ERIC Educational Resources Information Center
Tang, Thomas Li-Ping
Goal-setting literature has suggested that specific, difficult goals will produce higher performance levels than easy goals. A difficult task or one with negative performance feedback may increase an individual's perceived challenge of the task which may in turn enhance his motivation. Effects of the Protestant work ethic and perceived challenge…
Hinkle, Joshua C; Weisburd, David; Famega, Christine; Ready, Justin
2013-01-01
Hot spots policing is one of the most influential police innovations, with a strong body of experimental research showing it to be effective in reducing crime and disorder. However, most studies have been conducted in major cities, and we thus know little about whether it is effective in smaller cities, which account for a majority of police agencies. The lack of experimental studies in smaller cities is likely in part due to challenges designing statistically powerful tests in such contexts. The current article explores the challenges of statistical power and "noise" resulting from low base rates of crime in smaller cities and provides suggestions for future evaluations to overcome these limitations. Data from a randomized experimental evaluation of broken windows policing in hot spots are used to illustrate the challenges that low base rates present for evaluating hot spots policing programs in smaller cities. Analyses show low base rates make it difficult to detect treatment effects. Very large effect sizes would be required to reach sufficient power, and random fluctuations around low base rates make detecting treatment effects difficult, irrespective of power, by masking differences between treatment and control groups. Low base rates present strong challenges to researchers attempting to evaluate hot spots policing in smaller cities. As such, base rates must be taken directly into account when designing experimental evaluations. The article offers suggestions for researchers attempting to expand the examination of hot spots policing and other microplace-based interventions to smaller jurisdictions.
ERIC Educational Resources Information Center
Cohen, Lorraine
1995-01-01
Maintains that, during the 1980s, it was difficult to find classroom approaches that effectively challenged racial and class stereotypes. Describes a college community service project designed to teach students about racial, social, and gender discrimination. (CFR)
An Introductory Calculus-Based Mechanics Investigation
ERIC Educational Resources Information Center
Allen, Bradley
2017-01-01
One challenge for the introductory physics teacher is incorporating calculus techniques into the laboratory setting. It can be difficult to strike a balance between presenting an experimental task for which calculus is essential and making the mathematics accessible to learners who may be apprehensive about applying it. One-dimensional kinematics…
The Effects of Rhetorical and Content Subgoals on Writing and Learning
ERIC Educational Resources Information Center
Klein, Perry D.; Haug, Katrina N.; Arcon, Nina
2017-01-01
Argument writing is challenging for elementary students. Previous experimental research has focused on scaffolding rhetorical goals, leaving content goals relatively unexplored. In a randomized experiment, 73 students in grades 5, 6, and 7 wrote persuasive texts about difficult-to-classify vertebrates. Each student received one of three sets of…
The "Nut-Drop" Experiment--Bringing Millikan's Challenge to Introductory Students
ERIC Educational Resources Information Center
McCann, Lowell I.; Blodgett, Earl D.
2009-01-01
One of the difficulties in teaching 20th-century physics ideas in introductory physics is that many seminal experiments that are discussed in textbooks are difficult or expensive for students to access experimentally. In this paper, we discuss an analogous exercise to Millikan's oil-drop experiment that lets students experience some of the physics…
ERIC Educational Resources Information Center
Beebe, Dean W.; Fallone, Gahan; Godiwala, Neha; Flanigan, Matt; Martin, David; Schaffner, Laura; Amin, Raouf
2008-01-01
Background: Sleep deprivation is common among adolescents and has been associated with adverse behavioral and educational outcomes. However, it is difficult to draw strong causal conclusions because of a dearth of experimental sleep research. In part, this appears related to methodological challenges when working with this population. This study…
Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree
2016-12-01
Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. © The Author(s) 2016.
Graw, Frederik; Perelson, Alan S.
2016-01-01
The way in which a viral infection spreads within a host is a complex process that is not well understood. Different viruses, such as human immunodeficiency virus type 1 and hepatitis C virus, have evolved different strategies, including direct cell-to-cell transmission and cell-free transmission, to spread within a host. To what extent these two modes of transmission are exploited in vivo is still unknown. Mathematical modeling has been an essential tool to get a better systematic and quantitative understanding of viral processes that are difficult to discern through strictly experimental approaches. In this review, we discuss recent attempts that combine experimental data and mathematical modeling in order to determine and quantify viral transmission modes. We also discuss the current challenges for a systems-level understanding of viral spread, and we highlight the promises and challenges that novel experimental techniques and data will bring to the field. PMID:27618637
Singh, Vijay Pal; Pratap, Kunal; Sinha, Juhi; Desiraju, Koundinya; Bahal, Devika; Kukreti, Ritushree
2016-01-01
Animal experiments that are conducted worldwide contribute to significant findings and breakthroughs in the understanding of the underlying mechanisms of various diseases, bringing up appropriate clinical interventions. However, their predictive value is often low, leading to translational failure. Problems like translational failure of animal studies and poorly designed animal experiments lead to loss of animal lives and less translatable data which affect research outcomes ethically and economically. Due to increasing complexities in animal usage with changes in public perception and stringent guidelines, it is becoming difficult to use animals for conducting studies. This review deals with challenges like poor experimental design and ethical concerns and discusses key concepts like sample size, statistics in experimental design, humane endpoints, economic assessment, species difference, housing conditions, and systematic reviews and meta-analyses that are often neglected. If practiced, these strategies can refine the procedures effectively and help translate the outcomes efficiently. PMID:27694614
Why Nudges Coerce: Experimental Evidence on the Architecture of Regulation.
Hill, Adam
2017-07-04
Critics frequently argue that nudges are more covert, less transparent, and more difficult to monitor than traditional regulatory tools. Edward Glaeser, for example, argues that "[p]ublic monitoring of soft paternalism is much more difficult than public monitoring of hard paternalism". As one of the leading proponents of soft paternalism, Cass Sunstein, acknowledges, while "[m]andates and commands are highly visible", soft paternalism, "and some nudges in particular[,] may be invisible". In response to this challenge, proponents of nudging argue that invisibility for any given individual in a particular choice environment is compatible with "careful public scrutiny" of the nudge. This paper offers the first of its kind experimental evidence that tests whether nudges are, in fact, compatible with "careful public scrutiny". Using three sets of experiments, the paper argues that, even when entirely visible, nudges attract less scrutiny than their "hard law" counterparts.
Thermal-to-visible face recognition using partial least squares.
Hu, Shuowen; Choi, Jonghyun; Chan, Alex L; Schwartz, William Robson
2015-03-01
Although visible face recognition has been an active area of research for several decades, cross-modal face recognition has only been explored by the biometrics community relatively recently. Thermal-to-visible face recognition is one of the most difficult cross-modal face recognition challenges, because of the difference in phenomenology between the thermal and visible imaging modalities. We address the cross-modal recognition problem using a partial least squares (PLS) regression-based approach consisting of preprocessing, feature extraction, and PLS model building. The preprocessing and feature extraction stages are designed to reduce the modality gap between the thermal and visible facial signatures, and facilitate the subsequent one-vs-all PLS-based model building. We incorporate multi-modal information into the PLS model building stage to enhance cross-modal recognition. The performance of the proposed recognition algorithm is evaluated on three challenging datasets containing visible and thermal imagery acquired under different experimental scenarios: time-lapse, physical tasks, mental tasks, and subject-to-camera range. These scenarios represent difficult challenges relevant to real-world applications. We demonstrate that the proposed method performs robustly for the examined scenarios.
An, Hongjie; Tan, Beng Hau; Ohl, Claus-Dieter
2016-12-06
The widespread application of surface-attached nanobubbles and nanodroplets in biomedical engineering and nanotechnology is limited by numerous experimental challenges, in particular, the possibility of contamination in nucleation experiments. These challenges are complicated by recent reports that it can be difficult to distinguish between nanoscale drops and bubbles. Here we identify clear differences in the mechanical responses of nanobubbles and nanodroplets under various modes of AFM imaging that subject the objects to predominantly vertical or lateral forces. This allows us to distinguish among nanodroplets, nanobubbles, and oil-covered nanobubbles in water.
Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers
Chambers, Mark A.; Rogers, Fiona; Delahay, Richard J.; Lesellier, Sandrine; Ashford, Roland; Dalley, Deanna; Gowtage, Sonya; Davé, Dipesh; Palmer, Si; Brewer, Jacky; Crawshaw, Timothy; Clifton-Hadley, Richard; Carter, Steve; Cheeseman, Chris; Hanks, Chris; Murray, Alistair; Palphramand, Kate; Pietravalle, Stéphane; Smith, Graham C.; Tomlinson, Alexandra; Walker, Neil J.; Wilson, Gavin J.; Corner, Leigh A. L.; Rushton, Stephen P.; Shirley, Mark D. F.; Gettinby, George; McDonald, Robbie A.; Hewinson, R. Glyn
2011-01-01
Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle. PMID:21123260
Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J. Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V.; Craig, Timothy K.; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut; Ma, Xiaolei; Nelson, Daniel C.; van Raaij, Mark J.; Rohwer, Forest; Segall, Anca; Seguritan, Victor; Zeth, Kornelius; Schwede, Torsten
2014-01-01
For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict trans-membrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin IL-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fibre protein gp17 from bacteriophage T7; the Bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins. PMID:24318984
Chen, Wen-Jie; Xiao, Meng; Chan, C. T.
2016-01-01
Weyl points, as monopoles of Berry curvature in momentum space, have captured much attention recently in various branches of physics. Realizing topological materials that exhibit such nodal points is challenging and indeed, Weyl points have been found experimentally in transition metal arsenide and phosphide and gyroid photonic crystal whose structure is complex. If realizing even the simplest type of single Weyl nodes with a topological charge of 1 is difficult, then making a real crystal carrying higher topological charges may seem more challenging. Here we design, and fabricate using planar fabrication technology, a photonic crystal possessing single Weyl points (including type-II nodes) and multiple Weyl points with topological charges of 2 and 3. We characterize this photonic crystal and find nontrivial 2D bulk band gaps for a fixed kz and the associated surface modes. The robustness of these surface states against kz-preserving scattering is experimentally observed for the first time. PMID:27703140
Cross-Correlation-Based Structural System Identification Using Unmanned Aerial Vehicles
Yoon, Hyungchul; Hoskere, Vedhus; Park, Jong-Woong; Spencer, Billie F.
2017-01-01
Computer vision techniques have been employed to characterize dynamic properties of structures, as well as to capture structural motion for system identification purposes. All of these methods leverage image-processing techniques using a stationary camera. This requirement makes finding an effective location for camera installation difficult, because civil infrastructure (i.e., bridges, buildings, etc.) are often difficult to access, being constructed over rivers, roads, or other obstacles. This paper seeks to use video from Unmanned Aerial Vehicles (UAVs) to address this problem. As opposed to the traditional way of using stationary cameras, the use of UAVs brings the issue of the camera itself moving; thus, the displacements of the structure obtained by processing UAV video are relative to the UAV camera. Some efforts have been reported to compensate for the camera motion, but they require certain assumptions that may be difficult to satisfy. This paper proposes a new method for structural system identification using the UAV video directly. Several challenges are addressed, including: (1) estimation of an appropriate scale factor; and (2) compensation for the rolling shutter effect. Experimental validation is carried out to validate the proposed approach. The experimental results demonstrate the efficacy and significant potential of the proposed approach. PMID:28891985
A Protein Chimera Strategy Supports Production of a Model "Difficult-to-Express" Recombinant Target.
Hussain, Hirra; Fisher, David I; Roth, Robert G; Abbott, W Mark; Carballo-Amador, Manuel Alejandro; Warwicker, Jim; Dickson, Alan J
2018-06-22
Due in part to the needs of the biopharmaceutical industry, there has been an increased drive to generate high quality recombinant proteins in large amounts. However, achieving high yields can be a challenge as the novelty and increased complexity of new targets often makes them 'difficult-to-express'. This study aimed to define the molecular features that restrict the production of a model 'difficult-to-express' recombinant protein, Tissue Inhibitor Metalloproteinase-3 (TIMP-3). Building from experimental data, computational approaches were used to rationalise the re-design of this recombinant target to generate a chimera with enhanced secretion. The results highlight the importance of early identification of unfavourable sequence attributes, enabling the generation of engineered protein forms that bypass 'secretory' bottlenecks and result in efficient recombinant protein production. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V; Craig, Timothy K; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut; Ma, Xiaolei; Nelson, Daniel C; van Raaij, Mark J; Rohwer, Forest; Segall, Anca; Seguritan, Victor; Zeth, Kornelius; Schwede, Torsten
2014-02-01
For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, more than 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this article, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict transmembrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin (IL)-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fiber protein gene product 17 from bacteriophage T7; the bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally, an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins. Copyright © 2013 The Authors. Wiley Periodicals, Inc.
Determination of Membrane-Insertion Free Energies by Molecular Dynamics Simulations
Gumbart, James; Roux, Benoît
2012-01-01
The accurate prediction of membrane-insertion probability for arbitrary protein sequences is a critical challenge to identifying membrane proteins and determining their folded structures. Although algorithms based on sequence statistics have had moderate success, a complete understanding of the energetic factors that drive the insertion of membrane proteins is essential to thoroughly meeting this challenge. In the last few years, numerous attempts to define a free-energy scale for amino-acid insertion have been made, yet disagreement between most experimental and theoretical scales persists. However, for a recently resolved water-to-bilayer scale, it is found that molecular dynamics simulations that carefully mimic the conditions of the experiment can reproduce experimental free energies, even when using the same force field as previous computational studies that were cited as evidence of this disagreement. Therefore, it is suggested that experimental and simulation-based scales can both be accurate and that discrepancies stem from disparities in the microscopic processes being considered rather than methodological errors. Furthermore, these disparities make the development of a single universally applicable membrane-insertion free energy scale difficult. PMID:22385850
Three-dimensional broadband omnidirectional acoustic ground cloak
NASA Astrophysics Data System (ADS)
Zigoneanu, Lucian; Popa, Bogdan-Ioan; Cummer, Steven A.
2014-04-01
The control of sound propagation and reflection has always been the goal of engineers involved in the design of acoustic systems. A recent design approach based on coordinate transformations, which is applicable to many physical systems, together with the development of a new class of engineered materials called metamaterials, has opened the road to the unconstrained control of sound. However, the ideal material parameters prescribed by this methodology are complex and challenging to obtain experimentally, even using metamaterial design approaches. Not surprisingly, experimental demonstration of devices obtained using transformation acoustics is difficult, and has been implemented only in two-dimensional configurations. Here, we demonstrate the design and experimental characterization of an almost perfect three-dimensional, broadband, and, most importantly, omnidirectional acoustic device that renders a region of space three wavelengths in diameter invisible to sound.
First-Principles Study of Interfacial Boundaries in Ni-Ni3AL (Postprint)
2014-05-01
1,2] and extensions thereof. The experimental technique is difficult as accurate measurements of average particle size over time is challeng- ing...8]. There is significant scatter in the measured values of r and the result is strongly dependent on what model is used to describe the particle size ...binary Ni– Al alloys. This study focused on the evolution of particle size and IFB width of during annealing at two tempera- tures (823 and 873 K) for
Gestural cue analysis in automated semantic miscommunication annotation
Inoue, Masashi; Ogihara, Mitsunori; Hanada, Ryoko; Furuyama, Nobuhiro
2011-01-01
The automated annotation of conversational video by semantic miscommunication labels is a challenging topic. Although miscommunications are often obvious to the speakers as well as the observers, it is difficult for machines to detect them from the low-level features. We investigate the utility of gestural cues in this paper among various non-verbal features. Compared with gesture recognition tasks in human-computer interaction, this process is difficult due to the lack of understanding on which cues contribute to miscommunications and the implicitness of gestures. Nine simple gestural features are taken from gesture data, and both simple and complex classifiers are constructed using machine learning. The experimental results suggest that there is no single gestural feature that can predict or explain the occurrence of semantic miscommunication in our setting. PMID:23585724
Bass, Elizabeth; Kaplan-Liss, Evonne; Dorf, Dennis; Broderick, Joan E.
2012-01-01
Psychogenic illness during disasters can cripple emergency healthcare services. Almost all research into this phenomenon has been retrospective and observational, and much of it suggests that media coverage can amplify psychogenic outbreaks. But there is little empirical evidence that this is true or that, conversely, media reports can mitigate psychogenic symptoms. In their work experimentally inducing psychogenic illness, the authors became sharply aware that it is difficult to experimentally mimic real-time media coverage. Yet clarifying media’s effects on psychogenic illness is important if we want to prevent psychological disturbance. To meet this challenge, the authors advocate the funding and development of research protocols in advance of public emergencies, ready to be implemented in real-time. Coupled with digital media, which can track the reading and viewing behavior of millions of people, this approach can help us better understand media’s impact on public health during an emergency, for better or for worse. PMID:23125953
Mack, Jennifer W; Ilowite, Maya; Taddei, Sarah
2017-02-15
Previous work on difficult relationships between patients and physicians has largely focused on the adult primary care setting and has typically held patients responsible for challenges. Little is known about experiences in pediatrics and more serious illness; therefore, we examined difficult relationships between parents and physicians of children with cancer. This was a cross-sectional, semistructured interview study of parents and physicians of children with cancer at the Dana-Farber Cancer Institute and Boston Children's Hospital (Boston, Mass) in longitudinal primary oncology relationships in which the parent, physician, or both considered the relationship difficult. Interviews were audiotaped, transcribed, and subjected to a content analysis. Dyadic parent and physician interviews were performed for 29 relationships. Twenty were experienced as difficult by both parents and physicians; 1 was experienced as difficult by the parent only; and 8 were experienced as difficult by the physician only. Parent experiences of difficult relationships were characterized by an impaired therapeutic alliance with physicians; physicians experienced difficult relationships as demanding. Core underlying issues included problems of connection and understanding (n = 8), confrontational parental advocacy (n = 16), mental health issues (n = 2), and structural challenges to care (n = 3). Although problems of connection and understanding often improved over time, problems of confrontational advocacy tended to solidify. Parents and physicians both experienced difficult relationships as highly distressing. Although prior conceptions of difficult relationships have held patients responsible for challenges, this study has found that difficult relationships follow several patterns. Some challenges, such as problems of connection and understanding, offer an opportunity for healing. However, confrontational advocacy appears especially refractory to repair; special consideration of these relationships and avenues for repairing them are needed. Cancer 2017;123:675-681. © 2016 American Cancer Society. © 2016 American Cancer Society.
Communicating Difficult and Taboo Information: A How-To Guide for Commanders.
Moosey, Matthew
2016-01-01
Military commanders frequently mention that communicating difficult or taboo information is especially challenging. In the context of gender-integrated ground combat service there may be additional communication challenges for military commanders who may be unaccustomed to leading both men and women. Often, military commanders must communicate and deliver difficult information, or information that causes a negative emotional response from the communicator or the intended audience. This article is intended to identify some of these challenges and present practical examples and tips for military commanders to effectively communicate difficult or taboo topics and information. In addition, this article is a call for communication experts to reach out to military leaders and offer appropriate assistance in facilitating and delivering difficult communication. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.
NASA Technical Reports Server (NTRS)
Lockard, David P.
2011-01-01
Fifteen submissions in the tandem cylinders category of the First Workshop on Benchmark problems for Airframe Noise Computations are summarized. Although the geometry is relatively simple, the problem involves complex physics. Researchers employed various block-structured, overset, unstructured and embedded Cartesian grid techniques and considerable computational resources to simulate the flow. The solutions are compared against each other and experimental data from 2 facilities. Overall, the simulations captured the gross features of the flow, but resolving all the details which would be necessary to compute the noise remains challenging. In particular, how to best simulate the effects of the experimental transition strip, and the associated high Reynolds number effects, was unclear. Furthermore, capturing the spanwise variation proved difficult.
Time-resolved broadband cavity-enhanced absorption spectroscopy for chemical kinetics.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sheps, Leonid; Chandler, David W.
Experimental measurements of elementary reaction rate coefficients and product branching ratios are essential to our understanding of many fundamentally important processes in Combustion Chemistry. However, such measurements are often impossible because of a lack of adequate detection techniques. Some of the largest gaps in our knowledge concern some of the most important radical species, because their short lifetimes and low steady-state concentrations make them particularly difficult to detect. To address this challenge, we propose a novel general detection method for gas-phase chemical kinetics: time-resolved broadband cavity-enhanced absorption spectroscopy (TR-BB-CEAS). This all-optical, non-intrusive, multiplexed method enables sensitive direct probing of transientmore » reaction intermediates in a simple, inexpensive, and robust experimental package.« less
NASA Astrophysics Data System (ADS)
Barnard, Daniel; Chakrapani, Sunil Kishore; Dayal, Vinay
2013-01-01
Modern helicopter rotor blades constructed of composite materials offer significant inspection challenges, particularly at inner structures, where geometry and differing material properties and anisotropy make placement of the probing energy difficult. This paper presents an application of Lamb waves to these structures, where mode conversion occurs at internal geometric discontinuities. These additional modes were found to successfully propagate to the targeted regions inside the rotor and back out, allowing evaluation of the structure. A finite element model was developed to simulate wave propagation and mode conversion in the structure and aid in identifying the signals received in the laboratory experiment. A good correlation between numerical and experimental results was observed.
Trevors, J T
2010-06-01
Methods to research the origin of microbial life are limited. However, microorganisms were the first organisms on the Earth capable of cell growth and division, and interactions with their environment, other microbial cells, and eventually with diverse eukaryotic organisms. The origin of microbial life and the supporting scientific evidence are both an enigma and a scientific priority. Numerous hypotheses have been proposed, scenarios imagined, speculations presented in papers, insights shared, and assumptions made without supporting experimentation, which have led to limited progress in understanding the origin of microbial life. The use of the human imagination to envision the origin of life events, without supporting experimentation, observation and independently replicated experiments required for science, is a significant constraint. The challenge remains how to better understand the origin of microbial life using observations and experimental methods as opposed to speculation, assumptions, scenarios, envisioning events and un-testable hypotheses. This is not an easy challenge as experimental design and plausible hypothesis testing are difficult. Since past approaches have been inconclusive in providing evidence for the origin of microbial life mechanisms and the manner in which genetic instructions was encoded into DNA/RNA, it is reasonable and logical to propose that progress will be made when testable, plausible hypotheses and methods are used in the origin of microbial life research, and the experimental observations are, or are not reproduced in independent laboratories. These perspectives will be discussed in this article as well as the possibility that a pre-biotic film preceded a microbial biofilm as a possible micro-location for the origin of microbial cells capable of growth and division. 2010 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Morton, April M; Piburn, Jesse O; McManamay, Ryan A
2017-01-01
Monte Carlo simulation is a popular numerical experimentation technique used in a range of scientific fields to obtain the statistics of unknown random output variables. Despite its widespread applicability, it can be difficult to infer required input probability distributions when they are related to population counts unknown at desired spatial resolutions. To overcome this challenge, we propose a framework that uses a dasymetric model to infer the probability distributions needed for a specific class of Monte Carlo simulations which depend on population counts.
Layout optimization of DRAM cells using rigorous simulation model for NTD
NASA Astrophysics Data System (ADS)
Jeon, Jinhyuck; Kim, Shinyoung; Park, Chanha; Yang, Hyunjo; Yim, Donggyu; Kuechler, Bernd; Zimmermann, Rainer; Muelders, Thomas; Klostermann, Ulrich; Schmoeller, Thomas; Do, Mun-hoe; Choi, Jung-Hoe
2014-03-01
DRAM chip space is mainly determined by the size of the memory cell array patterns which consist of periodic memory cell features and edges of the periodic array. Resolution Enhancement Techniques (RET) are used to optimize the periodic pattern process performance. Computational Lithography such as source mask optimization (SMO) to find the optimal off axis illumination and optical proximity correction (OPC) combined with model based SRAF placement are applied to print patterns on target. For 20nm Memory Cell optimization we see challenges that demand additional tool competence for layout optimization. The first challenge is a memory core pattern of brick-wall type with a k1 of 0.28, so it allows only two spectral beams to interfere. We will show how to analytically derive the only valid geometrically limited source. Another consequence of two-beam interference limitation is a "super stable" core pattern, with the advantage of high depth of focus (DoF) but also low sensitivity to proximity corrections or changes of contact aspect ratio. This makes an array edge correction very difficult. The edge can be the most critical pattern since it forms the transition from the very stable regime of periodic patterns to non-periodic periphery, so it combines the most critical pitch and highest susceptibility to defocus. Above challenge makes the layout correction to a complex optimization task demanding a layout optimization that finds a solution with optimal process stability taking into account DoF, exposure dose latitude (EL), mask error enhancement factor (MEEF) and mask manufacturability constraints. This can only be achieved by simultaneously considering all criteria while placing and sizing SRAFs and main mask features. The second challenge is the use of a negative tone development (NTD) type resist, which has a strong resist effect and is difficult to characterize experimentally due to negative resist profile taper angles that perturb CD at bottom characterization by scanning electron microscope (SEM) measurements. High resist impact and difficult model data acquisition demand for a simulation model that hat is capable of extrapolating reliably beyond its calibration dataset. We use rigorous simulation models to provide that predictive performance. We have discussed the need of a rigorous mask optimization process for DRAM contact cell layout yielding mask layouts that are optimal in process performance, mask manufacturability and accuracy. In this paper, we have shown the step by step process from analytical illumination source derivation, a NTD and application tailored model calibration to layout optimization such as OPC and SRAF placement. Finally the work has been verified with simulation and experimental results on wafer.
Considering RNAi experimental design in parasitic helminths.
Dalzell, Johnathan J; Warnock, Neil D; McVeigh, Paul; Marks, Nikki J; Mousley, Angela; Atkinson, Louise; Maule, Aaron G
2012-04-01
Almost a decade has passed since the first report of RNA interference (RNAi) in a parasitic helminth. Whilst much progress has been made with RNAi informing gene function studies in disparate nematode and flatworm parasites, substantial and seemingly prohibitive difficulties have been encountered in some species, hindering progress. An appraisal of current practices, trends and ideals of RNAi experimental design in parasitic helminths is both timely and necessary for a number of reasons: firstly, the increasing availability of parasitic helminth genome/transcriptome resources means there is a growing need for gene function tools such as RNAi; secondly, fundamental differences and unique challenges exist for parasite species which do not apply to model organisms; thirdly, the inherent variation in experimental design, and reported difficulties with reproducibility undermine confidence. Ideally, RNAi studies of gene function should adopt standardised experimental design to aid reproducibility, interpretation and comparative analyses. Although the huge variations in parasite biology and experimental endpoints make RNAi experimental design standardization difficult or impractical, we must strive to validate RNAi experimentation in helminth parasites. To aid this process we identify multiple approaches to RNAi experimental validation and highlight those which we deem to be critical for gene function studies in helminth parasites.
Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots.
Hajdin, Christine E; Bellaousov, Stanislav; Huggins, Wayne; Leonard, Christopher W; Mathews, David H; Weeks, Kevin M
2013-04-02
A pseudoknot forms in an RNA when nucleotides in a loop pair with a region outside the helices that close the loop. Pseudoknots occur relatively rarely in RNA but are highly overrepresented in functionally critical motifs in large catalytic RNAs, in riboswitches, and in regulatory elements of viruses. Pseudoknots are usually excluded from RNA structure prediction algorithms. When included, these pairings are difficult to model accurately, especially in large RNAs, because allowing this structure dramatically increases the number of possible incorrect folds and because it is difficult to search the fold space for an optimal structure. We have developed a concise secondary structure modeling approach that combines SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) experimental chemical probing information and a simple, but robust, energy model for the entropic cost of single pseudoknot formation. Structures are predicted with iterative refinement, using a dynamic programming algorithm. This melded experimental and thermodynamic energy function predicted the secondary structures and the pseudoknots for a set of 21 challenging RNAs of known structure ranging in size from 34 to 530 nt. On average, 93% of known base pairs were predicted, and all pseudoknots in well-folded RNAs were identified.
2014-01-01
Background Accurate estimation of parameters of biochemical models is required to characterize the dynamics of molecular processes. This problem is intimately linked to identifying the most informative experiments for accomplishing such tasks. While significant progress has been made, effective experimental strategies for parameter identification and for distinguishing among alternative network topologies remain unclear. We approached these questions in an unbiased manner using a unique community-based approach in the context of the DREAM initiative (Dialogue for Reverse Engineering Assessment of Methods). We created an in silico test framework under which participants could probe a network with hidden parameters by requesting a range of experimental assays; results of these experiments were simulated according to a model of network dynamics only partially revealed to participants. Results We proposed two challenges; in the first, participants were given the topology and underlying biochemical structure of a 9-gene regulatory network and were asked to determine its parameter values. In the second challenge, participants were given an incomplete topology with 11 genes and asked to find three missing links in the model. In both challenges, a budget was provided to buy experimental data generated in silico with the model and mimicking the features of different common experimental techniques, such as microarrays and fluorescence microscopy. Data could be bought at any stage, allowing participants to implement an iterative loop of experiments and computation. Conclusions A total of 19 teams participated in this competition. The results suggest that the combination of state-of-the-art parameter estimation and a varied set of experimental methods using a few datasets, mostly fluorescence imaging data, can accurately determine parameters of biochemical models of gene regulation. However, the task is considerably more difficult if the gene network topology is not completely defined, as in challenge 2. Importantly, we found that aggregating independent parameter predictions and network topology across submissions creates a solution that can be better than the one from the best-performing submission. PMID:24507381
Ultrasound Velocity Measurement in a Liquid Metal Electrode
Perez, Adalberto; Kelley, Douglas H.
2015-01-01
A growing number of electrochemical technologies depend on fluid flow, and often that fluid is opaque. Measuring the flow of an opaque fluid is inherently more difficult than measuring the flow of a transparent fluid, since optical methods are not applicable. Ultrasound can be used to measure the velocity of an opaque fluid, not only at isolated points, but at hundreds or thousands of points arrayed along lines, with good temporal resolution. When applied to a liquid metal electrode, ultrasound velocimetry involves additional challenges: high temperature, chemical activity, and electrical conductivity. Here we describe the experimental apparatus and methods that overcome these challenges and allow the measurement of flow in a liquid metal electrode, as it conducts current, at operating temperature. Temperature is regulated within ±2 °C using a Proportional-Integral-Derivative (PID) controller that powers a custom-built furnace. Chemical activity is managed by choosing vessel materials carefully and enclosing the experimental setup in an argon-filled glovebox. Finally, unintended electrical paths are carefully prevented. An automated system logs control settings and experimental measurements, using hardware trigger signals to synchronize devices. This apparatus and these methods can produce measurements that are impossible with other techniques, and allow optimization and control of electrochemical technologies like liquid metal batteries. PMID:26273726
Hypnotherapy for labor and birth.
Beebe, Kathleen R
2014-01-01
Hypnotherapy is an integrative mind-body technique with therapeutic potential in various health care applications, including labor and birth. Evaluating the efficacy of this modality in controlled studies can be difficult, because of methodologic challenges, such as obtaining adequate sample sizes and standardizing experimental conditions. Women using hypnosis techniques for childbirth in hospital settings may face barriers related to caregiver resistance or institutional policies. The potential anxiolytic and analgesic effects of clinical hypnosis for childbirth merit further study. Nurses caring for women during labor and birth can increase their knowledge and skills with strategies for supporting hypnotherapeutic techniques. © 2014 AWHONN.
Karanfil, C; Bunker, G; Newville, M; Segre, C U; Chapman, D
2012-05-01
Third-generation synchrotron radiation sources pose difficult challenges for energy-dispersive detectors for XAFS because of their count rate limitations. One solution to this problem is the bent crystal Laue analyzer (BCLA), which removes most of the undesired scatter and fluorescence before it reaches the detector, effectively eliminating detector saturation due to background. In this paper experimental measurements of BCLA performance in conjunction with a 13-element germanium detector, and a quantitative analysis of the signal-to-noise improvement of BCLAs are presented. The performance of BCLAs are compared with filters and slits.
Lie, Richard; Abdullah, Christopher; He, Wenliang; Tour, Ella
2016-01-01
Primary literature offers rich opportunities to teach students how to “think like a scientist,” but the challenges students face when they attempt to read research articles are not well understood. Here, we present an analysis of what master’s students perceive as the most challenging aspects of engaging with primary literature. We examined 69 pairs of pre- and postcourse responses from students enrolled in a master’s-level course that offered a structured analysis of primary literature. On the basis of these responses, we identified six categories of challenges. Before instruction, “techniques” and “experimental data” were the most frequently identified categories of challenges. The majority of difficulties students perceived in the primary literature corresponded to Bloom’s lower-order cognitive skills. After instruction, “conclusions” were identified as the most difficult aspect of primary literature, and the frequency of challenges that corresponded to higher-order cognitive skills increased significantly among students who reported less experience with primary literature. These changes are consistent with a more competent perception of the primary literature, in which these students increasingly focus on challenges requiring critical thinking. Students’ difficulties identified here can inform the design of instructional approaches aimed to teach students how to critically read scientific papers. PMID:27909027
Infection control for norovirus
Barclay, L.; Park, G. W.; Vega, E.; Hall, A.; Parashar, U.; Vinjé, J.; Lopman, B.
