Meeting on Literacy Training, Berlin (West). Final Report. July 11-17, 1975.

ERIC Educational Resources Information Center

International Inst. for Adult Literacy Methods, Teheran (Iran).

This report's major points are highlighted in two sections: Section One sets forth the rational, design, and intended use of the training monograph series, "Literacy in Development", which (1) has been commissioned by the International Institute for Adult Literacy Methods, (2) is to be used as the basis for the Institute's future training…

Vector Design Tour de Force: Integrating Combinatorial and Rational Approaches to Derive Novel Adeno-associated Virus Variants

PubMed Central

Marsic, Damien; Govindasamy, Lakshmanan; Currlin, Seth; Markusic, David M; Tseng, Yu-Shan; Herzog, Roland W; Agbandje-McKenna, Mavis; Zolotukhin, Sergei

2014-01-01

Methodologies to improve existing adeno-associated virus (AAV) vectors for gene therapy include either rational approaches or directed evolution to derive capsid variants characterized by superior transduction efficiencies in targeted tissues. Here, we integrated both approaches in one unified design strategy of “virtual family shuffling” to derive a combinatorial capsid library whereby only variable regions on the surface of the capsid are modified. Individual sublibraries were first assembled in order to preselect compatible amino acid residues within restricted surface-exposed regions to minimize the generation of dead-end variants. Subsequently, the successful families were interbred to derive a combined library of ~8 × 105 complexity. Next-generation sequencing of the packaged viral DNA revealed capsid surface areas susceptible to directed evolution, thus providing guidance for future designs. We demonstrated the utility of the library by deriving an AAV2-based vector characterized by a 20-fold higher transduction efficiency in murine liver, now equivalent to that of AAV8. PMID:25048217

Failure: A Source of Progress in Maintenance and Design

NASA Astrophysics Data System (ADS)

Chaïb, R.; Taleb, M.; Benidir, M.; Verzea, I.; Bellaouar, A.

This approach, allows using the failure as a source of progress in maintenance and design to detect the most critical components in equipment, to determine the priority order maintenance actions to lead and direct the exploitation procedure towards the most penalizing links in this equipment, even define the necessary changes and recommendations for future improvement. Thus, appreciate the pathological behaviour of the material and increase its availability, even increase its lifespan and improve its future design. In this context and in the light of these points, the failures are important in managing the maintenance function. Indeed, it has become important to understand the phenomena of failure and degradation of equipments in order to establish an appropriate maintenance policy for the rational use of mechanical components and move to the practice of proactive maintenance [1], do maintenance at the design [2].

Rational design of high-yield and superior-quality rice.

PubMed

Zeng, Dali; Tian, Zhixi; Rao, Yuchun; Dong, Guojun; Yang, Yaolong; Huang, Lichao; Leng, Yujia; Xu, Jie; Sun, Chuan; Zhang, Guangheng; Hu, Jiang; Zhu, Li; Gao, Zhenyu; Hu, Xingming; Guo, Longbiao; Xiong, Guosheng; Wang, Yonghong; Li, Jiayang; Qian, Qian

2017-03-20

Rice (Oryza sativa L.) is a staple food for more than half of the world's population. To meet the ever-increasing demand for food, because of population growth and improved living standards, world rice production needs to double by 2030 1 . The development of new elite rice varieties with high yield and superior quality is challenging for traditional breeding approaches, and new strategies need to be developed. Here, we report the successful development of new elite varieties by pyramiding major genes that significantly contribute to grain quality and yield from three parents over five years. The new varieties exhibit higher yield potential and better grain quality than their parental varieties and the China's leading super-hybrid rice, Liang-you-pai-jiu (LYP9 or Pei-ai 64S/93-11). Our results demonstrate that rational design is a powerful strategy for meeting the challenges of future crop breeding, particularly in pyramiding multiple complex traits.

Rational Design of Tunnel Supports: An Interactive Graphics Based Analysis of the Support Requirements of Excavations in Jointed Rock Masses.

DTIC Science & Technology

1979-09-01

joint orientetion and joint slippage than to failure of the intact rock mass. Dixon (1971) noted the importance of including the confining influence of...dedicated computer. The area of research not covered by this investigation which holds promise for a future study is a detailed comparison of the results of...block data, type key "W". The program writes this data on Linc tapes for future retripval. This feature can be used to store the consolidated block

Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

DTIC Science & Technology

2015-12-21

SECURITY CLASSIFICATION OF: The overall goal of this project is to determine how electrode surface chemistry can be rationally designed to decrease...2015 Approved for Public Release; Distribution Unlimited Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for...ABSTRACT Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

Rapid humanitarian assessments and rationality: a value-of-information study from Iraq, 2003-04.

PubMed

Benini, Aldo; Conley, Charles

2007-03-01

Rapid assessments are one of the standard informational tools in humanitarian response and are supposed to contribute to rational decision-making.(1) The extent to which the assessment organisation itself behaves rationally, however, is an open question. This can be evaluated against multiple criteria, such as the cost and value of the information it collects and its ability to adapt flexibly design or samples when the survey environment changes unforeseeably. An unusual data constellation from two concurrent recent (2003-04) rapid assessments in northern Iraq permits us to model part of the actual assessment behaviour in terms of geographical, community and prior substantive information attributes. The model correctly predicts the decisions, in 79 per cent of the 2,425 local communities in focus, that data collector teams in the Emergency Mine Action Survey made to visit or not to visit. The analysis demonstrates variably rational behaviour under conditions of insecurity, repeated regrouping and incomplete sampling frames. A pronounced bias towards very small rural settlements is irrational for the overall results, but may be a rational strategy of individual survey workers seeking to prolong their employment. Implications for future assessments are sketched in the areas of tools for urban surveys, greater adaptability, including early feedback from users, and sensibility to value-of-information concepts.

Operational Rations Current and Future of the Department of Defense

DTIC Science & Technology

1982-09-01

with Spiced Sauce Beefsteak Chicken and Noodles Chicken or Turkey, Boned Apricots Peaches Chocolate Nut Roll Cookies Grape MEATS Ham and...Sauce Tuna Fish Turkey Loaf Fruit Cocktail Peacan Cake Roll Pound Cake Orange Tomato 16 ACCESSORY ITEMS Instant Coffee Instant Tea or Tea... INSTANT ACCESSORY PACKET FOOD PACKET, IN-FLIGHT INDIVIDUAL SPOON EARLY VERSION VI FOOD PACKET, LONG-RANGE Designed for troops in operations

On Organizations of the Future. Administrative and Policy Studies Series: Volume I, No. 03-006. A Sage Professional Paper.

ERIC Educational Resources Information Center

Argyris, Chris

Some of the most important causes for organizational deterioration and entropy are related to the fact that organizations have been designed and managed on a restricted view of man. Lack of interpersonal competence (and its consequences in group and intergroup behavior) has helped to create such an internal environment that the rational and…

Rationing critical care medicine: recent studies and current trends.

PubMed

Ward, Nicholas S

2005-12-01

This paper reviews the literature on the rationing of critical care resources. Although much has been written about the concept of rationing, there have been few scientific studies as to its prevalence. A recent meta-analysis reviewed all previously published studies on rationing access to intensive care units but little is known about practices within the intensive care unit. Much literature in the past few years has focused on the growing use of critical care resources and projections for the future. Several authors suggest there may be a crisis in financial or personnel resources if some rationing does not take place. Other papers have argued that the methods of rationing critical care previously proposed, such as limiting the care of dying patients or using cost-effectiveness analysis to determine care, may not be effective or viewed as ethical by some. Finally, several recent papers review how critical care is practiced and allocated in India and Asian countries that already practice open rationing in their health care systems. There is currently no published evidence that overt rationing is taking place in critical care medicine. There is growing evidence that in the future, the need for critical care may outstrip financial resources unless some form of rationing takes place. It is also clear from the literature that choosing how to ration critical care will be a difficult task.

Solution Synthesis of Atomically Precise Graphene Nanoribbons

NASA Astrophysics Data System (ADS)

Shekhirev, Mikhail; Sinitskii, Alexander

2017-05-01

Bottom-up fabrication of narrow strips of graphene, also known as graphene nanoribbons or GNRs, is an attractive way to open a bandgap in semimetallic graphene. In this chapter, we review recent progress in solution-based synthesis of GNRs with atomically precise structures. We discuss a variety of atomically precise GNRs and highlight theoretical and practical aspects of their structural design and solution synthesis. These GNRs are typically synthesized through a polymerization of rationally designed molecular precursors followed by a planarization through a cyclodehydrogenation reaction. We discuss various synthetic techniques for polymerization and planarization steps, possible approaches for chemical modification of GNRs, and compare the properties of GNRs that could be achieved by different synthetic methods. We also discuss the importance of the rational design of molecular precursors to avoid isomerization during the synthesis and achieve GNRs that have only one possible structure. Significant attention in this chapter is paid to the methods of material characterization of solution-synthesized GNRs. The chapter is concluded with the discussion of the most significant challenges in the field and the future outlook.

Computerized structural mechanics for 1990's: Advanced aircraft needs

NASA Technical Reports Server (NTRS)

Viswanathan, A. V.; Backman, B. F.

1989-01-01

The needs for computerized structural mechanics (CSM) as seen from the standpoint of the aircraft industry are discussed. These needs are projected into the 1990's with special focus on the new advanced materials. Preliminary design/analysis, research, and detail design/analysis are identified as major areas. The role of local/global analyses in these different areas is discussed. The lessons learned in the past are used as a basis for the design of a CSM framework that could modify and consolidate existing technology and include future developments in a rational and useful way. A philosophy is stated, and a set of analyses needs driven by the emerging advanced composites is enumerated. The roles of NASA, the universities, and the industry are identified. Finally, a set of rational research targets is recommended based on both the new types of computers and the increased complexity the industry faces. Computerized structural mechanics should be more than new methods in structural mechanics and numerical analyses. It should be a set of engineering applications software products that combines innovations in structural mechanics, numerical analysis, data processing, search and display features, and recent hardware advances and is organized in a framework that directly supports the design process.

Vaccine technologies: From whole organisms to rationally designed protein assemblies.

PubMed

Karch, Christopher P; Burkhard, Peter

2016-11-15

Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition of adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development. Copyright © 2016 Elsevier Inc. All rights reserved.

Hot-spot analysis for drug discovery targeting protein-protein interactions.

PubMed

Rosell, Mireia; Fernández-Recio, Juan

2018-04-01

Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

Rational design of a dual-mode optical and chemical prodrug.

PubMed

McCoy, Colin P; Rooney, Clare; Jones, David S; Gorman, Sean P; Nieuwenhuyzen, Mark

2007-01-01

The purpose of this study is to demonstrate the rational design and behaviour of the first dual-mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system. A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution. The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30x10(-2) s-1, while chemical, hydrolytic liberation proceeded independently at 1.89x10(-3) s-1. The photochemical and hydrolytic reactions were both quantitative. This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.

Mapping out past and future minds: The perceived trajectory of rationality versus emotionality over time.

PubMed

O'Brien, Ed

2015-06-01

Who do we see when envisioning our "past self" and "future self"? Extant research finds a motivation to perceive improvement over time, such that past selves are seen as worse versions, and future selves as better versions, of current selves. However, the broader components comprising "worse" or "better" beyond domain-specific achievement (e.g., "Last year I failed at dieting, but next year I'll succeed") are less well understood. Are there more general qualities ascribed to the person we recall versus imagine being? Six studies suggest so, extending the 2-dimensional mind perception framework to the self: Past selves seem to possess highly emotional but not very rational minds, whereas future selves seem to possess highly rational but not very emotional minds (Studies 1a, 1b, 1c). Consistent with motivated improvement, this asymmetry does not emerge in evaluating others and applies uniquely to self-judgment (Study 2). Thus, our pervasive belief in changing for the "better" specifically means becoming more rational types of people. This observation has asymmetric consequences. Participants who brought to mind future selves sought intellectual enrichment (Study 3) and performed better on a self-control task (Study 4); however, participants who brought to mind past selves sought emotional enrichment and performed better on the same task when allegedly measuring enjoyment. These findings build a bridge between mind perception and intertemporal dynamics, raising novel implications for the present. Thinking about the future may not uniformly "improve" decisions and behaviors; rather, it mostly facilitates rational-related pursuits, whereas thinking about the past may enhance feeling-related experiences. (c) 2015 APA, all rights reserved).

Reflections of the social environment in chimpanzee memory: applying rational analysis beyond humans.

PubMed

Stevens, Jeffrey R; Marewski, Julian N; Schooler, Lael J; Gilby, Ian C

2016-08-01

In cognitive science, the rational analysis framework allows modelling of how physical and social environments impose information-processing demands onto cognitive systems. In humans, for example, past social contact among individuals predicts their future contact with linear and power functions. These features of the human environment constrain the optimal way to remember information and probably shape how memory records are retained and retrieved. We offer a primer on how biologists can apply rational analysis to study animal behaviour. Using chimpanzees ( Pan troglodytes ) as a case study, we modelled 19 years of observational data on their social contact patterns. Much like humans, the frequency of past encounters in chimpanzees linearly predicted future encounters, and the recency of past encounters predicted future encounters with a power function. Consistent with the rational analyses carried out for human memory, these findings suggest that chimpanzee memory performance should reflect those environmental regularities. In re-analysing existing chimpanzee memory data, we found that chimpanzee memory patterns mirrored their social contact patterns. Our findings hint that human and chimpanzee memory systems may have evolved to solve similar information-processing problems. Overall, rational analysis offers novel theoretical and methodological avenues for the comparative study of cognition.

Reflections of the social environment in chimpanzee memory: applying rational analysis beyond humans

PubMed Central

Marewski, Julian N.; Schooler, Lael J.; Gilby, Ian C.

2016-01-01

In cognitive science, the rational analysis framework allows modelling of how physical and social environments impose information-processing demands onto cognitive systems. In humans, for example, past social contact among individuals predicts their future contact with linear and power functions. These features of the human environment constrain the optimal way to remember information and probably shape how memory records are retained and retrieved. We offer a primer on how biologists can apply rational analysis to study animal behaviour. Using chimpanzees (Pan troglodytes) as a case study, we modelled 19 years of observational data on their social contact patterns. Much like humans, the frequency of past encounters in chimpanzees linearly predicted future encounters, and the recency of past encounters predicted future encounters with a power function. Consistent with the rational analyses carried out for human memory, these findings suggest that chimpanzee memory performance should reflect those environmental regularities. In re-analysing existing chimpanzee memory data, we found that chimpanzee memory patterns mirrored their social contact patterns. Our findings hint that human and chimpanzee memory systems may have evolved to solve similar information-processing problems. Overall, rational analysis offers novel theoretical and methodological avenues for the comparative study of cognition. PMID:27853606

Rational design of novel cathode materials in solid oxide fuel cells using first-principles simulations

NASA Astrophysics Data System (ADS)

Choi, YongMan; Lin, M. C.; Liu, Meilin

The search for clean and renewable sources of energy represents one of the most vital challenges facing us today. Solid oxide fuel cells (SOFCs) are among the most promising technologies for a clean and secure energy future due to their high energy efficiency and excellent fuel flexibility (e.g., direct utilization of hydrocarbons or renewable fuels). To make SOFCs economically competitive, however, development of new materials for low-temperature operation is essential. Here we report our results on a computational study to achieve rational design of SOFC cathodes with fast oxygen reduction kinetics and rapid ionic transport. Results suggest that surface catalytic properties are strongly correlated with the bulk transport properties in several material systems with the formula of La 0.5Sr 0.5BO 2.75 (where B = Cr, Mn, Fe, or Co). The predictions seem to agree qualitatively with available experimental results on these materials. This computational screening technique may guide us to search for high-efficiency cathode materials for a new generation of SOFCs.

Hierarchical nanostructures for functional materials.

PubMed

Qin, Zhao; Buehler, Markus J

2018-07-13

Naturally occurring biomaterials often have amazing functions, such as mechanical, thermal, electromagnetic, biological, optical and acoustic. These superior performances are often due to their hierarchical organizations of natural materials, starting from the nanoscopic scale and extending all the way to the macroscopic level. This topical issue features articles dedicated to understanding, designing and characterizing complex de novo hierarchical materials for a variety of applications. This research area is quickly evolving, and we hope that future work will drive the rational designs of innovative functional materials and generate deep impacts to broad engineering fields that address major societal challenges and needs.

Hierarchical nanostructures for functional materials

NASA Astrophysics Data System (ADS)

Qin, Zhao; Buehler, Markus J.

2018-07-01

Naturally occurring biomaterials often have amazing functions, such as mechanical, thermal, electromagnetic, biological, optical and acoustic. These superior performances are often due to their hierarchical organizations of natural materials, starting from the nanoscopic scale and extending all the way to the macroscopic level. This topical issue features articles dedicated to understanding, designing and characterizing complex de novo hierarchical materials for a variety of applications. This research area is quickly evolving, and we hope that future work will drive the rational designs of innovative functional materials and generate deep impacts to broad engineering fields that address major societal challenges and needs.

Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

PubMed

Li, Minyong; Xia, Lin

2007-11-01

In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

Rational Design Methodology.

DTIC Science & Technology

1978-09-01

This report describes an effort to specify a software design methodology applicable to the Air Force software environment . Available methodologies...of techniques for proof of correctness, design specification, and performance assessment of static designs. The rational methodology selected is a

Modeling Addictive Consumption as an Infectious Disease*

PubMed Central

Alamar, Benjamin; Glantz, Stanton A.

2011-01-01

The dominant model of addictive consumption in economics is the theory of rational addiction. The addict in this model chooses how much they are going to consume based upon their level of addiction (past consumption), the current benefits and all future costs. Several empirical studies of cigarette sales and price data have found a correlation between future prices and consumption and current consumption. These studies have argued that the correlation validates the rational addiction model and invalidates any model in which future consumption is not considered. An alternative to the rational addiction model is one in which addiction spreads through a population as if it were an infectious disease, as supported by the large body of empirical research of addictive behaviors. In this model an individual's probability of becoming addicted to a substance is linked to the behavior of their parents, friends and society. In the infectious disease model current consumption is based only on the level of addiction and current costs. Price and consumption data from a simulation of the infectious disease model showed a qualitative match to the results of the rational addiction model. The infectious disease model can explain all of the theoretical results of the rational addiction model with the addition of explaining initial consumption of the addictive good. PMID:21339848

Assessment: Give Me a Place to Stand, and I Will Move the Earth

DTIC Science & Technology

2012-06-01

Theory , and Policy Keywords: C2 agility, bounded rationality, heuristics, uncertainty, assessment Authors: Erik Bjurström Mälardalen...of making decisions. Although the notion of bounded rationality and its associated theory rendered Herbert Simon the 1978 Nobel prize in economics...future and represents a more structuralistic approach. While making predictions about the future is often necessary it is not feasible as a general

Drug Design and Emotion

NASA Astrophysics Data System (ADS)

Folkers, Gerd; Wittwer, Amrei

2007-11-01

"Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors.

PubMed

Kellici, Tahsin F; Tzakos, Andreas G; Mavromoustakos, Thomas

2015-03-02

The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.

Structure-based engineering of a pectate lyase with improved specific activity for ramie degumming.

PubMed

Zhou, Zhanping; Liu, Yang; Chang, Zhenying; Wang, Huilin; Leier, André; Marquez-Lago, Tatiana T; Ma, Yanhe; Li, Jian; Song, Jiangning

2017-04-01

Biotechnological applications of microbial pectate lyases (Pels) in plant fiber processing are promising, eco-friendly substitutes for conventional chemical degumming processes. However, to potentiate the enzymes' use for industrial applications, resolving the molecular structure to elucidate catalytic mechanisms becomes necessary. In this manuscript, we report the high resolution (1.45 Å) crystal structure of pectate lyase (pelN) from Paenibacillus sp. 0602 in apo form. Through sequence alignment and structural superposition with other members of the polysaccharide lyase (PL) family 1 (PL1), we determined that pelN shares the characteristic right-handed β-helix and is structurally similar to other members of the PL1 family, while exhibiting key differences in terms of catalytic and substrate binding residues. Then, based on information from structure alignments with other PLs, we engineered a novel pelN. Our rational design yielded a pelN mutant with a temperature for enzymatic activity optimally shifted from 67.5 to 60 °C. Most importantly, this pelN mutant displayed both higher specific activity and ramie fiber degumming ability when compared with the wild-type enzyme. Altogether, our rational design method shows great potential for industrial applications. Moreover, we expect the reported high-resolution crystal structure to provide a solid foundation for future rational, structure-based engineering of genetically enhanced pelNs.

Developing and Testing Rational Models of Message Design.

ERIC Educational Resources Information Center

O'Keefe, Barbara J.

1992-01-01

Responds to an article in the same issue regarding research methods for conversational cognition. Argues for a noncognitive view of rational models in communication research. Sets out an analysis of the kinds of claims made by rational models of message design. Discusses the implications of this analysis for studies of the cognitive processes…

Clinical review: The hospital of the future - building intelligent environments to facilitate safe and effective acute care delivery

PubMed Central

2012-01-01

The translation of knowledge into rational care is as essential and pressing a task as the development of new diagnostic or therapeutic devices, and is arguably more important. The emerging science of health care delivery has identified the central role of human factor ergonomics in the prevention of medical error, omission, and waste. Novel informatics and systems engineering strategies provide an excellent opportunity to improve the design of acute care delivery. In this article, future hospitals are envisioned as organizations built around smart environments that facilitate consistent delivery of effective, equitable, and error-free care focused on patient-centered rather than provider-centered outcomes. PMID:22546172

Future vaccination strategies against tuberculosis: thinking outside the box.

PubMed

Kaufmann, Stefan H E

2010-10-29

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.

Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids

DOE PAGES

Bolt, H. L.; Williams, C. E. J.; Brooks, R. V.; ...

2017-01-13

Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing themore » former as a predictive tool in the rational design of biologically active peptoids.« less

Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids

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

Bolt, H. L.; Williams, C. E. J.; Brooks, R. V.

Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing themore » former as a predictive tool in the rational design of biologically active peptoids.« less

Engineering Metallic Nanoparticles for Enhancing and Probing Catalytic Reactions.

PubMed

Collins, Gillian; Holmes, Justin D

2016-07-01

Recent developments in tailoring the structural and chemical properties of colloidal metal nanoparticles (NPs) have led to significant enhancements in catalyst performance. Controllable colloidal synthesis has also allowed tailor-made NPs to serve as mechanistic probes for catalytic processes. The innovative use of colloidal NPs to gain fundamental insights into catalytic function will be highlighted across a variety of catalytic and electrocatalytic applications. The engineering of future heterogenous catalysts is also moving beyond size, shape and composition considerations. Advancements in understanding structure-property relationships have enabled incorporation of complex features such as tuning surface strain to influence the behavior of catalytic NPs. Exploiting plasmonic properties and altering colloidal surface chemistry through functionalization are also emerging as important areas for rational design of catalytic NPs. This news article will highlight the key developments and challenges to the future design of catalytic NPs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies.

PubMed

Grant, Steven

2018-06-01

Venetoclax (ABT-199) is a Bcl-2-specific BH3-mimetic that has shown significant promise in certain subtypes of CLL as well as in several other hematologic malignancies. As in the case of essentially all targeted agents, intrinsic or acquired resistance to this agent generally occurs, prompting the search for new strategies capable of circumventing this problem. A logical approach to this challenge involves rational combination strategies designed to disable preexisting or induced compensatory survival pathways. Many of these strategies involve downregulation of Mcl-1, a pro-survival Bcl-2 family member that is not targeted by venetoclax, and which often confers resistance to this agent. Given encouraging clinical results involving venetoclax in both lymphoid and myeloid malignancies, it is likely that such combination approaches will be incorporated into the therapeutic armamentarium for multiple hematologic malignancies in the near future.

Engineering in complex systems.

PubMed

Bujara, Matthias; Panke, Sven

2010-10-01

The implementation of the engineering design cycle of measure, model, manipulate would drastically enhance the success rate of biotechnological designs. Recent progress for the three elements suggests that the scope of the traditional engineering paradigm in biotechnology is expanding. Substantial advances were made in dynamic in vivo analysis of metabolism, which is essential for the accurate prediction of metabolic pathway behavior. Novel methods that require variable degrees of system knowledge facilitate metabolic system manipulation. The combinatorial testing of pre-characterized parts is particularly promising, because it can profit from automation and limits the search space. Finally, conceptual advances in orthogonalizing cells should enhance the reliability of engineering designs in the future. Coupled to improved in silico models of metabolism, these advances should allow a more rational design of metabolic systems. Copyright © 2010 Elsevier Ltd. All rights reserved.

Robust Engineering Designs for Infrastructure Adaptation to a Changing Climate

NASA Astrophysics Data System (ADS)

Samaras, C.; Cook, L.

2015-12-01

Infrastructure systems are expected to be functional, durable and safe over long service lives - 50 to over 100 years. Observations and models of climate science show that greenhouse gas emissions resulting from human activities have changed climate, weather and extreme events. Projections of future changes (albeit with uncertainties caused by inadequacies of current climate/weather models) can be made based on scenarios for future emissions, but actual future emissions are themselves uncertain. Most current engineering standards and practices for infrastructure assume that the probabilities of future extreme climate and weather events will match those of the past. Climate science shows that this assumption is invalid, but is unable, at present, to define these probabilities over the service lives of existing and new infrastructure systems. Engineering designs, plans, and institutions and regulations will need to be adaptable for a range of future conditions (conditions of climate, weather and extreme events, as well as changing societal demands for infrastructure services). For their current and future projects, engineers should: Involve all stakeholders (owners, financers, insurance, regulators, affected public, climate/weather scientists, etc.) in key decisions; Use low regret, adaptive strategies, such as robust decision making and the observational method, comply with relevant standards and regulations, and exceed their requirements where appropriate; Publish design studies and performance/failure investigations to extend the body of knowledge for advancement of practice. The engineering community should conduct observational and modeling research with climate/weather/social scientists and the concerned communities and account rationally for climate change in revised engineering standards and codes. This presentation presents initial research on decisionmaking under uncertainty for climate resilient infrastructure design.

Simulation technology - A key to effective man-machine integration for future combat rotorcraft systems

NASA Technical Reports Server (NTRS)

Kerr, Andrew W.

1990-01-01

The utilization of advanced simulation technology in the development of the non-real-time MANPRINT design tools in the Army/NASA Aircrew-Aircraft Integration (A3I) program is described. A description is then given of the Crew Station Research and Development Facilities, the primary tool for the application of MANPRINT principles. The purpose of the A3I program is to develop a rational, predictive methodology for helicopter cockpit system design that integrates human factors engineering with other principles at an early stage in the development process, avoiding the high cost of previous system design methods. Enabling technologies such as the MIDAS work station are examined, and the potential of low-cost parallel-processing systems is indicated.

Research and Practice on New Technology for Architectural Green Environment in Cities

NASA Astrophysics Data System (ADS)

Wu, Zhang; hvung Cho, Jeung

2018-03-01

The importance of urban development has become a topic that has been discussed in all industries for a long time. How to make rational use of existing limited resources for redevelopment has become the primary issue in the future construction of a city. Designers have introduced green three-dimensional environmental design for a city into modern urban design. At present, Japan and South Korea focus on development of green three-dimensional environmental projects for cities, in which application of green three-dimensional building design is particularly prominent. This article learns from successful cases on urban three-dimensional environment design in Japan and Korea and makes profound discussion about how new city-model agriculture develops in China for the purpose of solving the problem of urban construction in China in the aspects of theory and Practice.

The role of rational and experiential processing in influencing the framing effect.

PubMed

Stark, Emily; Baldwin, Austin S; Hertel, Andrew W; Rothman, Alexander J

2017-01-01

Research on individual differences and the framing effect has focused primarily on how variability in rational processing influences choice. However, we propose that measuring only rational processing presents an incomplete picture of how participants are responding to framed options, as orthogonal individual differences in experiential processing might be relevant. In two studies, we utilize the Rational Experiential Inventory, which captures individual differences in rational and experiential processing, to investigate how both processing types influence decisions. Our results show that differences in experiential processing, but not rational processing, moderated the effect of frame on choice. We suggest that future research should more closely examine the influence of experiential processing on making decisions, to gain a broader understanding of the conditions that contribute to the framing effect.

Deep Rationality: The Evolutionary Economics of Decision Making.

PubMed

Kenrick, Douglas T; Griskevicius, Vladas; Sundie, Jill M; Li, Norman P; Li, Yexin Jessica; Neuberg, Steven L

2009-10-01

What is a "rational" decision? Economists traditionally viewed rationality as maximizing expected satisfaction. This view has been useful in modeling basic microeconomic concepts, but falls short in accounting for many everyday human decisions. It leaves unanswered why some things reliably make people more satisfied than others, and why people frequently act to make others happy at a cost to themselves. Drawing on an evolutionary perspective, we propose that people make decisions according to a set of principles that may not appear to make sense at the superficial level, but that demonstrate rationality at a deeper evolutionary level. By this, we mean that people use adaptive domain-specific decision-rules that, on average, would have resulted in fitness benefits. Using this framework, we re-examine several economic principles. We suggest that traditional psychological functions governing risk aversion, discounting of future benefits, and budget allocations to multiple goods, for example, vary in predictable ways as a function of the underlying motive of the decision-maker and individual differences linked to evolved life-history strategies. A deep rationality framework not only helps explain why people make the decisions they do, but also inspires multiple directions for future research.

14 CFR 29.427 - Unsymmetrical loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conditions. (b) To meet the design criteria of paragraph (a) of this section, in the absence of more rational... selected so that the maximum design loads are obtained on each surface. In the absence of more rational...

14 CFR 27.427 - Unsymmetrical loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conditions. (b) To meet the design criteria of paragraph (a) of this section, in the absence of more rational... selected so the maximum design loads are obtained on each surface. In the absence of more rational data...

Addressing the Future in Ancient and Modern Times.

ERIC Educational Resources Information Center

Roshwald, Mordecai

1982-01-01

Explores the similarities between ancient prophecy and modern futures prediction. The article suggests that the perceived degree of certainty in predictions of the future affects the patterns of emotional and rational responses in those receiving them. (AM)

Resisting Consumerist Rationalities in Higher Vocational Education

ERIC Educational Resources Information Center

Puaca, Goran; Theandersson, Christer; Carlén, Margareta

2017-01-01

Swedish higher education policy is currently moving toward consumption ideals that focus on promoting the efficiency and economic viability of student choices. This paper scrutinizes students' practical considerations when making decisions regarding their education and future occupations and the choice rationalities and motives that these reflect.…

Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

PubMed

Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

2015-09-01

A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

From bricolage to BioBricks™: Synthetic biology and rational design.

PubMed

Lewens, Tim

2013-12-01

Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

A new rational-based optimal design strategy of ship structure based on multi-level analysis and super-element modeling method

NASA Astrophysics Data System (ADS)

Sun, Li; Wang, Deyu

2011-09-01

A new multi-level analysis method of introducing the super-element modeling method, derived from the multi-level analysis method first proposed by O. F. Hughes, has been proposed in this paper to solve the problem of high time cost in adopting a rational-based optimal design method for ship structural design. Furthermore, the method was verified by its effective application in optimization of the mid-ship section of a container ship. A full 3-D FEM model of a ship, suffering static and quasi-static loads, was used as the analyzing object for evaluating the structural performance of the mid-ship module, including static strength and buckling performance. Research results reveal that this new method could substantially reduce the computational cost of the rational-based optimization problem without decreasing its accuracy, which increases the feasibility and economic efficiency of using a rational-based optimal design method in ship structural design.

Structure and Computation in Immunoreagent Design: From Diagnostics to Vaccines.

PubMed

Gourlay, Louise; Peri, Claudio; Bolognesi, Martino; Colombo, Giorgio

2017-12-01

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic Virology: Engineering Viruses for Gene Delivery

PubMed Central

Guenther, Caitlin M.; Kuypers, Brianna E.; Lam, Michael T.; Robinson, Tawana M.; Zhao, Julia; Suh, Junghae

2014-01-01

The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or “bionic” viruses, feature engineered components, or “parts”, that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies – rational, combinatorial, and pseudo-rational – have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavours will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. PMID:25195922

Synthetic virology: engineering viruses for gene delivery.

PubMed

Guenther, Caitlin M; Kuypers, Brianna E; Lam, Michael T; Robinson, Tawana M; Zhao, Julia; Suh, Junghae

2014-01-01

The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or 'bionic' viruses, feature engineered components, or 'parts', that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies--rational, combinatorial, and pseudo-rational--have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavors will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. © 2014 Wiley Periodicals, Inc.

Mobility, Emotion, and Universality in Future Collaboration

NASA Astrophysics Data System (ADS)

Chignell, Mark; Hosono, Naotsune; Fels, Deborah; Lottridge, Danielle; Waterworth, John

The Graphical user interface has traditionally supported personal productivity, efficiency, and usability. With computer supported cooperative work, the focus has been on typical people, doing typical work in a highly rational model of interaction. Recent trends towards mobility, and emotional and universal design are extending the user interface paradigm beyond the routine. As computing moves into the hand and away from the desktop, there is a greater need for dealing with emotions and distractions. Busy and distracted people represent a new kind of disability, but one that will be increasingly prevalent. In this panel we examine the current state of the art, and prospects for future collaboration in non-normative computing requirements. This panel draws together researchers who are studying the problems of mobility, emotion and universality. The goal of the panel is to discuss how progress in these areas will change the nature of future collaboration.

Machine learning in the rational design of antimicrobial peptides.

PubMed

Rondón-Villarreal, Paola; Sierra, Daniel A; Torres, Rodrigo

2014-01-01

One of the most important public health issues is the microbial and bacterial resistance to conventional antibiotics by pathogen microorganisms. In recent years, many researches have been focused on the development of new antibiotics. Among these, antimicrobial peptides (AMPs) have raised as a promising alternative to combat antibioticresistant microorganisms. For this reason, many theoretical efforts have been done in the development of new computational tools for the rational design of both better and effective AMPs. In this review, we present an overview of the rational design of AMPs using machine learning techniques and new research fields.

Discriminating between stabilizing and destabilizing protein design mutations via recombination and simulation.

PubMed

Johnson, Lucas B; Gintner, Lucas P; Park, Sehoo; Snow, Christopher D

2015-08-01

Accuracy of current computational protein design (CPD) methods is limited by inherent approximations in energy potentials and sampling. These limitations are often used to qualitatively explain design failures; however, relatively few studies provide specific examples or quantitative details that can be used to improve future CPD methods. Expanding the design method to include a library of sequences provides data that is well suited for discriminating between stabilizing and destabilizing design elements. Using thermophilic endoglucanase E1 from Acidothermus cellulolyticus as a model enzyme, we computationally designed a sequence with 60 mutations. The design sequence was rationally divided into structural blocks and recombined with the wild-type sequence. Resulting chimeras were assessed for activity and thermostability. Surprisingly, unlike previous chimera libraries, regression analysis based on one- and two-body effects was not sufficient for predicting chimera stability. Analysis of molecular dynamics simulations proved helpful in distinguishing stabilizing and destabilizing mutations. Reverting to the wild-type amino acid at destabilized sites partially regained design stability, and introducing predicted stabilizing mutations in wild-type E1 significantly enhanced thermostability. The ability to isolate stabilizing and destabilizing elements in computational design offers an opportunity to interpret previous design failures and improve future CPD methods. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Computational approaches for rational design of proteins with novel functionalities

PubMed Central

Tiwari, Manish Kumar; Singh, Ranjitha; Singh, Raushan Kumar; Kim, In-Won; Lee, Jung-Kul

2012-01-01

Proteins are the most multifaceted macromolecules in living systems and have various important functions, including structural, catalytic, sensory, and regulatory functions. Rational design of enzymes is a great challenge to our understanding of protein structure and physical chemistry and has numerous potential applications. Protein design algorithms have been applied to design or engineer proteins that fold, fold faster, catalyze, catalyze faster, signal, and adopt preferred conformational states. The field of de novo protein design, although only a few decades old, is beginning to produce exciting results. Developments in this field are already having a significant impact on biotechnology and chemical biology. The application of powerful computational methods for functional protein designing has recently succeeded at engineering target activities. Here, we review recently reported de novo functional proteins that were developed using various protein design approaches, including rational design, computational optimization, and selection from combinatorial libraries, highlighting recent advances and successes. PMID:24688643

AIonAI: a humanitarian law of artificial intelligence and robotics.

PubMed

Ashrafian, Hutan

2015-02-01

The enduring progression of artificial intelligence and cybernetics offers an ever-closer possibility of rational and sentient robots. The ethics and morals deriving from this technological prospect have been considered in the philosophy of artificial intelligence, the design of automatons with roboethics and the contemplation of machine ethics through the concept of artificial moral agents. Across these categories, the robotics laws first proposed by Isaac Asimov in the twentieth century remain well-recognised and esteemed due to their specification of preventing human harm, stipulating obedience to humans and incorporating robotic self-protection. However the overwhelming predominance in the study of this field has focussed on human-robot interactions without fully considering the ethical inevitability of future artificial intelligences communicating together and has not addressed the moral nature of robot-robot interactions. A new robotic law is proposed and termed AIonAI or artificial intelligence-on-artificial intelligence. This law tackles the overlooked area where future artificial intelligences will likely interact amongst themselves, potentially leading to exploitation. As such, they would benefit from adopting a universal law of rights to recognise inherent dignity and the inalienable rights of artificial intelligences. Such a consideration can help prevent exploitation and abuse of rational and sentient beings, but would also importantly reflect on our moral code of ethics and the humanity of our civilisation.

Treatment limitation decisions under uncertainty: the value of subsequent euthanasia.

PubMed

Savulescu, Julian

1994-01-01

This paper examines how decisions to limit treatment to critically ill patients under uncertainty can be made rationally. Expected utility theory offers one way of making rational decisions under uncertainty. One problem with using this approach is that we may not know the value of each option. One rational course open is to treat until further information becomes available. However, treatment can limit the range of options open. With treatment, a patient may recover such that he no longer requires life-supporting treatment. However, his life may be not worth living. If active euthanasia of 'non-terminal' conditions is prohibited, the option of dying will no longer be available. Taking a rational 'wait and see' course may result in being trapped within an unbearable life. On the other hand, sometimes present practice 'lets nature take its course'. Critically ill patients are allowed to die because it is believed that their lives will be not worth living. It is likely that some patients are allowed to die when there is some objective chance of worthwhile future life. This paper argues that a policy of treating critically ill patients until the nature of future options can be better evaluated, in company with an offer of subsequent euthanasia where appropriate, allows a more rational and humane approach to treatment limitation decisions under uncertainty.

Critical Thinking and Rational Emotive Behavior Therapy.

ERIC Educational Resources Information Center

Hatcher, Donald; Brown, Tony; Gariglietti, Kelli P.

2001-01-01

Notes limitations of Rational Emotive Behavior Therapy (REBT). Suggests that should these weaknesses be addressed, teachers of critical thinking would do well to incorporate REBT into their critical thinking courses. Relates that A. Ellis has suggested that the future of REBT is in integrating it into the educational curriculum as a way of…

Rational Emotive Behavior Therapy after Ellis: Predictions for the Future.

ERIC Educational Resources Information Center

Weinrach, Stephen G.; Ellis, Albert; DiGiuseppe, Raymond; Bernard, Michael E.; Dryden, Windy; Kassinove, Howard; Morris, G. Barry; Vernon, Ann; Wolfe, Janet

1995-01-01

Nine members of the institute for Rational-Emotive Therapy's (REBT) International Training Standards and Review Committee predicted the status of REBT 25 to 50 years after the death of Albert Ellis. Will REBT continue to exist in its own right or be incorporated into newer forms of cognitive behavior therapy? (EMK)

From Whitlam to Economic Rationalism and Beyond: A Conceptual Framework for Political Activism in Children's Services

ERIC Educational Resources Information Center

Sumsion, Jennifer

2006-01-01

Thirty years after the dismissal of the Whitlam Government, the Australian political, economic and social landscape is dominated by discourses of economic rationalism. The reification of market forces presents challenges for early childhood professionals seeking to establish a viable future trajectory for children's services that includes…

Rational Emotive Education

ERIC Educational Resources Information Center

Knaus, William

1977-01-01

Rational Emotive Education--an outgrowth of theories developed by Albert Ellis--is a teaching design of mental health concepts and problem-solving activities designed to help students to approach and cope with their problems through experiential learning, via a structured, thematic sequence of emotive education lessons. (MJB)

DD-ligases as a potential target for antibiotics: past, present and future.

PubMed

Tytgat, I; Colacino, E; Tulkens, P M; Poupaert, J H; Prévost, M; Van Bambeke, F

2009-01-01

DD-ligases catalyze the synthesis of the D-Ala-D-Ala and D-Ala-D-Ser dipeptides or the D Ala-D-Lac depsipeptide in an early step of peptidoglycan synthesis. Their function is essential for bacterial growth and specific to bacteria, making them attractive targets for the development of novel antibiotics. This review examines the biochemical and structural features of these enzymes and presents the main families of inhibitors described so far. Over the last 20 years, 7 structures of DD-ligases have been solved by X-ray crystallography, giving a detailed view of the general topology of the active site and of the residues in the catalytic pocket that play a central role in substrate recognition. This has paved the way to the rational design of inhibitors, which can be classified as (i) analogues of substrates, (ii) analogues of the product of the reaction, (iii) analogues of the transition state, and (iv) original scaffolds discovered by screening or by rational computer-aided design. The three first strategies have led to molecules that are polar by nature and have therefore poor access to their cytosolic target. The fourth one is potentially most promising as it yields more diverse structures. The most active molecules show affinity constants in the microM range, but microbiological evaluation remains scarce (typical MIC 1-8 mg/L for the tested compounds). These data strongly suggest targeting DD-ligases is a promising approach for discovery of new antibiotics. Future research should, however, aim at finding more potent inhibitors endowed with the appropriate pharmacokinetic properties that ensure access to their intracellular target.

[Priority setting and bedside rationing: a discussion of empirical findings].

PubMed

Strech, Daniel

2011-01-01

In addition to empirical forecasts on the extent of the current and future limitations on health care resources, empirical data on the status quo of bedside rationing play a significant role in developing suitable alternatives in dealing with limited financial resources. This article presents and discusses selected results of the international and German survey research on bedside rationing. Survey studies among physicians could prove world-wide that rationing decisions are made already today by individual physicians in the in- and out-patient services. In German hospitals, rationing is also a wide-spread though non-transparent and not (yet) very common phenomenon for an individual physician. Varying criteria for bedside rationing contribute to the fact that the current approach to bedside rationing leads to dissatisfaction on the part of physicians and to a potential disadvantage of certain patient groups. Explicit, i.e. transparent and systematic, ways of rationing could remedy these deficiencies and are therefore clearly preferable in this context. However, further specification of the methods of explicit rationing and a critical evaluation of their application in practice are needed. Moreover, it is mainly the quality of the underlying evidence that determines whether or not the actual decisions become more reasonable and fair by means of more explicit rationing approaches. Copyright © 2011 S. Karger AG, Basel.

Recent Advances in Metal Chalcogenides (MX; X = S, Se) Nanostructures for Electrochemical Supercapacitor Applications: A Brief Review

PubMed Central

Theerthagiri, Jayaraman; Durai, Govindarajan; Rana, Abu ul Hassan Sarwar; Sangeetha, Kirubanandam; Kuppusami, Parasuraman; Kim, Hyun-Seok

2018-01-01

Supercapacitors (SCs) have received a great deal of attention and play an important role for future self-powered devices, mainly owing to their higher power density. Among all types of electrical energy storage devices, electrochemical supercapacitors are considered to be the most promising because of their superior performance characteristics, including short charging time, high power density, safety, easy fabrication procedures, and long operational life. An SC consists of two foremost components, namely electrode materials, and electrolyte. The selection of appropriate electrode materials with rational nanostructured designs has resulted in improved electrochemical properties for high performance and has reduced the cost of SCs. In this review, we mainly spotlight the non-metallic oxide, especially metal chalcogenides (MX; X = S, Se) based nanostructured electrode materials for electrochemical SCs. Different non-metallic oxide materials are highlighted in various categories, such as transition metal sulfides and selenides materials. Finally, the designing strategy and future improvements on metal chalcogenide materials for the application of electrochemical SCs are also discussed. PMID:29671823

The food additive vanillic acid controls transgene expression in mammalian cells and mice.

PubMed

Gitzinger, Marc; Kemmer, Christian; Fluri, David A; El-Baba, Marie Daoud; Weber, Wilfried; Fussenegger, Martin

2012-03-01

Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

Abnormality, rationality, and sanity.

PubMed

Hertwig, Ralph; Volz, Kirsten G

2013-11-01

A growing body of studies suggests that neurological and mental abnormalities foster conformity to norms of rationality that are widely endorsed in economics and psychology, whereas normality stands in the way of rationality thus defined. Here, we outline the main findings of these studies, discuss their implications for experimental design, and consider how 'sane' some benchmarks of rationality really are. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bright Futures in Malawi’s New Dawn: Educational Aspirations as Assertions of Identity1

PubMed Central

Frye, Margaret

2013-01-01

Imagined futures, once a vital topic of theoretical inquiry within the sociology of culture, have been sidelined in recent decades. Rational choice models cannot explain the seemingly irrational optimism of youth aspirations, pointing to the need to explore other alternatives. This article incorporates insights from pragmatist theory and cognitive sociology to examine the relationship between imagined futures and present actions and experiences in rural Malawi, where future optimism appears particularly unfounded. Drawing from in-depth interviews and archival sources documenting ideological campaigns promoting schooling, the author shows that four elements are understood to jointly produce educational success: ambitious career goals, sustained effort, unflagging optimism, and resistance to temptation. Aspirations should be interpreted not as rational calculations, but instead as assertions of a virtuous identity, claims to be “one who aspires.” PMID:23645932

Thwarting the Diseased Will: Ulysses Contracts, the Self and Addiction.

PubMed

Bell, Kirsten

2015-09-01

Ulysses contracts are a particular type of advance directive that has been advocated for use in mental health settings and addictions treatment. Taking their name from the legend of Ulysses, such contracts are distinctive insofar as they are designed to thwart certain anticipated future wishes rather than realize them. In this paper, I consider what Ulysses contracts reveal about contemporary conceptions of addiction and the self. Drawing on discussions of Ulysses contracts in the psychiatric and addictions literature, as well as historical and contemporary examples of such, I show that Ulysses contracts are premised on a split between the present 'rational' self and the future 'irrational' self, thereby reproducing a very particular notion of addiction--one that serves to naturalize certain ways of thinking about freedom, choice, coercion, and the self.

The political economy of rationing health care in England and the US: the 'accidental logics' of political settlements.

PubMed

Bevan, Gwyn; Brown, Lawrence D

2014-07-01

This article considers how the 'accidental logics' of political settlements for the English National Health Service (NHS) and the Medicare and Medicaid programmes in the United States have resulted in different institutional arrangements and different implicit social contracts for rationing, which we define to be the denial of health care that is beneficial but is deemed to be too costly. This article argues that rationing is designed into the English NHS and designed out of US Medicare; and compares rationing for the elderly in the United States and in England for acute care, care at the end of life, and chronic care.

System analysis in rotorcraft design: The past decade

NASA Technical Reports Server (NTRS)

Galloway, Thomas L.

