortega, Luis; Scalia Sucosky, Marissa; Jefferies, Taran; Bajcevic, Predrag; Parr, Valentina; Jones, Warren; Brown, Mary Jean; Painter, John

2012-02-01

Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described. Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary <3.3 µg/dL) blood lead levels participated in a case-control study. Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged <2 years had the highest prevalence (14.5%). Among children aged <2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin <10 g/dL, exposure to car batteries, and taking traditional medicines. The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children <2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.

Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.

PubMed

Ting, Pauline C; Lee, Joe F; Zorn, Nicolas; Kim, Hyunjin M; Aslanian, Robert G; Lin, Mingxiang; Smith, Michelle; Walker, Scott S; Cook, John; Van Heek, Margaret; Lachowicz, Jean

2013-02-15

The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described. The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pre-Algebra and Algebra Enrollment and Achievement. Leading Indicator Spotlight

ERIC Educational Resources Information Center

Musen, Lindsey

2010-01-01

In "Beyond Test Scores: Leading Indicators for Education," Foley and colleagues (2008) define "leading indicators" as those that "provide early signals of progress toward academic achievement" (p. 1) and stress that educators "need leading indicators to help them see the direction their efforts are going in and to take corrective action as soon as…

Optimization of cathodic arc deposition and pulsed plasma melting techniques for growing smooth superconducting Pb photoemissive films for SRF injectors

NASA Astrophysics Data System (ADS)

Nietubyć, Robert; Lorkiewicz, Jerzy; Sekutowicz, Jacek; Smedley, John; Kosińska, Anna

2018-05-01

Superconducting photoinjectors have a potential to be the optimal solution for moderate and high current cw operating free electron lasers. For this application, a superconducting lead (Pb) cathode has been proposed to simplify the cathode integration into a 1.3 GHz, TESLA-type, 1.6-cell long purely superconducting gun cavity. In the proposed design, a lead film several micrometres thick is deposited onto a niobium plug attached to the cavity back wall. Traditional lead deposition techniques usually produce very non-uniform emission surfaces and often result in a poor adhesion of the layer. A pulsed plasma melting procedure reducing the non-uniformity of the lead photocathodes is presented. In order to determine the parameters optimal for this procedure, heat transfer from plasma to the film was first modelled to evaluate melting front penetration range and liquid state duration. The obtained results were verified by surface inspection of witness samples. The optimal procedure was used to prepare a photocathode plug, which was then tested in an electron gun. The quantum efficiency and the value of cavity quality factor have been found to satisfy the requirements for an injector of the European-XFEL facility.

NATURAL PRODUCTS: A CONTINUING SOURCE OF NOVEL DRUG LEADS

PubMed Central

Cragg, Gordon M.; Newman, David J.

2013-01-01

1. Background Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench. 2. Scope of Review This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations. 3. Major Conclusions The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases. 4 General Significance: The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped. PMID:23428572

Pyrolysis Gas as a Renewable Reducing Agent for the Recycling of Zinc- and Lead-Bearing Residues: A Status Report

NASA Astrophysics Data System (ADS)

Pichler, C.; Antrekowitsch, J.

2017-04-01

The topic "Zero Waste" has been in existence for several years in the industry, and the metallurgical industry has also made efforts to reduce the amounts of residues occurring and have started several investigations to cut down on metallurgical by-products which have to be landfilled. Especially, the additional costs for CO2 emissions in different metallurgical steps have led to investigations into alternative carbon carriers. Charcoal has been identified to serve as an ideal substitute due its CO2-neutrality. For the applications of this renewable carbon carrier in metallurgical processes, charcoal production by means of a carbonization process needs to be optimized. As a by-product during the heating of agricultural wastes or wood by excluding air, pyrolysis gas occurs. Due to the existence of combustible compounds in this gas, an application as a reduction agent instead of fossil carbon carriers in metallurgy is possible. Based on the prevention of dumping metallurgical by-products, an investigation has been developed to treat zinc- and lead-containing materials. To realize this, a dedicated process concept has been designed and developed. As the main focuses, the usage of the pyrolysis gas from charcoal production for the Waelz kiln process and the recycling of zinc- and lead-containing Waelz slag, resulting from the processing of steel mill dust in a vertical retort, have to be mentioned. Within this research, the process concept was executed from laboratory-scale up to pilot-scale testing, described in this article.

USEPA LEAD AND COPPER CORROSION DS RESEARCH AND LCR REGULATORY UPDATE (AWWA WQTC 2006)

EPA Science Inventory

The USEPA is actively addressing lead and copper research needs which continue to develop. The objective of the presentation is to summarize current EPA lead and copper research efforts. Discussion includes project descriptions, a summary of relevant current findings, and discuss...

Wing-section optimization for supersonic viscous flow

NASA Technical Reports Server (NTRS)

Item, Cem C.; Baysal, Oktay (Editor)

1995-01-01

To improve the shape of a supersonic wing, an automated method that also includes higher fidelity to the flow physics is desirable. With this impetus, an aerodynamic optimization methodology incorporating thin-layer Navier-Stokes equations and sensitivity analysis had been previously developed. Prior to embarking upon the wind design task, the present investigation concentrated on testing the feasibility of the methodology, and the identification of adequate problem formulations, by defining two-dimensional, cost-effective test cases. Starting with two distinctly different initial airfoils, two independent shape optimizations resulted in shapes with similar features: slightly cambered, parabolic profiles with sharp leading- and trailing-edges. Secondly, the normal section to the subsonic portion of the leading edge, which had a high normal angle-of-attack, was considered. The optimization resulted in a shape with twist and camber which eliminated the adverse pressure gradient, hence, exploiting the leading-edge thrust. The wing section shapes obtained in all the test cases had the features predicted by previous studies. Therefore, it was concluded that the flowfield analyses and sensitivity coefficients were computed and fed to the present gradient-based optimizer correctly. Also, as a result of the present two-dimensional study, suggestions were made for the problem formulations which should contribute to an effective wing shape optimization.

Global, Multi-Objective Trajectory Optimization With Parametric Spreading

NASA Technical Reports Server (NTRS)

Vavrina, Matthew A.; Englander, Jacob A.; Phillips, Sean M.; Hughes, Kyle M.

2017-01-01

Mission design problems are often characterized by multiple, competing trajectory optimization objectives. Recent multi-objective trajectory optimization formulations enable generation of globally-optimal, Pareto solutions via a multi-objective genetic algorithm. A byproduct of these formulations is that clustering in design space can occur in evolving the population towards the Pareto front. This clustering can be a drawback, however, if parametric evaluations of design variables are desired. This effort addresses clustering by incorporating operators that encourage a uniform spread over specified design variables while maintaining Pareto front representation. The algorithm is demonstrated on a Neptune orbiter mission, and enhanced multidimensional visualization strategies are presented.

Simulation and Optimization of an Airfoil with Leading Edge Slat

NASA Astrophysics Data System (ADS)

Schramm, Matthias; Stoevesandt, Bernhard; Peinke, Joachim

2016-09-01

A gradient-based optimization is used in order to improve the shape of a leading edge slat upstream of a DU 91-W2-250 airfoil. The simulations are performed by solving the Reynolds-Averaged Navier-Stokes equations (RANS) using the open source CFD code OpenFOAM. Gradients are computed via the adjoint approach, which is suitable to deal with many design parameters, but keeping the computational costs low. The implementation is verified by comparing the gradients from the adjoint method with gradients obtained by finite differences for a NACA 0012 airfoil. The simulations of the leading edge slat are validated against measurements from the acoustic wind tunnel of Oldenburg University at a Reynolds number of Re = 6 • 105. The shape of the slat is optimized using the adjoint approach resulting in a drag reduction of 2%. Although the optimization is done for Re = 6 • 105, the improvements also hold for a higher Reynolds number of Re = 7.9 • 106, which is more realistic at modern wind turbines.

Non-optimal microbial response to antibiotics underlies suppressive drug interactions

PubMed Central

Bollenbach, Tobias; Quan, Selwyn; Chait, Remy; Kishony, Roy

2010-01-01

SUMMARY Antibiotics inhibiting translation can increase bacterial growth rate in the presence of DNA synthesis inhibitors. Here, we show that this extreme type of drug antagonism, termed suppression, results from non-optimal regulation of ribosomal genes, leading to sub-maximal growth in the presence of DNA stress. Using GFP-tagged transcription reporters in Escherichia coli, we find that ribosomal genes are not directly regulated by DNA stress, leading to an imbalance between cellular DNA and protein content. Sequential deletion of up to 6 of the 7 ribosomal RNA operons corrects this imbalance and leads to improved survival and growth under DNA synthesis inhibition. Further, this genetic manipulation completely removes the suppressive drug interaction. Mathematical modeling shows that non-optimal regulation of ribosome synthesis under DNA stress can be explained as a side-effect of optimal growth-rate-dependent regulation in different nutrient environments. Together, these results reveal the genetic mechanism underlying an important class of suppressive drug interactions. PMID:19914165

Latha Sethuraman | NREL

Science.gov Websites

aeroelastic simulation of drivetrain systems. At NREL, she supports the drivetrain modeling effort under the , electro-mechanical system design and optimization, structural analysis, and multi-body simulation. In

Development and Implementation of an Optimization Model for Hydropower and Total Dissolved Gas in the Mid-Columbia River System

DOE PAGES

Witt, Adam; Magee, Timothy; Stewart, Kevin; ...