2015-01-01
Norovirus infections are notoriously difficult to prevent and control, owing to their low infectious dose, high shedding titre, and environmental stability. The virus can spread through multiple transmission routes, of which person-to-person and foodborne are the most important. Recent advances in molecular diagnostics have helped to establish norovirus as the most common cause of sporadic gastroenteritis and the most common cause of outbreaks of acute gastroenteritis across all ages. In this article, we review the epidemiology and virology of noroviruses, and prevention and control guidelines, with a focus on the principles of disinfection and decontamination. Outbreak management relies on sound infection control principles, including hand hygiene, limiting exposure to infectious individuals, and thorough environmental decontamination. Ideally, all infection control recommendations would rely on empirical evidence, but a number of challenges, including the inability to culture noroviruses in the laboratory and the challenges of outbreak management in complex environments, has made it difficult to garner clear evidence of efficacy in certain areas of infection control. New experimental data on cultivable surrogates for human norovirus and on environmental survivability and relative resistance to commonly used disinfectants are providing new insights for further refinining disinfection practices. Finally, clinical trials are underway to evaluate the efficacy of vaccines, which may shift the current infection control principles to more targeted interventions. PMID:24813073
Lunkenheimer, Erika; Kemp, Christine J.; Lucas-Thompson, Rachel G.; Cole, Pamela M.; Albrecht, Erin C.
2016-01-01
Researchers have argued for more dynamic and contextually relevant measures of regulatory processes in interpersonal interactions. In response, we introduce and examine the effectiveness of a new task, the Parent-Child Challenge Task, designed to assess the self-regulation and coregulation of affect, goal-directed behavior, and physiology in parents and their preschoolers in response to an experimental perturbation. Concurrent and predictive validity was examined via relations with children’s externalizing behaviors. Mothers used only their words to guide their 3-year-old children to complete increasingly difficult puzzles in order to win a prize (N = 96). A challenge condition was initiated mid-way through the task with a newly introduced time limit. The challenge produced decreases in parental teaching and dyadic behavioral variability and increases in child negative affect and dyadic affective variability, measured by dynamic systems-based methods. Children rated lower on externalizing showed respiratory sinus arrhythmia (RSA) suppression in response to challenge, whereas those rated higher on externalizing showed RSA augmentation. Additionally, select task changes in affect, behavior, and physiology predicted teacher-rated externalizing behaviors four months later. Findings indicate the Parent-Child Challenge Task was effective in producing regulatory changes and suggest its utility in assessing biobehavioral self-regulation and coregulation in parents and their preschoolers. PMID:28458616
Lunkenheimer, Erika; Kemp, Christine J; Lucas-Thompson, Rachel G; Cole, Pamela M; Albrecht, Erin C
2017-01-01
Researchers have argued for more dynamic and contextually relevant measures of regulatory processes in interpersonal interactions. In response, we introduce and examine the effectiveness of a new task, the Parent-Child Challenge Task, designed to assess the self-regulation and coregulation of affect, goal-directed behavior, and physiology in parents and their preschoolers in response to an experimental perturbation. Concurrent and predictive validity was examined via relations with children's externalizing behaviors. Mothers used only their words to guide their 3-year-old children to complete increasingly difficult puzzles in order to win a prize ( N = 96). A challenge condition was initiated mid-way through the task with a newly introduced time limit. The challenge produced decreases in parental teaching and dyadic behavioral variability and increases in child negative affect and dyadic affective variability, measured by dynamic systems-based methods. Children rated lower on externalizing showed respiratory sinus arrhythmia (RSA) suppression in response to challenge, whereas those rated higher on externalizing showed RSA augmentation. Additionally, select task changes in affect, behavior, and physiology predicted teacher-rated externalizing behaviors four months later. Findings indicate the Parent-Child Challenge Task was effective in producing regulatory changes and suggest its utility in assessing biobehavioral self-regulation and coregulation in parents and their preschoolers.
NASA Astrophysics Data System (ADS)
Wikswo, John; Kolli, Aditya; Shankaran, Harish; Wagoner, Matthew; Mettetal, Jerome; Reiserer, Ronald; Gerken, Gregory; Britt, Clayton; Schaffer, David
Genetic, proteomic, and metabolic networks describing biological signaling can have 102 to 103 nodes. Transcriptomics and mass spectrometry can quantify 104 different dynamical experimental variables recorded from in vitro experiments with a time resolution approaching 1 s. It is difficult to infer metabolic and signaling models from such massive data sets, and it is unlikely that causality can be determined simply from observed temporal correlations. There is a need to design and apply specific system perturbations, which will be difficult to perform manually with 10 to 102 externally controlled variables. Machine learning and optimal experimental design can select an experiment that best discriminates between multiple conflicting models, but a remaining problem is to control in real time multiple variables in the form of concentrations of growth factors, toxins, nutrients and other signaling molecules. With time-division multiplexing, a microfluidic MicroFormulator (μF) can create in real time complex mixtures of reagents in volumes suitable for biological experiments. Initial 96-channel μF implementations control the exposure profile of cells in a 96-well plate to different temporal profiles of drugs; future experiments will include challenge compounds. Funded in part by AstraZeneca, NIH/NCATS HHSN271201600009C and UH3TR000491, and VIIBRE.
The effects of goal variation on adult physical activity behaviour.
Moon, Dal-Hyun; Yun, Joonkoo; McNamee, Jeff
2016-10-01
The purposes of this study were to examine the effects of varying levels of goals on increasing daily steps and the frequency of goal achievement among middle-aged adults. Ninety-six adults participated in a randomised control study. Participants were randomly assigned to five different step goal groups: (1) Easy (n = 19), (2) Medium (n = 19), (3) Difficult (n = 19), (4) Do-your-best (n = 19), and (5) No goal (n = 20) based on previous research. The participants wore a pedometer and were asked to reach a pre-established goal during the experimental period. In order to examine the effectiveness of the goal difficulty, (a) an average number of steps taken by different goal conditions and (b) the number of days meeting the assigned goal were tested. A one-way ANCOVA revealed significant step count differences among goal groups. Post hoc analyses indicated that the change in step count in both the Medium and Difficult goal groups was significantly greater than the remaining groups. However, there was no significant difference between the medium and difficult goal conditions. In addition, a one-way ANOVA indicated that there were no significant differences in the frequency of goal achievement among the Easy, Medium, and Difficult goal groups. Results suggest that when promoting physical activity through increasing step counts, researchers and clinicians should design goals that are specific and challenging.
Chaos, Fractals, and the Pedagogical Challenge of Jackson Pollock's "All-Over" Paintings
ERIC Educational Resources Information Center
Halsall, Francis
2008-01-01
The "all-over" abstract canvases that Jackson Pollock produced between 1943 and 1951 present a pedagogical challenge in how to account for their apparently chaotic structure. One reason that they are difficult to teach about is that they have proved notoriously difficult for art historians to come to terms with. This is undoubtedly a consequence…
Sparse Coding and Counting for Robust Visual Tracking
Liu, Risheng; Wang, Jing; Shang, Xiaoke; Wang, Yiyang; Su, Zhixun; Cai, Yu
2016-01-01
In this paper, we propose a novel sparse coding and counting method under Bayesian framework for visual tracking. In contrast to existing methods, the proposed method employs the combination of L0 and L1 norm to regularize the linear coefficients of incrementally updated linear basis. The sparsity constraint enables the tracker to effectively handle difficult challenges, such as occlusion or image corruption. To achieve real-time processing, we propose a fast and efficient numerical algorithm for solving the proposed model. Although it is an NP-hard problem, the proposed accelerated proximal gradient (APG) approach is guaranteed to converge to a solution quickly. Besides, we provide a closed solution of combining L0 and L1 regularized representation to obtain better sparsity. Experimental results on challenging video sequences demonstrate that the proposed method achieves state-of-the-art results both in accuracy and speed. PMID:27992474
Efficacy of postexposure therapy against glanders in mice.
Waag, David M
2015-04-01
Burkholderia mallei, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Efficacy of Postexposure Therapy against Glanders in Mice
2015-01-01
Burkholderia mallei, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated. PMID:25645854
Optimal experimental designs for fMRI when the model matrix is uncertain.
Kao, Ming-Hung; Zhou, Lin
2017-07-15
This study concerns optimal designs for functional magnetic resonance imaging (fMRI) experiments when the model matrix of the statistical model depends on both the selected stimulus sequence (fMRI design), and the subject's uncertain feedback (e.g. answer) to each mental stimulus (e.g. question) presented to her/him. While practically important, this design issue is challenging. This mainly is because that the information matrix cannot be fully determined at the design stage, making it difficult to evaluate the quality of the selected designs. To tackle this challenging issue, we propose an easy-to-use optimality criterion for evaluating the quality of designs, and an efficient approach for obtaining designs optimizing this criterion. Compared with a previously proposed method, our approach requires a much less computing time to achieve designs with high statistical efficiencies. Copyright © 2017 Elsevier Inc. All rights reserved.
Study on super-long deep-hole drilling of titanium alloy.
Liu, Zhanfeng; Liu, Yanshu; Han, Xiaolan; Zheng, Wencui
2018-01-01
In this study, the super-long deep-hole drilling of a titanium alloy was investigated. According to material properties of the titanium alloy, an experimental approach was designed to study three issues discovered during the drilling process: the hole-axis deflection, chip morphology, and tool wear. Based on the results of drilling experiments, crucial parameters for the super-long deep-hole drilling of titanium alloys were obtained, and the influences of these parameters on quality of the alloy's machining were also evaluated. Our results suggest that the developed drilling process is an effective method to overcome the challenge of super-long deep-hole drilling on difficult-to-cut materials.
Entropic Elasticity in the Giant Muscle Protein Titin
NASA Astrophysics Data System (ADS)
Morgan, Ian; Saleh, Omar
Intrinsically disordered proteins (IDPs) are a large and functionally important class of proteins that lack a fixed three-dimensional structure. Instead, they adopt a conformational ensemble of states which facilitates their biological function as molecular linkers, springs, and switches. Due to their conformational flexibility, it can be difficult to study IDPs using typical experimental methods. To overcome this challenge, we use a high-resolution single-molecule magnetic stretching technique to quantify IDP flexibility. We apply this technique to the giant muscle protein titin, measuring its elastic response at low forces. We present results demonstrating that titin's native elastic response derives from the combined entropic elasticity of its ordered and disordered domains.
A perspective on modeling the multiscale response of energetic materials
NASA Astrophysics Data System (ADS)
Rice, Betsy M.
2017-01-01
The response of an energetic material to insult is perhaps one of the most difficult processes to model due to concurrent chemical and physical phenomena occurring over scales ranging from atomistic to continuum. Unraveling the interdependencies of these complex processes across the scales through modeling can only be done within a multiscale framework. In this paper, I will describe progress in the development of a predictive, experimentally validated multiscale reactive modeling capability for energetic materials at the Army Research Laboratory. I will also describe new challenges and research opportunities that have arisen in the course of our development which should be pursued in the future.
Complete denture tooth arrangement technology driven by a reconfigurable rule.
Dai, Ning; Yu, Xiaoling; Fan, Qilei; Yuan, Fulai; Liu, Lele; Sun, Yuchun
2018-01-01
The conventional technique for the fabrication of complete dentures is complex, with a long fabrication process and difficult-to-control restoration quality. In recent years, digital complete denture design has become a research focus. Digital complete denture tooth arrangement is a challenging issue that is difficult to efficiently implement under the constraints of complex tooth arrangement rules and the patient's individualized functional aesthetics. The present study proposes a complete denture automatic tooth arrangement method driven by a reconfigurable rule; it uses four typical operators, including a position operator, a scaling operator, a posture operator, and a contact operator, to establish the constraint mapping association between the teeth and the constraint set of the individual patient. By using the process reorganization of different constraint operators, this method can flexibly implement different clinical tooth arrangement rules. When combined with a virtual occlusion algorithm based on progressive iterative Laplacian deformation, the proposed method can achieve automatic and individual tooth arrangement. Finally, the experimental results verify that the proposed method is flexible and efficient.
Strategies for Evaluating Complex Environmental Education Programs
NASA Astrophysics Data System (ADS)
Williams, V.
2011-12-01
Evidence for the effectiveness of environmental education programs has been difficult to establish for many reasons. Chief among them are the lack of clear program objectives and an inability to conceptualize how environmental education programs work. Both can lead to evaluations that make claims that are difficult to substantiate, such as significant changes in student achievement levels or behavioral changes based on acquisition of knowledge. Many of these challenges can be addressed by establishing the program theory and developing a logic model. However, claims of impact on larger societal outcomes are difficult to attribute solely to program activities. Contribution analysis may offer a promising method for addressing this challenge. Rather than attempt to definitively and causally link a program's activities to desired results, contribution analysis seeks to provide plausible evidence that can reduce uncertainty regarding the 'difference' a program is making to observed outcomes. It sets out to verify the theory of change behind a program and, at the same time, takes into consideration other influencing factors. Contribution analysis is useful in situations where the program is not experimental-there is little or no scope for varying how the program is implemented-and the program has been funded on the basis of a theory of change. In this paper, the author reviews the feasibility of using contribution analysis as a way of evaluating the impact of the GLOBE program, an environmental science and education program. Initially conceptualized by Al Gore in 1995, the program's implementation model is based on worldwide environmental monitoring by students and scientists around the globe. This paper will make a significant and timely contribution to the field of evaluation, and specifically environmental education evaluation by examining the usefulness of this analysis for developing evidence to assess the impact of environmental education programs.
Data-driven reverse engineering of signaling pathways using ensembles of dynamic models.
Henriques, David; Villaverde, Alejandro F; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R
2017-02-01
Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM's ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge.
Data-driven reverse engineering of signaling pathways using ensembles of dynamic models
Henriques, David; Villaverde, Alejandro F.; Banga, Julio R.
2017-01-01
Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM’s ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge. PMID:28166222
Olfactory language and abstraction across cultures
Burenhult, Niclas; Stensmyr, Marcus; de Valk, Josje; Hansson, Bill S.
2018-01-01
Olfaction presents a particularly interesting arena to explore abstraction in language. Like other abstract domains, such as time, odours can be difficult to conceptualize. An odour cannot be seen or held, it can be difficult to locate in space, and for most people odours are difficult to verbalize. On the other hand, odours give rise to primary sensory experiences. Every time we inhale we are using olfaction to make sense of our environment. We present new experimental data from 30 Jahai hunter-gatherers from the Malay Peninsula and 30 matched Dutch participants from the Netherlands in an odour naming experiment. Participants smelled monomolecular odorants and named odours while reaction times, odour descriptors and facial expressions were measured. We show that while Dutch speakers relied on concrete descriptors, i.e. they referred to odour sources (e.g. smells like lemon), the Jahai used abstract vocabulary to name the same odours (e.g. musty). Despite this differential linguistic categorization, analysis of facial expressions showed that the two groups, nevertheless, had the same initial emotional reactions to odours. Critically, these cross-cultural data present a challenge for how to think about abstraction in language. This article is part of the theme issue ‘Varieties of abstract concepts: development, use and representation in the brain’. PMID:29915007
ERIC Educational Resources Information Center
McDonald, James; Dominguez, Lynn
2012-01-01
As children develop misconceptions about animals they believe are dangerous, they also adopt attitudes that are difficult to change. Changing these attitudes is challenging for teachers. One animal that is easy to find but difficult for children to understand is a spider. As with most wild animals, they are difficult to teach about because…
Faculty Teaching Diversity through Difficult Dialogues: Stories of Challenges and Success
ERIC Educational Resources Information Center
Gayles, Joy Gaston; Kelly, Bridget Turner; Grays, Shaefny; Zhang, Jing Jing; Porter, Kamaria P.
2015-01-01
Teaching diversity courses in graduate preparation programs is likely to trigger difficult dialogues that evoke a range of emotional responses. Difficult dialogues on diversity topics must be managed effectively in order to enhance multicultural competence. This interpretive study examined the experiences of faculty who teach diversity courses in…
Modelling and validation of electromechanical shock absorbers
NASA Astrophysics Data System (ADS)
Tonoli, Andrea; Amati, Nicola; Girardello Detoni, Joaquim; Galluzzi, Renato; Gasparin, Enrico
2013-08-01
Electromechanical vehicle suspension systems represent a promising substitute to conventional hydraulic solutions. However, the design of electromechanical devices that are able to supply high damping forces without exceeding geometric dimension and mass constraints is a difficult task. All these challenges meet in off-road vehicle suspension systems, where the power density of the dampers is a crucial parameter. In this context, the present paper outlines a particular shock absorber configuration where a suitable electric machine and a transmission mechanism are utilised to meet off-road vehicle requirements. A dynamic model is used to represent the device. Subsequently, experimental tests are performed on an actual prototype to verify the functionality of the damper and validate the proposed model.
Extending the ARS Experimental Watersheds to Address Regional Issues
NASA Astrophysics Data System (ADS)
Marks, D.; Goodrich, D. C.; Winstral, A.; Bosch, D. D.; Pool, D.
2001-12-01
The USDA-Agricultural Research Service's (ARS) Watershed Research Program maintains and operates a diverse, geog raphically distributed, nested, multi-scale, national ex perimental watershed network. This network, much of which has been operational for more than 40 years (several more than 60 years), constitutes one the best networks of its kind in the world. The watershed network and its instrumentation was primarily established to assess the hydrologic impacts of watershed conservation and management practices. It has evolved, through development of long-term hydrologic data, as a network of high quality outdoor laboratories for addressing emerging science issues facing hydrologists and resource managers. While the value of the experimental watershed for investigating precipitation, climatic, and hydrologic processes is unquestioned, extending the results from these investigations to other sites and larger areas is more difficult. ARS experimental watersheds are a few hundred km2 or smaller making it challenging to address regional scale issues. To address this the ARS watershed program is, with a suite of partners from universities and other federal agencies, enlarging its research focus to extend beyond the boundaries of the experimental watershed. In this poster we present several examples of this effort, with suggestions on how, using the experimental watershed and its core, a larger scale hydrologic observatory could be developed and maintained.
Doing science in difficult socioeconomic circumstances.
Karasmanis, Eva P
2018-06-01
Doing scientific research can be a challenging, but creative and rewarding career. However, the challenge of doing research is orders of magnitude more difficult for scientists lacking access to the necessary resources. Resource-scarce environments are quite common worldwide and are highly contingent on the financial and social climate of one's location. Through the experiences of four scientists, this Perspective explores the challenges associated with doing research in disadvantaged socioeconomic circumstances. By reflecting on the humble beginnings of these scientists, we examine the motivation to stay in or leave one's home country, and how hardships can be leveraged to cultivate passionate and productive researchers.
Promoting the Multidimensional Character of Scientific Reasoning.
Bradshaw, William S; Nelson, Jennifer; Adams, Byron J; Bell, John D
2017-04-01
This study reports part of a long-term program to help students improve scientific reasoning using higher-order cognitive tasks set in the discipline of cell biology. This skill was assessed using problems requiring the construction of valid conclusions drawn from authentic research data. We report here efforts to confirm the hypothesis that data interpretation is a complex, multifaceted exercise. Confirmation was obtained using a statistical treatment showing that various such problems rank students differently-each contains a unique set of cognitive challenges. Additional analyses of performance results have allowed us to demonstrate that individuals differ in their capacity to navigate five independent generic elements that constitute successful data interpretation: biological context, connection to course concepts, experimental protocols, data inference, and integration of isolated experimental observations into a coherent model. We offer these aspects of scientific thinking as a "data analysis skills inventory," along with usable sample problems that illustrate each element. Additionally, we show that this kind of reasoning is rigorous in that it is difficult for most novice students, who are unable to intuitively implement strategies for improving these skills. Instructors armed with knowledge of the specific challenges presented by different types of problems can provide specific helpful feedback during formative practice. The use of this instructional model is most likely to require changes in traditional classroom instruction.
Perampanel and Challenging Behaviour in Intellectual Disability and Epilepsy: A Management Dilemma
Choudry, Ansar
2014-01-01
We describe a case of a patient with a diagnosis of moderate learning disability with challenging behaviour and treatment refractory epilepsy. Antiepileptics can increase challenging behaviour; however, antipsychotics can provoke seizures. This results in a difficult balance for patient care. Due to worsening seizures, the patient was prescribed perampanel. This increased her aggression and agitation resulting in admission. We trialled four antipsychotic drugs to reduce her challenging behaviour, two of which worsened her seizures. It was necessary to continue antiepileptic medication to maintain adequate seizure control. However, the resulting uncontrolled challenging behaviour persisted, meaning she was unable to return to her family home on discharge. This case emphasises the difficult scenario clinician's encounter when balancing the use of antipsychotics and antiepileptics. The case demonstrates the significant functional loss due to challenging behaviour, balanced against controlling life threatening seizures. PMID:25580340
Recent developments in deployment analysis simulation using a multi-body computer code
NASA Technical Reports Server (NTRS)
Housner, Jerrold M.
1989-01-01
Deployment is a candidate mode for construction of structural space systems components. By its very nature, deployment is a dynamic event, often involving large angle unfolding of flexible beam members. Validation of proposed designs and conceptual deployment mechanisms is enhanced through analysis. Analysis may be used to determine member loads thus helping to establish deployment rates and deployment control requirements for a given concept. Futhermore, member flexibility, joint free-play, manufacturing tolerances, and imperfections can affect the reliability of deployment. Analyses which include these effects can aid in reducing risks associated with a particular concept. Ground tests which can play a similar role to that of analyses are difficult and expensive to perform. Suspension systems just for vibration ground tests of large space structures in a 1 g environment present many challenges. Suspension of a structure which spatially expands is even more challenging. Analysis validation through experimental confirmation on relatively small simple models would permit analytical extrapolation to larger more complex space structures.
Stirling, András; Nair, Nisanth N; Lledós, Agustí; Ujaque, Gregori
2014-07-21
We present here a review of the mechanistic studies of the Wacker process stressing the long controversy about the key reaction steps. We give an overview of the previous experimental and theoretical studies on the topic. Then we describe the importance of the most recent Ab Initio Molecular Dynamics (AIMD) calculations in modelling organometallic reactivity in water. As a prototypical example of homogeneous catalytic reactions, the Wacker process poses serious challenges to modelling. The adequate description of the multiple role of the water solvent is very difficult by using static quantum chemical approaches including cluster and continuum solvent models. In contrast, such reaction systems are suitable for AIMD, and by combining with rare event sampling techniques, the method provides reaction mechanisms and the corresponding free energy profiles. The review also highlights how AIMD has helped to obtain a novel understanding of the mechanism and kinetics of the Wacker process.
Aziz, Michael
2015-01-01
Recent technological advances have made airway management safer. Because difficult intubation remains challenging to predict, having tools readily available that can be used to manage a difficult airway in any setting is critical. Fortunately, video technology has resulted in improvements for intubation performance while using laryngoscopy by various means. These technologies have been applied to rigid optical stylets, flexible intubation scopes, and, most notably, rigid laryngoscopes. These tools have proven effective for the anticipated difficult airway as well as the unanticipated difficult airway.
Object Segmentation and Ground Truth in 3D Embryonic Imaging.
Rajasekaran, Bhavna; Uriu, Koichiro; Valentin, Guillaume; Tinevez, Jean-Yves; Oates, Andrew C
2016-01-01
Many questions in developmental biology depend on measuring the position and movement of individual cells within developing embryos. Yet, tools that provide this data are often challenged by high cell density and their accuracy is difficult to measure. Here, we present a three-step procedure to address this problem. Step one is a novel segmentation algorithm based on image derivatives that, in combination with selective post-processing, reliably and automatically segments cell nuclei from images of densely packed tissue. Step two is a quantitative validation using synthetic images to ascertain the efficiency of the algorithm with respect to signal-to-noise ratio and object density. Finally, we propose an original method to generate reliable and experimentally faithful ground truth datasets: Sparse-dense dual-labeled embryo chimeras are used to unambiguously measure segmentation errors within experimental data. Together, the three steps outlined here establish a robust, iterative procedure to fine-tune image analysis algorithms and microscopy settings associated with embryonic 3D image data sets.
Object Segmentation and Ground Truth in 3D Embryonic Imaging
Rajasekaran, Bhavna; Uriu, Koichiro; Valentin, Guillaume; Tinevez, Jean-Yves; Oates, Andrew C.
2016-01-01
Many questions in developmental biology depend on measuring the position and movement of individual cells within developing embryos. Yet, tools that provide this data are often challenged by high cell density and their accuracy is difficult to measure. Here, we present a three-step procedure to address this problem. Step one is a novel segmentation algorithm based on image derivatives that, in combination with selective post-processing, reliably and automatically segments cell nuclei from images of densely packed tissue. Step two is a quantitative validation using synthetic images to ascertain the efficiency of the algorithm with respect to signal-to-noise ratio and object density. Finally, we propose an original method to generate reliable and experimentally faithful ground truth datasets: Sparse-dense dual-labeled embryo chimeras are used to unambiguously measure segmentation errors within experimental data. Together, the three steps outlined here establish a robust, iterative procedure to fine-tune image analysis algorithms and microscopy settings associated with embryonic 3D image data sets. PMID:27332860
A surprising role for conformational entropy in protein function
Wand, A. Joshua; Moorman, Veronica R.; Harpole, Kyle W.
2014-01-01
Formation of high-affinity complexes is critical for the majority of enzymatic reactions involving proteins. The creation of the family of Michaelis and other intermediate complexes during catalysis clearly involves a complicated manifold of interactions that are diverse and complex. Indeed, computing the energetics of interactions between proteins and small molecule ligands using molecular structure alone remains a grand challenge. One of the most difficult contributions to the free energy of protein-ligand complexes to experimentally access is that due to changes in protein conformational entropy. Fortunately, recent advances in solution nuclear magnetic resonance (NMR) relaxation methods have enabled the use of measures-of-motion between conformational states of a protein as a proxy for conformational entropy. This review briefly summarizes the experimental approaches currently employed to characterize fast internal motion in proteins, how this information is used to gain insight into conformational entropy, what has been learned and what the future may hold for this emerging view of protein function. PMID:23478875
NASA Astrophysics Data System (ADS)
Depalo, Rosanna;
2018-01-01
A precise knowledge of the cross section of nuclear fusion reactions is a crucial ingredient in understanding stellar evolution and nucleosynthesis. At stellar temperatures, fusion cross sections are extremely small and difficult to measure. Measuring nuclear cross sections at astrophysical energies is a challenge that triggered a huge amount of experimental work. A breakthrough in this direction was the first operation of an underground accelerator at the Laboratory for Underground Nuclear Astrophysics (LUNA) in Gran Sasso, Italy. The 1400 meters of rocks above the laboratory act as a natural shield against cosmic radiation, suppressing the background by orders of magnitude. The latest results achieved at LUNA are discussed, with special emphasis on the 22Ne(p,γ)23Na reaction. Future perspectives of the LUNA experiment are also illustrated.
Improvement of CFD Methods for Modeling Full Scale Circulating Fluidized Bed Combustion Systems
NASA Astrophysics Data System (ADS)
Shah, Srujal; Klajny, Marcin; Myöhänen, Kari; Hyppänen, Timo
With the currently available methods of computational fluid dynamics (CFD), the task of simulating full scale circulating fluidized bed combustors is very challenging. In order to simulate the complex fluidization process, the size of calculation cells should be small and the calculation should be transient with small time step size. For full scale systems, these requirements lead to very large meshes and very long calculation times, so that the simulation in practice is difficult. This study investigates the requirements of cell size and the time step size for accurate simulations, and the filtering effects caused by coarser mesh and longer time step. A modeling study of a full scale CFB furnace is presented and the model results are compared with experimental data.
Optimization of a Small Scale Linear Reluctance Accelerator
NASA Astrophysics Data System (ADS)
Barrera, Thor; Beard, Robby
2011-11-01
Reluctance accelerators are extremely promising future methods of transportation. Several problems still plague these devices, most prominently low efficiency. Variables to overcoming efficiency problems are many and difficult to correlate how they affect our accelerator. The study examined several differing variables that present potential challenges in optimizing the efficiency of reluctance accelerators. These include coil and projectile design, power supplies, switching, and the elusive gradient inductance problem. Extensive research in these areas has been performed from computational and theoretical to experimental. Findings show that these parameters share significant similarity to transformer design elements, thus general findings show current optimized parameters the research suggests as a baseline for further research and design. Demonstration of these current findings will be offered at the time of presentation.
Logarithm conformal mapping brings the cloaking effect
Xu, Lin; Chen, Huanyang
2014-01-01
Over the past years, invisibility cloaks have been extensively discussed since transformation optics emerges. Generally, the electromagnetic parameters of invisibility cloaks are complicated tensors, yet difficult to realize. As a special method of transformation optics, conformal mapping helps us design invisibility cloak with isotropic materials of a refractive index distribution. However, for all proposed isotropic cloaks, the refractive index range is at such a breadth that challenges current experimental fabrication. In this work, we propose two new kinds of logarithm conformal mappings for invisible device designs. For one of the mappings, the refractive index distribution of conformal cloak varies from 0 to 9.839, which is more feasible for future implementation. Numerical simulations by using finite element method are performed to confirm the theoretical analysis. PMID:25359138
2017-01-01
ExoU is a 74 kDa cytotoxin that undergoes substantial conformational changes as part of its function, that is, it has multiple thermodynamically stable conformations that interchange depending on its environment. Such flexible proteins pose unique challenges to structural biology: (1) not only is it often difficult to determine structures by X-ray crystallography for all biologically relevant conformations because of the flat energy landscape (2) but also experimental conditions can easily perturb the biologically relevant conformation. The first challenge can be overcome by applying orthogonal structural biology techniques that are capable of observing alternative, biologically relevant conformations. The second challenge can be addressed by determining the structure in the same biological state with two independent techniques under different experimental conditions. If both techniques converge to the same structural model, the confidence that an unperturbed biologically relevant conformation is observed increases. To this end, we determine the structure of the C-terminal domain of the effector protein, ExoU, from data obtained by electron paramagnetic resonance spectroscopy in conjunction with site-directed spin labeling and in silico de novo structure determination. Our protocol encompasses a multimodule approach, consisting of low-resolution topology sampling, clustering, and high-resolution refinement. The resulting model was compared with an ExoU model in complex with its chaperone SpcU obtained previously by X-ray crystallography. The two models converged to a minimal RMSD100 of 3.2 Å, providing evidence that the unbound structure of ExoU matches the fold observed in complex with SpcU. PMID:28691114
Lie, Richard; Abdullah, Christopher; He, Wenliang; Tour, Ella
Primary literature offers rich opportunities to teach students how to "think like a scientist," but the challenges students face when they attempt to read research articles are not well understood. Here, we present an analysis of what master's students perceive as the most challenging aspects of engaging with primary literature. We examined 69 pairs of pre- and postcourse responses from students enrolled in a master's-level course that offered a structured analysis of primary literature. On the basis of these responses, we identified six categories of challenges. Before instruction, "techniques" and "experimental data" were the most frequently identified categories of challenges. The majority of difficulties students perceived in the primary literature corresponded to Bloom's lower-order cognitive skills. After instruction, "conclusions" were identified as the most difficult aspect of primary literature, and the frequency of challenges that corresponded to higher-order cognitive skills increased significantly among students who reported less experience with primary literature. These changes are consistent with a more competent perception of the primary literature, in which these students increasingly focus on challenges requiring critical thinking. Students' difficulties identified here can inform the design of instructional approaches aimed to teach students how to critically read scientific papers. © 2016 R. Lie, C. Abdullah, et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Rao, Durga Prasada; Rao, Venkateswara A
2010-01-01
The purpose of this article is to review the fundamental aspects of obesity, pregnancy and a combination of both. The scientific aim is to understand the physiological changes, pathological clinical presentations and application of technical skills and pharmacological knowledge on this unique clinical condition. The goal of this presentation is to define the difficult airway, highlight the main reasons for difficult or failed intubation and propose a practical approach to management Throughout the review, an important component is the necessity for team work between the anaesthesiologist and the obstetrician. Certain protocols are recommended to meet the anaesthetic challenges and finally concluding with “what is new?” in obstetric anaesthesia. PMID:21224967
Fast flexible modeling of RNA structure using internal coordinates.