1988-01-01

Rapid advances in the technology of electronic digital computers and the need for an integrated synthesis approach in developing future rotorcraft programs has led to increased emphasis on system analysis techniques in rotorcraft design. The task in systems analysis is to deal with complex, interdependent, and conflicting requirements in a structured manner so rational and objective decisions can be made. Whether the results are wisdom or rubbish depends upon the validity and sometimes more importantly, the consistency of the inputs, the correctness of the analysis, and a sensible choice of measures of effectiveness to draw conclusions. In rotorcraft design this means combining design requirements, technology assessment, sensitivity analysis and reviews techniques currently in use by NASA and Army organizations in developing research programs and vehicle specifications for rotorcraft. These procedures span simple graphical approaches to comprehensive analysis on large mainframe computers. Examples of recent applications to military and civil missions are highlighted.

Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates

PubMed Central

Donaghy, Heather

2016-01-01

ABSTRACT Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a cytotoxic payload. They were designed to allow specific targeting of highly potent cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities that may be driven by any of the components of an ADC have been reported. There are currently more than 50 ADCs in active clinical development, and a further ∼20 that have been discontinued. For this review, the reported toxicities of ADCs were analysed, and the mechanisms for their effects are explored in detail. Methods to reduce toxicities, including dosing strategies and drug design, are discussed. The toxicities reported for active and discontinued drugs are important to drive the rational design and improve the therapeutic index of ADCs of the future. PMID:27045800

Research advances in polymer emulsion based on "core-shell" structure particle design.

PubMed

Ma, Jian-zhong; Liu, Yi-hong; Bao, Yan; Liu, Jun-li; Zhang, Jing

2013-09-01

In recent years, quite many studies on polymer emulsions with unique core-shell structure have emerged at the frontier between material chemistry and many other fields because of their singular morphology, properties and wide range of potential applications. Organic substance as a coating material onto either inorganic or organic internal core materials promises an unparalleled opportunity for enhancement of final functions through rational designs. This contribution provides a brief overview of recent progress in the synthesis, characterization, and applications of both inorganic-organic and organic-organic polymer emulsions with core-shell structure. In addition, future research trends in polymer composites with core-shell structure are also discussed in this review. Copyright © 2013 Elsevier B.V. All rights reserved.

Vaccines: From Empirical Development to Rational Design

PubMed Central

Rueckert, Christine; Guzmán, Carlos A.

2012-01-01

Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development. PMID:23144616

Clinical studies in restorative dentistry: New directions and new demands.

PubMed

Opdam, N J M; Collares, K; Hickel, R; Bayne, S C; Loomans, B A; Cenci, M S; Lynch, C D; Correa, M B; Demarco, F; Schwendicke, F; Wilson, N H F

2018-01-01

Clinical research of restorative materials is confounded by problems of study designs, length of trials, type of information collected, and costs for trials, despite increasing numbers and considerable development of trials during the past 50 years. This opinion paper aims to discuss advantages and disadvantages of different study designs and outcomes for evaluating survival of dental restorations and to make recommendations for future study designs. Advantages and disadvantages of randomized trials, prospective and retrospective longitudinal studies, practice-based, pragmatic and cohort studies are addressed and discussed. The recommendations of the paper are that clinical trials should have rational control groups, include confounders such as patient risk factors in the data and analysis and should use outcome parameters relevant for profession and patients. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Structure-guided design and functional characterization of an artificial red light-regulated guanylate/adenylate cyclase for optogenetic applications.

PubMed

Etzl, Stefan; Lindner, Robert; Nelson, Matthew D; Winkler, Andreas

2018-06-08

Genetically targeting biological systems to control cellular processes with light is the concept of optogenetics. Despite impressive developments in this field, underlying molecular mechanisms of signal transduction of the employed photoreceptor modules are frequently not sufficiently understood to rationally design new optogenetic tools. Here, we investigate the requirements for functional coupling of red light-sensing phytochromes with non-natural enzymatic effectors by creating a series of constructs featuring the Deinococcus radiodurans bacteriophytochrome linked to a Synechocystis guanylate/adenylate cyclase. Incorporating characteristic structural elements important for cyclase regulation in our designs, we identified several red light-regulated fusions with promising properties. We provide details of one light-activated construct with low dark-state activity and high dynamic range that outperforms previous optogenetic tools in vitro and expands our in vivo toolkit, as demonstrated by manipulation of Caenorhabditis elegans locomotor activity. The full-length crystal structure of this phytochrome-linked cyclase revealed molecular details of photoreceptor-effector coupling, highlighting the importance of the regulatory cyclase element. Analysis of conformational dynamics by hydrogen-deuterium exchange in different functional states enriched our understanding of phytochrome signaling and signal integration by effectors. We found that light-induced conformational changes in the phytochrome destabilize the coiled-coil sensor-effector linker, which releases the cyclase regulatory element from an inhibited conformation, increasing cyclase activity of this artificial system. Future designs of optogenetic functionalities may benefit from our work, indicating that rational considerations for the effector improve the rate of success of initial designs to obtain optogenetic tools with superior properties. © 2018 Etzl et al.

One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

PubMed

Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

2013-05-18

Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

A neuroeconomic theory of rational addiction and nonlinear time-perception.

PubMed

Takahashi, Taiki

2011-01-01

Neuroeconomic conditions for "rational addiction" (Becker & Murphy 1988) have been unknown. This paper derived the conditions for "rational addiction" by utilizing a nonlinear time-perception theory of "hyperbolic" discounting, which is mathematically equivalent to the q-exponential intertemporal choice model based on Tsallis' statistics. It is shown that (i) Arrow-Pratt measure for temporal cognition corresponds to the degree of irrationality (i.e., Prelec's "decreasing impatience" parameter of temporal discounting) and (ii) rationality in addicts is controlled by a nondimensionalization parameter of the logarithmic time-perception function. Furthermore, the present theory illustrates the possibility that addictive drugs increase impulsivity via dopaminergic neuroadaptation without increasing irrationality. Future directions in the application of the model to studies in neuroeconomics are discussed.

[Rational choice, prediction, and medical decision. Contribution of severity scores].

PubMed

Bizouarn, P; Fiat, E; Folscheid, D

2001-11-01

The aim of this study was to determine what type of representation the medical doctor adopted concerning the uncertainty about the future in critically ill patients in the context of preoperative evaluation and intensive care medicine and to explore through the representation of the patient health status the different possibilities of choice he was able to make. The role played by the severity classification systems in the process of medical decision-making under probabilistic uncertainty was assessed according to the theories of rational behaviour. In this context, a medical rationality needed to be discovered, going beyond the instrumental status of the objective and/or subjective constructions of rational choice theories and reaching a dimension where means and expected ends could be included.

Deep Rationality: The Evolutionary Economics of Decision Making

PubMed Central

Kenrick, Douglas T.; Griskevicius, Vladas; Sundie, Jill M.; Li, Norman P.; Li, Yexin Jessica; Neuberg, Steven L.

2009-01-01

What is a “rational” decision? Economists traditionally viewed rationality as maximizing expected satisfaction. This view has been useful in modeling basic microeconomic concepts, but falls short in accounting for many everyday human decisions. It leaves unanswered why some things reliably make people more satisfied than others, and why people frequently act to make others happy at a cost to themselves. Drawing on an evolutionary perspective, we propose that people make decisions according to a set of principles that may not appear to make sense at the superficial level, but that demonstrate rationality at a deeper evolutionary level. By this, we mean that people use adaptive domain-specific decision-rules that, on average, would have resulted in fitness benefits. Using this framework, we re-examine several economic principles. We suggest that traditional psychological functions governing risk aversion, discounting of future benefits, and budget allocations to multiple goods, for example, vary in predictable ways as a function of the underlying motive of the decision-maker and individual differences linked to evolved life-history strategies. A deep rationality framework not only helps explain why people make the decisions they do, but also inspires multiple directions for future research. PMID:20686634

Considering situational and dispositional approaches to rational self-interest: an extension and response to de Dreu (2006).

PubMed

Meglino, Bruce M; Korsgaard, M Audrey

2006-11-01

The authors respond to C. K. W. De Dreu's (2006) critique of their article (B. M. Meglino & M. A. Korsgaard, 2004) published in the special section on Theoretical Models and Conceptual Analyses of the Journal of Applied Psychology. They maintain that De Dreu misinterprets their definitions and the psychological processes they addressed and thus raises a number of issues that are not relevant to their model. Meglino and Korsgaard's model focuses on the distinction between rational self-interest and other orientation, whereas the approach taken by De Dreu focuses on the distinction between rational self-interest and collective rationality. In this response, the authors clarify this distinction, address discrepancies between these two approaches, consider the effect of goals and rationality on other orientated behavior, and suggest directions for future research. (c) 2006 APA, all rights reserved

Essential Tremor: What We Can Learn from Current Pharmacotherapy.

PubMed

Ondo, William

2016-01-01

The pathophysiology of essential tremor, especially at the cellular level, is poorly understood. Although no drug has been specifically designed to treat essential tremor, several medications improve tremor, and others worsen it. Studying the mechanism of actions of these medications can help our understanding of tremor pathophysiology and contribute to future rational drug design. We reviewed literature, concentrating on mechanisms of action, of various medications that mitigate tremor. Many medications have multiple mechanisms of actions, making simple correlations difficult. Medications that increase the duration of opening of gamma-aminobutyric acid (GABA)-A receptors are most consistently associated with tremor improvement. Interestingly, drugs that increase GABA availability have not been associated with improved tremor. Other mechanisms possibly associated with tremor improvement include antagonism of alpha-2 delta subunits associated with calcium channels, inhibition of carbonic anhydrase, and inhibition of the synaptic vesicle protein 2A. Drugs that block voltage-gaited sodium channels do not affect tremor. The ideal beta-adrenergic blocker requires B2 affinity (non-cardiac selective), has no sympathomimetic properties, does not require membrane stabilization properties, and may benefit from good central nervous system penetration. To date, serendipitous observations have provided most of our understanding of tremor cellular physiology. Based on similarities to currently effective drugs or rational approximations and inferences, several currently available agents should be considered for tremor trials.

Generation and development of RNA ligase ribozymes with modular architecture through "design and selection".

PubMed

Fujita, Yuki; Ishikawa, Junya; Furuta, Hiroyuki; Ikawa, Yoshiya

2010-08-26

In vitro selection with long random RNA libraries has been used as a powerful method to generate novel functional RNAs, although it often requires laborious structural analysis of isolated RNA molecules. Rational RNA design is an attractive alternative to avoid this laborious step, but rational design of catalytic modules is still a challenging task. A hybrid strategy of in vitro selection and rational design has been proposed. With this strategy termed "design and selection," new ribozymes can be generated through installation of catalytic modules onto RNA scaffolds with defined 3D structures. This approach, the concept of which was inspired by the modular architecture of naturally occurring ribozymes, allows prediction of the overall architectures of the resulting ribozymes, and the structural modularity of the resulting ribozymes allows modification of their structures and functions. In this review, we summarize the design, generation, properties, and engineering of four classes of ligase ribozyme generated by design and selection.

Milk Production, Physiological Condition and Performance of Etawa Crossbreed Goats Feed by Ration Supplemented with Mangosteen Peel Flour

NASA Astrophysics Data System (ADS)

Dzarnisa; Rachmadi, D.; Azhar, A.; Fakhrur Riza, R.; Hidayati, A.

2018-02-01

Study on the effect of the addition of mangosteen (Garcinia mangostana L.) peel flour on physiological condition and performance of Etawa crossbreed goats was done. This was to grant the use of mangosteen peel flour that rich of antioxidants and has variety good benefits for health as feed additive for cattle. This study used a Complete Randomized Block Design consisting of 4 treatment groups and 4 replications each. Subjects were 16 female Etawa crossbreed goats randomly designed into treatments group based on lactation periods. Subjects were feed with traditional rations (control, A), traditional rations and 2.5% mangosteen peel flour (B), tradition rations and 5% mangosteen peel flour (C), and traditional rations and 7,5 % mangosteen peel flour (D). Data on performance (milk production) and physiological condition (respiratory frequency, rectal temperature, and heart rate) obtained were analyzed using analysis of variance (ANOVA). The results showed that the addition of mangosteen peel flour as food additive in the rations resulted in variations in the milk production, physiological condition (rectal temperature, heart rate and respiration frequency) and performances (daily weigh gain, food consumption, ration conversion and breast volume) of Etawa crossbreed goats, but significant effect was only observed in the respiration frequency. The addition of 2.5% mangosteen peel flour in the ration caused the best, expected effects on milk production physiological condition and performance of Etawa crossbreed goats.

Design of Mechanisms for Deployable, Optical Instruments: Guidelines for Reducing Hysteresis

NASA Technical Reports Server (NTRS)

Lake, Mark S.; Hachkowski, M. Roman

2000-01-01

This paper is intended to facilitate the development of deployable, optical instruments by providing a rational approach for the design, testing, and qualification of high-precision (i.e., low-hysteresis) deployment mechanisms for these instruments. Many of the guidelines included herein come directly from the field of optomechanical engineering, and are, therefore, neither newly developed guidelines, nor are they uniquely applicable to the design of high-precision deployment mechanisms. This paper is to be regarded as a guide to design and not a set of NASA requirements, except as may be defined in formal project specifications. Furthermore, due to the rapid pace of advancement in the field of precision deployment, this paper should be regarded as a preliminary set of guidelines. However, it is expected that this paper, with revisions as experience may indicate to be desirable, might eventually form the basis for a set of uniform design requirements for high-precision deployment mechanisms on future NASA space-based science instruments.

Nutritional Criteria for Military Rations and Effects of Prolonged Feeding on Acceptability

NASA Technical Reports Server (NTRS)

Schnakenberg, D.

1985-01-01

Broad nutritional policies for operational rations are designed to insure that the nutritional content of the rations served will sustain combat effectiveness. Concern exists that these rations, although nutritionally complete, would become monotonous because of limited variety causing nutrient intake to decrease and body weight losses to occur with adverse effects on morale and combat effectiveness. Whenever possible, troops are now fed one or two hot meals per day containing fresh foods and a much greater variety of foods than are available in packaged rations. A laboratory test was conducted with student volunteers and the results are discussed.

Rational Behavior Training: A Seven Lesson Sequence for Teaching Rational Behavior Skills to Students with Social and Emotional Disabilities.

ERIC Educational Resources Information Center

Patton, Patricia Lucey

This seven lesson curriculum sequence is designed to help teachers teach principles of Rational Behavior Training (RBT) which targets thinking behaviors, feeling behaviors, and behavioral responses to the environment. The program is appropriate for students with social and emotional disabilities and also develops reading, writing, spelling,…

Drug delivery across length scales.

PubMed

Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

2018-02-20

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

Preliminary design method for deployable spacecraft beams

NASA Technical Reports Server (NTRS)

Mikulas, Martin M., Jr.; Cassapakis, Costas

1995-01-01

There is currently considerable interest in low-cost, lightweight, compactly packageable deployable elements for various future missions involving small spacecraft. These elements must also have a simple and reliable deployment scheme and possess zero or very small free-play. Although most small spacecraft do not experience large disturbances, very low stiffness appendages or free-play can couple with even small disturbances and lead to unacceptably large attitude errors which may involve the introduction of a flexible-body control system. A class of structures referred to as 'rigidized structures' offers significant promise in providing deployable elements that will meet these needs for small spacecraft. The purpose of this paper is to introduce several rigidizable concepts and to develop a design methodology which permits a rational comparison of these elements to be made with alternate concepts.

Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

PubMed

Littleson, Mairi M; Baker, Christopher M; Dalençon, Anne J; Frye, Elizabeth C; Jamieson, Craig; Kennedy, Alan R; Ling, Kenneth B; McLachlan, Matthew M; Montgomery, Mark G; Russell, Claire J; Watson, Allan J B

2018-03-16

Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

Moving Forward by Looking in the Rearview Mirror

DTIC Science & Technology

2016-06-01

the foreseeable future.1 As senior civilian and military leaders acknowledge that conventional military superiority does not guarantee victory in...charismatic, or rational legal. Traditional legitimacy refers to the respect afforded to traditional authorities, including tribal leaders such as those...found in southwest Asia and the Middle East.10 Charismatic legitimacy is linked to a specific person or ideology, often a religious leader . Rational

Photo-responsive block copolymer micelles: design and behavior.

PubMed

Gohy, Jean-François; Zhao, Yue

2013-09-07

Stimuli-responsive block copolymer micelles are the topic of intense research since they are able to show sharp and eventually reversible responses to various environmental changes and find applications in various fields including controlled drug delivery. Among all the available stimuli, light has recently attracted much attention since it can be localized in time and space, and it can also be triggered from outside of the system. In this tutorial review, we highlight the progress realized in recent years. More precisely, we provide some guidelines towards the rational design of photo-responsive block copolymers and we present the different photo-responsive moieties that have been used so far. We also discuss the different types of irreversible and reversible responses encountered by photo-responsive block copolymer micelles. Finally, we suggest possible future developments including the design of biocompatible systems operating at excitation wavelengths compatible for biomedical applications.

Rational design of new electrolyte materials for electrochemical double layer capacitors

NASA Astrophysics Data System (ADS)

Schütter, Christoph; Husch, Tamara; Viswanathan, Venkatasubramanian; Passerini, Stefano; Balducci, Andrea; Korth, Martin

2016-09-01

The development of new electrolytes is a centerpiece of many strategies to improve electrochemical double layer capacitor (EDLC) devices. We present here a computational screening-based rational design approach to find new electrolyte materials. As an example application, the known chemical space of almost 70 million compounds is investigated in search of electrochemically more stable solvents. Cyano esters are identified as especially promising new compound class. Theoretical predictions are validated with subsequent experimental studies on a selected case. These studies show that based on theoretical predictions only, a previously untested, but very well performing compound class was identified. We thus find that our rational design strategy is indeed able to successfully identify completely new materials with substantially improved properties.

Rational desires and the limitation of life-sustaining treatment.

PubMed

Savulescu, Julian

1994-07-01

It is accepted that treatment of previously competent, now incompetent patients can be limited if that is what the patient would desire, if she were now competent. Expressed past preferences or an advance directive are often taken to constitute sufficient evidence of what a patient would now desire. I distinguish between desires and rational desires. I argue that for a desire to be an expression of a person's autonomy, it must be or satisfy that person's rational desires. A person rationally desires a course of action if that person desires it while being in possession of all available relevant facts, without committing relevant error of logic, and "vividly imagining" what its consequences would be like for her. I argue that some competent, expressed desires obstruct autonomy. I show that several psychological mechanisms operate to prevent a person rationally evaluating what future life in a disabled state would be like. Rational evaluation is difficult. However, treatment limitation, if it is to respect autonomy, must be in accord with a patient's rational desires, and not merely her expressed desires. I illustrate the implications of these arguments for the use of advance directives and for the treatment of competent patients.

T Cell Determinants Incorporating [beta]-Amino Acid Residues Are Protease Resistant and Remain Immunogenic In Vivo

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

Webb, Andrew I.; Dunstone, Michelle A.; Williamson, Nicholas A.

2010-07-20

A major hurdle in designing successful epitope-based vaccines resides in the delivery, stability, and immunogenicity of the peptide immunogen. The short-lived nature of unmodified peptide-based vaccines in vivo limits their therapeutic application in the immunotherapy of cancers and chronic viral infections as well as their use in generating prophylactic immunity. The incorporation of {beta}-amino acids into peptides decreases proteolysis, yet its potential application in the rational design of T cell mimotopes is poorly understood. To address this, we have replaced each residue of the SIINFEKL epitope individually with the corresponding {beta}-amino acid and examined the resultant efficacy of these mimotopes.more » Some analogs displayed similar MHC binding and superior protease stability compared with the native epitope. Importantly, these analogs were able to generate cross-reactive CTLs in vivo that were capable of lysing tumor cells that expressed the unmodified epitope as a surrogate tumor Ag. Structural analysis of peptides in which anchor residues were substituted with {beta}-amino acids revealed the basis for enhanced MHC binding and retention of immunogenicity observed for these analogs and paves the way for future vaccine design using {beta}-amino acids. We conclude that the rational incorporation of {beta}-amino acids into T cell determinants is a powerful alternative to the traditional homologous substitution of randomly chosen naturally occurring {alpha}-amino acids, and these mimotopes may prove particularly useful for inclusion in epitope-based vaccines.« less

Towards a whole-cell modeling approach for synthetic biology

NASA Astrophysics Data System (ADS)

Purcell, Oliver; Jain, Bonny; Karr, Jonathan R.; Covert, Markus W.; Lu, Timothy K.

2013-06-01

Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole-cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline.

A Proposal for the use of the Consortium Method in the Design-build system

NASA Astrophysics Data System (ADS)

Miyatake, Ichiro; Kudo, Masataka; Kawamata, Hiroyuki; Fueta, Toshiharu

In view of the necessity for efficient implementation of public works projects, it is expected to utilize advanced technical skills of private firms, for the purpose of reducing project costs, improving performance and functions of construction objects, and reducing work periods, etc. The design-build system is a method to order design and construction as a single contract, including design of structural forms and main specifications of the construction object. This is a system in which high techniques of private firms can be utilized, as a means to ensure qualities of design and construction, rational design, and efficiency of the project. The objective of this study is to examine the use of a method to form a consortium of civil engineering consultants and construction companies, as it is an issue related to the implementation of the design-build method. Furthermore, by studying various forms of consortiums to be introduced in future, it proposes procedural items required to utilize this method, during the bid and after signing a contract, such as the estimate submission from the civil engineering consultants etc.

Porphyrin-Based Nanostructures for Photocatalytic Applications

PubMed Central

Chen, Yingzhi; Li, Aoxiang; Huang, Zheng-Hong; Wang, Lu-Ning; Kang, Feiyu

2016-01-01

Well-defined organic nanostructures with controllable size and morphology are increasingly exploited in optoelectronic devices. As promising building blocks, porphyrins have demonstrated great potentials in visible-light photocatalytic applications, because of their electrical, optical and catalytic properties. From this perspective, we have summarized the recent significant advances on the design and photocatalytic applications of porphyrin-based nanostructures. The rational strategies, such as texture or crystal modification and interfacial heterostructuring, are described. The applications of the porphyrin-based nanostructures in photocatalytic pollutant degradation and hydrogen evolution are presented. Finally, the ongoing challenges and opportunities for the future development of porphyrin nanostructures in high-quality nanodevices are also proposed. PMID:28344308

Computing organic stereoselectivity - from concepts to quantitative calculations and predictions.

PubMed

Peng, Qian; Duarte, Fernanda; Paton, Robert S

2016-11-07

Advances in theory and processing power have established computation as a valuable interpretative and predictive tool in the discovery of new asymmetric catalysts. This tutorial review outlines the theory and practice of modeling stereoselective reactions. Recent examples illustrate how an understanding of the fundamental principles and the application of state-of-the-art computational methods may be used to gain mechanistic insight into organic and organometallic reactions. We highlight the emerging potential of this computational tool-box in providing meaningful predictions for the rational design of asymmetric catalysts. We present an accessible account of the field to encourage future synergy between computation and experiment.

Photonic hydrogel sensors.

PubMed

Yetisen, Ali K; Butt, Haider; Volpatti, Lisa R; Pavlichenko, Ida; Humar, Matjaž; Kwok, Sheldon J J; Koo, Heebeom; Kim, Ki Su; Naydenova, Izabela; Khademhosseini, Ali; Hahn, Sei Kwang; Yun, Seok Hyun

2016-01-01

Analyte-sensitive hydrogels that incorporate optical structures have emerged as sensing platforms for point-of-care diagnostics. The optical properties of the hydrogel sensors can be rationally designed and fabricated through self-assembly, microfabrication or laser writing. The advantages of photonic hydrogel sensors over conventional assay formats include label-free, quantitative, reusable, and continuous measurement capability that can be integrated with equipment-free text or image display. This Review explains the operation principles of photonic hydrogel sensors, presents syntheses of stimuli-responsive polymers, and provides an overview of qualitative and quantitative readout technologies. Applications in clinical samples are discussed, and potential future directions are identified. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacological enhancement of drug cue extinction learning: translational challenges

PubMed Central

Kantak, K.M.; Nic Dhonnchadha, B.Á.

2010-01-01

Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may constitute a rational strategy for the clinical management of drug relapse. While certain success has been reported for this form of therapy in anxiety disorders, in this article we highlight several obstacles that may undermine the efficacy of exposure therapy for substance use disorders. We also review translational studies that have evaluated the facilitative effects of the cognitive enhancer D-cycloserine on extinction targeting drug-related cues. Finally, important considerations for the design and implementation of future studies evaluating exposure therapy combined with pharmacotherapy for substance use disorders are discussed. PMID:21272016

Rational Design of Plasmonic Nanoparticles for Enhanced Cavitation and Cell Perforation.

PubMed

Lachaine, Rémi; Boutopoulos, Christos; Lajoie, Pierre-Yves; Boulais, Étienne; Meunier, Michel

2016-05-11

Metallic nanoparticles are routinely used as nanoscale antenna capable of absorbing and converting photon energy with subwavelength resolution. Many applications, notably in nanomedicine and nanobiotechnology, benefit from the enhanced optical properties of these materials, which can be exploited to image, damage, or destroy targeted cells and subcellular structures with unprecedented precision. Modern inorganic chemistry enables the synthesis of a large library of nanoparticles with an increasing variety of shapes, composition, and optical characteristic. However, identifying and tailoring nanoparticles morphology to specific applications remains challenging and limits the development of efficient nanoplasmonic technologies. In this work, we report a strategy for the rational design of gold plasmonic nanoshells (AuNS) for the efficient ultrafast laser-based nanoscale bubble generation and cell membrane perforation, which constitute one of the most crucial challenges toward the development of effective gene therapy treatments. We design an in silico rational design framework that we use to tune AuNS morphology to simultaneously optimize for the reduction of the cavitation threshold while preserving the particle structural integrity. Our optimization procedure yields optimal AuNS that are slightly detuned compared to their plasmonic resonance conditions with an optical breakdown threshold 30% lower than randomly selected AuNS and 13% lower compared to similarly optimized gold nanoparticles (AuNP). This design strategy is validated using time-resolved bubble spectroscopy, shadowgraphy imaging and electron microscopy that confirm the particle structural integrity and a reduction of 51% of the cavitation threshold relative to optimal AuNP. Rationally designed AuNS are finally used to perforate cancer cells with an efficiency of 61%, using 33% less energy compared to AuNP, which demonstrate that our rational design framework is readily transferable to a cell environment. The methodology developed here thus provides a general strategy for the systematic design of nanoparticles for nanomedical applications and should be broadly applicable to bioimaging and cell nanosurgery.

Measuring Resilience.

PubMed

Hoffman, Robert R; Hancock, P A

2017-06-01

As human factors and ergonomics (HF/E) moves to embrace a greater systems perspective concerning human-machine technologies, new and emergent properties, such as resilience, have arisen. Our objective here is to promote discussion as to how to measure this latter, complex phenomenon. Resilience is now a much-referenced goal for technology and work system design. It subsumes the new movement of resilience engineering. As part of a broader systems approach to HF/E, this concept requires both a definitive specification and an associated measurement methodology. Such an effort epitomizes our present work. Using rational analytic and synthetic methods, we offer an approach to the measurement of resilience capacity. We explicate how our proposed approach can be employed to compare resilience across multiple systems and domains, and emphasize avenues for its future development and validation. Emerging concerns for the promise and potential of resilience and associated concepts, such as adaptability, are highlighted. Arguments skeptical of these emerging dimensions must be met with quantitative answers; we advance one approach here. Robust and validated measures of resilience will enable coherent and rational discussions of complex emergent properties in macrocognitive system science.

Rational Design of an Ultrasensitive Quorum-Sensing Switch.

PubMed

Zeng, Weiqian; Du, Pei; Lou, Qiuli; Wu, Lili; Zhang, Haoqian M; Lou, Chunbo; Wang, Hongli; Ouyang, Qi

2017-08-18

One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.

Appraisal of and response to social conditions in the great gulf wilderness: relationships among perceived crowding, rationalization, product shift, satisfaction, and future behavioral intentions

Treesearch

Rudy M. Schuster; David Cole; Troy Hall; Jennifer Baker; Rebecca Oreskes

2007-01-01

Purposes were to describe on-site social carrying capacity from the users' perspectives, provide management applications, and refi ne constructs of product shift and rationalization used by visitors as coping responses to crowding. Data were gathered using on-site exit surveys of hikers in the Great Gulf Wilderness and analyzed with descriptive statistics,...

Rational Design of Semiconductor Nanostructures for Functional Subcellular Interfaces.

PubMed

Parameswaran, Ramya; Tian, Bozhi

2018-05-15

One of the fundamental questions guiding research in the biological sciences is how cellular systems process complex physical and environmental cues and communicate with each other across multiple length scales. Importantly, aberrant signal processing in these systems can lead to diseases that can have devastating impacts on human lives. Biophysical studies in the past several decades have demonstrated that cells can respond to not only biochemical cues but also mechanical and electrical ones. Thus, the development of new materials that can both sense and modulate all of these pathways is necessary. Semiconducting nanostructures are an emerging class of discovery platforms and tools that can push the limits of our ability to modulate and sense biological behaviors for both fundamental research and clinical applications. These materials are of particular interest for interfacing with cellular systems due to their matched dimension with subcellular components (e.g., cytoskeletal filaments), and easily tunable properties in the electrical, optical and mechanical regimes. Rational design via traditional or new approaches, such as nanocasting and mesoscale chemical lithography, can allow us to control micro- and nanoscale features in nanowires to achieve new biointerfaces. Both processes endogenous to the target cell and properties of the material surface dictate the character of these interfaces. In this Account, we focus on (1) approaches for the rational design of semiconducting nanowires that exhibit unique structures for biointerfaces, (2) recent fundamental discoveries that yield robust biointerfaces at the subcellular level, (3) intracellular electrical and mechanical sensing, and (4) modulation of cellular behaviors through material topography and remote physical stimuli. In the first section, we discuss new approaches for the synthetic control of micro- and nanoscale features of these materials. In the second section, we focus on achieving biointerfaces with these rationally designed materials either intra- or extracellularly. We last delve into the use of these materials in sensing mechanical forces and electrical signals in various cellular systems as well as in instructing cellular behaviors. Future research in this area may shift the paradigm in fundamental biophysical research and biomedical applications through (1) the design and synthesis of new semiconductor-based materials and devices that interact specifically with targeted cells, (2) the clarification of many developmental, physiological, and anatomical aspects of cellular communications, (3) an understanding of how signaling between cells regulates synaptic development (e.g., information like this would offer new insight into how the nervous system works and provide new targets for the treatment of neurological diseases), (4) and the creation of new cellular materials that have the potential to open up completely new areas of application, such as in hybrid information processing systems.

Membership theory, rationalism, and the claim to adequacy in health services.

PubMed

Falck, H S

1997-01-01

The immediate, practical purpose of this paper is to discuss and elaborate upon the concept of adequacy, especially when applicable to an understanding of the social work role in health policy making. The relevant topics under the general category of adequacy are (1) the perception and definition of the citizen/client; (2) the concept of rationality in health planning broken down into conditionality and prioritization, and (3) the concept of adequacy itself. Each will be addressed from the standpoint of recent experience and what may be done in the future to clarify and rationalize each. Clarity about clients, about rational approaches to policy making and planning, leading to a clear idea about adequacy in health care are presented as the indispensable elements in social work. Conditionality and prioritization are significant because no society will bring within equal reach of all members the benefits of health care, which usually means that health care is not rendered arbitrarily but as a result, among other things, of rational planning.

Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design.

PubMed

Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Milan, Luis Aparecido; Stockton, Amanda M; Carrilho, Emanuel

2017-05-02

Paper-based devices are a portable, user-friendly, and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-μPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-μPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-μPADs.

Program Synthesizes UML Sequence Diagrams

NASA Technical Reports Server (NTRS)

Barry, Matthew R.; Osborne, Richard N.

2006-01-01

A computer program called "Rational Sequence" generates Universal Modeling Language (UML) sequence diagrams of a target Java program running on a Java virtual machine (JVM). Rational Sequence thereby performs a reverse engineering function that aids in the design documentation of the target Java program. Whereas previously, the construction of sequence diagrams was a tedious manual process, Rational Sequence generates UML sequence diagrams automatically from the running Java code.

Time domain simulation of novel photovoltaic materials

NASA Astrophysics Data System (ADS)

Chung, Haejun

Thin-film silicon-based solar cells have operated far from the Shockley- Queisser limit in all experiments to date. Novel light-trapping structures, however, may help address this limitation. Finite-difference time domain simulation methods offer the potential to accurately determine the light-trapping potential of arbitrary dielectric structures, but suffer from materials modeling problems. In this thesis, existing dispersion models for novel photovoltaic materials will be reviewed, and a novel dispersion model, known as the quadratic complex rational function (QCRF), will be proposed. It has the advantage of accurately fitting experimental semiconductor dielectric values over a wide bandwidth in a numerically stable fashion. Applying the proposed dispersion model, a statistically correlated surface texturing method will be suggested, and light absorption rates of it will be explained. In future work, these designs will be combined with other structures and optimized to help guide future experiments.

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab.

PubMed

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions.

Adaptive and Rational Anticipations in Risk Management Systems and Economy

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.; Holmberg, Stig C.

2010-11-01

The global financial crisis of year 2009 is explained as a result of uncoordinated risk management decisions in business firms and economic organisations. The underlying reason for this can be found in the current financial system. As the financial market has lost much of its direct coupling to the concrete economy it provides misleading information to economic decision makers at all levels. Hence, the financial system has moved from a state of moderate and slow cyclical fluctuations into a state of fast and chaotic ones. Those misleading decisions can further be described, but not explained, by help of adaptive and rational expectations from macroeconomic theory. In this context, AE, the Adaptive Expectations are related to weak passive Exo-anticipation, and RE, the Rational expectations can be related to a strong, active and design oriented anticipation. The shortcomings of conventional cures, which builds on a reactive paradigm, have already been demonstrated in economic literature and are here further underlined by help of Ashby's "Law of Requisite Variety", Weaver's distinction between systems of "Disorganized Complexity" and those of "Organized Complexity", and Klir's "Reconstructability Analysis". Anticipatory decision-making is hence here proposed as a replacement to current expectation based and passive risk management. An anticipatory model of the business cycle is presented for supporting that proposition. The model, which is an extension of the Kaldor-Kalecki model, includes both retardation and anticipation. While cybernetics with the feedback process in control system deals with an explicit goal or purpose given to a system, the anticipatory system discussed here deals with a behaviour for which the future state of the system is built by the system itself, without explicit goal. A system with weak anticipation is based on a predictive model of the system, while a system with strong anticipation builds its own future by itself. Numerical simulations on computer confirm the feasibility of this approach. Hence, functional differential equations with both retardation and anticipation are found to be useful tools for modelling financial systems.

Rational design of carbon and TiO2 assembly materials: covered or strewn, which is better for photocatalysis?

PubMed

Cui, Guan-wei; Wang, Wei-liang; Ma, Ming-yue; Zhang, Ming; Xia, Xin-yuan; Han, Feng-yun; Shi, Xi-feng; Zhao, Ying-qiang; Dong, Yu-bin; Tang, Bo

2013-07-21

The rational design of carbonaceous hybrid nanostructures is very important for obtaining high photoactivity. TiO2 particles strewn with an optimal quantity of carbon nanodots have a much higher photoactivity than that of TiO2 covered with a carbon layer, showing the importance of carbon morphology in the photocatalysis of carbonaceous hybrid nanostructures.

Combining theory and experiment in electrocatalysis: Insights into materials design

DOE PAGES

Seh, Zhi Wei; Kibsgaard, Jakob; Dickens, Colin F.; ...

2017-01-12

Electrocatalysis plays a central role in clean energy conversion, enabling a number of sustainable processes for future technologies. This review discusses design strategies for state-of-the-art heterogeneous electrocatalysts and associated materials for several different electrochemical transformations involving water, hydrogen, and oxygen, using theory as a means to rationalize catalyst performance. By examining the common principles that govern catalysis for different electrochemical reactions, we describe a systematic framework that clarifies trends in catalyzing these reactions, serving as a guide to new catalyst development while highlighting key gaps that need to be addressed. Here, we conclude by extending this framework to emerging cleanmore » energy reactions such as hydrogen peroxide production, carbon dioxide reduction, and nitrogen reduction, where the development of improved catalysts could allow for the sustainable production of a broad range of fuels and chemicals.« less

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Essential Tremor: What We Can Learn from Current Pharmacotherapy

PubMed Central

Ondo, William

2016-01-01

Background The pathophysiology of essential tremor, especially at the cellular level, is poorly understood. Although no drug has been specifically designed to treat essential tremor, several medications improve tremor, and others worsen it. Studying the mechanism of actions of these medications can help our understanding of tremor pathophysiology and contribute to future rational drug design. Methods We reviewed literature, concentrating on mechanisms of action, of various medications that mitigate tremor. Results Many medications have multiple mechanisms of actions, making simple correlations difficult. Medications that increase the duration of opening of gamma-aminobutyric acid (GABA)-A receptors are most consistently associated with tremor improvement. Interestingly, drugs that increase GABA availability have not been associated with improved tremor. Other mechanisms possibly associated with tremor improvement include antagonism of alpha-2 delta subunits associated with calcium channels, inhibition of carbonic anhydrase, and inhibition of the synaptic vesicle protein 2A. Drugs that block voltage-gaited sodium channels do not affect tremor. The ideal beta-adrenergic blocker requires B2 affinity (non-cardiac selective), has no sympathomimetic properties, does not require membrane stabilization properties, and may benefit from good central nervous system penetration. Discussion To date, serendipitous observations have provided most of our understanding of tremor cellular physiology. Based on similarities to currently effective drugs or rational approximations and inferences, several currently available agents should be considered for tremor trials. PMID:26989572

How to use Hydra as a model system to teach biology in the classroom.

PubMed

Bossert, Patricia; Galliot, Brigitte

2012-01-01

As scientists it is our duty to fight against obscurantism and loss of rational thinking if we want politicians and citizens to freely make the most intelligent choices for the future generations. With that aim, the scientific education and training of young students is an obvious and urgent necessity. We claim here that Hydra provides a highly versatile but cheap model organism to study biology at any age. Teachers of biology have the unenviable task of motivating young people, who with many other motivations that are quite valid, nevertheless must be guided along a path congruent with a 'syllabus' or a 'curriculum'. The biology of Hydra spans the history of biology as an experimental science from Trembley's first manipulations designed to determine if the green polyp he found was plant or animal to the dissection of the molecular cascades underpinning, regeneration, wound healing, stemness, aging and cancer. It is described here in terms designed to elicit its wider use in classrooms. Simple lessons are outlined in sufficient detail for beginners to enter the world of 'Hydra biology'. Protocols start with the simplest observations to experiments that have been pretested with students in the USA and in Europe. The lessons are practical and can be used to bring 'life', but also rational thinking into the study of life for the teachers of students from elementary school through early university.

Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

PubMed

Hadd, Andrew; Perona, John J

2014-12-19

We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

Rational assembly of nanoparticle superlattices with designed lattice symmetries

DOEpatents

Gang, Oleg; Lu, Fang; Tagawa, Miho

2017-09-05

A method for lattice design via multivalent linkers (LDML) is disclosed that introduces a rationally designed symmetry of connections between particles in order to achieve control over the morphology of their assembly. The method affords the inclusion of different programmable interactions within one linker that allow an assembly of different types of particles. The designed symmetry of connections is preferably provided utilizing DNA encoding. The linkers may include fabricated "patchy" particles, DNA scaffold constructs and Y-shaped DNA linkers, anisotropic particles, which are preferably functionalized with DNA, multimeric protein-DNA complexes, and particles with finite numbers of DNA linkers.

A Rational Design, Synthesis, Biological Evaluation and Structure--Activity Relationship Study of Novel Inhibitors against Cyanobacterial Fructose-1,6-bisphosphate Aldolase.

PubMed

Han, Xinya; Zhu, Xiuyun; Zhu, Shuaihua; Wei, Lin; Hong, Zongqin; Guo, Li; Chen, Haifeng; Chi, Bo; Liu, Yan; Feng, Lingling; Ren, Yanliang; Wan, Jian

2016-01-25

In the present study, a series of novel maleimide derivatives were rationally designed and optimized, and their inhibitory activities against cyanobacteria class-II fructose-1,6-bisphosphate aldolase (Cy-FBA-II) and Synechocystis sp. PCC 6803 were further evaluated. The experimental results showed that the introduction of a bigger group (Br, Cl, CH3, or C6H3-o-F) on the pyrrole-2',5'-dione ring resulted in a decrease in the Cy-FBA-II inhibitory activity of the hit compounds. Generally, most of the hit compounds with high Cy-FBA-II inhibitory activities could also exhibit high in vivo activities against Synechocystis sp. PCC 6803. Especially, compound 10 not only shows a high Cy-FBA-II activity (IC50 = 1.7 μM) but also has the highest in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.6 ppm). Thus, compound 10 was selected as a representative molecule, and its probable interactions with the surrounding important residues in the active site of Cy-FBA-II were elucidated by the joint use of molecular docking, molecular dynamics simulations, ONIOM calculations, and enzymatic assays to provide new insight into the binding mode of the inhibitors and Cy-FBA-II. The positive results indicate that the design strategy used in the present study is very likely to be a promising way to find novel lead compounds with high inhibitory activities against Cy-FBA-II in the future. The enzymatic and algal inhibition assays suggest that Cy-FBA-II is very likely to be a promising target for the design, synthesis, and development of novel specific algicides to solve cyanobacterial harmful algal blooms.

A decade of vaccines: Integrating immunology and vaccinology for rational vaccine design.

PubMed

D'Argenio, David A; Wilson, Christopher B

2010-10-29

Vaccination stands as one of the most successful public health measures of the last century. New approaches will be needed, however, to develop highly effective vaccines to prevent tuberculosis, HIV-AIDS, and malaria and to eradicate polio. Current advances in immunology and technology have set the stage for rational vaccine design to begin a "Decade of Vaccines." Copyright © 2010 Elsevier Inc. All rights reserved.

Design of Mobile Augmented Reality in Health Care Education: A Theory-Driven Framework.

PubMed

Zhu, Egui; Lilienthal, Anneliese; Shluzas, Lauren Aquino; Masiello, Italo; Zary, Nabil

2015-09-18

Augmented reality (AR) is increasingly used across a range of subject areas in health care education as health care settings partner to bridge the gap between knowledge and practice. As the first contact with patients, general practitioners (GPs) are important in the battle against a global health threat, the spread of antibiotic resistance. AR has potential as a practical tool for GPs to combine learning and practice in the rational use of antibiotics. This paper was driven by learning theory to develop a mobile augmented reality education (MARE) design framework. The primary goal of the framework is to guide the development of AR educational apps. This study focuses on (1) identifying suitable learning theories for guiding the design of AR education apps, (2) integrating learning outcomes and learning theories to support health care education through AR, and (3) applying the design framework in the context of improving GPs' rational use of antibiotics. The design framework was first constructed with the conceptual framework analysis method. Data were collected from multidisciplinary publications and reference materials and were analyzed with directed content analysis to identify key concepts and their relationships. Then the design framework was applied to a health care educational challenge. The proposed MARE framework consists of three hierarchical layers: the foundation, function, and outcome layers. Three learning theories-situated, experiential, and transformative learning-provide foundational support based on differing views of the relationships among learning, practice, and the environment. The function layer depends upon the learners' personal paradigms and indicates how health care learning could be achieved with MARE. The outcome layer analyzes different learning abilities, from knowledge to the practice level, to clarify learning objectives and expectations and to avoid teaching pitched at the wrong level. Suggestions for learning activities and the requirements of the learning environment form the foundation for AR to fill the gap between learning outcomes and medical learners' personal paradigms. With the design framework, the expected rational use of antibiotics by GPs is described and is easy to execute and evaluate. The comparison of specific expected abilities with the GP personal paradigm helps solidify the GP practical learning objectives and helps design the learning environment and activities. The learning environment and activities were supported by learning theories. This paper describes a framework for guiding the design, development, and application of mobile AR for medical education in the health care setting. The framework is theory driven with an understanding of the characteristics of AR and specific medical disciplines toward helping medical education improve professional development from knowledge to practice. Future research will use the framework as a guide for developing AR apps in practice to validate and improve the design framework.

Design of Mobile Augmented Reality in Health Care Education: A Theory-Driven Framework

PubMed Central

Lilienthal, Anneliese; Shluzas, Lauren Aquino; Masiello, Italo; Zary, Nabil

2015-01-01

Background Augmented reality (AR) is increasingly used across a range of subject areas in health care education as health care settings partner to bridge the gap between knowledge and practice. As the first contact with patients, general practitioners (GPs) are important in the battle against a global health threat, the spread of antibiotic resistance. AR has potential as a practical tool for GPs to combine learning and practice in the rational use of antibiotics. Objective This paper was driven by learning theory to develop a mobile augmented reality education (MARE) design framework. The primary goal of the framework is to guide the development of AR educational apps. This study focuses on (1) identifying suitable learning theories for guiding the design of AR education apps, (2) integrating learning outcomes and learning theories to support health care education through AR, and (3) applying the design framework in the context of improving GPs’ rational use of antibiotics. Methods The design framework was first constructed with the conceptual framework analysis method. Data were collected from multidisciplinary publications and reference materials and were analyzed with directed content analysis to identify key concepts and their relationships. Then the design framework was applied to a health care educational challenge. Results The proposed MARE framework consists of three hierarchical layers: the foundation, function, and outcome layers. Three learning theories—situated, experiential, and transformative learning—provide foundational support based on differing views of the relationships among learning, practice, and the environment. The function layer depends upon the learners’ personal paradigms and indicates how health care learning could be achieved with MARE. The outcome layer analyzes different learning abilities, from knowledge to the practice level, to clarify learning objectives and expectations and to avoid teaching pitched at the wrong level. Suggestions for learning activities and the requirements of the learning environment form the foundation for AR to fill the gap between learning outcomes and medical learners’ personal paradigms. With the design framework, the expected rational use of antibiotics by GPs is described and is easy to execute and evaluate. The comparison of specific expected abilities with the GP personal paradigm helps solidify the GP practical learning objectives and helps design the learning environment and activities. The learning environment and activities were supported by learning theories. Conclusions This paper describes a framework for guiding the design, development, and application of mobile AR for medical education in the health care setting. The framework is theory driven with an understanding of the characteristics of AR and specific medical disciplines toward helping medical education improve professional development from knowledge to practice. Future research will use the framework as a guide for developing AR apps in practice to validate and improve the design framework. PMID:27731839

Rational design of aerobic digestion systems

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

Rich, L.G.

1987-06-01

Deficiencies are identified in state-of-the-art procedures used in the design of systems for the aerobic digestion of waste-activated sludge solids. A procedure for the design of such systems on a rational basis is presented. Such a procedure not only includes a well-defined stabilization objective, but takes into account the stabilization that occurs in the activated sludge process. Related methods are discussed by which coefficients used in the design procedure can be evaluated. A design example is given. Further research and performance data derived from systems designed by the procedure are needed to better evaluate the parameters used and to testmore » the assumptions made in applying the procedure.« less

Rational design of aerobic digestion systems

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

Rich, L.G.

1987-06-01

Deficiencies are identified in state-of-the-art procedures used in the design of systems for the aerobic digestion of waste-activated sludge solids. A procedure for the design of such systems on a rational basis is presented. Such a procedure not only includes a well-defined stabilization objective, but takes into account the stabilization that occurs in the activated sludge process. Related methods are discussed by which coefficients used in the design procedure can be evaluated. A design example is given. Further research and performance data derived from systems designed by the procedure are needed to better evaluate the parameters used and to testmore » the assumptions made in applying the procedure. (Refs. 28).« less

Simon and the Sirens: A Commentary.