2017-08-10

Managing energy, water, and environmental priorities and constraints within a cascade hydropower system is a challenging multiobjective optimization effort that requires advanced modeling and forecasting tools. Within the mid-Columbia River system, there is currently a lack of specific solutions for predicting how coordinated operational decisions can mitigate the impacts of total dissolved gas (TDG) supersaturation while satisfying multiple additional policy and hydropower generation objectives. In this study, a reduced-order TDG uptake equation is developed that predicts tailrace TDG at seven hydropower facilities on the mid-Columbia River. The equation is incorporated into a general multiobjective river, reservoir, and hydropower optimization toolmore » as a prioritized operating goal within a broader set of system-level objectives and constraints. A test case is presented to assess the response of TDG and hydropower generation when TDG supersaturation is optimized to remain under state water-quality standards. Satisfaction of TDG as an operating goal is highly dependent on whether constraints that limit TDG uptake are implemented at a higher priority than generation requests. According to the model, an opportunity exists to reduce TDG supersaturation and meet hydropower generation requirements by shifting spillway flows to different time periods. In conclusion, a coordinated effort between all project owners is required to implement systemwide optimized solutions that satisfy the operating policies of all stakeholders.« less

Development and Implementation of an Optimization Model for Hydropower and Total Dissolved Gas in the Mid-Columbia River System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witt, Adam; Magee, Timothy; Stewart, Kevin

Managing energy, water, and environmental priorities and constraints within a cascade hydropower system is a challenging multiobjective optimization effort that requires advanced modeling and forecasting tools. Within the mid-Columbia River system, there is currently a lack of specific solutions for predicting how coordinated operational decisions can mitigate the impacts of total dissolved gas (TDG) supersaturation while satisfying multiple additional policy and hydropower generation objectives. In this study, a reduced-order TDG uptake equation is developed that predicts tailrace TDG at seven hydropower facilities on the mid-Columbia River. The equation is incorporated into a general multiobjective river, reservoir, and hydropower optimization toolmore » as a prioritized operating goal within a broader set of system-level objectives and constraints. A test case is presented to assess the response of TDG and hydropower generation when TDG supersaturation is optimized to remain under state water-quality standards. Satisfaction of TDG as an operating goal is highly dependent on whether constraints that limit TDG uptake are implemented at a higher priority than generation requests. According to the model, an opportunity exists to reduce TDG supersaturation and meet hydropower generation requirements by shifting spillway flows to different time periods. In conclusion, a coordinated effort between all project owners is required to implement systemwide optimized solutions that satisfy the operating policies of all stakeholders.« less

Do we have biomarkers to predict response to neoadjuvant and adjuvant chemotherapy and immunotherapy in bladder cancer?

PubMed Central

Wezel, Felix; Vallo, Stefan

2017-01-01

Radical cystectomy (RC) is the standard of care treatment of localized muscle-invasive bladder cancer (BC). However, about 50% of patients develop metastases within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival (OS) in patients with muscle-invasive BC. Pathological response to neoadjuvant treatment is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from chemotherapy. The identification of reliable biomarkers enabling clinicians to identify patients who might benefit from chemotherapy is a very important clinical task. An identification tool could lead to individualized therapy, optimizing response rates. In addition, unnecessary treatment with chemotherapy which potentially leads to a loss of quality of life and which might also might cause a delay of cystectomy in a neoadjuvant setting could be avoided. The present review aims to summarize and discuss the current literature on biomarkers for the prediction of response to systemic therapy in muscle-invasive BC. Tremendous efforts in genetic and molecular characterization have led to the identification of predictive candidate biomarkers in urothelial carcinoma (UC), although prospective validation is pending. Ongoing clinical trials examining the benefit of individual therapies in UC of the bladder (UCB) by molecular patient selection hold promise to shed light on this question. PMID:29354494

Laser-based rework in electronics production

NASA Astrophysics Data System (ADS)

Albert, Florian; Mys, Ihor; Schmidt, Michael

2007-02-01

Despite the electronic manufacturing is well-established mass production process for a long time, the problem of reworking, i.a. reject and replace of defect components, still exists. The rework operations (soldering, replacement and desoldering) are performed in most cases manually. However, this practice is characterized by an inconsistent quality of the reworked solder joints and a high degree of physiological stress for the employees. In this paper, we propose a novel full-automated laser based soldering and rework process. Our developed soldering system is a pick-and-place unit with an integrated galvanometer scanner, a fiber coupled diode laser for quasi-simultaneous soldering and a pyrometer-based process control. The developed system provides soldering and reworking processes taking into account a kind of defect, a type of electronic component and quality requirements from the IPC- 610 norm. The paper spends a great deal of efforts to analyze quality of laser reworked solder joints. The quality depends mainly on the type and thickness of intermetallic phases between solder, pads and leads; the wetting angles between pad, solder and lead; and finally, the joint microstructure with its mechanical properties. The influence of the rework soldering on these three factors is discussed and compared to conventional laser soldering results. In order to optimize the quality of reworked joints, the different strategies of energy input are applied.

An adaptive response to uncertainty can lead to weight gain during dieting attempts

PubMed Central

Higginson, A. D.; McNamara, J. M.

2016-01-01

Background and objectives: Peoples’ attempts to lose weight by low calorie diets often result in weight gain because of over-compensatory overeating during lapses. Animals usually respond to a change in food availability by adjusting their foraging effort and altering how much energy reserves they store. But in many situations the long-term availability of food is uncertain, so animals may attempt to estimate it to decide the appropriate level of fat storage. Methodology: We report the results of a conceptual model of feeding in which the animal knows whether food is currently abundant or limited, but does not know the proportion of time, there will be an abundance in the long-term and has to learn it. Results: If the food supply is limited much of the time, such as during cycles of dieting attempts, the optimal response is to gain a lot of weight when food is abundant. Conclusions and implications: This implies that recurring attempts to diet, by signalling to the body that the food supply is often insufficient, will lead to a greater fat storage than if food was always abundant. Our results shed light on the widespread phenomenon of weight gain during weight cycling and indicate possible interventions that may reduce the incidence of obesity. PMID:27920041

Non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase: synthesis, structure-activity relationships, and pharmacokinetics.

PubMed

Ndungu, J Maina; Krumm, Stefanie A; Yan, Dan; Arrendale, Richard F; Reddy, G Prabhakar; Evers, Taylor; Howard, Randy; Natchus, Michael G; Saindane, Manohar T; Liotta, Dennis C; Plemper, Richard K; Snyder, James P; Sun, Aiming

2012-05-10

The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC(50) = 60 nM) with an aqueous solubility of approximately 60 μg/mL. The agent shows a 10-fold exposure (AUC/C(max)) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg, and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.

New catalysts for coal liquefaction and new nanocrystalline catalysts synthesis methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linehan, J.C.; Matson, D.W.; Darab, J.G.

1994-09-01

The use of coal as a source of transportation fuel is currently economically unfavorable due to an abundant world petroleum supply and the relatively high cost of coal liquefaction. Consequently, a reduction in the cost of coal liquefaction, for example by using less and/or less costly catalysts or lower liquefaction temperatures, must be accomplished if coal is to play an significant role as a source of liquid feedstock for the petrochemical industry. The authors and others have investigated the applicability of using inexpensive iron-based catalysts in place of more costly and environmentally hazardous metal catalysts for direct coal liquefaction. Iron-basedmore » catalysts can be effective in liquefying coal and in promoting carbon-carbon bond cleavage in model compounds. The authors have been involved in an ongoing effort to develop and optimize iron-based powders for use in coal liquefaction and related petrochemical applications. Research efforts in this area have been directed at three general areas. The authors have explored ways to optimize the effectiveness of catalyst precursor species through use of nanocrystalline materials and/or finely divided powders. In this effort, the authors have developed two new nanophase material production techniques, Modified Reverse Micelle (MRM) and the Rapid Thermal Decomposition of precursors in Solution (RTDS). A second effort has been aimed at optimizing the effectiveness of catalysts by variations in other factors. To this, the authors have investigated the effect that the crystalline phase has on the capacity of iron-based oxide and oxyhydroxide powders to be effectively converted to an active catalyst phase under liquefaction conditions. And finally, the authors have developed methods to produce active catalyst precursor powders in quantities sufficient for pilot-scale testing. Major results in these three areas are summarized.« less

Optimal dynamic control of invasions: applying a systematic conservation approach.

PubMed

Adams, Vanessa M; Setterfield, Samantha A

2015-06-01

The social, economic, and environmental impacts of invasive plants are well recognized. However, these variable impacts are rarely accounted for in the spatial prioritization of funding for weed management. We examine how current spatially explicit prioritization methods can be extended to identify optimal budget allocations to both eradication and control measures of invasive species to minimize the costs and likelihood of invasion. Our framework extends recent approaches to systematic prioritization of weed management to account for multiple values that are threatened by weed invasions with a multi-year dynamic prioritization approach. We apply our method to the northern portion of the Daly catchment in the Northern Territory, which has significant conservation values that are threatened by gamba grass (Andropogon gayanus), a highly invasive species recognized by the Australian government as a Weed of National Significance (WONS). We interface Marxan, a widely applied conservation planning tool, with a dynamic biophysical model of gamba grass to optimally allocate funds to eradication and control programs under two budget scenarios comparing maximizing gain (MaxGain) and minimizing loss (MinLoss) optimization approaches. The prioritizations support previous findings that a MinLoss approach is a better strategy when threats are more spatially variable than conservation values. Over a 10-year simulation period, we find that a MinLoss approach reduces future infestations by ~8% compared to MaxGain in the constrained budget scenarios and ~12% in the unlimited budget scenarios. We find that due to the extensive current invasion and rapid rate of spread, allocating the annual budget to control efforts is more efficient than funding eradication efforts when there is a constrained budget. Under a constrained budget, applying the most efficient optimization scenario (control, minloss) reduces spread by ~27% compared to no control. Conversely, if the budget is unlimited it is more efficient to fund eradication efforts and reduces spread by ~65% compared to no control.

MO-DE-204-01: Radiation Doses in Over 50 Developing Countries of Asia, Africa, Eastern European and Latin America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rehani, M.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

MO-DE-204-03: Radiology Dose Optimisation - An Australian Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schick, D.