Flores, Samuel Coulbourn; Sherman, Michael A; Bruns, Christopher M; Eastman, Peter; Altman, Russ Biagio
2011-01-01
Modeling the structure and dynamics of large macromolecules remains a critical challenge. Molecular dynamics (MD) simulations are expensive because they model every atom independently, and are difficult to combine with experimentally derived knowledge. Assembly of molecules using fragments from libraries relies on the database of known structures and thus may not work for novel motifs. Coarse-grained modeling methods have yielded good results on large molecules but can suffer from difficulties in creating more detailed full atomic realizations. There is therefore a need for molecular modeling algorithms that remain chemically accurate and economical for large molecules, do not rely on fragment libraries, and can incorporate experimental information. RNABuilder works in the internal coordinate space of dihedral angles and thus has time requirements proportional to the number of moving parts rather than the number of atoms. It provides accurate physics-based response to applied forces, but also allows user-specified forces for incorporating experimental information. A particular strength of RNABuilder is that all Leontis-Westhof basepairs can be specified as primitives by the user to be satisfied during model construction. We apply RNABuilder to predict the structure of an RNA molecule with 160 bases from its secondary structure, as well as experimental information. Our model matches the known structure to 10.2 Angstroms RMSD and has low computational expense.
HRD in Difficult Times. Symposium.
ERIC Educational Resources Information Center
2002
This document contains three papers on challenges facing human resource development today. "In Difficult Times: Influences of Attitudes and Expectations Towards Training and Redeployment Opportunities in a Hospital Retraction Programme" (Sandra Watson, Jeff Hyman) presents reasons behind the low uptake of training and redeployment…
Biofilm growth in porous media: Experiments, computational modeling at the porescale, and upscaling
NASA Astrophysics Data System (ADS)
Peszynska, Malgorzata; Trykozko, Anna; Iltis, Gabriel; Schlueter, Steffen; Wildenschild, Dorthe
2016-09-01
Biofilm growth changes many physical properties of porous media such as porosity, permeability and mass transport parameters. The growth depends on various environmental conditions, and in particular, on flow rates. Modeling the evolution of such properties is difficult both at the porescale where the phase morphology can be distinguished, as well as during upscaling to the corescale effective properties. Experimental data on biofilm growth is also limited because its collection can interfere with the growth, while imaging itself presents challenges. In this paper we combine insight from imaging, experiments, and numerical simulations and visualization. The experimental dataset is based on glass beads domain inoculated by biomass which is subjected to various flow conditions promoting the growth of biomass and the appearance of a biofilm phase. The domain is imaged and the imaging data is used directly by a computational model for flow and transport. The results of the computational flow model are upscaled to produce conductivities which compare well with the experimentally obtained hydraulic properties of the medium. The flow model is also coupled to a newly developed biomass-nutrient growth model, and the model reproduces morphologies qualitatively similar to those observed in the experiment.
LGBT Students in Community College: Characteristics, Challenges, and Recommendations
ERIC Educational Resources Information Center
Ivory, Brian T.
2005-01-01
Due to the transitory nature of students at community colleges, it is often difficult for student affairs professionals to connect with lesbian, gay, bisexual, and transgender (LGBT) students and even more difficult for them to provide services for this invisible population.
Promoting the Multidimensional Character of Scientific Reasoning †
Bradshaw, William S.; Nelson, Jennifer; Adams, Byron J.; Bell, John D.
2017-01-01
This study reports part of a long-term program to help students improve scientific reasoning using higher-order cognitive tasks set in the discipline of cell biology. This skill was assessed using problems requiring the construction of valid conclusions drawn from authentic research data. We report here efforts to confirm the hypothesis that data interpretation is a complex, multifaceted exercise. Confirmation was obtained using a statistical treatment showing that various such problems rank students differently—each contains a unique set of cognitive challenges. Additional analyses of performance results have allowed us to demonstrate that individuals differ in their capacity to navigate five independent generic elements that constitute successful data interpretation: biological context, connection to course concepts, experimental protocols, data inference, and integration of isolated experimental observations into a coherent model. We offer these aspects of scientific thinking as a “data analysis skills inventory,” along with usable sample problems that illustrate each element. Additionally, we show that this kind of reasoning is rigorous in that it is difficult for most novice students, who are unable to intuitively implement strategies for improving these skills. Instructors armed with knowledge of the specific challenges presented by different types of problems can provide specific helpful feedback during formative practice. The use of this instructional model is most likely to require changes in traditional classroom instruction. PMID:28512524
Neural mechanisms of rhythm perception: current findings and future perspectives.
Grahn, Jessica A
2012-10-01
Perception of temporal patterns is fundamental to normal hearing, speech, motor control, and music. Certain types of pattern understanding are unique to humans, such as musical rhythm. Although human responses to musical rhythm are universal, there is much we do not understand about how rhythm is processed in the brain. Here, I consider findings from research into basic timing mechanisms and models through to the neuroscience of rhythm and meter. A network of neural areas, including motor regions, is regularly implicated in basic timing as well as processing of musical rhythm. However, fractionating the specific roles of individual areas in this network has remained a challenge. Distinctions in activity patterns appear between "automatic" and "cognitively controlled" timing processes, but the perception of musical rhythm requires features of both automatic and controlled processes. In addition, many experimental manipulations rely on participants directing their attention toward or away from certain stimulus features, and measuring corresponding differences in neural activity. Many temporal features, however, are implicitly processed whether attended to or not, making it difficult to create controlled baseline conditions for experimental comparisons. The variety of stimuli, paradigms, and definitions can further complicate comparisons across domains or methodologies. Despite these challenges, the high level of interest and multitude of methodological approaches from different cognitive domains (including music, language, and motor learning) have yielded new insights and hold promise for future progress. Copyright © 2012 Cognitive Science Society, Inc.
Teaching Difficult Topics with Primary Sources
ERIC Educational Resources Information Center
Potter, Lee Ann
2011-01-01
"Difficult" or "challenging" topics to teach include racism, violence, genocide, bullying, gangs, abuse (physical, emotional, and substance), slavery, suffering, hatred, terrorism, war, disease, loss, addiction, and more. But by confronting them with students, in the safety of a classroom through thoughtfully constructed lessons (ones that take…
Scientific evidence and research in antimicrobial stewardship.
Almirante, Benito; Garnacho-Montero, José; Pachón, Jerónimo; Pascual, Álvaro; Rodríguez-Baño, Jesús
2013-09-01
Evaluating the impact of antibiotic stewardship programs is challenging. There is evidence that they are effective in terms of reducing the consumption and cost of antibiotics, although establishing their impact on antimicrobial resistance (beyond restrictive policies in outbreaks caused by specific antimicrobial resistant organisms) and clinical outcomes is more difficult. Proper definitions of exposure and outcome variables, the use of advanced and appropriate statistical analyses and well-designed quasi-experimental studies would more accurately support the conclusions. Cluster randomized trials should be used whenever possible and appropriate, although the limitations of this approach should also be acknowledged. These issues are reviewed in this paper. We conclude that there are good research opportunities in the field of antibiotic stewardship. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.
Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle
2018-05-09
Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.
Dugas, Matthew B
2015-11-01
An often underappreciated function of signals is to notify receivers of the presence and position of senders. The colours that ornament the mouthparts of nestling birds, for example, have been hypothesized to evolve via selective pressure generated by parents' inability to efficiently detect and feed nestlings without such visually conspicuous targets. This proposed mechanism has primarily been evaluated with comparative studies and experimental tests for parental allocation bias, leaving untested the central assumption of this detectability hypothesis, that provisioning offspring is a visually challenging task for avian parents and conspicuous mouths help. To test this assumption, I manipulated the mouths of nestling house sparrows to appear minimally and maximally conspicuous, and quantified prey transfer difficulty as the total duration of a feeding event and the number of transfer attempts required. Prey transfer to inconspicuous nestlings was, as predicted, more difficult. While this suggests that detectability constraints could shape nestling mouth colour evolution, even minimally conspicuous nestlings were not prohibitively difficult for parents to feed, indicating that a more nuanced explanation for interspecific diversity in this trait is needed. © 2015 The Author(s).
Zika vaccines and therapeutics: landscape analysis and challenges ahead.
Wilder-Smith, Annelies; Vannice, Kirsten; Durbin, Anna; Hombach, Joachim; Thomas, Stephen J; Thevarjan, Irani; Simmons, Cameron P
2018-06-06
Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.
Challenge and Retention in Games
ERIC Educational Resources Information Center
Debeauvais, Thomas
2016-01-01
Game designers and researchers agree that the main motivation for starting playing a game is challenge. It is only a small step to say that when the game becomes too difficult, players can become frustrated and quit. While extensive work shows that challenge is central in player enjoyment, its influence on player retention has received little…
Grand Challenges and Great Potential in Foreign Language Teaching and Learning
ERIC Educational Resources Information Center
Hlas, Anne Cummings
2018-01-01
This article argues for the field of foreign languages to begin to identify and define our Grand Challenges, which are difficult yet solvable problems facing our field. Seeking answers to these challenges can provide new opportunities for collaboration and can spur new directions and innovation within language learning and teaching. Researchable…
AFRICOM: An Effective Organization or a Military Hurdle?
2010-12-01
challenges that impact their effectiveness and therefore success. These challenges are not easy to visualize, thus making it more difficult to derive and...BLANK v ABSTRACT Many organizations face challenges that impact their effectiveness and therefore success. These challenges are not easy to visualize...examination of the variables that have the potential to adversely impact AFRICOM’s effectiveness. First, throughout the literature there are no specific
Crop diversity effects on soil health
USDA-ARS?s Scientific Manuscript database
Concurrent demands for abundant, healthy food, thriving rural economies, and an unpolluted physical environment represents a significant agricultural challenge in the 21st century. Trends in human population growth and changing weather patterns will make this challenge exceedingly difficult. Soil ...
NASA Astrophysics Data System (ADS)
Ollinger, S. V.; Ouimette, A.; Sullivan, F.; Sanders-DeMott, R.; Palace, M. W.; Xiao, J.; Braswell, B. H., Jr.; Lepine, L. C.
2017-12-01
The question of how biological diversity influences the functioning of ecosystems has been of interest for decades and represents a grand challenge question in ecology. In terrestrial ecosystems, most of the work on this topic has come from grasslands and other systems dominated by low stature vegetation that can be experimentally manipulated. Mature forests present a challenge because the size and lifespans of trees make it difficult to conduct manipulative diversity experiments. Although some studies have focused on previously established plantation forests, these opportunities are limited and often don't coincide with measurements of whole-ecosystem function. The accumulation of data from eddy covariance networks provides a unique opportunity in that the growing temporal coverage over a large number of sites should eventually make it feasible to examine the influence of diversity using statistical, as opposed to experimental, approaches. Realizing this potential will require new approaches to characterizing functional, as well as floristic, diversity of individual sites and methods for incorporating results in broad-scale syntheses. Here, we present early results from a project designed to examine forest canopy diversity in relation to ecosystem fluxes of carbon, water and energy over North American forests. In 2017, we focused on field and remote sensing measurements at the Bartlett Experimental Forest in New Hampshire, U.S.A. We conducted plot-scale measurements of physiological, biochemical and structural canopy traits and combined them with hyperspectral and lidar remote sensing, plot-based forest growth estimates and carbon fluxes from eddy covariance. Results will be presented with respect to inter-relations among structural and functional properties that influence C cycling and the potential to apply this approach in regional- or continental-scale analyses.
Tahmasbi, Amir; Ward, E. Sally; Ober, Raimund J.
2015-01-01
Fluorescence microscopy is a photon-limited imaging modality that allows the study of subcellular objects and processes with high specificity. The best possible accuracy (standard deviation) with which an object of interest can be localized when imaged using a fluorescence microscope is typically calculated using the Cramér-Rao lower bound, that is, the inverse of the Fisher information. However, the current approach for the calculation of the best possible localization accuracy relies on an analytical expression for the image of the object. This can pose practical challenges since it is often difficult to find appropriate analytical models for the images of general objects. In this study, we instead develop an approach that directly uses an experimentally collected image set to calculate the best possible localization accuracy for a general subcellular object. In this approach, we fit splines, i.e. smoothly connected piecewise polynomials, to the experimentally collected image set to provide a continuous model of the object, which can then be used for the calculation of the best possible localization accuracy. Due to its practical importance, we investigate in detail the application of the proposed approach in single molecule fluorescence microscopy. In this case, the object of interest is a point source and, therefore, the acquired image set pertains to an experimental point spread function. PMID:25837101
Guidelines and algorithms for managing the difficult airway.
Gómez-Ríos, M A; Gaitini, L; Matter, I; Somri, M
2018-01-01
The difficult airway constitutes a continuous challenge for anesthesiologists. Guidelines and algorithms are key to preserving patient safety, by recommending specific plans and strategies that address predicted or unexpected difficult airway. However, there are currently no "gold standard" algorithms or universally accepted standards. The aim of this article is to present a synthesis of the recommendations of the main guidelines and difficult airway algorithms. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Individual differences in social information gathering revealed through Bayesian hierarchical models
Pearson, John M.; Watson, Karli K.; Klein, Jeffrey T.; Ebitz, R. Becket; Platt, Michael L.
2013-01-01
As studies of the neural circuits underlying choice expand to include more complicated behaviors, analysis of behaviors elicited in laboratory paradigms has grown increasingly difficult. Social behaviors present a particular challenge, since inter- and intra-individual variation are expected to play key roles. However, due to limitations on data collection, studies must often choose between pooling data across all subjects or using individual subjects' data in isolation. Hierarchical models mediate between these two extremes by modeling individual subjects as drawn from a population distribution, allowing the population at large to serve as prior information about individuals' behavior. Here, we apply this method to data collected across multiple experimental sessions from a set of rhesus macaques performing a social information valuation task. We show that, while the values of social images vary markedly between individuals and between experimental sessions for the same individual, individuals also differentially value particular categories of social images. Furthermore, we demonstrate covariance between values for image categories within individuals and find evidence suggesting that magnitudes of stimulus values tend to diminish over time. PMID:24062635
MAJIQ-SPEL: Web-tool to interrogate classical and complex splicing variations from RNA-Seq data.
Green, Christopher J; Gazzara, Matthew R; Barash, Yoseph
2017-09-11
Analysis of RNA sequencing (RNA-Seq) data have highlighted the fact that most genes undergo alternative splicing (AS) and that these patterns are tightly regulated. Many of these events are complex, resulting in numerous possible isoforms that quickly become difficult to visualize, interpret, and experimentally validate. To address these challenges we developed MAJIQ-SPEL, a web-tool that takes as input local splicing variations (LSVs) quantified from RNA-Seq data and provides users with visualization and quantification of gene isoforms associated with those. Importantly, MAJIQ-SPEL is able to handle both classical (binary) and complex, non-binary, splicing variations. Using a matching primer design algorithm it also suggests users possible primers for experimental validation by RT-PCR and displays those, along with the matching protein domains affected by the LSV, on UCSC Genome Browser for further downstream analysis. Program and code will be available at http://majiq.biociphers.org/majiq-spel. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
NASA Astrophysics Data System (ADS)
Huebner, Torsten; Martens, Ulrike; Walowski, Jakob; Münzenberg, Markus; Thomas, Andy; Reiss, Günter; Kuschel, Timo
2018-06-01
In general, it is difficult to access the thermal conductivity of thin insulating films experimentally by electrical means. Here, we present a new approach utilizing the tunnel magneto-Seebeck effect (TMS) in combination with finite-element modeling (FEM). We detect the laser-induced TMS and the absolute thermovoltage of laser-heated magnetic tunnel junctions with 2.6 nm thin barriers of MgAl2O4 (MAO) and MgO, respectively. A second measurement of the absolute thermovoltage after a dielectric breakdown of the barrier grants insight into the remaining thermovoltage of the stack. Thus, the pure TMS without any parasitic Nernst contributions from the leads can be identified. In combination with FEM via COMSOL, we are able to extract values for the thermal conductivity of MAO (0.7 W (K · m)‑1) and MgO (5.8 W (K · m)‑1), which are in very good agreement with theoretical predictions. Our method provides a new promising way to extract the experimentally challenging parameter of the thermal conductivity of thin insulating films.
Molecular Modeling of a Probe in 2D IR Spectroscopy
NASA Astrophysics Data System (ADS)
Cooper, Anthony; Larini, Luca
Proteins must adopt a precise three dimensional structure in the folding process in order to perform its designated function. Although much has been learned about folding, there are still many details in structural dynamics that are difficult to characterize by existing experimental techniques. In order to overcome these challenges, novel infrared and fluorescent spectroscopic techniques have recently been employed to probe the molecular structure at the atomistic scale. These techniques rely on the spectroscopic properties of the nitrile group attached to a phenylalanine. In this study, we model this probe and we compute its properties in different solvents. This is done by performing Molecular Dynamics simulations with a PheCN solvated in water, urea and TMAO. We measure the decay rate of the vibrational stretching of the CN group in order to characterize the effects of different solvents on the local structure of the molecule. This data can be used to identify non-trivial conformational changes of the protein in the folding process. Preliminary results show agreement with current experimental data on 2D IR spectroscopy.
Combinatorial Characterization of TiO2 Chemical Vapor Deposition Utilizing Titanium Isopropoxide.
Reinke, Michael; Ponomarev, Evgeniy; Kuzminykh, Yury; Hoffmann, Patrik
2015-07-13
The combinatorial characterization of the growth kinetics in chemical vapor deposition processes is challenging because precise information about the local precursor flow is usually difficult to access. In consequence, combinatorial chemical vapor deposition techniques are utilized more to study functional properties of thin films as a function of chemical composition, growth rate or crystallinity than to study the growth process itself. We present an experimental procedure which allows the combinatorial study of precursor surface kinetics during the film growth using high vacuum chemical vapor deposition. As consequence of the high vacuum environment, the precursor transport takes place in the molecular flow regime, which allows predicting and modifying precursor impinging rates on the substrate with comparatively little experimental effort. In this contribution, we study the surface kinetics of titanium dioxide formation using titanium tetraisopropoxide as precursor molecule over a large parameter range. We discuss precursor flux and temperature dependent morphology, crystallinity, growth rates, and precursor deposition efficiency. We conclude that the surface reaction of the adsorbed precursor molecules comprises a higher order reaction component with respect to precursor surface coverage.
Modeling, Detection, and Disambiguation of Sensor Faults for Aerospace Applications
NASA Technical Reports Server (NTRS)
Balaban, Edward; Saxena, Abhinav; Bansal, Prasun; Goebel, Kai F.; Curran, Simon
2009-01-01
Sensor faults continue to be a major hurdle for systems health management to reach its full potential. At the same time, few recorded instances of sensor faults exist. It is equally difficult to seed particular sensor faults. Therefore, research is underway to better understand the different fault modes seen in sensors and to model the faults. The fault models can then be used in simulated sensor fault scenarios to ensure that algorithms can distinguish between sensor faults and system faults. The paper illustrates the work with data collected from an electro-mechanical actuator in an aerospace setting, equipped with temperature, vibration, current, and position sensors. The most common sensor faults, such as bias, drift, scaling, and dropout were simulated and injected into the experimental data, with the goal of making these simulations as realistic as feasible. A neural network based classifier was then created and tested on both experimental data and the more challenging randomized data sequences. Additional studies were also conducted to determine sensitivity of detection and disambiguation efficacy to severity of fault conditions.
A spiking neural network model of 3D perception for event-based neuromorphic stereo vision systems
Osswald, Marc; Ieng, Sio-Hoi; Benosman, Ryad; Indiveri, Giacomo
2017-01-01
Stereo vision is an important feature that enables machine vision systems to perceive their environment in 3D. While machine vision has spawned a variety of software algorithms to solve the stereo-correspondence problem, their implementation and integration in small, fast, and efficient hardware vision systems remains a difficult challenge. Recent advances made in neuromorphic engineering offer a possible solution to this problem, with the use of a new class of event-based vision sensors and neural processing devices inspired by the organizing principles of the brain. Here we propose a radically novel model that solves the stereo-correspondence problem with a spiking neural network that can be directly implemented with massively parallel, compact, low-latency and low-power neuromorphic engineering devices. We validate the model with experimental results, highlighting features that are in agreement with both computational neuroscience stereo vision theories and experimental findings. We demonstrate its features with a prototype neuromorphic hardware system and provide testable predictions on the role of spike-based representations and temporal dynamics in biological stereo vision processing systems. PMID:28079187
A spiking neural network model of 3D perception for event-based neuromorphic stereo vision systems.
Osswald, Marc; Ieng, Sio-Hoi; Benosman, Ryad; Indiveri, Giacomo
2017-01-12
Stereo vision is an important feature that enables machine vision systems to perceive their environment in 3D. While machine vision has spawned a variety of software algorithms to solve the stereo-correspondence problem, their implementation and integration in small, fast, and efficient hardware vision systems remains a difficult challenge. Recent advances made in neuromorphic engineering offer a possible solution to this problem, with the use of a new class of event-based vision sensors and neural processing devices inspired by the organizing principles of the brain. Here we propose a radically novel model that solves the stereo-correspondence problem with a spiking neural network that can be directly implemented with massively parallel, compact, low-latency and low-power neuromorphic engineering devices. We validate the model with experimental results, highlighting features that are in agreement with both computational neuroscience stereo vision theories and experimental findings. We demonstrate its features with a prototype neuromorphic hardware system and provide testable predictions on the role of spike-based representations and temporal dynamics in biological stereo vision processing systems.
A spiking neural network model of 3D perception for event-based neuromorphic stereo vision systems
NASA Astrophysics Data System (ADS)
Osswald, Marc; Ieng, Sio-Hoi; Benosman, Ryad; Indiveri, Giacomo
2017-01-01
Stereo vision is an important feature that enables machine vision systems to perceive their environment in 3D. While machine vision has spawned a variety of software algorithms to solve the stereo-correspondence problem, their implementation and integration in small, fast, and efficient hardware vision systems remains a difficult challenge. Recent advances made in neuromorphic engineering offer a possible solution to this problem, with the use of a new class of event-based vision sensors and neural processing devices inspired by the organizing principles of the brain. Here we propose a radically novel model that solves the stereo-correspondence problem with a spiking neural network that can be directly implemented with massively parallel, compact, low-latency and low-power neuromorphic engineering devices. We validate the model with experimental results, highlighting features that are in agreement with both computational neuroscience stereo vision theories and experimental findings. We demonstrate its features with a prototype neuromorphic hardware system and provide testable predictions on the role of spike-based representations and temporal dynamics in biological stereo vision processing systems.
Pixel-based parametric source depth map for Cerenkov luminescence imaging
NASA Astrophysics Data System (ADS)
Altabella, L.; Boschi, F.; Spinelli, A. E.
2016-01-01
Optical tomography represents a challenging problem in optical imaging because of the intrinsically ill-posed inverse problem due to photon diffusion. Cerenkov luminescence tomography (CLT) for optical photons produced in tissues by several radionuclides (i.e.: 32P, 18F, 90Y), has been investigated using both 3D multispectral approach and multiviews methods. Difficult in convergence of 3D algorithms can discourage to use this technique to have information of depth and intensity of source. For these reasons, we developed a faster 2D corrected approach based on multispectral acquisitions, to obtain source depth and its intensity using a pixel-based fitting of source intensity. Monte Carlo simulations and experimental data were used to develop and validate the method to obtain the parametric map of source depth. With this approach we obtain parametric source depth maps with a precision between 3% and 7% for MC simulation and 5-6% for experimental data. Using this method we are able to obtain reliable information about the source depth of Cerenkov luminescence with a simple and flexible procedure.
Monteagudo, Paula L; Lacasta, Anna; López, Elisabeth; Bosch, Laia; Collado, Javier; Pina-Pedrero, Sonia; Correa-Fiz, Florencia; Accensi, Francesc; Navas, María Jesús; Vidal, Enric; Bustos, María J; Rodríguez, Javier M; Gallei, Andreas; Nikolin, Veljko; Salas, María L; Rodríguez, Fernando
2017-11-01
African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8 + T cells capable of recognizing both BA71 and E75 viruses in vitro Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe. Copyright © 2017 Monteagudo et al.
Monteagudo, Paula L.; Lacasta, Anna; López, Elisabeth; Bosch, Laia; Collado, Javier; Pina-Pedrero, Sonia; Correa-Fiz, Florencia; Accensi, Francesc; Navas, María Jesús; Vidal, Enric; Bustos, María J.; Rodríguez, Javier M.; Gallei, Andreas; Nikolin, Veljko; Salas, María L.
2017-01-01
ABSTRACT African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe. PMID:28814514
Girls' Challenge Seeking: How Outdoor Exposure Can Support Girls in Taking Positive Risks
ERIC Educational Resources Information Center
Tsikalas, Kallen; Martin, Karyn L.
2015-01-01
Challenge seeking is an important component of children's personal and academic development. Defined in this paper as a set of beliefs and behaviors that propels individuals to initiate and persist at difficult ventures, challenge seeking is a key indicator of mastery goal orientation. This orientation has been linked with a number of positive and…
Social Software: A Powerful Paradigm for Building Technology for Global Learning
ERIC Educational Resources Information Center
Wooding, Amy; Wooding, Kjell
2018-01-01
It is not difficult to imagine a world where internet-connected mobile devices are accessible to everyone. Can these technologies be used to help solve the challenges of global education? This was the challenge posed by the Global Learning XPRIZE--a $15 million grand challenge competition aimed at addressing this global teaching shortfall. In…
A Combined Experimental and Computational Approach to Subject-Specific Analysis of Knee Joint Laxity
Harris, Michael D.; Cyr, Adam J.; Ali, Azhar A.; Fitzpatrick, Clare K.; Rullkoetter, Paul J.; Maletsky, Lorin P.; Shelburne, Kevin B.
2016-01-01
Modeling complex knee biomechanics is a continual challenge, which has resulted in many models of varying levels of quality, complexity, and validation. Beyond modeling healthy knees, accurately mimicking pathologic knee mechanics, such as after cruciate rupture or meniscectomy, is difficult. Experimental tests of knee laxity can provide important information about ligament engagement and overall contributions to knee stability for development of subject-specific models to accurately simulate knee motion and loading. Our objective was to provide combined experimental tests and finite-element (FE) models of natural knee laxity that are subject-specific, have one-to-one experiment to model calibration, simulate ligament engagement in agreement with literature, and are adaptable for a variety of biomechanical investigations (e.g., cartilage contact, ligament strain, in vivo kinematics). Calibration involved perturbing ligament stiffness, initial ligament strain, and attachment location until model-predicted kinematics and ligament engagement matched experimental reports. Errors between model-predicted and experimental kinematics averaged <2 deg during varus–valgus (VV) rotations, <6 deg during internal–external (IE) rotations, and <3 mm of translation during anterior–posterior (AP) displacements. Engagement of the individual ligaments agreed with literature descriptions. These results demonstrate the ability of our constraint models to be customized for multiple individuals and simultaneously call attention to the need to verify that ligament engagement is in good general agreement with literature. To facilitate further investigations of subject-specific or population based knee joint biomechanics, data collected during the experimental and modeling phases of this study are available for download by the research community. PMID:27306137
Baccalaureate Student Perceptions of Challenging Family Problems: Building Bridges to Acceptance
ERIC Educational Resources Information Center
Floyd, Melissa; Gruber, Kenneth J.
2011-01-01
This study explored the attitudes of 147 undergraduate social work majors to working with difficult families. Students indicated which problems (from a list of 42, including hot topics such as homosexuality, transgender issues, abortion, and substance abuse) they believed they would find most difficult to work with and provided information…
Classroom Techniques to Illustrate Water Transport in Plants
ERIC Educational Resources Information Center
Lakrim, Mohamed
2013-01-01
The transport of water in plants is among the most difficult and challenging concepts to explain to students. It is even more difficult for students enrolled in an introductory general biology course. An easy approach is needed to demonstrate this complex concept. I describe visual and pedagogical examples that can be performed quickly and easily…
Using Curriculum-Based Measurement to Drive IEPs and Instruction in Written Expression
ERIC Educational Resources Information Center
Hessler, Terri; Konrad, Moira
2008-01-01
Setting meaningful individualized education program (IEP) goals and objectives is one of the challenges that special education teachers face. In written expression, this task is even more difficult. Not only is assessing writing a subjective and difficult endeavor, but writing itself is a complicated task. Because many students with disabilities…
ERIC Educational Resources Information Center
Auduc, Jean-Louis
This book outlines challenges involved in ensuring that teacher training becomes the gateway to implementation of appropriate strategies for students to achieve and for managing the problems of authority, discipline, and aggressive behavior. The six chapters examine: (1) "Teaching in Schools or Classes Considered Difficult: A Contemporary…
Schumann, Karina; Zaki, Jamil; Dweck, Carol S
2014-09-01
Empathy is often thought to occur automatically. Yet, empathy frequently breaks down when it is difficult or distressing to relate to people in need, suggesting that empathy is often not felt reflexively. Indeed, the United States as a whole is said to be displaying an empathy deficit. When and why does empathy break down, and what predicts whether people will exert effort to experience empathy in challenging contexts? Across 7 studies, we found that people who held a malleable mindset about empathy (believing empathy can be developed) expended greater empathic effort in challenging contexts than did people who held a fixed theory (believing empathy cannot be developed). Specifically, a malleable theory of empathy--whether measured or experimentally induced--promoted (a) more self-reported effort to feel empathy when it is challenging (Study 1); (b) more empathically effortful responses to a person with conflicting views on personally important sociopolitical issues (Studies 2-4); (c) more time spent listening to the emotional personal story of a racial outgroup member (Study 5); and (d) greater willingness to help cancer patients in effortful, face-to-face ways (Study 6). Study 7 revealed a possible reason for this greater empathic effort in challenging contexts: a stronger interest in improving one's empathy. Together, these data suggest that people's mindsets powerfully affect whether they exert effort to empathize when it is needed most, and these data may represent a point of leverage in increasing empathic behaviors on a broad scale. 2014 APA, all rights reserved
Govender, Samantha; Khan, Nasim
2016-01-01
Audiologists managing children with auditory processing disorders (APD) encounter challenges that include conflicting definitions, several classification profiles, problems with differential diagnosis and a lack of standardised guidelines. The heterogeneity of the disorder and its concomitant childhood disorders makes diagnosis difficult. Linguistic and cultural issues are additional challenges faced by South African audiologists. The study aimed to describe the practices, challenges and recommendations of South African audiologists managing children with APD. A quantitative, non-experimental descriptive survey was used to obtain data from 156 audiologists registered with the Health Professions of South Africa. Findings revealed that 67% screened for APD, 42% assessed while 43% provided intervention. A variety of screening and assessment procedures were being administered, with no standard test battery identified. A range of intervention strategies being used are discussed. When the relationship between the number of years of experience and the audiologists’ level of preparedness to practice in the field of APD was compared, a statistically significant difference (p = 0.049) was seen in that participants with more than 10 years of experience were more prepared to practice in this area. Those participants having qualified as speech-language therapists and audiologists were significantly more prepared (p = 0.03) to practice than the audiologists who comprised the sample. Challenges experienced by the participants included the lack of linguistically and culturally appropriate screening and assessment tools and limited normative data. Recommendations included reviewing the undergraduate audiology training programmes, reinstituting the South African APD Taskforce, developing linguistically and culturally appropriate normative data, creating awareness among educators and involving them in the multidisciplinary team. PMID:27380913
Simulating Ideal Assistive Devices to Reduce the Metabolic Cost of Running
Uchida, Thomas K.; Seth, Ajay; Pouya, Soha; Dembia, Christopher L.; Hicks, Jennifer L.; Delp, Scott L.
2016-01-01
Tools have been used for millions of years to augment the capabilities of the human body, allowing us to accomplish tasks that would otherwise be difficult or impossible. Powered exoskeletons and other assistive devices are sophisticated modern tools that have restored bipedal locomotion in individuals with paraplegia and have endowed unimpaired individuals with superhuman strength. Despite these successes, designing assistive devices that reduce energy consumption during running remains a substantial challenge, in part because these devices disrupt the dynamics of a complex, finely tuned biological system. Furthermore, designers have hitherto relied primarily on experiments, which cannot report muscle-level energy consumption and are fraught with practical challenges. In this study, we use OpenSim to generate muscle-driven simulations of 10 human subjects running at 2 and 5 m/s. We then add ideal, massless assistive devices to our simulations and examine the predicted changes in muscle recruitment patterns and metabolic power consumption. Our simulations suggest that an assistive device should not necessarily apply the net joint moment generated by muscles during unassisted running, and an assistive device can reduce the activity of muscles that do not cross the assisted joint. Our results corroborate and suggest biomechanical explanations for similar effects observed by experimentalists, and can be used to form hypotheses for future experimental studies. The models, simulations, and software used in this study are freely available at simtk.org and can provide insight into assistive device design that complements experimental approaches. PMID:27656901
Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.
Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian
2018-02-23
Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.
Ruggiero, Michael T; Zeitler, J Axel
2016-11-17
Anharmonicity has been shown to be an important piece of the fundamental framework that dictates numerous observable phenomena. In particular, anharmonicity is the driving force of vibrational relaxation processes, mechanisms that are integral to the proper function of numerous chemical processes. However, elucidating its origins has proven difficult due to experimental and theoretical challenges, specifically related to separating the anharmonic contributions from other unrelated effects. While no one technique is particularly suited for providing a complete picture of anharmonicity, by combining multiple complementary methods such a characterization can be made. In this study the role of individual atomic interactions on the anharmonic properties of crystalline purine, the building block of many DNA and RNA nucleobases, is studied by experimental terahertz time-domain spectroscopy and first-principles density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD). In particular, the detailed vibrational information provided by the DFT calculations is used to interpret the atomic origins of anharmonic-related effects as determined by the AIMD calculations, which are in good agreement with the experimental data. The results highlight that anharmonicity is especially pronounced in the intermolecular interactions, particularly along the amine hydrogen bond coordinate, and yields valuable insight into what is similarly observed complex biosystems and crystalline solids.
The Challenges of Digital Leadership
ERIC Educational Resources Information Center
McLeod, Scott
2015-01-01
Because digital devices and online environments can simultaneously be transformatively empowering and maddeningly disruptive, the work of integrating digital learning tools into schools is usually difficult and complex. Common challenges arise, however, and can be thoughtfully addressed by proactive leadership. In the end, technology change in…
Monitoring challenges and innovative ideas
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Neill, R.V.; Hunsaker, C.T.; Levine, D.A.
1990-01-01
Monitoring programs are difficult to design even when they focus on specific problems. Ecosystems are complex, and it is often impossible to predetermine what aspects of system structure or dynamics will respond to a specific insult. It is equally difficult to interpret whether a response is a stabilizing compensatory mechanism or a real loss of capacity to maintain the ecosystem. The problems are compounded in a broad monitoring program designed to assess ecosystem health'' at regional and continental scales. It is challenging in the extreme to monitor ecosystem response, at any scale, to past insults as well as an unknownmore » future array of impacts. The present paper will examine some of the fundamental issues and challenges raised by large-scale monitoring efforts. The challenges will serve as a framework and as an excuse to discuss several important topics in more detail. Following the discussion of challenges, we suggest some basic innovations that could be important across a range of monitoring programs. The innovations include integrative measures, innovative methodology, and creative interpretation. 59 refs., 1 tab.« less
O’Doherty, John P.
2015-01-01
Neural correlates of value have been extensively reported in a diverse set of brain regions. However, in many cases it is difficult to determine whether a particular neural response pattern corresponds to a value-signal per se as opposed to an array of alternative non-value related processes, such as outcome-identity coding, informational coding, encoding of autonomic and skeletomotor consequences, alongside previously described “salience” or “attentional” effects. Here, I review a number of experimental manipulations that can be used to test for value, and I identify the challenges in ascertaining whether a particular neural response is or is not a value signal. Finally, I emphasize that some non-value related signals may be especially informative as a means of providing insight into the nature of the decision-making related computations that are being implemented in a particular brain region. PMID:24726573
CFD Analysis in Advance of the NASA Juncture Flow Experiment
NASA Technical Reports Server (NTRS)
Lee, H. C.; Pulliam, T. H.; Neuhart, D. H.; Kegerise, M. A.
2017-01-01
NASA through its Transformational Tools and Technologies Project (TTT) under the Advanced Air Vehicle Program, is supporting a substantial effort to investigate the formation and origin of separation bubbles found on wing-body juncture zones. The flow behavior in these regions is highly complex, difficult to measure experimentally, and challenging to model numerically. Multiple wing configurations were designed and evaluated using Computational Fluid Dynamics (CFD), and a series of wind tunnel risk reduction tests were performed to further down-select the candidates for the final experiment. This paper documents the CFD analysis done in conjunction with the 6 percent scale risk reduction experiment performed in NASA Langley's 14- by 22-Foot Subsonic Tunnel. The combined CFD and wind tunnel results ultimately helped the Juncture Flow committee select the wing configurations for the final experiment.
Saeidi Pour, Reza; Edelhoff, Daniel; Prandtner, Otto; Liebermann, Anja
2015-01-01
The complete dental rehabilitation of patients with a vertical dimension loss (VDL) caused by structural enamel deficits associated with amelogenesis imperfecta (AI) represents a difficult challenge for restorative teams. Accurate analysis and treatment planning that includes esthetic and functional evaluations and adequate material selection are important prerequisites for successful results. Long-term provisional restorations play an important role in exploring and elucidating the patients' esthetic demands and functional needs. Restorative treatment options can vary from requiring only oral hygiene instructions to extensive dental restorations that include composite fillings, ceramic veneers, metal-ceramic, or all-ceramic crowns. This case report describes a full-mouth rehabilitation of a patient with amelogenesis imperfecta including the case planning, bite replacement, preparation, and restoration setting steps with an experimental CAD/CAM polymer and porcelain veneers.
Visualization study of counterflow in superfluid 4He using metastable helium molecules.
Guo, W; Cahn, S B; Nikkel, J A; Vinen, W F; McKinsey, D N
2010-07-23
Heat is transferred in superfluid 4He via a process known as thermal counterflow. It has been known for many years that above a critical heat current the superfluid component in this counterflow becomes turbulent. It has been suspected that the normal-fluid component may become turbulent as well, but experimental verification is difficult without a technique for visualizing the flow. Here we report a series of visualization studies on the normal-fluid component in a thermal counterflow performed by imaging the motion of seeded metastable helium molecules using a laser-induced-fluorescence technique. We present evidence that the flow of the normal fluid is indeed turbulent at relatively large velocities. Thermal counterflow in which both components are turbulent presents us with a theoretically challenging type of turbulent behavior that is new to physics.
Visualizing uncertainty about the future.
Spiegelhalter, David; Pearson, Mike; Short, Ian
2011-09-09
We are all faced with uncertainty about the future, but we can get the measure of some uncertainties in terms of probabilities. Probabilities are notoriously difficult to communicate effectively to lay audiences, and in this review we examine current practice for communicating uncertainties visually, using examples drawn from sport, weather, climate, health, economics, and politics. Despite the burgeoning interest in infographics, there is limited experimental evidence on how different types of visualizations are processed and understood, although the effectiveness of some graphics clearly depends on the relative numeracy of an audience. Fortunately, it is increasingly easy to present data in the form of interactive visualizations and in multiple types of representation that can be adjusted to user needs and capabilities. Nonetheless, communicating deeper uncertainties resulting from incomplete or disputed knowledge--or from essential indeterminacy about the future--remains a challenge.
The U.S. Army is confronting a number of challenges. It has relatively well- established organizations and procedures for some challenges, such as... deployments . Some soldiers perceptions that seeking help for stress is a sign of weakness complicate these challenges. Other difficult issues pertain to the workplace, including sexual harassment and assault.
Side-branch technique for difficult guidewire placement in coronary bifurcation lesion.
He, Xingwei; Gao, Bo; Liu, Yujian; Li, Zhuxi; Zeng, Hesong
2016-01-01
Despite tremendous advances in technology and skills, percutaneous coronary intervention (PCI) of bifurcation lesion (BL) remains a particular challenge for the interventionalist. During bifurcation PCI, safe guidewire placement in the main branch (MB) and the side branch (SB) is the first step for successful procedure. However, in certain cases, the complex pattern of vessel anatomy and the mix of plaque distribution may make target vessel wiring highly challenging. Therefore, specific techniques are required for solving this problem. Hereby, we describe a new use of side-branch technique for difficult guidewire placement in BL. Copyright © 2015 Elsevier Inc. All rights reserved.
Wilson, Kris; Webster, Scott P; Iredale, John P; Zheng, Xiaozhong; Homer, Natalie Z; Pham, Nhan T; Auer, Manfred; Mole, Damian J
2017-12-15
The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.
NASA Astrophysics Data System (ADS)
Wilson, Kris; Webster, Scott P.; Iredale, John P.; Zheng, Xiaozhong; Homer, Natalie Z.; Pham, Nhan T.; Auer, Manfred; Mole, Damian J.
2018-01-01
The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.
Evaluating methods for monitoring populations of Mexican spotted owls: A case study
Jospeh L. Ganey; Gary C. White; David C. Bowden; Alan B. Franklin
2004-01-01
Monitoring population status of rare or elusive species presents special challenges. Understanding population trends requires separating signal (true and important changes in abundance) from noise (normal temporal and sampling variation; e.g., Block et al. 2001). This is particularly difficult when small numbers or elusive habits make it difficult to obtain precise...
ERIC Educational Resources Information Center
Hill, George B.; Sweeney, Joseph B.
2015-01-01
Reaction workup can be a complex problem for those facing novel synthesis of difficult compounds for the first time. Workup problem solving by systematic thinking should be inculcated as mid-graduate-level is reached. A structured approach is proposed, building decision tree flowcharts to analyze challenges, and an exemplar flowchart is presented…
[Partnership around difficult teenagers in Brest].
Saint-André, Stéphane; Botbol, Michel
2013-01-01
The issues surrounding difficult teenagers results in professionals formalising a partnership. Certain areas of focus are identified such as getting to know each other better in order to understand each other better, working in a "common language", understanding professional identities, or embracing long term partnership. Pressure to assess and rationalise spending, as well as political challenges, must be taken into consideration.
The Effect of Outsourcing on the Performance of Public Schools
ERIC Educational Resources Information Center
Rivera, Lonny J.
2009-01-01
Public education in the 21st century is faced with many difficult challenges. The first and probably most common issue is related to finance. As the economy continues to worsen, school districts are forced to find new revenue streams while at the same time reducing expenditures. In the current economic climate, it is becoming more difficult for…
DOE Office of Scientific and Technical Information (OSTI.GOV)
J. Vernon Cole; Abhra Roy; Ashok Damle
2012-10-02
Water management in Proton Exchange Membrane, PEM, Fuel Cells is challenging because of the inherent conflicts between the requirements for efficient low and high power operation. Particularly at low powers, adequate water must be supplied to sufficiently humidify the membrane or protons will not move through it adequately and resistance losses will decrease the cell efficiency. At high power density operation, more water is produced at the cathode than is necessary for membrane hydration. This excess water must be removed effectively or it will accumulate in the Gas Diffusion Layers, GDLs, between the gas channels and catalysts, blocking diffusion pathsmore » for reactants to reach the catalysts and potentially flooding the electrode. As power density of the cells is increased, the challenges arising from water management are expected to become more difficult to overcome simply due to the increased rate of liquid water generation relative to fuel cell volume. Thus, effectively addressing water management based issues is a key challenge in successful application of PEMFC systems. In this project, CFDRC and our partners used a combination of experimental characterization, controlled experimental studies of important processes governing how water moves through the fuel cell materials, and detailed models and simulations to improve understanding of water management in operating hydrogen PEM fuel cells. The characterization studies provided key data that is used as inputs to all state-of-the-art models for commercially important GDL materials. Experimental studies and microscopic scale models of how water moves through the GDLs showed that the water follows preferential paths, not branching like a river, as it moves toward the surface of the material. Experimental studies and detailed models of water and airflow in fuel cells channels demonstrated that such models can be used as an effective design tool to reduce operating pressure drop in the channels and the associated costs and weight of blowers and pumps to force air and hydrogen gas through the fuel cell. Promising improvements to materials structure and surface treatments that can potentially aid in managing the distribution and removal of liquid water were developed; and improved steady-state and freeze-thaw performance was demonstrated for a fuel cell stack under the self-humidified operating conditions that are promising for stationary power generation with reduced operating costs.« less
Getting to 2014: The Choices and Challenges Ahead
ERIC Educational Resources Information Center
Balfanz, Robert; Cohen, Michael; Hassel, Bryan C.; Hassel, Emily Ayscue; Hyslop, Anne; Odden, Allan; Tucker, Bill
2012-01-01
Over the next few years, educators and policymakers have committed to implementing an array of challenging, but potentially transformative, reforms--reforms that could go beyond rearranging furniture to fundamentally restructuring and improving teaching and learning. Facing this much simultaneous change would be difficult even without the…
Recruiting and Rewarding Faculty for Medical Student Teaching
ERIC Educational Resources Information Center
Pessar, Linda F.; Levine, Ruth E.; Bernstein, Carol A.; Cabaniss, Deborah S.; Dickstein, Leah J.; Graff, Sarah V.; Hales, Deborah J.; Nadelson, Carol; Robinowitz, Carolyn B.; Scheiber, Stephen C.; Jones, Paul M.; Silberman, Edward K.
2006-01-01
Objective: Finding time to teach psychiatry has become increasingly difficult. Concurrently, changes in medical student education are elevating demands for teaching. Academic psychiatry is challenged by these pressures to find innovative ways to recruit, retain, and reward faculty for teaching efforts. To address this challenge, the authors…
ERIC Educational Resources Information Center
Richmond, Tom; Young, Aaron
2013-01-01
"Instant Insanity II" is a sliding mechanical puzzle whose solution requires the special alignment of 16 colored tiles. We count the number of solutions of the puzzle's classic challenge and show that the more difficult ultimate challenge has, up to row permutation, exactly two solutions, and further show that no…
Sex Work Research: Methodological and Ethical Challenges
ERIC Educational Resources Information Center
Shaver, Frances M.
2005-01-01
The challenges involved in the design of ethical, nonexploitative research projects with sex workers or any other marginalized population are significant. First, the size and boundaries of the population are unknown, making it extremely difficult to get a representative sample. Second, because membership in hidden populations often involves…
Molecular Rotation Signals: Molecule Chemistry and Particle Physics
NASA Astrophysics Data System (ADS)
Grabow, Jens-Uwe
2015-06-01
Molecules - large or small - are attractive academic resources, with numerous questions on their chemical behaviour as well as problems in fundamental physics now (or still) waiting to be answered: Targeted by high-resolution spectroscopy, a rotating molecular top can turn into a laboratory for molecule chemistry or a laboratory for particle physics. Once successfully entrained (many species - depending on size and chemical composition - have insufficient vapour pressures or are of transient nature, such that specifically designed pulsed-jet sources are required for their transfer into the gas phase or in-situ generation) into the collision-free environment of a supersonic-jet expansion, each molecular top comes with its own set of challenges, theoretically and experimentally: Multiple internal interactions are causing complicated energy level schemes and the resulting spectra will be rather difficult to predict theoretically. Experimentally, these spectra are difficult to assess and assign. With today's broad-banded chirp microwave techniques, finding and identifying such spectral features have lost their major drawback of being very time consuming for many molecules. For other molecules, the unrivalled resolution and sensitivity of the narrow-banded impulse microwave techniques provide a window to tackle - at the highest precision available to date - fundamental questions in physics, even particle physics - potentially beyond the standard model. Molecular charge distribution, properties of the chemical bond, details on internal dynamics and intermolecular interaction, the (stereo-chemical) molecular structure (including the possibility of their spatial separation) as well as potential evidence for tiny yet significant interactions encode their signature in pure molecular rotation subjected to time-domain microwave spectroscopic techniques. Ongoing exciting technical developments promise rapid progress. We present recent examples from Hannover, new directions, and an outlook at the future of molecular rotation spectroscopy.
Evaluation of target efficiencies for solid-liquid separation steps in biofuels production.
Kochergin, Vadim; Miller, Keith
2011-01-01
Development of liquid biofuels has entered a new phase of large scale pilot demonstration. A number of plants that are in operation or under construction face the task of addressing the engineering challenges of creating a viable plant design, scaling up and optimizing various unit operations. It is well-known that separation technologies account for 50-70% of both capital and operating cost. Additionally, reduction of environmental impact creates technological challenges that increase project cost without adding to the bottom line. Different technologies vary in terms of selection of unit operations; however, solid-liquid separations are likely to be a major contributor to the overall project cost. Despite the differences in pretreatment approaches, similar challenges arise for solid-liquid separation unit operations. A typical process for ethanol production from biomass includes several solid-liquid separation steps, depending on which particular stream is targeted for downstream processing. The nature of biomass-derived materials makes it either difficult or uneconomical to accomplish complete separation in a single step. Therefore, setting realistic efficiency targets for solid-liquid separations is an important task that influences overall process recovery and economics. Experimental data will be presented showing typical characteristics for pretreated cane bagasse at various stages of processing into cellulosic ethanol. Results of generic material balance calculations will be presented to illustrate the influence of separation target efficiencies on overall process recoveries and characteristics of waste streams.
Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.
Halldorsson, Skarphedinn; Lucumi, Edinson; Gómez-Sjöberg, Rafael; Fleming, Ronan M T
2015-01-15
Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Inferring gene expression from ribosomal promoter sequences, a crowdsourcing approach
Meyer, Pablo; Siwo, Geoffrey; Zeevi, Danny; Sharon, Eilon; Norel, Raquel; Segal, Eran; Stolovitzky, Gustavo; Siwo, Geoffrey; Rider, Andrew K.; Tan, Asako; Pinapati, Richard S.; Emrich, Scott; Chawla, Nitesh; Ferdig, Michael T.; Tung, Yi-An; Chen, Yong-Syuan; Chen, Mei-Ju May; Chen, Chien-Yu; Knight, Jason M.; Sahraeian, Sayed Mohammad Ebrahim; Esfahani, Mohammad Shahrokh; Dreos, Rene; Bucher, Philipp; Maier, Ezekiel; Saeys, Yvan; Szczurek, Ewa; Myšičková, Alena; Vingron, Martin; Klein, Holger; Kiełbasa, Szymon M.; Knisley, Jeff; Bonnell, Jeff; Knisley, Debra; Kursa, Miron B.; Rudnicki, Witold R.; Bhattacharjee, Madhuchhanda; Sillanpää, Mikko J.; Yeung, James; Meysman, Pieter; Rodríguez, Aminael Sánchez; Engelen, Kristof; Marchal, Kathleen; Huang, Yezhou; Mordelet, Fantine; Hartemink, Alexander; Pinello, Luca; Yuan, Guo-Cheng
2013-01-01
The Gene Promoter Expression Prediction challenge consisted of predicting gene expression from promoter sequences in a previously unknown experimentally generated data set. The challenge was presented to the community in the framework of the sixth Dialogue for Reverse Engineering Assessments and Methods (DREAM6), a community effort to evaluate the status of systems biology modeling methodologies. Nucleotide-specific promoter activity was obtained by measuring fluorescence from promoter sequences fused upstream of a gene for yellow fluorescence protein and inserted in the same genomic site of yeast Saccharomyces cerevisiae. Twenty-one teams submitted results predicting the expression levels of 53 different promoters from yeast ribosomal protein genes. Analysis of participant predictions shows that accurate values for low-expressed and mutated promoters were difficult to obtain, although in the latter case, only when the mutation induced a large change in promoter activity compared to the wild-type sequence. As in previous DREAM challenges, we found that aggregation of participant predictions provided robust results, but did not fare better than the three best algorithms. Finally, this study not only provides a benchmark for the assessment of methods predicting activity of a specific set of promoters from their sequence, but it also shows that the top performing algorithm, which used machine-learning approaches, can be improved by the addition of biological features such as transcription factor binding sites. PMID:23950146
Winkler, Dirk F H; Tian, Kerry
2015-04-01
Difficult peptides are a constant challenge in solid-phase peptide synthesis. In particular, hydroxyl amino acids such as serine can cause severe breakdowns in coupling yields even several amino acids after the insertion of the critical amino acid. This paper investigates several methods of improving synthesis yields of difficult peptides including the use of different resins, activators and the incorporation of a structure-breaking pseudoproline dipeptide building block both alone and in combination with each other.
Chopra, Vanilla; Mehta, Nandita; Dar, Mohd Reidwan
2017-01-01
Enlarged thyroid gland with retrosternal extension has an increased incidence of difficult intubation, and it poses real airway challenge for the anesthesiologists. Here, we present a case of successful management of a difficult airway in a female patient of enlarged thyroid gland, planned for open reduction and internal fixation of the upper end of humerus. Endotracheal intubation was achieved after deliberate insertion of an endotracheal tube in esophagus. The patient was extubated over a ventilating bougie, with uneventful postoperative course. PMID:29284880
Using Data to Guide Difficult Conversations around Structural Racism
ERIC Educational Resources Information Center
Myers, Lesli C.; Finnigan, Kara S.
2018-01-01
Challenging and confronting educational systems and structures, the vast majority of which come from a place of privilege, is uncomfortable but necessary. Education, from early childhood to post-secondary, should challenge and address the racial inequities that inevitably characterize such systems and structures. Yet, we do not always do this…
Curriculum Reform as Adaptive Leadership Challenge
ERIC Educational Resources Information Center
Wolfe, Kathy J.
2015-01-01
Serious curricular reform is both exhilarating in its possibilities and exhausting in its particulars. When its scope is significant and it is undertaken in response to a variety of difficult challenges, curriculum revision becomes more about cultural change than a mere matter of logistics. While studying adaptive leadership with colleagues at the…
Organisational Legitimacy of the Singapore Ministry of Education
ERIC Educational Resources Information Center
Tan, Cheng Yong
2013-01-01
This paper analyses the perceived organisational legitimacy of the Singapore Ministry of Education (MOE) in preparing the population for work in the knowledge-based economy (KBE). It is argued that challenges to MOE's legitimacy are emerging with ramifications that are difficult to ignore. These challenges relate to equipping the population with…
USDA-ARS?s Scientific Manuscript database
Prevention of bacterial infections via immunization presents particular challenges. While outer membrane extracts are often protective; they are difficult and expensive to isolate and standardize, and thus often impractical for development and implementation in vaccination programs. In contrast, ind...
Critical Performative Pedagogy: Emergent Bilingual Learners Challenge Local Immigration Issues
ERIC Educational Resources Information Center
Harman, Ruth; Varga-Dobai, Kinga
2012-01-01
Recent anti-immigration policies and practices in the Southeast of the United States have presented difficult challenges for newly arrived bilingual learners and their families. To validate student voices within this socio-political context, our school/university collaboration implemented an arts-based participatory approach to English Language…
A Zone for Deliberation? Methodological Challenges in Fields of Political Unrest
ERIC Educational Resources Information Center
Westrheim, Kariane; Lillejord, Solvi
2007-01-01
This article outlines certain problems and challenges facing the qualitative researcher who enters fields that are either extremely difficult to access or potentially hostile towards outsiders. Problems and dilemmas in such contexts are highlighted by reference to fieldwork research among PKK (Kurdistan Worker's Party) guerrillas in North…
Expressing Adaptation Strategies Using Adaptation Patterns
ERIC Educational Resources Information Center
Zemirline, N.; Bourda, Y.; Reynaud, C.
2012-01-01
Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…
School Leader Relationships: The Need for Explicit Training on Rapport, Trust, and Communication
ERIC Educational Resources Information Center
Lasater, Kara
2016-01-01
An important aspect of school leadership is relationship development, but developing meaningful relationships as a school leader is challenging. School leader relationships are challenged by diverse stakeholder groups, varied contexts, and difficult situations. The complex nature of school leader relationships necessitates explicit training for…
The role of public-private partnerships in addressing the biomedical innovation challenge.
Said, Maya; Zerhouni, Elias
2014-11-01
Without a step change in the productivity of pharmaceutical research and development, it will be difficult to tackle the public health challenges facing societies worldwide. Public–private partnerships could play a key role in achieving this step change, but they need to be well designed and led.
Assessment Challenges for Business Education in Changing Times
ERIC Educational Resources Information Center
Hazari, Sunil; Gaytan, Jorge; North, Alexa
2008-01-01
In addition to the difficult task of identifying teaching methods that ensure student learning, the American educational system is facing significant challenges. Schools are struggling to maintain standards for high-quality teaching while trying to address the learning needs of students with Limited English Proficiency (LEP). The same struggle is…
ERIC Educational Resources Information Center
Hunter, William; Haydon, Todd
2013-01-01
Challenging behaviors displayed in both general education classrooms and self-contained classrooms by students with emotional behavioral disorders (EBD) can be a difficult challenge for novice and experienced teachers (Kennedy & Jolivette, 2008; Turnbull, Turnbull, & Wehmeyer, 2010). Furthermore, students with EBD demonstrate broad…
ERIC Educational Resources Information Center
Bowen, Alec S.; Reid, Daniel R.; Koretsky, Milo D.
2015-01-01
In this project, we explore the use of threshold concept theory as a design basis for development of Interactive Virtual Laboratories in thermodynamics. Thermodynamics is a difficult subject for chemical and biological engineering students to master. One reason for the difficulty is the diverse and challenging set of threshold concepts that they…
How to Handle Difficult Parents: Proven Solutions for Teachers. Second Edition
ERIC Educational Resources Information Center
Tingley, Suzanne Capek
2012-01-01
"How to Handle Difficult Parents" is a funny, but practical, guide to working effectively with parents and avoiding unnecessary conflict. Whether you're a teacher (regular or special education) or a coach, this book will give you practical suggestions regarding what to say and how to say it to parents who question your lesson plans, challenge your…
ERIC Educational Resources Information Center
Dean, John F.
For a variety of reasons, collection care in Southeast Asia, especially in the northern regions, is fraught with many difficult challenges. Climates that are unfriendly to paper-based materials, poor economies, war, and civil unrest, are just a few of the reasons that librarians and archivists find it extremely difficult to ensure the survival of…
Turning limited experimental information into 3D models of RNA.
Flores, Samuel Coulbourn; Altman, Russ B
2010-09-01
Our understanding of RNA functions in the cell is evolving rapidly. As for proteins, the detailed three-dimensional (3D) structure of RNA is often key to understanding its function. Although crystallography and nuclear magnetic resonance (NMR) can determine the atomic coordinates of some RNA structures, many 3D structures present technical challenges that make these methods difficult to apply. The great flexibility of RNA, its charged backbone, dearth of specific surface features, and propensity for kinetic traps all conspire with its long folding time, to challenge in silico methods for physics-based folding. On the other hand, base-pairing interactions (either in runs to form helices or isolated tertiary contacts) and motifs are often available from relatively low-cost experiments or informatics analyses. We present RNABuilder, a novel code that uses internal coordinate mechanics to satisfy user-specified base pairing and steric forces under chemical constraints. The code recapitulates the topology and characteristic L-shape of tRNA and obtains an accurate noncrystallographic structure of the Tetrahymena ribozyme P4/P6 domain. The algorithm scales nearly linearly with molecule size, opening the door to the modeling of significantly larger structures.
Statistical Engineering in Air Traffic Management Research
NASA Technical Reports Server (NTRS)
Wilson, Sara R.
2015-01-01
NASA is working to develop an integrated set of advanced technologies to enable efficient arrival operations in high-density terminal airspace for the Next Generation Air Transportation System. This integrated arrival solution is being validated and verified in laboratories and transitioned to a field prototype for an operational demonstration at a major U.S. airport. Within NASA, this is a collaborative effort between Ames and Langley Research Centers involving a multi-year iterative experimentation process. Designing and analyzing a series of sequential batch computer simulations and human-in-the-loop experiments across multiple facilities and simulation environments involves a number of statistical challenges. Experiments conducted in separate laboratories typically have different limitations and constraints, and can take different approaches with respect to the fundamental principles of statistical design of experiments. This often makes it difficult to compare results from multiple experiments and incorporate findings into the next experiment in the series. A statistical engineering approach is being employed within this project to support risk-informed decision making and maximize the knowledge gained within the available resources. This presentation describes a statistical engineering case study from NASA, highlights statistical challenges, and discusses areas where existing statistical methodology is adapted and extended.
A novel swarm intelligence algorithm for finding DNA motifs.
Lei, Chengwei; Ruan, Jianhua
2009-01-01
Discovering DNA motifs from co-expressed or co-regulated genes is an important step towards deciphering complex gene regulatory networks and understanding gene functions. Despite significant improvement in the last decade, it still remains one of the most challenging problems in computational molecular biology. In this work, we propose a novel motif finding algorithm that finds consensus patterns using a population-based stochastic optimisation technique called Particle Swarm Optimisation (PSO), which has been shown to be effective in optimising difficult multidimensional problems in continuous domains. We propose to use a word dissimilarity graph to remap the neighborhood structure of the solution space of DNA motifs, and propose a modification of the naive PSO algorithm to accommodate discrete variables. In order to improve efficiency, we also propose several strategies for escaping from local optima and for automatically determining the termination criteria. Experimental results on simulated challenge problems show that our method is both more efficient and more accurate than several existing algorithms. Applications to several sets of real promoter sequences also show that our approach is able to detect known transcription factor binding sites, and outperforms two of the most popular existing algorithms.
NASA Astrophysics Data System (ADS)
Buongiorno Nardelli, Marco
2015-03-01
High-Throughput Quantum-Mechanics computation of materials properties by ab initio methods has become the foundation of an effective approach to materials design, discovery and characterization. This data driven approach to materials science currently presents the most promising path to the development of advanced technological materials that could solve or mitigate important social and economic challenges of the 21st century. In particular, the rapid proliferation of computational data on materials properties presents the possibility to complement and extend materials property databases where the experimental data is lacking and difficult to obtain. Enhanced repositories such as AFLOWLIB, open novel opportunities for structure discovery and optimization, including uncovering of unsuspected compounds, metastable structures and correlations between various properties. The practical realization of these opportunities depends on the the design effcient algorithms for electronic structure simulations of realistic material systems, the systematic compilation and classification of the generated data, and its presentation in easily accessed form to the materials science community, the primary mission of the AFLOW consortium. This work was supported by ONR-MURI under Contract N00014-13-1-0635 and the Duke University Center for Materials Genomics.
Tubular filamentation for laser material processing
Xie, Chen; Jukna, Vytautas; Milián, Carles; Giust, Remo; Ouadghiri-Idrissi, Ismail; Itina, Tatiana; Dudley, John M.; Couairon, Arnaud; Courvoisier, Francois
2015-01-01
An open challenge in the important field of femtosecond laser material processing is the controlled internal structuring of dielectric materials. Although the availability of high energy high repetition rate femtosecond lasers has led to many advances in this field, writing structures within transparent dielectrics at intensities exceeding 1013 W/cm2 has remained difficult as it is associated with significant nonlinear spatial distortion. This letter reports the existence of a new propagation regime for femtosecond pulses at high power that overcomes this challenge, associated with the generation of a hollow uniform and intense light tube that remains propagation invariant even at intensities associated with dense plasma formation. This regime is seeded from higher order nondiffracting Bessel beams, which carry an optical vortex charge. Numerical simulations are quantitatively confirmed by experiments where a novel experimental approach allows direct imaging of the 3D fluence distribution within transparent solids. We also analyze the transitions to other propagation regimes in near and far fields. We demonstrate how the generation of plasma in this tubular geometry can lead to applications in ultrafast laser material processing in terms of single shot index writing, and discuss how it opens important perspectives for material compression and filamentation guiding in atmosphere. PMID:25753215
Nanofinishing of freeform/sculptured surfaces: state-of-the-art
NASA Astrophysics Data System (ADS)
Nagdeve, Leeladhar; Jain, V. K.; Ramkumar, J.
2018-06-01
Freeform surfaces are being used in a multiplicity of applications in different kinds of industries related to Bio-medical (Bio-implants), micro channels in micro fluidics, automotives, turbine blades, impellers of artificial heart pumps, automobiles etc. Different parts in these industries need nano-level surface finish as their functional inevitability. It is very difficult and challenging to achieve high level of surface finish, especially on the components having freeform (or sculptured) surfaces, complex shapes, and 3-D features. Surface finish is a significant factor, which affects life and functionality of a product. Many traditional and advanced finishing processes have been developed for finishing of freeform/sculptured surfaces but still it has not been possible to achieve uniform nano level surface finish specially in case of freeform surfaces. To overcome the limitations of the existing nanofinishing processes, researchers are developing new processes for uniform nanofinishing of freeform surfaces. In this article, an attempt has been made to review different nanofinishing processes employed for freeform surfaces useful in different types of applications. In addition, experimental work, theoretical analysis and existing challenges of the finishing processes have been identified to fill the research gap.