PubMed

Daston, Lorraine

2015-09-01

Even in its extended usage, the concept of bounded rationality bears the birthmark of its origins in economics. First and most obviously, it is about seeking the most efficient (not necessarily the best) means toward a given end, whether that is curing patients or proving theorems. Second, the means are whittled down to the most parsimonious possible, not only acknowledging cognitive limitations but actually imposing them, whether in the form of Morgan's canon, Methodist agnosticism about causes, or Entscheidungsproblem-like restrictions on the acceptable formulation of mathematical proofs. Third, these parsimonious restrictions all tend to minimize the role of reasonable deliberation in rationality, albeit in different ways. As an object of inquiry for the history of science, bounded rationality has great promise. But as a model of the history of science, as one long exercise in bounded rationality, its utility may apply more to future than past science.

Fate, morals and rational calculations: Freezing eggs for non-medical reasons in Turkey.

PubMed

Kılıç, Azer; Göçmen, İpek

2018-04-01

This article aims to explore women's decisions to freeze their eggs for non-medical reasons in Turkey. It draws on semi-structured interviews conducted with twenty-one women who were either in the process of freezing their eggs, or had completed the process within the previous year. Being highly educated and holding prestigious occupations, on the one hand, and faced with traditional gender norms, on the other, these women are confronted with a challenging decision. When making such a decision to freeze their eggs, women act under the constraints defined by biomedical paradigms, the society they live in, and the future uncertainty of their lives. However, it becomes apparent that women are able to reconcile different kinds of rationalities and concerns in their decisions to freeze eggs. They engage in rational calculations to find a solution to their reproductive concerns; they turn to their own belief systems when dealing with future uncertainty; and they negotiate social norms concerning virginity, while trying to conform to traditional reproductive roles. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Plotkowski, A.; Rios, O.; Sridharan, N.

Our present research in metal additive manufacturing (AM) focuses on designing processing parameters around existing alloys designed for traditional manufacturing. However, to maximize the benefits of AM, alloys should be designed to specifically take advantage of the unique thermal conditions of these processes. Furthermore, our study focuses on the development of a design methodology for alloys in AM, using a newly developed Al-Ce alloy as an initial case study. To evaluate the candidacy of this system for fusion based additive manufacturing, single-line laser melts were made on cast Al-12Ce plates using three different beam velocities (100, 200, and 300 mm/min).more » The microstructure was evaluated in the as-melted and heat treated conditions (24 hrs at 300°C). An extremely fine microstructure was observed within the weld pools, evolving from eutectic at the outer solid-liquid boundaries to a primary Al FCC dendritic/cellular structure nearer the melt-pool centerline. We rationalized the observed microstructures through the construction of a microstructure selection map for the Al-Ce binary system, which will be used to enable future alloy design. Interestingly, the heat treated samples exhibited no microstructural coarsening.« less

Scoping the polymer genome: A roadmap for rational polymer dielectrics design and beyond

DOE PAGES

Mannodi-Kanakkithodi, Arun; Chandrasekaran, Anand; Kim, Chiho; ...

2017-12-19

The Materials Genome Initiative (MGI) has heralded a sea change in the philosophy of materials design. In an increasing number of applications, the successful deployment of novel materials has benefited from the use of computational methodologies, data descriptors, and machine learning. Polymers have long suffered from a lack of data on electronic, mechanical, and dielectric properties across large chemical spaces, causing a stagnation in the set of suitable candidates for various applications. Extensive efforts over the last few years have seen the fruitful application of MGI principles toward the accelerated discovery of attractive polymer dielectrics for capacitive energy storage. Here,more » we review these efforts, highlighting the importance of computational data generation and screening, targeted synthesis and characterization, polymer fingerprinting and machine-learning prediction models, and the creation of an online knowledgebase to guide ongoing and future polymer discovery and design. We lay special emphasis on the fingerprinting of polymers in terms of their genome or constituent atomic and molecular fragments, an idea that pays homage to the pioneers of the human genome project who identified the basic building blocks of the human DNA. As a result, by scoping the polymer genome, we present an essential roadmap for the design of polymer dielectrics, and provide future perspectives and directions for expansions to other polymer subclasses and properties.« less

Scoping the polymer genome: A roadmap for rational polymer dielectrics design and beyond

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

Mannodi-Kanakkithodi, Arun; Chandrasekaran, Anand; Kim, Chiho

The Materials Genome Initiative (MGI) has heralded a sea change in the philosophy of materials design. In an increasing number of applications, the successful deployment of novel materials has benefited from the use of computational methodologies, data descriptors, and machine learning. Polymers have long suffered from a lack of data on electronic, mechanical, and dielectric properties across large chemical spaces, causing a stagnation in the set of suitable candidates for various applications. Extensive efforts over the last few years have seen the fruitful application of MGI principles toward the accelerated discovery of attractive polymer dielectrics for capacitive energy storage. Here,more » we review these efforts, highlighting the importance of computational data generation and screening, targeted synthesis and characterization, polymer fingerprinting and machine-learning prediction models, and the creation of an online knowledgebase to guide ongoing and future polymer discovery and design. We lay special emphasis on the fingerprinting of polymers in terms of their genome or constituent atomic and molecular fragments, an idea that pays homage to the pioneers of the human genome project who identified the basic building blocks of the human DNA. As a result, by scoping the polymer genome, we present an essential roadmap for the design of polymer dielectrics, and provide future perspectives and directions for expansions to other polymer subclasses and properties.« less

Understanding and exploiting the phase behavior of mixtures of oppositely charged polymers and surfactants in water.

PubMed

Piculell, Lennart

2013-08-20

Complexes of oppositely charged polymers and surfactants (OCPS) in water come in many varieties, including liquid-crystalline materials, soluble complexes, structured nanoparticles, and water-insoluble surface layers. The range of available structures and properties increases even further with the addition of other amphiphilic substances that may enter, or even dissolve, the complexes, depending on the nature of the additive. Simple operations may change the properties of OCPS systems dramatically. For instance, dilution with water can induce a phase separation in an initially stable OCPS solution. More complicated processes, involving chemical reactions, can be used to either create or disintegrate OCPS particles or surface layers. The richness of their properties has made OCPS mixtures ubiquitous in everyday household products, such as shampoos and laundry detergents, and also attractive ingredients in the design of new types of responsive particles, surfaces, and delivery agents of potential use in future applications. A challenge for the rational design of an OCPS system is, however, to obtain a good fundamental understanding of how to select molecular shapes and sizes and how to tune the hydrophobic and electrostatic interactions such that the desired properties are obtained. Recent studies of OCPS phase equilibria, using a strategy where the minimum number of components is always used to address a particular question, have brought out general rules and trends that can be used for such a rational design. Those fundamental studies are reviewed here, together with more application-oriented studies where fundamental learning has been put to use.

Validation of mobile phone text messages for nicotine and tobacco risk communication among college students: A content analysis.

PubMed

Khalil, Georges E; Calabro, Karen S; Crook, Brittani; Machado, Tamara C; Perry, Cheryl L; Prokhorov, Alexander V

2018-02-01

In the United States, young adults have the highest prevalence of tobacco use. The dissemination of mobile phone text messages is a growing strategy for tobacco risk communication among young adults. However, little has been done concerning the design and validation of such text messages. The Texas Tobacco Center of Regulatory Science (Texas-TCORS) has developed a library of messages based on framing (gain- or loss-framed), depth (simple or complex) and appeal (emotional or rational). This study validated the library based on depth and appeal, identified text messages that may need improvement, and explored new themes. The library formed the study sample (N=976 messages). The Linguistic Inquiry and Word Count (LIWC) software of 2015 was used to code for word count, word length and frequency of emotional and cognitive words. Analyses of variance, logistic regression and scatter plots were conducted for validation. In all, 874 messages agreed with LIWC-coding. Several messages did not agree with LIWC. Ten messages designed to be complex indicated simplicity, while 51 messages designed to be rational exhibited no cognitive words. New relevant themes were identified, such as health (e.g. 'diagnosis', 'cancer'), death (e.g. 'dead', 'lethal') and social connotations (e.g. 'parents', 'friends'). Nicotine and tobacco researchers can safely use, for young adults, messages from the Texas-TCORS library to convey information in the intended style. Future work may expand upon the new themes. Findings will be utilized to develop new campaigns, so that risks of nicotine and tobacco products can be widely disseminated.

Monotonicity preserving splines using rational cubic Timmer interpolation

NASA Astrophysics Data System (ADS)

Zakaria, Wan Zafira Ezza Wan; Alimin, Nur Safiyah; Ali, Jamaludin Md

2017-08-01

In scientific application and Computer Aided Design (CAD), users usually need to generate a spline passing through a given set of data, which preserves certain shape properties of the data such as positivity, monotonicity or convexity. The required curve has to be a smooth shape-preserving interpolant. In this paper a rational cubic spline in Timmer representation is developed to generate interpolant that preserves monotonicity with visually pleasing curve. To control the shape of the interpolant three parameters are introduced. The shape parameters in the description of the rational cubic interpolant are subjected to monotonicity constrained. The necessary and sufficient conditions of the rational cubic interpolant are derived and visually the proposed rational cubic Timmer interpolant gives very pleasing results.

A Study on the Application of the Information-Motivation-Behavioral Skills (IMB) Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China.

PubMed

Bian, Cheng; Xu, Shuman; Wang, Heng; Li, Niannian; Wu, Jingya; Zhao, Yunwu; Li, Peng; Lu, Hua

2015-01-01

The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge.

A Study on the Application of the Information-Motivation-Behavioral Skills (IMB) Model on Rational Drug Use Behavior among Second-Level Hospital Outpatients in Anhui, China

PubMed Central

Wang, Heng; Li, Niannian; Wu, Jingya; Zhao, Yunwu; Li, Peng; Lu, Hua

2015-01-01

Background The high prevalence of risky irrational drug use behaviors mean that outpatients face high risks of drug resistance and even death. This study represents the first application of the Information-Motivation-Behavioral Skills (IMB) model on rational drug use behavior among second-level hospital outpatients from three prefecture-level cities in Anhui, China. Using the IMB model, our study examined predictors of rational drug use behavior and determined the associations between the model constructs. Methods This study was conducted with a sample of 1,214 outpatients aged 18 years and older in Anhui second-level hospitals and applied the structural equation model (SEM) to test predictive relations among the IMB model variables related to rational drug use behavior. Results Age, information and motivation had significant direct effects on rational drug use behavior. Behavioral skills as an intermediate variable also significantly predicted more rational drug use behavior. Female gender, higher educational level, more information and more motivation predicted more behavioral skills. In addition, there were significant indirect impacts on rational drug use behavior mediated through behavioral skills. Conclusions The IMB-based model explained the relationships between the constructs and rational drug use behavior of outpatients in detail, and it suggests that future interventions among second-level hospital outpatients should consider demographic characteristics and should focus on improving motivation and behavioral skills in addition to the publicity of knowledge. PMID:26275301

Mechanistic Basis for Plant Responses to Drought Stress : Regulatory Mechanism of Abscisic Acid Signaling

NASA Astrophysics Data System (ADS)

Miyakawa, Takuya; Tanokura, Masaru

The phytohormone abscisic acid (ABA) plays a key role in the rapid adaptation of plants to environmental stresses such as drought and high salinity. Accumulated ABA in plant cells promotes stomatal closure in guard cells and transcription of stress-tolerant genes. Our understanding of ABA responses dramatically improved by the discovery of both PYR/PYL/RCAR as a soluble ABA receptor and inhibitory complex of a protein phospatase PP2C and a protein kinase SnRK2. Moreover, several structural analyses of PYR/PYL/RCAR revealed the mechanistic basis for the regulatory mechanism of ABA signaling, which provides a rational framework for the design of alternative agonists in future.

Novel FeII and CoII Complexes of Natural Product Tryptanthrin: Synthesis and Binding with G-Quadruplex DNA

PubMed Central

Zhong, Yi-ning; Zhang, Yan; Gu, Yun-qiong; Wu, Shi-yun; Shen, Wen-ying

2016-01-01

Tryptanthrin is one of the most important members of indoloquinoline alkaloids. We obtained this alkaloid from Isatis. Two novel FeII and CoII complexes of tryptanthrin were first synthesized. Single-crystal X-ray diffraction analyses show that these complexes display distorted four-coordinated tetrahedron geometry via two heterocyclic nitrogen and oxygen atoms from tryptanthrin ligand. Binding with G-quadruplex DNA properties revealed that both complexes were found to exhibit significant interaction with G-quadruplex DNA. This study may potentially serve as the basis of future rational design of metal-based drugs from natural products that target the G-quadruplex DNA. PMID:27698647

Development of a scale to assess Hwa-Byung, a Korean culture-bound syndrome, using the Korean MMPI-2.

PubMed

Roberts, Miguel E; Han, Kyunghee; Weed, Nathan C

2006-09-01

This study documents the development of an MMPI-2 scale designed to assess features of the Korean culture-bound syndrome, Hwa-Byung (HB). An American research team and psychiatric practitioners in Korea created an 18-item HB scale via rational item selection and psycho-metric refinement. Principal components analysis of scale items revealed four components, reflecting content domains of general health, gastrointestinal symptoms, hopelessness, and anger. This four-component solution applied well to both Korean men and women, but not to an American sample. Although some findings were encouraging, future studies employing clinical samples are needed to provide further validation of this scale.

Turbine airfoil deposition models and their hot corrosion implications

NASA Technical Reports Server (NTRS)

Rosner, D. E.; Nagarajan, R.

1985-01-01

This research project deals with the prediction of single- and multi-component salt(-solution) deposition, flow and oxide dissolution and their effects on the lifetime of turbine blades. Goals include rationalizing and helping to predict corrosion patterns on operational gas turbine (GT) rotor blades and stator vanes, and ultimately providing some of the tools required to design laboratory simulators and future corrosion resistant high-performance engines. Necessary background developments are reviewed. Results and tentative conclusions for single species (Na sub 2 SO sub 4 (1)) condensation, binary salt-solution (Na sub 2 SO sub 4-K sub 2 SO sub 4) condensation, and burner-rig testing of alloy materials are outlined.

Review of Dynamic Modeling and Simulation of Large Scale Belt Conveyor System

NASA Astrophysics Data System (ADS)

He, Qing; Li, Hong

Belt conveyor is one of the most important devices to transport bulk-solid material for long distance. Dynamic analysis is the key to decide whether the design is rational in technique, safe and reliable in running, feasible in economy. It is very important to study dynamic properties, improve efficiency and productivity, guarantee conveyor safe, reliable and stable running. The dynamic researches and applications of large scale belt conveyor are discussed. The main research topics, the state-of-the-art of dynamic researches on belt conveyor are analyzed. The main future works focus on dynamic analysis, modeling and simulation of main components and whole system, nonlinear modeling, simulation and vibration analysis of large scale conveyor system.

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

PubMed Central

Williams, Charles H.; Hong, Charles C.

2011-01-01

In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET) properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design. PMID:21731440

Tunable emission in lanthanide coordination polymer gels based on a rationally designed blue emissive gelator.

PubMed

Sutar, Papri; Suresh, Venkata M; Maji, Tapas Kumar

2015-06-18

Rational design and synthesis of a new low molecular weight gelator (LMWG) having 9,10-diphenylanthracene core and terminal terpyridine is reported. Tb(III) and Eu(III) ion coordination to a LMWG results in green and pink emissive coordination polymer gels, respectively, with coiled nanofiber morphology. Further, control over stoichiometry of LMWG:Tb(III):Eu(III) leads to yellow and white light emitting bimetallic gels.

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

PubMed Central

Ciceri, Pietro; Müller, Susanne; O’Mahony, Alison; Fedorov, Oleg; Filippakopoulos, Panagis; Hunt, Jeremy P.; Lasater, Elisabeth A.; Pallares, Gabriel; Picaud, Sarah; Wells, Christopher; Martin, Sarah; Wodicka, Lisa M.; Shah, Neil P.; Treiber, Daniel K.; Knapp, Stefan

2014-01-01

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination therapies, which can pose significant clinical development challenges. Epigenetic reader domains of the bromodomain family have recently emerged as novel targets for cancer therapy. Here we report that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase/bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, is particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a novel strategy for rational single agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identify design features that enable a general platform for the rational design of dual kinase/bromodomain inhibitors. PMID:24584101

TRO-2D - A code for rational transonic aerodynamic optimization

NASA Technical Reports Server (NTRS)

Davis, W. H., Jr.

1985-01-01

Features and sample applications of the transonic rational optimization (TRO-2D) code are outlined. TRO-2D includes the airfoil analysis code FLO-36, the CONMIN optimization code and a rational approach to defining aero-function shapes for geometry modification. The program is part of an effort to develop an aerodynamically smart optimizer that will simplify and shorten the design process. The user has a selection of drag minimization and associated minimum lift, moment, and the pressure distribution, a choice among 14 resident aero-function shapes, and options on aerodynamic and geometric constraints. Design variables such as the angle of attack, leading edge radius and camber, shock strength and movement, supersonic pressure plateau control, etc., are discussed. The results of calculations of a reduced leading edge camber transonic airfoil and an airfoil with a natural laminar flow are provided, showing that only four design variables need be specified to obtain satisfactory results.

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

PubMed

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways.

Rational-Emotive Therapy versus Systematic Desensitization: A Comment on Moleski and Tosi.

ERIC Educational Resources Information Center

Atkinson, Leslie

1983-01-01

Questioned the statistical analyses of the Moleski and Tosi investigation of rational-emotive therapy versus systematic desensitization. Suggested means for lowering the error rate through a more efficient experimental design. Recommended a reanalysis of the original data. (LLL)

Discounting the future: influence of the economic model.

PubMed

West, R R

1996-06-01

To consider the effect of the economic discount rate on health care policy and the rationale for discounting the collective future of society generally. A review of the concept of discounting the future vis à vis the present from the points of view of individuals (who pass on) and of societies (that continue) and reconsideration of the application of discounting to typical public health scenarios. A public health service, within a basically stable society, which can reasonably anticipate a nearly certain future. Discounting necessarily overvalues the "here and now" compared with the future. While applications of discount rates, typical of those employed in health economic studies in recent years, may seem rational in health care programmes directed at middle aged employed people, they do not for the young and the elderly, important recipients of health care. The consequences of discounting do not accord with the aims and objectives of public health. The "time preferences" of transient individuals within a stable society do not provide a rational basis for time preference of a stable society collectively. Discounting inevitably encourages "short termism" and hence biases public policy decision making. The neoclassical theory that gave rise to the concept of discounting requires revision.

Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab

PubMed Central

Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

2016-01-01

The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions. PMID:26514585

What Future for Educational Research in Europe? Political, Epistemological and Ethical Challenges

ERIC Educational Resources Information Center

Grimaldi, Emiliano

2015-01-01

This article reflects on the future of European educational research (EER) and its politics of knowledge. EER is interpreted as a field of power/knowledge, where a hegemonic epistemic framework is raised that assembles an evidence-based epistemology, a "what works" political rationality and a technocratic model of educational research.…

Options as information: rational reversals of evaluation and preference.

PubMed

Sher, Shlomi; McKenzie, Craig R M

2014-06-01

This article develops a rational analysis of an important class of apparent preference reversals-joint-separate reversals traditionally explained by the evaluability hypothesis. The "options-as-information" model considers a hypothetical rational actor with limited knowledge about the market distribution of a stimulus attribute. The actor's evaluations are formed via a 2-stage process-an inferential stage in which beliefs are updated on the basis of the sample of options received, followed by an assessment stage in which options are evaluated in light of these updated beliefs. This process generates joint-separate reversals in standard experimental designs. The normative model explains why the evaluability hypothesis works when it does, identifies boundary conditions for the hypothesis, and clarifies some common misconceptions about these effects. In particular, it implies that joint-separate reversals are not irrational; in fact, they are not preference reversals. However, in expanded designs where more than 2 options are jointly evaluated, the model predicts that genuine (and rational) preference reversals will sometimes emerge. Results of 3 experiments suggest an excellent fit between the rational actor model and the judgments of human actors in joint-separate experiments. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Spectromicroscopic insights for rational design of redox-based memristive devices

PubMed Central

Baeumer, Christoph; Schmitz, Christoph; Ramadan, Amr H. H.; Du, Hongchu; Skaja, Katharina; Feyer, Vitaliy; Müller, Philipp; Arndt, Benedikt; Jia, Chun-Lin; Mayer, Joachim; De Souza, Roger A.; Michael Schneider, Claus; Waser, Rainer; Dittmann, Regina

2015-01-01

The demand for highly scalable, low-power devices for data storage and logic operations is strongly stimulating research into resistive switching as a novel concept for future non-volatile memory devices. To meet technological requirements, it is imperative to have a set of material design rules based on fundamental material physics, but deriving such rules is proving challenging. Here, we elucidate both switching mechanism and failure mechanism in the valence-change model material SrTiO3, and on this basis we derive a design rule for failure-resistant devices. Spectromicroscopy reveals that the resistance change during device operation and failure is indeed caused by nanoscale oxygen migration resulting in localized valence changes between Ti4+ and Ti3+. While fast reoxidation typically results in retention failure in SrTiO3, local phase separation within the switching filament stabilizes the retention. Mimicking this phase separation by intentionally introducing retention-stabilization layers with slow oxygen transport improves retention times considerably. PMID:26477940

The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design

PubMed Central

Cozza, Giorgio

2017-01-01

Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by “trial and error testing”. In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range. The screening of big chemical libraries and the optimization of hit compounds by Structure Based Drug Design (SBDD) provide telling examples of a fruitful application of rational drug design to the development of CK2 inhibitors. Ligand Based Drug Design (LBDD) models have been also applied to CK2 drug discovery, however they were mainly focused on methodology improvements rather than being critical for de novo design and optimization. This manuscript provides detailed description of in silico methodologies whose applications to the design and development of CK2 inhibitors proved successful and promising. PMID:28230762

Nutrition for Health and Performance, 2000: Nutritional Guidance for Military Operations in Temperate and Extreme Environments.

DTIC Science & Technology

1999-12-01

processed , high-salt foods (read food labels). • If You Drink Alcoholic Beverages, Do So in Moderation - Alcoholic beverages supply calories but...military. Rations are made from "real foods" (commercially grown and processed ). Commercial brand name foods and military ration items are often...designed to simplify and streamline the process of providing group meals in the field by integrating components of A-Rations, and Heat & Serve (H & S

Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design

PubMed Central

Kong, Leopold; Sattentau, Quentin J

2012-01-01

Neutralizing antibodies can protect from infection by immunodeficiency viruses. However, the induction by active vaccination of antibodies that can potently neutralize a broad range of circulating virus strains is a goal not yet achieved, despite more than 2 decades of research. Here we review progress made in the field, from early empirical studies to today’s rational structure-based vaccine antigen design. We discuss the existence of broadly neutralizing antibodies, their implications for epitope discovery and recent progress made in antigen design. Finally, we consider the relationship between antigenicity and immunogenicity for B cell recognition and antibody production, a major hurdle for rational vaccine design to overcome. PMID:23227445

Molecular simulations for energy, environmental and pharmaceutical applications of nanoporous materials: from zeolites, metal-organic frameworks to protein crystals.

PubMed

Jiang, Jianwen; Babarao, Ravichandar; Hu, Zhongqiao

2011-07-01

Nanoporous materials have widespread applications in chemical industry, but the pathway from laboratory synthesis and testing to practical utilization of nanoporous materials is substantially challenging and requires fundamental understanding from the bottom up. With ever-growing computational resources, molecular simulations have become an indispensable tool for material characterization, screening and design. This tutorial review summarizes the recent simulation studies in zeolites, metal-organic frameworks and protein crystals, and provides a molecular overview for energy, environmental and pharmaceutical applications of nanoporous materials with increasing degree of complexity in building blocks. It is demonstrated that molecular-level studies can bridge the gap between physical and engineering sciences, unravel microscopic insights that are otherwise experimentally inaccessible, and assist in the rational design of new materials. The review is concluded with major challenges in future simulation exploration of novel nanoporous materials for emerging applications.

Tunable Molecular-Scale Materials for Catalyzing the Low-Overpotential Electrochemical Conversion of CO2.

PubMed

Rosen, Brian A; Hod, Idan

2018-04-25

Electrochemical CO 2 reduction provides a clean and viable alternative for mitigating the environmental aspects of global greenhouse gas emissions. To date, the simultaneous goals of CO 2 reduction at high selectivity and activity have yet to be achieved. Here, the importance of engineering both sides of the electrode-electrolyte interface as a rational strategy for achieving this milestone is highlighted. An emphasis is placed on researchers contributing to the design of solid electrodes based on metal-organic frameworks (MOFs) and electrolytes based on room-temperature ionic liquids (RTILs). Future research geared toward optimizing the electrode-electrolyte interface for efficient and selective CO 2 reduction can be achieved by understanding the structure of newly designed RTILs at the electrified interface, as well as structure-activity relationships in highly tunable MOF platforms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding glass formation and ion transport in polymeric ionic liquids using computer simulations

NASA Astrophysics Data System (ADS)

Patra, Tarak; Yang, Junhong; Cheng, Yiz; Simmons, David

Polymeric ionic liquids (PILs) are very promising materials to enable more environmentally stable high density energy storage devices. Realization of PILs providing high environmental and mechanical stability while maximizing ion conductivity would be accelerated by an improved molecular level understanding of their structure and dynamics. Extensive evidence suggests that both mechanical properties and ion conductivity in anhydrous PILs are intimately related to the PIL's glass formation behavior. This represents a major challenge to the rational design of these materials, given that the basic nature of glass formation and its connection to molecular properties remains a substantial open question in polymer and condensed matter physics. Here we describe coarse-grained and atomistic molecular dynamics simulations probing the relationship between PIL architecture and interactions, glass formation behavior, and ion transport characteristics. These studies provide guidance towards the design of PILs with improved stability and ion conductivity for future energy applications.

Rational Design of Glycomimetic Compounds Targeting the Saccharomyces cerevisiae Transglycosylase Gas2.

PubMed

Delso, Ignacio; Valero-González, Jessika; Marca, Eduardo; Tejero, Tomás; Hurtado-Guerrero, Ramón; Merino, Pedro

2016-02-01

The transglycosylase Saccharomyces cerevisiae Gas2 (ScGas2) belongs to a large family of enzymes that are key players in yeast cell wall remodeling. Despite its biologic importance, no studies on the synthesis of substrate-based compounds as potential inhibitors have been reported. We have synthesized a series of docking-guided glycomimetics that were evaluated by fluorescence spectroscopy and saturation-transfer difference (STD) NMR experiments, revealing that a minimum of three glucose units linked via a β-(1,3) linkage are required for achieving molecular recognition at the binding donor site. The binding mode of our compounds is further supported by STD-NMR experiments using the active site-mutants Y107Q and Y244Q. Our results are important for both understanding of ScGas2-substrate interactions and setting up the basis for future design of glycomimetics as new antifungal agents. © 2015 John Wiley & Sons A/S.

Game Theory for Wireless Sensor Networks: A Survey

PubMed Central

Shi, Hai-Yan; Wang, Wan-Liang; Kwok, Ngai-Ming; Chen, Sheng-Yong

2012-01-01

Game theory (GT) is a mathematical method that describes the phenomenon of conflict and cooperation between intelligent rational decision-makers. In particular, the theory has been proven very useful in the design of wireless sensor networks (WSNs). This article surveys the recent developments and findings of GT, its applications in WSNs, and provides the community a general view of this vibrant research area. We first introduce the typical formulation of GT in the WSN application domain. The roles of GT are described that include routing protocol design, topology control, power control and energy saving, packet forwarding, data collection, spectrum allocation, bandwidth allocation, quality of service control, coverage optimization, WSN security, and other sensor management tasks. Then, three variations of game theory are described, namely, the cooperative, non-cooperative, and repeated schemes. Finally, existing problems and future trends are identified for researchers and engineers in the field. PMID:23012533

Identification and design principles of low hole effective mass p-type transparent conducting oxides

PubMed Central

Hautier, Geoffroy; Miglio, Anna; Ceder, Gerbrand; Rignanese, Gian-Marco; Gonze, Xavier

2013-01-01

The development of high-performance transparent conducting oxides is critical to many technologies from transparent electronics to solar cells. Whereas n-type transparent conducting oxides are present in many devices, their p-type counterparts are not largely commercialized, as they exhibit much lower carrier mobilities due to the large hole effective masses of most oxides. Here we conduct a high-throughput computational search on thousands of binary and ternary oxides and identify several highly promising compounds displaying exceptionally low hole effective masses (up to an order of magnitude lower than state-of-the-art p-type transparent conducting oxides), as well as wide band gaps. In addition to the discovery of specific compounds, the chemical rationalization of our findings opens new directions, beyond current Cu-based chemistries, for the design and development of future p-type transparent conducting oxides. PMID:23939205

Edible Nanoencapsulation Vehicles for Oral Delivery of Phytochemicals: A Perspective Paper.

PubMed

Xiao, Jie; Cao, Yong; Huang, Qingrong

2017-08-16

Edible nanoencapsulation vehicles (ENVs) designed for the delivery of phytochemicals have gained increasing research interest. The major driving force for this trend is the potential bioavailability enhancement effect for phytochemicals when delivered via ENVs. ENVs affect the bioefficacy of phytochemicals by influencing their dispersion and gastrointestinal stability, rate and site of release, transportation efficiency across the endothelial layer, systemic circulation and biodistribution, and regulation of gut microflora. Enhanced bioefficacy can be achieved by rational design of the size, surface property, matrix materials, and compartment structure of ENVs according to properties of phytochemicals. Future investigations may lay particular emphasis on examining the relevance between results gained by in vitro digestion simulations and those obtained via in vivo digestion simulations, structural evolutions of ENVs during digestion and absorption, impacts of ENVs on the metabolism of phytochemicals, and using ENVs for deciphering the reciprocal interactions between phytochemicals and gut microbiota.

Emotional and rational disease acceptance in patients with depression and alcohol addiction.

PubMed

Büssing, Arndt; Matthiessen, Peter F; Mundle, Götz

2008-01-21

The concept of a rational respectively emotional acceptance of disease is highly valued in the treatment of patients with depression or addiction. Due to the importance of this concept for the long-term course of disease, there is a strong interest to develop a tool to identify the levels and factors of acceptance. We thus intended to test an instrument designed to assess the level of positive psychological wellbeing and coping, particularly emotional disease acceptance and life satisfaction In an anonymous cross-sectional survey enrolling 115 patients (51% female, 49% male; mean age 47.6 +/- 10.0 years) with depression and/or alcohol addiction, the ERDA questionnaire was tested. Factor analysis of the 29-item construct (Cronbach's alpha = 0.933) revealed a 4-factor solution, which explained 59.4% of variance: (1) Positive Life Construction, Contentedness and Well-Being; (2) Conscious Dealing with Illness; (3) Rejection of an Irrational Dealing with Disease; (4) Disease Acceptance. Two factors could be ascribed to a rational, and two to an emotional acceptance. All factors correlated negatively with Depression and Escape, while several aspects of Life Satisfaction" (i.e. myself, overall life, where I live, and future prospects) correlated positively. The highest factor scores were found for the rational acceptance styles (i.e. Conscious Dealing with Illness; Disease Acceptance). Emotional acceptance styles were not valued in a state of depression. Escape from illness was the strongest predictor for several acceptance aspects, while life satisfaction was the most relevant predictor for "Positive Life Construction, Contentedness and Well-Being". The ERDA questionnaire was found to be a reliable and valid assessment of disease acceptance strategies in patients with depressive disorders and drug abuses. The results indicate the preferential use of rational acceptance styles even in depression. Disease acceptance should not be regarded as a coping style with an attitude of fatalistic resignation, but as a complex and active process of dealing with a chronic disease. One may assume that an emotional acceptance of disease will result in a therapeutic coping process associated with higher level of life satisfaction and overall quality of life.

Depressive symptoms and occupational stress among Chinese female nurses: the mediating effects of social support and rational coping.

PubMed

Wu, Hui; Ge, Cui Xia; Sun, Wei; Wang, Jia Na; Wang, Lie

2011-10-01

The study reported here was designed to investigate the relationship between depressive symptoms and occupational stress in female nurses in China during the period June-July 2008. The hypothesis tested was that social support and rational coping would mediate the effects of occupational stress on depressive symptoms. Our structural equation modeling revealed that social support and rational coping were negatively correlated with depressive symptoms. Social support and rational coping mediated the effects of occupational stress on depressive symptoms. Role overload, role insufficiency, and role boundary were predictive of depressive symptoms. These results indicated that lessening occupational stress and strengthening social support and rational coping could decrease depressive symptoms among Chinese female nurses. Copyright © 2011 Wiley Periodicals, Inc.

Selected approaches for rational drug design and high throughput screening to identify anti-cancer molecules.

PubMed

Hedvat, Michael; Emdad, Luni; Das, Swadesh K; Kim, Keetae; Dasgupta, Santanu; Thomas, Shibu; Hu, Bin; Zhu, Shan; Dash, Rupesh; Quinn, Bridget A; Oyesanya, Regina A; Kegelman, Timothy P; Sokhi, Upneet K; Sarkar, Siddik; Erdogan, Eda; Menezes, Mitchell E; Bhoopathi, Praveen; Wang, Xiang-Yang; Pomper, Martin G; Wei, Jun; Wu, Bainan; Stebbins, John L; Diaz, Paul W; Reed, John C; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2012-11-01

Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. The present review focuses on these two approaches using explicit examples based on specific derivatives of Gossypol generated through rational design and applications of a cancer-specificpromoter derived from Progression Elevated Gene-3. The Gossypol derivative Sabutoclax (BI-97C1) displays potent anti-tumor activity against a diverse spectrum of human tumors. The model of the docked structure of Gossypol bound to Bcl-XL provided a virtual structure-activity-relationship where appropriate modifications were predicted on a rational basis. These structure-based studies led to the isolation of Sabutoclax, an optically pure isomer of Apogossypol displaying superior efficacy and reduced toxicity. These studies illustrate the power of combining structure-based modeling with rational design to predict appropriate derivatives of lead compounds to be empirically tested and evaluated for bioactivity. Another approach to cancer drug discovery utilizes a cancer-specific promoter as readouts of the transformed state. The promoter region of Progression Elevated Gene-3 is such a promoter with cancer-specific activity. The specificity of this promoter has been exploited as a means of constructing cancer terminator viruses that selectively kill cancer cells and as a systemic imaging modality that specifically visualizes in vivo cancer growth with no background from normal tissues. Screening of small molecule inhibitors that suppress the Progression Elevated Gene-3-promoter may provide relevant lead compounds for cancer therapy that can be combined with further structure-based approaches leading to the development of novel compounds for cancer therapy.

Do Students Use Contextual Protective Behaviors to Reduce Alcohol-Related Sexual Risk? Examination of a Dual-Process Decision-Making Model

PubMed Central

Scaglione, Nichole M.; Hultgren, Brittney A.; Reavy, Racheal; Mallett, Kimberly A.; Turrisi, Rob; Cleveland, Michael J.; Sell, Nichole M.

2015-01-01

Objective Recent studies suggest drinking protective behaviors (DPBs) and contextual protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in college students. Few studies have examined CPBs independently, and even fewer have utilized theory to examine modifiable psychosocial predictors of students’ decisions to use CPBs. The current study used a prospective design to examine 1) rational and reactive pathways and psychosocial constructs predictive of CPB use, and 2) how gender might moderate these influences in a sample of college students. Method Students (n = 508) completed web-based baseline (mid-spring semester) and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs (expectancies, normative beliefs, attitudes, and self-concept); and rational and reactive pathways (intentions and willingness). Regression was used to examine rational and reactive influences as proximal predictors of CPB use at the 6-month follow-up. Subsequent path analyses examined the effects of psychosocial constructs, as distal predictors of CPB use, mediated through the rational and reactive pathways. Results Both rational (intentions to use CPB) and reactive (willingness to use CPB) influences were significantly associated with increased CPB use. The examined distal predictors were found to effect CPB use differentially through the rational and reactive pathways. Gender did not significantly moderate any relationships within in the model. Discussion Findings suggest potential entry points for increasing CPB use that include both rational and reactive pathways. Overall, this study demonstrates the mechanisms underlying how to increase the use of CPBs in programs designed to reduce alcohol-related sexual consequences and victimization. PMID:26415062

Do students use contextual protective behaviors to reduce alcohol-related sexual risk? Examination of a dual-process decision-making model.

PubMed

Scaglione, Nichole M; Hultgren, Brittney A; Reavy, Racheal; Mallett, Kimberly A; Turrisi, Rob; Cleveland, Michael J; Sell, Nichole M

2015-09-01

Recent studies suggest drinking protective behaviors (DPBs) and contextual protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in college students. Few studies have examined CPBs independently, and even fewer have utilized theory to examine modifiable psychosocial predictors of students' decisions to use CPBs. The current study used a prospective design to examine (a) rational and reactive pathways and psychosocial constructs predictive of CPB use and (b) how gender might moderate these influences in a sample of college students. Students (n = 508) completed Web-based baseline (mid-Spring semester) and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs (expectancies, normative beliefs, attitudes, and self-concept); and rational and reactive pathways (intentions and willingness). Regression was used to examine rational and reactive influences as proximal predictors of CPB use at the 6-month follow-up. Subsequent path analyses examined the effects of psychosocial constructs, as distal predictors of CPB use, mediated through the rational and reactive pathways. Both rational (intentions to use CPB) and reactive (willingness to use CPB) influences were significantly associated with increased CPB use. The examined distal predictors were found to effect CPB use differentially through the rational and reactive pathways. Gender did not significantly moderate any relationships within in the model. Findings suggest potential entry points for increasing CPB use that include both rational and reactive pathways. Overall, this study demonstrates the mechanisms underlying how to increase the use of CPBs in programs designed to reduce alcohol-related sexual consequences and victimization. (c) 2015 APA, all rights reserved).

Exploring protein-protein intermolecular recognition between meprin-α and endogenous protease regulator cystatinC coupled with pharmacophore elucidation.

PubMed

Chaudhuri, Ankur; Biswas, Sampa; Chakraborty, Sibani

2018-02-07

Meprins are a group of zinc metalloproteases of the astacin family which play a pivotal role in several physiological and pathologocal diseases. The inhibition of the meprins by various inhibitors, macromolecular and small molecules, is crucial in the control of several diseases. Human cystatinC, an amyloidogenic protein, is reported to be an endogenous inhibitor of meprin-α. In this computational study, we elucidate a rational model for meprinα-cystatinC complex using protein-protein docking. The complex model as well as the unbound form was evaluated by molecular dynamics simulation. A simulation study revealed higher stability of the complex owing to the presence of several interactions. Virtual alanine mutagenesis helps in identifying the hotspots on both proteins. Based on the frequency of occurrence of hotspot amino acids, it was possible to enumerate the important amino acids primarily responsible for protein stability present at the amino-terminal end of cystatin. Finally, pharmacophore elucidation carried out based on the information obtained from a series of small molecular inhibitors against meprin-α can be utilized in future for rational drug design and therapy.

Les objectifs des « réseaux futurs » vus par l'UIT

NASA Astrophysics Data System (ADS)

Mur, Jean-Michel

2017-12-01

Pour faire face à l'explosion de la demande en débits et la diversité des services souhaités, l'Union internationale des télécommunications a développé le concept de « Future Networks » (réseaux futurs) visant à remplacer les actuels « réseaux de prochaine génération » (Next Generation Networks). Panorama des principaux objectifs fixés à ces futurs réseaux de communication…

Prevalence and Determinants of Physician Bedside Rationing

PubMed Central

Hurst, Samia A; Slowther, Anne-Marie; Forde, Reidun; Pegoraro, Renzo; Reiter-Theil, Stella; Perrier, Arnaud; Garrett-Mayer, Elizabeth; Danis, Marion

2006-01-01

BACKGROUND Bedside rationing by physicians is controversial. The debate, however, is clouded by lack of information regarding the extent and character of bedside rationing. DESIGN, SETTING, AND PARTICIPANTS We developed a survey instrument to examine the frequency, criteria, and strategies used for bedside rationing. Content validity was assessed through expert assessment and scales were tested for internal consistency. The questionnaire was translated and administered to General Internists in Norway, Switzerland, Italy, and the United Kingdom. Logistic regression was used to identify the variables associated with reported rationing. RESULTS Survey respondents (N =656, response rate 43%) ranged in age from 28 to 82, and averaged 25 years in practice. Most respondents (82.3%) showed some degree of agreement with rationing, and 56.3% reported that they did ration interventions. The most frequently mentioned criteria for rationing were a small expected benefit (82.3%), low chances of success (79.8%), an intervention intended to prolong life when quality of life is low (70.6%), and a patient over 85 years of age (70%). The frequency of rationing by clinicians was positively correlated with perceived scarcity of resources (odds ratio [OR]=1.11, 95% confidence interval [CI] 1.06 to 1.16), perceived pressure to ration (OR=2.14, 95% CI 1.52 to 3.01), and agreement with rationing (OR=1.13, 95% CI 1.05 to 1.23). CONCLUSION Bedside rationing is prevalent in all surveyed European countries and varies with physician attitudes and resource availability. The prevalence of physician bedside rationing, which presents physicians with difficult moral dilemmas, highlights the importance of discussions regarding how to ration care in the most ethically justifiable manner. PMID:16836629

Optimal design of piezoelectric transformers: a rational approach based on an analytical model and a deterministic global optimization.

PubMed

Pigache, Francois; Messine, Frédéric; Nogarede, Bertrand

2007-07-01

This paper deals with a deterministic and rational way to design piezoelectric transformers in radial mode. The proposed approach is based on the study of the inverse problem of design and on its reformulation as a mixed constrained global optimization problem. The methodology relies on the association of the analytical models for describing the corresponding optimization problem and on an exact global optimization software, named IBBA and developed by the second author to solve it. Numerical experiments are presented and compared in order to validate the proposed approach.

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

Ronold, K.O.; Nielsen, N.J.R.; Tura, F.

This paper demonstrates how a structural reliability method can be applied as a rational means to analyze free spans of submarine pipelines with respect to failure in ultimate loading, and to establish partial safety factors for design of such free spans against this failure mode. It is important to note that the described procedure shall be considered as an illustration of a structural reliability methodology, and that the results do not represent a set of final design recommendations. A scope of design cases, consisting of a number of available site-specific pipeline spans, is established and is assumed representative for themore » future occurrence of submarine pipeline spans. Probabilistic models for the wave and current loading and its transfer to stresses in the pipe wall of a pipeline span is established together with a stochastic representation of the material resistance. The event of failure in ultimate loading is considered as based on a limit state which is reached when the maximum stress over the design life of the pipeline exceeds the yield strength of the pipe material. The yielding limit state is considered an ultimate limit state (ULS).« less

Impacts of changing food webs in Lake Ontario: Implications of dietary fatty acids on growth of alewives

USGS Publications Warehouse

Snyder, R.J.; Demarche, C.J.; Honeyfield, D.C.

2011-01-01

Declines in the abundance and condition of Great Lakes Alewives have been reported periodically during the last two decades, and the reasons for these declines remain unclear. To better understand how food web changes may influence Alewife growth and Wisconsin growth model predictions, we fed Alewives isocaloric diets high in omega-6 fatty acids (corn oil) or high in omega-3 fatty acids (fish oil). Alewives were fed the experimental diets at either 1% (“low ration”) or 3% (“high ration”) of their wet body weight per day. After six weeks, Alewives maintained on the high ration diets were significantly larger than those fed the low ration diets. Moreover, Alewives given the high ration fish oil diet were significantly larger than those maintained on the high ration corn oil diet after six weeks of growth. Body lipid, energy density and total body energy of Alewives on the high ration diets were significantly higher than those fed the low ration diets, and total body energy was significantly higher in Alewives given the high ration fish oil diet compared to those on the high ration corn oil diet. The current Wisconsin bioenergetics model underestimated growth and overestimated food consumption by Alewives in our study. Alewife thiaminase activity was similar among treatment groups. Overall, our results suggest that future food web changes in Lake Ontario, particularly if they involve decreases in the abundance of lipid rich prey items such as Mysis, may reduce Alewife growth rates and total body energy due to reductions in the availability of dietary omega-3 fatty acids.

Personal Autonomy and Rational Suicide.

ERIC Educational Resources Information Center

Webber, May A.; Shulman, Ernest

That certain suicides (which can be designated as rational) ought not to be interfered with is closely tied to the notion of the "right to autonomy." Specifically it is because the individual in question has this right that interference is prohibited. A proper understanding of the right to autonomy, while essential to understanding why…

The Feminist Supervision Scale: A Rational/Theoretical Approach

ERIC Educational Resources Information Center

Szymanski, Dawn M.

2003-01-01

This article reports the development and psychometric properties of the Feminist Supervision Scale (FSS), a new scale designed to assess feminist supervision practices in clinical supervision. This 32-item measure was developed using a rational/theoretical approach of test construction and includes four subscales: (a) collaborative relationships,…

Working with the private sector for child health.

PubMed

Waters, Hugh; Hatt, Laurel; Peters, David

2003-06-01

Private sector providers are the most commonly consulted source of care for child illnesses in many countries, offering significant opportunities to expand the reach of essential child health services and products. Yet collaboration with private providers presents major challenges - the suitability and quality of the services they provide is often questionable and governments' capacity to regulate them is limited. This article assesses the actual and potential contributions of the private sector to child health, and classifies and evaluates public sector strategies to promote and rationalize the contributions of private sector actors. Governments and international organizations can use a variety of strategies to collaborate with and influence private sector actors to improve child health - including contracting, regulating, financing and social marketing, training, coordinating and informing the public. These mutually reinforcing strategies can both improve the quality of services currently delivered in the private sector, and expand and rationalize the coverage of these services. One lesson from this review is that the private sector is very heterogeneous. At the country level, feasible strategies depend on the potential of the different components of the private sector and the capacity of governments and their partners for collaboration. To date, experience with private sector strategies offers considerable promise for children's health, but also raises many questions about the feasibility and impact of these strategies. Where possible, future interventions should be designed as experiments, with careful assessment of the intervention design and the environment in which they are implemented.

Designing and developing suppository formulations for anti-HIV drug delivery.

PubMed

Ham, Anthony S; Buckheit, Robert W

2017-08-01

Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.

Multitarget drug discovery projects in CNS diseases: quantitative systems pharmacology as a possible path forward.

PubMed

Geerts, Hugo; Kennis, Ludo

2014-01-01

Clinical development in brain diseases has one of the lowest success rates in the pharmaceutical industry, and many promising rationally designed single-target R&D projects fail in expensive Phase III trials. By contrast, successful older CNS drugs do have a rich pharmacology. This article will provide arguments suggesting that highly selective single-target drugs are not sufficiently powerful to restore complex neuronal circuit homeostasis. A rationally designed multitarget project can be derisked by dialing in an additional symptomatic treatment effect on top of a disease modification target. Alternatively, we expand upon a hypothetical workflow example using a humanized computer-based quantitative systems pharmacology platform. The hope is that incorporating rationally multipharmacology drug discovery could potentially lead to more impactful polypharmacy drugs.

Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

PubMed Central

Nishio, Yousuke; Usuda, Yoshihiro; Matsui, Kazuhiko; Kurata, Hiroyuki

2008-01-01

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided design (CAD) system and verified the simulated results with biological experiments. CAD supports construction of a biochemical map, mathematical modeling, simulation, and system analysis. Assuming that the PTS aims at controlling the glucose uptake rate, the PTS was decomposed into hierarchical modules, functional and flux modules, and the effect of changes in gene expression on the glucose uptake rate was simulated to make a rational strategy of how the gene regulatory network is engineered. Such design and analysis predicted that the mlc knockout mutant with ptsI gene overexpression would greatly increase the specific glucose uptake rate. By using biological experiments, we validated the prediction and the presented strategy, thereby enhancing the specific glucose uptake rate. PMID:18197177

Science as a general education: Conceptual science should constitute the compulsory core of multi-disciplinary undergraduate degrees.

PubMed

Charlton, Bruce G

2006-01-01

It is plausible to assume that in the future science will form the compulsory core element both of school curricula and multi-disciplinary undergraduate degrees. But for this to happen entails a shift in the emphasis and methods of science teaching, away from the traditional concern with educating specialists and professionals. Traditional science teaching was essentially vocational, designed to provide precise and comprehensive scientific knowledge for practical application. By contrast, future science teaching will be a general education, hence primarily conceptual. Its aim should be to provide an education in flexible rationality. Vocational science teaching was focused on a single-discipline undergraduate degree, but a general education in abstract systematic thinking is best inculcated by studying several scientific disciplines. In this sense, 'science' is understood as mathematics and the natural sciences, but also the abstract and systematic aspects of disciplines such as economics, linguistics, music theory, history, sociology, political science and management science. Such a wide variety of science options in a multi-disciplinary degree will increase the possibility of student motivation and aptitude. Specialist vocational science education will progressively be shifted to post-graduate level, in Masters and Doctoral programs. A multi-disciplinary and conceptually-based science core curriculum should provide an appropriate preparation for dealing with the demands of modern societies; their complex and rapidly changing social systems; and the need for individual social and professional mobility. Training in rational conceptual thinking also has potential benefits to human health and happiness, since it allows people to over-ride inappropriate instincts, integrate conflicting desires and pursue long-term goals.

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

Microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices and medical applications, etc. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights inmore » designing the structural microbatteries for emerging technologies.« less

Evolutionary dynamics in finite populations can explain the full range of cooperative behaviors observed in the centipede game.

PubMed

Rand, David G; Nowak, Martin A

2012-05-07

Classical economic models make behavioral predictions based on the assumption that people are fully rational and care only about maximizing their own payoffs. Although this approach successfully explains human behavior in many situations, there is a wealth of experimental evidence demonstrating conditions where people deviate from the predictions of these models. One setting that has received particular attention is fixed length repeated games. Iterating a social dilemma can promote cooperation through direct reciprocity, even if it is common knowledge that all players are rational and self-interested. However, this is not the case if the length of the game is known to the players. In the final round, a rational player will defect, because there is no future to be concerned with. But if you know the other player will defect in the last round, then you should defect in the second to last round, and so on. This logic of backwards induction leads to immediate defection as the only rational (sub-game perfect Nash equilibrium) strategy. When people actually play such games, however, immediate defection is rare. Here we use evolutionary dynamics in finite populations to study the centipede game, which is designed to explore this issue of backwards induction. We make the following observation: since full cooperation can risk-dominate immediate defection in the centipede game, stochastic evolutionary dynamics can favor both delayed defection and even full cooperation. Furthermore, our evolutionary model can quantitatively reproduce human behavior from two experiments by fitting a single free parameter, which is the product of population size and selection intensity. Thus we provide evidence that people's cooperative behavior in fixed length games, which is often called 'irrational', may in fact be the favored outcome of natural selection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Surface, Bulk, and Interface: Rational Design of Hematite Architecture toward Efficient Photo-Electrochemical Water Splitting.

PubMed

Li, Chengcheng; Luo, Zhibin; Wang, Tuo; Gong, Jinlong

2018-05-11

Collecting and storing solar energy to hydrogen fuel through a photo-electrochemical (PEC) cell provides a clean and renewable pathway for future energy demands. Having earth-abundance, low biotoxicity, robustness, and an ideal n-type band position, hematite (α-Fe 2 O 3 ), the most common natural form of iron oxide, has occupied the research hotspot for decades. Here, a close look into recent progress of hematite photoanodes for PEC water splitting is provided. Effective approaches are introduced, such as cocatalysts loading and surface passivation layer deposition, to improve the hematite surface reaction in thermodynamics and kinetics. Second, typical methods for enhancing light absorption and accelerating charge transport in hematite bulk are reviewed, concentrating upon doping and nanostructuring. Third, the back contact between hematite and substrate, which affects interface states and electron transfer, is deliberated. In addition, perspectives on the key challenges and future prospects for the development of hematite photoelectrodes for PEC water splitting are given. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

One Cold Fusion Speaker is One Too Many for a Future Energy Conference

NASA Astrophysics Data System (ADS)

Vallone, Thomas

2001-04-01

In 1998, a Conference on Future Energy (COFE) was scheduled to take place at the State Department Open Forum in April, 1999. Only one speaker, Ed Storms (formerly with Los Alamos Lab), was scheduled to talk about cold fusion as part of fourteen plenary lectures over a two-day period. However, the entire meeting was labeled a "cold fusion" conference by APS Spokesperson Bob Park who repeated the words four times in one 1999 What's New column. What transpired afterwards has become a part of the cold fusion suppression history, including several APS ``pseudoscience" presentations mocking COFE scientists. A review of the actual COFE contents reveals the rational side of emerging energy technologies normally associated with the scientific process. The Park-related events display an opposite pattern of behavior ultimately designed to discredit the COFE organizer and deprive him of his livelihood (see APS News, March, 2000). The compiled record shows how the communication of scientific information becomes distorted by undue prejudice and unethical lobbying.

Emerging Biomimetic Applications of DNA Nanotechnology.

PubMed

Shen, Haijing; Wang, Yingqian; Wang, Jie; Li, Zhihao; Yuan, Quan

2018-06-25

Re-engineering cellular components and biological processes has received great interest and promised compelling advantages in applications ranging from basic cell biology to biomedicine. With the advent of DNA nanotechnology, the programmable self-assembly ability makes DNA an appealing candidate for rational design of artificial components with different structures and functions. This Forum Article summarizes recent developments of DNA nanotechnology in mimicking the structures and functions of existing cellular components. We highlight key successes in the achievements of DNA-based biomimetic membrane proteins and discuss the assembly behavior of these artificial proteins. Then, we focus on the construction of higher-order structures by DNA nanotechnology to recreate cell-like structures. Finally, we explore the current challenges and speculate on future directions of DNA nanotechnology in biomimetics.

Transition Metal Carbides and Nitrides in Energy Storage and Conversion

PubMed Central

Zhong, Yu; Shi, Fan; Zhan, Jiye; Tu, Jiangping

2016-01-01

High‐performance electrode materials are the key to advances in the areas of energy conversion and storage (e.g., fuel cells and batteries). In this Review, recent progress in the synthesis and electrochemical application of transition metal carbides (TMCs) and nitrides (TMNs) for energy storage and conversion is summarized. Their electrochemical properties in Li‐ion and Na‐ion batteries as well as in supercapacitors, and electrocatalytic reactions (oxygen evolution and reduction reactions, and hydrogen evolution reaction) are discussed in association with their crystal structure/morphology/composition. Advantages and benefits of nanostructuring (e.g., 2D MXenes) are highlighted. Prospects of future research trends in rational design of high‐performance TMCs and TMNs electrodes are provided at the end. PMID:27812464

Stopping bacterial adhesion: a novel approach to treating infections.

PubMed

Bavington, C; Page, C

2005-01-01

Adhesion and colonization are prerequisites for the establishment of bacterial pathogenesis. The prevention of adhesion is an attractive target for the development of new therapies in the prevention of infection. Bacteria have developed a multiplicity of adhesion mechanisms commonly targeting surface carbohydrate structures, but our ability to rationally design effective antiadhesives is critically affected by the limitations of our knowledge of the human 'glycome' and of the bacterial function in relation to it. The potential for the future development of carbohydrate-based antiadhesives has been demonstrated by a significant number of in vitro and in vivo studies. Such therapies will be particularly relevant for infections of mucosal surfaces where topical application or delivery is possible. (c) 2005 S. Karger AG, Basel

Effect of ordering of PtCu₃ nanoparticle structure on the activity and stability for the oxygen reduction reaction.

PubMed

Hodnik, Nejc; Jeyabharathi, Chinnaiah; Meier, Josef C; Kostka, Alexander; Phani, Kanala L; Rečnik, Aleksander; Bele, Marjan; Hočevar, Stanko; Gaberšček, Miran; Mayrhofer, Karl J J

2014-07-21

In this study the performance enhancement effect of structural ordering for the oxygen reduction reaction (ORR) is systematically studied. Two samples of PtCu3 nanoparticles embedded on a graphitic carbon support are carefully prepared with identical initial composition, particle dispersion and size distribution, yet with different degrees of structural ordering. Thus we can eliminate all coinciding effects and unambiguously relate the improved activity of the ORR and more importantly the enhanced stability to the ordered nanostructure. Interestingly, the electrochemically induced morphological changes are common to both ordered and disordered samples. The observed effect could have a groundbreaking impact on the future directions in the rational design of active and stable platinum alloyed ORR catalysts.

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

PubMed

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

Prescription drug samples--does this marketing strategy counteract policies for quality use of medicines?

PubMed

Groves, K E M; Sketris, I; Tett, S E

2003-08-01

Prescription drug samples, as used by the pharmaceutical industry to market their products, are of current interest because of their influence on prescribing, and their potential impact on consumer safety. Very little research has been conducted into the use and misuse of prescription drug samples, and the influence of samples on health policies designed to improve the rational use of medicines. This is a topical issue in the prescription drug debate, with increasing costs and increasing concerns about optimizing use of medicines. This manuscript critically evaluates the research that has been conducted to date about prescription drug samples, discusses the issues raised in the context of traditional marketing theory, and suggests possible alternatives for the future.

Selective interface transparency in graphene nanoribbon based molecular junctions.

PubMed

Dou, K P; Kaun, C C; Zhang, R Q

2018-03-08

A clear understanding of electrode-molecule interfaces is a prerequisite for the rational engineering of future generations of nanodevices that will rely on single-molecule coupling between components. With a model system, we reveal a peculiar dependence on interfaces in all graphene nanoribbon-based carbon molecular junctions. The effect can be classified into two types depending on the intrinsic feature of the embedded core graphene nanoflake (GNF). For metallic GNFs with |N A - N B | = 1, good/poor contact transparency occurs when the core device aligns with the center/edge of the electrode. The situation is reversed when a semiconducting GNF is the device, where N A = N B . These results may shed light on the design of real connecting components in graphene-based nanocircuits.

A Capped Dipeptide Which Simultaneously Exhibits Gelation and Crystallization Behavior.

PubMed

Martin, Adam D; Wojciechowski, Jonathan P; Bhadbhade, Mohan M; Thordarson, Pall

2016-03-08

Short peptides capped at their N-terminus are often highly efficient gelators, yet notoriously difficult to crystallize. This is due to strong unidirectional interactions within fibers, resulting in structure propagation only along one direction. Here, we synthesize the N-capped dipeptide, benzimidazole-diphenylalanine, which forms both hydrogels and single crystals. Even more remarkably, we show using atomic force microscopy the coexistence of these two distinct phases. We then use powder X-ray diffraction to investigate whether the single crystal structure can be extrapolated to the molecular arrangement within the hydrogel. The results suggest parallel β-sheet arrangement as the dominant structural motif, challenging existing models for gelation of short peptides, and providing new directions for the future rational design of short peptide gelators.

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

PubMed Central

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

Enhancing the response rate of strand displacement-based electrochemical aptamer sensors using bivalent binding aptamer-cDNA probes.

PubMed

Zhang, Ziping; Tao, Cancan; Yin, Jungang; Wang, Yunhui; Li, Yanshen

2018-04-30

Electrochemical aptamer (EA) sensors based on aptamer-cDNA duplex probes (cDNA: complementary DNA) and target induced strand displacement (TISD) recognition are sensitive, selective and capable of detecting a wide variety of target analytes. While substantial research efforts have focused on engineering of new signaling mechanisms for the improvement of sensor sensitivity, little attention was paid to the enhancement of sensor response rate. Typically, the previous TISD based EA sensors exhibited relatively long response times larger than 30min, which mainly resulted from the suboptimal aptamer-cDNA probe structure in which most of aptamer bases were paired to the cDNA bases. In an effort to improve the response rate of this type of sensors, we report here the rational engineering of a quickly responsive and sensitive aptamer-cDNA probe by employing the conception of bivalent interaction in supramolecular chemistry. We design a bivalent cDNA strand through linking two short monovalent cDNA sequences, and it is simultaneously hybridized to two electrode-immobilized aptamer probes to form a bivalent binding (BB) aptamer-cDNA probe. This class of BB probe possesses the advantages of less aptamer bases paired to the cDNA bases for quick response rate and good structural stability for high sensor sensitivity. By use of the rationally designed BB aptamer-cDNA probe, a TISD based EA sensor against ATP with significantly enhanced response rate (with a displacement equilibrium time of 4min) and high sensitivity was successfully constructed. We believe that our BB probe conception will help guide future designs and applications of TISD based EA sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of mobile phone text messages for nicotine and tobacco risk communication among college students: A content analysis

PubMed Central

Khalil, Georges E.; Calabro, Karen S.; Crook, Brittani; Machado, Tamara C.; Perry, Cheryl L.; Prokhorov, Alexander V.

2018-01-01

INTRODUCTION In the United States, young adults have the highest prevalence of tobacco use. The dissemination of mobile phone text messages is a growing strategy for tobacco risk communication among young adults. However, little has been done concerning the design and validation of such text messages. The Texas Tobacco Center of Regulatory Science (Texas-TCORS) has developed a library of messages based on framing (gain- or loss-framed), depth (simple or complex) and appeal (emotional or rational). This study validated the library based on depth and appeal, identified text messages that may need improvement, and explored new themes. METHODS The library formed the study sample (N=976 messages). The Linguistic Inquiry and Word Count (LIWC) software of 2015 was used to code for word count, word length and frequency of emotional and cognitive words. Analyses of variance, logistic regression and scatter plots were conducted for validation. RESULTS In all, 874 messages agreed with LIWC-coding. Several messages did not agree with LIWC. Ten messages designed to be complex indicated simplicity, while 51 messages designed to be rational exhibited no cognitive words. New relevant themes were identified, such as health (e.g. ‘diagnosis’, ‘cancer’), death (e.g. ‘dead’, ‘lethal’) and social connotations (e.g. ‘parents’, ‘friends’). CONCLUSIONS Nicotine and tobacco researchers can safely use, for young adults, messages from the Texas-TCORS library to convey information in the intended style. Future work may expand upon the new themes. Findings will be utilized to develop new campaigns, so that risks of nicotine and tobacco products can be widely disseminated. PMID:29888338

Economic reasoning and artificial intelligence.

PubMed

Parkes, David C; Wellman, Michael P

2015-07-17

The field of artificial intelligence (AI) strives to build rational agents capable of perceiving the world around them and taking actions to advance specified goals. Put another way, AI researchers aim to construct a synthetic homo economicus, the mythical perfectly rational agent of neoclassical economics. We review progress toward creating this new species of machine, machina economicus, and discuss some challenges in designing AIs that can reason effectively in economic contexts. Supposing that AI succeeds in this quest, or at least comes close enough that it is useful to think about AIs in rationalistic terms, we ask how to design the rules of interaction in multi-agent systems that come to represent an economy of AIs. Theories of normative design from economics may prove more relevant for artificial agents than human agents, with AIs that better respect idealized assumptions of rationality than people, interacting through novel rules and incentive systems quite distinct from those tailored for people. Copyright © 2015, American Association for the Advancement of Science.

Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

PubMed Central

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

2016-01-01

Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

PubMed

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

2015-12-01

Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

Development of a Preventive HIV Vaccine Requires Solving Inverse Problems Which Is Unattainable by Rational Vaccine Design

PubMed Central

Van Regenmortel, Marc H. V.

2018-01-01

Hypotheses and theories are essential constituents of the scientific method. Many vaccinologists are unaware that the problems they try to solve are mostly inverse problems that consist in imagining what could bring about a desired outcome. An inverse problem starts with the result and tries to guess what are the multiple causes that could have produced it. Compared to the usual direct scientific problems that start with the causes and derive or calculate the results using deductive reasoning and known mechanisms, solving an inverse problem uses a less reliable inductive approach and requires the development of a theoretical model that may have different solutions or none at all. Unsuccessful attempts to solve inverse problems in HIV vaccinology by reductionist methods, systems biology and structure-based reverse vaccinology are described. The popular strategy known as rational vaccine design is unable to solve the multiple inverse problems faced by HIV vaccine developers. The term “rational” is derived from “rational drug design” which uses the 3D structure of a biological target for designing molecules that will selectively bind to it and inhibit its biological activity. In vaccine design, however, the word “rational” simply means that the investigator is concentrating on parts of the system for which molecular information is available. The economist and Nobel laureate Herbert Simon introduced the concept of “bounded rationality” to explain why the complexity of the world economic system makes it impossible, for instance, to predict an event like the financial crash of 2007–2008. Humans always operate under unavoidable constraints such as insufficient information, a limited capacity to process huge amounts of data and a limited amount of time available to reach a decision. Such limitations always prevent us from achieving the complete understanding and optimization of a complex system that would be needed to achieve a truly rational design process. This is why the complexity of the human immune system prevents us from rationally designing an HIV vaccine by solving inverse problems. PMID:29387066

Pricing the Future in the Seventeenth Century: Calculating Technologies in Competition.

PubMed

Deringer, William

Time is money. But how much? What is money in the future worth to you today? This question of "present value" arises in myriad economic activities, from valuing financial securities to real estate transactions to governmental cost-benefit analysis-even the economics of climate change. In modern capitalist practice, one calculation offers the only "rational" way to answer: compound-interest discounting. In the early modern period, though, economic actors used at least two alternative calculating technologies for thinking about present value, including a vernacular technique called years purchase and discounting by simple interest. All of these calculations had different strengths and affordances, and none was unquestionably better or more "rational" than the others at the time. The history of technology offers distinct resources for understanding such technological competitions, and thus for understanding the emergence of modern economic temporality.

Natural selection can favour 'irrational' behaviour.

PubMed

McNamara, J M; Trimmer, P C; Houston, A I

2014-01-01

Understanding decisions is the fundamental aim of the behavioural sciences. The theory of rational choice is based on axiomatic principles such as transitivity and independence of irrelevant alternatives (IIA). Empirical studies have demonstrated that the behaviour of humans and other animals often seems irrational; there can be a lack of transitivity in choice and seemingly irrelevant alternatives can alter decisions. These violations of transitivity and IIA undermine rational choice theory. However, we show that an individual that is maximizing its rate of food gain can exhibit failure of transitivity and IIA. We show that such violations can be caused because a current option may disappear in the near future or a better option may reappear soon. Current food options can be indicative of food availability in the near future, and this key feature can result in apparently irrational behaviour.

Research activities to improve the utilization of antibiotics in Africa.

PubMed

Massele, Amos; Tiroyakgosi, Celda; Matome, Matshediso; Desta, Abayneh; Muller, Arno; Paramadhas, Bene D Anand; Malone, Brighid; Kurusa, Gobuiwang; Didimalang, Thatayaone; Moyo, Mosana; Godman, Brian

2017-02-01

There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

A supermolecular building approach for the design and construction of metal-organic frameworks.

PubMed

Guillerm, Vincent; Kim, Dongwook; Eubank, Jarrod F; Luebke, Ryan; Liu, Xinfang; Adil, Karim; Lah, Myoung Soo; Eddaoudi, Mohamed

2014-08-21

In this review, we describe two recently implemented conceptual approaches facilitating the design and deliberate construction of metal–organic frameworks (MOFs), namely supermolecular building block (SBB) and supermolecular building layer (SBL) approaches. Our main objective is to offer an appropriate means to assist/aid chemists and material designers alike to rationally construct desired functional MOF materials, made-to-order MOFs. We introduce the concept of net-coded building units (net-cBUs), where precise embedded geometrical information codes uniquely and matchlessly a selected net, as a compelling route for the rational design of MOFs. This concept is based on employing pre-selected 0-periodic metal–organic polyhedra or 2-periodic metal–organic layers, SBBs or SBLs respectively, as a pathway to access the requisite net-cBUs. In this review, inspired by our success with the original rht-MOF, we extrapolated our strategy to other known MOFs via their deconstruction into more elaborate building units (namely polyhedra or layers) to (i) elucidate the unique relationship between edge-transitive polyhedra or layers and minimal edge-transitive 3-periodic nets, and (ii) illustrate the potential of the SBB and SBL approaches as a rational pathway for the design and construction of 3-periodic MOFs. Using this design strategy, we have also identified several new hypothetical MOFs which are synthetically targetable.

Computational protein design: a review

NASA Astrophysics Data System (ADS)

Coluzza, Ivan

2017-04-01

Proteins are one of the most versatile modular assembling systems in nature. Experimentally, more than 110 000 protein structures have been identified and more are deposited every day in the Protein Data Bank. Such an enormous structural variety is to a first approximation controlled by the sequence of amino acids along the peptide chain of each protein. Understanding how the structural and functional properties of the target can be encoded in this sequence is the main objective of protein design. Unfortunately, rational protein design remains one of the major challenges across the disciplines of biology, physics and chemistry. The implications of solving this problem are enormous and branch into materials science, drug design, evolution and even cryptography. For instance, in the field of drug design an effective computational method to design protein-based ligands for biological targets such as viruses, bacteria or tumour cells, could give a significant boost to the development of new therapies with reduced side effects. In materials science, self-assembly is a highly desired property and soon artificial proteins could represent a new class of designable self-assembling materials. The scope of this review is to describe the state of the art in computational protein design methods and give the reader an outline of what developments could be expected in the near future.

Multifunctional Self-Assembled Monolayers for Organic Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Cernetic, Nathan

Organic field effect transistors (OFETs) have the potential to reach commercialization for a wide variety of applications such as active matrix display circuitry, chemical and biological sensing, radio-frequency identification devices and flexible electronics. In order to be commercially competitive with already at-market amorphous silicon devices, OFETs need to approach similar performance levels. Significant progress has been made in developing high performance organic semiconductors and dielectric materials. Additionally, a common route to improve the performance metric of OFETs is via interface modification at the critical dielectric/semiconductor and electrode/semiconductor interface which often play a significant role in charge transport properties. These metal oxide interfaces are typically modified with rationally designed multifunctional self-assembled monolayers. As means toward improving the performance metrics of OFETs, rationally designed multifunctional self-assembled monolayers are used to explore the relationship between surface energy, SAM order, and SAM dipole on OFET performance. The studies presented within are (1) development of a multifunctional SAM capable of simultaneously modifying dielectric and metal surface while maintaining compatibility with solution processed techniques (2) exploration of the relationship between SAM dipole and anchor group on graphene transistors, and (3) development of self-assembled monolayer field-effect transistor in which the traditional thick organic semiconductor is replaced by a rationally designed self-assembled monolayer semiconductor. The findings presented within represent advancement in the understanding of the influence of self-assembled monolayers on OFETs as well as progress towards rationally designed monolayer transistors.

Is there a future for GMOs?

PubMed

Beringer, J E

2000-04-01

Despite strict regulation and a clean safety record, research and development of genetically modified (GM) crops and other organisms has been confronted with tremendous public hostility. Why has this happened, and how can scientists try to guide the debate into more rational channels? The answers may determine the future of GM technology and our ability to provide for a growing world population.

Effect of duration of fasting and a short-term high-roughage ration on the concentration of Escherichia coli biotype 1 in cattle feces.

PubMed

Jordan, D; McEwen, S A

1998-05-01

A field trial using cattle from a commercial feedlot was conducted to quantify the effect of duration of fasting and a temporary change in ration on the concentration of Escherichia coli biotype 1 in feces. A nested hierarchical design with repeated measures through time was used. Two groups of 20 British x European breed beef steers having reached slaughter weight (mean live weight 685 kg; SD 50 kg) were fed entirely on a high-energy ration typical of that used in the Ontario beef finishing industry or were switched for 4 days onto a high-roughage ration. This was followed by a period of fasting and water deprivation to mimic that which occurs prior to slaughter. Fecal samples were collected at 0, 24, and 48 h of fasting, and for each sample the total presumptive E. coli (biotype 1) CFU/g of feces was enumerated by spiral plating. Estimates of effect for the design factors were obtained by restricted maximum likelihood, and these were compared to robust counterparts obtained from generalized estimating equations. Results indicated that the ration, the duration of fasting, and their interaction had significant effects on total log E. coli concentration in feces. Cattle on the high-roughage ration for four days had a significantly lower initial log E. coli CFU/g of feces compared to cattle on the normal ration, but after 48 h of fasting they had a significantly higher concentration. It is concluded that while a temporary change in ration and duration of fasting does affect E. coli concentration in feces, these changes do not seem large enough to deliver a drastic improvement in beef carcass hygiene should they be incorporated in hazard analysis and critical control point (HACCP) plans for the preslaughter period of beef production.

Refusals and Rejections: Designing Messages to Serve Multiple Goals.

ERIC Educational Resources Information Center

Saeki, Mimako; O'Keefe, Barbara J.

1994-01-01

Tests a rational model of the elaboration of themes found in rejection messages, using Japanese and American participants. Finds partial support for the initial rational model but notes two key revisions: identifies two new themes in rejection messages and suggests substantial differences in the way Americans and Japanese elaborate themes to serve…

Decision-Making: Are Plants More Rational than Animals?

PubMed

Schmid, Bernhard

2016-07-25

A new study presents a novel experimental design and allows a test of risk sensitivity in plants. Faced with a choice between constant and variable resource supply, they make a rational decision for the option that maximizes fitness, a fact rarely observed in animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Joint Tactics, Techniques, and Procedures for Joint Special Operations Task Force Operations

DTIC Science & Technology

2001-12-19

phase? Is a ration cycle proposed? •• Are fresh eggs, fresh fruits and vegetables, fresh meats, juices, milk , and canned soft-drink supplements to ration...measures designed to mislead the enemy by manipulation, distortion, or falsification of evidence to induce the enemy to react in a manner prejudicial to

Calibration of the live load factor in LRFD design guidelines.

DOT National Transportation Integrated Search

2010-09-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is : more rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD : Specification ...

Calibration of the live load factor in LRFD design guidelines : [revised].

DOT National Transportation Integrated Search

2011-07-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is : more rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD : Specification ...

Understanding rational non-adherence to medications. A discrete choice experiment in a community sample in Australia

PubMed Central

2012-01-01

Background In spite of the potential impact upon population health and expenditure, interventions promoting medication adherence have been found to be of moderate effectiveness and cost effectiveness. Understanding the relative influence of factors affecting patient medication adherence decisions and the characteristics of individuals associated with variation in adherence will lead to a better understanding of how future interventions should be designed and targeted. This study aims to explore medication-taking decisions that may underpin intentional medication non-adherence behaviour amongst a community sample and the relative importance of medication specific factors and patient background characteristics contributing to those decisions. Methods A discrete choice experiment conducted through a web-enabled online survey was used to estimate the relative importance of eight medication factors (immediate and long-term medication harms and benefits, cost, regimen, symptom severity, alcohol restrictions) on the preference to continue taking a medication. To reflect more closely what usually occurs in practice, non-disease specific medication and health terms were used to mimic decisions across multiple medications and conditions.161 general community participants, matching the national Australian census data (age, gender) were recruited through an online panel provider (participation rate: 10%) in 2010. Results Six of the eight factors (i.e. immediate and long-term medication harms and benefits, cost, and regimen) had a significant influence on medication choice. Patient background characteristics did not improve the model. Respondents with private health insurance appeared less sensitive to cost then those without private health insurance. In general, health outcomes, framed as a side-effect, were found to have a greater influence over adherence than outcomes framed as therapeutic benefits. Conclusions Medication-taking decisions are the subject of rational choices, influenced by the attributes of treatments and potentially amenable to intervention through education, strategic pricing and the altering of dosing characteristics. Understanding individual treatment preferences is thus an important step to improving adherence support provision in practice. Re-framing future interventions and policies to support rational and informed individual patient choices, is the way forward to realising the full potential health and economic benefits from the efficacious use of medications. PMID:22715853

Understanding rational non-adherence to medications. A discrete choice experiment in a community sample in Australia.

PubMed

Laba, Tracey-Lea; Brien, Jo-Anne; Jan, Stephen

2012-06-20

In spite of the potential impact upon population health and expenditure, interventions promoting medication adherence have been found to be of moderate effectiveness and cost effectiveness. Understanding the relative influence of factors affecting patient medication adherence decisions and the characteristics of individuals associated with variation in adherence will lead to a better understanding of how future interventions should be designed and targeted. This study aims to explore medication-taking decisions that may underpin intentional medication non-adherence behaviour amongst a community sample and the relative importance of medication specific factors and patient background characteristics contributing to those decisions. A discrete choice experiment conducted through a web-enabled online survey was used to estimate the relative importance of eight medication factors (immediate and long-term medication harms and benefits, cost, regimen, symptom severity, alcohol restrictions) on the preference to continue taking a medication. To reflect more closely what usually occurs in practice, non-disease specific medication and health terms were used to mimic decisions across multiple medications and conditions.161 general community participants, matching the national Australian census data (age, gender) were recruited through an online panel provider (participation rate: 10%) in 2010. Six of the eight factors (i.e. immediate and long-term medication harms and benefits, cost, and regimen) had a significant influence on medication choice. Patient background characteristics did not improve the model. Respondents with private health insurance appeared less sensitive to cost then those without private health insurance. In general, health outcomes, framed as a side-effect, were found to have a greater influence over adherence than outcomes framed as therapeutic benefits. Medication-taking decisions are the subject of rational choices, influenced by the attributes of treatments and potentially amenable to intervention through education, strategic pricing and the altering of dosing characteristics. Understanding individual treatment preferences is thus an important step to improving adherence support provision in practice. Re-framing future interventions and policies to support rational and informed individual patient choices, is the way forward to realising the full potential health and economic benefits from the efficacious use of medications.

Inventing and improving ribozyme function: rational design versus iterative selection methods

NASA Technical Reports Server (NTRS)

Breaker, R. R.; Joyce, G. F.

1994-01-01

Two major strategies for generating novel biological catalysts exist. One relies on our knowledge of biopolymer structure and function to aid in the 'rational design' of new enzymes. The other, often called 'irrational design', aims to generate new catalysts, in the absence of detailed physicochemical knowledge, by using selection methods to search a library of molecules for functional variants. Both strategies have been applied, with considerable success, to the remodeling of existing ribozymes and the development of ribozymes with novel catalytic function. The two strategies are by no means mutually exclusive, and are best applied in a complementary fashion to obtain ribozymes with the desired catalytic properties.

Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

PubMed

Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

2013-01-01

Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

Evaluation of an Al-Ce alloy for laser additive manufacturing

DOE PAGES

Plotkowski, A.; Rios, O.; Sridharan, N.; ...

2016-12-27

Our present research in metal additive manufacturing (AM) focuses on designing processing parameters around existing alloys designed for traditional manufacturing. However, to maximize the benefits of AM, alloys should be designed to specifically take advantage of the unique thermal conditions of these processes. Furthermore, our study focuses on the development of a design methodology for alloys in AM, using a newly developed Al-Ce alloy as an initial case study. To evaluate the candidacy of this system for fusion based additive manufacturing, single-line laser melts were made on cast Al-12Ce plates using three different beam velocities (100, 200, and 300 mm/min).more » The microstructure was evaluated in the as-melted and heat treated conditions (24 hrs at 300°C). An extremely fine microstructure was observed within the weld pools, evolving from eutectic at the outer solid-liquid boundaries to a primary Al FCC dendritic/cellular structure nearer the melt-pool centerline. We rationalized the observed microstructures through the construction of a microstructure selection map for the Al-Ce binary system, which will be used to enable future alloy design. Interestingly, the heat treated samples exhibited no microstructural coarsening.« less

Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens

PubMed Central

Liljeroos, Lassi; Malito, Enrico; Ferlenghi, Ilaria; Bottomley, Matthew James

2015-01-01

Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10–20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease. PMID:26526043

Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens.

PubMed

Liljeroos, Lassi; Malito, Enrico; Ferlenghi, Ilaria; Bottomley, Matthew James

2015-01-01

Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10-20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease.

The impact of chief executive officer optimism on hospital strategic decision making.

PubMed

Langabeer, James R; Yao, Emery

2012-01-01

Previous strategic decision making research has focused mostly on the analytical positioning approach, which broadly emphasizes an alignment between rationality and the external environment. In this study, we propose that hospital chief executive optimism (or the general tendency to expect positive future outcomes) will moderate the relationship between comprehensively rational decision-making process and organizational performance. The purpose of this study was to explore the impact that dispositional optimism has on the well-established relationship between rational decision-making processes and organizational performance. Specifically, we hypothesized that optimism will moderate the relationship between the level of rationality and the organization's performance. We further suggest that this relationship will be more negative for those with high, as opposed to low, optimism. We surveyed 168 hospital CEOs and used moderated hierarchical regression methods to statically test our hypothesis. On the basis of a survey study of 168 hospital CEOs, we found evidence of a complex interplay of optimism in the rationality-organizational performance relationship. More specifically, we found that the two-way interactions between optimism and rational decision making were negatively associated with performance and that where optimism was the highest, the rationality-performance relationship was the most negative. Executive optimism was positively associated with organizational performance. We also found that greater perceived environmental turbulence, when interacting with optimism, did not have a significant interaction effect on the rationality-performance relationship. These findings suggest potential for broader participation in strategic processes and the use of organizational development techniques that assess executive disposition and traits for recruitment processes, because CEO optimism influences hospital-level processes. Research implications include incorporating greater use of behavior and cognition constructs to better depict decision-making processes in complex organizations like hospitals.

Sexual harassment in healthcare: classification of harassers and rationalizations of sex-based harassment behavior.

PubMed

Madison, J; Minichiello, V

2001-11-01

This study identified how 16 Australian registered nurses classified sex-based harassers and explained their own behavior and the behavior of the harasser. A qualitative research design, relying on in-depth interviews, was used to collect the data. The study found that harassment is linked to gender roles and that the harassed are reluctant to blame the harasser--the harassed had "sound" rationalizations for harassment. Awareness of the interactional dynamics of self-blame and these rationalizations will help nurse executives ensure a harassment-free workplace.

Post-compulsory Education and Training: A Modernist Project.

ERIC Educational Resources Information Center

Chappell, Clive

1996-01-01

Explores how modernist paradigms (empiricism, rationalism, positivism, humanism, and critical theory) have shaped postcompulsory education. Suggests the potential influence of postmodernism in terms of critiquing modernist views and developing future education and training systems. (SK)

Fundamental understanding and rational design of high energy structural microbatteries

DOE PAGES

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; ...

2017-11-21

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Silicon as a potential anode material for Li-ion batteries: where size, geometry and structure matter.

PubMed

Ashuri, Maziar; He, Qianran; Shaw, Leon L

2016-01-07

Silicon has attracted huge attention in the last decade because it has a theoretical capacity ∼10 times that of graphite. However, the practical application of Si is hindered by three major challenges: large volume expansion during cycling (∼300%), low electrical conductivity, and instability of the SEI layer caused by repeated volume changes of the Si material. Significant research efforts have been devoted to addressing these challenges, and significant breakthroughs have been made particularly in the last two years (2014 and 2015). In this review, we have focused on the principles of Si material design, novel synthesis methods to achieve such structural designs, and the synthesis-structure-performance relationships to enhance the properties of Si anodes. To provide a systematic overview of the Si material design strategies, we have grouped the design strategies into several categories: (i) particle-based structures (containing nanoparticles, solid core-shell structures, hollow core-shell structures, and yolk-shell structures), (ii) porous Si designs, (iii) nanowires, nanotubes and nanofibers, (iv) Si-based composites, and (v) unusual designs. Finally, our personal perspectives on outlook are offered with an aim to stimulate further discussion and ideas on the rational design of durable and high performance Si anodes for the next generation Li-ion batteries in the near future.

Advances in drying: Volume 4

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

Mujumdar, A.S.

1987-01-01

Topics covered in this volume include recent thoughts in modeling of drying phenomena, use of computers in rational design of drying particulates, recent advances in drying of wood, and heat/mass transfer phenomena in drying of solids. As the readers will no doubt notice, special effort is made to ensure the truly international nature of the contents of this serial publication. As existing knowledge on drying and dryers becomes more widely and readily accessible, it is expected that more and more dryers will be designed rationally rather than built solely with the benefit of empiricism.

Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

NASA Technical Reports Server (NTRS)

Carter, Daniel C. (Inventor)

1994-01-01

This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

Testing the limits of rational design by engineering pH sensitivity into membrane-active peptides.

PubMed

Wiedman, Gregory; Wimley, William C; Hristova, Kalina

2015-04-01

In this work, we sought to rationally design membrane-active peptides that are triggered by low pH to form macromolecular-sized pores in lipid bilayers. Such peptides could have broad utility in biotechnology and in nanomedicine as cancer therapeutics or drug delivery vehicles that promote release of macromolecules from endosomes. Our approach to rational design was to combine the properties of a pH-independent peptide, MelP5, which forms large pores allowing passage of macromolecules, with the properties of two pH-dependent membrane-active peptides, pHlip and GALA. We created two hybrid sequences, MelP5_Δ4 and MelP5_Δ6, by using the distribution of acidic residues on pHlip and GALA as a guide to insert acidic amino acids into the amphipathic helix of MelP5. We show that the new peptides bind to lipid bilayers and acquire secondary structure in a pH-dependent manner. The peptides also destabilize bilayers in a pH-dependent manner, such that lipid vesicles release the small molecules ANTS/DPX at low pH only. Thus, we were successful in designing pH-triggered pore-forming peptides. However, no macromolecular release was observed under any conditions. Therefore, we abolished the unique macromolecular poration properties of MelP5 by introducing pH sensitivity into its sequence. We conclude that the properties of pHlip, GALA, and MelP5 are additive, but only partially so. We propose that this lack of additivity is a limitation in the rational design of novel membrane-active peptides, and that high-throughput approaches to discovery will be critical for continued progress in the field. Copyright © 2015 Elsevier B.V. All rights reserved.

Knowledge Utilization Strategies in the Design and Implementation of New Schools--Symbolic Functions.

ERIC Educational Resources Information Center

Sieber, Sam D.

An examination of case studies suggests that rational processes were not entirely at work in the planning and conception of new, innovative schools. The rational model that serves as the foundation of our information systems assumes that a compelling professional need triggers a search for solutions; and, therefore, school personnel are eager to…

Clarifying the scope of Italian NHS coverage. Is it feasible? Is it desirable?

PubMed

Fattore, G

1999-12-01

The reduction in National Health Service (NHS) expenditure as a share of total health care expenditure, the fragmentation of the NHS into 21 regional systems and the implementation of a 'quasi-market' on the provider side of the system has pressed the government to define and specify, in detail, the set of services that are to be guaranteed by the public sector. To understand whether rationing can be more rational and explicit in the Italian NHS, the following are analysed: (i) the new positive list of drugs, as a major example of limiting and making more rational NHS pharmaceutical coverage; (ii) the Di Bella case, as an example of the difficulties of rational policy-making on sensitive issues; (iii) what Italian people think about health care rationing and priority setting (using the 1998 Eurobarometer Survey);( iv) the criteria defining the set of 'essential services' to be guaranteed to all Italian citizens, which are contained in the recently released National Health Plan. The 'revolution' that has taken place in the pharmaceutical sector shows it is feasible to limit, in an explicit and rational way, the extent of NHS coverage. However, the re-classification of the positive list should be regarded as an exceptional event in the history of Italian social policy. The 'Di Bella' case, on the contrary, shows that limiting NHS coverage can be very unpopular, and that the Italian cultural and social context can be unfavourable for the implementation of hard choices. Public attitude toward rationing seems to confirm that Italians are not familiar with rationing issues. Thus, it is very difficult to predict whether the national government will really go ahead with the implementation of a 'list of essential services' and whether this attempt will be successful. Rationing and priority setting should be discussed in the context of a general debate concerning the future of the Italian NHS.

Reliability-based evaluation of bridge components for consistent safety margins.

DOT National Transportation Integrated Search

2010-10-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is more : rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD Specification fo...

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006–2015 data for China’s 22 provinces

PubMed Central

Pang, Jinbo; Deng, Lingfei

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a “buy” strategy and speculators adopt a “do not speculate” strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies. PMID:28241024

An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006-2015 data for China's 22 provinces.

PubMed

Pang, Jinbo; Deng, Lingfei; Wang, Gangyi

2017-01-01

Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a "buy" strategy and speculators adopt a "do not speculate" strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies.

Rational Design of Hyperbranched Nanowire Systems for Tunable Superomniphobic Surfaces Enabled by Atomic Layer Deposition

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

Bielinski, Ashley R.; Boban, Mathew; He, Yang

2017-01-24

A method for tunable control of geometry in hyperbranched ZnO nanowire (NW) systems is reported, which enables the rational design and fabrication of superomniphobic surfaces. Branched NWs with tunable density and orientation were grown via a sequential hydrothermal process, in which atomic layer deposition (ALD) was used for NW seeding, disruption of epitaxy, and selective blocking of NW nucleation. This approach allows for the rational design and optimization of three-level hierarchical structures, in which the geometric parameters of each level of hierarchy can be individually controlled. We demonstrate the coupled relationships between geometry and contact angle for a variety ofmore » liquids, which is supported by mathematical models of structural superomniphobicity. The highest performing superomniphobic surface was designed with three levels of hierarchy and achieved the following advancing/receding contact angles, water: 172°/170°, hexadecane: 166°/156°, octane: 162°/145°, and heptane: 160°/130°. Low surface tension liquids were shown to bounce off the surface from a height of 7 cm without breaking through and wetting. This approach demonstrates the power of ALD as an enabling technique for hierarchical materials by design, spanning the macro, micro, and nano length scales.« less

Science, Policy, and Rationality in a Partisan Era

NASA Astrophysics Data System (ADS)

Kirchner, J. W.

2017-12-01

Science plays an essential role in public policy by outlining the factual foundations of policy decisions. Political partisans, however, often use science the way drunkards use lampposts: for support rather than illumination. Thus science can become a political football, with partisans dismissing or misrepresenting scientific findings that conflict with their political views. Presenting and defending science in a highly charged political environment is therefore challenging. Here I argue that scientists can most effectively speak out, not as activists supporting particular political causes, but instead as advocates for a fundamentally rational public discourse, one that starts from the facts - not from whatever one might choose to believe - and then explores how society should respond. Recognizing the distinction between facts and values, and respecting their different roles in the policy process, are essential not only for the future of science, but also for the future of democratic institutions in the broadest sense.

Design principles for electrolytes and interfaces for stable lithium-metal batteries

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

Tikekar, Mukul D.; Choudhury, Snehashis; Tu, Zhengyuan

2016-09-08

The future of electrochemical energy storage hinges on the advancement of science and technology that enables rechargeable batteries that utilize reactive metals as anodes. With specific capacity more than ten times that of the LiC6 anode used in present-day lithium-ion batteries, cells based on Li-metal anodes are of particular interest. Effective strategies for stabilizing the anode in such cells are now understood to be a requirement for progress on exceptional storage technologies, including Li–S and Li–O2 batteries. Multiple challenges—parasitic reactions of Li-metal with liquid electrolytes, unstable and dendritic electrodeposition, and dendrite-induced short circuits—derailed early efforts to commercialize such lithium-metal batteries.more » Here we consider approaches for rationally designing electrolytes and Li-metal/electrolyte interfaces for stable, dendrite-free operation of lithium-metal batteries. On the basis of fundamental understanding of the failure modes of reactive metal anodes, we discuss the key variables that govern the stability of electrodeposition at the Li anode and propose a universal framework for designing stable electrolytes and interfaces for lithium-metal batteries.« less

Design principles for electrolytes and interfaces for stable lithium-metal batteries

NASA Astrophysics Data System (ADS)

Tikekar, Mukul D.; Choudhury, Snehashis; Tu, Zhengyuan; Archer, Lynden A.

2016-09-01

The future of electrochemical energy storage hinges on the advancement of science and technology that enables rechargeable batteries that utilize reactive metals as anodes. With specific capacity more than ten times that of the LiC6 anode used in present-day lithium-ion batteries, cells based on Li-metal anodes are of particular interest. Effective strategies for stabilizing the anode in such cells are now understood to be a requirement for progress on exceptional storage technologies, including Li-S and Li-O2 batteries. Multiple challenges—parasitic reactions of Li-metal with liquid electrolytes, unstable and dendritic electrodeposition, and dendrite-induced short circuits—derailed early efforts to commercialize such lithium-metal batteries. Here we consider approaches for rationally designing electrolytes and Li-metal/electrolyte interfaces for stable, dendrite-free operation of lithium-metal batteries. On the basis of fundamental understanding of the failure modes of reactive metal anodes, we discuss the key variables that govern the stability of electrodeposition at the Li anode and propose a universal framework for designing stable electrolytes and interfaces for lithium-metal batteries.

From STEM to STEAM: Toward a Human-Centered Education

NASA Technical Reports Server (NTRS)

Boy, Guy A.

2013-01-01

The 20th century was based on local linear engineering of complicated systems. We made cars, airplanes and chemical plants for example. The 21st century has opened a new basis for holistic non-linear design of complex systems, such as the Internet, air traffic management and nanotechnologies. Complexity, interconnectivity, interaction and communication are major attributes of our evolving society. But, more interestingly, we have started to understand that chaos theories may be more important than reductionism, to better understand and thrive on our planet. Systems need to be investigated and tested as wholes, which requires a cross-disciplinary approach and new conceptual principles and tools. Consequently, schools cannot continue to teach isolated disciplines based on simple reductionism. Science; Technology, Engineering, and Mathematics (STEM) should be integrated together with the Arts1 to promote creativity together with rationalization, and move to STEAM (with an "A" for Arts). This new concept emphasizes the possibility of longer-term socio-technical futures instead of short-term financial predictions that currently lead to uncontrolled economies. Human-centered design (HCD) can contribute to improving STEAM education technologies, systems and practices. HCD not only provides tools and techniques to build useful and usable things, but also an integrated approach to learning by doing, expressing and critiquing, exploring possible futures, and understanding complex systems.

An open trial of a comprehensive anger treatment program on an outpatient sample.

PubMed

Fuller, J Ryan; Digiuseppe, Raymond; O'Leary, Siobhan; Fountain, Tina; Lang, Colleen

2010-07-01

This pilot study was designed to investigate the efficacy of a cognitive behavioral treatment for anger. Twelve (5 men and 7 women) outpatient adults completed 2-hour group sessions for 16 sessions. Participants were diagnosed with 29 Axis I and 34 Axis II disorders with high rates of comorbidity. Empirically supported techniques of skills training, cognitive restructuring, and relaxation were utilized. In this protocol, cognitive restructuring emphasized the use of the ABC model to understand anger episodes and the Rational Emotive Behavior Therapy (REBT) techniques of disputing irrational beliefs and rehearsing rational coping statements, but additional cognitive techniques were used, e.g. self-instructional training (SIT). Skills training included problem-solving and assertiveness. Relaxation training was paced respiration. Motivational interviewing, imaginal exposure with coping, and relapse prevention were also included. Significant improvements were found from pre- to post-treatment on the following measures: the Trait Anger Scale of the State-Trait Anger Expression Inventory-II; and Anger Disorder Scale total scores; idiosyncratic anger measurements of situational intensity and symptom severity; and the Beck Depression Inventory-II. In order to extend the significant research findings of this pilot study, future investigations should involve larger sample sizes, populations drawn from various settings, and contact control groups.