2016-06-15

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kofler, J.

The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less

Achieving a Prioritized Research and Technology Development Portfolio for the Dust Management Project

NASA Technical Reports Server (NTRS)

Hyatt, Mark J.; Abel, Phillip; Delaune, Paul; Fishman, Julianna; Kohli, Rajiv

2009-01-01

Mission architectures for human exploration of the lunar surface continue to advance as well as the definitions of capability needs, best practices and engineering design to mitigate the impact of lunar dust on exposed systems. The NASA DMP has been established as the agency focal point for dust characterization, technology, and simulant development. As described in this paper, the DMP has defined a process for selecting and justifying its R&T portfolio. The technology prioritization process, which is based on a ranking system according to weighted criteria, has been successfully applied to the current DMP dust mitigation technology portfolio. Several key findings emerged from this assessment. Within the dust removal and cleaning technologies group, there are critical technical challenges that must be overcome for these technologies to be implemented for lunar applications. For example, an in-situ source of CO2 on the moon is essential to the CO2 shower technology. Also, significant development effort is required to achieve technology readiness level TRL 6 for the electrostatic cleaning system for removal of particles smaller than 50 pm. The baseline materials related technologies require considerable development just to achieve TRL 6. It is also a nontrivial effort to integrate the materials in hardware for lunar application. At present, there are no terrestrial applications that are readily adaptable to lunar surface applications nor are there any obvious leading candidates. The unique requirements of dust sealing systems for lunar applications suggest an extensive development effort will be necessary to mature dust sealing systems to TRL 6 and beyond. As discussed here, several alternate materials and technologies have achieved high levels of maturity for terrestrial applications and warrant due diligence in ongoing assessment of the technology portfolio. The present assessment is the initial step in an ongoing effort to continually evaluate the DMP technology portfolio and external non-NASA relevant technology developments efforts to maintain an optimal investment profile. At the same time, there is an ongoing review of agency-wide dust-related R&T activities. The results of these ongoing assessments will be reported in future publications.

Binding Free Energy Calculations for Lead Optimization: Assessment of Their Accuracy in an Industrial Drug Design Context.

PubMed

Homeyer, Nadine; Stoll, Friederike; Hillisch, Alexander; Gohlke, Holger

2014-08-12

Correctly ranking compounds according to their computed relative binding affinities will be of great value for decision making in the lead optimization phase of industrial drug discovery. However, the performance of existing computationally demanding binding free energy calculation methods in this context is largely unknown. We analyzed the performance of the molecular mechanics continuum solvent, the linear interaction energy (LIE), and the thermodynamic integration (TI) approach for three sets of compounds from industrial lead optimization projects. The data sets pose challenges typical for this early stage of drug discovery. None of the methods was sufficiently predictive when applied out of the box without considering these challenges. Detailed investigations of failures revealed critical points that are essential for good binding free energy predictions. When data set-specific features were considered accordingly, predictions valuable for lead optimization could be obtained for all approaches but LIE. Our findings lead to clear recommendations for when to use which of the above approaches. Our findings also stress the important role of expert knowledge in this process, not least for estimating the accuracy of prediction results by TI, using indicators such as the size and chemical structure of exchanged groups and the statistical error in the predictions. Such knowledge will be invaluable when it comes to the question which of the TI results can be trusted for decision making.

Experimental Investigation of a 2D Supercritical Circulation-Control Airfoil Using Particle Image Velocimetry

NASA Technical Reports Server (NTRS)

Jones, Gregory S.; Yao, Chung-Sheng; Allan, Brian G.

2006-01-01

Recent efforts in extreme short takeoff and landing aircraft configurations have renewed the interest in circulation control wing design and optimization. The key to accurately designing and optimizing these configurations rests in the modeling of the complex physics of these flows. This paper will highlight the physics of the stagnation and separation regions on two typical circulation control airfoil sections.

Uplink Packet-Data Scheduling in DS-CDMA Systems

NASA Astrophysics Data System (ADS)

Choi, Young Woo; Kim, Seong-Lyun

In this letter, we consider the uplink packet scheduling for non-real-time data users in a DS-CDMA system. As an effort to jointly optimize throughput and fairness, we formulate a time-span minimization problem incorporating the time-multiplexing of different simultaneous transmission schemes. Based on simple rules, we propose efficient scheduling algorithms and compare them with the optimal solution obtained by linear programming.

The Federal Aviation Administration Plan for Research, Engineering and Development, 1994

DTIC Science & Technology

1994-05-01

Aeronautical Data Link Communications and (COTS) runway incursion system software will Applications, and 051-130 Airport Safety be demonstrated as a... airport departure and ar- efforts rival scheduling plans that optimize daily traffic flows for long-range flights between major city- * OTFP System to...Expanded HARS planning capabilities to in- aviation dispatchers to develop optimized high clude enhanced communications software for altitude flight

Decision Through Optimism: The North Peruvian Pipeline.

DTIC Science & Technology

1987-05-01

corporations. Another factor, optimism, is more intangible, but influenced the decision strongly. This paper discusses the need for, construction of...decision, the construction effort, and financing to accomplish this endeavor. Finally, it notes Peru’s oil situation after completion of the pipeline and...decision strongly. This paper discusses the need for, construction of, and results of building the Northern Peru Oil Pipeline. The paper reviews the

A Systems Engineering Approach to Multiple Attribute Utility Theory and Multiple Objective Optimization Theory: With Application To Aircraft Retrofit Design.

DTIC Science & Technology

1980-01-01

me produce this dissertation. I wish to thank Professors John E. Gibson and Chelsea C. White, III for their advice and contributions in this effort. My...National Meeting, Los Angeles, Ca., 1ov., 97$ Everett, J., Hax, A., Lewison , V. and 4utts, D., "Optimization of a Fleet of Large Tarkers and Bulkers...Arrow, C. J., Mardecai, K., Public Investment, The Rate of Return and Optimal Fiscal Policy, Johns Hopkins Press, Baltimore, Maryland, 1970. Banker

[Challenges and strategies of drug innovation].

PubMed

Guo, Zong-Ru; Zhao, Hong-Yu

2013-07-01

Drug research involves scientific discovery, technological inventions and product development. This multiple dimensional effort embodies both high risk and high reward and is considered one of the most complicated human activities. Prior to the initiation of a program, an in-depth analysis of "what to do" and "how to do it" must be conducted. On the macro level, market prospects, capital required, risk assessment, necessary human resources, etc. need to be evaluated critically. For execution, drug candidates need to be optimized in multiple properties such as potency, selectivity, pharmacokinetics, safety, formulation, etc., all with the constraint of finite amount of time and resources, to maximize the probability of success in clinical development. Drug discovery is enormously complicated, both in terms of technological innovation and organizing capital and other resources. A deep understanding of the complexity of drug research and our competitive edge is critical for success. Our unique government-enterprise-academia system represents a distinct advantage. As a new player, we have not heavily invested in any particular discovery paradigm, which allows us to select the optimal approach with little organizational burden. Virtue R&D model using CROs has gained momentum lately and China is a global leader in CRO market. Essentially all technological support for drug discovery can be found in China, which greatly enables domestic R&D efforts. The information technology revolution ensures the globalization of drug discovery knowledge, which has bridged much of the gap between China and the developed countries. The blockbuster model and the target-centric drug discovery paradigm have overlooked the research in several important fields such as injectable drugs, orphan drugs, and following high quality therapeutic leads, etc. Prejudice against covalent ligands, prodrugs, nondrug-like ligands can also be taken advantage of to find novel medicines. This article will discuss the current challenges and future opportunities for drug innovation in China.

Good Data Can Be Better Data - How Data Management Maturity Can Help Repositories Improve Operations, Data Quality, And Usability, Helping Researchers

NASA Astrophysics Data System (ADS)

Stall, S.

2015-12-01

Much earth and space science data and metadata are managed and supported by an infrastructure of repositories, ranging from large agency or instrument facilities, to institutions, to smaller repositories including labs. Scientists face many challenges in this ecosystem both on storing their data and in accessing data from others for new research. Critical for all uses is ensuring the credibility and integrity of the data and conveying that and provenance information now and in the future. Accurate information is essential for future researchers to find (or discover) the data, evaluate the data for use (content, temporal, geolocation, precision) and finally select (or discard) that data as meeting a "fit-for-purpose" criteria. We also need to optimize the effort it takes in describing the data for these determinations, which means making it efficient for the researchers who collect the data. At AGU we are developing a program aimed at helping repositories, and thereby researchers, improve data quality and data usability toward these goals. AGU has partnered with the CMMI Institute to develop their Data Management Maturity (DMM) framework within the Earth and space sciences. The CMMI DMM framework guides best practices in a range of data operations, and the application of the DMM, through an assessment, reveals how repositories and institutions can best optimize efforts to improve operations and functionality throughout the data lifecycle and elevate best practices across a variety of data management operations. Supporting processes like data operations, data governance, and data architecture are included. An assessment involves identifying accomplishment, and weaknesses compared to leading practices for data management. Broad application of the DMM can help improve quality in data and operations, and consistency across the community that will facilitate interoperability, discovery, preservation, and reuse. Good data can be better data. Consistency results in sustainability.

The clinical profile of women with stable ischaemic heart disease in Spain. More effort is needed in secondary prevention. SIRENA study.