Breard, Emmanuel; Belbis, Guillaume; Viarouge, Cyril; Nomikou, Kyriaki; Haegeman, Andy; De Clercq, Kris; Hudelet, Pascal; Hamers, Claude; Moreau, Francis; Lilin, Thomas; Durand, Benoit; Mertens, Peter; Vitour, Damien; Sailleau, Corinne; Zientara, Stéphan
2015-01-15
Eradication of bluetongue virus is possible, as has been shown in several European countries. New serotypes have emerged, however, for which there are no specific commercial vaccines. This study addressed whether heterologous vaccines would help protect against 2 serotypes. Thirty-seven sheep were randomly allocated to 7 groups of 5 or 6 animals. Four groups were vaccinated with commercial vaccines against BTV strains 2, 4, and 9. A fifth positive control group was given a vaccine against BTV-8. The other 2 groups were unvaccinated controls. Sheep were then challenged by subcutaneous injection of either BTV-16 (2 groups) or BTV-8 (5 groups). Taken together, 24/25 sheep from the 4 experimental groups developed detectable antibodies against the vaccinated viruses. Furthermore, sheep that received heterologous vaccines showed significantly reduced viraemia and clinical scores for BTV-16 when compared to unvaccinated controls. Reductions in clinical signs and viraemia among heterologously vaccinated sheep were not as common after challenge with BTV-8. This study shows that heterologous protection can occur, but that it is difficult to predict if partial or complete protection will be achieved following inactivated-BTV vaccination. Copyright © 2014 Elsevier Ltd. All rights reserved.
Protein Modelling: What Happened to the “Protein Structure Gap”?
Schwede, Torsten
2013-01-01
Computational modeling and prediction of three-dimensional macromolecular structures and complexes from their sequence has been a long standing vision in structural biology as it holds the promise to bypass part of the laborious process of experimental structure solution. Over the last two decades, a paradigm shift has occurred: starting from a situation where the “structure knowledge gap” between the huge number of protein sequences and small number of known structures has hampered the widespread use of structure-based approaches in life science research, today some form of structural information – either experimental or computational – is available for the majority of amino acids encoded by common model organism genomes. Template based homology modeling techniques have matured to a point where they are now routinely used to complement experimental techniques. With the scientific focus of interest moving towards larger macromolecular complexes and dynamic networks of interactions, the integration of computational modeling methods with low-resolution experimental techniques allows studying large and complex molecular machines. Computational modeling and prediction techniques are still facing a number of challenges which hamper the more widespread use by the non-expert scientist. For example, it is often difficult to convey the underlying assumptions of a computational technique, as well as the expected accuracy and structural variability of a specific model. However, these aspects are crucial to understand the limitations of a model, and to decide which interpretations and conclusions can be supported. PMID:24010712
Courage and Compassion: Virtues in Caring for So-Called "Difficult" Patients.
Hawking, Michael; Curlin, Farr A; Yoon, John D
2017-04-01
What, if anything, can medical ethics offer to assist in the care of the "difficult" patient? We begin with a discussion of virtue theory and its application to medical ethics. We conceptualize the "difficult" patient as an example of a "moral stress test" that especially challenges the physician's character, requiring the good physician to display the virtues of courage and compassion. We then consider two clinical vignettes to flesh out how these virtues might come into play in the care of "difficult" patients, and we conclude with a brief proposal for how medical educators might cultivate these essential character traits in physicians-in-training. © 2017 American Medical Association. All Rights Reserved.
Abisa, Michael
2017-01-01
To explore the challenges Health Information Technology (HIT) vendors face to satisfy the requirements for Meaningful Use (MU) and Electronic Laboratory Reporting (ELR) of reportable diseases to the public health departments in Kentucky. A survey was conducted of Health Information Exchange (HIE) vendors in Kentucky through the Kentucky Health Information Exchange (KHIE). The survey was cross-sectional. Data were collected between February and March 2014. Participants were recruited from KHIE vendors. Participants received online survey link and by email and asked to submit their responses. Vendors' feedback were summarized and analyzed to identify their challenges. Out of the 55 vendors who received the survey, 35(63.64%) responded. Of the seven transport protocol options for ELR, vendors selected virtual private network (VPN) as the most difficult to implement (31.7%). Secure File Transfer Protocol (SFTP) was selected as preferred ELR transport protocol (31.4%). Most of the respondents, 80% responded that they do not have any challenge with the Health Level 7 (HL7) standard implementation guide required by MU for 2014 ELR certification. The study found that the most difficult transport protocol to implement for ELR is VPN and if vendors have preference, they would use SFTP for ELR over KHIE choice of VPN and Simple Object Access Protocol (SOAP). KHIE vendors do not see any variability in what is reportable by different jurisdiction and also it is not difficult for them to detect what is reportable from one jurisdiction verse the other.
A virtual experimenter to increase standardization for the investigation of placebo effects.
Horing, Bjoern; Newsome, Nathan D; Enck, Paul; Babu, Sabarish V; Muth, Eric R
2016-07-18
Placebo effects are mediated by expectancy, which is highly influenced by psychosocial factors of a treatment context. These factors are difficult to standardize. Furthermore, dedicated placebo research often necessitates single-blind deceptive designs where biases are easily introduced. We propose a study protocol employing a virtual experimenter - a computer program designed to deliver treatment and instructions - for the purpose of standardization and reduction of biases when investigating placebo effects. To evaluate the virtual experimenter's efficacy in inducing placebo effects via expectancy manipulation, we suggest a partially blinded, deceptive design with a baseline/retest pain protocol (hand immersions in hot water bath). Between immersions, participants will receive an (actually inert) medication. Instructions pertaining to the medication will be delivered by one of three metaphors: The virtual experimenter, a human experimenter, and an audio/text presentation (predictor "Metaphor"). The second predictor includes falsely informing participants that the medication is an effective pain killer, or correctly informing them that it is, in fact, inert (predictor "Instruction"). Analysis will be performed with hierarchical linear modelling, with a sample size of N = 50. Results from two pilot studies are presented that indicate the viability of the pain protocol (N = 33), and of the virtual experimenter software and placebo manipulation (N = 48). It will be challenging to establish full comparability between all metaphors used for instruction delivery, and to account for participant differences in acceptance of their virtual interaction partner. Once established, the presence of placebo effects would suggest that the virtual experimenter exhibits sufficient cues to be perceived as a social agent. He could consequently provide a convenient platform to investigate effects of experimenter behavior, or other experimenter characteristics, e.g., sex, age, race/ethnicity or professional status. More general applications are possible, for example in psychological research such as bias research, or virtual reality research. Potential applications also exist for standardizing clinical research by documenting and communicating instructions used in clinical trials.
Siminoff, Laura A.; Rogers, Heather L.; Waller, Allison C.; Harris-Haywood, Sonja; Esptein, Ronald M.; Borrell Carrio, Francesc; Gliva-McConvey, Gayle; Longo, Daniel R.
2011-01-01
Objective This paper provides an overview of the implementation of using Unannounced Standardized Patients (USPs) to conduct health communication research in clinical settings. Methods Certain types of health communication situations are difficult to capture because of their rarity or unpredictable nature. In primary care the real reasons for a visit are frequently unknown until the consultation is well under way. Therefore, it is logistically difficult for communication studies to capture many real-time communications between patients and their physicians. Although the USP methodology is ideal for capturing these communication behaviors, challenges to using this method include developing collaborative relationships with clinical practices, logistical issues such as safeguarding the identity of the USP, training USPs and creating their identities, maintaining fidelity to the role, and analyzing the resultant data. Results This paper discusses the challenges and solutions to USP implementation. We provide an example of how to implement a USP study using an on-going study being conducted in primary care practices. Conclusion This paper explores the advantages and challenges as well as strategies to overcome obstacles to implementing a USP study. Practice Implications Despite the challenges, USP methodology can contribute much to our understanding of health communication and practice. PMID:21316182
Luo, Yanting; Yang, Yongmin; Chen, Zhongsheng
2014-04-10
Sub-resonances often happen in wireless power transmission (WPT) systems using coupled magnetic resonances (CMR) due to environmental changes, coil movements or component degradations, which is a serious challenge for high efficiency power transmission. Thus self-tuning is very significant to keep WPT systems following strongly magnetic resonant conditions in practice. Traditional coupled-mode ways is difficult to solve this problem. In this paper a two-port power wave model is presented, where power matching and the overall systemic power transmission efficiency are firstly defined by scattering (S) parameters. Then we propose a novel self-tuning scheme based on on-line S parameters measurements and two-side power matching. Experimental results testify the feasibility of the proposed method. These findings suggest that the proposed method is much potential to develop strongly self-adaptive WPT systems with CMR.
Natural extension of fast-slow decomposition for dynamical systems
NASA Astrophysics Data System (ADS)
Rubin, J. E.; Krauskopf, B.; Osinga, H. M.
2018-01-01
Modeling and parameter estimation to capture the dynamics of physical systems are often challenging because many parameters can range over orders of magnitude and are difficult to measure experimentally. Moreover, selecting a suitable model complexity requires a sufficient understanding of the model's potential use, such as highlighting essential mechanisms underlying qualitative behavior or precisely quantifying realistic dynamics. We present an approach that can guide model development and tuning to achieve desired qualitative and quantitative solution properties. It relies on the presence of disparate time scales and employs techniques of separating the dynamics of fast and slow variables, which are well known in the analysis of qualitative solution features. We build on these methods to show how it is also possible to obtain quantitative solution features by imposing designed dynamics for the slow variables in the form of specified two-dimensional paths in a bifurcation-parameter landscape.
Keshavan, J; Gremillion, G; Escobar-Alvarez, H; Humbert, J S
2014-06-01
Safe, autonomous navigation by aerial microsystems in less-structured environments is a difficult challenge to overcome with current technology. This paper presents a novel visual-navigation approach that combines bioinspired wide-field processing of optic flow information with control-theoretic tools for synthesis of closed loop systems, resulting in robustness and performance guarantees. Structured singular value analysis is used to synthesize a dynamic controller that provides good tracking performance in uncertain environments without resorting to explicit pose estimation or extraction of a detailed environmental depth map. Experimental results with a quadrotor demonstrate the vehicle's robust obstacle-avoidance behaviour in a straight line corridor, an S-shaped corridor and a corridor with obstacles distributed in the vehicle's path. The computational efficiency and simplicity of the current approach offers a promising alternative to satisfying the payload, power and bandwidth constraints imposed by aerial microsystems.
Spectral unfolding of fast neutron energy distributions
NASA Astrophysics Data System (ADS)
Mosby, Michelle; Jackman, Kevin; Engle, Jonathan
2015-10-01
The characterization of the energy distribution of a neutron flux is difficult in experiments with constrained geometry where techniques such as time of flight cannot be used to resolve the distribution. The measurement of neutron fluxes in reactors, which often present similar challenges, has been accomplished using radioactivation foils as an indirect probe. Spectral unfolding codes use statistical methods to adjust MCNP predictions of neutron energy distributions using quantified radioactive residuals produced in these foils. We have applied a modification of this established neutron flux characterization technique to experimentally characterize the neutron flux in the critical assemblies at the Nevada National Security Site (NNSS) and the spallation neutron flux at the Isotope Production Facility (IPF) at Los Alamos National Laboratory (LANL). Results of the unfolding procedure are presented and compared with a priori MCNP predictions, and the implications for measurements using the neutron fluxes at these facilities are discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fang, Yin; Jiang, Yuanwen; Cherukara, Mathew J.
Large-scale assembly of individual atoms over smooth surfaces is difficult to achieve. A configuration of an atom reservoir, in which individual atoms can be readily extracted, may successfully address this challenge. In this work, we demonstrate that a liquid gold-silicon alloy established in classical vapor-liquid-solid growth can deposit ordered and three-dimensional rings of isolated gold atoms over silicon nanowire sidewalls. Here, we perform ab initio molecular dynamics simulation and unveil a surprising single atomic gold-catalyzed chemical etching of silicon. Experimental verification of this catalytic process in silicon nanowires yields dopant-dependent, massive and ordered 3D grooves with spacing down to similarmore » to 5 nm. Finally, we use these grooves as self-labeled and ex situ markers to resolve several complex silicon growths, including the formation of nodes, kinks, scale-like interfaces, and curved backbones.« less
Correlations between reaction product yields as a tool for probing heavy-ion reaction scenarios
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gawlikowicz, W.; Heavy-Ion Laboratory, Warsaw University, PL-02-093 Warsaw; Agnihotri, D. K.
2010-01-15
Experimental multidimensional joint distributions of neutrons and charged reaction products were analyzed for {sup 136}Xe + {sup 209}Bi reactions at E/A=28, 40, and 62 MeV and were found to exhibit several different types of prominent correlation patterns. Some of these correlations have a simple explanation in terms of the system excitation energy and pose little challenge to most statistical decay theories. However, several other types of correlation patterns are difficult to reconcile with some, but not other, possible reaction scenarios. In this respect, correlations between the average atomic numbers of intermediate-mass fragments, on the one hand, and light particle multiplicities,more » on the other, are notable. This kind of multiparticle correlation provides a useful tool for probing reaction scenarios, which is different from the traditional approach of interpreting inclusive yields of individual reaction products.« less
Laser fabrication of perfect absorbers
NASA Astrophysics Data System (ADS)
Mizeikis, V.; Faniayeu, I.
2018-01-01
We describe design and characterization of electromagnetic metasurfaces consisting of sub-wavelength layers of artificially structured 3D metallic elements arranged into two-dimensional arrays. Such metasurfaces allow novel ways to control propagation, absorption, emission, and polarization state of electromagnetic waves, but their practical realization using traditional planar micro-/nano-fabrication techniques is extremely difficult at infra- red frequencies, where unit cell size must be reduced to few micrometers. We have addressed this challenge by using femtosecond direct laser write (DLW) technique as a high-resolution patterning tool for the fabrication of dielectric templates, followed by a simple metallization process. Functional metasurfaces consisting of metallic helices and vertical split-ring resonators that can be used as perfect absorbers and polarization converters at infra- red frequencies were obtained and characterized experimentally and theoretically. In the future they may find applications in narrow-band infra-red detectors and emitters, spectral filters, and combined into multi-functional, multi-layered structures.
Targeted Approach for Proteomic Analysis of a Hidden Membrane Protein.
Martins-Marques, Tania; Anjo, Sandra I; Ribeiro-Rodrigues, Teresa; Manadas, Bruno; Girao, Henrique
2017-01-01
Given the properties of plasma membrane proteins, namely, their hydrophobicity, low solubility, and high resistance to digestion and extraction, their identification by traditional mass spectrometry (MS) has been a challenging task. Hence, proteomic studies involving the transmembrane protein connexin43 (Cx43) are scarce. Additionally, studies demonstrating the presence of proteins embedded in the lipid bilayer of extracellular vesicles (EVs) are difficult to perform and require specific changes and fine adjustments in the experimental and technical procedure to allow their detection by MS. In this review, we provide a detailed description of the protocol we have used to detect Cx43 in EVs of human peripheral blood. This includes some of the modifications that we have introduced in order to improve the detection of Cx43 in EVs, including an optimization of vesicle isolation, Cx43 purification, MS acquisition data, and further analysis.
Booth, D; Rittenhouse, S T; Yang, J; Sadeghpour, H R; Shaffer, J P
2015-04-03
Permanent electric dipole moments are important for understanding symmetry breaking in molecular physics, control of chemical reactions, and realization of strongly correlated many-body quantum systems. However, large molecular permanent electric dipole moments are challenging to realize experimentally. We report the observation of ultralong-range Rydberg molecules with bond lengths of ~100 nanometers and kilo-Debye permanent electric dipole moments that form when an ultracold ground-state cesium (Cs) atom becomes bound within the electronic cloud of an extended Cs electronic orbit. The electronic character of this hybrid class of "trilobite" molecules is dominated by degenerate Rydberg manifolds, making them difficult to produce by conventional photoassociation. We used detailed coupled-channel calculations to reproduce their properties quantitatively. Our findings may lead to progress in ultracold chemistry and strongly correlated many-body physics. Copyright © 2015, American Association for the Advancement of Science.
Analysis of Turbulent Combustion in Simplified Stratified Charge Conditions
NASA Astrophysics Data System (ADS)
Moriyoshi, Yasuo; Morikawa, Hideaki; Komatsu, Eiji
The stratified charge combustion system has been widely studied due to the significant potentials for low fuel consumption rate and low exhaust gas emissions. The fuel-air mixture formation process in a direct-injection stratified charge engine is influenced by various parameters, such as atomization, evaporation, and in-cylinder gas motion at high temperature and high pressure conditions. It is difficult to observe the in-cylinder phenomena in such conditions and also challenging to analyze the following stratified charge combustion. Therefore, the combustion phenomena in simplified stratified charge conditions aiming to analyze the fundamental stratified charge combustion are examined. That is, an experimental apparatus which can control the mixture distribution and the gas motion at ignition timing was developed, and the effects of turbulence intensity, mixture concentration distribution, and mixture composition on stratified charge combustion were examined. As a result, the effects of fuel, charge stratification, and turbulence on combustion characteristics were clarified.
An Improved Rank Correlation Effect Size Statistic for Single-Case Designs: Baseline Corrected Tau.
Tarlow, Kevin R
2017-07-01
Measuring treatment effects when an individual's pretreatment performance is improving poses a challenge for single-case experimental designs. It may be difficult to determine whether improvement is due to the treatment or due to the preexisting baseline trend. Tau- U is a popular single-case effect size statistic that purports to control for baseline trend. However, despite its strengths, Tau- U has substantial limitations: Its values are inflated and not bound between -1 and +1, it cannot be visually graphed, and its relatively weak method of trend control leads to unacceptable levels of Type I error wherein ineffective treatments appear effective. An improved effect size statistic based on rank correlation and robust regression, Baseline Corrected Tau, is proposed and field-tested with both published and simulated single-case time series. A web-based calculator for Baseline Corrected Tau is also introduced for use by single-case investigators.
Barriers to the use of genetic information for the development of new epilepsy treatments.
Ferraro, Thomas N
2016-01-01
Genetic analysis is providing new information on the biological basis of epilepsy at a rapid pace; this article identifies factors acting as major barriers to use of these data for therapy development. Disease heterogeneity is a primary obstacle since so many genes can cause or predispose to epilepsy and the clinical presentation of epilepsy is so diverse, thus making it difficult to define the most therapeutically relevant targets. Further, many epilepsy genes affect brain development, an observation that represents a barrier unto itself given the challenge of reversing or preventing genetically mediated alterations of brain pathway formation. Finally, the lack of appropriate models for testing new therapies is also recognized as a fundamental limitation. Overcoming these barriers will be aided by full characterization of the genetic landscape of epilepsy, elucidation of key pathway points for therapeutic intervention and creation of unique experimental models to validate results.
NASA Astrophysics Data System (ADS)
Deris, A. M.; Zain, A. M.; Sallehuddin, R.; Sharif, S.
2017-09-01
Electric discharge machine (EDM) is one of the widely used nonconventional machining processes for hard and difficult to machine materials. Due to the large number of machining parameters in EDM and its complicated structural, the selection of the optimal solution of machining parameters for obtaining minimum machining performance is remain as a challenging task to the researchers. This paper proposed experimental investigation and optimization of machining parameters for EDM process on stainless steel 316L work piece using Harmony Search (HS) algorithm. The mathematical model was developed based on regression approach with four input parameters which are pulse on time, peak current, servo voltage and servo speed to the output response which is dimensional accuracy (DA). The optimal result of HS approach was compared with regression analysis and it was found HS gave better result y giving the most minimum DA value compared with regression approach.
Models for preclinical studies in aging-related disorders: One is not for all
Santulli, Gaetano; Borras, Consuelo; Bousquet, Jean; Calzà, Laura; Cano, Antonio; Illario, Maddalena; Franceschi, Claudio; Liotta, Giuseppe; Maggio, Marcello; Molloy, William D.; Montuori, Nunzia; O’Caoimh, Rónán; Orfila, Francesc; Rauter, Amelia P.; Santoro, Aurelia; Iaccarino, Guido
2015-01-01
Preclinical studies are essentially based on animal models of a particular disease. The primary purpose of preclinical efficacy studies is to support generalization of treatment–effect relationships to human subjects. Researchers aim to demonstrate a causal relationship between an investigational agent and a disease-related phenotype in such models. Numerous factors can muddle reliable inferences about such cause-effect relationships, including biased outcome assessment due to experimenter expectations. For instance, responses in a particular inbred mouse might be specific to the strain, limiting generalizability. Selecting well-justified and widely acknowledged model systems represents the best start in designing preclinical studies, especially to overcome any potential bias related to the model itself. This is particularly true in the research that focuses on aging, which carries unique challenges, mainly attributable to the fact that our already long lifespan makes designing experiments that use people as subjects extremely difficult and largely impractical. PMID:27042427
Sentiment Propagation in Social Networks: A Case Study in LiveJournal
NASA Astrophysics Data System (ADS)
Zafarani, Reza; Cole, William D.; Liu, Huan
Social networking websites have facilitated a new style of communication through blogs, instant messaging, and various other techniques. Through collaboration, millions of users participate in millions of discussions every day. However, it is still difficult to determine the extent to which such discussions affect the emotions of the participants. We surmise that emotionally-oriented discussions may affect a given user's general emotional bent and be reflected in other discussions he or she may initiate or participate in. It is in this way that emotion (or sentiment) may propagate through a network. In this paper, we analyze sentiment propagation in social networks, review the importance and challenges of such a study, and provide methodologies for measuring this kind of propagation. A case study has been conducted on a large dataset gathered from the LiveJournal social network. Experimental results are promising in revealing some aspects of the sentiment propagation taking place in social networks.
Fang, Yin; Jiang, Yuanwen; Cherukara, Mathew J.; ...
2017-12-08
Large-scale assembly of individual atoms over smooth surfaces is difficult to achieve. A configuration of an atom reservoir, in which individual atoms can be readily extracted, may successfully address this challenge. In this work, we demonstrate that a liquid gold-silicon alloy established in classical vapor-liquid-solid growth can deposit ordered and three-dimensional rings of isolated gold atoms over silicon nanowire sidewalls. Here, we perform ab initio molecular dynamics simulation and unveil a surprising single atomic gold-catalyzed chemical etching of silicon. Experimental verification of this catalytic process in silicon nanowires yields dopant-dependent, massive and ordered 3D grooves with spacing down to similarmore » to 5 nm. Finally, we use these grooves as self-labeled and ex situ markers to resolve several complex silicon growths, including the formation of nodes, kinks, scale-like interfaces, and curved backbones.« less
On the way to unveiling the atomic structure of superheavy elements
NASA Astrophysics Data System (ADS)
Laatiaoui, Mustapha
2016-12-01
Optical spectroscopy of the transfermium elements (atomic number Z > 100) is nowadays one of the most fascinating and simultaneously challenging tasks in atomic physics. On the one hand, key atomic and even nuclear ground-state properties may be obtained by studying the spectral lines of these heaviest elements. On the other hand, these elements have to be produced "online" by heavy-ion induced fusion-evaporation reactions yielding rates on the order of a few atoms per second at most, which renders their optical spectroscopy extremely difficult. Only recently, a first foray of laser spectroscopy into this heaviest element region was reported. Several atomic transitions in the element nobelium (Z = 102) were observed and characterized, using an ultra-sensitive and highly efficient resonance ionization technique. The findings confirm the predictions and additionally provide a benchmark for theoretical modelling. The work represents an important stepping stone towards experimental studies of the atomic structure of superheavy elements.
Linear finite-difference bond graph model of an ionic polymer actuator
NASA Astrophysics Data System (ADS)
Bentefrit, M.; Grondel, S.; Soyer, C.; Fannir, A.; Cattan, E.; Madden, J. D.; Nguyen, T. M. G.; Plesse, C.; Vidal, F.
2017-09-01
With the recent growing interest for soft actuation, many new types of ionic polymers working in air have been developed. Due to the interrelated mechanical, electrical, and chemical properties which greatly influence the characteristics of such actuators, their behavior is complex and difficult to understand, predict and optimize. In light of this challenge, an original linear multiphysics finite difference bond graph model was derived to characterize this ionic actuation. This finite difference scheme was divided into two coupled subparts, each related to a specific physical, electrochemical or mechanical domain, and then converted into a bond graph model as this language is particularly suited for systems from multiple energy domains. Simulations were then conducted and a good agreement with the experimental results was obtained. Furthermore, an analysis of the power efficiency of such actuators as a function of space and time was proposed and allowed to evaluate their performance.
Unified modelling of the thermoelectric properties in SrTiO3
NASA Astrophysics Data System (ADS)
Bouzerar, G.; Thébaud, S.; Adessi, Ch.; Debord, R.; Apreutesei, M.; Bachelet, R.; Pailhès, S.
2017-06-01
Thermoelectric materials are opening a promising pathway to address energy conversion issues governed by a competition between thermal and electronic transport. Improving the efficiency is a difficult task, a challenge that requires new strategies to unearth optimized compounds. We present a theory of thermoelectric transport in electron-doped SrTiO3, based on a realistic tight-binding model that includes relevant scattering processes. We compare our calculations against a wide panel of experimental data, both bulk and thin films. We find a qualitative and quantitative agreement over both a wide range of temperatures and carrier concentrations, from light to heavily doped. Moreover, the results appear insensitive to the nature of the dopant La, B, Gd and Nb. Thus, the quantitative success found in the case of SrTiO3, reveals an efficient procedure to explore new routes to improve the thermoelectric properties in oxides.
Ezri, T.; Gewürtz, G.; Sessler, D.I.; Medalion, B.; Szmuk, P.; Hagberg, C.; Susmallian, S.
2005-01-01
Prediction of difficult laryngoscopy in obese patients is challenging. In 50 morbidly obese patients, we quantified the neck soft tissue from skin to anterior aspect of trachea at the vocal cords using ultrasound. Thyromental distance <6 cm, mouth opening <4 cm, limited neck mobility, Mallampati score >2, abnormal upper teeth, neck circumference >45 cm, and sleep apnoea were considered predictors of difficult laryngoscopy. Of the nine (18%) difficult laryngoscopy cases, seven had obstructive sleep apnoea history; whereas, only 2 of the 41 easy laryngoscopy patients did (P<0.001). Difficult laryngoscopy patients had larger neck circumference [50 (3.8) vs. 43.5 (2.2) cm; P<0.001] and more pre-tracheal soft tissue [28 (2.7) mm vs. 17.5 (1.8) mm; P<0.001] [mean (SD)]. Soft tissue values completely separated difficult and easy laryngoscopies. None of the other predictors correlated with difficult laryngoscopy. Thus, an abundance of pretracheal soft tissue at the level of vocal cords is a good predictor of difficult laryngoscopy in obese patients. PMID:14616599
Selecting Models for Measuring Change When True Experimental Conditions Do Not Exist.
ERIC Educational Resources Information Center
Fortune, Jim C.; Hutson, Barbara A.
1984-01-01
Measuring change when true experimental conditions do not exist is a difficult process. This article reviews the artifacts of change measurement in evaluations and quasi-experimental designs, delineates considerations in choosing a model to measure change under nonideal conditions, and suggests ways to organize models to facilitate selection.…
Experimental Labs for Start-Ups: The Role of the "Venture-Sitter"
ERIC Educational Resources Information Center
Matricano, Diego; Pietrobon, Alberto
2010-01-01
Curley and Formica's (2008, 2010) studies of high-expectation entrepreneurship focus on the role of "experimental laboratories" in promoting the start-up and successful development of high-expectation firms. Although it is not difficult to understand the potential usefulness of these experimental labs--business simulators in which skilled partners…
Attenuation and Dispersion in Earth's Materials
NASA Astrophysics Data System (ADS)
Gueguen, Y.
2012-04-01
One of the last challenges of Pr. Luigi Burlini has been to set up an experimental apparatus that would measure elastic wave attenuation under high pressure conditions. This project has since been developed by his colleagues and students at ETH. As a tribute to Luigi Burlini, this presentation aims at recalling why such measurements are important , how challenging such a project is, and what the main issues ahead are. Most of our knowledge about either crustal layers (seismic exploration) or deeper layers (seismology) results from data related to elastic wave propagation inside the Earth. The large amount of available data as well as the huge capability of computers are such that descriptions in terms of isotropic homogeneous layers appear to be very crude today. Anisotropic, heterogeneous models are reported at various scales. In addition, accounting for wave attenuation (the Q factor) is potentially of great interest. The Q factor is highly sensitive to processes that involve some departure from perfect elasticity. Its knowledge may provide information on possible fluid content, temperature, etc. This is because various processes may dissipate energy (and thus lower Q value) as a result of fluid flow, solid flow, etc., depending on the precise P-T conditions at depth. This points immediately to the theoretical challenge of Q investigations: there are many possible ways for a rock to not behave as a perfect elastic body. To model these various mechanisms and identify in which conditions they can take place is a first major challenge. The second challenge is on the experimental ground. What is looked for is to get low frequencies (f close to seismic frequencies) Q data on crustal (or mantle) rocks at high pressure P-high temperature T. Experiments in such highT-high P-low f conditions are extremely difficult to perform. Only in Canberra (I. Jackson) and now in Zurich such conditions have been achieved. Attenuation and dispersion (frequency dependence) of elastic waves are related through Kramers-Kronig equations. Using simple viscoelastic models such as the Zener model, one can show that Q-1 is maximum at a critical frequency fc, and, correlatively, that the wavespeed increases from low to high f by an amount ?V/V = (Q-1)max. This means that another (equivalent) way to look at attenuation is to look at dispersion. Experimentally, this implies to measure high and low frequency wavespeeds or elastic moduli. High frequency measurements have been performed for a long time (including high P-high T conditions) but low frequency measurements remain a challenge. Such data are however of major importance: seismic velocities data (1 H-1 kHz range) are obtained at much lower frequencies than laboratory data (MHz range). A difference by up to 6 orders of magnitudes in frequency exist between both set of data. Yet it has been mainly assumed that the frequency dependence can be neglected. Several set of experimental data show that it is not true. The implications for the crust and for the mantle will be discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Bingxiao; Awartani, Omar; O'Connor, Brendan
2016-05-02
Large charge mobilities of semi-crystalline organic semiconducting films could be obtained by mechanically aligning the material phases of the film with the loading axis. A key element is to utilize the inherent stiffness of the material for optimal or desired alignment. However, experimentally determining the moduli of semi-crystalline organic thin films for different loading directions is difficult, if not impossible, due to film thickness and material anisotropy. In this paper, we address these challenges by presenting an approach based on combining a composite mechanics stiffness orientation formulation with a Gaussian statistical distribution to directly estimate the in-plane stiffness (transverse isotropy)more » of aligned semi-crystalline polymer films based on crystalline orientation distributions obtained by X-ray diffraction experimentally at different applied strains. Our predicted results indicate that the in-plane stiffness of an annealing film was initially isotropic, and then it evolved to transverse isotropy with increasing mechanical strains. This study underscores the significance of accounting for the crystalline orientation distributions of the film to obtain an accurate understanding and prediction of the elastic anisotropy of semi-crystalline polymer films.« less
Mastoid vibration affects dynamic postural control during gait in healthy older adults
NASA Astrophysics Data System (ADS)
Chien, Jung Hung; Mukherjee, Mukul; Kent, Jenny; Stergiou, Nicholas
2017-01-01
Vestibular disorders are difficult to diagnose early due to the lack of a systematic assessment. Our previous work has developed a reliable experimental design and the result shows promising results that vestibular sensory input while walking could be affected through mastoid vibration (MV) and changes are in the direction of motion. In the present paper, we wanted to extend this work to older adults and investigate how manipulating sensory input through mastoid vibration (MV) could affect dynamic postural control during walking. Three levels of MV (none, unilateral, and bilateral) applied via vibrating elements placed on the mastoid processes were combined with the Locomotor Sensory Organization Test (LSOT) paradigm to challenge the visual and somatosensory systems. We hypothesized that the MV would affect sway variability during walking in older adults. Our results revealed that MV significantly not only increased the amount of sway variability but also decreased the temporal structure of sway variability only in anterior-posterior direction. Importantly, the bilateral MV stimulation generally produced larger effects than the unilateral. This is an important finding that confirmed our experimental design and the results produced could guide a more reliable screening of vestibular system deterioration.
Reverse Engineering Validation using a Benchmark Synthetic Gene Circuit in Human Cells
Kang, Taek; White, Jacob T.; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas
2013-01-01
Multi-component biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. PMID:23654266
Reverse engineering validation using a benchmark synthetic gene circuit in human cells.
Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas
2013-05-17
Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.
Zone analysis in biology articles as a basis for information extraction.
Mizuta, Yoko; Korhonen, Anna; Mullen, Tony; Collier, Nigel
2006-06-01
In the field of biomedicine, an overwhelming amount of experimental data has become available as a result of the high throughput of research in this domain. The amount of results reported has now grown beyond the limits of what can be managed by manual means. This makes it increasingly difficult for the researchers in this area to keep up with the latest developments. Information extraction (IE) in the biological domain aims to provide an effective automatic means to dynamically manage the information contained in archived journal articles and abstract collections and thus help researchers in their work. However, while considerable advances have been made in certain areas of IE, pinpointing and organizing factual information (such as experimental results) remains a challenge. In this paper we propose tackling this task by incorporating into IE information about rhetorical zones, i.e. classification of spans of text in terms of argumentation and intellectual attribution. As the first step towards this goal, we introduce a scheme for annotating biological texts for rhetorical zones and provide a qualitative and quantitative analysis of the data annotated according to this scheme. We also discuss our preliminary research on automatic zone analysis, and its incorporation into our IE framework.