Shape optimization using a NURBS-based interface-enriched generalized FEM

DOE PAGES

Najafi, Ahmad R.; Safdari, Masoud; Tortorelli, Daniel A.; ...

2016-11-26

This study presents a gradient-based shape optimization over a fixed mesh using a non-uniform rational B-splines-based interface-enriched generalized finite element method, applicable to multi-material structures. In the proposed method, non-uniform rational B-splines are used to parameterize the design geometry precisely and compactly by a small number of design variables. An analytical shape sensitivity analysis is developed to compute derivatives of the objective and constraint functions with respect to the design variables. Subtle but important new terms involve the sensitivity of shape functions and their spatial derivatives. As a result, verification and illustrative problems are solved to demonstrate the precision andmore » capability of the method.« less

Rational design of class I MHC ligands

NASA Astrophysics Data System (ADS)

Rognan, D.; Scapozza, L.; Folkers, G.; Daser, Angelika

1995-04-01

From the knowledge of the three-dimensional structure of a class I MHC protein, several non natural peptides were designed in order to either optimize the interactions of one secondary anchor amino acid with its HLA binding pocket or to substitute the non interacting part with spacer residues. All peptides were synthesized and tested for binding to the class I MHC protein in an in vitro reconstitution assay. As predicted, the non natural peptides present an enhanced binding to the HLA-B27 molecule with respect to their natural parent peptides. This study constitutes the first step towards the rational design of non peptidic MHC ligands that should be very promising tools for the selective immunotherapy of autoimmune diseases.

Towards the rational design of the Py5-ligand framework for ruthenium-based water oxidation catalysts.

PubMed

Schilling, Mauro; Böhler, Michael; Luber, Sandra

2018-05-21

In order to rationally design water oxidation catalysts (WOCs), an in-depth understanding of the reaction mechanism is essential. In this study we showcase the complexity of catalytic water oxidation, by elucidating how modifications of the pentapyridyl (Py5) ligand-framework influence the thermodynamics and kinetics of the process. In the reaction mechanism the pyridine-water exchange was identified as a key reaction which appears to determine the reactivity of the Py5-WOCs. Exploring the capabilities of in silico design we show which modifications of the ligand framework appear promising when attempting to improve the catalytic performance of WOCs derived from Py5.

The effects of mortality salience and conceptual focus in CISM providers: implications for mental health response to mass fatality disasters.

PubMed

Morrow, Hope E; Haussmann, Robert

2012-01-01

On the basis of terror management theory (TMT) and cognitive-experiential self-theory (CEST), research has demonstrated that when individuals are experientially (rather than rationally)focused, mortality salience (MS) can engender world view defense in the form of increased in-group bias, increased favoritism toward others who uphold cultural values, and greater derogation of those who threaten them. The goal of the present study was to replicate previously observed effects of mortality salience on world view defense in a sample of disaster responders, specifically Criticallncident Stress Management (CISM) providers, and to examine the potential moderating effect of conceptual mode (rational versus experiential) on these effects. Sixty-two participants at the International Critical Incident Stress Foundation's 2011 World Congress were selected for participation in the study. Subsequent manipulation checks revealed that neither,manipulation (mortality salience: MS versus non-MS or conceptual mode: rational versus experiential) was effective. This failure is discussed in terms of the potentially mortality salient nature of conference proceedings that preceded data collection, the depletion of self-control resources required to maintain a rational focus on conference presentations, participants 'need to maintain their focus during future conference presentations, and profession-related practice effects that may have made it easier for some participants to maintain a rational focus.

Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

PubMed

García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

2017-08-01

Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bearing the right to healthcare, autonomy and hope.

PubMed

Nkomo, Nkululeko

2015-12-01

In this article, I discuss the significance of understanding within the context of the campaign for affordable and accessible HIV/AIDS treatments in South Africa, the transformational effects of the interplay between political rationality and affect for HIV-positive subjectivities. The article focuses on the policy tactics, in 2001, of the lobbying for a policy to prevent mother-to-child-transmission of HIV. A close reading of the lobby groups' rationalization of healthcare as a fundamental human right reveals a strategic attempt to recast a sense of helplessness into self-responsibilization, which concurrently involved nourishing hope in the preferred future for women with HIV to be afforded the right to individual choice associated with self-determination. Therefore, the struggle for a policy to prevent mother-to-child-transmission of HIV - an exemplary initiative to reconstitute HIV-positive subjectivity - maneuvered within both rationalizing and emotive spaces. Ongoing engagement of the broader campaign's contribution to redefining being HIV-positive thus also necessitates accounting for the effects of the convergence of political rationality and emotion in its tactically emancipatory project. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kant on euthanasia and the duty to die: clearing the air.

PubMed

Cholbi, Michael

2015-08-01

Thanks to recent scholarship, Kant is no longer seen as the dogmatic opponent of suicide that he appears to be at first glance. However, some interpreters have recently argued for a Kantian view of the morality of suicide with surprising, even radical, implications. More specifically, they have argued that Kantianism (1) requires that those with dementia or other rationality-eroding conditions end their lives before their condition results in their loss of identity as moral agents and (2) requires subjecting the fully demented or those confronting future dementia to non-voluntary euthanasia. Properly understood, Kant's ethics have neither of these implications (1) wrongly assumes that rational agents' duty of self-preservation entails a duty of self-destruction when they become non-rational, (2) further neglects Kant's distinction between duties to self and duties to others and wrongly assumes that duties can be owed to rational agents only during the time of their existence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Rationality and drug use: an experimental approach.

PubMed

Blondel, Serge; Lohéac, Youenn; Rinaudo, Stéphane

2007-05-01

In rational addiction theory, higher discount rates encourage drug use. We test this hypothesis in the general framework of rationality and behaviour under risk. We do so using an experimental design with real monetary incentives. The decisions of 34 drug addicts are compared with those of a control group. The decisions of drug users (DU) are not any less consistent with standard theories of behaviour over time and under risk. Further, there is no difference in the estimated discount rate between drug users and the control group, but the former do appear to be more risk-seeking.

Rational tuning of high-energy visible light absorption for panchromatic small molecules by a two-dimensional conjugation approach

DOE PAGES

He, B.; Zherebetskyy, D.; Wang, H.; ...

2016-02-29

We have demonstrated a rational two-dimensional (2D) conjugation approach towards achieving panchromatic absorption of small molecules. Furthermore, by extending the conjugation on two orthogonal axes of an electron acceptor, namely, bay-annulated indigo (BAI), the optical absorptions could be tuned independently in both high- and low-energy regions. The unconventional modulation of the high-energy absorption is rationalized by density functional theory (DFT) calculations. Finally, we determine that a 2D tuning strategy provides novel guidelines for the design of molecular materials with tailored optoelectronic properties.

Toward a rational, value-based drug benefit for Medicare.

PubMed

Lopert, Ruth; Moon, Marilyn

2007-01-01

A major challenge facing Congress is what changes, if any, to make to Medicare Part D. With the apparent failure of the Democrats' attempt to remove the prohibition on government intervention in drug price negotiations, the party's next steps are unclear. One suggested option is a plan administered by the Centers for Medicare and Medicaid Services (CMS), to compete with private plans and facilitate a transition to a more rational structure. We discuss issues surrounding the design of such a mechanism and how it might provide a transition toward a more rational and sustainable drug benefit in the longer term.

Designing Inhibitors of Anthrax Toxin

PubMed Central

Nestorovich, Ekaterina M.; Bezrukov, Sergey M.

2014-01-01

Introduction Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates, and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded “for the development of multiscale models for complex chemical systems” once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial and error approach to a minimum. The “rational drug design” term is rather comprehensive as it includes all contemporary methods of drug discovery where serendipity and screening are substituted by the information-guided search for new and existing compounds. Successful implementation of these innovative drug discovery approaches is inevitably preceded by learning the physics, chemistry, and physiology of functioning of biological structures under normal and pathological conditions. Areas covered This article provides an overview of the recent rational drug design approaches to discover inhibitors of anthrax toxin. Some of the examples include small-molecule and peptide-based post-exposure therapeutic agents as well as several polyvalent compounds. The review also directs the reader to the vast literature on the recognized advances and future possibilities in the field. Expert opinion Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (PA-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, in our view, the situation is still insecure. The FDA’s animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Besides, unlike PA, which is known to be unstable, LF remains active in cells and in animal tissues for days. Therefore, the effectiveness of the post-exposure treatment of the individuals with anti-PA therapeutics can be time-dependent, requiring coordinated use of membrane permeable small-molecule inhibitors, which block the LF and EF enzymatic activity intracellularly. The desperate search for an ideal anthrax antitoxin allowed researchers to gain important knowledge of the basic principles of small-molecule interactions with their protein targets that could be easily transferred to other systems. At the same time, better identification and validation of anthrax toxin therapeutic targets at the molecular level, which include understanding of the physical forces underlying the target/drug interaction, as well as elucidation of the parameters determining the corresponding therapeutic windows, require further examination. PMID:24447197

Surface modification of nanoporous anodic alumina photonic crystals for photocatalytic applications

NASA Astrophysics Data System (ADS)

Lim, Siew Yee; Law, Cheryl Suwen; Santos, Abel

2018-01-01

Herein, we report on the development of a rationally designed composite photocatalyst material by combining nanoporous anodic alumina-rugate filters (NAA-RFs) with photo-active layers of titanium dioxide (TiO2). NAA-RFs are synthesised by sinusoidal pulse anodisation and subsequently functionalised with TiO2 by sol-gel method to provide the photonic structures with photocatalytic properties. We demonstrate that the characteristic photonic stopband (PSB) of the surface-modified NAA-RFs can be precisely tuned across the UV-visible-NIR spectrum to enhance the photon-toelectron conversion of TiO2 by `slow photon effect'. We systematically investigate the effect of the anodisation parameters (i.e. anodisation period and pore widening time) on the position of the PSB of NAA-RFs as well as the photocatalytic performances displayed by these photonic crystal structures. When the edges of the PSB of surfacemodified NAA-RFs are positioned closely to the absorption peak of the model organic dye (i.e. methyl orange - MO), the photocatalytic performance of the system to degrade these molecules is enhanced under simulated solar light irradiation due to slow photon effect. Our investigation also reveals that the photocatalytic activity of surface-modified NAA-RFs is independent of slow photon effect and enhances with increasing period length (i.e. increasing anodisation period) of the photonic structures when there is no overlap between the PSB and the absorption peak of MO. This study therefore provides a rationale towards the photocatalytic enhancement of photonic crystals by a rational design of the PSB, creating new opportunities for the future development of high-performance photocatalysts.

Promoter and Terminator Discovery and Engineering.

PubMed

Deaner, Matthew; Alper, Hal S

Control of gene expression is crucial to optimize metabolic pathways and synthetic gene networks. Promoters and terminators are stretches of DNA upstream and downstream (respectively) of genes that control both the rate at which the gene is transcribed and the rate at which mRNA is degraded. As a result, both of these elements control net protein expression from a synthetic construct. Thus, it is highly important to discover and engineer promoters and terminators with desired characteristics. This chapter highlights various approaches taken to catalogue these important synthetic elements. Specifically, early strategies have focused largely on semi-rational techniques such as saturation mutagenesis to diversify native promoters and terminators. Next, in an effort to reduce the length of the synthetic biology design cycle, efforts in the field have turned towards the rational design of synthetic promoters and terminators. In this vein, we cover recently developed methods such as hybrid engineering, high throughput characterization, and thermodynamic modeling which allow finer control in the rational design of novel promoters and terminators. Emphasis is placed on the methodologies used and this chapter showcases the utility of these methods across multiple host organisms.

Virtual screening and rational drug design method using structure generation system based on 3D-QSAR and docking.

PubMed

Chen, H F; Dong, X C; Zen, B S; Gao, K; Yuan, S G; Panaye, A; Doucet, J P; Fan, B T

2003-08-01

An efficient virtual and rational drug design method is presented. It combines virtual bioactive compound generation with 3D-QSAR model and docking. Using this method, it is possible to generate a lot of highly diverse molecules and find virtual active lead compounds. The method was validated by the study of a set of anti-tumor drugs. With the constraints of pharmacophore obtained by DISCO implemented in SYBYL 6.8, 97 virtual bioactive compounds were generated, and their anti-tumor activities were predicted by CoMFA. Eight structures with high activity were selected and screened by the 3D-QSAR model. The most active generated structure was further investigated by modifying its structure in order to increase the activity. A comparative docking study with telomeric receptor was carried out, and the results showed that the generated structures could form more stable complexes with receptor than the reference compound selected from experimental data. This investigation showed that the proposed method was a feasible way for rational drug design with high screening efficiency.

Rational design for the stability improvement of Armillariella tabescens β-mannanase MAN47 based on N-glycosylation modification.

PubMed

Hu, Weixiong; Liu, Xiaoyun; Li, Yufeng; Liu, Daling; Kuang, Zhihe; Qian, Chuiwen; Yao, Dongsheng

2017-02-01

β-Mannanase has been widely used in industries such as food and feed processing and thus has been a target enzyme for biotechnological development. In this study, we sought to improve the stability and protease resistance of a recombinant β-mannanase, MAN47 from Armillariella tabescens, through rationally designed N-glycosylation. Based on homology modeling, molecular docking, secondary structure analysis and glycosylation feasibility analysis, an enhanced aromatic sequon sequence was introduced into specific MAN47 loop regions to facilitate N-glycosylation. The mutant enzymes were expressed in Pichia pastoris SMD1168, and their thermal stability, pH stability, trypsin resistance and pepsin resistance were determined. Two mutant MAN47 enzymes, g-123 and g-347, were glycosylated as expected when expressed in yeast, and their thermal stability, pH stability, and protease resistance were significantly improved compared to the wild-type enzyme. An enzyme with multiple stability characterizations has broad prospects in practical applications, and the rational design N-glycosylation strategy may have applications in simultaneously improving several properties of other biotechnological targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Surrogate biochemical markers: precise measurement for strategic drug and biologics development.

PubMed

Lee, J W; Hulse, J D; Colburn, W A

1995-05-01

More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making.

A model for interprovincial air pollution control based on futures prices.

PubMed

Zhao, Laijun; Xue, Jian; Gao, Huaizhu Oliver; Li, Changmin; Huang, Rongbing

2014-05-01

Based on the current status of research on tradable emission rights futures, this paper introduces basic market-related assumptions for China's interprovincial air pollution control problem. The authors construct an interprovincial air pollution control model based on futures prices: the model calculated the spot price of emission rights using a classic futures pricing formula, and determined the identities of buyers and sellers for various provinces according to a partitioning criterion, thereby revealing five trading markets. To ensure interprovincial cooperation, a rational allocation result for the benefits from this model was achieved using the Shapley value method to construct an optimal reduction program and to determine the optimal annual decisions for each province. Finally, the Beijing-Tianjin-Hebei region was used as a case study, as this region has recently experienced serious pollution. It was found that the model reduced the overall cost of reducing SO2 pollution. Moreover, each province can lower its cost for air pollution reduction, resulting in a win-win solution. Adopting the model would therefore enhance regional cooperation and promote the control of China's air pollution. The authors construct an interprovincial air pollution control model based on futures prices. The Shapley value method is used to rationally allocate the cooperation benefit. Interprovincial pollution control reduces the overall reduction cost of SO2. Each province can lower its cost for air pollution reduction by cooperation.

Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA.

PubMed

Lai, Cheng-Tsung; Li, Huei-Jiun; Yu, Weixuan; Shah, Sonam; Bommineni, Gopal R; Perrone, Victoria; Garcia-Diaz, Miguel; Tonge, Peter J; Simmerling, Carlos

2015-08-04

Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens.

APPLICATION OF STEEL PIPE PILE LOADING TESTS TO DESIGN VERIFICATION OF FOUNDATION OF THE TOKYO GATE BRIDGE

NASA Astrophysics Data System (ADS)

Saitou, Yutaka; Kikuchi, Yoshiaki; Kusakabe, Osamu; Kiyomiya, Osamu; Yoneyama, Haruo; Kawakami, Taiji

Steel sheet pipe pile foundations with large diameter steel pipe sheet pile were used for the foundation of the main pier of the Tokyo Gateway bridge. However, as for the large diameter steel pipe pile, the bearing mechanism including a pile tip plugging effect is still unclear due to lack of the practical examinations even though loading tests are performed on Trans-Tokyo Bay Highway. In the light of the foregoing problems, static pile loading tests both vertical and horizontal directions, a dynamic loading test, and cone penetration tests we re conducted for determining proper design parameters of the ground for the foundations. Design parameters were determined rationally based on the tests results. Rational design verification was obtained from this research.

Recent Advances in Silicon Nanomaterial-Based Fluorescent Sensors.

PubMed

Wang, Houyu; He, Yao

2017-02-03

During the past decades, owing to silicon nanomaterials' unique optical properties, benign biocompatibility, and abundant surface chemistry, different dimensional silicon nanostructures have been widely employed for rationally designing and fabricating high-performance fluorescent sensors for the detection of various chemical and biological species. Among of these, zero-dimensional silicon nanoparticles (SiNPs) and one-dimensional silicon nanowires (SiNWs) are of particular interest. Herein, we focus on reviewing recent advances in silicon nanomaterials-based fluorescent sensors from a broad perspective and discuss possible future directions. Firstly, we introduce the latest achievement of zero-dimensional SiNP-based fluorescent sensors. Next, we present recent advances of one-dimensional SiNW-based fluorescent sensors. Finally, we discuss the major challenges and prospects for the development of silicon-based fluorescent sensors.

An introduction to minimally invasive therapy.

PubMed

Wickham, J E

1993-01-01

Minimally invasive therapy (MIT) has as its basic premise the reduction of iatrogenic trauma to the patient by surgeon, physician or radiologist. This approach must also imply that the therapeutic procedure succeeds in its aim of cure in a manner no less effective than is currently achievable by established methods of treatment. Acceptance of this principal has many identifiable sequelae, including profound changes in hospital design, increasingly expensive technological instrumentation, more sophisticated teaching and learning patterns, and a massive redirection of health care financial resources. These changes cannot be contemplated at leisure, because they are dynamically imperative and progressing with relentless rapidity, being directly driven by the consumer. It is vital that this shift in clinical emphasis should be appreciated so that future planning can be undertaken with some rationality.

Functionalized graphene-based cathode for highly reversible lithium-sulfur batteries.

PubMed

Kim, Jin Won; Ocon, Joey D; Park, Dong-Won; Lee, Jaeyoung

2014-05-01

In this article, we highlight the salient issues in the development of lithium-sulfur battery (LSB) cathodes, present different points of view in solving them, and argue, why in the future, functionalized graphene or graphene oxide might be the ultimate solution towards LSB commercialization. As shown by previous studies and also in our recent work, functionalized graphene and graphene oxide enhance the reversibility of the charge-discharge process by trapping polysulfides in the oxygen functional groups on the graphene surface, thus minimizing polysulfide dissolution. This will be helpful for the rational design of new cathode structures based on graphene for LSBs with minimal capacity fading, low extra cost, and without the unnecessary weight increase caused by metal/metal oxide additives. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanostructured Ion-Exchange Membranes for Fuel Cells: Recent Advances and Perspectives.

PubMed

He, Guangwei; Li, Zhen; Zhao, Jing; Wang, Shaofei; Wu, Hong; Guiver, Michael D; Jiang, Zhongyi

2015-09-23

Polymer-based materials with tunable nanoscale structures and associated microenvironments hold great promise as next-generation ion-exchange membranes (IEMs) for acid or alkaline fuel cells. Understanding the relationships between nanostructure, physical and chemical microenvironment, and ion-transport properties are critical to the rational design and development of IEMs. These matters are addressed here by discussing representative and important advances since 2011, with particular emphasis on aromatic-polymer-based nanostructured IEMs, which are broadly divided into nanostructured polymer membranes and nanostructured polymer-filler composite membranes. For each category of membrane, the core factors that influence the physical and chemical microenvironments of the ion nanochannels are summarized. In addition, a brief perspective on the possible future directions of nanostructured IEMs is presented. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An improved Burgers cellular automaton model for bicycle flow

NASA Astrophysics Data System (ADS)

Xue, Shuqi; Jia, Bin; Jiang, Rui; Li, Xingang; Shan, Jingjing

2017-12-01

As an energy-efficient and healthy transport mode, bicycling has recently attracted the attention of governments, transport planners, and researchers. The dynamic characteristics of the bicycle flow must be investigated to improve the facility design and traffic operation of bicycling. We model the bicycle flow by using an improved Burgers cellular automaton model. Through a following move mechanism, the modified model enables bicycles to move smoothly and increase the critical density to a more rational level than the original model. The model is calibrated and validated by using experimental data and field data. The results show that the improved model can effectively simulate the bicycle flow. The performance of the model under different parameters is investigated and discussed. Strengths and limitations of the improved model are suggested for future work.

Obesity Pharmacotherapy: Current Perspectives and Future Directions

PubMed Central

Misra, Monika

2013-01-01

The rising tide of obesity and its related disorders is one of the most pressing health concerns worldwide, yet existing medicines to combat the problem are disappointingly limited in number and effectiveness. Recent advances in mechanistic insights into the neuroendocrine regulation of body weight have revealed an expanding list of molecular targets for novel, rationally designed antiobesity pharmaceutical agents. Antiobesity drugs act via any of four mechanisms: 1) decreasing energy intake, 2) increasing energy expenditure or modulating lipid metabolism, 3) modulating fat stores or adipocyte differentiation, and 4) mimicking caloric restriction. Various novel drug candidates and targets directed against obesity are currently being explored. A few of them are also in the later phases of clinical trials. This review discusses the development of novel antiobesity drugs based on current understanding of energy homeostasis PMID:23092275

Temporal trade-offs in psychophysics.

PubMed

Barack, David L; Gold, Joshua I

2016-04-01

Psychophysical techniques typically assume straightforward relationships between manipulations of real-world events, their effects on the brain, and behavioral reports of those effects. However, these relationships can be influenced by many complex, strategic factors that contribute to task performance. Here we discuss several of these factors that share two key features. First, they involve subjects making flexible use of time to process information. Second, this flexibility can reflect the rational regulation of information-processing trade-offs that can play prominent roles in particular temporal epochs: sensitivity to stability versus change for past information, speed versus accuracy for current information, and exploitation versus exploration for future goals. Understanding how subjects manage these trade-offs can be used to help design and interpret psychophysical studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanomedicine of synergistic drug combinations for cancer therapy – strategies and perspectives

PubMed Central

Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

2016-01-01

Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. PMID:27287891

Recent Advances in Silicon Nanomaterial-Based Fluorescent Sensors

PubMed Central

Wang, Houyu; He, Yao

2017-01-01

During the past decades, owing to silicon nanomaterials’ unique optical properties, benign biocompatibility, and abundant surface chemistry, different dimensional silicon nanostructures have been widely employed for rationally designing and fabricating high-performance fluorescent sensors for the detection of various chemical and biological species. Among of these, zero-dimensional silicon nanoparticles (SiNPs) and one-dimensional silicon nanowires (SiNWs) are of particular interest. Herein, we focus on reviewing recent advances in silicon nanomaterials-based fluorescent sensors from a broad perspective and discuss possible future directions. Firstly, we introduce the latest achievement of zero-dimensional SiNP-based fluorescent sensors. Next, we present recent advances of one-dimensional SiNW-based fluorescent sensors. Finally, we discuss the major challenges and prospects for the development of silicon-based fluorescent sensors. PMID:28165357

An oracle: antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future.

PubMed

Pasipanodya, Jotam; Gumbo, Tawanda

2011-01-01

Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration.

Porous One-Dimensional Nanomaterials: Design, Fabrication and Applications in Electrochemical Energy Storage.

PubMed

Wei, Qiulong; Xiong, Fangyu; Tan, Shuangshuang; Huang, Lei; Lan, Esther H; Dunn, Bruce; Mai, Liqiang

2017-05-01

Electrochemical energy storage technology is of critical importance for portable electronics, transportation and large-scale energy storage systems. There is a growing demand for energy storage devices with high energy and high power densities, long-term stability, safety and low cost. To achieve these requirements, novel design structures and high performance electrode materials are needed. Porous 1D nanomaterials which combine the advantages of 1D nanoarchitectures and porous structures have had a significant impact in the field of electrochemical energy storage. This review presents an overview of porous 1D nanostructure research, from the synthesis by bottom-up and top-down approaches with rational and controllable structures, to several important electrochemical energy storage applications including lithium-ion batteries, sodium-ion batteries, lithium-sulfur batteries, lithium-oxygen batteries and supercapacitors. Highlights of porous 1D nanostructures are described throughout the review and directions for future research in the field are discussed at the end. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies for Efficient Charge Separation and Transfer in Artificial Photosynthesis of Solar Fuels.

PubMed

Xu, Yuxing; Li, Ailong; Yao, Tingting; Ma, Changtong; Zhang, Xianwen; Shah, Jafar Hussain; Han, Hongxian

2017-11-23

Converting sunlight to solar fuels by artificial photosynthesis is an innovative science and technology for renewable energy. Light harvesting, photogenerated charge separation and transfer (CST), and catalytic reactions are the three primary steps in the processes involved in the conversion of solar energy to chemical energy (SE-CE). Among the processes, CST is the key "energy pump and delivery" step in determining the overall solar-energy conversion efficiency. Efficient CST is always high priority in designing and assembling artificial photosynthesis systems for solar-fuel production. This Review not only introduces the fundamental strategies for CST but also the combinatory application of these strategies to five types of the most-investigated semiconductor-based artificial photosynthesis systems: particulate, Z-scheme, hybrid, photoelectrochemical, and photovoltaics-assisted systems. We show that artificial photosynthesis systems with high SE-CE efficiency can be rationally designed and constructed through combinatory application of these strategies, setting a promising blueprint for the future of solar fuels. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A redox-mediated Kemp eliminase

NASA Astrophysics Data System (ADS)

Li, Aitao; Wang, Binju; Ilie, Adriana; Dubey, Kshatresh D.; Bange, Gert; Korendovych, Ivan V.; Shaik, Sason; Reetz, Manfred T.

2017-03-01

The acid/base-catalysed Kemp elimination of 5-nitro-benzisoxazole forming 2-cyano-4-nitrophenol has long served as a design platform of enzymes with non-natural reactions, providing new mechanistic insights in protein science. Here we describe an alternative concept based on redox catalysis by P450-BM3, leading to the same Kemp product via a fundamentally different mechanism. QM/MM computations show that it involves coordination of the substrate's N-atom to haem-Fe(II) with electron transfer and concomitant N-O heterolysis liberating an intermediate having a nitrogen radical moiety Fe(III)-N. and a phenoxyl anion. Product formation occurs by bond rotation and H-transfer. Two rationally chosen point mutations cause a notable increase in activity. The results shed light on the prevailing mechanistic uncertainties in human P450-catalysed metabolism of the immunomodulatory drug leflunomide, which likewise undergoes redox-mediated Kemp elimination by P450-BM3. Other isoxazole-based pharmaceuticals are probably also metabolized by a redox mechanism. Our work provides a basis for designing future artificial enzymes.

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy.

PubMed

Zhu, Hai; Zhou, Binwei; Chan, Leung; Du, Yanxin; Chen, Tianfeng

2017-01-01

Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology.

PubMed

Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N; Mantalaris, Athanasios

2012-01-01

The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology

PubMed Central

Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N.; Mantalaris, Athanasios

2013-01-01

The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals. PMID:24688682

Synthetic biology: new engineering rules for an emerging discipline

PubMed Central

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development. PMID:16738572

Synthetic biology: new engineering rules for an emerging discipline.

PubMed

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

Regret and rationalization among smokers in Thailand and Malaysia: findings from the International Tobacco Control Southeast Asia Survey.

PubMed

Lee, Wonkyong B; Fong, Geoffrey T; Zanna, Mark P; Omar, Maizurah; Sirirassamee, Buppha; Borland, Ron

2009-07-01

To test whether differences of history and strength in tobacco control policies will influence social norms, which, in turn, will influence quit intentions, by influencing smokers' regret and rationalization. The data were from the International Tobacco Control (ITC) Policy Evaluation Southeast Asia Survey, a cohort survey of representative samples of adult smokers in Thailand (N = 2,000) and Malaysia (N = 2,006). The survey used a stratified multistage sampling design. Measures included regret, rationalization, social norms, and quit intention. Thai smokers were more likely to have quit intentions than Malaysian smokers. This difference in quit intentions was, in part, explained by the country differences in social norms, regret, and rationalization. Reflecting Thailand's history of stronger tobacco control policies, Thai smokers, compared with Malaysian smokers, perceived more negative social norms toward smoking, were more likely to regret, and less likely to rationalize smoking. Mediational analyses revealed that these differences in social norms, accounted, in part, for the country-quit intention relation and that regret and rationalization accounted, in part, for the social norm-quit intention relation. The results suggest that social norms toward smoking, which are shaped by tobacco control policies, and smokers' regret and rationalization influence quit intentions.

Oligoalanine helical callipers for cell penetration.

PubMed

Pazo, Marta; Juanes, Marisa; Lostalé-Seijo, Irene; Montenegro, Javier

2018-06-04

Even for short peptides that are enriched in basic amino acids, the large chemical space that can be spanned by combinations of natural amino acids hinders the rational design of cell penetrating peptides. We here report on short oligoalanine scaffolds for the fine-tuning of peptide helicity in different media and the study of cell penetrating properties. This strategy allowed the extraction of the structure/activity features required for maximal membrane interaction and cellular penetration at minimal toxicity. These results confirmed oligoalanine helical callipers as optimal scaffolds for the rational design and the identification of cell penetrating peptides.

Drug rationing in the UK National Health Service. Current status and future prospects.

PubMed

Walley, T; Haycox, A; Barton, S

1997-09-01

There are major problems in attempting to ration drug use in the UK. These include the large indigenous pharmaceutical industry, the nature of funding of drugs within the National Health Service (NHS) and the political sensitivities of rationing. Rationing of services within the NHS has therefore usually been implicit rather than explicit, and there is little public debate about rationing of health services. In relation to drug therapy, prescribing in primary care technically can only be rationed by encouraging the general practitioner (GP) to contain his or her own costs-effectively moving the difficult decision to the GP. Direct incentives to the GP, in the form of incentive payments or by fundholding seem to have some success in containing costs, largely by simple generic substitution. There are established systems in hospitals to control the costs of drugs, including formularies and drug management committees. Hospitals commonly try to transfer drug costs to the GP budget. While in part this is clinically appropriate, it can lead to tensions. Health authorities and GP fundholders now include prescribing, particularly at this interface, in their contracts with hospitals. Economic evaluations currently play little part in aiding decisions about choice of drug. These decisions tend to be dominated by the need for short term cost containment in the UK. Recent reforms of the NHS have moved responsibility for the rationing of services to the local authorities or purchasers; this might in time create an additional, local hurdle for pharmaceutical companies trying to market new drugs. A proposal to introduce a national limited formulary in which drugs will be selected partly on the basis of an economic evaluation seems impractical, although similar ideas might be further developed.

Late-Life Suicide in Terminal Cancer: A Rational Act or Underdiagnosed Depression?

PubMed

Cheung, Gary; Douwes, Gwendolyn; Sundram, Frederick

2017-12-01

Previous studies have reported significantly elevated standardized mortality rates in older people with cancer. Terminally ill people represent a unique group where suicide may be considered as rational. The aims of this study are to compare the sociodemographic and clinical characteristics of older people with and without terminal cancer who died by suicide and analyze the suicide motives of those with terminal cancer to determine whether they represent rational suicide. The New Zealand Coronial Services provided records of all older people (aged 65 years and older) who died by suicide between July 2007 and December 2012. Sociodemographic and clinical data were extracted from the records. Using the characteristics for defining rational suicide, we determined whether the motives in terminal cancer cases represented rational suicide. Of the 214 suicide cases, 23 (10.7%) older people were diagnosed with a terminal cancer. Univariate analysis found that older people with terminal cancer who died by suicide were less likely to have a diagnosis of depression (8.7% vs. 46.6%; P = 0.001) or previous contact with mental health services (4.5% vs. 35.0%; P = 0.004) than those without terminal cancer. About 82.6% of the terminal cancer cases had a motivational basis that would be understandable to uninvolved observers. A high proportion of those with terminal cancer had motives suggestive of rational suicide. Future studies are needed to clarify whether the low rate of depression is secondary to underdiagnosis of depression or people with terminal cancer choosing to end their life as a rational act to alleviate suffering. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Experiential and rational decision making: a survey to determine how emergency physicians make clinical decisions.

PubMed

Calder, Lisa A; Forster, Alan J; Stiell, Ian G; Carr, Laura K; Brehaut, Jamie C; Perry, Jeffrey J; Vaillancourt, Christian; Croskerry, Patrick

2012-10-01

Dual-process psychological theories argue that clinical decision making is achieved through a combination of experiential (fast and intuitive) and rational (slower and systematic) cognitive processes. To determine whether emergency physicians perceived their clinical decisions in general to be more experiential or rational and how this compared with other physicians. A validated psychometric tool, the Rational Experiential Inventory (REI-40), was sent through postal mail to all emergency physicians registered with the College of Physicians and Surgeons of Ontario, according to their website in November 2009. Forty statements were ranked on a Likert scale from 1 (Definitely False) to 5 (Definitely True). An initial survey was sent out, followed by reminder cards and a second survey to non-respondents. Analysis included descriptive statistics, Student t tests, analysis of variance and comparison of mean scores with those of cardiologists from New Zealand. The response rate in this study was 46.9% (434/925). The respondents' median age was 41-50 years; they were mostly men (72.6%) and most had more than 10 years of clinical experience (66.8%). The mean REI-40 rational scores were higher than the experiential scores (3.93/5 (SD 0.35) vs 3.33/5 (SD 0.49), p<0.0001), similar to the mean scores of cardiologists from New Zealand (mean rational 3.93/5, mean experiential 3.05/5). The mean experiential scores were significantly higher for female respondents than for male respondents (3.40/5 (SD 0.49) vs 3.30/5 (SD 0.48), p=0.003). Overall, emergency physicians favoured rational decision making rather than experiential decision making; however, female emergency physicians had higher experiential scores than male emergency physicians. This has important implications for future knowledge translation and decision support efforts among emergency physicians.

Predicting differences in the perceived relevance of crime's costs and benefits in a test of rational choice theory.

PubMed

Bouffard, Jeffrey A

2007-08-01

Previous hypothetical scenario tests of rational choice theory have presented all participants with the same set of consequences, implicitly assuming that these consequences would be relevant for each individual. Recent research demonstrates that those researcher-presented consequences do not accurately reflect those considered by study participants and that there is individual variation in the relevance of various consequences. Despite this and some theoretical propositions that such differences should exist, little empirical research has explored the possibility of predicting such variation. This study allows participants to develop their own set of relevant consequences for three hypothetical offenses and examines how several demographic and theoretical variables impact those consequences' relevance. Exploratory results suggest individual factors impact the perceived relevance of several cost and benefit types, even among a relatively homogenous sample of college students. Implications for future tests of rational choice theory, as well as policy implications are discussed.

Rational management of epilepsy.

PubMed

Viswanathan, Venkataraman

2014-09-01

Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.

Uncomfortable realities: the challenge of creating real change in Europe's consolidating hospital sector.

PubMed

Jeurissen, Patrick; Duran, Antonio; Saltman, Richard B

2016-05-24

This article examines uncomfortable realities that the European hospital sector currently faces and the potential impact of wide-spread rationalization policies such as (hospital) payment reform and privatization. Review of relevant international literature. Based on the evidence we present, rationalization policies such as (hospital) payment reform and privatization will probably fall short in delivering better quality of care and lower growth in health expenses. Reasons can be sought in a mix of evidence on the effectiveness of these rationalization policies. Nevertheless, pressures for different business models will gradually continue to increase and it seems safe to assume that more value-added process business and facilitated network models will eventually emerge. The overall argument of this article holds important implications for future research: how can policymakers generate adequate leverage to introduce such changes without destroying necessary hospital capacity and the ability to produce quality healthcare.

Linking patient satisfaction with nursing care: the case of care rationing - a correlational study.

PubMed

Papastavrou, Evridiki; Andreou, Panayiota; Tsangari, Haritini; Merkouris, Anastasios

2014-01-01

Implicit rationing of nursing care is the withholding of or failure to carry out all necessary nursing measures due to lack of resources. There is evidence supporting a link between rationing of nursing care, nurses' perceptions of their professional environment, negative patient outcomes, and placing patient safety at risk. The aims of the study were: a) To explore whether patient satisfaction is linked to nurse-reported rationing of nursing care and to nurses' perceptions of their practice environment while adjusting for patient and nurse characteristics. b) To identify the threshold score of rationing by comparing the level of patient satisfaction factors across rationing levels. A descriptive, correlational design was employed. Participants in this study included 352 patients and 318 nurses from ten medical and surgical units of five general hospitals. Three measurement instruments were used: the BERNCA scale for rationing of care, the RPPE scale to explore nurses' perceptions of their work environment and the Patient Satisfaction scale to assess the level of patient satisfaction with nursing care. The statistical analysis included the use of Kendall's correlation coefficient to explore a possible relationship between the variables and multiple regression analysis to assess the effects of implicit rationing of nursing care together with organizational characteristics on patient satisfaction. The mean score of implicit rationing of nursing care was 0.83 (SD = 0.52, range = 0-3), the overall mean of RPPE was 2.76 (SD = 0.32, range = 1.28 - 3.69) and the two scales were significantly correlated (τ = -0.234, p < 0.001). The regression analysis showed that care rationing and work environment were related to patient satisfaction, even after controlling for nurse and patient characteristics. The results from the adjusted regression models showed that even at the lowest level of rationing (i.e. 0.5) patients indicated low satisfaction. The results support the relationships between organizational and environmental variables, care rationing and patient satisfaction. The identification of thresholds at which rationing starts to influence patient outcomes in a negative way may allow nurse managers to introduce interventions so as to keep rationing at a level at which patient safety is not jeopardized.

Modeling charge transport in organic photovoltaic materials.

PubMed

Nelson, Jenny; Kwiatkowski, Joe J; Kirkpatrick, James; Frost, Jarvist M

2009-11-17

The performance of an organic photovoltaic cell depends critically on the mobility of charge carriers within the constituent molecular semiconductor materials. However, a complex combination of phenomena that span a range of length and time scales control charge transport in disordered organic semiconductors. As a result, it is difficult to rationalize charge transport properties in terms of material parameters. Until now, efforts to improve charge mobilities in molecular semiconductors have proceeded largely by trial and error rather than through systematic design. However, recent developments have enabled the first predictive simulation studies of charge transport in disordered organic semiconductors. This Account describes a set of computational methods, specifically molecular modeling methods, to simulate molecular packing, quantum chemical calculations of charge transfer rates, and Monte Carlo simulations of charge transport. Using case studies, we show how this combination of methods can reproduce experimental mobilities with few or no fitting parameters. Although currently applied to material systems of high symmetry or well-defined structure, further developments of this approach could address more complex systems such anisotropic or multicomponent solids and conjugated polymers. Even with an approximate treatment of packing disorder, these computational methods simulate experimental mobilities within an order of magnitude at high electric fields. We can both reproduce the relative values of electron and hole mobility in a conjugated small molecule and rationalize those values based on the symmetry of frontier orbitals. Using fully atomistic molecular dynamics simulations of molecular packing, we can quantitatively replicate vertical charge transport along stacks of discotic liquid crystals which vary only in the structure of their side chains. We can reproduce the trends in mobility with molecular weight for self-organizing polymers using a cheap, coarse-grained structural simulation method. Finally, we quantitatively reproduce the field-effect mobility in disordered C60 films. On the basis of these results, we conclude that all of the necessary building blocks are in place for the predictive simulation of charge transport in macromolecular electronic materials and that such methods can be used as a tool toward the future rational design of functional organic electronic materials.

The space technology demand on materials and processes

NASA Technical Reports Server (NTRS)

Dauphin, J.

1983-01-01

Space technology requires a rational and accurate policy of materials and processes selection. This paper examines some areas of space technology where materials and process problems have occurred in the past and how they can be solved in the future.

Vaccines Meet Big Data: State-of-the-Art and Future Prospects. From the Classical 3Is (“Isolate–Inactivate–Inject”) Vaccinology 1.0 to Vaccinology 3.0, Vaccinomics, and Beyond: A Historical Overview

PubMed Central

Bragazzi, Nicola Luigi; Gianfredi, Vincenza; Villarini, Milena; Rosselli, Roberto; Nasr, Ahmed; Hussein, Amr; Martini, Mariano; Behzadifar, Masoud

2018-01-01

Vaccines are public health interventions aimed at preventing infections-related mortality, morbidity, and disability. While vaccines have been successfully designed for those infectious diseases preventable by preexisting neutralizing specific antibodies, for other communicable diseases, additional immunological mechanisms should be elicited to achieve a full protection. “New vaccines” are particularly urgent in the nowadays society, in which economic growth, globalization, and immigration are leading to the emergence/reemergence of old and new infectious agents at the animal–human interface. Conventional vaccinology (the so-called “vaccinology 1.0”) was officially born in 1796 thanks to the contribution of Edward Jenner. Entering the twenty-first century, vaccinology has shifted from a classical discipline in which serendipity and the Pasteurian principle of the three Is (isolate, inactivate, and inject) played a major role to a science, characterized by a rational design and plan (“vaccinology 3.0”). This shift has been possible thanks to Big Data, characterized by different dimensions, such as high volume, velocity, and variety of data. Big Data sources include new cutting-edge, high-throughput technologies, electronic registries, social media, and social networks, among others. The current mini-review aims at exploring the potential roles as well as pitfalls and challenges of Big Data in shaping the future vaccinology, moving toward a tailored and personalized vaccine design and administration. PMID:29556492

Vaccines Meet Big Data: State-of-the-Art and Future Prospects. From the Classical 3Is ("Isolate-Inactivate-Inject") Vaccinology 1.0 to Vaccinology 3.0, Vaccinomics, and Beyond: A Historical Overview.

PubMed

Bragazzi, Nicola Luigi; Gianfredi, Vincenza; Villarini, Milena; Rosselli, Roberto; Nasr, Ahmed; Hussein, Amr; Martini, Mariano; Behzadifar, Masoud

2018-01-01

Vaccines are public health interventions aimed at preventing infections-related mortality, morbidity, and disability. While vaccines have been successfully designed for those infectious diseases preventable by preexisting neutralizing specific antibodies, for other communicable diseases, additional immunological mechanisms should be elicited to achieve a full protection. "New vaccines" are particularly urgent in the nowadays society, in which economic growth, globalization, and immigration are leading to the emergence/reemergence of old and new infectious agents at the animal-human interface. Conventional vaccinology (the so-called "vaccinology 1.0") was officially born in 1796 thanks to the contribution of Edward Jenner. Entering the twenty-first century, vaccinology has shifted from a classical discipline in which serendipity and the Pasteurian principle of the three I s (isolate, inactivate, and inject) played a major role to a science, characterized by a rational design and plan ("vaccinology 3.0"). This shift has been possible thanks to Big Data, characterized by different dimensions, such as high volume, velocity, and variety of data. Big Data sources include new cutting-edge, high-throughput technologies, electronic registries, social media, and social networks, among others. The current mini-review aims at exploring the potential roles as well as pitfalls and challenges of Big Data in shaping the future vaccinology, moving toward a tailored and personalized vaccine design and administration.

Drug Information Services Today: Current Role and Future Perspectives in Rational Drug Therapy.

PubMed

Amundstuen Reppe, Linda; Spigset, Olav; Schjøtt, Jan

2016-02-01

Polypharmacy and complex drug treatment regimens are becoming increasingly common, which may lead to adverse drug reactions, drug interactions, medication nonadherence, and increasing costs and thus challenge the rational use of drugs. At the same time, the accessibility of drug information increases, and health care professionals may have limited opportunities and capabilities to search and critically evaluate drug information. Clinicians have reported difficulties in searching the best evidence and translating study findings into clinically meaningful information applicable to specific patients. Consequently, it remains a challenge to ensure the rational use of drugs in the years to come. Drug information centers (DICs) have been established to promote the rational use of drugs. One of the most important tasks of DICs is the question and answer services for health care professionals posing drug-related questions. DICs staffed by pharmacists and clinical pharmacologists hold expertise in searching for drug information and critical evaluation of the literature. The uniqueness in this service lies not only in the identification and interpretation of the scientific literature but also in the adaptation of the findings into specific clinical situations and the discussion of possible solutions with the enquirer. Thus, DICs could provide valuable decision support to the clinic. Taking into account the increasing number of possible drug-related questions that will arise today and in the future, the DICs will remain highly relevant in the years to come. However, the DICs must follow the developments in health information technology to disseminate relevant, unbiased drug information to old and new users of the service. Moreover, the DICs are important tools to counterbalance the drug information published by the pharmaceutical industry. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Method for automation of tool preproduction

NASA Astrophysics Data System (ADS)

Rychkov, D. A.; Yanyushkin, A. S.; Lobanov, D. V.; Arkhipov, P. V.

2018-03-01

The primary objective of tool production is a creation or selection of such tool design which could make it possible to secure high process efficiency, tool availability as well as a quality of received surfaces with minimum means and resources spent on it. It takes much time of application people, being engaged in tool preparation, to make a correct selection of the appropriate tool among the set of variants. Program software has been developed to solve the problem, which helps to create, systematize and carry out a comparative analysis of tool design to identify the rational variant under given production conditions. The literature indicates that systematization and selection of the tool rational design has been carried out in accordance with the developed modeling technology and comparative design analysis. Software application makes it possible to reduce the period of design by 80....85% and obtain a significant annual saving.

MIRATE: MIps RATional dEsign Science Gateway.

PubMed

Busato, Mirko; Distefano, Rosario; Bates, Ferdia; Karim, Kal; Bossi, Alessandra Maria; López Vilariño, José Manuel; Piletsky, Sergey; Bombieri, Nicola; Giorgetti, Alejandro

2018-06-13

Molecularly imprinted polymers (MIPs) are high affinity robust synthetic receptors, which can be optimally synthesized and manufactured more economically than their biological equivalents (i.e. antibody). In MIPs production, rational design based on molecular modeling is a commonly employed technique. This mostly aids in (i) virtual screening of functional monomers (FMs), (ii) optimization of monomer-template ratio, and (iii) selectivity analysis. We present MIRATE, an integrated science gateway for the intelligent design of MIPs. By combining and adapting multiple state-of-the-art bioinformatics tools into automated and innovative pipelines, MIRATE guides the user through the entire process of MIPs' design. The platform allows the user to fully customize each stage involved in the MIPs' design, with the main goal to support the synthesis in the wet-laboratory. MIRATE is freely accessible with no login requirement at http://mirate.di.univr.it/. All major browsers are supported.