PubMed

Gámez, J M; Ripoll, T; Barrios, V; Anguita, M; Pedreira, M; Madariaga, I

2016-01-01

Cardiovascular diseases are the leading cause of death for women, especially ischaemic heart disease, which is still considered a man's disease. In Spain, there are various registries on ischaemic heart disease, although none are exclusively for women. The objectives of the SIRENA study were to describe the clinical profile of women with ischaemic heart disease treated in cardiology consultations, to estimate its prevalence of cardiovascular risk factors and understand its clinical management. A multicentre observational study was conducted with a sample of 631 women with stable ischaemic heart disease, consecutively included during cardiology consultations. Forty-one researchers from all over Spain participated in the study. The mean age was 68.5 years. The clinical presentation was in the form of acute coronary syndrome in up to 67.2% of the patients. The prevalence of cardiovascular risk factors was high (77.7% of the patients had hypertension, 40.7% had diabetes and 68% had dyslipidaemia), with 30.7% having uncontrolled hypertension, 78.4% having LDL-cholesterol levels higher than 70mg/dL and 49.2% having HbA1c levels greater than 7%. The considerable majority of the patients underwent optimal medical treatment with antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers and hypolipidaemic agents. Coronary angiography was performed for 88.3% of the patients, and 63.4% underwent percutaneous coronary intervention. Women with stable ischaemic heart disease in Spain initially present some form of acute coronary syndrome and a high prevalence of inadequately controlled cardiovascular risk factors, despite undergoing optimal medical therapy. A high percentage of these women undergo coronary revascularisation. Increased efforts are required for secondary prevention in women with stable ischaemic heart disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

FY 1986 current fiscal year work plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This Current Year Work Plan presents in detail a description of the activities to be performed by the Joint Integration Office/RI during FY86. It breaks down the activities into two major work areas: Program Management and Program Analysis. Program Management is performed by the JIO/RI by providing technical planning and guidance for the development of advanced TRU waste management capabilities. This includes equipment/facility design, engineering, construction, and operations. These functions are integrated to allow transition from interim storage to final disposition. JIO/RI tasks include program requirements identification, long-range technical planning, budget development, program planning document preparation, task guidance development, taskmore » monitoring, task progress information gathering and reporting to DOE, interfacing with other agencies and DOE lead programs, integrating public involvement with program efforts, and preparation of reports for DOE detailing program status. Program Analysis is performed by the JIO/RI to support identification and assessment of alternatives, and development of long-term TRU waste program capabilities. These analyses include short term analyses in response to DOE information requests, along with performing an RH Cost/Schedule Optimization report. System models will be developed, updated, and upgraded as needed to enhance JIO/RI's capability to evaluate the adequacy of program efforts in various fields. A TRU program data base will be maintained and updated to provide DOE with timely responses to inventory related questions.« less

Modeling interfacial fracture in Sierra.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Arthur A.; Ohashi, Yuki; Lu, Wei-Yang

2013-09-01

This report summarizes computational efforts to model interfacial fracture using cohesive zone models in the SIERRA/SolidMechanics (SIERRA/SM) finite element code. Cohesive surface elements were used to model crack initiation and propagation along predefined paths. Mesh convergence was observed with SIERRA/SM for numerous geometries. As the funding for this project came from the Advanced Simulation and Computing Verification and Validation (ASC V&V) focus area, considerable effort was spent performing verification and validation. Code verification was performed to compare code predictions to analytical solutions for simple three-element simulations as well as a higher-fidelity simulation of a double-cantilever beam. Parameter identification was conductedmore » with Dakota using experimental results on asymmetric double-cantilever beam (ADCB) and end-notched-flexure (ENF) experiments conducted under Campaign-6 funding. Discretization convergence studies were also performed with respect to mesh size and time step and an optimization study was completed for mode II delamination using the ENF geometry. Throughout this verification process, numerous SIERRA/SM bugs were found and reported, all of which have been fixed, leading to over a 10-fold increase in convergence rates. Finally, mixed-mode flexure experiments were performed for validation. One of the unexplained issues encountered was material property variability for ostensibly the same composite material. Since the variability is not fully understood, it is difficult to accurately assess uncertainty when performing predictions.« less

Population health outcome models in suicide prevention policy.

PubMed

Lynch, Frances L

2014-09-01

Suicide is a leading cause of death in the U.S. and results in immense suffering and significant cost. Effective suicide prevention interventions could reduce this burden, but policy makers need estimates of health outcomes achieved by alternative interventions to focus implementation efforts. To illustrate the utility of health outcome models to help in achieving goals defined by the National Action Alliance for Suicide Prevention's Research Prioritization Task Force. The approach is illustrated specifically with psychotherapeutic interventions to prevent suicide reattempt in emergency department settings. A health outcome model using decision analysis with secondary data was applied to estimate suicide attempts and deaths averted from evidence-based interventions. Under optimal conditions, the model estimated that over 1 year, implementing evidence-based psychotherapeutic interventions in emergency departments could decrease the number of suicide attempts by 18,737, and if offered over 5 years, it could avert 109,306 attempts. Over 1 year, the model estimated 2,498 fewer deaths from suicide, and over 5 years, about 13,928 fewer suicide deaths. Health outcome models could aid in suicide prevention policy by helping focus implementation efforts. Further research developing more sophisticated models of the impact of suicide prevention interventions that include a more complex understanding of suicidal behavior, longer time frames, and inclusion of additional outcomes that capture the full benefits and costs of interventions would be helpful next steps. Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.

2010 Annual Report (National Defense Center for Energy and Environment)

DTIC Science & Technology

2010-01-01

a prototype system for reforming JP-8 to enable the use of fuel cells in theater. Energy, water, and waste reduction are tied to NDCEE efforts to...modernize Army ammunition plants , reducing costs and ensuring a steady supply of ammunition to the warfighter. At Fort Campbell, KY, newly...operating costs at Holston and Radford Army Ammunition Plants . Weapon systems ESOHE efforts also included optimizing various depot maintenance processes

Toward optimizing the delivery and use of climate science for natural resource management: lessons learned from recent adaptation efforts in the southwestern U.S.

NASA Astrophysics Data System (ADS)

Enquist, C.

2014-12-01

Within the past decade, a wealth of federal, state, and NGO-driven initiatives has emerged across managed landscapes in the United States with the goal of facilitating a coordinated response to rapidly changing climate and environmental conditions. In addition to acquisition and translation of the latest climate science, climate vulnerability assessment and scenario planning at multiple spatial and temporal scales are typically major components of such broad adaptation efforts. Numerous approaches for conducting this work have emerged in recent years and have culminated in general guidance and trainings for resource professionals that are specifically designed to help practitioners face the challenges of climate change. In particular, early engagement of stakeholders across multiple jurisdictions is particularly critical to cultivate buy-in and other enabling conditions for moving the science to on-the-ground action. I report on a suite of adaptation efforts in the southwestern US and interior Rockies, highlighting processes used, actions taken, lessons learned, and recommended next steps to facilitate achieving desired management outcomes. This includes a discussion of current efforts to optimize funding for actionable climate science, formalize science-management collaborations, and facilitate new investments in approaches for strategic climate-informed monitoring and evaluation.

Handling Uncertain Gross Margin and Water Demand in Agricultural Water Resources Management using Robust Optimization

NASA Astrophysics Data System (ADS)

Chaerani, D.; Lesmana, E.; Tressiana, N.

2018-03-01

In this paper, an application of Robust Optimization in agricultural water resource management problem under gross margin and water demand uncertainty is presented. Water resource management is a series of activities that includes planning, developing, distributing and managing the use of water resource optimally. Water resource management for agriculture can be one of the efforts to optimize the benefits of agricultural output. The objective function of agricultural water resource management problem is to maximizing total benefits by water allocation to agricultural areas covered by the irrigation network in planning horizon. Due to gross margin and water demand uncertainty, we assume that the uncertain data lies within ellipsoidal uncertainty set. We employ robust counterpart methodology to get the robust optimal solution.

Progress Report on Optimizing X-ray Optical Prescriptions for Wide-Field Applications

NASA Technical Reports Server (NTRS)

Elsner, R. F.; O'Dell, S. L.; Ramsey, B. D.; Weisskopf, M. C.

2011-01-01

We report on the present status of our continuing efforts to develop a method for optimizing wide-field nested x-ray telescope mirror prescriptions. Utilizing extensive Monte-Carlo ray trace simulations, we find an analytic form for the root-mean-square dispersion of rays from a Wolter I optic on the surface of a flat focal plane detector as a function of detector tilt away from the nominal focal plane and detector displacement along the optical axis. The configuration minimizing the ray dispersion from a nested array of Wolter I telescopes is found by solving a linear system of equations for tilt and individual mirror pair displacement. Finally we outline our initial efforts at expanding this method to include higher order polynomial terms in the mirror prescriptions.

Control and structural optimization for maneuvering large spacecraft

NASA Technical Reports Server (NTRS)

Chun, H. M.; Turner, J. D.; Yu, C. C.

1990-01-01

Presented here are the results of an advanced control design as well as a discussion of the requirements for automating both the structures and control design efforts for maneuvering a large spacecraft. The advanced control application addresses a general three dimensional slewing problem, and is applied to a large geostationary platform. The platform consists of two flexible antennas attached to the ends of a flexible truss. The control strategy involves an open-loop rigid body control profile which is derived from a nonlinear optimal control problem and provides the main control effort. A perturbation feedback control reduces the response due to the flexibility of the structure. Results are shown which demonstrate the usefulness of the approach. Software issues are considered for developing an integrated structures and control design environment.