Defects and Small Polarons on Oxide Surfaces
NASA Astrophysics Data System (ADS)
Janotti, Anderson
The presence and behavior of defects on the surface of oxides are central in many research areas, including catalysis, photochemistry, solar cells, and surface science in general. Experimental characterization of individual defects and their activities are challenging and often requires special preparations of the surface. First-principles calculations based on density functional theory are a powerful tool to study surfaces and defects, often providing information on properties that are difficult to access experimentally. Here we discuss the behavior of defects on oxide surfaces from the perspective on first-principles calculations. We use the oxygen vacancy on TiO2 surface as example, a system that has been extensively reported in the literature. Using DFT with a hybrid function, we discuss surface states induced by the defect and localization of the excess charge in the form of small polarons. We then discuss the effects of hydrogen and compare the behavior of these defects on the surface with that in the bulk. We also compare our recent results with previous theoretical studies and experiments. Finally, we generalize the findings on TiO2 to the surfaces of other oxides. This work was supported by the NSF.
Density functional theory in the solid state
Hasnip, Philip J.; Refson, Keith; Probert, Matt I. J.; Yates, Jonathan R.; Clark, Stewart J.; Pickard, Chris J.
2014-01-01
Density functional theory (DFT) has been used in many fields of the physical sciences, but none so successfully as in the solid state. From its origins in condensed matter physics, it has expanded into materials science, high-pressure physics and mineralogy, solid-state chemistry and more, powering entire computational subdisciplines. Modern DFT simulation codes can calculate a vast range of structural, chemical, optical, spectroscopic, elastic, vibrational and thermodynamic phenomena. The ability to predict structure–property relationships has revolutionized experimental fields, such as vibrational and solid-state NMR spectroscopy, where it is the primary method to analyse and interpret experimental spectra. In semiconductor physics, great progress has been made in the electronic structure of bulk and defect states despite the severe challenges presented by the description of excited states. Studies are no longer restricted to known crystallographic structures. DFT is increasingly used as an exploratory tool for materials discovery and computational experiments, culminating in ex nihilo crystal structure prediction, which addresses the long-standing difficult problem of how to predict crystal structure polymorphs from nothing but a specified chemical composition. We present an overview of the capabilities of solid-state DFT simulations in all of these topics, illustrated with recent examples using the CASTEP computer program. PMID:24516184
ERIC Educational Resources Information Center
Wagner, Mary; Newman, Lynn; Cameto, Renee; Garza, Nicolle; Levine, Phyllis
2005-01-01
Background: The transition from high school can be difficult for any youth, but it can be particularly difficult for youth with disabilities, who may encounter additional challenges to negotiating the transition to young adulthood. Purpose: To describe the experiences of youth with disabilities in the postsecondary education, employment,…
ERIC Educational Resources Information Center
Castanho, Miguel A. R. B.
2002-01-01
The main distinction between the overlapping fields of molecular biophysics and biochemistry resides in their different approaches to the same problems. Molecular biophysics makes more use of physical techniques and focuses on quantitative data. This difference encounters two difficult pedagogical challenges when teaching molecular biophysics to…
ERIC Educational Resources Information Center
Wilkie, Karina J.
2016-01-01
Senior secondary mathematics students who develop conceptual understanding that moves them beyond "rules without reasons" to connections between related concepts are in a strong place to tackle the more difficult mathematics application problems. Current research is examining how the use of challenging tasks at different levels of…
Papier-Mache Animals: An Integrating Theme for Elementary Classrooms
ERIC Educational Resources Information Center
Duran, Emilio; Ballone Duran, Lena; Worch, Eric A.
2009-01-01
One of the biggest present challenges for teachers, especially in primary classrooms, is the need to address the content standards in all subject areas with the same amount of instructional time. While curriculum integration continues to be a powerful strategy to meet this challenge, teachers often find it difficult to bridge the gap between…
"This Group of Difficult Kids": The Discourse Preservice English Teachers Use to Label Students
ERIC Educational Resources Information Center
Salerno, April S.; Kibler, Amanda K.
2016-01-01
This study attempts to understand how "achievement gap Discourse" might be present in preservice teachers' (PSTs) Discourse about students they found challenging to teach. Using a Discourse analytic approach, the project considers: How do PSTs describe challenging students in their written reflections? Do PSTs draw on students' multiple…
ERIC Educational Resources Information Center
Reid, Alan; Payne, Phillip G.; Cutter-Mackenzie, Amy
2010-01-01
This not quite "final" ending of this special issue of "Environmental Education Research" traces a series of hopeful, if somewhat difficult and at times challenging, openings for researching experiences of environment and place through children's literature. In the first instance, we draw inspiration from the contributors who…
Selective Teaching of L2 Pronunciation
ERIC Educational Resources Information Center
Husby, Olaf; Koreman, Jacques; Martínez-Paricio, Violeta; Abrahamsen, Jardar E.; Albertsen, Egil; Hedayatfar, Keivan; Bech, Øyvind
2015-01-01
The pronunciation of a second or foreign language is often very challenging for L2 learners. It is difficult to address this topic in the classroom, because learners with different native languages (L1s) can have very different challenges. We have therefore developed a Computer-Assisted Listening and Speaking Tutor (CALST), which selectively…
Learning Thermochemistry: Understanding the Challenges and Promoting Its Success
ERIC Educational Resources Information Center
Chang, Karen
2009-01-01
This study was conducted to investigate how students approach the learning of thermochemistry, what the challenges are and how instruction can make learning of thermochemistry more accessible. Specifically, this study seeks to understand: 1) which topics in thermochemistry are more difficult to learn and which topics are easier; 2) why the…
ERIC Educational Resources Information Center
Loke, Swee-Kin; Al-Sallami, Hesham S.; Wright, Daniel F. B.; McDonald, Jenny; Jadhav, Sheetal; Duffull, Stephen B.
2012-01-01
Complex systems are typically difficult for students to understand and computer simulations offer a promising way forward. However, integrating such simulations into conventional classes presents numerous challenges. Framed within an educational design research, we studied the use of an in-house built simulation of the coagulation network in four…
ERIC Educational Resources Information Center
Briggs, Linda L.
2007-01-01
Today, as difficult as it is for large institutions to keep software and hardware up-to-date, the challenge and expense of keeping up is only amplified for smaller colleges and universities. In the area of data-driven decision-making (DDD), the challenge can be even greater. Because smaller schools are pressed for time and resources on nearly all…
ERIC Educational Resources Information Center
Buchanan, John; Burridge, Nina; Andrew Chodkiewicz
2018-01-01
Teaching students about global citizenship remains a critical challenge for schools and communities, especially in a developed country like Australia. With increasingly difficult national and international contexts and its marginal place in the school curriculum, there is an urgent need to help maintain support for global citizenship education.…
Post-Adoption Issues Related to Cloud-Based IT Solutions: A Multi-Method Investigation
ERIC Educational Resources Information Center
Xiao, Xiao
2013-01-01
Due to their low cost of implementation and considerable elasticity, cloud-based IT solutions are being widely adopted or considered in organizations across various industries. However, such IT solutions bring forth several unique challenges--challenges that make it difficult for organizations to achieve successful utilization of cloud-based…
Executive Leadership: Another Lever in the System?
ERIC Educational Resources Information Center
Harris, Alma; Brown, David; Abbott, Ian
2006-01-01
The leadership challenges facing most head teachers can at times be daunting but for those leading schools in difficulty, the challenges are acute. This article draws upon the personal experience of an executive leader in a school facing difficult circumstances. It will firstly, outline and analyse this model of leadership and secondly, look at…
U(1) Wilson lattice gauge theories in digital quantum simulators
NASA Astrophysics Data System (ADS)
Muschik, Christine; Heyl, Markus; Martinez, Esteban; Monz, Thomas; Schindler, Philipp; Vogell, Berit; Dalmonte, Marcello; Hauke, Philipp; Blatt, Rainer; Zoller, Peter
2017-10-01
Lattice gauge theories describe fundamental phenomena in nature, but calculating their real-time dynamics on classical computers is notoriously difficult. In a recent publication (Martinez et al 2016 Nature 534 516), we proposed and experimentally demonstrated a digital quantum simulation of the paradigmatic Schwinger model, a U(1)-Wilson lattice gauge theory describing the interplay between fermionic matter and gauge bosons. Here, we provide a detailed theoretical analysis of the performance and the potential of this protocol. Our strategy is based on analytically integrating out the gauge bosons, which preserves exact gauge invariance but results in complicated long-range interactions between the matter fields. Trapped-ion platforms are naturally suited to implementing these interactions, allowing for an efficient quantum simulation of the model, with a number of gate operations that scales polynomially with system size. Employing numerical simulations, we illustrate that relevant phenomena can be observed in larger experimental systems, using as an example the production of particle-antiparticle pairs after a quantum quench. We investigate theoretically the robustness of the scheme towards generic error sources, and show that near-future experiments can reach regimes where finite-size effects are insignificant. We also discuss the challenges in quantum simulating the continuum limit of the theory. Using our scheme, fundamental phenomena of lattice gauge theories can be probed using a broad set of experimentally accessible observables, including the entanglement entropy and the vacuum persistence amplitude.
Roadmap to clinical use of gold nanoparticles for radiosensitization
Schuemann, J.; Berbeco, R.; Chithrani, B. D.; Cho, S.; Kumar, R.; McMahon, S.; Sridhar, S.; Krishnan, S.
2015-01-01
The past decade has seen a dramatic increase in interest in the use of Gold Nanoparticles (GNPs) as radiation sensitizers for radiotherapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs’ efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X-rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiosensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes and preparations. As a result, mechanisms of uptake and radiosensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiosensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage. PMID:26700713
The Difficult Gallbladder: A Safe Approach to a Dangerous Problem.
Santos, B Fernando; Brunt, L Michael; Pucci, Michael J
2017-06-01
Laparoscopic cholecystectomy is a common surgical procedure, and remains the gold standard for the management of benign gallbladder and biliary disease. While this procedure can be technically straightforward, it can also represent one of the most challenging operations facing surgeons. This dichotomy of a routine operation performed so commonly that poses such a hidden risk of severe complications, such as bile duct injury, must keep surgeons steadfast in the pursuit of safety. The "difficult gallbladder" requires strict adherence to the Culture of Safety in Cholecystectomy, which promotes safety first and assists surgeons in managing or avoiding difficult operative situations. This review will discuss the management of the difficult gallbladder and propose the use of subtotal fenestrating cholecystectomy as a definitive option during this dangerous situation.
Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors
Frimurer, Thomas M.; Meiler, Jens
2013-01-01
The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone and side-chain conformational space with Rosetta can be leveraged to meet this challenge. This study performs unbiased comparative modeling and docking methodologies using 14 distinct high-resolution GPCRs and proposes knowledge-based filtering methods for improvement of sampling performance and identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD) of 2.2 Å for the transmembrane region and 5 Å for the second extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves, however, it remains difficult to unambiguously identify correct binding modes by score alone. On average, sampling performance was improved by 103 fold over random using knowledge-based and energy-based filters. In assessing the applicability of experimental constraints, we found that sampling performance is increased by one order of magnitude for every 10 residues known to contact the ligand. Additionally, in the case of DOR, knowledge of a single specific ligand-protein contact improved sampling efficiency 7 fold. These findings offer specific guidelines which may lead to increased success in determining receptor-ligand complexes. PMID:23844000
Challenges for Synchrotron X-Ray Optics
NASA Astrophysics Data System (ADS)
Freund, Andreas K.
2002-12-01
It is the task of x-ray optics to adapt the raw beam generated by modern sources such as synchrotron storage rings to a great variety of experimental requirements in terms of intensity, spot size, polarization and other parameters. The very high quality of synchrotron radiation (source size of a few microns and beam divergence of a few micro-radians) and the extreme x-ray flux (power of several hundred Watts in a few square mm) make this task quite difficult. In particular the heat load aspect is very important in the conditioning process of the brute x-ray power to make it suitable for being used on the experimental stations. Cryogenically cooled silicon crystals and water-cooled diamond crystals can presently fulfill this task, but limits will soon be reached and new schemes and materials must be envisioned. A major tendency of instrument improvement has always been to concentrate more photons into a smaller spot utilizing a whole variety of focusing devices such as Fresnel zone plates, refractive lenses and systems based on bent surfaces, for example, Kirkpatrick-Baez systems. Apart from the resistance of the sample, the ultimate limits are determined by the source size and strength on one side, by materials properties, cooling, mounting and bending schemes on the other side, and fundamentally by the diffraction process. There is also the important aspect of coherence that can be both a nuisance and a blessing for the experiments, in particular for imaging techniques. Its conservation puts additional constraints on the quality of the optical elements. The overview of the present challenges includes the properties of present and also mentions aspects of future x-ray sources such as the "ultimate" storage ring and free electron lasers. These challenges range from the thermal performances of monochromators to the surface quality of mirrors, from coherence preservation of modern multilayers to short pulse preservation by crystals, and from micro- and nano-focusing techniques to the accuracy and stability of mechanical supports.
A Novel Ex Vivo Method for Visualizing Live-Cell Calcium Response Behavior in Intact Human Tumors.
Koh, James; Hogue, Joyce A; Sosa, Julie A
2016-01-01
The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.
Ukrainian prisoners and community reentry challenges: implications for transitional care
Morozova, Olga; Azbel, Lyuba; Grishaev, Yevgeny; Dvoryak, Sergii; Wickersham, Jeffrey A.; Altice, Frederick L.
2013-01-01
Purpose The study aims to assess reentry challenges faced by Ukrainian prisoners and to determine the factors associated with having a greater number of challenges in order to suggest pre- and post-release interventions with the aim of facilitating community reintegration. Design/methodology/approach A representative national cross-sectional study with a sample size of 402 prisoners was conducted among imprisoned adults within six months of release. The study consisted of interviews and biological testing for infectious diseases. Anticipated reentry challenges were assessed using a structured questionnaire. Findings The most difficult and relatively important challenges identified were finding a job or a stable source of income and staying out of prison following release. Risk-specific challenges pertinent to drug users and HIV-infected individuals were assessed as difficult, but generally less important. Similarly, challenges associated with reducing drug relapse were ranked as less important, with only 0.6 percent identifying opioid substitution therapy as a helpful measure. In the multivariate analysis, having a greater number of challenges is associated with previous incarcerations, drug use immediately before incarceration and lower levels of social support. Practical implications To facilitate community re-integration, it is vital to design interventions aimed at reducing recidivism and improvement of social support through comprehensive case management as well as to improve understanding about and address drug dependence issues among inmates by implementing evidence-based treatment both within prisons and after release. Originality/value This is the first comprehensive assessment of community reentry challenges by prisoners in the former Soviet Union. PMID:25152767
ERIC Educational Resources Information Center
Rands, Sean A.
2011-01-01
The design of experimental ecological fieldwork is difficult to teach to classes, particularly when protocols for data collection are normally carefully controlled by the class organiser. Normally, reinforcement of the some problems of experimental design such as the avoidance of pseudoreplication and appropriate sampling techniques does not occur…
Exploring Experimental Design: An Excel-Based Simulation Using Steller Sea Lion Behavior
ERIC Educational Resources Information Center
Ryan, Wendy L.; St. Iago-McRae, Ezry
2016-01-01
Experimentation is the foundation of science and an important process for students to understand and experience. However, it can be difficult to teach some aspects of experimentation within the time and resource constraints of an academic semester. Interactive models can be a useful tool in bridging this gap. This freely accessible simulation…
Encountering unexpected difficult airway: relationship with the intubation difficulty scale
Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin
2016-01-01
Background An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. Methods We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. Results For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Conclusions Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID:27274369
NASA Astrophysics Data System (ADS)
Cayirci, Erdal; Rong, Chunming; Huiskamp, Wim; Verkoelen, Cor
Military/civilian education training and experimentation networks (ETEN) are an important application area for the cloud computing concept. However, major security challenges have to be overcome to realize an ETEN. These challenges can be categorized as security challenges typical to any cloud and multi-level security challenges specific to an ETEN environment. The cloud approach for ETEN is introduced and its security challenges are explained in this paper.
Difficult airway in a pediatric case of pycodysostosis
Alkhalaf, Maizar M.; Ali, Hassan Mohamed; Al Otaibi, Rashed
2015-01-01
Pycodysostosis is a genetic autosomal rare disease with an incidence of 1:1.7 million births; the pathophysiology of the disease is related to mutation of cathepsin K gene. Sleep apnea, respiratory difficulties because of chest and oral abnormalities may cause a challenge to the anesthetist during intubation and/or mechanical ventilation. In this case report we will discuss a case of pycodysostosis with a difficult airway. PMID:25886438
Association for Academic Surgery presidential address: sticky floors and glass ceilings.
Greenberg, Caprice C
2017-11-01
This 2017 Presidential Address for the Association for Academic Surgery was delivered on February 8, 2017. It addresses the difficult topic of gender disparities in surgery. Mixing empirical data with personal anecdotes, Dr. Caprice Greenberg provides an insightful overview of this difficult challenge facing the surgical discipline and practical advice on how we can begin to address it. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bernardin, John D; Baca, Allen G
This paper presents the mechanical design, fabrication and dynamic testing of an electrostatic analyzer spacecraft instrument. The functional and environmental requirements combined with limited spacecraft accommodations, resulted in complex component geometries, unique material selections, and difficult fabrication processes. The challenging aspects of the mechanical design and several of the more difficult production processes are discussed. In addition, the successes, failures, and lessons learned from acoustic and random vibration testing of a full-scale prototype instrument are presented.
NASA Astrophysics Data System (ADS)
Koskinen, H. E.
2008-12-01
Plasma physics as the backbone of space physics is difficult and thus the space physics students need to have strong foundations in general physics, in particular in classical electrodynamics and thermodynamics, and master the basic mathematical tools for physicists. In many universities the number of students specializing in space physics at Master's and Doctoral levels is rather small and the students may have quite different preferences ranging from experimental approach to hard-core space plasma theory. This poses challenges in building up a study program that has both the variety and depth needed to motivate the best students to choose this field. At the University of Helsinki we require all beginning space physics students, regardless whether they enter the field as Master's or Doctoral degree students, to take a one-semester package consisting of plasma physics and its space applications. However, some compromises are necessary. For example, it is not at all clear, how thoroughly Landau damping should be taught at the first run or how deeply should the intricacies of collisionless reconnection be discussed. In both cases we have left the details to an optional course in advanced space physics, even with the risk that the student's appreciation of, e.g., reconnection may remain at the level of a magic wand. For learning experimental work, data analysis or computer simulations we have actively pursued arrangements for the Master's degree students to get a summer employments in active research groups, which usually lead to the Master's theses. All doctoral students are members of research groups and participate in experimental work, data analysis, simulation studies or theory development, or any combination of these. We emphasize strongly "learning by doing" all the way from the weekly home exercises during the lecture courses to the PhD theses which in Finland consist typically of 4-6 peer-reviewed articles with a comprehensive introductory part.
2017-01-01
Objectives To explore the challenges Health Information Technology (HIT) vendors face to satisfy the requirements for Meaningful Use (MU) and Electronic Laboratory Reporting (ELR) of reportable diseases to the public health departments in Kentucky. Methodology A survey was conducted of Health Information Exchange (HIE) vendors in Kentucky through the Kentucky Health Information Exchange (KHIE). The survey was cross-sectional. Data were collected between February and March 2014. Participants were recruited from KHIE vendors. Participants received online survey link and by email and asked to submit their responses. Vendors’ feedback were summarized and analyzed to identify their challenges. Out of the 55 vendors who received the survey, 35(63.64%) responded. Results Of the seven transport protocol options for ELR, vendors selected virtual private network (VPN) as the most difficult to implement (31.7%). Secure File Transfer Protocol (SFTP) was selected as preferred ELR transport protocol (31.4%). Most of the respondents, 80% responded that they do not have any challenge with the Health Level 7 (HL7) standard implementation guide required by MU for 2014 ELR certification. Conclusion The study found that the most difficult transport protocol to implement for ELR is VPN and if vendors have preference, they would use SFTP for ELR over KHIE choice of VPN and Simple Object Access Protocol (SOAP). KHIE vendors do not see any variability in what is reportable by different jurisdiction and also it is not difficult for them to detect what is reportable from one jurisdiction verse the other PMID:29403575
Note-Taking and Secondary Students with Learning Disabilities: Challenges and Solutions
ERIC Educational Resources Information Center
Boyle, Joseph R.
2012-01-01
As more secondary students with learning disabilities (LD) enroll in advanced content-area classes and are expected to pass state exams, they are faced with the challenge of mastering difficult concepts and abstract vocabulary while learning content. Once in these classes, students must learn from lectures that move at a quick pace, record…
Image Processing Algorithms in the Secondary School Programming Education
ERIC Educational Resources Information Center
Gerják, István
2017-01-01
Learning computer programming for students of the age of 14-18 is difficult and requires endurance and engagement. Being familiar with the syntax of a computer language and writing programs in it are challenges for youngsters, not to mention that understanding algorithms is also a big challenge. To help students in the learning process, teachers…
ERIC Educational Resources Information Center
Ecclestone, Kathryn
2012-01-01
It is difficult to challenge a strong consensus that governments must intervene in a worsening crisis of emotional and psychological well-being. The article relates rising estimates of problems and corresponding calls for intervention in educational settings to the increasingly blurred boundaries between a cultural therapeutic ethos, academic…
Christine Esposito
2006-01-01
Bringing the right people into a collaborative process can be difficult. Potential collaborators must all feel they have something to gain to justify investing resources, sharing knowledge, and perhaps compromising on goals and actions. This fact sheet discusses some of the common challenges that individuals, communities, and institutions face in collaboration.
ERIC Educational Resources Information Center
Liu, Edward; Rosenstein, Joseph G.; Swan, Aubrie E.; Khalil, Deena
2008-01-01
Administrators in six urban districts were interviewed to understand the nature and extent of their problems with recruiting and retaining high quality mathematics teachers. Findings suggest that the math staffing challenge is quite complex, and administrators have had to make difficult compromises because of deficiencies in the quantity and…
Changing Jobs in Difficult Financial Times
ERIC Educational Resources Information Center
Brown, Wayne
2009-01-01
Starting a new CIO job is always a challenge. There is a new department and institution to learn about, people to meet, and problems to solve. There is always plenty to learn and projects to realize. Throwing in economic challenges to the new-job transition can feel like one is attempting to climb a mountain without any gear. Fortunately, there…
The Labour Market Relevance of PhDs: An Issue for Academic Research and Policy-Makers
ERIC Educational Resources Information Center
Boulos, Aurélie
2016-01-01
In the difficult current socio-economic context, overqualified graduates are increasingly facing challenges in terms of entering the job market and finding jobs which fit their levels of qualifications and satisfaction. Grounded in an auto-ethnography approach, this paper reflects on the challenges that the author (a young female European PhD…
ERIC Educational Resources Information Center
Munday, Jenni; Smith, Wyverne
2010-01-01
Pre-service teacher degree programs are increasingly crowded with subjects covering the wide gamut of knowledge a teacher requires. Ensuring musical knowledge and language for classroom teaching poses a difficult problem for teacher educators. This article examines the challenges of including in the pre-service classroom teaching program a music…
ERIC Educational Resources Information Center
Gunn, Holly
2005-01-01
Although there are many news search engines on the Web, finding the news items one wants can be challenging. Choosing appropriate search terms is one of the biggest challenges. Unless one has seen the article that one is seeking, it is often difficult to select words that were used in the headline or text of the article. The limited archives of…
ERIC Educational Resources Information Center
Chen, Hao; Ni, Ju-Hua
2013-01-01
Biochemistry occupies a unique place in the medical school curricula, but the teaching of biochemistry presents certain challenges. One of these challenges is facilitating students' interest in and mastery of metabolism. The many pathways and modes of regulation can be overwhelming for students to learn and difficult for professors to teach in an…
Lin, Li-Wei; Weng, Shu-Chuan; Wu, Hua-Shan; Tsai, Lu-Jen; Lin, Ya-Ling; Yeh, Shu-Hui
2018-02-01
The aging of society is a global trend, and care of older adults with dementia is an urgent challenge. As dementia progresses, patients exhibit negative emotions, memory disorders, sleep disorders, and agitated behavior. Agitated behavior is one of the most difficult problems for family caregivers and healthcare providers to handle when caring for older adults with dementia. The aim of this study was to investigate the effectiveness of white noise in improving agitated behavior, mental status, and activities of daily living in older adults with dementia. An experimental research design was used to study elderly participants two times (pretest and posttest). Six dementia care centers in central and southern Taiwan were targeted to recruit participants. There were 63 participants: 28 were in the experimental group, and 35 were in the comparison group. Experimental group participants received 20 minutes of white noise consisting of ocean, rain, wind, and running water sounds between 4 and 5 P.M. daily over a period of 4 weeks. The comparison group received routine care. Questionnaires were completed, and observations of agitated behaviors were collected before and after the intervention. Agitated behavior in the experimental group improved significantly between pretest and posttest. Furthermore, posttest scores on the Mini-Mental Status Examination and Barthel Index were slightly better for this group than at pretest. However, the experimental group registered no significant difference in mental status or activities of daily living at posttest. For the comparison group, agitated behavior was unchanged between pretest and posttest. The results of this study support white noise as a simple, convenient, and noninvasive intervention that improves agitated behavior in older adults with dementia. These results may provide a reference for related healthcare providers, educators, and administrators who care for older adults with dementia.
Vlastarakos, Petros V; Vasileiou, Alexandra; Nikolopoulos, Thomas P
2017-12-01
We conducted an analysis to assess the relative contribution of auditory brainstem response (ABR) testing and auditory steady-state response (ASSR) testing in providing appropriate hearing aid fitting in hearing-impaired children with difficult or unreliable behavioral audiometry. Of 150 infants and children who had been referred to us for hearing assessment as part of a neonatal hearing screening and cochlear implantation program, we identified 5 who exhibited significant discrepancies between click-ABR and ASSR testing results and difficult or unreliable behavioral audiometry. Hearing aid fitting in pediatric cochlear implant candidates for a trial period of 3 to 6 months is a common practice in many implant programs, but monitoring the progress of the amplified infants and providing appropriate hearing aid fitting can be challenging. If we accept the premise that we can assess the linguistic progress of amplified infants with an acceptable degree of certainty, the auditory behavior that we are monitoring presupposes appropriate bilateral hearing aid fitting. This may become very challenging in young children, or even in older children with difficult or unreliable behavioral audiometry results. This challenge can be addressed by using data from both ABR and ASSR testing. Fitting attempts that employ data from only ABR testing provide amplification that involves the range of spoken language but is not frequency-specific. Hearing aid fitting should also incorporate and take into account ASSR data because reliance on ABR testing alone might compromise the validity of the monitoring process. In conclusion, we believe that ASSR threshold-based bilateral hearing aid fitting is necessary to provide frequency-specific amplification of hearing and appropriate propulsion in the prelinguistic vocalizations of monitored infants.
[Clinical and health economic challenges of personalized medicine].
Brüggenjürgen, B; Kornbluth, L; Ferrara, J V; Willich, S N
2012-05-01
Healthcare systems across the globe are currently challenged by aging populations, increases in chronic diseases and the difficult task of managing a healthcare budget. In this health economic climate, personalized medicine promises not only an improvement in healthcare delivery but also the possibility of more cost-effective therapies. It is important to remember, however, that personalized medicine has the potential to both increase and decrease costs. Each targeted therapy must be evaluated individually. However, standard clinical trial design is not suitable for personalized therapies. Therefore, both scientists and regulatory authorities will need to accept innovative study designs in order to validate personalized therapies. Hence correct economic evaluations are difficult to carry out due to lack of clear clinical evidence, longitudinal accounting and experience with patient/clinician behavior in the context of personalized medicine. In terms of reimbursement, payers, pharmaceutical companies and companion diagnostic manufacturers will also need to explore creative risk-sharing concepts. Germany is no exception to the challenges that face personalized medicine and for personalized medicine to really become the future of medicine many health economic challenges first need to be overcome. The health economic implications of personalized medicine remain unclear but it is certain that the expansion of targeted therapies in current healthcare systems will create a host of challenges.
Gone with the Wind: Conceiving of Moral Responsibility in the Case of GMO Contamination.
Robaey, Zoë
2016-06-01
Genetically modified organisms are a technology now used with increasing frequency in agriculture. Genetically modified seeds have the special characteristic of being living artefacts that can reproduce and spread; thus it is difficult to control where they end up. In addition, genetically modified seeds may also bring about uncertainties for environmental and human health. Where they will go and what effect they will have is therefore very hard to predict: this creates a puzzle for regulators. In this paper, I use the problem of contamination to complicate my ascription of forward-looking moral responsibility to owners of genetically modified organisms. Indeed, how can owners act responsibly if they cannot know that contamination has occurred? Also, because contamination creates new and unintended ownership, it challenges the ascription of forward-looking moral responsibility based on ownership. From a broader perspective, the question this paper aims to answer is as follows: how can we ascribe forward-looking moral responsibility when the effects of the technologies in question are difficult to know or unknown? To solve this problem, I look at the epistemic conditions for moral responsibility and connect them to the normative notion of the social experiment. Indeed, examining conditions for morally responsible experimentation helps to define a range of actions and to establish the related epistemic virtues that owners should develop in order to act responsibly where genetically modified organisms are concerned.
Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue
2013-02-01
Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Unsupervised Sequential Outlier Detection With Deep Architectures.
Lu, Weining; Cheng, Yu; Xiao, Cao; Chang, Shiyu; Huang, Shuai; Liang, Bin; Huang, Thomas
2017-09-01
Unsupervised outlier detection is a vital task and has high impact on a wide variety of applications domains, such as image analysis and video surveillance. It also gains long-standing attentions and has been extensively studied in multiple research areas. Detecting and taking action on outliers as quickly as possible are imperative in order to protect network and related stakeholders or to maintain the reliability of critical systems. However, outlier detection is difficult due to the one class nature and challenges in feature construction. Sequential anomaly detection is even harder with more challenges from temporal correlation in data, as well as the presence of noise and high dimensionality. In this paper, we introduce a novel deep structured framework to solve the challenging sequential outlier detection problem. We use autoencoder models to capture the intrinsic difference between outliers and normal instances and integrate the models to recurrent neural networks that allow the learning to make use of previous context as well as make the learners more robust to warp along the time axis. Furthermore, we propose to use a layerwise training procedure, which significantly simplifies the training procedure and hence helps achieve efficient and scalable training. In addition, we investigate a fine-tuning step to update all parameters set by incorporating the temporal correlation in the sequence. We further apply our proposed models to conduct systematic experiments on five real-world benchmark data sets. Experimental results demonstrate the effectiveness of our model, compared with other state-of-the-art approaches.
The relationship between specific cognitive impairment and behaviour in Prader-Willi syndrome.
Woodcock, K A; Oliver, C; Humphreys, G W
2011-02-01
Individuals with Prader-Willi syndrome (PWS) have been shown to demonstrate a particular cognitive deficit in attention switching and high levels of preference for routine and temper outbursts. This study assesses whether a specific pathway between a cognitive deficit and behaviour via environmental interaction can exist in individuals with PWS. Four individuals with PWS participated in a series of three single-case experiments including laboratory-based and natural environment designs. Cognitive (computer-based) challenges placed varying demands on attention switching or controlled for the cognitive demands of the tasks while placing no demands on switching. Unexpected changes to routines or expectations were presented in controlled games, or imposed on participants' natural environments and compared with control conditions during which no unexpected changes occurred. Behaviour was observed and heart rate was measured. Participants showed significantly increased temper outburst related behaviours during cognitive challenges that placed demands on attention switching, relative to the control cognitive challenges. Participants showed significantly increased temper outburst related behaviours when unexpected changes occurred in an experimental or the natural environment compared with when no changes occurred. Difficult behaviours that could be triggered reliably in an individual by a specific cognitive demand could also be triggered via manipulation of the environment. Results suggest that a directional relationship between a specific cognitive deficit and behaviour, via environmental interaction, can exist in individuals with PWS. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.