Beyond directed evolution - semi-rational protein engineering and design

PubMed Central

Lutz, Stefan

2010-01-01

Over the last two decades, directed evolution has transformed the field of protein engineering. The advances in understanding protein structure and function, in no insignificant part a result of directed evolution studies, are increasingly empowering scientists and engineers to device more effective methods for manipulating and tailoring biocatalysts. Abandoning large combinatorial libraries, the focus has shifted to small, functionally-rich libraries and rational design. A critical component to the success of these emerging engineering strategies are computational tools for the evaluation of protein sequence datasets and the analysis of conformational variations of amino acids in proteins. Highlighting the opportunities and limitations of such approaches, this review focuses on recent engineering and design examples that require screening or selection of small libraries. PMID:20869867

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

PubMed

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

PubMed Central

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples. PMID:28035082

Transitioning Rationally Designed Catalytic Materials to Real 'Working' Catalysts Produced at Commercial Scale: Nanoparticle Materials

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

Schaidle, Joshua A.; Habas, Susan E.; Baddour, Frederick G.

Catalyst design, from idea to commercialization, requires multi-disciplinary scientific and engineering research and development over 10-20 year time periods. Historically, the identification of new or improved catalyst materials has largely been an empirical trial-and-error process. However, advances in computational capabilities (new tools and increased processing power) coupled with new synthetic techniques have started to yield rationally-designed catalysts with controlled nano-structures and tailored properties. This technological advancement represents an opportunity to accelerate the catalyst development timeline and to deliver new materials that outperform existing industrial catalysts or enable new applications, once a number of unique challenges associated with the scale-up ofmore » nano-structured materials are overcome.« less

Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

PubMed

Fox, Christopher B

2013-09-01

The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

Design of a small molecule against an oncogenic noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Cameron, Michael D; Haga, Christopher L; Rosenberg, Laura H; Lafitte, Marie; Duckett, Derek R; Phinney, Donald G; Disney, Matthew D

2016-05-24

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif-small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm.

Analytic Procedures For Designing and Evaluating Decision Aids.

DTIC Science & Technology

1980-04-01

the taxonomy of decision charateristics . Chapter 5 applies the taxonomies to the information processing functions needed for AAW decisions, and...rationality emphasizes the extent to which organizations and other social institutions consist of individuals who pursue individual objectives by means of...adaptive rationality is always wrong or naive; most of us know persons that seem to be naturally good decision-makers. There is no logic that guarantees

Effect of supplementing orchardgrass herbage with a total mixed ration or flaxseed fermentation profile and bacterial protein synthesis in continuous culture

USDA-ARS?s Scientific Manuscript database

A 4-unit dual-flow continuous culture fermentor system was used to evaluate the effects of herbage, a total mixed ration (TMR) and flaxseed on nutrient digestibility and microbial N synthesis. Treatments were randomly assigned to fermentors in a 4 x 4 Latin square design. Each fermentor was fed a to...

A Rational Reconstruction of the Kinetic Molecular Theory of Gases Based on History and Philosophy of Science and Its Implications for Chemistry Textbooks.

ERIC Educational Resources Information Center

Niaz, Mansoor

2000-01-01

Describes a study that was designed to develop a framework for examining the way in which chemistry textbooks describe the kinetic theory and related issues. The framework was developed by a rational reconstruction of the kinetic molecular theory of gases based on historians and philosophers of science. (Contains 102 references.)(Author/LRW)

Rational design of hierarchical ZnO@Carbon nanoflower for high performance lithium ion battery anodes

NASA Astrophysics Data System (ADS)

liu, Huichao; Shi, Ludi; Li, Dongzhi; Yu, Jiali; Zhang, Han-Ming; Ullah, Shahid; Yang, Bo; Li, Cuihua; Zhu, Caizhen; Xu, Jian

2018-05-01

The rational structure design and strong interfacial bonding are crucially desired for high performance zinc oxide (ZnO)/carbon composite electrodes. In this context, micro-nano secondary structure design and strong dopamine coating strategies are adopted for the fabrication of flower-like ZnO/carbon (ZnO@C nanoflowers) composite electrodes. The results show the ZnO@C nanoflowers (2-6 μm) are assembled by hierarchical ZnO nanosheets (∼27 nm) and continuous carbon framework. The micro-nano secondary architecture can facilitate the penetration of electrolyte, shorten lithium ions diffusion length, and hinder the aggregation of the nanosheets. Moreover, the strong chemical interaction between ZnO and coating carbon layer via C-Zn bond improves structure stability as well as the electronic conductivity. As a synergistic result, when evaluated as lithium ion batteries (LIBs) anode, the ZnO@C nanoflower electrodes show high reversible capacity of ca. 1200 mA h g-1 at 0.1 A g-1 after 80 cycles. As well as good long-cycling stability (638 and 420 mA h g-1 at 1 and 5 A g-1 after 500 cycles, respectively) and excellent rate capability. Therefore, this rational design of ZnO@C nanoflowers electrode is a promising anode for high-performance LIBs.

Rational Design Approach for Enhancing Higher-Mode Response of a Microcantilever in Vibro-Impacting Mode.

PubMed

Migliniene, Ieva; Ostasevicius, Vytautas; Gaidys, Rimvydas; Dauksevicius, Rolanas; Janusas, Giedrius; Jurenas, Vytautas; Krasauskas, Povilas

2017-12-12

This paper proposes an approach for designing an efficient vibration energy harvester based on a vibro-impacting piezoelectric microcantilever with a geometric shape that has been rationally modified in accordance with results of dynamic optimization. The design goal is to increase the amplitudes of higher-order vibration modes induced during the vibro-impact response of the piezoelectric transducer, thereby providing a means to improve the energy conversion efficiency and power output. A rational configuration of the energy harvester is proposed and it is demonstrated that the new design retains essential modal characteristics of the optimal microcantilever structures, further providing the added benefit of less costly fabrication. The effects of structural dynamics associated with advantageous exploitation of higher vibration modes are analyzed experimentally by means of laser vibrometry as well as numerically via transient simulations of microcantilever response to random excitation. Electrical characterization results indicate that the proposed harvester outperforms its conventional counterpart (based on the microcantilever of the constant cross-section) in terms of generated electrical output. Reported results may serve for the development of impact-type micropower generators with harvesting performance that is enhanced by virtue of self-excitation of large intensity higher-order mode responses when the piezoelectric transducer is subjected to relatively low-frequency excitation with strongly variable vibration magnitudes.

Estimation of parameters in rational reaction rates of molecular biological systems via weighted least squares

NASA Astrophysics Data System (ADS)

Wu, Fang-Xiang; Mu, Lei; Shi, Zhong-Ke

2010-01-01

The models of gene regulatory networks are often derived from statistical thermodynamics principle or Michaelis-Menten kinetics equation. As a result, the models contain rational reaction rates which are nonlinear in both parameters and states. It is challenging to estimate parameters nonlinear in a model although there have been many traditional nonlinear parameter estimation methods such as Gauss-Newton iteration method and its variants. In this article, we develop a two-step method to estimate the parameters in rational reaction rates of gene regulatory networks via weighted linear least squares. This method takes the special structure of rational reaction rates into consideration. That is, in the rational reaction rates, the numerator and the denominator are linear in parameters. By designing a special weight matrix for the linear least squares, parameters in the numerator and the denominator can be estimated by solving two linear least squares problems. The main advantage of the developed method is that it can produce the analytical solutions to the estimation of parameters in rational reaction rates which originally is nonlinear parameter estimation problem. The developed method is applied to a couple of gene regulatory networks. The simulation results show the superior performance over Gauss-Newton method.

Starlings uphold principles of economic rationality for delay and probability of reward.

PubMed

Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

2013-04-07

Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed.

Starlings uphold principles of economic rationality for delay and probability of reward

PubMed Central

Monteiro, Tiago; Vasconcelos, Marco; Kacelnik, Alex

2013-01-01

Rationality principles are the bedrock of normative theories of decision-making in biology and microeconomics, but whereas in microeconomics, consistent choice underlies the notion of utility; in biology, the assumption of consistent selective pressures justifies modelling decision mechanisms as if they were designed to maximize fitness. In either case, violations of consistency contradict expectations and attract theoretical interest. Reported violations of rationality in non-humans include intransitivity (i.e. circular preferences) and lack of independence of irrelevant alternatives (changes in relative preference between options when embedded in different choice sets), but the extent to which these observations truly represent breaches of rationality is debatable. We tested both principles with starlings (Sturnus vulgaris), training subjects either with five options differing in food delay (exp. 1) or with six options differing in reward probability (exp. 2), before letting them choose repeatedly one option out of several binary and trinary sets of options. The starlings conformed to economic rationality on both tests, showing strong stochastic transitivity and no violation of the independence principle. These results endorse the rational choice and optimality approaches used in behavioural ecology, and highlight the need for functional and mechanistic enquiring when apparent violations of such principles are observed. PMID:23390098

Mammalian designer cells: Engineering principles and biomedical applications.

PubMed

Xie, Mingqi; Fussenegger, Martin

2015-07-01

Biotechnology is a widely interdisciplinary field focusing on the use of living cells or organisms to solve established problems in medicine, food production and agriculture. Synthetic biology, the science of engineering complex biological systems that do not exist in nature, continues to provide the biotechnology industry with tools, technologies and intellectual property leading to improved cellular performance. One key aspect of synthetic biology is the engineering of deliberately reprogrammed designer cells whose behavior can be controlled over time and space. This review discusses the most commonly used techniques to engineer mammalian designer cells; while control elements acting on the transcriptional and translational levels of target gene expression determine the kinetic and dynamic profiles, coupling them to a variety of extracellular stimuli permits their remote control with user-defined trigger signals. Designer mammalian cells with novel or improved biological functions not only directly improve the production efficiency during biopharmaceutical manufacturing but also open the door for cell-based treatment strategies in molecular and translational medicine. In the future, the rational combination of multiple sets of designer cells could permit the construction and regulation of higher-order systems with increased complexity, thereby enabling the molecular reprogramming of tissues, organisms or even populations with highest precision. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress and Design Concerns of Nanostructured Solar Energy Harvesting Devices.

PubMed

Leung, Siu-Fung; Zhang, Qianpeng; Tavakoli, Mohammad Mahdi; He, Jin; Mo, Xiaoliang; Fan, Zhiyong

2016-05-01

Integrating devices with nanostructures is considered a promising strategy to improve the performance of solar energy harvesting devices such as photovoltaic (PV) devices and photo-electrochemical (PEC) solar water splitting devices. Extensive efforts have been exerted to improve the power conversion efficiencies (PCE) of such devices by utilizing novel nanostructures to revolutionize device structural designs. The thicknesses of light absorber and material consumption can be substantially reduced because of light trapping with nanostructures. Meanwhile, the utilization of nanostructures can also result in more effective carrier collection by shortening the photogenerated carrier collection path length. Nevertheless, performance optimization of nanostructured solar energy harvesting devices requires a rational design of various aspects of the nanostructures, such as their shape, aspect ratio, periodicity, etc. Without this, the utilization of nanostructures can lead to compromised device performance as the incorporation of these structures can result in defects and additional carrier recombination. The design guidelines of solar energy harvesting devices are summarized, including thin film non-uniformity on nanostructures, surface recombination, parasitic absorption, and the importance of uniform distribution of photo-generated carriers. A systematic view of the design concerns will assist better understanding of device physics and benefit the fabrication of high performance devices in the future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational approaches in the design of synthetic receptors - A review.

PubMed

Cowen, Todd; Karim, Kal; Piletsky, Sergey

2016-09-14

The rational design of molecularly imprinted polymers (MIPs) has been a major contributor to their reputation as "plastic antibodies" - high affinity robust synthetic receptors which can be optimally designed, and produced for a much reduced cost than their biological equivalents. Computational design has become a routine procedure in the production of MIPs, and has led to major advances in functional monomer screening, selection of cross-linker and solvent, optimisation of monomer(s)-template ratio and selectivity analysis. In this review the various computational methods will be discussed with reference to all the published relevant literature since the end of 2013, with each article described by the target molecule, the computational approach applied (whether molecular mechanics/molecular dynamics, semi-empirical quantum mechanics, ab initio quantum mechanics (Hartree-Fock, Møller-Plesset, etc.) or DFT) and the purpose for which they were used. Detailed analysis is given to novel techniques including analysis of polymer binding sites, the use of novel screening programs and simulations of MIP polymerisation reaction. The further advances in molecular modelling and computational design of synthetic receptors in particular will have serious impact on the future of nanotechnology and biotechnology, permitting the further translation of MIPs into the realms of analytics and medical technology. Copyright © 2016 Elsevier B.V. All rights reserved.

Appendix G : end region design models.

DOT National Transportation Integrated Search

2013-03-01

The 2007 AASHTO LRFD Bridge Design Specifications contain prescriptive : requirements for the quantity and placement of confinement reinforcement located in the bottom : flange of pretensioned concrete I-girders. This chapter proposes a rational mode...

Design, Synthesis and Affinity Properties of Biologically Active Peptide and Protein Conjugates of Cotton Cellulose

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

Edwards, J. V.; Goheen, Steven C.

The formation of peptide and protein conjugates of cellulose on cotton fabrics provides promising leads for the development of wound healing, antibacterial, and decontaminating textiles. An approach to the design, synthesis, and analysis of bioconjugates containing cellulose peptide and protein conjugates includes: 1) computer graphic modeling for a rationally designed structure; 2) attachment of the peptide or protein to cotton cellulose through a linker amino acid, and 3) characterization of the resulting bioconjugate. Computer graphic simulation of protein and peptide cellulose conjugates gives a rationally designed biopolymer to target synthetic modifications to the cotton cellulose. Techniques for preparing these typesmore » of conjugates involve both sequential assembly of the peptide on the fabric and direct crosslinking of the peptide or protein as cellulose bound esters or carboxymethylcellulose amides.« less

Supracolloidal fullerene-like cages: design principles and formation mechanisms.

PubMed

Li, Zhan-Wei; Zhu, You-Liang; Lu, Zhong-Yuan; Sun, Zhao-Yan

2016-11-30

How to create novel desired structures by rational design of building blocks represents a significant challenge in materials science. Here we report a conceptually new design principle for creating supracolloidal fullerene-like cages through the self-assembly of soft patchy particles interacting via directional nonbonded interactions by mimicking non-planar sp 2 hybridized carbon atoms in C 60 . Our numerical investigations demonstrate that the rational design of patch configuration, size, and interaction can drive soft three-patch particles to reversibly self-assemble into a vast collection of supracolloidal fullerene-like cages. We further elucidate the formation mechanisms of supracolloidal fullerene-like cages by analyzing the structural characteristics and the formation process. Our results provide conceptual and practical guidance towards the experimental realization of supracolloidal fullerene-like cages, as well as a new perspective on understanding the fullerene formation mechanisms.

Applying energy-conservation retrofits to standard Army buildings: Data analysis and recommendations. Final report

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

Westervelt, E.T.; Northup, G.R.; Lawrie, L.K.

1990-09-01

This report describes the data analysis and recommendations of a project demonstrating the energy performance of theoretically based retrofit packages on existing standard Army building at Fort Carson, CO. Four standard designs were investigated: a motor vehicle repair shop, the Type 64 (L-shaped) barracks, an enlisted personnel mess hall, and a two-company, rolling-pin-shaped barracks for enlisted personnel. The tested conservation measures included envelope and system modifications. Energy data were gathered and analyzed from 14 buildings. Based on measured savings and current costs of fuel and construction, none of the four original packages are life-cycle cost-effective at present, but two maymore » become effective in the near future. Of higher priority for energy and cost savings is the improvement of building operations, in particular heat production and distribution systems, which lack efficiency and control. Followup work at the L-shaped barracks yielded substantial savings, with a saving-to-investment ration of 5 to 1. Cost scenarios, energy models, and building were developed for the original retrofits to assess applicability elsewhere and in the future.« less

Investigating the Non-Covalent Functionalization and Chemical Transformation of Graphene

NASA Astrophysics Data System (ADS)

Sham, Chun-Hong

Trend in device miniatures demands capabilities to produce rationally designed patterns in ever-shrinking length scale. The research community has examined various techniques to push the current lithography resolution to sub-10nm scale. One of the ideas is to utilize the natural nanoscale patterns of molecular assemblies. In this thesis, the self-assembling phenomenon of a photoactive molecule on epitaxial graphene (EG) grown on SiC was discussed. This molecular assembly enables manipulation of chemical contrast in nanoscale through UV exposure or atomic layer deposition. Future development of nanoelectronics industry will be fueled by innovations in electronics materials, which could be discovered through covalent modification of graphene. In a study reported in this thesis, silicon is deposited onto EG. After annealing, a new surface reconstruction, identified to be (3x3)-SiC, was formed. Raman spectroscopy finds no signature of graphene after annealing, indicating a complete chemical transformation of graphene. DFT calculations reveal a possible conversion mechanism. Overall, these studies provide insights for future device miniaturization; contribute to the search of novel materials and help bridging the gap between graphene and current silicon-based industrial infrastructures.

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

PubMed Central

Unemo, Magnus

2014-01-01

SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. PMID:24982323

PROCESS DESIGN MANUAL: LAND TREATMENT OF MUNICIPAL WASTEWATER

EPA Science Inventory

The manual presents a rational procedure for the design of land treatment systems. Slow rate, rapid infiltration, and overland flow processes for the treatment of municipal wastewaters are discussed in detail, and the design concepts and criteria are presented. A two-phased plann...

The Benefits of saying YES!

ERIC Educational Resources Information Center

Ehrlich, Paul R.

1975-01-01

The author contends that scientists must learn to bear the risks they create and can not put voluntary safeguards and restrictions upon scientific research. Scientists must make rational decisions about future risks and be fully aware of the technological imperatives that must control human destiny. (BT)

The Future of Educational Media.

ERIC Educational Resources Information Center

Wason, Walter P.

Electronic media, particularly television, influence children to develop composite, plastic personalities striving after unreal goals, but the teacher can help children identify and develop rational goals and role models without completely abandoning media. Television has influenced children, and many adults, to create personalities assembled from…

Strategies for rational utilization of bituminous coal deposits in the German Federal Republic

NASA Astrophysics Data System (ADS)

Erasmus, F. C.; Lenhartz, R.

1980-09-01

The status and economic conditions for coal mining in the GFR are examined, and the production of the individual coal regions is reviewed. Exploratory work, conducted in the light of inevitable production increases in the future, is noted. Some changes in the present coal production and utilization strategies which may be needed to meet future requirements and at the same time optimize the mining procedures are discussed.

Climate change may affect fish through an interaction of parental and juvenile environments

NASA Astrophysics Data System (ADS)

Donelson, J. M.; Munday, P. L.; McCormick, M. I.

2012-09-01

Changes to tropical sea surface temperature and plankton communities are expected to occur over the next 100 years due to climate change. There is a limited understanding of how these environmental changes are likely to impact coral reef fishes, especially in terms of population replenishment through the quality of progeny produced. The present study investigated the effect that elevated sea water temperature and changes to food availability may have on the production of offspring by the reef fish Acanthochromis polyacanthus (Pomacentridae), as well as the performance of progeny in environments of varying food availability. An orthogonal design of three water temperatures and two food availabilities (high and low ration) was used, with water temperatures being the current-day average for the collection location (28.5 °C), +1.5 °C (30.0 °C) and +3.0 °C (31.5 °C), representing likely temperatures by 2100. Generally, an increase in the water temperature for adults resulted in a reduction in the size, weight and amount of yolk possessed by newly hatched offspring. Offspring whose parents were maintained under elevated temperature (30.0 °C high ration) had lower survival than offspring produced by parents at the current-day temperature (28.5 °C high ration) at 15 days post-hatching, but only when juveniles were reared under conditions of low food availability. In contrast, by 30 days post-hatching, the growth and condition of these offspring produced by parents held under elevated temperature (30.0 °C high ration) were the best of all treatment groups in all levels of juvenile food availability. This result illustrates the potential for initial parental effects to be modified by compensatory growth early in life (within 1 month) and that parental effects are not necessarily long lasting. These findings suggest that the performance of juvenile reef fish in future ocean conditions may not only depend on initial parental effects, but the interaction between their parentally mediated phenotype and their present food availability.

Economic theory and evidence on smoking behavior of adults.

PubMed

Sloan, Frank A; Wang, Yang

2008-11-01

To describe: (i) three alternative conceptual frameworks used by economists to study addictive behaviors: rational, imperfectly rational and irrational addiction; (ii) empirical economic evidence on each framework and specific channels to explain adult smoking matched to the frameworks; and (iii) policy implications for each framework. A systematic review and appraisal of important theoretical and empirical economic studies on smoking. There is some empirical support for each framework. For rational and imperfectly rational addiction there is some evidence that anticipated future cigarette prices influence current cigarette consumption, and quitting costs are high for smokers. Smokers are more risk-tolerant in the financial domain than are others and tend to attach a lower value to being in good health. Findings on differences in rates of time preference by smoking status are mixed; however, short-term rates are higher than long-term rates for both smokers and non-smokers, a stylized fact consistent with hyperbolic discounting. The economic literature lends no empirical support to the view that mature adults smoke because they underestimate the probability of harm to health from smoking. In support of the irrationality framework, smokers tend to be more impulsive than others in domains not related directly to smoking, implying that they may be sensitive to cues that trigger smoking. Much promising economic research uses the imperfectly rational addiction framework, but empirical research based on this framework is still in its infancy.

Nutrient digestibility and energy value of sheep rations differing in protein level, main protein source and non-forage fibre source.

PubMed

Milis, Ch; Liamadis, D

2008-02-01

Two in vivo digestion trials were conducted to evaluate the effects of diet's crude protein (CP) level, N degradability, and non-forage fibre source (NFFS) on nutrient digestibility and energy value of sheep rations. In each trial, rams were fed four isocaloric and isofibrous rations, differing in main protein and/or NFFS source. At the first trial, mean CP/metabolizable energy (ME) ratio of the diets was 17 g/MJ ME and at the second trial, 13 g/MJ ME. At both trials, the first ration contained cotton seed cake (CSC) and wheat bran (WB), the second CSC and corn gluten feed (CGF), the third corn gluten meal (CGM) and WB and the fourth CGM and CGF. Data of both trials were analysed in common as 2 x 2 x 2 factorial experimental design. Low N degradability (CGM) had positive effect on CP, neutral detergent fibre (NDF) and acid detergent fibre (ADF) digestibility of the ration. Those results suggest that an increase in rumen undegradable protein (RUP) content does not negatively affect nutrient digestibility of sheep rations. Corn gluten feed significantly elevated crude fibre (CF) digestibility, in comparison with WB. Rations having high CP/ME ratio had higher digestibility of CP in comparison with those having low CP/ME ratio; the opposite was true for ether extract, CF, NDF and ADF digestibilities. CP level x N degradability interaction negatively affected energy value of the rations that had high CP level and high N degradability. Former suggest that when CP content is high then N degradability should be low otherwise ration's ME is negatively affected. CP digestibility and coefficient q of the rations containing WB and having high N degradability (N degradability x NFFS interaction) were the lowest suggesting that the combination of CSC and WB negatively affected CP digestibility and energy value of the ration. This could be explained by a reduced microbial CP synthesis, or lower RUP digestibility or both.

Drought Water Rationing Necessitates an Equitable and Multidimensional Approach: Evidence from California

NASA Astrophysics Data System (ADS)

Ponce de Leon Barido, D.; Fildier, B.; Cucchi, K.

2016-12-01

Since 2011 many areas across California have experienced their driest years on record, with conditions barely improving since then. Reservoirs and snowpack water content have recorded some of the lowest measurements ever, with users (individuals, towns and cities) using groundwater to buffer the potentially devastating effects of the drought. Among other strategies, rationing has been one of they key interventions that the state has adopted to better manage its water resources. April 1st 2015 marked the first day in California's history when mandatory water reductions were instated statewide. By executive order, Governor Brown directed the State Water Resources Control Board to impose a 25% reduction on California's 400 local water supply agencies, which serve 90% of California residents. Since then, local agencies have been responsible for allocating restrictions to reduce water consumption and monitor compliance. A variety of research organizations and media outlets have begun exploring the equity considerations of the drought, but their analyses are often one-dimensional (water consumption per capita). Here we explore the multi-dimensional dynamics of rationing and drought in California using Census and California Water Resources Board data for over 300 communities in the state. We use data mining, parallel coordinates, and a nearest neighbors clustering algorithm to explore relationships between rationing and community spatial distribution, weather, drought related climate variables, economic sector employment, race, localized income inequality, household size, and income. The data suggests that there are nine distinct rationing groups across the state, that rationing was performed without taking into account the localized effects of the drought (hard hit communities rationing as much as less affected communities), that severely drought affected low-income communities (using SPI and SPEI 3 year indices) were asked to ration as much (and sometimes more) than less drought affected high-income communities, and that even after tight conservation standards on large consumers, high-income communities still consumed 30% more water per capita than low-income communities. We conclude with a suggested framework for how more equitable rationing could be implemented in the future.

Back to the future: Rational maps for exploring acetylcholine receptor space and time.

PubMed

Tessier, Christian J G; Emlaw, Johnathon R; Cao, Zhuo Qian; Pérez-Areales, F Javier; Salameh, Jean-Paul J; Prinston, Jethro E; McNulty, Melissa S; daCosta, Corrie J B

2017-11-01

Global functions of nicotinic acetylcholine receptors, such as subunit cooperativity and compatibility, likely emerge from a network of amino acid residues distributed across the entire pentameric complex. Identification of such networks has stymied traditional approaches to acetylcholine receptor structure and function, likely due to the cryptic interdependency of their underlying amino acid residues. An emerging evolutionary biochemistry approach, which traces the evolutionary history of acetylcholine receptor subunits, allows for rational mapping of acetylcholine receptor sequence space, and offers new hope for uncovering the amino acid origins of these enigmatic properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of rational emotive therapy (RET) with children: a critical re-appraisal.

PubMed

Gossette, R L; O'Brien, R M

1993-03-01

Proponents of rational-emotive therapy (RET) advocate its use within the school curriculum to forestall future maladjustment through the early detection and eradication of irrational beliefs. A review of 33 unpublished dissertations and four published reports found RET effective in about 25% of comparisons with wait-list, placebo, and other treatment conditions. The major effects of RET were changes in scores on self-report measures of irrational beliefs, less on emotional distress, and little or no change in behavior; essentially the same pattern of effects previously found in a similar analysis of RET in adult populations. Little justification was found for continued use of RET in schools.

That's not funny! - But it should be: effects of humorous emotion regulation on emotional experience and memory.

PubMed

Kugler, Lisa; Kuhbandner, Christof

2015-01-01

Previous research has shown that humorous reappraisal can reduce elicited negative emotions, suggesting that humor may be a functional strategy to cope with emotionally negative situations. However, the effect of humorous reappraisal on later memory about the emotion-eliciting situation is currently unknown, although this is crucial for more adaptive responding in future situations. To address this issue, we examined the effects of humorous reappraisal on both emotional experience and memory, compared to non-humorous rational reappraisal and a non-reappraisal control condition. Replicating previous findings, humorous reappraisal reduced evoked negative valence and arousal levels very effectively, and the down-regulation of experienced negative emotions was even more pronounced after humorous compared to rational reappraisal. Regarding later memory for emotion-eliciting stimuli, both humorous and rational reappraisal reduced free recall, but recognition memory was unaffected, with memory strength being stronger after humorous than after rational reappraisal. These results indicate that humor seems to be indeed an optimal strategy to cope with negative situations because humor can help us to feel better when confronted with negative stimuli, but still allows us to retrieve stimulus information later when afforded to do so by the presence of appropriate contextual features.

Rational subjects, marriage counselling and the conundrums of eugenics.

PubMed

Gerodetti, Natalia

2008-06-01

Against the background of degeneration and the perceived threat to the nation's health and stock, family politics came to constitute an important site for eugenic discourses and interventions. Eugenic regulation of reproductive sexuality and marriage was not only pursued through 'negative' eugenics but also through educational policies targeted at young adults and youth. Switzerland serves as a useful case to explore a general idea, namely the limitations for eugenicists of exploiting the concept of a rational subject in order to achieve their ends. Practices of 'positive eugenics' crucially hinged on the utilitarian principle of rationality underpinning positive eugenics which this paper seeks to elaborate. Eugenicists devised tools to deal efficiently with social problems on a collective as well as an individual basis by deploying technologies of government which conceived individuals to be members of a population who were each held responsible for the generation of healthy future generations. As a form of 'sustaining, multiplying and ordering life' eugenics thus relied on the premise that its ideas would be adopted through an appeal to rationality and, where this was insufficient, through a series of coercive measures. Relying on conviction and education about the merits of eugenics, however, posed particular problems to positive eugenic thinking and practice.

Suggestions for Library Network Design.

ERIC Educational Resources Information Center

Salton, Gerald

1979-01-01

Various approaches to the design of automatic library systems are described, suggestions for the design of rational and effective automated library processes are posed, and an attempt is made to assess the importance and effect of library network systems on library operations and library effectiveness. (Author/CWM)

The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

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

Makabe, Koki; Koide, Shohei

2009-06-17

Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success ofmore » the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.« less

Research of Acoustic Properties of Materials with the Purpose of Their Use at Design of Special Noise Protective Clothes for Oil and Gas Industry

NASA Astrophysics Data System (ADS)

Drofa, E. A.; Lipilina, E. Yu

2018-01-01

The article is devoted to the substantiation of the choice of a rational package of materials, which has the greatest noise-protective properties when designing special clothes with reference to the oil and gas industry. Studies were conducted to assess the factors that have the most significant effect on the noise-protective properties of clothing. Conclusions are made about the possibility of using the developed technique for studying the noise-protective properties of materials in selecting rational packages of materials for the production of special clothes with high noise-protective properties.

Game among interdependent networks: The impact of rationality on system robustness

NASA Astrophysics Data System (ADS)

Fan, Yuhang; Cao, Gongze; He, Shibo; Chen, Jiming; Sun, Youxian

2016-12-01

Many real-world systems are composed of interdependent networks that rely on one another. Such networks are typically designed and operated by different entities, who aim at maximizing their own payoffs. There exists a game among these entities when designing their own networks. In this paper, we study the game investigating how the rational behaviors of entities impact the system robustness. We first introduce a mathematical model to quantify the interacting payoffs among varying entities. Then we study the Nash equilibrium of the game and compare it with the optimal social welfare. We reveal that the cooperation among different entities can be reached to maximize the social welfare in continuous game only when the average degree of each network is constant. Therefore, the huge gap between Nash equilibrium and optimal social welfare generally exists. The rationality of entities makes the system inherently deficient and even renders it extremely vulnerable in some cases. We analyze our model for two concrete systems with continuous strategy space and discrete strategy space, respectively. Furthermore, we uncover some factors (such as weakening coupled strength of interdependent networks, designing a suitable topology dependence of the system) that help reduce the gap and the system vulnerability.

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

PubMed

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

Assessing the Needs of Adults for Continuing Education: A Model.

ERIC Educational Resources Information Center

Moore, Donald E., Jr.

1980-01-01

Reviews the needs assessment studies described in this journal issue. Concludes that (1) lessons from completed needs assessments can help continuing education practitioners plan and conduct future studies, and (2) a rational, need-reduction, decision-making approach can improve continuing education programs. (CT)

Indigenous Intelligence: Have We Lost Our Indigenous Mind?

ERIC Educational Resources Information Center

Dumont, Jim

2002-01-01

Eurocentric intelligence is restricted to rational, linear, competitive, and hierarchical thinking. Indigenous intelligence encompasses the body, mind, heart, and experience in total responsiveness and total relationship to the whole environment, which includes the seven generations past and future. Implementation of major changes to indigenous…

[Utilization suitability of forest resources in typical forest zone of Changbai Mountains].

PubMed

Hao, Zhanqing; Yu, Deyong; Xiong, Zaiping; Ye, Ji

2004-10-01

Conservation of natural forest does not simply equal to no logging. The Northeast China Forest Region has a logging quota of mature forest as part of natural forest conservation project. How to determine the logging spots rationally and scientifically is very important. Recent scientific theories of forest resources management advocate that the utilization of forest resources should stick to the principle of sustaining use, and pay attention to the ecological function of forest resources. According to the logging standards, RS and GIS techniques can be used to detect the precise location of forest resources and obtain information of forest areas and types, and thus, provide more rational and scientific support for space choice about future utilization of forest resources. In this paper, the Lushuihe Forest Bureau was selected as a typical case in Changbai Mountains Forest Region to assess the utilization conditions of forest resources, and some advices on spatial choice for future management of forest resources in the study area were offered.

Relation of knowledge and level of education to the rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta

NASA Astrophysics Data System (ADS)

Dania, H.; Ihsan, M. N.

2017-11-01

Self-medication as an alternative is used to reduce the severity of diarrhea. Optimal treatment can be done by increasing the rationalization of self-medication on diarrhea. This can be achieved with good knowledge about self-medication, which is in turn influenced by level of education. The aim of this study was to determine the relationship of knowledge and education level to rationality of self-medication on childhood diarrhea around the Code River in Jogoyudan, Jetis, Yogyakarta. The study was conducted by cross-sectional analytical observational design. The subjects were mothers who had children aged 2-11 years who had experienced diarrhea and had self-medication. Questionnaires were used to assess the rationality of self-medication on children's diarrhea by the parents. The respondents were askeds to fill out about indications, right drugs, doses, time intervals and periods of drug administration. Data were analyzed using chi- square. It was showed that of 40 respondents, 14 respondents (35%) performed rational self-medication on children's diarrhea and 26 respondents (65%). did not rationalize the treatment. The results of a bivariate test obtained a chi-square value of 9.808 (> 3.841) and a p value of 0.002 (<0.05) on the relationship between education level and rationality of self-medication and a chi-square value of 19.476 (> 3.841) and a p value of 0.000 (<0.05) on relationship between knowledge and rationality of self- medication. The conclusion of this study is that there is a correlation between knowledge and level of education and rationality of self-medication on childhood diarrhea on the Code River banks in Jogoyudan, Jetis, Yogyakarta.

Factors related to rational antibiotic prescriptions in community health centers in Depok City, Indonesia.

PubMed

Andrajati, Retnosari; Tilaqza, Andri; Supardi, Sudibyo

Irrational antibiotic prescription is common in developing countries, including in Indonesia. The aims of this study were to evaluate antibiotic prescription patterns and the factors related to the rationale for antibiotic prescriptions in community health centers in Depok City, Indonesia. The study employed a cross-sectional design in eleven primary health centers in Depok City, Indonesia. The sample consisted of 28 physicians and 788 oral antibiotic prescriptions, 392 of which were evaluated for rationality according to local guidelines issued by the Ministry of Health Republic of Indonesia from October to December 2012. Data were analyzed with chi-square tests and logistic regression analysis. The most widely prescribed antibiotics were amoxicillin (73.5%) and co-trimoxazole (17.4%). The most frequent diseases were acute pharyngitis (40.2%) and non-specific respiratory infection (25.4%). Approximately 220 of the 392 prescriptions did not meet the criteria for rational antibiotic prescriptions with regard to antibiotic selection (22.7%), duration of administration (72.3%), frequency of administration (3.2%), or duration and frequency of administration (1.8%). Physicians who had attended training for rational drug use were 2.01 times more rational than physicians who had never attended training. Physicians with a short working period (i.e., <7 years) were 3.95 times more rational in prescribing antibiotics than physicians who had been working for longer periods (i.e., >7 years). Most antibiotics were prescribed irrationally. Training for rational drug use and length of practice were factors related to the rationality of antibiotic prescriptions. Suitable interventions are urgently required to encourage the rational prescription of antibiotics in the PHCs. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Effect of Chicken Bone Meal as Phosphorus Supplement on Blood Metabolites in Fattening Lambs

NASA Astrophysics Data System (ADS)

Pujiastuti, A.; Muktiani, A.

2018-02-01

The aim of this study was to evaluate the effect of chicken bone meal (CBM) as phosphorus supplementon blood metabolites in fattening lambs. The experiment used 16 of 12 months old local male lambs with initial body weight 27.01 ± 1.51 kg. The experiment used a complete randomized design with 4 treatments and 4 replications. The treatments were T0 (basal ration = native grass + soybean curd waste), T1 (basal ration + 0.49% P Dicalcium phosphate), T2 (basal ration + 0.70% P CBM), T3 (basal ration + 1.39 % P CBM). The results indicated that CBM as phosphorus supplement was significantly different (P<0,05) on P intake, phosphorus and glucose serum and did not different significantly on dry matter intake and alkaline phosphatase activity. In conclusion, CBM is one of requirement organic phosphorus supplement which can be applied on ruminants.

Rationality and antiemotionality as a risk factor for cancer: concept differentiation.

PubMed

van der Ploeg, H M; Kleijn, W C; Mook, J; van Donge, M; Pieters, A M; Leer, J W

1989-01-01

Control and repression of emotions may be coping styles or personality characteristics found more often in patients with cancer than in other patients and healthy subjects. Previous research indicated a possible relationship between high scores on a 'rationality and antiemotionality' scale and cancer. In the two studies reported, the psychometric properties of this scale and the meaning of the concept as a personality variable related to the control of emotions were investigated. It was found that the internal consistency of the scale could be improved by re-designing it into a personality inventory. Factor analysis repeatedly yielded more than one factor, indicating the complexity of the concept. 'Rationality and antiemotionality' seems related to the control, suppression or repression of anger. Our findings tentatively support the view that rationality and antiemotionality may be an important distinctive personality characteristic in patients with cancer.

Advanced electrolyte/additive for lithium-ion batteries with silicon anode

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

Zhang, Shuo; He, Meinan; Su, Chi-Cheung

State-of-the-art lithium-ion batteries (LIBs) are based on a lithium transition metal oxide cathode, a graphite anode and a nonaqueous carbonate electrolyte. To further increase the energy and power density of LIBs, silicon anodes have been intensively explored due to their high theoretical capacity, low operation potential, and low cost. However, the main challenges for Si anode are the large volume change during lithiation/delithiation process and the instability of the solid-electrolyte-interphase associated with this process. Recently, significant progress has been achieved via advanced material fabrication technologies and rational electrolyte design in terms of improving the Coulombic efficiency and capacity retention. Inmore » this paper, new developments in advanced electrolyte and additive for LIBs with Si anode were systematically reviewed, and perspectives over future research were suggested.« less

A bio-synthetic interface for discovery of viral entry mechanisms.

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

Gutzler, Mike; Maar, Dianna; Negrete, Oscar

2010-09-01

Understanding and defending against pathogenic viruses is an important public health and biodefense challenge. The focus of our LDRD project has been to uncover the mechanisms enveloped viruses use to identify and invade host cells. We have constructed interfaces between viral particles and synthetic lipid bilayers. This approach provides a minimal setting for investigating the initial events of host-virus interaction - (i) recognition of, and (ii) entry into the host via membrane fusion. This understanding could enable rational design of therapeutics that block viral entry as well as future construction of synthetic, non-proliferating sensors that detect live virus in themore » environment. We have observed fusion between synthetic lipid vesicles and Vesicular Stomatitis virus particles, and we have observed interactions between Nipah virus-like particles and supported lipid bilayers and giant unilamellar vesicles.« less

The Effect of Molecular Diagnostics on the Treatment of Glioma.

PubMed

Bush, Nancy Ann Oberheim; Butowski, Nicholas

2017-04-01

This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient.

Catalyst–substrate interaction and growth delay in vapor–liquid–solid nanowire growth

NASA Astrophysics Data System (ADS)

Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

2018-05-01

Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

Catalyst-substrate interaction and growth delay in vapor-liquid-solid nanowire growth.

PubMed

Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

2018-05-18

Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

Counterion Size and Nature Control Structural and Mechanical Response in Cellulose Nanofibril Nanopapers.

PubMed

Benítez, Alejandro J; Walther, Andreas

2017-05-08

Nanopapers formed from aqueous dispersions of cellulose nanofibrils (CNFs) combine stiffness, strength, and toughness. Yet, delicate interactions operate between the CNFs during nanopaper formation and mechanical deformation. We unravel in detail how counterions, being either of the organic alkyl ammonium kind (NR 4 + ) or of the earth metal series (Li + , Na + , Cs + ), need to be chosen to achieve outstanding combinations of stiffness, strength, and toughness, extending to previously unreached territories. We relate structure formation processes in terms of colloidal stabilization to nanostructural details such as porosity and ability for swelling, as well as to interfibrillar interactions in bulk and macroscale mechanical properties. We demonstrate that our understanding also leads to new levels of ductility in bioinspired CNF/polymer nanocomposites at high levels of reinforcements. These results contribute to future rational design of CNF-based high-performance materials.

The best of both worlds: reaping the benefits from mammalian and bacterial therapeutic circuits.

PubMed

Bojar, Daniel; Fussenegger, Martin

2016-10-01

Synthetic biology has revolutionized the field of biology in the last two decades. By taking apart natural systems and recombining engineered parts in novel constellations, it has not only unlocked a staggering variety of biological control mechanisms but it has also created a panoply of biomedical achievements, such as innovative diagnostics and therapies. The most common mode of action in the field of synthetic biology is mediated by synthetic gene circuits assembled in a systematic and rational manner. This review covers the most recent therapeutic gene circuits implemented in mammalian and bacterial cells designed for the diagnosis and therapy of an extensive array of diseases. Highlighting new tools for therapeutic gene circuits, we describe a future that holds a plethora of potentialities for the medicine of tomorrow. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endoradiotherapy in cancer treatment--basic concepts and future trends.

PubMed

Zoller, Frederic; Eisenhut, Michael; Haberkorn, Uwe; Mier, Walter

2009-12-25

Endoradiotherapy represents an alternative therapeutic method in cancer treatment with advantageous features compared to chemotherapy and radiation therapy. Intelligent dose delivery concepts using small drugs, peptides or antibodies as radionuclide carriers enable the verification of a selective accumulation in the tumour lesion and to reduce radiation toxicity for the peripheral organs. The development of endoradiotherapeutic agents, especially chelator-conjugated biomolecules, for example ibritumomab tiuxetan or DOTATOC, gains importance due to the stable complexation of versatile radiometals, such as (90)Y or (177)Lu. The rational design of novel target binding sides and their grafting into a drug scaffold is a highly promising strategy, which may promote further implication in endoradiotherapy. This review highlights the basic concepts of endoradiotherapy and discusses the potential of targeted therapy and the properties of energy-rich particles emitted by radionuclides for tumour therapy.

Oleoplaning droplets on lubricated surfaces

NASA Astrophysics Data System (ADS)

Daniel, Dan; Timonen, Jaakko V. I.; Li, Ruoping; Velling, Seneca J.; Aizenberg, Joanna

2017-10-01

Recently, there has been much interest in using lubricated surfaces to achieve extreme liquid repellency: a foreign droplet immiscible with the underlying lubricant layer was shown to slide off at a small tilt angle <5°. This behaviour was hypothesized to arise from a thin lubricant overlayer film sandwiched between the droplet and solid substrate, but this has not been observed experimentally. Here, using thin-film interference, we are able to visualize the intercalated film under both static and dynamic conditions. We further demonstrate that for a moving droplet, the film thickness follows the Landau-Levich-Derjaguin law. The droplet is therefore oleoplaning--akin to tyres hydroplaning on a wet road--with minimal dissipative force and no contact line pinning. The techniques and insights presented in this study will inform future work on the fundamentals of wetting for lubricated surfaces and enable their rational design.

Surface-Enhanced Raman Scattering Spectroscopy for Label-Free Analysis of P. aeruginosa Quorum Sensing

PubMed Central

Bodelón, Gustavo; Montes-García, Verónica; Pérez-Juste, Jorge; Pastoriza-Santos, Isabel

2018-01-01

Bacterial quorum sensing systems regulate the production of an ample variety of bioactive extracellular compounds that are involved in interspecies microbial interactions and in the interplay between the microbes and their hosts. The development of new approaches for enabling chemical detection of such cellular activities is important in order to gain new insight into their function and biological significance. In recent years, surface-enhanced Raman scattering (SERS) spectroscopy has emerged as an ultrasensitive analytical tool employing rationally designed plasmonic nanostructured substrates. This review highlights recent advances of SERS spectroscopy for label-free detection and imaging of quorum sensing-regulated processes in the human opportunistic pathogen Pseudomonas aeruginosa. We also briefly describe the challenges and limitations of the technique and conclude with a summary of future prospects for the field. PMID:29868499

Linking patient satisfaction with nursing care: the case of care rationing - a correlational study

PubMed Central

2014-01-01

Background Implicit rationing of nursing care is the withholding of or failure to carry out all necessary nursing measures due to lack of resources. There is evidence supporting a link between rationing of nursing care, nurses’ perceptions of their professional environment, negative patient outcomes, and placing patient safety at risk. The aims of the study were: a) To explore whether patient satisfaction is linked to nurse-reported rationing of nursing care and to nurses’ perceptions of their practice environment while adjusting for patient and nurse characteristics. b) To identify the threshold score of rationing by comparing the level of patient satisfaction factors across rationing levels. Methods A descriptive, correlational design was employed. Participants in this study included 352 patients and 318 nurses from ten medical and surgical units of five general hospitals. Three measurement instruments were used: the BERNCA scale for rationing of care, the RPPE scale to explore nurses’ perceptions of their work environment and the Patient Satisfaction scale to assess the level of patient satisfaction with nursing care. The statistical analysis included the use of Kendall’s correlation coefficient to explore a possible relationship between the variables and multiple regression analysis to assess the effects of implicit rationing of nursing care together with organizational characteristics on patient satisfaction. Results The mean score of implicit rationing of nursing care was 0.83 (SD = 0.52, range = 0–3), the overall mean of RPPE was 2.76 (SD = 0.32, range = 1.28 – 3.69) and the two scales were significantly correlated (τ = −0.234, p < 0.001). The regression analysis showed that care rationing and work environment were related to patient satisfaction, even after controlling for nurse and patient characteristics. The results from the adjusted regression models showed that even at the lowest level of rationing (i.e. 0.5) patients indicated low satisfaction. Conclusions The results support the relationships between organizational and environmental variables, care rationing and patient satisfaction. The identification of thresholds at which rationing starts to influence patient outcomes in a negative way may allow nurse managers to introduce interventions so as to keep rationing at a level at which patient safety is not jeopardized. PMID:25285040

Rational design for multifunctional non-liposomal lipid-based nanocarriers for cancer management: theory to practice

PubMed Central

2013-01-01

Nanomedicines have gained more and more attention in cancer therapy thanks to their ability to enhance the tumour accumulation and the intracellular uptake of drugs while reducing their inactivation and toxicity. In parallel, nanocarriers have been successfully employed as diagnostic tools increasing imaging resolution holding great promises both in preclinical research and in clinical settings. Lipid-based nanocarriers are a class of biocompatible and biodegradable vehicles that provide advanced delivery of therapeutic and imaging agents, improving pharmacokinetic profile and safety. One of most promising engineering challenges is the design of innovative and versatile multifunctional targeted nanotechnologies for cancer treatment and diagnosis. This review aims to highlight rational approaches to design multifunctional non liposomal lipid-based nanocarriers providing an update of literature in this field. PMID:24564841

Epidemiological, Serological, and Virological Features of Dengue in Nha Trang City, Vietnam

PubMed Central

Quyen, Duong Le; Thanh Le, Nguyen; Van Anh, Cao Thi; Nguyen, Nguyen Binh; Hoang, Dong Van; Montgomery, Jacqui L.; Kutcher, Simon C.; Hoang Le, Nguyen; Hien, Nguyen Tran; Hue Kien, Duong Thi; Rabaa, Maia; O’Neill, Scott L.; Simmons, Cameron P.; Anh, Dang Duc; Anders, Katherine L.