Networks in ATLAS

NASA Astrophysics Data System (ADS)

McKee, Shawn; ATLAS Collaboration

2017-10-01

Networks have played a critical role in high-energy physics (HEP), enabling us to access and effectively utilize globally distributed resources to meet the needs of our physicists. Because of their importance in enabling our grid computing infrastructure many physicists have taken leading roles in research and education (R&E) networking, participating in, and even convening, network related meetings and research programs with the broader networking community worldwide. This has led to HEP benefiting from excellent global networking capabilities for little to no direct cost. However, as other science domains ramp-up their need for similar networking it becomes less clear that this situation will continue unchanged. What this means for ATLAS in particular needs to be understood. ATLAS has evolved its computing model since the LHC started based upon its experience with using globally distributed resources. The most significant theme of those changes has been increased reliance upon, and use of, its networks. We will report on a number of networking initiatives in ATLAS including participation in the global perfSONAR network monitoring and measuring efforts of WLCG and OSG, the collaboration with the LHCOPN/LHCONE effort, the integration of network awareness into PanDA, the use of the evolving ATLAS analytics framework to better understand our networks and the changes in our DDM system to allow remote access to data. We will also discuss new efforts underway that are exploring the inclusion and use of software defined networks (SDN) and how ATLAS might benefit from: • Orchestration and optimization of distributed data access and data movement. • Better control of workflows, end to end. • Enabling prioritization of time-critical vs normal tasks • Improvements in the efficiency of resource usage

Taking action on overuse: Creating the culture for change.

PubMed

Parchman, Michael L; Henrikson, Nora B; Blasi, Paula R; Buist, Diana S; Penfold, Robert; Austin, Brian; Ganos, Emily H

2017-12-01

Unnecessary care contributes to high costs and places patients at risk of harm. While most providers support reducing low-value care, changing established practice patterns is difficult and requires active engagement in sustained behavioral, organizational, and cultural change. Here we describe an action-planning framework to engage providers in reducing overused services. The framework is informed by a comprehensive review of social science theory and literature, published reports of successful and unsuccessful efforts to reduce low-value care, and interviews with innovators of value-based care initiatives in twenty-three health care organizations across the United States. A multi-stakeholder advisory committee provided feedback on the framework and guidance on optimizing it for use in practice. The framework describes four conditions necessary for change: prioritize addressing low-value care; build a culture of trust, innovation and improvement; establish shared language and purpose; and commit resources to measurements. These conditions foster productive sense-making conversations between providers, between providers and patients, and among members of the health care team about the potential for harm from overuse and reflection on current frequency of use. Through these conversations providers, patients and team members think together as a group, learn how to coordinate individual behaviors, and jointly develop possibilities for coordinated action around specific areas of overuse. Organizational efforts to engage providers in value-based care focused on creating conditions for productive sense-making conversations that lead to change. Organizations can use this framework to enhance and strengthen provider engagement efforts to do less of what potentially harms and more of what truly helps patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Self-transcending meditation is good for mental health: why this should be the case.

PubMed

Hankey, Alex; Shetkar, Rashmi

2016-06-01

A simple theory of health has recently been proposed: while poor quality regulation corresponds to poor quality health so that improving regulation should improve health, optimal regulation optimizes function and optimizes health. Examining the term 'optimal regulation' in biological systems leads to a straightforward definition in terms of 'criticality' in complexity biology, a concept that seems to apply universally throughout biology. Criticality maximizes information processing and sensitivity of response to external stimuli, and for these reasons may be held to optimize regulation. In this way a definition of health has been given in terms of regulation, a scientific concept, which ties into detailed properties of complex systems, including brain cortices, and mental health. Models of experience and meditation built on complexity also point to criticality: it represents the condition making self-awareness possible, and is strengthened by meditation practices leading to the state of pure consciousness-the content-free state of mind in deep meditation. From this it follows that healthy function of the brain cortex, its sensitivity,y and consistency of response to external challenges should improve by practicing techniques leading to content-free awareness-transcending the original focus introduced during practice. Evidence for this is reviewed.

Some Results of Weak Anticipative Concept Applied in Simulation Based Decision Support in Enterprise

NASA Astrophysics Data System (ADS)

Kljajić, Miroljub; Kofjač, Davorin; Kljajić Borštnar, Mirjana; Škraba, Andrej

2010-11-01

The simulation models are used as for decision support and learning in enterprises and in schools. Tree cases of successful applications demonstrate usefulness of weak anticipative information. Job shop scheduling production with makespan criterion presents a real case customized flexible furniture production optimization. The genetic algorithm for job shop scheduling optimization is presented. Simulation based inventory control for products with stochastic lead time and demand describes inventory optimization for products with stochastic lead time and demand. Dynamic programming and fuzzy control algorithms reduce the total cost without producing stock-outs in most cases. Values of decision making information based on simulation were discussed too. All two cases will be discussed from optimization, modeling and learning point of view.

Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials.

PubMed

Zhang, Yiqun; Clark, Julie A; Connelly, Michele C; Zhu, Fangyi; Min, Jaeki; Guiguemde, W Armand; Pradhan, Anupam; Iyer, Lalitha; Furimsky, Anna; Gow, Jason; Parman, Toufan; El Mazouni, Farah; Phillips, Margaret A; Kyle, Dennis E; Mirsalis, Jon; Guy, R Kiplin

2012-05-10

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

PubMed Central

Zhang, Yiqun; Clark, Julie A; Connelly, Michele C.; Zhu, Fangyi; Min, Jaeki; Guiguemde, W. Armand; Pradhan, Anupam; Iyer, Lalitha; Furimsky, Anna; Gow, Jason; Parman, Toufan; El Mazouni, Farah; Phillips, Margaret A.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin

2012-01-01

Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization. PMID:22435599

Pilot Project to Optimize Superfund-financed Pump and Treat Systems: Summary Report and Lessons Learned

EPA Pesticide Factsheets

This report summarizes Phase II (site optimization) of the Nationwide Fund-lead Pump and Treat Optimization Project. This phase included conducting Remediation System Evaluations (RSEs) at each of the 20 sites selected in Phase I.

Occupational Health Management in the Lead Industry: The Korean Experience

PubMed Central

2011-01-01

In 1967, the problem of occupational lead exposure came to public attention in Korea. Since then, regular progress has been made in lowering workplace lead exposures, instituting new workplace controls, and implementing health examinations of exposed workers. Past serious lead poisoning episodes made it possible to introduce biological monitoring programs on a voluntary basis in high-lead-exposure facilities in Korea. Industry-specific occupational health services for lead workers in Korea during the last 22 years can be categorized into three phases. During the first phase (1988-1993), efforts were directed at increasing awareness among workers about the hazards of lead exposure, biological monitoring of blood zinc protoporphyrin began, and a respiratory protection program was introduced. During the second phase (1994-1997), a computerized health management system for lead workers was developed, blood-lead measurement was added to biologic monitoring, and engineering controls were introduced in the workplace to lower air-lead levels to comply with air-lead regulations. Finally, during the third phase (1998-present), a new biomarker, bone-lead measurement by X-ray fluorescence, was introduced. Bone-lead measurement proved to be useful for assessing body burden and to demonstrate past lead exposure in retired workers. Occupational health service practice for lead workers, including the industry-specific group occupational health system, has brought considerable success in the prevention of lead poisoning and in reducing the lead burden in Korean lead workers during the last several decades. The successful achievement of prevention of lead poisoning in Korea was a result of the combined efforts of lead workers, employers, relevant government agencies, and academic institutes. PMID:22953192

Strategies for the generation, validation and application of in silico ADMET models in lead generation and optimization.

PubMed

Gleeson, Matthew Paul; Montanari, Dino

2012-11-01

The most desirable chemical starting point in drug discovery is a hit or lead with a good overall profile, and where there may be issues; a clear SAR strategy should be identifiable to minimize the issue. Filtering based on drug-likeness concepts are a first step, but more accurate theoretical methods are needed to i) estimate the biological profile of molecule in question and ii) based on the underlying structure-activity relationships used by the model, estimate whether it is likely that the molecule in question can be altered to remove these liabilities. In this paper, the authors discuss the generation of ADMET models and their practical use in decision making. They discuss the issues surrounding data collation, experimental errors, the model assessment and validation steps, as well as the different types of descriptors and statistical models that can be used. This is followed by a discussion on how the model accuracy will dictate when and where it can be used in the drug discovery process. The authors also discuss how models can be developed to more effectively enable multiple parameter optimization. Models can be applied in lead generation and lead optimization steps to i) rank order a collection of hits, ii) prioritize the experimental assays needed for different hit series, iii) assess the likelihood of resolving a problem that might be present in a particular series in lead optimization and iv) screen a virtual library based on a hit or lead series to assess the impact of diverse structural changes on the predicted properties.

Extending flood forecasting lead time in a large watershed by coupling WRF QPF with a distributed hydrological model

NASA Astrophysics Data System (ADS)

Li, Ji; Chen, Yangbo; Wang, Huanyu; Qin, Jianming; Li, Jie; Chiao, Sen

2017-03-01

Long lead time flood forecasting is very important for large watershed flood mitigation as it provides more time for flood warning and emergency responses. The latest numerical weather forecast model could provide 1-15-day quantitative precipitation forecasting products in grid format, and by coupling this product with a distributed hydrological model could produce long lead time watershed flood forecasting products. This paper studied the feasibility of coupling the Liuxihe model with the Weather Research and Forecasting quantitative precipitation forecast (WRF QPF) for large watershed flood forecasting in southern China. The QPF of WRF products has three lead times, including 24, 48 and 72 h, with the grid resolution being 20 km  × 20 km. The Liuxihe model is set up with freely downloaded terrain property; the model parameters were previously optimized with rain gauge observed precipitation, and re-optimized with the WRF QPF. Results show that the WRF QPF has bias with the rain gauge precipitation, and a post-processing method is proposed to post-process the WRF QPF products, which improves the flood forecasting capability. With model parameter re-optimization, the model's performance improves also. This suggests that the model parameters be optimized with QPF, not the rain gauge precipitation. With the increasing of lead time, the accuracy of the WRF QPF decreases, as does the flood forecasting capability. Flood forecasting products produced by coupling the Liuxihe model with the WRF QPF provide a good reference for large watershed flood warning due to its long lead time and rational results.

Aging infrastructure creates opportunities for cost-efficient restoration of aquatic ecosystem connectivity.