Sarkar, Sumona; Lund, Steven P; Vyzasatya, Ravi; Vanguri, Padmavathy; Elliott, John T; Plant, Anne L; Lin-Gibson, Sheng
2017-12-01
Cell counting measurements are critical in the research, development and manufacturing of cell-based products, yet determining cell quantity with accuracy and precision remains a challenge. Validating and evaluating a cell counting measurement process can be difficult because of the lack of appropriate reference material. Here we describe an experimental design and statistical analysis approach to evaluate the quality of a cell counting measurement process in the absence of appropriate reference materials or reference methods. The experimental design is based on a dilution series study with replicate samples and observations as well as measurement process controls. The statistical analysis evaluates the precision and proportionality of the cell counting measurement process and can be used to compare the quality of two or more counting methods. As an illustration of this approach, cell counting measurement processes (automated and manual methods) were compared for a human mesenchymal stromal cell (hMSC) preparation. For the hMSC preparation investigated, results indicated that the automated method performed better than the manual counting methods in terms of precision and proportionality. By conducting well controlled dilution series experimental designs coupled with appropriate statistical analysis, quantitative indicators of repeatability and proportionality can be calculated to provide an assessment of cell counting measurement quality. This approach does not rely on the use of a reference material or comparison to "gold standard" methods known to have limited assurance of accuracy and precision. The approach presented here may help the selection, optimization, and/or validation of a cell counting measurement process. Published by Elsevier Inc.
Lallouette, Jules; De Pittà, Maurizio; Ben-Jacob, Eshel; Berry, Hugues
2014-01-01
Traditionally, astrocytes have been considered to couple via gap-junctions into a syncytium with only rudimentary spatial organization. However, this view is challenged by growing experimental evidence that astrocytes organize as a proper gap-junction mediated network with more complex region-dependent properties. On the other hand, the propagation range of intercellular calcium waves (ICW) within astrocyte populations is as well highly variable, depending on the brain region considered. This suggests that the variability of the topology of gap-junction couplings could play a role in the variability of the ICW propagation range. Since this hypothesis is very difficult to investigate with current experimental approaches, we explore it here using a biophysically realistic model of three-dimensional astrocyte networks in which we varied the topology of the astrocyte network, while keeping intracellular properties and spatial cell distribution and density constant. Computer simulations of the model suggest that changing the topology of the network is indeed sufficient to reproduce the distinct ranges of ICW propagation reported experimentally. Unexpectedly, our simulations also predict that sparse connectivity and restriction of gap-junction couplings to short distances should favor propagation while long–distance or dense connectivity should impair it. Altogether, our results provide support to recent experimental findings that point toward a significant functional role of the organization of gap-junction couplings into proper astroglial networks. Dynamic control of this topology by neurons and signaling molecules could thus constitute a new type of regulation of neuron-glia and glia-glia interactions. PMID:24795613
A Quantitative Review of Functional Analysis Procedures in Public School Settings
ERIC Educational Resources Information Center
Solnick, Mark D.; Ardoin, Scott P.
2010-01-01
Functional behavioral assessments can consist of indirect, descriptive and experimental procedures, such as a functional analysis. Although the research contains numerous examples demonstrating the effectiveness of functional analysis procedures, experimental conditions are often difficult to implement in classroom settings and analog conditions…
Leadership and Work-Life Balance.
Mattock, Sarah L
2015-01-01
Simply stated, work-life balance is something that is both difficult to define and difficult to achieve. Leaders, throughout the continuum of trauma care, need to have a sound understanding of what work-life balance means and set an example of a healthy work-life balance for those they lead. This article offers strategies for enhancing work-life balance and challenges individuals to use self-reflection as a means to furthering their personal and professional growth.
Inhaled Antibiotic Therapy in Chronic Respiratory Diseases
Maselli, Diego J.; Keyt, Holly; Restrepo, Marcos I.
2017-01-01
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases. PMID:28509852
Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.
Maselli, Diego J; Keyt, Holly; Restrepo, Marcos I
2017-05-16
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa , Methicillin-resistant Staphylococcus aureus , Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.
Seedling distribution on a spruce-hemlock clearcut.
Carl M. Berntsen
1955-01-01
A better job of regeneration on cutover areas can be done if foresters know what areas are difficult to regenerate and what sort of practices are best for the difficult areas. A study recently completed at Cascade Head Experimental Forest has supplied that sort of information for a typical spruce-hemlock clearcut. Nearly a fifth of the area was still unstocked 6 years...
NASA Astrophysics Data System (ADS)
Zhang, P. P.; Guo, Y.; Wang, B.
2017-05-01
The main problems in milling difficult-to-machine materials are the high cutting temperature and rapid tool wear. However it is impossible to investigate tool wear in machining. Tool wear and cutting chip formation are two of the most important representations for machining efficiency and quality. The purpose of this paper is to develop the model of tool wear with cutting chip formation (width of chip and radian of chip) on difficult-to-machine materials. Thereby tool wear is monitored by cutting chip formation. A milling experiment on the machining centre with three sets cutting parameters was performed to obtain chip formation and tool wear. The experimental results show that tool wear increases gradually along with cutting process. In contrast, width of chip and radian of chip decrease. The model is developed by fitting the experimental data and formula transformations. The most of monitored errors of tool wear by the chip formation are less than 10%. The smallest error is 0.2%. Overall errors by the radian of chip are less than the ones by the width of chip. It is new way to monitor and detect tool wear by cutting chip formation in milling difficult-to-machine materials.
Reframing the Path to School Leadership: A Guide for Teachers and Principals.
ERIC Educational Resources Information Center
Bolman, Lee G.; Deal, Terrence E.
The best leaders use multiple frames or lenses to view common challenges and to solve their most difficult problems. This book contains a series of dialogs between a novice and a master teacher, and between a new and a seasoned principal as they demonstrate how framing and reframing challenges can bring clarity, help to anticipate problems, and…
ERIC Educational Resources Information Center
White, Charles S.
Arguing that the foundation of a free civilization is an informed citizenry, this ERIC digest discusses the new challenges faced by the government and libraries in the wake of the Information Age. As electronic technology has accelerated the production and transmission of information, it has become more difficult for the average citizen to access,…
Threats to cross-border wildlife linkages in the Sky Islands Wildlands Network
Kim Vacariu
2005-01-01
One of the greatest challenges facing conservationists in the Sky Islands region is finding a realistic means to maintain historic travel routes for wide-ranging species crossing the United States-Mexico border. This challenge is made difficult due to the ongoing efforts by the Federal government to install additional security infrastructure to stem the flood of...
ERIC Educational Resources Information Center
Eells, Gregory T.; Rockland-Miller, Harry S.
2011-01-01
Behavioral and mental health issues challenge institutions of higher education with difficult decisions around response. Interests of the individual and safety of the community must be constantly considered and balanced. A primary way institutions of higher education are responding to these challenges is through the formation of campus assessment…
"Don't Be Uneasy, My Children": Finding Strength in Stories of the Enslaved
ERIC Educational Resources Information Center
Gilbert, Lisa
2014-01-01
Tackling challenging topics in history can be difficult, and sometimes teachers struggle to find age-appropriate ways to help students confront painful stories from the past. About four years ago, this author spearheaded a focus group with the purpose of taking on such a challenge. In the initial meetings, members of the group (four educators from…
ERIC Educational Resources Information Center
Basantia, Tapan Kumar
2018-01-01
Implementing practical based courses under Open and Distance Learning (ODL) system is a very difficult and challenging task as the teaching of practical based courses involves intensive practical work. For removing the difficulties and challenges in implementing the practical based courses under ODL system, there is a need to study the existing…
Last electroweak WIMP standing: pseudo-dirac higgsino status and compact stars as future probes
NASA Astrophysics Data System (ADS)
Krall, Rebecca; Reece, Matthew
2018-04-01
Electroweak WIMPs are under intense scrutiny from direct detection, indirect detection, and collider experiments. Nonetheless the pure (pseudo-Dirac) higgsino, one of the simplest such WIMPs, remains elusive. We present an up-to-date assessment of current experimental constraints on neutralino dark matter. The strongest bound on pure higgsino dark matter currently may arise from AMS-02 measurements of antiprotons, though the interpretation of these results has sizable uncertainty. We discuss whether future astrophysical observations could offer novel ways to test higgsino dark matter, especially in the challenging regime with order MeV mass splitting between the two neutral higgsinos. We find that heating of white dwarfs by annihilation of higgsinos captured via inelastic scattering could be one useful probe, although it will require challenging observations of distant dwarf galaxies or a convincing case to be made for substantial dark matter content in ω Cen, a globular cluster that may be a remnant of a disrupted dwarf galaxy. White dwarfs and neutron stars give a target for astronomical observations that could eventually help to close the last, most difficult corner of parameter space for dark matter with weak interactions. Supported by NSF (PHY-1415548) and NASA ATP (NNX16AI12G)
BLIND ordering of large-scale transcriptomic developmental timecourses.
Anavy, Leon; Levin, Michal; Khair, Sally; Nakanishi, Nagayasu; Fernandez-Valverde, Selene L; Degnan, Bernard M; Yanai, Itai
2014-03-01
RNA-Seq enables the efficient transcriptome sequencing of many samples from small amounts of material, but the analysis of these data remains challenging. In particular, in developmental studies, RNA-Seq is challenged by the morphological staging of samples, such as embryos, since these often lack clear markers at any particular stage. In such cases, the automatic identification of the stage of a sample would enable previously infeasible experimental designs. Here we present the 'basic linear index determination of transcriptomes' (BLIND) method for ordering samples comprising different developmental stages. The method is an implementation of a traveling salesman algorithm to order the transcriptomes according to their inter-relationships as defined by principal components analysis. To establish the direction of the ordered samples, we show that an appropriate indicator is the entropy of transcriptomic gene expression levels, which increases over developmental time. Using BLIND, we correctly recover the annotated order of previously published embryonic transcriptomic timecourses for frog, mosquito, fly and zebrafish. We further demonstrate the efficacy of BLIND by collecting 59 embryos of the sponge Amphimedon queenslandica and ordering their transcriptomes according to developmental stage. BLIND is thus useful in establishing the temporal order of samples within large datasets and is of particular relevance to the study of organisms with asynchronous development and when morphological staging is difficult.
Bentzon, Jacob F; Falk, Erling
2010-01-01
Smooth muscle cells play a critical role in the development of atherosclerosis and its clinical complications. They were long thought to derive entirely from preexisting smooth muscle cells in the arterial wall, but this understanding has been challenged by the claim that circulating bone marrow-derived smooth muscle progenitor cells are an important source of plaque smooth muscle cells in human and experimental atherosclerosis. This theory is today accepted by many cardiovascular researchers and authors of contemporary review articles. Recently, however, we and others have refuted the existence of bone marrow-derived smooth muscle cells in animal models of atherosclerosis and other arterial diseases based on new experiments with high-resolution microscopy and improved techniques for smooth muscle cell identification and tracking. These studies have also pointed to a number of methodological deficiencies in some of the seminal papers in the field. For those unaccustomed with the methods used in this research area, it must be difficult to decide what to believe and why to do so. In this review, we summarize current knowledge about the origin of smooth muscle cells in atherosclerosis and direct the reader's attention to the methodological challenges that have contributed to the confusion in the field. 2009 Elsevier Inc. All rights reserved.
Hybrid Methods in Quantum Information
NASA Astrophysics Data System (ADS)
Marshall, Kevin
Today, the potential power of quantum information processing comes as no surprise to physicist or science-fiction writer alike. However, the grand promises of this field remain unrealized, despite significant strides forward, due to the inherent difficulties of manipulating quantum systems. Simply put, it turns out that it is incredibly difficult to interact, in a controllable way, with the quantum realm when we seem to live our day to day lives in a classical world. In an effort to solve this challenge, people are exploring a variety of different physical platforms, each with their strengths and weaknesses, in hopes of developing new experimental methods that one day might allow us to control a quantum system. One path forward rests in combining different quantum systems in novel ways to exploit the benefits of different systems while circumventing their respective weaknesses. In particular, quantum systems come in two different flavours: either discrete-variable systems or continuous-variable ones. The field of hybrid quantum information seeks to combine these systems, in clever ways, to help overcome the challenges blocking the path between what is theoretically possible and what is achievable in a laboratory. In this thesis we explore four topics in the context of hybrid methods in quantum information, in an effort to contribute to the resolution of existing challenges and to stimulate new avenues of research. First, we explore the manipulation of a continuous-variable quantum system consisting of phonons in a linear chain of trapped ions where we use the discretized internal levels to mediate interactions. Using our proposed interaction we are able to implement, for example, the acoustic equivalent of a beam splitter with modest experimental resources. Next we propose an experimentally feasible implementation of the cubic phase gate, a primitive non-Gaussian gate required for universal continuous-variable quantum computation, based off sequential photon subtraction. We then discuss the notion of embedding a finite dimensional state into a continuous-variable system, and propose a method of performing quantum computations on encrypted continuous-variable states. This protocol allows for a client, of limited quantum ability, to outsource a computation while hiding their information. Next, we discuss the possibility of performing universal quantum computation on discrete-variable logical states encoded in mixed continuous-variable quantum states. Finally, we present an account of open problems related to our results, and possible future avenues of research.
Barriers and Negative Nudges: Exploring Challenges in Food Journaling
Cordeiro, Felicia; Epstein, Daniel A.; Thomaz, Edison; Bales, Elizabeth; Jagannathan, Arvind K.; Abowd, Gregory D.; Fogarty, James
2016-01-01
Although food journaling is understood to be both important and difficult, little work has empirically documented the specific challenges people experience with food journals. We identify key challenges in a qualitative study combining a survey of 141 current and lapsed food journalers with analysis of 5,526 posts in community forums for three mobile food journals. Analyzing themes in this data, we find and discuss barriers to reliable food entry, negative nudges caused by current techniques, and challenges with social features. Our results motivate research exploring a wider range of approaches to food journal design and technology. PMID:26894233
Barriers and Negative Nudges: Exploring Challenges in Food Journaling.
Cordeiro, Felicia; Epstein, Daniel A; Thomaz, Edison; Bales, Elizabeth; Jagannathan, Arvind K; Abowd, Gregory D; Fogarty, James
2015-04-01
Although food journaling is understood to be both important and difficult, little work has empirically documented the specific challenges people experience with food journals. We identify key challenges in a qualitative study combining a survey of 141 current and lapsed food journalers with analysis of 5,526 posts in community forums for three mobile food journals. Analyzing themes in this data, we find and discuss barriers to reliable food entry, negative nudges caused by current techniques, and challenges with social features. Our results motivate research exploring a wider range of approaches to food journal design and technology.
Matsushima, G K; Morell, P
2001-01-01
Myelin of the adult CNS is vulnerable to a variety of metabolic, toxic, and autoimmune insults. That remyelination can ensue, following demyelinating insult, has been well demonstrated. Details of the process of remyelination are, however difficult to ascertain since in most experimental models of demyelination/remyelination the severity, localization of lesion site, or time course of the pathophysiology is variable from animal to animal. In contrast, an experimental model in which massive demyelination can be reproducibly induced in large areas of mouse brain is exposure to the copper chelator, cuprizone, in the diet. We review work from several laboratories over the past 3 decades, with emphasis on our own recent studies, which suggest an overall picture of cellular events involved in demyelination/remyelination. When 8 week old C57BL/6 mice are fed 0.2% cuprizone in the diet, mature olidgodendroglia are specifically insulted (cannot fulfill the metabolic demand of support of vast amounts of myelin) and go through apoptosis. This is closely followed by recruitment of microglia and phagoctytosis of myelin. Studies of myelin gene expression, coordinated with morphological studies, indicate that even in the face of continued metabolic challenge, oligodendroglial progenitor cells proliferate and invade demyelinated areas. If the cuprizone challenge is terminated, an almost complete remyelination takes place in a matter of weeks. Communication between different cell types by soluble factors may be inferred. This material is presented in the context of a model compatible with present data -- and which can be tested more rigorously with the cuprizone model. The reproducibility of the model indicates that it may allow for testing of manipulations (e.g. available knockouts or transgenics on the common genetic background, or pharmacological treatments) which may accelerate or repress the process of demyelination and or remyelination.
NASA Astrophysics Data System (ADS)
Temme, Andrew Kenneth Gerken
Finding people trapped inside of a burning house is extremely difficult, dangerous, and time consuming. Smoke, heat, unfamiliar floor plans, and possible structural collapse all combine to challenge a firefighter's ability to find a person. Thermal imaging cameras, the most advanced technology available to firefighters today, are able to see through smoke but are unable to see through walls and household items. Through-wall radar and vital-sign detection radar offer an imaging modality that may be able to help firefighters find victims from outside of a room or even a house. Flames can interact with electromagnetic (radar) waves because the flames create a weakly-ionized plasma. Previous work has looked at small flames fueled by pure gases or flames from wildfires. Combustable items in a house are typically petroleum-based products that have different combustion reactions compared to previously studied flames and fire-induced plasmas. Because of this, it is unknown how electromagnetic waves interact with flames found in a house fire. This dissertation investigates the question of how electromagnetic waves interact with flames in a house fire. This is an open problem, with many variables, that poses a subtle and difficult measurement task. This work focuses on creating experimental techniques to explore this problem. From an electromagnetic metrology perspective, the physical phenomena of interest are difficult to measure due to ill-defined physical boundaries, characteristics lengths of varying magnitude, inhomogeneity, and varying time scales. The experimental methods studied here primarily focus on transmission measurements through flames a few feet in height. Additionally, this work presents a proof-of-concept two-wire transmission line for bench-scale, material-characterization of solids, liquids, gases, and flames. Results from this work provide a metrological foundation for future studies in this area. An experimental setup that can withstand direct exposure to flames was developed and preliminary measurements recorded. Data taken during the development of this setup showed a time-dependance that corresponded to transmissions through the flame and the solid fuel being consumed. Calibration procedures were used to verify measurements of standard materials; the calibration procedure should be refined for larger flame measurements. Transmitters were placed inside of a burning house and signal propagation was measured, which required the design of fire-proof enclosures for the transmitters. Measured results demonstrated that transmissions may not be affected when sent from a firefighter inside of a house with fire conditions suitable for an offensive, interior attack. It is unknown if severe conditions, such as a flashover, would affect transmissions. Plasmas were observed in interferometric measurements of live-fire experiments performed in the laboratory. This work has explored an open problem in electromagnetics with live-saving applications to the fire service. Results from this work warrant additional study in this area to improve techniques, with the goal of putting search-and-rescue radars into the hands of firefighters.
Experimental Evolution of Antibiotic Resistance in Bacteria
ERIC Educational Resources Information Center
Krist, Amy C.; Showsh, Sasha A.
2007-01-01
Evolution is typically measured as a change in allele or genotype frequencies over one or more generations. Consequently, evolution is difficult to show experimentally in a semester-long lab course because most organisms have longer generation times than 15 weeks. In this article, the authors present an experiment to demonstrate and study…
The effects of riparian vegetation on the reduction of agricultural nitrogen export to streams have been well described experimentally, but a clear understanding of process-level hydrological and biogeochemical controls can be difficult to ascertain from data alone. We apply a ne...
Optimal Experimental Design for Model Discrimination
ERIC Educational Resources Information Center
Myung, Jay I.; Pitt, Mark A.
2009-01-01
Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it…
The Effects of Test Preparation on Second-Language Listening Test Performance
ERIC Educational Resources Information Center
Winke, Paula; Lim, Hyojung
2017-01-01
To examine the effects of listening test preparation, we had three groups, two experimental and one control (63 learners total), partake in three types of instruction sandwiched between two equally difficult listening tests (pretests and posttests). The first experimental group took four practice tests and received "explicit"…
Donovan, Wilberta; Leavitt, Lewis; Taylor, Nicole
2005-09-01
The impact of differences in maternal self-efficacy and infant difficulty on mothers' sensitivity to small changes in the fundamental frequency of an audiotaped infant's cry was explored in 2 experiments. The experiments share in common experimental manipulations of infant difficulty, a laboratory derived measure of maternal efficacy (low, moderate, and high illusory control), and the use of signal detection methodology to measure maternal sensory sensitivity. In Experiment 1 (N = 72), easy and difficult infant temperament was manipulated by varying the amount of crying (i.e., frequency of cry termination) in a simulated child-care task. In Experiment 2 (N = 51), easy and difficult infant temperament was manipulated via exposure to the solvable or unsolvable pretreatment of a learned helplessness task to mirror mothers' ability to soothe a crying infant. In both experiments, only mothers with high illusory control showed reduced sensory sensitivity under the difficult infant condition compared with the easy infant condition. Copyright 2005 APA, all rights reserved.
End-of-life issues: difficult decisions and dealing with grief.
Loomis, Beth
2009-06-01
People face many challenging psychosocial and spiritual issues as they approach the end of their lives, and caregivers need advice on how to help them. Choosing among treatment options, handling grief, addressing unfinished business, and coping with loss of self-sufficiency are difficult for the dying person, and caregivers must deal with surrogate decision making, raw emotions in the patient and in family members, and the caregivers' own grief. Listening and coping skills are discussed.
NASA Astrophysics Data System (ADS)
Dattani, Nikesh S.; Li, Xuan
2013-06-01
Recent high-resolution (± 0.00002 cm^{-1}) photo-association spectroscopy (PAS) data of seven previously unexplored vibrational levels of the 1^3Σ_g^+ state of Li_2 have allowed for the first ever experimental determination of the spin-spin (λ_v) and spin-rotation (γ_v) coupling constants in a diatomic lithium system. For triplet states of diatomic molecules such as the 1^3Σ_g^+ state of Li_2, the three spin-spin/spin-rotation resolved energies associated with a ro-vibrational state |v,N> were expressed explicity in terms of B_v, λ_v, and γ_v in 1929 by Kramer's first-order formulas and then in 1937 by Schlapp's more refined formulas. Given spectroscopic data, while it has never been difficult to extract λ_v and γ_v from Schlapp's formulas, it has been a challenge to reliably predict how accurate these extracted values are. This is for two reasons: (1) the lack of a rigorous method to estimate the uncertainty in B_v, (2) the non-linearity of Schlapp's coupled equations has meant that traditionally they have had to be solved numerically by Newton iterations which makes error propagation difficult. The former challenge has been this year solved by Le Roy with a modification of Hutson's perturbation theory of, and the latter problem has now been solved by symbolic computing software that solves Schlapp's coupled non-linear equations analytically for the first time since their introduction in 1937. M. Semczuk, X. Li, W. Gunton, M. Haw, N. Dattani, J. Witz, A. Mills, D. Jones, K. Madison, Physical Review A {87}, XX (2013) H. Kramers, Zeitschrift fur Physik {53}, 422 (1929) R. Schlapp, Physical Review {51}, 342 (1937) J. Hutson, J. Phys. B, {14}, 851 (1981)
ERIC Educational Resources Information Center
Agboghoroma, Tim E.; Oyovwi, E. O.
2015-01-01
This study evaluated the effect of students' academic achievement on identified difficult concepts or topics in Senior Secondary School Biology in Delta State, Nigeria. The study was quasi-experimental and the design was a 2X2 factorial non-randomized pretest-posttest control group design. The sample was drawn from intact classes from four…
Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu; Berbeco, Ross; Chithrani, Devika B.
2016-01-01
The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translationmore » of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.« less
NASA Astrophysics Data System (ADS)
Mehmood, Faisal; Pachter, Ruth; Murphy, Neil R.; Johnson, Walter E.
2015-11-01
Prediction of the frequency-dependent dielectric function of thin films poses computational challenges, and at the same time experimental characterization by spectroscopic ellipsometry remains difficult to interpret because of changes in stoichiometry and surface morphology, temperature, thickness of the film, or substrate. In this work, we report calculations for titanium nitride (TiN), a promising material for plasmonic applications because of less loss and other practical advantages compared to noble metals. We investigated structural, electronic, and optical properties of stoichiometric bulk TiN, as well as of the TiN(100), TiN(110), and TiN(111) outermost surfaces. Density functional theory (DFT) and many-body GW methods (Green's (G) function-based approximation with screened Coulomb interaction (W)) were used, ranging from G0W0, GW0 to partially self-consistent sc-GW0, as well as the GW-BSE (Bethe-Salpeter equation) and time-dependent DFT (TDDFT) methods for prediction of the optical properties. Structural parameters and the band structure for bulk TiN were shown to be consistent with previous work. Calculated dielectric functions, plasma frequencies, reflectivity, and the electron energy loss spectrum demonstrated consistency with experiment at the GW0-BSE level. Deviations from experimental data are expected due to varying experimental conditions. Comparison of our results to spectroscopic ellipsometry data for realistic nanostructures has shown that although TDDFT may provide a computationally feasible level of theory in evaluation of the dielectric function, application is subject to validation with GW-BSE calculations.
Modeling sediment transport after ditch network maintenance of a forested peatland
NASA Astrophysics Data System (ADS)
Haahti, K.; Marttila, H.; Warsta, L.; Kokkonen, T.; Finér, L.; Koivusalo, H.
2016-11-01
Elevated suspended sediment (SS) loads released from peatlands after drainage operations and the resulting negative effect on the ecological status of the receiving water bodies have been widely recognized. Understanding the processes controlling erosion and sediment transport within the ditch network forms a prerequisite for adequate sediment control. While numerous experimental studies have been reported in this field, model based assessments are rare. This study presents a modeling approach to investigate sediment transport in a peatland ditch network. The transport model describes bed erosion, rain-induced bank erosion, floc deposition, and consolidation of the bed. Coupled to a distributed hydrological model, sediment transport was simulated in a 5.2 ha forestry-drained peatland catchment for 2 years after ditch cleaning. Comparing simulation results to measured SS concentrations suggested that the loose peat material, produced during excavation, contributed markedly to elevated SS concentrations immediately after ditch cleaning. Both snowmelt and summer rainstorms contributed critically to annual loads. Springtime peat erosion during snowmelt was driven by ditch flow whereas during summer rainfalls, bank erosion by raindrop impact was identified as an important process. Relating modeling results to observed spatial topographic changes in the ditch network was challenging and the results were difficult to verify. Nevertheless, the model has potential to identify risk areas for erosion. The results demonstrate that modeling is effective in separating the importance of different processes and complements pure experimental approaches. Modeling results can aid planning and designing efficient sediment control measures and guide the focus of experimental studies.
NASA Astrophysics Data System (ADS)
Gildfind, D. E.; Jacobs, P. A.; Morgan, R. G.; Chan, W. Y. K.; Gollan, R. J.
2018-07-01
Large-scale free-piston driven expansion tubes have uniquely high total pressure capabilities which make them an important resource for development of access-to-space scramjet engine technology. However, many aspects of their operation are complex, and their test flows are fundamentally unsteady and difficult to measure. While computational fluid dynamics methods provide an important tool for quantifying these flows, these calculations become very expensive with increasing facility size and therefore have to be carefully constructed to ensure sufficient accuracy is achieved within feasible computational times. This study examines modelling strategies for a Mach 10 scramjet test condition developed for The University of Queensland's X3 facility. The present paper outlines the challenges associated with test flow reconstruction, describes the experimental set-up for the X3 experiments, and then details the development of an experimentally tuned quasi-one-dimensional CFD model of the full facility. The 1-D model, which accurately captures longitudinal wave processes, is used to calculate the transient flow history in the shock tube. This becomes the inflow to a higher-fidelity 2-D axisymmetric simulation of the downstream facility, detailed in the Part 2 companion paper, leading to a validated, fully defined nozzle exit test flow.
A prior-based integrative framework for functional transcriptional regulatory network inference
Siahpirani, Alireza F.
2017-01-01
Abstract Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization. PMID:27794550
NASA Astrophysics Data System (ADS)
Yazji, S.; Swinkels, M. Y.; De Luca, M.; Hoffmann, E. A.; Ercolani, D.; Roddaro, S.; Abstreiter, G.; Sorba, L.; Bakkers, E. P. A. M.; Zardo, I.
2016-06-01
The peculiar shape and dimensions of nanowires (NWs) have opened the way to their exploitation in thermoelectric applications. In general, the parameters entering into the thermoelectric figure of merit are strongly interdependent, which makes it difficult to realize an optimal thermoelectric material. In NWs, instead, the power factor can be increased and the thermal conductivity reduced, thus boosting the thermoelectric efficiency compared to bulk materials. However, the assessment of all the thermoelectric properties of a NW is experimentally very challenging. Here, we focus on InSb NWs, which have proved to be promising thermoelectric materials. The figure of merit is accurately determined by using a novel method based on a combination of Raman spectroscopy and electrical measurements. Remarkably, this type of experiment provides a powerful approach allowing us to neglect the role played by thermal contact resistance. Furthermore, we compare the thermal conductivity determined by this novel method to the one determined on the same sample by the thermal bridge method. In this latter approach, the thermal contact resistance is a non-negligible parameter, especially in NWs with large diameters. We provide experimental evidence of the crucial role played by thermal contact resistance in the assessment of the thermal properties of nanostructures, using two different measurement methods of the thermal conductivity.
NASA Astrophysics Data System (ADS)
Gildfind, D. E.; Jacobs, P. A.; Morgan, R. G.; Chan, W. Y. K.; Gollan, R. J.
2017-11-01
Large-scale free-piston driven expansion tubes have uniquely high total pressure capabilities which make them an important resource for development of access-to-space scramjet engine technology. However, many aspects of their operation are complex, and their test flows are fundamentally unsteady and difficult to measure. While computational fluid dynamics methods provide an important tool for quantifying these flows, these calculations become very expensive with increasing facility size and therefore have to be carefully constructed to ensure sufficient accuracy is achieved within feasible computational times. This study examines modelling strategies for a Mach 10 scramjet test condition developed for The University of Queensland's X3 facility. The present paper outlines the challenges associated with test flow reconstruction, describes the experimental set-up for the X3 experiments, and then details the development of an experimentally tuned quasi-one-dimensional CFD model of the full facility. The 1-D model, which accurately captures longitudinal wave processes, is used to calculate the transient flow history in the shock tube. This becomes the inflow to a higher-fidelity 2-D axisymmetric simulation of the downstream facility, detailed in the Part 2 companion paper, leading to a validated, fully defined nozzle exit test flow.
Multiscale approach to the determination of the photoactive yellow protein signaling state ensemble.
A Rohrdanz, Mary; Zheng, Wenwei; Lambeth, Bradley; Vreede, Jocelyne; Clementi, Cecilia
2014-10-01
The nature of the optical cycle of photoactive yellow protein (PYP) makes its elucidation challenging for both experiment and theory. The long transition times render conventional simulation methods ineffective, and yet the short signaling-state lifetime makes experimental data difficult to obtain and interpret. Here, through an innovative combination of computational methods, a prediction and analysis of the biological signaling state of PYP is presented. Coarse-grained modeling and locally scaled diffusion map are first used to obtain a rough bird's-eye view of the free energy landscape of photo-activated PYP. Then all-atom reconstruction, followed by an enhanced sampling scheme; diffusion map-directed-molecular dynamics are used to focus in on the signaling-state region of configuration space and obtain an ensemble of signaling state structures. To the best of our knowledge, this is the first time an all-atom reconstruction from a coarse grained model has been performed in a relatively unexplored region of molecular configuration space. We compare our signaling state prediction with previous computational and more recent experimental results, and the comparison is favorable, which validates the method presented. This approach provides additional insight to understand the PYP photo cycle, and can be applied to other systems for which more direct methods are impractical.
Nair, Ajay K; Sasidharan, Arun; John, John P; Mehrotra, Seema; Kutty, Bindu M
2016-01-01
The present study describes the development of a neurocognitive paradigm: "Assessing Neurocognition via Gamified Experimental Logic" (ANGEL), for performing the parametric evaluation of multiple neurocognitive functions simultaneously. ANGEL employs an audiovisual sensory motor design for the acquisition of multiple event related potentials (ERPs)-the C1, P50, MMN, N1, N170, P2, N2pc, LRP, P300, and ERN. The ANGEL paradigm allows assessment of 10 neurocognitive variables over the course of three "game" levels of increasing complexity ranging from simple passive observation to complex discrimination and response in the presence of multiple distractors. The paradigm allows assessment of several levels of rapid decision making: speeded up response vs. response-inhibition; responses to easy vs. difficult tasks; responses based on gestalt perception of clear vs. ambiguous stimuli; and finally, responses with set shifting during challenging tasks. The paradigm has been tested using 18 healthy participants from both sexes and the possibilities of varied data analyses have been presented in this paper. The ANGEL approach provides an ecologically valid assessment (as compared to existing tools) that quickly yields a very rich dataset and helps to assess multiple ERPs that can be studied extensively to assess cognitive functions in health and disease conditions.
Nair, Ajay K.; Sasidharan, Arun; John, John P.; Mehrotra, Seema; Kutty, Bindu M.