2018-01-01

Abstract. Vietnam is endemic for dengue. We conducted a series of retrospective and prospective studies to characterize the epidemiology of dengue and population mobility patterns in Nha Trang city, Vietnam, with a view to rational design of trials of community-level interventions. A 10-year time series of dengue case notifications showed pronounced interannual variability, as well as spatial heterogeneity in ward-level dengue incidence (median annual coefficient of variation k = 0.47). Of 451 children aged 1–10 years enrolled in a cross-sectional serosurvey, almost one-third had evidence of a past dengue virus (DENV) infection, with older children more likely to have a multitypic response indicative of past exposure to ≥ 1 serotype. All four DENV serotypes were detected in hospitalized patients during 8 months of sampling in 2015. Mobility data collected from 1,000 children and young adults via prospective travel diaries showed that, although all ages spent approximately half of their daytime hours (5:00 am–9:00 pm) at home, younger age groups (≤ 14 years) spent a significantly greater proportion of their time within 500 m of home than older respondents. Together these findings inform the rational design of future trials of dengue preventive interventions in this setting by identifying 1) children < 7 years as an optimal target group for a flavivirus-naive serological cohort, 2) children and young adults as the predominant patient population for a study with a clinical end point of symptomatic dengue, and 3) substantial spatial and temporal variations in DENV transmission, with a consequent requirement for a trial to be large enough and of long enough duration to overcome this heterogeneity. PMID:29313471

Optogenetically inspired deep brain stimulation: linking basic with clinical research.

PubMed

Lüscher, Christian; Pollak, Pierre

2016-01-01

In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.

Structure-Based Rational Design of Novel Inhibitors Against Fructose-1,6-Bisphosphate Aldolase from Candida albicans.

PubMed

Han, Xinya; Zhu, Xiuyun; Hong, Zongqin; Wei, Lin; Ren, Yanliang; Wan, Fen; Zhu, Shuaihua; Peng, Hao; Guo, Li; Rao, Li; Feng, Lingling; Wan, Jian

2017-06-26

Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In this study, several novel inhibitors of FBA-II from C. albicans (Ca-FBA-II) with potent antifungal effects were rationally designed by jointly using a specific protocols of molecular docking-based virtual screening, accurate binding-conformation evaluation strategy, synthesis and enzymatic assays. The enzymatic assays reveal that the compounds 3c, 3e-g, 3j and 3k exhibit high inhibitory activity against Ca-FBA-II (IC 50 < 10 μM), and the most potential inhibitor is 3g, with IC 50 value of 2.7 μM. Importantly, the compounds 3f, 3g, and 3l possess not only high inhibitions against Ca-FBA-II, but also moderate antifungal activities against C. glabrata (MIC 80 = 4-64 μg/mL). The compounds 3g, 3l, and 3k in combination with fluconazole (8 μg/mL) displayed significantly synergistic antifungal activities (MIC 80 < 0.0625 μg/mL) against resistant Candida strains, which are resistant to azoles drugs. The probable binding modes between 3g and the active site of Ca-FBA-II have been proposed by using the DOX (docking, ONIOM, and XO) strategy. To our knowledge, no FBA-II inhibitors with antifungal activities against wild type and resistant strains from Candida were reported previously. The positive results suggest that the strategy adopted in this study are a promising method for the discovery of novel drugs against azole-resistant fungal pathogens in the future.

Design Principles for Covalent Organic Frameworks as Efficient Electrocatalysts in Clean Energy Conversion and Green Oxidizer Production.

PubMed

Lin, Chun-Yu; Zhang, Lipeng; Zhao, Zhenghang; Xia, Zhenhai

2017-05-01

Covalent organic frameworks (COFs), an emerging class of framework materials linked by covalent bonds, hold potential for various applications such as efficient electrocatalysts, photovoltaics, and sensors. To rationally design COF-based electrocatalysts for oxygen reduction and evolution reactions in fuel cells and metal-air batteries, activity descriptors, derived from orbital energy and bonding structures, are identified with the first-principle calculations for the COFs, which correlate COF structures with their catalytic activities. The calculations also predict that alkaline-earth metal-porphyrin COFs could catalyze the direct production of H 2 O 2 , a green oxidizer and an energy carrier. These predictions are supported by experimental data, and the design principles derived from the descriptors provide an approach for rational design of new electrocatalysts for both clean energy conversion and green oxidizer production. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nonlinear machine learning and design of reconfigurable digital colloids.

PubMed

Long, Andrew W; Phillips, Carolyn L; Jankowksi, Eric; Ferguson, Andrew L

2016-09-14

Digital colloids, a cluster of freely rotating "halo" particles tethered to the surface of a central particle, were recently proposed as ultra-high density memory elements for information storage. Rational design of these digital colloids for memory storage applications requires a quantitative understanding of the thermodynamic and kinetic stability of the configurational states within which information is stored. We apply nonlinear machine learning to Brownian dynamics simulations of these digital colloids to extract the low-dimensional intrinsic manifold governing digital colloid morphology, thermodynamics, and kinetics. By modulating the relative size ratio between halo particles and central particles, we investigate the size-dependent configurational stability and transition kinetics for the 2-state tetrahedral (N = 4) and 30-state octahedral (N = 6) digital colloids. We demonstrate the use of this framework to guide the rational design of a memory storage element to hold a block of text that trades off the competing design criteria of memory addressability and volatility.

Forecasting The Future Of The Islamic State: An Agent Based Rational Choice Model And Social Network Analysis Approach

DTIC Science & Technology

2017-12-01

Mesquita, B., Smith, A., Siverson, M. R., & Morrow, D. J . (2005). The logic of political survival. Cambridge, MA: MIT Press. Bunzel, C . (2015). From...communications-legacy-is-here-to-stay/ Clarke, P. C ., Jackson, K., Johnston, B. P., Robinson, E., & Shatz, J . H. (2017). Financial futures of the...Cunningham, C . F., & Braithwaite, J . (2013). Bridges, brokers and boundary spanners in collaborative networks: A systematic review. BMC Health Services

Economic modeling of the rational consumption of addictive substances.

PubMed

Ferguson, Brian S

2006-01-01

This article gives an overview of the way economists model the decision to consume addictive commodities and reviews some of the relevant literature testing aspects of the model. It aims to answer the question of how it is that economists can speak of the consumption of addictive harmful commodities as a rational decision. Health economics treats the consumption of commodities that have beneficial (or harmful) effects on health, and therefore on utility or well-being, as intertemporal decisions with regard to investment decisions. In investment in health, the payoff to an action comes appreciably later than the action itself. The decision to consume harmful, and even addictive, commodities fits into the investment in health framework, with the benefit comes now, in the form of the pleasure derived from consuming them, and the costs, in terms of damage to the individual's health, comes later. The value that a person places on the future vs. the present is called time preference or subjective rate of time discounting, which represents the weight he places on the future relative to the present when he makes decisions that have future consequences. The more they discount the future, the more myopic they are and the more likely to undertake risky behaviors, including smoking or using drugs such as amphetamines or heroin, as well as dropping out of school or taking on high risk jobs.

Rational optimization of drug-target residence time: Insights from inhibitor binding to the S. aureus FabI enzyme-product complex

PubMed Central

Chang, Andrew; Schiebel, Johannes; Yu, Weixuan; Bommineni, Gopal R.; Pan, Pan; Baxter, Michael V.; Khanna, Avinash; Sotriffer, Christoph A.; Kisker, Caroline; Tonge, Peter J.

2013-01-01

Drug-target kinetics has recently emerged as an especially important facet of the drug discovery process. In particular, prolonged drug-target residence times may confer enhanced efficacy and selectivity in the open in vivo system. However, the lack of accurate kinetic and structural data for series of congeneric compounds hinders the rational design of inhibitors with decreased off-rates. Therefore, we chose the Staphylococcus aureus enoyl-ACP reductase (saFabI) - an important target for the development of new anti-staphylococcal drugs - as a model system to rationalize and optimize the drug-target residence time on a structural basis. Using our new, efficient and widely applicable mechanistically informed kinetic approach, we obtained a full characterization of saFabI inhibition by a series of 20 diphenyl ethers complemented by a collection of 9 saFabI-inhibitor crystal structures. We identified a strong correlation between the affinities of the investigated saFabI diphenyl ether inhibitors and their corresponding residence times, which can be rationalized on a structural basis. Due to its favorable interactions with the enzyme, the residence time of our most potent compound exceeds 10 hours. In addition, we found that affinity and residence time in this system can be significantly enhanced by modifications predictable by a careful consideration of catalysis. Our study provides a blueprint for investigating and prolonging drug-target kinetics and may aid in the rational design of long-residence-time inhibitors targeting the essential saFabI enzyme. PMID:23697754

Chronic sublethal effects of San Francisco Bay sediments on nereis (neanthes) arenaceodentata; effect of food ration on sediment toxicity. Final report

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

Moore, D.W.; Dillon, T.M.

1993-09-01

This report is designed to address concerns regarding the effect of food ration on toxicity during chronic sublethal sediment bioassays. To this end, a contaminated San Francisco Bay sediment and a clean control sediment were evaluated in a chronic sublethal test under a series of different food rations, with the marine polychaete worm Nereis (Neanthes) arenaceodentata. Animals were exposed from early juvenile stage through the onset of gametogenesis. Treatments were 2.OX, 1.OX, 0.5X, and 0.25X where X is the recommended food ration for laboratory cultures. Test end points were survival, growth, and reproduction. The contaminated sediment was a composite ofmore » several cores taken to project depth (38 ft (11.6 m) below mean low water mark) from an area in Oakland Inner Harbor known to be contaminated with polycyclic aromatic hydrocarbons and metals. Comparisons were made with a clean control sediment. The control sediment is used in the laboratory cultures of N. arenaceodentata and was collected from Sequim, WA. Mean percent survival of Neanthes was high (>90 percent) in both the contaminated and control sediment across all food ration treatments. Individual wet weights were significantly reduced with decreasing food ration in both contaminated and control sediments. Significant differences in wet weight between sediment types were observed at the 1.OX, 0.5X, and 0.25X rations. Reproduction (fecundity and emergent juvenile (EJ) production) was also Chronic sublethal, Neanthes, Dredged material, San Francisco Bay, Food ration, Sediment.« less

Male Youth Perceptions of Violent Extremism: towards a Test of Rational Choice Theory.

PubMed

Dhami, Mandeep K; Murray, Jennifer

2016-09-20

Understanding how people perceive the pros and cons of risky behaviors such as terrorism or violent extremism represents a first step in developing research testing rational choice theory aiming to explain and predict peoples' intentions to engage in, or support, these behaviors. Accordingly, the present study provides a qualitative, exploratory analysis of a sample of 57 male youths' perceptions of the benefits and drawbacks of: (a) accessing a violent extremist website, (b) joining a violent extremist group, and (c) leaving such a group. Youth perceived significantly more drawbacks than benefits of joining a violent extremist group (p = .001, d = .46) and accessing a violent extremist website (p = .001, d = .46). The perceived benefits of engagement referred to gaining knowledge/awareness, being part of a group/similar people, and fighting the enemy/for a cause. The drawbacks referred to being exposed to negative material and emotions, having violent/criminal beliefs and behaviors, and getting in trouble with the law. The perceived benefits of disengagement referred to no longer committing illegal acts, and regaining independence/not being manipulated. The drawbacks referred to exposing oneself to harm and reprisal. These findings provide an insight into how male youth think about (dis)engagement in violent extremism, and can inform future quantitative research designed to explain and predict (dis)engagement in violent extremism. Eventually, such research may inform the development of evidence-based prevention and intervention strategies.

Design of a small molecule against an oncogenic noncoding RNA

PubMed Central

Velagapudi, Sai Pradeep; Cameron, Michael D.; Haga, Christopher L.; Rosenberg, Laura H.; Lafitte, Marie; Duckett, Derek R.; Phinney, Donald G.; Disney, Matthew D.

2016-01-01

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif–small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm. PMID:27170187

Should Quality School Education Be a Kaizen (Improvement) or an Innovation?

ERIC Educational Resources Information Center

Sun-Keung Pang, Nicholas

1998-01-01

Reviews Hong Kong's School Management Initiative implementation strategies (rational-empirical, power-coercive, and normative-reeducative), compares them with New South Wales, Australia's strategies, and suggests an appropriate strategy for future reforms. In Australia, changes were radical and thorough (using power-coercive strategies), whereas…

Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design

PubMed Central

Li, Jianguo; Koh, Jun-Jie; Liu, Shouping; Lakshminarayanan, Rajamani; Verma, Chandra S.; Beuerman, Roger W.

2017-01-01

Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress. Technological developments are now enabling multidisciplinary approaches including molecular dynamics simulations combined with biophysics and microbiology toward providing valuable insights into the interactions of AMPs with membranes at atomic level. This has led to increasingly robust models of the mechanisms of action of AMPs and has begun to contribute meaningfully toward the discovery of new AMPs. This review discusses the detailed action mechanisms that have been put forward, with detailed atomistic insights into how the AMPs interact with bacterial membranes. The review further discusses how this knowledge is exploited toward developing design principles for novel AMPs. Finally, the current status, associated challenges, and future directions for the development of AMP therapeutics are discussed. PMID:28261050

Programmable single-cell mammalian biocomputers.

PubMed

Ausländer, Simon; Ausländer, David; Müller, Marius; Wieland, Markus; Fussenegger, Martin

2012-07-05

Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms. Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits. Using trigger-controlled transcription factors, which independently control gene expression, and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs, we have designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.

Control of microtubule trajectory within an electric field by altering surface charge density

PubMed Central

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-01

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins. PMID:25567007

Control of microtubule trajectory within an electric field by altering surface charge density.

PubMed

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-08

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins.

Combining density functional theory calculations, supercomputing, and data-driven methods to design new materials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jain, Anubhav

2017-04-01

Density functional theory (DFT) simulations solve for the electronic structure of materials starting from the Schrödinger equation. Many case studies have now demonstrated that researchers can often use DFT to design new compounds in the computer (e.g., for batteries, catalysts, and hydrogen storage) before synthesis and characterization in the lab. In this talk, I will focus on how DFT calculations can be executed on large supercomputing resources in order to generate very large data sets on new materials for functional applications. First, I will briefly describe the Materials Project, an effort at LBNL that has virtually characterized over 60,000 materials using DFT and has shared the results with over 17,000 registered users. Next, I will talk about how such data can help discover new materials, describing how preliminary computational screening led to the identification and confirmation of a new family of bulk AMX2 thermoelectric compounds with measured zT reaching 0.8. I will outline future plans for how such data-driven methods can be used to better understand the factors that control thermoelectric behavior, e.g., for the rational design of electronic band structures, in ways that are different from conventional approaches.

Cosmetics-triggered percutaneous remote control of transgene expression in mice.

PubMed

Wang, Hui; Ye, Haifeng; Xie, Mingqi; Daoud El-Baba, Marie; Fussenegger, Martin

2015-08-18

Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cosmetics-triggered percutaneous remote control of transgene expression in mice

PubMed Central

Wang, Hui; Ye, Haifeng; Xie, Mingqi; Daoud El-Baba, Marie; Fussenegger, Martin

2015-01-01

Synthetic biology has significantly advanced the rational design of trigger-inducible gene switches that program cellular behavior in a reliable and predictable manner. Capitalizing on genetic componentry, including the repressor PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae pathovar tomato DC3000 to sense and resist plant-defence metabolites of the paraben class, we have designed a set of inducible and repressible mammalian transcription-control devices that could dose-dependently fine-tune transgene expression in mammalian cells and mice in response to paraben derivatives. With an over 60-years track record as licensed preservatives in the cosmetics industry, paraben derivatives have become a commonplace ingredient of most skin-care products including shower gels, cleansing toners and hand creams. As parabens can rapidly reach the bloodstream of mice following topical application, we used this feature to percutaneously program transgene expression of subcutaneous designer cell implants using off-the-shelf commercial paraben-containing skin-care cosmetics. The combination of non-invasive, transdermal and orthogonal trigger-inducible remote control of transgene expression may provide novel opportunities for dynamic interventions in future gene and cell-based therapies. PMID:25943548

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

PubMed

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+ T cell responses.

PubMed

Bazhan, S I; Karpenko, L I; Ilyicheva, T N; Belavin, P A; Seregin, S V; Danilyuk, N K; Antonets, D V; Ilyichev, A A

2010-04-01

Advances in defining HIV-1 CD8+ T cell epitopes and understanding endogenous MHC class I antigen processing enable the rational design of polyepitope vaccines for eliciting broadly targeted CD8+ T cell responses to HIV-1. Here we describe the construction and comparison of experimental DNA vaccines consisting of ten selected HLA-A2 epitopes from the major HIV-1 antigens Env, Gag, Pol, Nef, and Vpr. The immunogenicity of designed gene constructs was assessed after double DNA prime, single vaccinia virus boost immunization of HLA-A2 transgenic mice. We compared a number of parameters including different strategies for fusing ubiquitin to the polyepitope and including spacer sequences between epitopes to optimize proteasome liberation and TAP transport. It was demonstrated that the vaccine construct that induced in vitro the largest number of [peptide-MHC class I] complexes was also the most immunogenic in the animal experiments. This most immunogenic vaccine construct contained the N-terminal ubiquitin for targeting the polyepitope to the proteasome and included both proteasome liberation and TAP transport optimized spacer sequences that flanked the epitopes within the polyepitope construct. The immunogenicity of determinants was strictly related to their affinities for HLA-A2. Our finding supports the concept of rational vaccine design based on detailed knowledge of antigen processing. Copyright 2010 Elsevier Ltd. All rights reserved.

A Comparison Study of Second-Order Screening Designs and Their Extension

DTIC Science & Technology

2013-12-01

H2 97 V. Nonlinear Screening Designs for Defense Testing: An Overview and Case Study 5.1 Introduction “Necessity is the Mother of Invention.” Plato is...involved concepts like design resolution, minimum aber- ration , power, the number of clear (non-confounded) effects, concepts like rotatability

Permeation profiles of Antibiotics

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

Lopez Bautista, Cesar Augusto; Gnanakaran, Sandrasegaram

Presentation describes motivation: Combating bacterial inherent resistance; Drug development mainly uses brute force rather than rational design; Current experimental approaches lack molecular detail.

Texas M-E flexible pavement design system: literature review and proposed framework.

DOT National Transportation Integrated Search

2012-04-01

Recent developments over last several decades have offered an opportunity for more rational and rigorous pavement design procedures. Substantial work has already been completed in Texas, nationally, and internationally, in all aspects of modeling, ma...

In-vitro engineering of novel bioactivity in the natural enzymes

NASA Astrophysics Data System (ADS)

Tiwari, Vishvanath

2016-10-01

Enzymes catalyze various biochemical functions with high efficiency and specificity. In-vitro design of the enzyme leads to novel bioactivity in this natural biomolecule that give answers of some vital questions like crucial residues in binding with substrate, molecular evolution, cofactor specificity etc. Enzyme engineering technology involves directed evolution, rational designing, semi-rational designing and structure-based designing using chemical modifications. Similarly, combined computational and in-vitro evolution approaches together help in artificial designing of novel bioactivity in the natural enzyme. DNA shuffling, error prone PCR and staggered extension process are used to artificially redesign active site of enzyme, which can alter its efficiency and specificity. Modifications of the enzyme can lead to the discovery of new path of molecular evolution, designing of efficient enzymes, locating active sites and crucial residues, shift in substrate and cofactor specificity. The methods and thermodynamics of in-vitro designing of the enzyme are also discussed. Similarly, engineered thermophilic and psychrophilic enzymes attain substrate specificity and activity of mesophilic enzymes that may also be beneficial for industry and therapeutics.

Total System Design (TSD) Methodology Assessment.

DTIC Science & Technology

1983-01-01

hardware implementation. Author: Martin - Marietta Aerospace Title: Total System Design Methodology Source: Martin - Marietta Technical Report MCR -79-646...systematic, rational approach to computer systems design is needed. Martin - Marietta has produced a Total System Design Methodology to support such design...gathering and ordering. The purpose of the paper is to document the existing TSD methoeology at Martin - Marietta , describe the supporting tools, and

'In-between' and other reasonable ways to deal with risk and uncertainty: A review article.

PubMed

Zinn, Jens O

2016-11-16

How people deal with risk and uncertainty has fuelled public and academic debate in recent decades. Researchers have shown that common distinctions between rational and 'irrational' strategies underestimate the complexity of how people approach an uncertain future. I suggested in 2008 that strategies in-between do not follow standards of instrumental rationality nor they are 'irrational' but follow their own logic which works well under particular circumstances. Strategies such as trust, intuition and emotion are an important part of the mix when people deal with risk and uncertainty. In this article, I develop my original argument. It explores in-between strategies to deal with possible undesired outcomes of decisions. I examine 'non-rational strategies' and in particular the notions of active, passive and reflexive hope. Furthermore, I argue that my original typology should be seen as a triangular of reasonable strategies which work well under specific circumstances. Finally, I highlight a number of different ways in which these strategies combine.

Beyond the "science of sophomores": does the rational choice explanation of crime generalize from university students to an actual offender sample?

PubMed

Bouffard, Jeff; Bry, Jeff; Smith, Shamayne; Bry, Rhonda

2008-12-01

Much of the criminological literature testing rational choice theory has utilized hypothetical scenarios presented to university students. Although this research generally supports rational choice theory, a common criticism is that conclusions from these studies may not generalize to samples of actual offenders. This study proceeds to examine this issue in two steps. First, a traditional sample of university students is examined to determine how various costs and benefits relate to their hypothetical likelihood of offending. Then the same data collection procedures are employed with a somewhat different sample of younger, adjudicated, and institutionalized offenders to determine whether the conclusions drawn from the student sample generalize to this offender sample. Results generally suggest that the content and process of hypothetical criminal decision making differ in the sample of known offenders relative to the university students. Limitations of the current study, as well as suggestions for future research, are discussed.

Behavioral economics.

PubMed

Chambers, David W

2009-01-01

It is human nature to overestimate how rational we are, both in general and even when we are trying to be. Such irrationality is not random, and the search for and explanation of patterns of fuzzy thinking is the basis for a new academic discipline known as behavioral economics. Examples are given of some of the best understood of our foibles, including prospect theory, framing, anchoring, salience, confirmation bias, superstition, and ownership. Humans have two cognitive systems: one conscious, deliberate, slow, and rational; the other fast, pattern-based, emotionally tinged, and intuitive. Each is subject to its own kind of error. In the case of rational thought, we tend to exaggerate our capacity; for intuition, we fail to train it or recognize contexts where it is inappropriate. Humans are especially poor at estimating probabilities, or even understanding what they are. It is a common human failing to reason backwards from random outcomes that are favorable to beliefs about our power to predict the future. Five suggestions are offered for thinking within our means.

‘In-between’ and other reasonable ways to deal with risk and uncertainty: A review article

PubMed Central

Zinn, Jens O.

2016-01-01

How people deal with risk and uncertainty has fuelled public and academic debate in recent decades. Researchers have shown that common distinctions between rational and ‘irrational’ strategies underestimate the complexity of how people approach an uncertain future. I suggested in 2008 that strategies in-between do not follow standards of instrumental rationality nor they are ‘irrational’ but follow their own logic which works well under particular circumstances. Strategies such as trust, intuition and emotion are an important part of the mix when people deal with risk and uncertainty. In this article, I develop my original argument. It explores in-between strategies to deal with possible undesired outcomes of decisions. I examine ‘non-rational strategies’ and in particular the notions of active, passive and reflexive hope. Furthermore, I argue that my original typology should be seen as a triangular of reasonable strategies which work well under specific circumstances. Finally, I highlight a number of different ways in which these strategies combine. PMID:28392747

Rational design of the column of a heavy multipurpose machining center

NASA Astrophysics Data System (ADS)

Atapin, V. V.; Kurlaev, N. V.

2016-04-01

The main purpose in the design of supporting constructions of heavy multipurpose machining center is the reduction of mass at the given precision and productivity of machining. Accomplish these ends the technology of rational design of supporting constructions is offered. This technology is based on the decomposition method and the finite elements method in the combination with optimization methods. The technology has four stages: 1) calculation of external forces and loads, 2) as a result the boundary conditions (force, kinematics) for individual supporting constructions are formed, 3) a problem about final optimal distribution of a material by the individual supporting constructions with the real cross-section is solved; 4) dynamic analysis. By the example of design of the column of a heavy multipurpose machining center the main stages of rational design of the individual supporting constructions are shown. At a design stage of the carrying system consisting of load-bearing structures with simplified geometry, optimum overall dimensions of the column are identified. For the admitted system of preferences, it is necessary to accept the fact that the carrying system with the column with the sizes of cross section of 1.8 m (along x axis) and 2.6 m (along y axis) is the best. The analysis of the work of the column under the torsion condition with the use of method of mechanics shows that the column with square cross sections = 2.46·2.46 m which rigidity on torsion is 26 % higher in comparison with a production version is the best. The results of calculation show that a production-release design of the column with longitudinal and transverse edges of rigidity is 24 % heavier than the column with the edges located on a diagonally at equal rigidity.

Dismantling the Built Drawing: Working with Mood in Architectural Design

ERIC Educational Resources Information Center

Teal, Randall

2010-01-01

From the late Middle Ages onward an emphasis on the rational and the technical aspects of design and design drawing gained hold of architectural practice. In this transformation, the phenomenon of mood has been frequently overlooked or seen as something to be added on to a design; yet the fundamental grounding of mood, as described in Martin…

Integrating Software-Architecture-Centric Methods into the Rational Unified Process

DTIC Science & Technology

2004-07-01

Architecture Design ...................................................................................... 19...QAW in a life- cycle context. One issue that needs to be addressed is how scenarios produced in a QAW can be used by a software architecture design method...implementation testing. 18 CMU/SEI-2004-TR-011 CMU/SEI-2004-TR-011 19 4 Architecture Design The Attribute-Driven Design (ADD) method

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

Daly, G.G.; Mayor, T.H.

This paper develops a technique for extracting the expectations embedded in the current prices of energy-using durable goods and applies it to be used-car markets during the two energy crises of the 1970s. The resulting estimates indicate that consumers took the energy crises seriously and formed expectations about future gasoline prices that appear rational when compared with the historical gasoline price series, with the forecasts of specialists and experts, or with the actual postsample behavior of gasoline prices. The evidence therefore supports the view that consumers are able to make rather complex choices with a great deal of rationality andmore » casts doubt on the wisdom of policies based on assumptions to the contrary. 17 references, 2 figures.« less

A Simulation Game for the Study of State Policies.

ERIC Educational Resources Information Center

Enzer, Selwyn; And Others

A simulated planning conference used both informed experts (simulating state planners and societal groups) and "Monte Carlo" procedures (simulating random events) to identify some possible futures for the state of Connecticut and to examine rational planning behavior patterns. In the simulation the participants were divided into two…

The Effects of Maternal Verbal Aggression on the Adult Child's Future Romantic Relationships.

ERIC Educational Resources Information Center

Weber, Keith; Patterson, Brian R.

1997-01-01

Considers maternal verbal aggression and its effects on the adult-children's romantic relationships later in life. Introduces solidarity, emotional support, and relationship quality as rational outcomes and uses them to evaluate the effects of maternal verbal aggression on relationships. Indicates undergraduate students who report receiving high…

Toward an Expanded Definition of Adaptive Decision Making.

ERIC Educational Resources Information Center

Phillips, Susan D.

1997-01-01

Uses the lifespan, life-space model to examine the definition of adaptive decision making. Reviews the existing definition of adaptive decision making as "rational" decision making and offers alternate perspectives on decision making with an emphasis on the implications of using the model. Makes suggestions for future theory, research,…

Exchange Rates and Fundamentals.

ERIC Educational Resources Information Center

Engel, Charles; West, Kenneth D.

2005-01-01

We show analytically that in a rational expectations present-value model, an asset price manifests near-random walk behavior if fundamentals are I (1) and the factor for discounting future fundamentals is near one. We argue that this result helps explain the well-known puzzle that fundamental variables such as relative money supplies, outputs,…

A Framework for the Study of Emotions in Organizational Contexts.

ERIC Educational Resources Information Center

Fiebig, Greg V.; Kramer, Michael W.

1998-01-01

Approaches the study of emotions in organizations holistically, based on a proposed framework. Provides descriptive data that suggests the presence of the framework's major elements. States that future examination of emotions based on this framework should assist in understanding emotions, which are frequently ignored in a rational model. (PA)

Values for Human-to-Human Reference.

ERIC Educational Resources Information Center

Gorman, Michael

2001-01-01

Defines "values" and lists the eight values (stewardship, service, intellectual freedom, rationalism, literacy and learning, equity of access, privacy, democracy) derived by the author in an earlier work. Gives a brief history of the evolution of human-to-human reference service and discusses its future. Relates each of the author's eight values…

The Jomtien Plan of Action in the Sub-Saharan Context.

ERIC Educational Resources Information Center

Thiam, Iba Der

1990-01-01

Suggests that the means to eliminate illiteracy are available in Africa if nations devise and implement a strategy of action based on an effective political will and adopting a methodical, rational approach. Discusses the current situation, negative factors, repercussions on development, and future demands. Argues that promoting basic education…

Academe Sings the Blues

ERIC Educational Resources Information Center

Wood, Robert

1975-01-01

Lack of an overall strategy for change, hostile political and social environment, and a mood of hesitancy to defend themselves, have contributed to the current problems of higher education. New directions for the future are proposed which include rational decision making based upon how the university fits the purposes and problems of the times.…

The Externalities Influencing Higher Education

ERIC Educational Resources Information Center

Ford, Marcus

2007-01-01

Modern universities fully recognize the importance of strategic planning, but such planning tends to be short term (five years out). As a result, there is a tendency to assume that the future will greatly resemble the immediate present. While this is rational thinking, institutions do change quite dramatically because the alternative is to cease…

Institutions Devise New Ways to Help Families Meet College Costs.

ERIC Educational Resources Information Center

Klinger, Donna J.

1986-01-01

Colleges are offering innovative financing plans, some risky, that allow families to pay college costs in a rational manner and in turn keep enrollment up. They include tuition futures plans, electronic funds transfer, gift certificates, credit card payments, megaloans, tuition stabilization plans, institutional loans, tuition matching, and…

An Economy at Risk: Does Anyone Care?

ERIC Educational Resources Information Center

Brenneke, Judith Staley, Ed.

Attempting to scrutinize the rational for economics education, this book is a collection of papers by economics educators who seek to envision what economics skills and knowledge will be needed in the future and whether these justify teaching economics at the pre-college level. Twelve economics educators contributed articles: (1) "The Case…

[INFORMATION AWARENESS OF STUDENTS--FUTURE TECHNOLOGY FOR HEALTHY LIFESTYLES TEACHERS AND TRAINING IN THEIR EDUCATIONAL ACTIVITIES IN AREA OF HUMAN HEALTH PRESERVATION].

PubMed

Kalinina, I A

2015-01-01

In the article there are presented results of the questionnaire survey of students--future technology for healthy lifestyles teachers on issues of shaping of health and a healthy lifestyle. There is given an estimation of the degree of the formedness in students adjustment for healthy lifestyle, including eating behavior and nutrition ration. There were determined basic directions of the shaping of the health-saving competence of the school teacher.

The 1986 world oil puzzle: Confusion and anxiety

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

Field, S.

1986-01-01

The turbulent international political and economic events of the 1970s and 1980s reinforce the instinctive feeling that the future is inherently unpredictable. Yet we continue to strive for a perception of the future because it is a necessary component of a rational framework for intelligent decision making. In this paper, the chronological evolution of oil pricing is presented to provide an historical perspective to view current events. The outlook for the main determinants of oil price is then examined.

Hybrid Airships for Lift: A New Lift Paradigm and a Pragmatic Assessment of the Vehicle’s Key Operational Challenges

DTIC Science & Technology

2011-12-01

prepares for storms.” 11 RAND, High Altitude Airships for the Future Force Army, 32. 12 Boyd to author, email, 23 September 2011. 27...2011). High Altitude Airships for the Future Force Army, RAND Technical Report DASW01-01-C-0003. Santa Monica, CA: RAND, 2005. www.rand.org/pubs...beginning to realize the potential capabilities of HA for lift, misinformed opinions on airship challenges continue to plague a rational analysis on

Medicinal chemistry inspired fragment-based drug discovery.

PubMed

Lanter, James; Zhang, Xuqing; Sui, Zhihua

2011-01-01

Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.

Revealing Nucleic Acid Mutations Using Förster Resonance Energy Transfer-Based Probes

PubMed Central

Junager, Nina P. L.; Kongsted, Jacob; Astakhova, Kira

2016-01-01

Nucleic acid mutations are of tremendous importance in modern clinical work, biotechnology and in fundamental studies of nucleic acids. Therefore, rapid, cost-effective and reliable detection of mutations is an object of extensive research. Today, Förster resonance energy transfer (FRET) probes are among the most often used tools for the detection of nucleic acids and in particular, for the detection of mutations. However, multiple parameters must be taken into account in order to create efficient FRET probes that are sensitive to nucleic acid mutations. In this review; we focus on the design principles for such probes and available computational methods that allow for their rational design. Applications of advanced, rationally designed FRET probes range from new insights into cellular heterogeneity to gaining new knowledge of nucleic acid structures directly in living cells. PMID:27472344

The solvation structure of alprazolam.

PubMed

Sridhar, Akshay; Johnston, Andrew J; Varathan, Luxmmi; McLain, Sylvia E; Biggin, Philip C

2016-08-10

Alprazolam is a benzodiazepine that is commonly prescribed for the treatment of anxiety and other related disorders. Like other benzodiazepines, it is thought to exert its effect through interaction with GABAA receptors. However, it has also been described as a potent and selective protein interaction inhibitor of bromodomain and extra-terminal (BET) proteins. Indeed, the only crystal structure of alprazolam bound to a protein is a complex between alprazolam and the BRD4 bromodomain. The structure shows that the complex also involves many water interactions that mediate contacts between the drug and the protein, a scenario that exists in many drug-protein complexes. How such waters relate to solvation patterns of small molecules may improve our understanding of what dictates their appearance or absence in bridging positions within complexes and thus will be important in terms of future rational drug-design. Here, we use neutron diffraction in conjunction with molecular dynamics simulations to provide a detailed analysis of how water molecules interact with alprazolam in methanol/water mixtures. The agreement between the neutron diffraction and the molecular dynamics is extremely good. We discuss the results in the context of drug design.

Simulations of molecular self-assembled monolayers on surfaces: packing structures, formation processes and functions tuned by intermolecular and interfacial interactions.

PubMed

Wen, Jin; Li, Wei; Chen, Shuang; Ma, Jing

2016-08-17

Surfaces modified with a functional molecular monolayer are essential for the fabrication of nano-scale electronics or machines with novel physical, chemical, and/or biological properties. Theoretical simulation based on advanced quantum chemical and classical models is at present a necessary tool in the development, design, and understanding of the interfacial nanostructure. The nanoscale surface morphology, growth processes, and functions are controlled by not only the electronic structures (molecular energy levels, dipole moments, polarizabilities, and optical properties) of building units but also the subtle balance between intermolecular and interfacial interactions. The switchable surfaces are also constructed by introducing stimuli-responsive units like azobenzene derivatives. To bridge the gap between experiments and theoretical models, opportunities and challenges for future development of modelling of ferroelectricity, entropy, and chemical reactions of surface-supported monolayers are also addressed. Theoretical simulations will allow us to obtain important and detailed information about the structure and dynamics of monolayer modified interfaces, which will guide the rational design and optimization of dynamic interfaces to meet challenges of controlling optical, electrical, and biological functions.

Solid cryogen: a cooling system for future MgB2 MRI magnet.

PubMed

Patel, Dipak; Hossain, Md Shahriar Al; Qiu, Wenbin; Jie, Hyunseock; Yamauchi, Yusuke; Maeda, Minoru; Tomsic, Mike; Choi, Seyong; Kim, Jung Ho

2017-03-02

An efficient cooling system and the superconducting magnet are essential components of magnetic resonance imaging (MRI) technology. Herein, we report a solid nitrogen (SN 2 ) cooling system as a valuable cryogenic feature, which is targeted for easy usability and stable operation under unreliable power source conditions, in conjunction with a magnesium diboride (MgB 2 ) superconducting magnet. The rationally designed MgB 2 /SN 2 cooling system was first considered by conducting a finite element analysis simulation, and then a demonstrator coil was empirically tested under the same conditions. In the SN 2 cooling system design, a wide temperature distribution on the SN 2 chamber was observed due to the low thermal conductivity of the stainless steel components. To overcome this temperature distribution, a copper flange was introduced to enhance the temperature uniformity of the SN 2 chamber. In the coil testing, an operating current as high as 200 A was applied at 28 K (below the critical current) without any operating or thermal issues. This work was performed to further the development of SN 2 cooled MgB 2 superconducting coils for MRI applications.

Solid cryogen: a cooling system for future MgB2 MRI magnet

NASA Astrophysics Data System (ADS)

Patel, Dipak; Hossain, Md Shahriar Al; Qiu, Wenbin; Jie, Hyunseock; Yamauchi, Yusuke; Maeda, Minoru; Tomsic, Mike; Choi, Seyong; Kim, Jung Ho

2017-03-01

An efficient cooling system and the superconducting magnet are essential components of magnetic resonance imaging (MRI) technology. Herein, we report a solid nitrogen (SN2) cooling system as a valuable cryogenic feature, which is targeted for easy usability and stable operation under unreliable power source conditions, in conjunction with a magnesium diboride (MgB2) superconducting magnet. The rationally designed MgB2/SN2 cooling system was first considered by conducting a finite element analysis simulation, and then a demonstrator coil was empirically tested under the same conditions. In the SN2 cooling system design, a wide temperature distribution on the SN2 chamber was observed due to the low thermal conductivity of the stainless steel components. To overcome this temperature distribution, a copper flange was introduced to enhance the temperature uniformity of the SN2 chamber. In the coil testing, an operating current as high as 200 A was applied at 28 K (below the critical current) without any operating or thermal issues. This work was performed to further the development of SN2 cooled MgB2 superconducting coils for MRI applications.

The Rational Patient and Beyond: Implications for Treatment Adherence in People with Psychiatric Disabilities

PubMed Central

Corrigan, Patrick W.; Rüsch, Nicolas; Ben-Zeev, Dror; Sher, Tamara

2014-01-01

Purpose/Objective Many people with psychiatric disabilities do not benefit from evidence-based practices because they often do not seek out or fully adhere to them. One way psychologists have made sense of this rehabilitation and health decision process and subsequent behaviors (of which adherence might be viewed as one) is by proposing a “rational patient;” namely, that decisions are made deliberatively by weighing perceived costs and benefits of intervention options. Social psychological research, however, suggests limitations to a rational patient theory that impact models of health decision making. Design The research literature was reviewed for studies of rational patient models and alternative theories with empirical support. Special focus was on models specifically related to decisions about rehabilitation strategies for psychiatric disability. Results Notions of the rational patient evolved out of several psychological models including the health belief model, protection motivation theory, and theory of planned behavior. A variety of practice strategies evolved to promote rational decision making. However, research also suggests limitations to rational deliberations of health. (1) Rather than carefully and consciously considered, many health decisions are implicit, potentially occurring outside awareness. (2) Decisions are not always planful; often it is the immediate exigencies of a context rather than an earlier balance of costs and benefits that has the greatest effects. (3) Cool cognitions often do not dictate the process; emotional factors have an important role in health decisions. Each of these limitations suggests additional practice strategies that facilitate a person’s health decisions. Conclusions/Implications Old models of rational decision making need to be supplanted by multi-process models that explain supra-deliberative factors in health decisions and behaviors. PMID:24446671

Rational design of metal nitride redox materials for solar-driven ammonia synthesis.

PubMed

Michalsky, Ronald; Pfromm, Peter H; Steinfeld, Aldo

2015-06-06

Fixed nitrogen is an essential chemical building block for plant and animal protein, which makes ammonia (NH3) a central component of synthetic fertilizer for the global production of food and biofuels. A global project on artificial photosynthesis may foster the development of production technologies for renewable NH3 fertilizer, hydrogen carrier and combustion fuel. This article presents an alternative path for the production of NH3 from nitrogen, water and solar energy. The process is based on a thermochemical redox cycle driven by concentrated solar process heat at 700-1200°C that yields NH3 via the oxidation of a metal nitride with water. The metal nitride is recycled via solar-driven reduction of the oxidized redox material with nitrogen at atmospheric pressure. We employ electronic structure theory for the rational high-throughput design of novel metal nitride redox materials and to show how transition-metal doping controls the formation and consumption of nitrogen vacancies in metal nitrides. We confirm experimentally that iron doping of manganese nitride increases the concentration of nitrogen vacancies compared with no doping. The experiments are rationalized through the average energy of the dopant d-states, a descriptor for the theory-based design of advanced metal nitride redox materials to produce sustainable solar thermochemical ammonia.

Rational design of metal nitride redox materials for solar-driven ammonia synthesis

PubMed Central

Michalsky, Ronald; Pfromm, Peter H.; Steinfeld, Aldo

2015-01-01

Fixed nitrogen is an essential chemical building block for plant and animal protein, which makes ammonia (NH3) a central component of synthetic fertilizer for the global production of food and biofuels. A global project on artificial photosynthesis may foster the development of production technologies for renewable NH3 fertilizer, hydrogen carrier and combustion fuel. This article presents an alternative path for the production of NH3 from nitrogen, water and solar energy. The process is based on a thermochemical redox cycle driven by concentrated solar process heat at 700–1200°C that yields NH3 via the oxidation of a metal nitride with water. The metal nitride is recycled via solar-driven reduction of the oxidized redox material with nitrogen at atmospheric pressure. We employ electronic structure theory for the rational high-throughput design of novel metal nitride redox materials and to show how transition-metal doping controls the formation and consumption of nitrogen vacancies in metal nitrides. We confirm experimentally that iron doping of manganese nitride increases the concentration of nitrogen vacancies compared with no doping. The experiments are rationalized through the average energy of the dopant d-states, a descriptor for the theory-based design of advanced metal nitride redox materials to produce sustainable solar thermochemical ammonia. PMID:26052421

Rational design and application of responsive alpha-helical peptide hydrogels.

PubMed

Banwell, Eleanor F; Abelardo, Edgardo S; Adams, Dave J; Birchall, Martin A; Corrigan, Adam; Donald, Athene M; Kirkland, Mark; Serpell, Louise C; Butler, Michael F; Woolfson, Derek N

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely alpha-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of alpha-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

Rational design and application of responsive α-helical peptide hydrogels

PubMed Central

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-01-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture. PMID:19543314

Rational design and application of responsive α-helical peptide hydrogels

NASA Astrophysics Data System (ADS)

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-07-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs, and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here, we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks of fibrils melt on heating, whereas those formed through hydrophobic fibril-fibril interactions strengthen when warmed. The hSAFs are dual-peptide systems that gel only on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.

That’s not funny! – But it should be: effects of humorous emotion regulation on emotional experience and memory

PubMed Central

Kugler, Lisa; Kuhbandner, Christof

2015-01-01

Previous research has shown that humorous reappraisal can reduce elicited negative emotions, suggesting that humor may be a functional strategy to cope with emotionally negative situations. However, the effect of humorous reappraisal on later memory about the emotion-eliciting situation is currently unknown, although this is crucial for more adaptive responding in future situations. To address this issue, we examined the effects of humorous reappraisal on both emotional experience and memory, compared to non-humorous rational reappraisal and a non-reappraisal control condition. Replicating previous findings, humorous reappraisal reduced evoked negative valence and arousal levels very effectively, and the down-regulation of experienced negative emotions was even more pronounced after humorous compared to rational reappraisal. Regarding later memory for emotion-eliciting stimuli, both humorous and rational reappraisal reduced free recall, but recognition memory was unaffected, with memory strength being stronger after humorous than after rational reappraisal. These results indicate that humor seems to be indeed an optimal strategy to cope with negative situations because humor can help us to feel better when confronted with negative stimuli, but still allows us to retrieve stimulus information later when afforded to do so by the presence of appropriate contextual features. PMID:26379608

75 FR 80765 - Hazardous Materials: Adoption of ASME Code Section XII and the National Board Inspection Code

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... requirement for allowable peak secondary stresses for MC 331 cargo tanks. 4. Rational Design of Non-circular... the design, construction, and certification of cargo tank motor vehicles, cryogenic portable tanks and... CTMV: Cargo Tank Motor Vehicle DCE: Design Certifying Engineer FMCSA: Federal Motor Carrier Safety...

Project-Based Pedagogy for the Facilitation of Webpage Design

ERIC Educational Resources Information Center

Jakovljevic, Maria; Ankiewicz, Piet

2016-01-01

Real issues of web design and development include many problem-solving tasks. There are, however, some inadequacies associated with the implementation of appropriate pedagogy for organised and structured instruction that supports the rational problem-solving paradigm. The purpose of this article is to report on a study for the design and…

Developing a (Non-Linear) Practice of Design Thinking

ERIC Educational Resources Information Center

Teal, Randall

2010-01-01

Design thinking can be a powerful way to engage the world, allowing interactive understandings that are both analytic and experiential. When fully functioning, design thinking necessarily calls upon faculties often considered a-rational, a-causal and a-logical. Unfortunately, such faculties often give rise to academic suspicion. That is to say,…

The Special Education Teacher as an Instructional Designer. Rational, Content, and Strategy for an Innovative Individualized Course on Instructional Design in Special Education. Working Paper 9.14.

ERIC Educational Resources Information Center

Thiagarajan, Sivasailam

Provided are the rationale, content and strategy for an introductory course in instructional design for special education teachers. The teacher's need for varied competencies in instructional design, management and interaction are discussed. It is recommended that teacher training include development of such design skills as task analysis, learner…

Two-color SERS microscopy for protein co-localization in prostate tissue with primary antibody-protein A/G-gold nanocluster conjugates

NASA Astrophysics Data System (ADS)

Salehi, Mohammad; Schneider, Lilli; Ströbel, Philipp; Marx, Alexander; Packeisen, Jens; Schlücker, Sebastian

2014-01-01

SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates.SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05890e

The equivalence of a human observer and an ideal observer in binary diagnostic tasks

NASA Astrophysics Data System (ADS)

He, Xin; Samuelson, Frank; Gallas, Brandon D.; Sahiner, Berkman; Myers, Kyle

2013-03-01

The Ideal Observer (IO) is "ideal" for given data populations. In the image perception process, as the raw images are degraded by factors such as display and eye optics, there is an equivalent IO (EIO). The EIO uses the statistical information that exits the perception/cognitive degradations as the data. We assume a human observer who received sufficient training, e.g., radiologists, and hypothesize that such a human observer can be modeled as if he is an EIO. To measure the likelihood ratio (LR) distributions of an EIO, we formalize experimental design principles that encourage rationality based on von Neumann and Morgenstern's (vNM) axioms. We present examples to show that many observer study design refinements, although motivated by empirical principles explicitly, implicitly encourage rationality. Our hypothesis is supported by a recent review paper on ROC curve convexity by Pesce, Metz, and Berbaum. We also provide additional evidence based on a collection of observer studies in medical imaging. EIO theory shows that the "sub-optimal" performance of a human observer can be mathematically formalized in the form of an IO, and measured through rationality encouragement.