PubMed

Neeson, Thomas M; Moody, Allison T; O'Hanley, Jesse R; Diebel, Matthew; Doran, Patrick J; Ferris, Michael C; Colling, Timothy; McIntyre, Peter B

2018-06-09

A hallmark of industrialization is the construction of dams for water management and roads for transportation, leading to fragmentation of aquatic ecosystems. Many nations are striving to address both maintenance backlogs and mitigation of environmental impacts as their infrastructure ages. Here, we test whether accounting for road repair needs could offer opportunities to boost conservation efficiency by piggybacking connectivity restoration projects on infrastructure maintenance. Using optimization models to align fish passage restoration sites with likely road repair priorities, we find potential increases in conservation return-on-investment ranging from 17% to 25%. Importantly, these gains occur without compromising infrastructure or conservation priorities; simply communicating openly about objectives and candidate sites enables greater accomplishment at current funding levels. Society embraces both reliable roads and thriving fisheries, so overcoming this coordination challenge should be feasible. Given deferred maintenance crises for many types of infrastructure, there could be widespread opportunities to enhance the cost effectiveness of conservation investments by coordinating with infrastructure renewal efforts. © 2018 by the Ecological Society of America.

Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.

PubMed

Petros, Andrew M; Swann, Steven L; Song, Danying; Swinger, Kerren; Park, Chang; Zhang, Haichao; Wendt, Michael D; Kunzer, Aaron R; Souers, Andrew J; Sun, Chaohong

2014-03-15

Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

PubMed Central

He, Fei; Murabito, Ettore; Westerhoff, Hans V.

2016-01-01

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000

Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer.

PubMed

Yi, Chunling; Maksimoska, Jasna; Marmorstein, Ronen; Kissil, Joseph L

2010-09-01

The p21-activated kinases (PAKs), immediate downstream effectors of the small G-proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and as such, have been implicated in pathological conditions including cancer. Recent studies have validated the requirement for PAKs in promoting tumorigenesis in breast carcinoma and neurofibromatosis. Thus, there has been considerable interest in the development of inhibitors to the PAKs, as biological markers and leads for the development of therapeutics. While initial approaches were based on screening for competitive organic inhibitors, more recent efforts have focused on the identification of allosteric inhibitors, organometallic ATP-competitive inhibitors and the use of PAK1/inhibitor crystal structures for inhibitor optimization. This has led to the identification of highly selective and potent inhibitors, which will serve as a basis for further development of inhibitors for therapeutic applications. Copyright 2010 Elsevier Inc. All rights reserved.

Creating a safer operating room: Groups, team dynamics and crew resource management principles.

PubMed

Wakeman, Derek; Langham, Max R

2018-04-01

The operating room (OR) is a special place wherein groups of highly skilled individuals must work in a coordinated and harmonious fashion to deliver optimal patient care. Team dynamics and human factors principles were initially studied by the aviation industry to better understand and prevent airline accidents. As a result, crew resource management (CRM) training was designed for all flight personnel to create a highly reliable industry with a commitment to a culture of safety. CRM has since been adapted to health care, resulting in care improvement and harm reduction across a wide variety of medical specialties. When implemented in the OR, CRM has been shown not only to improve communication and morale for OR staff, but also reduce morbidity and mortality for patients. As increasing focus is placed on quality, safety, and high-reliability, surgeons will be expected to participate and lead efforts to facilitate a team approach in this new era of patient care. Copyright © 2018 Elsevier Inc. All rights reserved.

Re-Emerging Vaccine-Preventable Diseases in War-Affected Peoples of the Eastern Mediterranean Region—An Update

PubMed Central

Raslan, Rasha; El Sayegh, Skye; Chams, Sana; Chams, Nour; Leone, Angelo; Hajj Hussein, Inaya

2017-01-01

For the past few decades, the Eastern Mediterranean Region has been one area of the world profoundly shaped by war and political instability. On-going conflict and destruction have left the region struggling with innumerable health concerns that have claimed the lives of many. Wars, and the chaos they leave behind, often provide the optimal conditions for the growth and re-emergence of communicable diseases. In this article, we highlight a few of the major re-emerging vaccine preventable diseases in four countries of the Eastern Mediterranean Region that are currently affected by war leading to a migration crisis: Iraq, South Sudan, Syria, and Yemen. We will also describe the impact these infections have had on patients, societies, and national health care services. This article also describes the efforts, both local and international, which have been made to address these crises, as well as future endeavors that can be done to contain and control further devastation left by these diseases. PMID:29119098

Algorithmic aspects for the reconstruction of spatio-spectral data cubes in the perspective of the SKA

NASA Astrophysics Data System (ADS)

Mary, D.; Ferrari, A.; Ferrari, C.; Deguignet, J.; Vannier, M.

2016-12-01

With millions of receivers leading to TerraByte data cubes, the story of the giant SKA telescope is also that of collaborative efforts from radioastronomy, signal processing, optimization and computer sciences. Reconstructing SKA cubes poses two challenges. First, the majority of existing algorithms work in 2D and cannot be directly translated into 3D. Second, the reconstruction implies solving an inverse problem and it is not clear what ultimate limit we can expect on the error of this solution. This study addresses (of course partially) both challenges. We consider an extremely simple data acquisition model, and we focus on strategies making it possible to implement 3D reconstruction algorithms that use state-of-the-art image/spectral regularization. The proposed approach has two main features: (i) reduced memory storage with respect to a previous approach; (ii) efficient parallelization and ventilation of the computational load over the spectral bands. This work will allow to implement and compare various 3D reconstruction approaches in a large scale framework.

Evolutionary Design and Simulation of a Tube Crawling Inspection Robot

NASA Technical Reports Server (NTRS)

Craft, Michael; Howsman, Tom; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

2002-01-01

The Space Robotics Assembly Team Simulation (SpaceRATS) is an expansive concept that will hopefully lead to a space flight demonstration of a robotic team cooperatively assembling a system from its constitutive parts. A primary objective of the SpaceRATS project is to develop a generalized evolutionary design approach for multiple classes of robots. The portion of the overall SpaceRats program associated with the evolutionary design and simulation of an inspection robot's morphology is the subject of this paper. The vast majority of this effort has concentrated on the use and modification of Darwin2K, a robotic design and simulation software package, to analyze the design of a tube crawling robot. This robot is designed for carrying out inspection duties in relatively inaccessible locations within a liquid rocket engine similar to the SSME. A preliminary design of the tube crawler robot was completed, and the mechanical dynamics of the system were simulated. An evolutionary approach to optimizing a few parameters of the system was utilized, resulting in a more optimum design.

An international aerospace information system: A cooperative opportunity

NASA Technical Reports Server (NTRS)

Cotter, Gladys A.; Blados, Walter R.

1992-01-01

Scientific and technical information (STI) is a valuable resource which represents the results of large investments in research and development (R&D), and the expertise of a nation. NASA and its predecessor organizations have developed and managed the preeminent aerospace information system. We see information and information systems changing and becoming more international in scope. In Europe, consistent with joint R&D programs and a view toward a united Europe, we have seen the emergence of a European Aerospace Database concept. In addition, the development of aeronautics and astronautics in individual nations have also lead to initiatives for national aerospace databases. Considering recent technological developments in information science and technology, as well as the reality of scarce resources in all nations, it is time to reconsider the mutually beneficial possibilities offered by cooperation and international resource sharing. The new possibilities offered through cooperation among the various aerospace database efforts toward an international aerospace database initiative which can optimize the cost/benefit equation for all participants are considered.

Real-time moving horizon estimation for a vibrating active cantilever

NASA Astrophysics Data System (ADS)

Abdollahpouri, Mohammad; Takács, Gergely; Rohaľ-Ilkiv, Boris

2017-03-01

Vibrating structures may be subject to changes throughout their operating lifetime due to a range of environmental and technical factors. These variations can be considered as parameter changes in the dynamic model of the structure, while their online estimates can be utilized in adaptive control strategies, or in structural health monitoring. This paper implements the moving horizon estimation (MHE) algorithm on a low-cost embedded computing device that is jointly observing the dynamic states and parameter variations of an active cantilever beam in real time. The practical behavior of this algorithm has been investigated in various experimental scenarios. It has been found, that for the given field of application, moving horizon estimation converges faster than the extended Kalman filter; moreover, it handles atypical measurement noise, sensor errors or other extreme changes, reliably. Despite its improved performance, the experiments demonstrate that the disadvantage of solving the nonlinear optimization problem in MHE is that it naturally leads to an increase in computational effort.

Advanced Ceramics for NASA's Current and Future Needs

NASA Technical Reports Server (NTRS)

Jaskowiak, Martha H.

2006-01-01

Ceramic composites and monolithics are widely recognized by NASA as enabling materials for a variety of aerospace applications. Compared to traditional materials, ceramic materials offer higher specific strength which can enable lighter weight vehicle and engine concepts, increased payloads, and increased operational margins. Additionally, the higher temperature capabilities of these materials allows for increased operating temperatures within the engine and on the vehicle surfaces which can lead to improved engine efficiency and vehicle performance. To meet the requirements of the next generation of both rocket and air-breathing engines, NASA is actively pursuing the development and maturation of a variety of ceramic materials. Anticipated applications for carbide, nitride and oxide-based ceramics will be presented. The current status of these materials and needs for future goals will be outlined. NASA also understands the importance of teaming with other government agencies and industry to optimize these materials and advance them to the level of maturation needed for eventual vehicle and engine demonstrations. A number of successful partnering efforts with NASA and industry will be highlighted.

Asian Tracer Experiment and Atmospheric Modeling (TEAM) Project: Draft Field Work Plan for the Asian Long-Range Tracer Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allwine, K Jerry; Flaherty, Julia E.

2007-08-01

This report provides an experimental plan for a proposed Asian long-range tracer study as part of the international Tracer Experiment and Atmospheric Modeling (TEAM) Project. The TEAM partners are China, Japan, South Korea and the United States. Optimal times of year to conduct the study, meteorological measurements needed, proposed tracer release locations, proposed tracer sampling locations and the proposed durations of tracer releases and subsequent sampling are given. Also given are the activities necessary to prepare for the study and the schedule for completing the preparation activities leading to conducting the actual field operations. This report is intended to providemore » the TEAM members with the information necessary for planning and conducting the Asian long-range tracer study. The experimental plan is proposed, at this time, to describe the efforts necessary to conduct the Asian long-range tracer study, and the plan will undoubtedly be revised and refined as the planning goes forward over the next year.« less

Private versus social incentives for pharmaceutical innovation.

PubMed

González, Paula; Macho-Stadler, Inés; Pérez-Castrillo, David

2016-12-01

We provide a theoretical framework to contribute to the current debate regarding the tendency of pharmaceutical companies to direct their R&D toward marketing products that are "follow-on" drugs of already existing drugs, rather than toward the development of breakthrough drugs. We construct a model with a population of patients who can be treated with drugs that are horizontally and vertically differentiated. In addition to a pioneering drug, a new drug can be marketed as the result of an innovative process. We analyze physician prescription choices and the optimal pricing decision of an innovative firm. We also characterize the incentives of the innovative firm to conduct R&D activities, disentangling the quest for breakthrough drugs from the firm effort to develop follow-on drugs. Our results offer theoretical support for the conventional wisdom that pharmaceutical firms devote too many resources to conducting R&D activities that lead to incremental innovations. Copyright © 2016 Elsevier B.V. All rights reserved.

Alpha: A real-time decentralized operating system for mission-oriented system integration and operation

NASA Technical Reports Server (NTRS)

Jensen, E. Douglas

1988-01-01

Alpha is a new kind of operating system that is unique in two highly significant ways. First, it is decentralized transparently providing reliable resource management across physically dispersed nodes, so that distributed applications programming can be done largely as though it were centralized. And second, it provides comprehensive, high technology support for real-time system integration and operation, an application area which consists predominately of aperiodic activities having critical time constraints such as deadlines. Alpha is extremely adaptable so that it can be easily optimized for a wide range of problem-specific functionality, performance, and cost. Alpha is the first systems effort of the Archons Project, and the prototype was created at Carnegie-Mellon University directly on modified Sun multiprocessor workstation hardware. It has been demonstrated with a real-time C(sup 2) application. Continuing research is leading to a series of enhanced follow-ons to Alpha; these are portable but initially hosted on Concurrent's MASSCOMP line of multiprocessor products.

Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.

PubMed

Mulvihill, Mark J; Cooke, Andrew; Rosenfeld-Franklin, Maryland; Buck, Elizabeth; Foreman, Ken; Landfair, Darla; O'Connor, Matthew; Pirritt, Caroline; Sun, Yingchaun; Yao, Yan; Arnold, Lee D; Gibson, Neil W; Ji, Qun-Sheng

2009-09-01

The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents. Our lead optimization efforts that blended structure-based design and empirical medicinal chemistry led to the discovery of OSI-906, a novel small-molecule dual IGF-1R/insulin receptor (IR) kinase inhibitor. OSI-906 potently and selectively inhibits autophosphorylation of both human IGF-1R and IR, displays in vitro antiproliferative effects in a variety of tumor cell lines and shows robust in vivo anti-tumor efficacy in an IGF-1R-driven xenograft model when administered orally once daily. OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing.

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

DOE PAGES

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang; ...

2018-02-09

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

Competing charge transfer pathways at the photosystem II-electrode interface

PubMed Central

Zhang, Jenny Z.; Sokol, Katarzyna P.; Paul, Nicholas; Romero, Elisabet; van Grondelle, Rienk; Reisner, Erwin

2016-01-01

The integration of the water-oxidation enzyme, photosystem II (PSII), into electrodes allows the electrons extracted from water-oxidation to be harnessed for enzyme characterization and driving novel endergonic reactions. However, PSII continues to underperform in integrated photoelectrochemical systems despite extensive optimization efforts. Here, we performed protein-film photoelectrochemistry on spinach and Thermosynechococcus elongatus PSII, and identified a competing charge transfer pathway at the enzyme-electrode interface that short-circuits the known water-oxidation pathway: photo-induced O2 reduction occurring at the chlorophyll pigments. This undesirable pathway is promoted by the embedment of PSII in an electron-conducting matrix, a common strategy of enzyme immobilization. Anaerobicity helps to recover the PSII photoresponses, and unmasked the onset potentials relating to the QA/QB charge transfer process. These findings have imparted a fuller understanding of the charge transfer pathways within PSII and at photosystem-electrode interfaces, which will lead to more rational design of pigment-containing photoelectrodes in general. PMID:27723748

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

Development Status of a CVD System to Deposit Tungsten onto UO2 Powder via the WCI6 Process

NASA Technical Reports Server (NTRS)

Mireles, O. R.; Kimberlin, A.; Broadway, J.; Hickman, R.

2014-01-01

Nuclear Thermal Propulsion (NTP) is under development for deep space exploration. NTP's high specific impulse (> 850 second) enables a large range of destinations, shorter trip durations, and improved reliability. W-60vol%UO2 CERMET fuel development efforts emphasize fabrication, performance testing and process optimization to meet service life requirements. Fuel elements must be able to survive operation in excess of 2850 K, exposure to flowing hydrogen (H2), vibration, acoustic, and radiation conditions. CTE mismatch between W and UO2 result in high thermal stresses and lead to mechanical failure as a result UO2 reduction by hot hydrogen (H2) [1]. Improved powder metallurgy fabrication process control and mitigated fuel loss can be attained by coating UO2 starting powders within a layer of high density tungsten [2]. This paper discusses the advances of a fluidized bed chemical vapor deposition (CVD) system that utilizes the H2-WCl6 reduction process.

Discovery of chiral dihydropyridopyrimidinones as potent, selective and orally bioavailable inhibitors of AKT.

PubMed

Parthasarathy, Saravanan; Henry, Kenneth; Pei, Huaxing; Clayton, Josh; Rempala, Mark; Johns, Deidre; De Frutos, Oscar; Garcia, Pablo; Mateos, Carlos; Pleite, Sehila; Wang, Yong; Stout, Stephanie; Condon, Bradley; Ashok, Sheela; Lu, Zhohai; Ehlhardt, William; Raub, Tom; Lai, Mei; Geeganage, Sandaruwan; Burkholder, Timothy P

2018-06-01

During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK 2 . A key challenge in this program was the poor physicochemical properties of the initial lead compound 5. Integration of structure-based drug design and physical properties-based design resulted in replacement of a highly hydrophobic poly fluorinated aryl ring by a simple trifluoromethyl that led to identification of compound 6 with much improved physicochemical properties. Subsequent SAR studies led to the synthesis of new pyran analog 7 with improved cell potency. Further optimization of pharmacokintetics properties by increasing permeability with appropriate fluorinated alkyl led to compound 8 as a potent, selective AKT inhibitors that blocks the phosphorylation of GSK3β in vivo and had robust, dose and concentration dependent efficacy in the U87MG tumor xenograft model. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Free-radical reactions in diabetes mellitus].

PubMed

Mrowicka, Małgorzata

2005-10-01

Type 2 diabetes mellitus (DM), characterized by decreased insulin secretion, hypoinsulinemia and/or insulin resistance, accounts for 90% of all cases of DM. Oxidative stress is considered as an essential prerequisite for the pathogenesis of this disease. On one hand, current theory of oxidative stress is associated with autooxidation of glucose, which leads to the reactive ketoaldehydes formation, on the other hand it intensifies non-enzymatic glycation of proteins. The increase in reactive oxygen species (ROS) production and a decline in the activity of antioxidants is not only a result of hyperglycemia, but also of hyperinsulinemia and decreased tissue sensitivity to insulin. Because of a significant role of (ROS) in the pathogenesis of chronic diabetic complications, efforts should be made to diminish their toxic effects. Scientific research revealed that the best method for the prevention and treatment of diabetic complications was a long-term compensation of diabetes. To obtain optimal glycemia is crucial, since hyperglycemia is the main source of oxidative stress in patients with diabetes mellitus.

Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA

PubMed Central

Doritchamou, Justin; Sabbagh, Audrey; Jespersen, Jakob S.; Renard, Emmanuelle; Salanti, Ali; Nielsen, Morten A.; Deloron, Philippe; Tuikue Ndam, Nicaise

2015-01-01

The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. PMID:26393516

EMR-based TeleGeriatric system.

PubMed

Pallawala, P M; Lun, K C

2001-01-01

As medical services improve due to new technologies and breakthroughs, it has lead to an increasingly aging population. There has been much discussion and debate on how to solve various aspects such as psychological, socio-economic and medical problems related to aging. Our effort is to implement a feasible telegeriatric medical service with the use of the state of the art technology to deliver medical services efficiently to remote sites where elderly homes are based. The TeleGeriatric system will lead to rapid decision-making in the presence of acute or subacute emergencies. This triage will also lead to a reduction of unnecessary admission. It will enable the doctors who visit these elderly homes once a week basis to improve their geriatric management skills by communication with geriatric specialist. Nursing skills in the geriatric care will also benefit from this system. Integrated electronic medical record (EMR) system will be indispensable in the face of emergency admissions to hospitals. Evolution of EMR database would lead to future research in telegeriatrics and will help to identify the areas where telegeriatrics can be optimally used. This system is based on current web browsing technology and broadband communication. The TeleGeriatric web based server is developed using Java Technology. The TeleGeriatric database server was developed using Microsoft SQL server. Both are based at the Medical Informatics Programme, National University of Singapore. Two elderly homes situated in the periphery of Singapore and a leading government hospital in geriatric care have been chosen for the project. These 3 institutions and National University of Singapore are connected via ADSL protocol. ADSL connection supports high bandwidth, which is necessary for high quality videoconferencing. Each time a patient needs a teleconsultation a nurse or a doctor in the remote site sends the patient's record to the TeleGeriatric server. The TeleGeriatric server forwards the request to the Alexandra Hospital for consultation. Geriatrics specialists at the Alexandra Hospital carry out teleward rounds twice weekly and on demand basis. Following the implementation of the system, a trial run has been done. Total results have demonstrated a high degree of coordination and cooperation between remote site and the Alexandra Hospital. Also the patient compliance is very high and they prefer teleconsultation. Initial results show that the TeleGeriatric system has definite advantages in managing geriatric patients at a remote site. As the system evolves, further research will show the areas where telegeriatrics can be used optimally.