Nano-array based monolithic catalysts: Concept, rational materials design and tunable catalytic performance

DOE PAGES

Ren, Zheng; Guo, Yanbing; Gao, Pu-Xian

2015-03-20

Monolithic catalysts, also known as structured catalysts, represent an important catalyst configuration widely used in automotive, chemical, and energy industries. However, several issues associated with washcoat based monolithic catalyst preparation are ever present, such as compromised materials utilization efficiency due to a less-than-ideal wash coating process, difficulty in precise and optimum microstructure control and lack of structure-property correlation. Here, in this mini-review, we introduce the concept of nano-array catalyst, a new type of monolithic catalyst featuring high catalyst utilization efficiency, good thermal/mechanical robustness, and catalytic performance tunability. A comprehensive overview is presented with detailed discussion of the strategies for nano-arraymore » catalyst preparation and rational catalytic activity adjustment enabled by the well-defined nano-array geometry. Specifically their scalable fabrication processes are reviewed in conjunction with discussion of their various catalytic oxidation reaction performances at low temperature. Finally, we hope this review will serve as a timely and useful research guide for rational design and utilization of the new type of monolithic catalysts.« less

Effect of Rational-Emotive Behavior Therapy Program on the Symptoms of Burnout Syndrome Among Undergraduate Electronics Work Students in Nigeria.

PubMed

Ogbuanya, Theresa C; Eseadi, Chiedu; Orji, Chibueze T; Omeje, Joachim C; Anyanwu, Joy I; Ugwoke, Samuel C; Edeh, Nkechinyere C

2018-01-01

This research aimed to investigate the effect that rational-emotive behavior therapy had on the symptoms of burnout among undergraduate electronics work students in Southeast Nigeria. This study utilized a pretest-posttest design involving a no-intervention group versus an intervention group. Participants were 124 undergraduate electronics work students who met the inclusion criteria of the study. The intervention consisted of 12 weeks of rational-emotive behavior therapy treatment and 2 weeks of follow-up meetings conducted at 6 months. Self-report questionnaire was used for data collection. Repeated measures analysis of variance and t test were used for data analysis. The results show that rational-emotive behavior therapy had a significant effect on the symptoms of burnout syndrome among the electronics work students in the treatment group compared to their counterparts in the no-intervention group. Finally, the positive gains were significantly maintained by the treatment group at the follow-up. The current study suggests that rational-emotive behavior therapy program can be effective for dealing with burnout syndrome among the population of undergraduates in Nigeria. Further clinical evaluation is needed.

Utilization of Cacao Pod Husk Silage as Cattle Ration Mixture at Taluditi, Pohuwatu Regency, Gorontalo Province

NASA Astrophysics Data System (ADS)

Hidayat, M.; Pratama, H. Y.; Martono, E.

2018-02-01

Cacao plantation produces cacao pod husks (CPHs) by-products during the harvest period. This research aimed to make benefits the CPH, preserved with silage technology as cattle ration mixture, investigate the adequacy of nutrient for the cattle after treated with addition of CPH silage, and investigate the quota of cattle treated with CPH silage addition. The research design was conducted by giving extension and field observation that was carried out at Taluditi on July to August 2015 during the activity of Student Community Service (KKN PPM UGM Unit Gorontalo 02). The secondary data was gathered from the Department of Agriculture and Plantation Pohuwatu Regency, and also supporting references. The number of respondents in each location was about 30 - 40 people. The research results showed that the silage preservation technology can be well received by the farmers. There was improvement of cattle ration nutrient supplemented with CPH compared to that of ration nutrient which was usually be used by the farmers or standard ration nutrient. The research also resulted in fresh CPH production 2,625.741 tons/year, CPH silage production 2,140.549 tons/year and load capacity + 575 heads/day weight 250-300 kg.

The limited impact of indeterminacy for healthcare rationing: how indeterminacy problems show the need for a hybrid theory, but nothing more.

PubMed

Herlitz, Anders

2016-01-01

A notorious debate in the ethics of healthcare rationing concerns whether to address rationing decisions with substantial principles or with a procedural approach. One major argument in favour of procedural approaches is that substantial principles are indeterminate so that we can reasonably disagree about how to apply them. To deal with indeterminacy, we need a just decision process. In this paper I argue that it is a mistake to abandon substantial principles just because they are indeterminate. It is true that reasonable substantial principles designed to deal with healthcare rationing can be expected to be indeterminate. Yet, the indeterminacy is only partial. In some situations we can fully determine what to do in light of the principles, in some situations we cannot. The conclusion to draw from this fact is not that we need to develop procedural approaches to healthcare rationing, but rather that we need a more complex theory in which both substantial principles and procedural approaches are needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Rational and Safe Design of Concrete Transportation Structures for Size Effect and Multi-Decade Sustainability

DOT National Transportation Integrated Search

2012-10-01

The overall goal of this project was to improve the safety and sustainability in the design of large : prestressed concrete bridges and other transportation structures. The safety of large concrete : structures, including bridges, has been insufficie...

DEVELOPMENT OF A RATIONALLY BASED DESIGN PROTOCOL FOR THE ULTRAVIOLET LIGHT DISINFECTION PROCESS

EPA Science Inventory

A protocol is demonstrated for the design and evaluation of ultraviolet (UV) disinfection systems based on a mathematical model. The disinfection model incorporates the system's physical dimensions, the residence time distribution of the reactor and dispersion characteristics, th...

SUSTAINABLE ALLOY DESIGN: SEARCHING FOR RARE EARTH ELEMENT ALTERNATIVES THROUGH CRYSTAL ENGINEERING

DTIC Science & Technology

2016-02-26

Property Maps to Guide Materials Design via Statistical Learning Summer Research Group Meeting – Materials by Design Los Alamos National Laboratory, July...Informatics, Rational design , Quantitative correlative spectroscopy and imaging, DFT, In situ high pressure mechanical property measurements, Superalloy...final, technical, interim, memorandum, master’s thesis, progress, quarterly, research , special, group study, etc. 3. DATES COVERED. Indicate the

Determination of cell metabolite VEGF₁₆₅ and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe.

PubMed

Lin, Xuexia; Leung, Ka-Ho; Lin, Ling; Lin, Luyao; Lin, Sheng; Leung, Chung-Hang; Ma, Dik-Lung; Lin, Jin-Ming

2016-05-15

In this paper, we rationally design a novel G-quadruplex-selective luminescent iridium (III) complex for rapid detection of oligonucleotide and VEGF165 in microfluidics. This new probe is applied as a convenient biosensor for label-free quantitative analysis of VEGF165 protein from cell metabolism, as well as for studying the kinetics of the aptamer-protein interaction combination with a microfluidic platform. As a result, we have successfully established a quantitative analysis of VEGF165 from cell metabolism. Furthermore, based on the principles of hydrodynamic focusing and diffusive mixing, different transient states during kinetics process were monitored and recorded. Thus, the combination of microfluidic technique and G-quadruplex luminescent probe will be potentially applied in the studies of intramolecular interactions and molecule recognition in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Understanding trends in C-H bond activation in heterogeneous catalysis.

PubMed

Latimer, Allegra A; Kulkarni, Ambarish R; Aljama, Hassan; Montoya, Joseph H; Yoo, Jong Suk; Tsai, Charlie; Abild-Pedersen, Frank; Studt, Felix; Nørskov, Jens K

2017-02-01

While the search for catalysts capable of directly converting methane to higher value commodity chemicals and liquid fuels has been active for over a century, a viable industrial process for selective methane activation has yet to be developed. Electronic structure calculations are playing an increasingly relevant role in this search, but large-scale materials screening efforts are hindered by computationally expensive transition state barrier calculations. The purpose of the present letter is twofold. First, we show that, for the wide range of catalysts that proceed via a radical intermediate, a unifying framework for predicting C-H activation barriers using a single universal descriptor can be established. Second, we combine this scaling approach with a thermodynamic analysis of active site formation to provide a map of methane activation rates. Our model successfully rationalizes the available empirical data and lays the foundation for future catalyst design strategies that transcend different catalyst classes.

Understanding trends in C–H bond activation in heterogeneous catalysis

DOE PAGES

Latimer, Allegra A.; Kulkarni, Ambarish R.; Aljama, Hassan; ...

2016-10-10

While the search for catalysts capable of directly converting methane to higher value commodity chemicals and liquid fuels has been active for over a century, a viable industrial process for selective methane activation has yet to be developed1. Electronic structure calculations are playing an increasingly relevant role in this search, but large-scale materials screening efforts are hindered by computationally expensive transition state barrier calculations. The purpose of the present letter is twofold. First, we show that, for the wide range of catalysts that proceed via a radical intermediate, a unifying framework for predicting C–H activation barriers using a single universalmore » descriptor can be established. Second, we combine this scaling approach with a thermodynamic analysis of active site formation to provide a map of methane activation rates. Lastly, our model successfully rationalizes the available empirical data and lays the foundation for future catalyst design strategies that transcend different catalyst classes.« less

One-dimensional CdS nanostructures: a promising candidate for optoelectronics.

PubMed

Li, Huiqiao; Wang, Xi; Xu, Junqi; Zhang, Qi; Bando, Yoshio; Golberg, Dmitri; Ma, Ying; Zhai, Tianyou

2013-06-11

As a promising candidate for optoelectronics, one-dimensional CdS nanostructures have drawn great scientific and technical interest due to their interesting fundamental properties and possibilities of utilization in novel promising optoelectronical devices with augmented performance and functionalities. This progress report highlights a selection of important topics pertinent to optoelectronical applications of one-dimensional CdS nanostructures over the last five years. This article begins with the description of rational design and controlled synthesis of CdS nanostructure arrays, alloyed nanostructucures and kinked nanowire superstructures, and then focuses on the optoelectronical properties, and applications including cathodoluminescence, lasers, light-emitting diodes, waveguides, field emitters, logic circuits, memory devices, photodetectors, gas sensors, photovoltaics and photoelectrochemistry. Finally, the general challenges and the potential future directions of this exciting area of research are highlighted. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding trends in C-H bond activation in heterogeneous catalysis

NASA Astrophysics Data System (ADS)

Latimer, Allegra A.; Kulkarni, Ambarish R.; Aljama, Hassan; Montoya, Joseph H.; Yoo, Jong Suk; Tsai, Charlie; Abild-Pedersen, Frank; Studt, Felix; Nørskov, Jens K.

2017-02-01

While the search for catalysts capable of directly converting methane to higher value commodity chemicals and liquid fuels has been active for over a century, a viable industrial process for selective methane activation has yet to be developed. Electronic structure calculations are playing an increasingly relevant role in this search, but large-scale materials screening efforts are hindered by computationally expensive transition state barrier calculations. The purpose of the present letter is twofold. First, we show that, for the wide range of catalysts that proceed via a radical intermediate, a unifying framework for predicting C-H activation barriers using a single universal descriptor can be established. Second, we combine this scaling approach with a thermodynamic analysis of active site formation to provide a map of methane activation rates. Our model successfully rationalizes the available empirical data and lays the foundation for future catalyst design strategies that transcend different catalyst classes.

Death receptors as targets in cancer.

PubMed

Micheau, O; Shirley, S; Dufour, F

2013-08-01

Anti-tumour therapies based on the use pro-apoptotic receptor agonists, including TNF-related apoptosis-inducing ligand (TRAIL) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future clinical trials. This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8. © 2013 The British Pharmacological Society.

A definition of the degree of controllability - A criterion for actuator placement

NASA Technical Reports Server (NTRS)

Viswanathan, C. N.; Longman, R. W.; Likins, P. W.

1979-01-01

The unsolved problem of how to control the attitude and shape of future very large flexible satellite structures represents a challenging problem for modern control theory. One aspect of this problem is the question of how to choose the number and locations throughout the spacecraft of the control system actuators. Starting from basic physical considerations, this paper develops a concept of the degree of controllability of a control system, and then develops numerical methods to generate approximate values of the degree of controllability for any spacecraft. These results offer the control system designer a tool which allows him to rank the effectiveness of alternative actuator distributions, and hence to choose the actuator locations on a rational basis. The degree of controllability is shown to take a particularly simple form when the satellite dynamics equations are in modal form. Examples are provided to illustrate the use of the concept on a simple flexible spacecraft.

Bio-Inspired Self-Cleaning Surfaces

NASA Astrophysics Data System (ADS)

Liu, Kesong; Jiang, Lei

2012-08-01

Self-cleaning surfaces have drawn a lot of interest for both fundamental research and practical applications. This review focuses on the recent progress in mechanism, preparation, and application of self-cleaning surfaces. To date, self-cleaning has been demonstrated by the following four conceptual approaches: (a) TiO2-based superhydrophilic self-cleaning, (b) lotus effect self-cleaning (superhydrophobicity with a small sliding angle), (c) gecko setae-inspired self-cleaning, and (d) underwater organisms-inspired antifouling self-cleaning. Although a number of self-cleaning products have been commercialized, the remaining challenges and future outlook of self-cleaning surfaces are also briefly addressed. Through evolution, nature, which has long been a source of inspiration for scientists and engineers, has arrived at what is optimal. We hope this review will stimulate interdisciplinary collaboration among material science, chemistry, biology, physics, nanoscience, engineering, etc., which is essential for the rational design and reproducible construction of bio-inspired multifunctional self-cleaning surfaces in practical applications.

Towards 3rd generation organic tandem solar cells with 20% efficiency: Accelerated discovery and rational design of carbon-based photovoltaic materials through massive distributed volunteer computing

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

Aspuru-Guzik, Alan

2016-11-04

Clean, affordable, and renewable energy sources are urgently needed to satisfy the 10s of terawatts (TW) energy need of human beings. Solar cells are one promising choice to replace traditional energy sources. Our broad efforts have expanded the knowledge of possible donor materials for organic photovoltaics, while increasing access of our results to the world through the Clean Energy Project database (www.molecularspace.org). Machine learning techniques, including Gaussian Processes have been used to calibrate frontier molecular orbital energies, and OPV bulk properties (open-circuit voltage, percent conversion efficiencies, and short-circuit current). This grant allowed us to delve into the solid-state properties ofmore » OPVs (charge-carrier dynamics). One particular example allowed us to predict charge-carrier dynamics and make predictions about future hydrogen-bonded materials.« less

Biofilm based attached cultivation technology for microalgal biorefineries-A review.

PubMed

Wang, Junfeng; Liu, Wen; Liu, Tianzhong

2017-11-01

The attached cultivation for microalga has many superiorities over the conventional aqua-suspend methods, which make it a promising pathway to supply feedstock for microalgae based bio-refinery attempts. In this review, the current reports on bioreactor, application, modeling, substratum material and engineering aspects were summarized and the future research and developments should be focused on the following aspects: 1) Build principles and guidelines for rational structure design by studying the relationship of physiological properties with typical structures and light regimes; 2) Set up theory foundation of substratum material selection by studying the physic-chemical properties of algal cells and substratum materials; 3) Further understanding the mass transfer behaviors of both CO 2 and nutrients in biofilm for enhanced growth rate and products accumulation; 4) New equipment and machines for inoculation, harvesting and moisture keeping should be developed and integrated with bioreactor structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent Progresses and Development of Advanced Atomic Layer Deposition towards High-Performance Li-Ion Batteries

PubMed Central

Lu, Wei; Liang, Longwei; Sun, Xuan; Sun, Xiaofei; Wu, Chen; Hou, Linrui; Sun, Jinfeng

2017-01-01

Electrode materials and electrolytes play a vital role in device-level performance of rechargeable Li-ion batteries (LIBs). However, electrode structure/component degeneration and electrode-electrolyte sur-/interface evolution are identified as the most crucial obstacles in practical applications. Thanks to its congenital advantages, atomic layer deposition (ALD) methodology has attracted enormous attention in advanced LIBs. This review mainly focuses upon the up-to-date progress and development of the ALD in high-performance LIBs. The significant roles of the ALD in rational design and fabrication of multi-dimensional nanostructured electrode materials, and finely tailoring electrode-electrolyte sur-/interfaces are comprehensively highlighted. Furthermore, we clearly envision that this contribution will motivate more extensive and insightful studies in the ALD to considerably improve Li-storage behaviors. Future trends and prospects to further develop advanced ALD nanotechnology in next-generation LIBs were also presented. PMID:29036916

Cation-Induced Stabilization and Denaturation of DNA Origami Nanostructures in Urea and Guanidinium Chloride.

PubMed

Ramakrishnan, Saminathan; Krainer, Georg; Grundmeier, Guido; Schlierf, Michael; Keller, Adrian

2017-11-01

The stability of DNA origami nanostructures under various environmental conditions constitutes an important issue in numerous applications, including drug delivery, molecular sensing, and single-molecule biophysics. Here, the effect of Na + and Mg 2+ concentrations on DNA origami stability is investigated in the presence of urea and guanidinium chloride (GdmCl), two strong denaturants commonly employed in protein folding studies. While increasing concentrations of both cations stabilize the DNA origami nanostructures against urea denaturation, they are found to promote DNA origami denaturation by GdmCl. These inverse behaviors are rationalized by a salting-out of Gdm + to the hydrophobic DNA base stack. The effect of cation-induced DNA origami denaturation by GdmCl deserves consideration in the design of single-molecule studies and may potentially be exploited in future applications such as selective denaturation for purification purposes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Current status and future prospects of yellow fever vaccines.

PubMed

Beck, Andrew S; Barrett, Alan D T

2015-01-01

Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.

Current Status and Future Prospects of Yellow Fever Vaccines

PubMed Central

Beck, Andrew S.; Barrett, Alan D.T.

2017-01-01

Summary Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized for historically immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be life-long. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID:26366673

MPD Thruster Performance Analytic Models

NASA Technical Reports Server (NTRS)

Gilland, James; Johnston, Geoffrey

2003-01-01

Magnetoplasmadynamic (MPD) thrusters are capable of accelerating quasi-neutral plasmas to high exhaust velocities using Megawatts (MW) of electric power. These characteristics make such devices worthy of consideration for demanding, far-term missions such as the human exploration of Mars or beyond. Assessment of MPD thrusters at the system and mission level is often difficult due to their status as ongoing experimental research topics rather than developed thrusters. However, in order to assess MPD thrusters utility in later missions, some adequate characterization of performance, or more exactly, projected performance, and system level definition are required for use in analyses. The most recent physical models of self-field MPD thrusters have been examined, assessed, and reconfigured for use by systems and mission analysts. The physical models allow for rational projections of thruster performance based on physical parameters that can be measured in the laboratory. The models and their implications for the design of future MPD thrusters are presented.

MPD Thruster Performance Analytic Models

NASA Technical Reports Server (NTRS)

Gilland, James; Johnston, Geoffrey

2007-01-01

Magnetoplasmadynamic (MPD) thrusters are capable of accelerating quasi-neutral plasmas to high exhaust velocities using Megawatts (MW) of electric power. These characteristics make such devices worthy of consideration for demanding, far-term missions such as the human exploration of Mars or beyond. Assessment of MPD thrusters at the system and mission level is often difficult due to their status as ongoing experimental research topics rather than developed thrusters. However, in order to assess MPD thrusters utility in later missions, some adequate characterization of performance, or more exactly, projected performance, and system level definition are required for use in analyses. The most recent physical models of self-field MPD thrusters have been examined, assessed, and reconfigured for use by systems and mission analysts. The physical models allow for rational projections of thruster performance based on physical parameters that can be measured in the laboratory. The models and their implications for the design of future MPD thrusters are presented.

Considerations of informed consent and decision-making competence in older adults with cognitive impairment.

PubMed

Mayo, Ann M; Wallhagen, Margaret I

2009-04-01

Including older adults with cognitive impairment in research studies is necessary to ensure that interventions designed to improve care are effective for all older adults. However, issues related to capacity to consent raise many difficult questions that nurse researchers must address. Protecting vulnerable participants while simultaneously maintaining autonomy and moving important research forward can be challenging. Assessing the decision-making abilities of understanding, appreciation, reasoning, and expressing a choice is an important aspect of determining decision-making capacity. Yet although this is the prominent rational method for judging decision-making competence, it does not take into consideration the importance of culture, values, and emotions. This article focuses on the assessment of decision-making capacity to consent, recommendations for obtaining informed consent in older adults with cognitive impairment, the use of surrogate decision makers, strategies to maximize research participation, and directions for future research. Copyright 2009, SLACK Incorporated.

RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

PubMed

Ashraf, Muhammad; Abid, Farah; Riffat, Sualeha; Bashir, Sajid; Iqbal, Javed; Sarfraz, Muhammad; Afzal, Attia; Zaheer, Muhammad

2015-01-01

The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

Engineering charge transport by heterostructuring solution-processed semiconductors

NASA Astrophysics Data System (ADS)

Voznyy, Oleksandr; Sutherland, Brandon R.; Ip, Alexander H.; Zhitomirsky, David; Sargent, Edward H.

2017-06-01

Solution-processed semiconductor devices are increasingly exploiting heterostructuring — an approach in which two or more materials with different energy landscapes are integrated into a composite system. Heterostructured materials offer an additional degree of freedom to control charge transport and recombination for more efficient optoelectronic devices. By exploiting energetic asymmetry, rationally engineered heterostructured materials can overcome weaknesses, augment strengths and introduce emergent physical phenomena that are otherwise inaccessible to single-material systems. These systems see benefit and application in two distinct branches of charge-carrier manipulation. First, they influence the balance between excitons and free charges to enhance electron extraction in solar cells and photodetectors. Second, they promote radiative recombination by spatially confining electrons and holes, which increases the quantum efficiency of light-emitting diodes. In this Review, we discuss advances in the design and composition of heterostructured materials, consider their implementation in semiconductor devices and examine unexplored paths for future advancement in the field.

Time-Resolved In Situ Liquid-Phase Atomic Force Microscopy and Infrared Nanospectroscopy during the Formation of Metal-Organic Framework Thin Films.

PubMed

Mandemaker, Laurens D B; Filez, Matthias; Delen, Guusje; Tan, Huanshu; Zhang, Xuehua; Lohse, Detlef; Weckhuysen, Bert M

2018-04-19

Metal-organic framework (MOF) thin films show unmatched promise as smart membranes and photocatalytic coatings. However, their nucleation and growth resulting from intricate molecular assembly processes are not well understood yet are crucial to control the thin film properties. Here, we directly observe the nucleation and growth behavior of HKUST-1 thin films by real-time in situ AFM at different temperatures in a Cu-BTC solution. In combination with ex situ infrared (nano)spectroscopy, synthesis at 25 °C reveals initial nucleation of rapidly growing HKUST-1 islands surrounded by a continuously nucleating but slowly growing HKUST-1 carpet. Monitoring at 13 and 50 °C shows the strong impact of temperature on thin film formation, resulting in (partial) nucleation and growth inhibition. The nucleation and growth mechanisms as well as their kinetics provide insights to aid in future rational design of MOF thin films.

Epitaxial growth of hybrid nanostructures

NASA Astrophysics Data System (ADS)

Tan, Chaoliang; Chen, Junze; Wu, Xue-Jun; Zhang, Hua

2018-02-01

Hybrid nanostructures are a class of materials that are typically composed of two or more different components, in which each component has at least one dimension on the nanoscale. The rational design and controlled synthesis of hybrid nanostructures are of great importance in enabling the fine tuning of their properties and functions. Epitaxial growth is a promising approach to the controlled synthesis of hybrid nanostructures with desired structures, crystal phases, exposed facets and/or interfaces. This Review provides a critical summary of the state of the art in the field of epitaxial growth of hybrid nanostructures. We discuss the historical development, architectures and compositions, epitaxy methods, characterization techniques and advantages of epitaxial hybrid nanostructures. Finally, we provide insight into future research directions in this area, which include the epitaxial growth of hybrid nanostructures from a wider range of materials, the study of the underlying mechanism and determining the role of epitaxial growth in influencing the properties and application performance of hybrid nanostructures.

Communicative versus Strategic Rationality: Habermas Theory of Communicative Action and the Social Brain

PubMed Central

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action. PMID:23734238

Systems metabolic engineering: the creation of microbial cell factories by rational metabolic design and evolution.

PubMed

Furusawa, Chikara; Horinouchi, Takaaki; Hirasawa, Takashi; Shimizu, Hiroshi

2013-01-01

It is widely acknowledged that in order to establish sustainable societies, production processes should shift from petrochemical-based processes to bioprocesses. Because bioconversion technologies, in which biomass resources are converted to valuable materials, are preferable to processes dependent on fossil resources, the former should be further developed. The following two approaches can be adopted to improve cellular properties and obtain high productivity and production yield of target products: (1) optimization of cellular metabolic pathways involved in various bioprocesses and (2) creation of stress-tolerant cells that can be active even under severe stress conditions in the bioprocesses. Recent progress in omics analyses has facilitated the analysis of microorganisms based on bioinformatics data for molecular breeding and bioprocess development. Systems metabolic engineering is a new area of study, and it has been defined as a methodology in which metabolic engineering and systems biology are integrated to upgrade the designability of industrially useful microorganisms. This chapter discusses multi-omics analyses and rational design methods for molecular breeding. The first is an example of the rational design of metabolic networks for target production by flux balance analysis using genome-scale metabolic models. Recent progress in the development of genome-scale metabolic models and the application of these models to the design of desirable metabolic networks is also described in this example. The second is an example of evolution engineering with omics analyses for the creation of stress-tolerant microorganisms. Long-term culture experiments to obtain the desired phenotypes and omics analyses to identify the phenotypic changes are described here.

Additively Manufactured and Surface Biofunctionalized Porous Nitinol.

PubMed

Gorgin Karaji, Z; Speirs, M; Dadbakhsh, S; Kruth, J-P; Weinans, H; Zadpoor, A A; Amin Yavari, S

2017-01-18

Enhanced bone tissue regeneration and improved osseointegration are among the most important goals in design of multifunctional orthopedic biomaterials. In this study, we used additive manufacturing (selective laser melting) to develop multifunctional porous nitinol that combines superelasticity with a rationally designed microarchitecture and biofunctionalized surface. The rational design based on triply periodic minimal surfaces aimed to properly adjust the pore size, increase the surface area (thereby amplifying the effects of surface biofunctionalization), and resemble the curvature characteristics of trabecular bone. The surface of additively manufactured (AM) porous nitinol was biofunctionalized using polydopamine-immobilized rhBMP2 for better control of the release kinetics. The actual morphological properties of porous nitinol measured by microcomputed tomography (e.g., open/close porosity, and surface area) closely matched the design values. The superelasticity originated from the austenite phase formed in the nitinol porous structure at room temperature. Polydopamine and rhBMP2 signature peaks were confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy tests. The release of rhBMP2 continued until 28 days. The early time and long-term release profiles were found to be adjustable independent of each other. In vitro cell culture showed improved cell attachment, cell proliferation, cell morphology (spreading, spindle-like shape), and cell coverage as well as elevated levels of ALP activity and increased calcium content for biofunctionalized surfaces as compared to as-manufactured specimens. The demonstrated functionalities of porous nitinol could be used as a basis for deployable orthopedic implants with rationally designed microarchitectures that maximize bone tissue regeneration performance by release of biomolecules with adjustable and well-controlled release profiles.

Towards a rational strategy for monitoring of microbiological quality of ambient waters

PubMed Central

Poma, Hugo Ramiro; Cacciabue, Dolores Gutiérrez; Garcé, Beatriz; Gonzo, Elio Emilio; Rajal, Verónica Beatriz

2012-01-01

Water is one of the main sources of human exposure to microbiological hazards. Although legislation establishes regulatory standards in terms of fecal indicator bacteria to assess the microbiological quality of water, these do not necessarily predict the presence of pathogens such as parasites and viruses. Better surveillance and management strategies are needed to assess the risk of pathogens waterborne transmission. We established a baseline dataset to characterize river water quality, identify changes over time, and design a rational monitoring strategy. Data from a year-long monthly monitoring campaign of the polluted Arenales River (Argentina), were analyzed to statistically correlate physicochemical and microbiological variables, the seasonal and longitudinal variation of the water quality and determine the similarity between study sites. The measured variables (sixteen) reflected the deterioration in the river quality through the city. Different viruses and parasites found did not correlate with the concentration of total and thermotolerant coliforms. There was significant seasonal variation for temperature, turbidity, conductivity, dissolved oxygen, enterococci, and norovirus. Strong correlations between some variables were found; we selected eight variables (dissolved oxygen, conductivity, turbidity, total and thermotolerant coliforms, Enterococcus, and adenovirus and Microsporidium as viral and parasitological indicators, respectively) for future monitoring. There was similarity between the monitoring locations, which were grouped into four clusters validated by cophenetic correlation and supported by discriminant analysis. This allowed us to reduce the number of sites, from eleven down to five. Sixty seven percent of the total variance and the correlation structure between variables was explained using five principal components. All these analyses led to a new long-term systematic monitoring scheme A rational monitoring strategy based on the selection of the most suitable monitoring points and of the most significant variables to measure, will result in optimal use of the limited resources available to adequately protect public and environmental health. PMID:22771467

Pathophysiologic mechanisms of biomedical nanomaterials

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

Wang, Liming, E-mail: wangliming@ihep.ac.cn; Chen, Chunying, E-mail: chenchy@nanoctr.cn

Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future.more » We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs.« less

Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens.

PubMed

Song, Mengjia; Chen, Xinfeng; Wang, Liping; Zhang, Yi

2018-04-01

Programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) blockade has shown promising effects in cancer immunotherapy. Removing the so-called " brakes" on T cell immune responses by blocking the PD-1/PD-L1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients. However, 30%-60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site, immunosuppressive factors in the tumor microenvironment (TME), and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.

Recent advances in rational approaches for enzyme engineering

PubMed Central

Steiner, Kerstin; Schwab, Helmut

2012-01-01

Enzymes are an attractive alternative in the asymmetric syntheses of chiral building blocks. To meet the requirements of industrial biotechnology and to introduce new functionalities, the enzymes need to be optimized by protein engineering. This article specifically reviews rational approaches for enzyme engineering and de novo enzyme design involving structure-based approaches developed in recent years for improvement of the enzymes’ performance, broadened substrate range, and creation of novel functionalities to obtain products with high added value for industrial applications. PMID:24688651

Serving two masters: quality teaching and learning versus economic rationalism.

PubMed

Kenny, A J; Kendall, S

2001-11-01

Nurse educators face the challenge of competing pressures. Programmes must be developed that more adequately prepare students to meet the demands of a changing and complex health care system. These programmes must reflect excellence in teaching and learning and this needs to be achieved within the constraints of economic rationalism. The design of a model based on principles of self directed learning assisted one university to deliver a high quality clinical skills programme. Copyright 2001 Harcourt Publishers Ltd.

Persuasive messages. Development of persuasive messages may help increase mothers' compliance of their children's immunization schedule.

PubMed

Gore, P; Madhavan, S; Curry, D; McClurg, G; Castiglia, M; Rosenbluth, S A; Smego, R A

1998-01-01

Effective immunization campaigns can be designed by determining which persuasion strategy is most effective in attracting the attention of mothers of preschoolers. The authors assess the impact of three persuasional strategies: fear-arousal, motherhood-arousal, and rational messages, on mothers of preschoolers who are late for their immunizations. The fear-arousal message was found to be most effective, followed by the motherhood-arousal, and then the rational message, in attracting mothers' attention to their child's immunization status.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Management of high-grade dysplasia in Barrett's esophagus.

PubMed

Palley, S L; Sampliner, R E; Garewal, H S

1989-08-01

When Barrett's esophagus is complicated by adenocarcinoma, surgery is indicated in appropriate patients. Until now, high-grade dysplasia in Barrett's esophagus has been managed in a similar fashion. We explore this approach and review reported cases of high-grade dysplasia to suggest guidelines for collection of data to make future clinical decisions more rational.

Critical Thinking: Attitudes, Skills, and Ambiguity.

ERIC Educational Resources Information Center

Shaughnessy, Michael F.

This paper provides an overview of the realm of critical thinking. The document explores the development of a critical thinking attitude and specific skills relative to logic, rationality, and reasoning that must be fostered to facilitate and enhance future learning. The issue of ambiguity also is addressed as a central construct of the critical…

Expanding Rational Molecular Design beyond Pharma: Metrics to Guide Safer Chemical Design

EPA Science Inventory

The demand for safer, healthier and sustainable products, materials and processes has been increasing over the past several years. Differentiating which chemicals are relatively less hazardous than others, often referred to as “greener” or “sustainable, demands a comprehensive, h...

Muck Utilization Planning - Urban Transportation Tunneling : A Handbook of Rational Practices for Planners and Designers

DOT National Transportation Integrated Search

1977-05-01

This handbook alerts transportation system planners and designers to planning methods which can lead to more efficient use of earth and rock materials produced during excavation for transportation tunnels and large excavations. The earth and rock mat...

Stress Management: A Rational Approach.

ERIC Educational Resources Information Center

Reeves, Cecil

This workbook was designed for use as the primary resource tool during a l-day participatory stress management seminar in which participants identify stressful situations, conduct analyses, and develop approaches to manage the stressful situations more effectively. Small group warm-up activities designed to introduce participants, encourage…

Expanding Rational Molecular Design beyond Pharma: Metrics toGuide Safer Chemical Design

EPA Science Inventory

The demand for safer, healthier and sustainable products, materials and processes has been increasing over the past several years. Differentiating which chemicals are relatively less hazardous than others, often referred to as “greener” or “sustainable, demands a comprehensive, h...

Rational Design of Si@SiO2/C Composites Using Sustainable Cellulose as a Carbon Resource for Anodes in Lithium-Ion Batteries.

PubMed

Shen, Dazhi; Huang, Chaofan; Gan, Lihui; Liu, Jian; Gong, Zhengliang; Long, Minnan

2018-03-07

In this work, we propose a novel and facile route for the rational design of Si@SiO 2 /C anode materials by using sustainable and environment-friendly cellulose as a carbon resource. To simultaneously obtain a SiO 2 layer and a carbon scaffold, a specially designed homogeneous cellulose solution and commercial Si nanopowder are used as the starting materials, and the cellulose/Si composite is directly assembled by an in situ regenerating method. Subsequently, Si@SiO 2 /C composite is obtained after carbonization. As expected, Si@SiO 2 is homogeneously encapsulated in the cellulose-derived carbon network. The obtained Si@SiO 2 /C composite shows a high reversible capacity of 1071 mA h g -1 at a current density of 420 mA g -1 and 70% capacity retention after 200 cycles. This novel, sustainable, and effective design is a promising approach to obtain high-performance and cost-effective composite anodes for practical applications.

Structural optimization of large ocean-going structures

NASA Technical Reports Server (NTRS)

Hughes, O. F.

1984-01-01

Ocean-going vehicles and platforms are among the largest structures in the world and are subjected to relatively harsh conditions of motions and loads. Some of them, such as semi-submersible platforms, are a relatively new type of structure and hence there is no formal, well evolved and established structural design code as there is for more traditional structures. More recently, efforts have also been made to develop a design method of this type for ships and other ocean structures. One of the many advantages of a rationally based design method is versatility; it can be used for structures that have widely differing purposes, measures of merit, shapes and sizes. The purpose is to describe a rationally based design method that has been developed within the field of ocean structures, in order that persons dealing with other types of structure can judge whether and to what extent its various features may be useful for those other types. Also, even though some features may not be applicable they might stimulate some useful ideas.

Theory and simulation of DNA-coated colloids: a guide for rational design.

PubMed

Angioletti-Uberti, Stefano; Mognetti, Bortolo M; Frenkel, Daan

2016-03-07

By exploiting the exquisite selectivity of DNA hybridization, DNA-coated colloids (DNACCs) can be made to self-assemble in a wide variety of structures. The beauty of this system stems largely from its exceptional versatility and from the fact that a proper choice of the grafted DNA sequences yields fine control over the colloidal interactions. Theory and simulations have an important role to play in the optimal design of self assembling DNACCs. At present, the powerful model-based design tools are not widely used, because the theoretical literature is fragmented and the connection between different theories is often not evident. In this Perspective, we aim to discuss the similarities and differences between the different models that have been described in the literature, their underlying assumptions, their strengths and their weaknesses. Using the tools described in the present Review, it should be possible to move towards a more rational design of novel self-assembling structures of DNACCs and, more generally, of systems where ligand-receptor are used to control interactions.

Drug delivery systems: optimising the structure of peptide carriers for synthetic antimicrobial drugs.

PubMed

Payne, J W

1986-01-01

This paper discusses the concept of smugglins, i.e., molecules that are formed by attaching to, or incorporating into, normal cell nutrients varied moieties as a means of transporting otherwise impermeant substances into cells. Examples of antimicrobial smugglins that use this principle in Nature are described. The rationally designed antibiotic smugglins investigated to date are critically reviewed. Criteria for the design of optimal peptide carriers for antimicrobial smugglins are considered. A computer-linked, continuous-flow system for rapid measurement of the kinetic parameters for substrate transport via peptide permeases is described which, together with current molecular, genetic and biochemical techniques, now provides the means to obtain the information on which rational design should be based; examples are given for Escherichia coli and Candida albicans. After an uncertain commercial start, it now seems likely that increasing understanding of the uptake processes and other relevant features will make drug targeting using peptide carriers an achievable goal. Certainly their widespread occurrence in Nature should provide added incentive for the design of synthetic smugglins.

The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

PubMed

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

2015-07-14

A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

Rational design of the exchange-spring permanent magnet.

PubMed

Jiang, J S; Bader, S D

2014-02-12

The development of the optimal exchange-spring permanent magnet balances exchange hardening, magnetization enhancement, and the feasibility of scalable fabrication. These requirements can be met with a rational design of the microstructural characteristics. The magnetization processes in several model exchange-spring structures with different geometries have been analyzed with both micromagnetic simulations and nucleation theory. The multilayer geometry and the soft-cylinders-in-hard-matrix geometry have the highest achievable figure of merit (BH)max, while the soft-spheres-in-hard-matrix geometry has the lowest upper limit for (BH)max. The cylindrical geometry permits the soft phase to be larger and does not require strict size control. Exchange-spring permanent magnets based on the cylindrical geometry may be amenable to scaled-up fabrication.

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent advances in the rational design and development of LIM kinase inhibitors are not enough to enter clinical trials.

PubMed

Manetti, Fabrizio

2018-06-08

LIM kinases are involved in various pathophysiological processes that depend on actin organization. Alteration of microtubule dynamics by LIMK dysregulation is in fact related to tumor progression and metastasis, viral infection, and ocular diseases, such as glaucoma. As a consequence, many efforts have been done in recent years to rationally design small molecules able to inhibit LIMK activity selectively, without affecting other kinases. As a result, compounds optimized in terms of binding affinity and pharmacokinetic parameters have been discovered, that however failed to access clinical trials. In this review, a comprehensive survey of recent LIMK inhibitors is reported, together with SAR considerations and optimization processes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Web-Based DNA Vaccine Database DNAVaxDB and Its Usage for Rational DNA Vaccine Design.

PubMed

Racz, Rebecca; He, Yongqun

2016-01-01

A DNA vaccine is a vaccine that uses a mammalian expression vector to express one or more protein antigens and is administered in vivo to induce an adaptive immune response. Since the 1990s, a significant amount of research has been performed on DNA vaccines and the mechanisms behind them. To meet the needs of the DNA vaccine research community, we created DNAVaxDB ( http://www.violinet.org/dnavaxdb ), the first Web-based database and analysis resource of experimentally verified DNA vaccines. All the data in DNAVaxDB, which includes plasmids, antigens, vaccines, and sources, is manually curated and experimentally verified. This chapter goes over the detail of DNAVaxDB system and shows how the DNA vaccine database, combined with the Vaxign vaccine design tool, can be used for rational design of a DNA vaccine against a pathogen, such as Mycobacterium bovis.

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

NASA Astrophysics Data System (ADS)

Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

2014-01-01

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

Design flood hydrograph estimation procedure for small and fully-ungauged basins

NASA Astrophysics Data System (ADS)

Grimaldi, S.; Petroselli, A.

2013-12-01

The Rational Formula is the most applied equation in practical hydrology due to its simplicity and the effective compromise between theory and data availability. Although the Rational Formula is affected by several drawbacks, it is reliable and surprisingly accurate considering the paucity of input information. However, after more than a century, the recent computational, theoretical, and large-scale monitoring progresses compel us to try to suggest a more advanced yet still empirical procedure for estimating peak discharge in small and ungauged basins. In this contribution an alternative empirical procedure (named EBA4SUB - Event Based Approach for Small and Ungauged Basins) based on the common modelling steps: design hyetograph, rainfall excess, and rainfall-runoff transformation, is described. The proposed approach, accurately adapted for the fully-ungauged basin condition, provides a potentially better estimation of the peak discharge, a design hydrograph shape, and, most importantly, reduces the subjectivity of the hydrologist in its application.

Towards the engineering of in vitro systems.

PubMed

Hold, Christoph; Panke, Sven

2009-08-06

Synthetic biology aims at rationally implementing biological systems from scratch. Given the complexity of living systems and our current lack of understanding of many aspects of living cells, this is a major undertaking. The design of in vitro systems can be considerably easier, because they can consist of fewer constituents, are quasi time invariant, their parameter space can be better accessed and they can be much more easily perturbed and then analysed chemically and mathematically. However, even for simplified in vitro systems, following a comprehensively rational design procedure is still difficult. When looking at a comparatively simple system, such as a medium-sized enzymatic reaction network as it is represented by glycolysis, major issues such as a lack of comprehensive enzyme kinetics and of suitable knowledge on crucial design parameters remain. Nevertheless, in vitro systems are very suitable to overcome these obstacles and therefore well placed to act as a stepping stone to engineering living systems.

Rational design of competitive electrocatalysts for the oxygen reduction reaction in hydrogen fuel cells

NASA Astrophysics Data System (ADS)

Stolbov, Sergey; Alcántara Ortigoza, Marisol

2012-02-01

The large-scale application of one of the most promising clean and renewable sources of energy, hydrogen fuel cells, still awaits efficient and cost-effective electrocatalysts for the oxygen reduction reaction (ORR) occurring on the cathode. We demonstrate that truly rational design renders electrocatalysts possessing both qualities. By unifying the knowledge on surface morphology, composition, electronic structure and reactivity, we solve that sandwich-like structures are an excellent choice for optimization. Their constituting species couple synergistically yielding reaction-environment stability, cost-effectiveness and tunable reactivity. This cooperative-action concept enabled us to predict two advantageous ORR electrocatalysts. Density functional theory calculations of the reaction free-energy diagrams confirm that these materials are more active toward ORR than the so far best Pt-based catalysts. Our designing concept advances also a general approach for engineering materials in heterogeneous catalysis.

Rational In Silico Design of an Organic Semiconductor with Improved Electron Mobility.

PubMed

Friederich, Pascal; Gómez, Verónica; Sprau, Christian; Meded, Velimir; Strunk, Timo; Jenne, Michael; Magri, Andrea; Symalla, Franz; Colsmann, Alexander; Ruben, Mario; Wenzel, Wolfgang

2017-11-01

Organic semiconductors find a wide range of applications, such as in organic light emitting diodes, organic solar cells, and organic field effect transistors. One of their most striking disadvantages in comparison to crystalline inorganic semiconductors is their low charge-carrier mobility, which manifests itself in major device constraints such as limited photoactive layer thicknesses. Trial-and-error attempts to increase charge-carrier mobility are impeded by the complex interplay of the molecular and electronic structure of the material with its morphology. Here, the viability of a multiscale simulation approach to rationally design materials with improved electron mobility is demonstrated. Starting from one of the most widely used electron conducting materials (Alq 3 ), novel organic semiconductors with tailored electronic properties are designed for which an improvement of the electron mobility by three orders of magnitude is predicted and experimentally confirmed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design Principles for the Atomic and Electronic Structure of Halide Perovskite Photovoltaic Materials: Insights from Computation.

PubMed

Berger, Robert F

2018-02-09

In the current decade, perovskite solar cell research has emerged as a remarkably active, promising, and rapidly developing field. Alongside breakthroughs in synthesis and device engineering, halide perovskite photovoltaic materials have been the subject of predictive and explanatory computational work. In this Minireview, we focus on a subset of this computation: density functional theory (DFT)-based work highlighting the ways in which the electronic structure and band gap of this class of materials can be tuned via changes in atomic structure. We distill this body of computational literature into a set of underlying design principles for the band gap engineering of these materials, and rationalize these principles from the viewpoint of band-edge orbital character. We hope that this perspective provides guidance and insight toward the rational design and continued improvement of perovskite photovoltaics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational design of capillary-driven flows for paper-based microfluidics.

PubMed

Elizalde, Emanuel; Urteaga, Raúl; Berli, Claudio L A

2015-05-21

The design of paper-based assays that integrate passive pumping requires a precise programming of the fluid transport, which has to be encoded in the geometrical shape of the substrate. This requirement becomes critical in multiple-step processes, where fluid handling must be accurate and reproducible for each operation. The present work theoretically investigates the capillary imbibition in paper-like substrates to better understand fluid transport in terms of the macroscopic geometry of the flow domain. A fluid dynamic model was derived for homogeneous porous substrates with arbitrary cross-sectional shapes, which allows one to determine the cross-sectional profile required for a prescribed fluid velocity or mass transport rate. An extension of the model to slit microchannels is also demonstrated. Calculations were validated by experiments with prototypes fabricated in our lab. The proposed method constitutes a valuable tool for the rational design of paper-based assays.

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

PubMed

Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

2018-02-12

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

Using Fitness Landscapes for Rational Hepatitis C Immunogen Design

NASA Astrophysics Data System (ADS)

Hart, Gregory; Ferguson, Andrew

2015-03-01

Hepatitis C virus afflicts 170 million people worldwide, 2-3% of the global population. Prophylactic vaccination offers the most realistic and cost effective hope of controlling this epidemic, particularly in the developing world where expensive drug therapies are unavailable. Despite 20 years of research, the high mutability of the virus, and lack of knowledge of what constitutes effective immune responses, have impeded development of an effective vaccine. Coupling data mining of sequence databases with the Potts model, we have developed a computational approach to systematically identify viral vulnerabilities and perform rational design of vaccine immunogens. We applied our approach to the nonstructural proteins NS3, NSA, NSA, and NSB which are crucial for viral replication.The predictions of our model are in good accord with experimental measurements and clinical observations, and we have used our model to design immunogen candidates to elicit T-cell responses against vulnerable regions of theseviral proteins.

Attenuation of Vibrio fischeri quorum sensing using rationally designed polymers.

PubMed

Piletska, Elena V; Stavroulakis, Georgios; Karim, Kal; Whitcombe, Michael J; Chianella, Iva; Sharma, Anant; Eboigbodin, Kevin E; Robinson, Gary K; Piletsky, Sergey A

2010-04-12

A first attempt to attenuate the quorum sensing (QS) of a marine heterotroph microorganism, Vibrio fischeri , using signal molecule-sequestering polymers (SSPs) is presented. A set of rationally designed polymers with affinity toward a signal molecule of V. fischeri , N-(beta-ketocaproyl)-l-homoserine lactone (3-oxo-C6-AHL) was produced. It is reported that computationally designed polymers could sequester a signal molecule of V. fischeri and prevent QS-controlled phenotypes (in this case, bioluminescence) from being up-regulated. It was proven that the attenuation of bioluminescence of V. fischeri was due to sequestration of the signal molecule by specific polymers and not due to the toxicity of polymer or nonspecific depletion of nutrients. The ability to disrupt the bacterial communication using easy to synthesize and chemically inert polymers could provide a new concept for the development of pharmaceuticals and susceptible device coatings such as catheters.

Structural and conformational determinants of macrocycle cell permeability.

PubMed

Over, Björn; Matsson, Pär; Tyrchan, Christian; Artursson, Per; Doak, Bradley C; Foley, Michael A; Hilgendorf, Constanze; Johnston, Stephen E; Lee, Maurice D; Lewis, Richard J; McCarren, Patrick; Muncipinto, Giovanni; Norinder, Ulf; Perry, Matthew W D; Duvall, Jeremy R; Kihlberg, Jan

2016-12-01

Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.