A traditional and a less-invasive robust design: choices in optimizing effort allocation for seabird population studies

USGS Publications Warehouse

Converse, S.J.; Kendall, W.L.; Doherty, P.F.; Naughton, M.B.; Hines, J.E.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

2009-01-01

For many animal populations, one or more life stages are not accessible to sampling, and therefore an unobservable state is created. For colonially-breeding populations, this unobservable state could represent the subset of adult breeders that have foregone breeding in a given year. This situation applies to many seabird populations, notably albatrosses, where skipped breeders are either absent from the colony, or are present but difficult to capture or correctly assign to breeding state. Kendall et al. have proposed design strategies for investigations of seabird demography where such temporary emigration occurs, suggesting the use of the robust design to permit the estimation of time-dependent parameters and to increase the precision of estimates from multi-state models. A traditional robust design, where animals are subject to capture multiple times in a sampling season, is feasible in many cases. However, due to concerns that multiple captures per season could cause undue disturbance to animals, Kendall et al. developed a less-invasive robust design (LIRD), where initial captures are followed by an assessment of the ratio of marked-to-unmarked birds in the population or sampled plot. This approach has recently been applied in the Northwestern Hawaiian Islands to populations of Laysan (Phoebastria immutabilis) and black-footed (P. nigripes) albatrosses. In this paper, we outline the LIRD and its application to seabird population studies. We then describe an approach to determining optimal allocation of sampling effort in which we consider a non-robust design option (nRD), and variations of both the traditional robust design (RD), and the LIRD. Variations we considered included the number of secondary sampling occasions for the RD and the amount of total effort allocated to the marked-to-unmarked ratio assessment for the LIRD. We used simulations, informed by early data from the Hawaiian study, to address optimal study design for our example cases. We found that the LIRD performed as well or nearly as well as certain variations of the RD in terms of root mean square error, especially when relatively little of the total effort was allocated to the assessment of the marked-to-unmarked ratio versus to initial captures. For the RD, we found no clear benefit of using 2, 4, or 6 secondary sampling occasions per year, though this result will depend on the relative effort costs of captures versus recaptures and on the length of the study. We also found that field-readable bands, which may be affixed to birds in addition to standard metal bands, will be beneficial in longer-term studies of albatrosses in the Northwestern Hawaiian Islands. Field-readable bands reduce the effort cost of recapturing individuals, and in the long-term this cost reduction can offset the additional effort expended in affixing the bands. Finally, our approach to determining optimal study design can be generally applied by researchers, with little seed data, to design their studies at the outset.

Nonlinear optimal control for the synchronization of chaotic and hyperchaotic finance systems

NASA Astrophysics Data System (ADS)

Rigatos, G.; Siano, P.; Loia, V.; Ademi, S.; Ghosh, T.

2017-11-01

It is possible to make specific finance systems get synchronized to other finance systems exhibiting chaotic and hyperchaotic dynamics, by applying nonlinear optimal (H-infinity) control. This signifies that chaotic behavior can be generated in finance systems by exerting a suitable control input. Actually, a lead financial system is considered which exhibits inherently chaotic dynamics. Moreover, a follower finance system is introduced having parameters in its model that inherently prohibit the appearance of chaotic dynamics. Through the application of a suitable nonlinear optimal (H-infinity) control input it is proven that the follower finance system can replicate the chaotic dynamics of the lead finance system. By applying Lyapunov analysis it is proven that asymptotically the follower finance system gets synchronized with the lead system and that the tracking error between the state variables of the two systems vanishes.

Optimization of the magnetic dynamo.

PubMed

Willis, Ashley P

2012-12-21

In stars and planets, magnetic fields are believed to originate from the motion of electrically conducting fluids in their interior, through a process known as the dynamo mechanism. In this Letter, an optimization procedure is used to simultaneously address two fundamental questions of dynamo theory: "Which velocity field leads to the most magnetic energy growth?" and "How large does the velocity need to be relative to magnetic diffusion?" In general, this requires optimization over the full space of continuous solenoidal velocity fields possible within the geometry. Here the case of a periodic box is considered. Measuring the strength of the flow with the root-mean-square amplitude, an optimal velocity field is shown to exist, but without limitation on the strain rate, optimization is prone to divergence. Measuring the flow in terms of its associated dissipation leads to the identification of a single optimal at the critical magnetic Reynolds number necessary for a dynamo. This magnetic Reynolds number is found to be only 15% higher than that necessary for transient growth of the magnetic field.

QuEST: Qualifying Environmentally Sustainable Technologies. Volume 6

NASA Technical Reports Server (NTRS)

Lewis, Pattie

2011-01-01

QuEST is a publication of the NASA Technology Evaluation for Environmental Risk Mitigation Principal Center (TEERM). This issue contains brief articles on: Risk Identification and Mitigation, Material Management and Substitution Efforts--Hexavalent Chrome-free Coatings and Low volatile organic compounds (VOCs) Coatings, Lead-Free Electronics, Corn-Based Depainting Media; Alternative Energy Efforts Hydrogen Sensors and Solar Air Conditioning. Other TEERM Efforts include: Energy and Water Management and Remediation Technology Collaboration.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singer, M.; Daley, R.

This report focuses on the National Renewable Energy Laboratory's (NREL) fiscal year (FY) 2012 effort that used the NREL Optimal Vehicle Acquisition (NOVA) analysis to identify optimal vehicle acquisition recommendations for eleven diverse federal agencies. Results of the study show that by following a vehicle acquisition plan that maximizes the reduction in greenhouse gas (GHG) emissions, significant progress is also made toward the mandated complementary goals of acquiring alternative fuel vehicles, petroleum use reduction, and alternative fuel use increase.

Optimal Cost Avoidance Investment and Pricing Strategies for Performance-Based Post-Production Service Contracts

DTIC Science & Technology

2011-04-30

a BS degree in Mathematics and an MS degree in Statistics and Financial and Actuarial Mathematics from Kiev National Taras Shevchenko University...degrees from Rutgers University in Industrial Engineering (PhD and MS) and Statistics (MS) and from Universidad Nacional Autonoma de Mexico in Actuarial ...Science. His research efforts focus on developing mathematical models for the analysis, computation, and optimization of system performance with

Development of a solar-powered residential air conditioner

NASA Technical Reports Server (NTRS)

1975-01-01

The initial objective of the program was the optimization (in terms of cost and performance) of a Rankine cycle mechanical refrigeration system which utilizes thermal energy from a flat solar collector for air conditioning residential buildings. However, feasibility investigations of the adsorption process revealed that a dessicant-type air conditioner offers many significant advantages. As a result, limited efforts were expended toward the optimization of such a system.

Storyline Visualization: A Compelling Way to Understand Patterns over Time and Space

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2017-10-16

Storyline visualization is a compelling way to understand patterns over time and space. Much effort has been spent developing efficient and aesthetically pleasing layout optimization algorithms. But what if those algorithms are optimizing the wrong things? To answer this question, we conducted a design study with different storyline layout algorithms. We found that users with our new design principles for storyline visualization outperform existing methods.

Trajectory Optimization Using Adjoint Method and Chebyshev Polynomial Approximation for Minimizing Fuel Consumption During Climb

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Hornby, Gregory; Ishihara, Abe

2013-01-01

This paper describes two methods of trajectory optimization to obtain an optimal trajectory of minimum-fuel- to-climb for an aircraft. The first method is based on the adjoint method, and the second method is based on a direct trajectory optimization method using a Chebyshev polynomial approximation and cubic spine approximation. The approximate optimal trajectory will be compared with the adjoint-based optimal trajectory which is considered as the true optimal solution of the trajectory optimization problem. The adjoint-based optimization problem leads to a singular optimal control solution which results in a bang-singular-bang optimal control.

Field Turbidity Methods for the Determination of Lead in Acid Extracts of Dried Paint

EPA Science Inventory

Lead, which can be found in old paint, soil, and dust, has been clearly shown to have adverse health effects on the neurological systems of both children and adults. As part of an ongoing effort to reduce childhood lead poisoning, the U.S. Environmental Protection Agency promulga...

The Ideologies of American Social Critics: An Empirical Test of Kadushin's Theory

ERIC Educational Resources Information Center

Simon, David R.

1977-01-01

Examines Kadushin's earlier empirical efforts to determine the leading social critics and organizations of social criticism in America and investigates his theory through content analysis of leading journals of social criticism. (MH)

Dynamics and control of detumbling a disabled spacecraft during rescue operations

NASA Technical Reports Server (NTRS)

Kaplan, M. H.

1973-01-01

Results of a two-year research effort on dynamics and control of detumbling a disabled spacecraft during rescue operations are summarized. Answers to several basic questions about associated techniques and hardware requirements were obtained. Specifically, efforts have included development of operational procedures, conceptual design of remotely controlled modules, feasibility of internal moving mass for stabilization, and optimal techniques for minimum-time detumbling. Results have been documented in several reports and publications.