2016-01-01
The present study describes the development of a neurocognitive paradigm: “Assessing Neurocognition via Gamified Experimental Logic” (ANGEL), for performing the parametric evaluation of multiple neurocognitive functions simultaneously. ANGEL employs an audiovisual sensory motor design for the acquisition of multiple event related potentials (ERPs)—the C1, P50, MMN, N1, N170, P2, N2pc, LRP, P300, and ERN. The ANGEL paradigm allows assessment of 10 neurocognitive variables over the course of three “game” levels of increasing complexity ranging from simple passive observation to complex discrimination and response in the presence of multiple distractors. The paradigm allows assessment of several levels of rapid decision making: speeded up response vs. response-inhibition; responses to easy vs. difficult tasks; responses based on gestalt perception of clear vs. ambiguous stimuli; and finally, responses with set shifting during challenging tasks. The paradigm has been tested using 18 healthy participants from both sexes and the possibilities of varied data analyses have been presented in this paper. The ANGEL approach provides an ecologically valid assessment (as compared to existing tools) that quickly yields a very rich dataset and helps to assess multiple ERPs that can be studied extensively to assess cognitive functions in health and disease conditions. PMID:26858586
Carroll, Sean Michael; Chubiz, Lon M.; Agashe, Deepa; Marx, Christopher J.
2015-01-01
Bioengineering holds great promise to provide fast and efficient biocatalysts for methanol-based biotechnology, but necessitates proven methods to optimize physiology in engineered strains. Here, we highlight experimental evolution as an effective means for optimizing an engineered Methylobacterium extorquens AM1. Replacement of the native formaldehyde oxidation pathway with a functional analog substantially decreased growth in an engineered Methylobacterium, but growth rapidly recovered after six hundred generations of evolution on methanol. We used whole-genome sequencing to identify the basis of adaptation in eight replicate evolved strains, and examined genomic changes in light of other growth and physiological data. We observed great variety in the numbers and types of mutations that occurred, including instances of parallel mutations at targets that may have been “rationalized” by the bioengineer, plus other “illogical” mutations that demonstrate the ability of evolution to expose unforeseen optimization solutions. Notably, we investigated mutations to RNA polymerase, which provided a massive growth benefit but are linked to highly aberrant transcriptional profiles. Overall, we highlight the power of experimental evolution to present genetic and physiological solutions for strain optimization, particularly in systems where the challenges of engineering are too many or too difficult to overcome via traditional engineering methods. PMID:27682084
Data communication through multiple physical media: applications to munitions
NASA Astrophysics Data System (ADS)
Dhadwal, Harbans S.; Rastegar, Jahangir; Feng, Dake; Kwok, Philip
2015-05-01
Electronic systems comprising of subassemblies, distributed across different physical media, require seamless communication between processors and sensors embedded in the disparate volumes. For example, smart munitions systems embed sensors and other key control electronics, throughout the structure, in vastly different physical media. In addition to the obvious space constraints, these structures are subjected to high G forces during launch. Thus, communications through wire harnesses becomes cumbersome, make assembly process and testing difficult, and challenging to make survive high G firing. Here we focus on an approach that takes advantage of the partial optical transparency of epoxy material commonly used in potting electronic components in munitions, as well as the wave guiding that is possible through the body of the munitions wall which is made from composite materials. Experimental results show that a wireless optical link, connecting various parts of the distributed system, is possible at near IR frequencies. Data can be rapidly parsed between a processor, sensors and actuators. We present experimental data for a commercial epoxy system, which is used to embed a number of IrDA devices inside the cone of 120 mm mortar shell. IrDA devices using the FIR data rates establish point-to-point communication through various media, representative of the environment inside the 120 mm mortar cone.
Arora, Sanjeevani; Huwe, Peter J.; Sikder, Rahmat; Shah, Manali; Browne, Amanda J.; Lesh, Randy; Nicolas, Emmanuelle; Deshpande, Sanat; Hall, Michael J.; Dunbrack, Roland L.; Golemis, Erica A.
2017-01-01
ABSTRACT The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major challenge for clinical diagnosis of LS is the frequent identification of variants of uncertain significance (VUS) in these genes, as it is often difficult to determine variant pathogenicity, particularly for missense variants. Generic programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON-MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS in MMR genes. We evaluated the performance of multiple predictive programs in the context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using cell line models, we characterized VUS predicted to range from neutral to pathogenic on mRNA and protein expression, basal cellular viability, viability following treatment with a panel of DNA-damaging agents, and functionality in DNA damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our results suggest that the MMR gene-specific classifiers do not always align with the experimental phenotypes related to DDR. Our study highlights the importance of complementary experimental and computational assessment to develop future predictors for the assessment of VUS. PMID:28494185
Molecular mechanisms of system responses to novel stimuli are predictable from public data
Danziger, Samuel A.; Ratushny, Alexander V.; Smith, Jennifer J.; Saleem, Ramsey A.; Wan, Yakun; Arens, Christina E.; Armstrong, Abraham M.; Sitko, Katherine; Chen, Wei-Ming; Chiang, Jung-Hsien; Reiss, David J.; Baliga, Nitin S.; Aitchison, John D.
2014-01-01
Systems scale models provide the foundation for an effective iterative cycle between hypothesis generation, experiment and model refinement. Such models also enable predictions facilitating the understanding of biological complexity and the control of biological systems. Here, we demonstrate the reconstruction of a globally predictive gene regulatory model from public data: a model that can drive rational experiment design and reveal new regulatory mechanisms underlying responses to novel environments. Specifically, using ∼1500 publically available genome-wide transcriptome data sets from Saccharomyces cerevisiae, we have reconstructed an environment and gene regulatory influence network that accurately predicts regulatory mechanisms and gene expression changes on exposure of cells to completely novel environments. Focusing on transcriptional networks that induce peroxisomes biogenesis, the model-guided experiments allow us to expand a core regulatory network to include novel transcriptional influences and linkage across signaling and transcription. Thus, the approach and model provides a multi-scalar picture of gene dynamics and are powerful resources for exploiting extant data to rationally guide experimentation. The techniques outlined here are generally applicable to any biological system, which is especially important when experimental systems are challenging and samples are difficult and expensive to obtain—a common problem in laboratory animal and human studies. PMID:24185701
Genzen, Jonathan R.; Kenney, Barton
2009-01-01
Aspergillus terreus was identified in an intra-dural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid (CSF) was non-diagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case. PMID:19717262
ERIC Educational Resources Information Center
Craig-Oldsen, Heather; Craig, J. Ann; Morton, Thomas
2006-01-01
Foster parents have increasingly assumed new and challenging roles during the past decade. Meeting the developmental, attachment, and grieving needs of children and youth in out of home care is challenging by itself, but can become even more difficult with the issues that arise when the child is lesbian, gay, bisexual, transgender, or questioning…
Service Approaches to Young People with Complex Needs Leaving Out-of-Home Care
ERIC Educational Resources Information Center
Malvaso, Catia; Delfabbro, Paul; Hackett, Louisa; Mills, Hayley
2016-01-01
Although leaving statutory out-of-home care can be a challenging time for many young people, it is recognised that young people who have multiple or complex needs find this transition particularly difficult. This study aims to gain a deeper understanding of the challenges faced by care leavers who have complex needs, as well as to identify some of…
Challenges in Computational Social Modeling and Simulation for National Security Decision Making
2011-06-01
This study is grounded within a system-activity theory , a logico-philosophical model of interdisciplinary research [13, 14], the concepts of social...often a difficult challenge. Ironically, social science research methods , such as ethnography , may be tremendously helpful in designing these...social sciences. Moreover, CSS projects draw on knowledge and methods from other fields of study , including graph theory , information visualization
"Did You Pay Your Taxes?" How (Not) to Conduct Tax Evasion Surveys in Transition Countries
ERIC Educational Resources Information Center
Gerxhani, Klarita
2007-01-01
Gathering large-scale data on tax evasion is an undisputable challenge in and of itself. Doing so in a country in transition from a communist to a democratic system is even more difficult. This paper discusses the challenges and presents a case study to show how they can be dealt with effectively. One important implication of the paper is that…
Nanotechnology: Its Promise and Challenges
DOE Office of Scientific and Technical Information (OSTI.GOV)
Colvin, Vicki
2009-05-14
Vicki Colvin of Rice University talks about how nanotechnology-enabled systems, with dimensions on the scale of a billionth of a meter, offer great promise for solving difficult social problems and creating enormous possibilities.
Rosetta Structure Prediction as a Tool for Solving Difficult Molecular Replacement Problems.
DiMaio, Frank
2017-01-01
Molecular replacement (MR), a method for solving the crystallographic phase problem using phases derived from a model of the target structure, has proven extremely valuable, accounting for the vast majority of structures solved by X-ray crystallography. However, when the resolution of data is low, or the starting model is very dissimilar to the target protein, solving structures via molecular replacement may be very challenging. In recent years, protein structure prediction methodology has emerged as a powerful tool in model building and model refinement for difficult molecular replacement problems. This chapter describes some of the tools available in Rosetta for model building and model refinement specifically geared toward difficult molecular replacement cases.
EPA is a government leader in tapping the power of contributions from the public to help solve difficult problems that affect the environment and public health. Prize competitions allow federal agencies to pay only for successful solutions.
SRTM Stereo Pair with Landsat Overlay: Los Angeles to San Joaquin Valley, California
2000-09-21
California topography poses challenges for road builders. Northwest of Los Angeles, deformation of Earth crust along the Pacific-North American crustal plate boundary has made transportation difficult.
Where systems biology meets postharvest
USDA-ARS?s Scientific Manuscript database
Interpreting fruit metabolism, particularly tree fruit metabolism, presents unique challenges. Long periods from tree establishment to fruiting render techniques directed towards reducing the complexity of metabolic mechanisms, such as genomic modification, relatively difficult. Consequently, holi...
Mergers and acquisitions in professional organizations: a complex adaptive systems approach.
Walls, M E; McDaniel, R R
1999-09-01
Nurse managers face unique challenges as they cope with mergers and acquisitions among health care organizations. These challenges can be better understood if it is recognized that health care institutions are professional organizations and that the transformations required are extremely difficult. These difficulties are caused, in part, by the institutionalized nature of professional organizations, and this nature is explicated. Professional organizations are stubborn. They are repositories of expertise and values that are societal in origin and difficult to change. When professional organizations are understood as complex adaptive systems, complexity theory offers insight that provide strategies for managing mergers and acquisitions that may not be apparent when more traditional conceptualizations of professional organizations are used. Specific managerial techniques consistent with both the institutionalized characteristics and the complex adaptive systems characteristics of professional organizations are offered to nurse managers.
Bubble coalescence in a Newtonian fluid
NASA Astrophysics Data System (ADS)
Garg, Vishrut; Basaran, Osman
2017-11-01
Bubble coalescence plays a central role in the hydrodynamics of gas-liquid systems such as bubble column reactors, spargers, and foams. Two bubbles approaching each other at velocity V coalesce when the thin film between them ruptures, which is often the rate-limiting step. Experimental studies of this system are difficult, and recent works provide conflicting results on the effect of V on coalescence times. We simulate the head-on approach of two bubbles of equal radii R in an incompressible Newtonian fluid (density ρ, viscosity μ, and surface tension σ) by solving numerically the free boundary problem comprised of the Navier Stokes and continuity equations. Simulations are made challenging by the existence of highly disparate lengthscales, i.e. film thickness and drop radii, which are resolved by using the method of elliptic mesh generation. For a given liquid, the bubbles are shown to coalesce for all velocities below a critical value. The effects of Ohnesorge number Oh = μ /√{ ρσR } on coalescence time and critical velocity are also investigated.
Where in the world are my field plots? Using GPS effectively in environmental field studies
Johnson, Chris E.; Barton, Christopher C.
2004-01-01
Global positioning system (GPS) technology is rapidly replacing tape, compass, and traditional surveying instruments as the preferred tool for estimating the positions of environmental research sites. One important problem, however, is that it can be difficult to estimate the uncertainty of GPS-derived positions. Sources of error include various satellite- and site-related factors, such as forest canopy and topographic obstructions. In a case study from the Hubbard Brook Experimental Forest in New Hampshire, hand-held, mapping-grade GPS receivers generally estimated positions with 1–5 m precision in open, unobstructed settings, and 20–30 m precision under forest canopy. Surveying-grade receivers achieved precisions of 10 cm or less, even in challenging terrain. Users can maximize the quality of their GPS measurements by “mission planning” to take advantage of high-quality satellite conditions. Repeated measurements and simultaneous data collection at multiple points can be used to assess accuracy and precision.
Thomas, Thaddeus P.; Anderson, Donald D.; Willis, Andrew R.; Liu, Pengcheng; Frank, Matthew C.; Marsh, J. Lawrence; Brown, Thomas D.
2011-01-01
Reconstructing highly comminuted articular fractures poses a difficult surgical challenge, akin to solving a complicated three-dimensional (3D) puzzle. Pre-operative planning using CT is critically important, given the desirability of less invasive surgical approaches. The goal of this work is to advance 3D puzzle solving methods toward use as a pre-operative tool for reconstructing these complex fractures. Methodology for generating typical fragmentation/dispersal patterns was developed. Five identical replicas of human distal tibia anatomy, were machined from blocks of high-density polyetherurethane foam (bone fragmentation surrogate), and were fractured using an instrumented drop tower. Pre- and post-fracture geometries were obtained using laser scans and CT. A semi-automatic virtual reconstruction computer program aligned fragment native (non-fracture) surfaces to a pre-fracture template. The tibias were precisely reconstructed with alignment accuracies ranging from 0.03-0.4mm. This novel technology has potential to significantly enhance surgical techniques for reconstructing comminuted intra-articular fractures, as illustrated for a representative clinical case. PMID:20924863
Evidence for teaching practice: the impact of clickers in a large classroom environment.
Patterson, Barbara; Kilpatrick, Judith; Woebkenberg, Eric
2010-10-01
As the number of nursing students increases, the ability to actively engage all students in a large classroom is challenging and increasingly difficult. Clickers, or student response systems (SRS), are a relatively new technology in nursing education that use wireless technology and enable students to select individual responses to questions posed to them during class. The study design was a quasi-experimental comparison with one section of an adult medical-surgical course using the SRS and one receiving standard teaching. No significant differences between groups on any measure of performance were found. Focus groups were conducted to describe student perceptions of SRS. Three themes emerged: Being able to respond anonymously, validating an answer while providing immediate feedback, and providing an interactive and engaging environment. Although the clickers did not improve learning outcomes as measured by objective testing, perceptions shared by students indicated an increased degree of classroom engagement. Future research needs to examine other potential outcome variables. Copyright © 2009 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Po, Hoi Chun; Zhou, Qi
2015-08-01
Bosons have a natural instinct to condense at zero temperature. It is a long-standing challenge to create a high-dimensional quantum liquid that does not exhibit long-range order at the ground state, as either extreme experimental parameters or sophisticated designs of microscopic Hamiltonians are required for suppressing the condensation. Here we show that synthetic gauge fields for ultracold atoms, using either the Raman scheme or shaken lattices, provide physicists a simple and practical scheme to produce a two-dimensional algebraic quantum liquid at the ground state. This quantum liquid arises at a critical Lifshitz point, where a two-dimensional quartic dispersion emerges in the momentum space, and many fundamental properties of two-dimensional bosons are changed in its proximity. Such an ideal simulator of the quantum Lifshitz model allows experimentalists to directly visualize and explore the deconfinement transition of topological excitations, an intriguing phenomenon that is difficult to access in other systems.
Faure, Emmanuel; Savy, Thierry; Rizzi, Barbara; Melani, Camilo; Stašová, Olga; Fabrèges, Dimitri; Špir, Róbert; Hammons, Mark; Čúnderlík, Róbert; Recher, Gaëlle; Lombardot, Benoît; Duloquin, Louise; Colin, Ingrid; Kollár, Jozef; Desnoulez, Sophie; Affaticati, Pierre; Maury, Benoît; Boyreau, Adeline; Nief, Jean-Yves; Calvat, Pascal; Vernier, Philippe; Frain, Monique; Lutfalla, Georges; Kergosien, Yannick; Suret, Pierre; Remešíková, Mariana; Doursat, René; Sarti, Alessandro; Mikula, Karol; Peyriéras, Nadine; Bourgine, Paul
2016-01-01
The quantitative and systematic analysis of embryonic cell dynamics from in vivo 3D+time image data sets is a major challenge at the forefront of developmental biology. Despite recent breakthroughs in the microscopy imaging of living systems, producing an accurate cell lineage tree for any developing organism remains a difficult task. We present here the BioEmergences workflow integrating all reconstruction steps from image acquisition and processing to the interactive visualization of reconstructed data. Original mathematical methods and algorithms underlie image filtering, nucleus centre detection, nucleus and membrane segmentation, and cell tracking. They are demonstrated on zebrafish, ascidian and sea urchin embryos with stained nuclei and membranes. Subsequent validation and annotations are carried out using Mov-IT, a custom-made graphical interface. Compared with eight other software tools, our workflow achieved the best lineage score. Delivered in standalone or web service mode, BioEmergences and Mov-IT offer a unique set of tools for in silico experimental embryology. PMID:26912388
Matsuzaki, Ryosuke; Tachikawa, Takeshi; Ishizuka, Junya
2018-03-01
Accurate simulations of carbon fiber-reinforced plastic (CFRP) molding are vital for the development of high-quality products. However, such simulations are challenging and previous attempts to improve the accuracy of simulations by incorporating the data acquired from mold monitoring have not been completely successful. Therefore, in the present study, we developed a method to accurately predict various CFRP thermoset molding characteristics based on data assimilation, a process that combines theoretical and experimental values. The degree of cure as well as temperature and thermal conductivity distributions during the molding process were estimated using both temperature data and numerical simulations. An initial numerical experiment demonstrated that the internal mold state could be determined solely from the surface temperature values. A subsequent numerical experiment to validate this method showed that estimations based on surface temperatures were highly accurate in the case of degree of cure and internal temperature, although predictions of thermal conductivity were more difficult.
NASA Astrophysics Data System (ADS)
Sakib, M. S.; Rahman, Motiur; Ferdous, M.; Dhar, N. R.
2017-12-01
Polymer Matrix Composites are extending a wide range of applications in aviation in recent eras because of their better economics, well established processing, high temperature properties, high resistance to corrosion and fatigue. Directional properties of composites are dependent on the fibre orientation. Composites being anisotropic in nature are difficult to drill and machining and tooling of the composites remained a great challenge over time. This paper addresses the issues of various machining problems such as delamination, fibre pull-out, cracks on varying drilling parameters like feed rate and drilling speed. Experimental drilling was carried out on Fibre Reinforced Plastic composites with HSS drill bit. Results reveal that as the number of holes increases the entry and exit diameter and tapper of holes vary and also varying composite thickness results in a difference in hole roundness and tapper. This experiment summarizes that for achieving acceptable tool life and hole quality demands a drill designed with composites.
Solenoid for Laser Induced Plasma Experiments at Janus
NASA Astrophysics Data System (ADS)
Klein, Sallee; Leferve, Heath; Kemp, Gregory; Mariscal, Derek; Rasmus, Alex; Williams, Jackson; Gillespie, Robb; Manuel, Mario; Kuranz, Carolyn; Keiter, Paul; Drake, R.
2017-10-01
Creating invariant magnetic fields for experiments involving laser induced plasmas is particularly challenging due to the high voltages at which the solenoid must be pulsed. Creating a solenoid resilient enough to survive through large numbers of voltage discharges, enabling it to endure a campaign lasting several weeks, is exceptionally difficult. Here we present a solenoid that is robust through 40 μs pulses at a 13 kV potential. This solenoid is a vast improvement over our previously fielded designs in peak magnetic field capabilities and robustness. Designed to be operated at small-scale laser facilities, the solenoid housing allows for versatility of experimental set-ups among diagnostic and target positions. Within the perpendicular field axis at the center there is 300 degrees of clearance which can be easily modified to meet the needs of a specific experiment, as well as an f/3 cone for transmitted or backscattered light. After initial design efforts, these solenoids are relatively inexpensive to manufacture.
Gregg, Robert D; Lenzi, Tommaso; Hargrove, Levi J; Sensinger, Jonathon W
2014-12-01
Recent powered (or robotic) prosthetic legs independently control different joints and time periods of the gait cycle, resulting in control parameters and switching rules that can be difficult to tune by clinicians. This challenge might be addressed by a unifying control model used by recent bipedal robots, in which virtual constraints define joint patterns as functions of a monotonic variable that continuously represents the gait cycle phase. In the first application of virtual constraints to amputee locomotion, this paper derives exact and approximate control laws for a partial feedback linearization to enforce virtual constraints on a prosthetic leg. We then encode a human-inspired invariance property called effective shape into virtual constraints for the stance period. After simulating the robustness of the partial feedback linearization to clinically meaningful conditions, we experimentally implement this control strategy on a powered transfemoral leg. We report the results of three amputee subjects walking overground and at variable cadences on a treadmill, demonstrating the clinical viability of this novel control approach.
Schein, Perry; Ashcroft, Colby K; O'Dell, Dakota; Adam, Ian S; DiPaolo, Brian; Sabharwal, Manit; Shi, Ce; Hart, Robert; Earhart, Christopher; Erickson, David
2015-08-15
Nanoparticles are quickly becoming commonplace in many commercial and industrial products, ranging from cosmetics to pharmaceuticals to medical diagnostics. Predicting the stability of the engineered nanoparticles within these products a priori remains an important and difficult challenge. Here we describe our techniques for measuring the mechanical interactions between nanoparticles and surfaces using near-field light scattering. Particle-surface interfacial forces are measured by optically "pushing" a particle against a reference surface and observing its motion using scattered near-field light. Unlike atomic force microscopy, this technique is not limited by thermal noise, but instead takes advantage of it. The integrated waveguide and microfluidic architecture allow for high-throughput measurements of about 1000 particles per hour. We characterize the reproducibility of and experimental uncertainty in the measurements made using the NanoTweezer surface instrument. We report surface interaction studies on gold nanoparticles with 50 nm diameters, smaller than previously reported in the literature using similar techniques.
Super Spy variants implicate flexibility in chaperone action.
Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl At; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James Ca
2014-01-01
Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These "Super Spy" variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001.
Super Spy variants implicate flexibility in chaperone action
Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl AT; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James CA
2014-01-01
Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These “Super Spy” variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001 PMID:24497545
Speedy routing recovery protocol for large failure tolerance in wireless sensor networks.
Lee, Joa-Hyoung; Jung, In-Bum
2010-01-01
Wireless sensor networks are expected to play an increasingly important role in data collection in hazardous areas. However, the physical fragility of a sensor node makes reliable routing in hazardous areas a challenging problem. Because several sensor nodes in a hazardous area could be damaged simultaneously, the network should be able to recover routing after node failures over large areas. Many routing protocols take single-node failure recovery into account, but it is difficult for these protocols to recover the routing after large-scale failures. In this paper, we propose a routing protocol, referred to as ARF (Adaptive routing protocol for fast Recovery from large-scale Failure), to recover a network quickly after failures over large areas. ARF detects failures by counting the packet losses from parent nodes, and upon failure detection, it decreases the routing interval to notify the neighbor nodes of the failure. Our experimental results indicate that ARF could provide recovery from large-area failures quickly with less packets and energy consumption than previous protocols.
Single shot imaging through turbid medium and around corner using coherent light
NASA Astrophysics Data System (ADS)
Li, Guowei; Li, Dayan; Situ, Guohai
2018-01-01
Optical imaging through turbid media and around corner is a difficult challenge. Even a very thin layer of a turbid media, which randomly scatters the probe light, can appear opaque and hide any objects behind it. Despite many recent advances, no current method can image the object behind turbid media with single record using coherent laser illumination. Here we report a method that allows non-invasive single-shot optical imaging through turbid media and around corner via speckle correlation. Instead of being as an obstacle in forming diffractionlimited images, speckle actually can be a carrier that encodes sufficient information to imaging through visually opaque layers. Optical imaging through turbid media and around corner is experimentally demonstrated using traditional imaging system with the aid of iterative phase retrieval algorithm. Our method require neither scan of illumination nor two-arm interferometry or long-time exposure in acquisition, which has new implications in optical sensing through common obscurants such as fog, smoke and haze.
Lenzi, Tommaso; Hargrove, Levi J.; Sensinger, Jonathon W.
2014-01-01
Recent powered (or robotic) prosthetic legs independently control different joints and time periods of the gait cycle, resulting in control parameters and switching rules that can be difficult to tune by clinicians. This challenge might be addressed by a unifying control model used by recent bipedal robots, in which virtual constraints define joint patterns as functions of a monotonic variable that continuously represents the gait cycle phase. In the first application of virtual constraints to amputee locomotion, this paper derives exact and approximate control laws for a partial feedback linearization to enforce virtual constraints on a prosthetic leg. We then encode a human-inspired invariance property called effective shape into virtual constraints for the stance period. After simulating the robustness of the partial feedback linearization to clinically meaningful conditions, we experimentally implement this control strategy on a powered transfemoral leg. We report the results of three amputee subjects walking overground and at variable cadences on a treadmill, demonstrating the clinical viability of this novel control approach. PMID:25558185
Klemuk, Sarah A; Jaiswal, Sanyukta; Titze, Ingo R
2008-10-01
Effects of vibration on human vocal fold extracellular matrix composition and the resultant tissue viscoelastic properties are difficult to study in vivo. Therefore, an in vitro bioreactor, simulating the in vivo physiological environment, was explored. A stress-controlled commercial rheometer was used to administer shear vibrations to living tissues at stresses and frequencies corresponding to male phonation, while simultaneously measuring tissue viscoelastic properties. Tissue environment was evaluated and adjustments made in order to sustain cell life for short term experimentation up to 6 h. Cell nutrient medium evaporation, osmolality, pH, and cell viability of cells cultured in three-dimensional synthetic scaffolds were quantified under comparably challenging environments to the rheometer bioreactor for 4 or 6 h. The functionality of the rheometer bioreactor was demonstrated by applying three vibration regimes to cell-seeded three-dimensional substrates for 2 h. Resulting strain was quantified throughout the test period. Rheologic data and cell viability are reported for each condition, and future improvements are discussed.
Black, Carolyn; Tesfaigzi, Yohannes; Bassein, Jed A; Miller, Lisa A
2017-10-01
Understanding the effect of wildfire smoke exposure on human health represents a unique interdisciplinary challenge to the scientific community. Population health studies indicate that wildfire smoke is a risk to human health and increases the healthcare burden of smoke-impacted areas. However, wildfire smoke composition is complex and dynamic, making characterization and modeling difficult. Furthermore, current efforts to study the effect of wildfire smoke are limited by availability of air quality measures and inconsistent air quality reporting among researchers. To help address these issues, we conducted a substantive review of wildfire smoke effects on population health, wildfire smoke exposure in occupational health, and experimental wood smoke exposure. Our goal was to evaluate the current literature on wildfire smoke and highlight important gaps in research. In particular we emphasize long-term health effects of wildfire smoke, recovery following wildfire smoke exposure, and health consequences of exposure in children. Copyright © 2017 Elsevier B.V. All rights reserved.
Road Lane Detection Robust to Shadows Based on a Fuzzy System Using a Visible Light Camera Sensor.
Hoang, Toan Minh; Baek, Na Rae; Cho, Se Woon; Kim, Ki Wan; Park, Kang Ryoung
2017-10-28
Recently, autonomous vehicles, particularly self-driving cars, have received significant attention owing to rapid advancements in sensor and computation technologies. In addition to traffic sign recognition, road lane detection is one of the most important factors used in lane departure warning systems and autonomous vehicles for maintaining the safety of semi-autonomous and fully autonomous systems. Unlike traffic signs, road lanes are easily damaged by both internal and external factors such as road quality, occlusion (traffic on the road), weather conditions, and illumination (shadows from objects such as cars, trees, and buildings). Obtaining clear road lane markings for recognition processing is a difficult challenge. Therefore, we propose a method to overcome various illumination problems, particularly severe shadows, by using fuzzy system and line segment detector algorithms to obtain better results for detecting road lanes by a visible light camera sensor. Experimental results from three open databases, Caltech dataset, Santiago Lanes dataset (SLD), and Road Marking dataset, showed that our method outperformed conventional lane detection methods.
Design Considerations for Developing Biodegradable Magnesium Implants
NASA Astrophysics Data System (ADS)
Brar, Harpreet S.; Keselowsky, Benjamin G.; Sarntinoranont, Malisa; Manuel, Michele V.
The integration of biodegradable and bioabsorbable magnesium implants into the human body is a complex undertaking that faces major challenges. The complexity arises from the fact that biomaterials must meet both engineering and physiological requirements to ensure the desired properties. Historically, efforts have been focused on the behavior of commercial magnesium alloys in biological environments and their resultant effect on cell-mediated processes. Developing causal relationships between alloy chemistry and micro structure, and its effect on cellular behavior can be a difficult and time intensive process. A systems design approach driven by thermodynamics has the power to provide significant contributions in developing the next generation of magnesium alloy implants with controlled degradability, biocompatibility, and optimized mechanical properties, at reduced time and cost. This approach couples experimental research with theory and mechanistic modeling for the accelerated development of materials. The aim of this article is to enumerate this strategy, design considerations and hurdles for developing new magnesium alloys for use as biodegradable implant materials [1].
Deformations of the gyroid and Lidinoid minimal surfaces using flat structures
NASA Astrophysics Data System (ADS)
Weyhaupt, Adam
2015-03-01
Mathematically, the challenge in proving the existence of a purported triply periodic minimal surface is in computing parameter values that depend on a system of equations defined by elliptic integrals. This is generally very difficult. In the presence of some symmetry, however, a technique developed by Weber and Wolf can reduce these elliptic integrals to basic algebra and geometry of polygons. These techniques can easily prove the existence of some surfaces and the presence of a family of solutions. Families of surfaces are important mathematically, but recent work by Seddon, et. al., experimentally confirms that these families of surfaces can occur physically as well. In this talk, we give a brief overview of the technique and show how it can be applied to prove the existence of several families of surfaces, including lower symmetry variants of the gyroid and Lidinoid such as the rG, rPD, tG, and rL. We also conjecture a map of the moduli space of triply periodic minimal surfaces of genus 3.
A few of our favorite unconfirmed ideas
2015-01-01
Medical practice is rooted in our dependence on the best available evidence from incremental scientific experimentation and rigorous clinical trials. Progress toward determining the true worth of ongoing practice or suggested innovations can be glacially slow when we insist on following the stepwise scientific pathway, and a prevailing but imperfect paradigm often proves difficult to challenge. Yet most experienced clinicians and clinical scientists harbor strong thoughts about how care could or should be improved, even if the existing evidence base is thin or lacking. One of our Future of Critical Care Medicine conference sessions encouraged sharing of novel ideas, each presented with what the speaker considers a defensible rationale. Our intent was to stimulate insightful thinking and free interchange, and perhaps to point in new directions toward lines of innovative theory and improved care of the critically ill. In what follows, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter. PMID:26728101
Nanoparticle Superlattices: The Roles of Soft Ligands
Si, Kae Jye; Chen, Yi; Shi, Qianqian
2017-01-01
Abstract Nanoparticle superlattices are periodic arrays of nanoscale inorganic building blocks including metal nanoparticles, quantum dots and magnetic nanoparticles. Such assemblies can exhibit exciting new collective properties different from those of individual nanoparticle or corresponding bulk materials. However, fabrication of nanoparticle superlattices is nontrivial because nanoparticles are notoriously difficult to manipulate due to complex nanoscale forces among them. An effective way to manipulate these nanoscale forces is to use soft ligands, which can prevent nanoparticles from disordered aggregation, fine‐tune the interparticle potential as well as program lattice structures and interparticle distances – the two key parameters governing superlattice properties. This article aims to review the up‐to‐date advances of superlattices from the viewpoint of soft ligands. We first describe the theories and design principles of soft‐ligand‐based approach and then thoroughly cover experimental techniques developed from soft ligands such as molecules, polymer and DNA. Finally, we discuss the remaining challenges and future perspectives in nanoparticle superlattices. PMID:29375958
Improved fuzzy clustering algorithms in segmentation of DC-enhanced breast MRI.
Kannan, S R; Ramathilagam, S; Devi, Pandiyarajan; Sathya, A
2012-02-01
Segmentation of medical images is a difficult and challenging problem due to poor image contrast and artifacts that result in missing or diffuse organ/tissue boundaries. Many researchers have applied various techniques however fuzzy c-means (FCM) based algorithms is more effective compared to other methods. The objective of this work is to develop some robust fuzzy clustering segmentation systems for effective segmentation of DCE - breast MRI. This paper obtains the robust fuzzy clustering algorithms by incorporating kernel methods, penalty terms, tolerance of the neighborhood attraction, additional entropy term and fuzzy parameters. The initial centers are obtained using initialization algorithm to reduce the computation complexity and running time of proposed algorithms. Experimental works on breast images show that the proposed algorithms are effective to improve the similarity measurement, to handle large amount of noise, to have better results in dealing the data corrupted by noise, and other artifacts. The clustering results of proposed methods are validated using Silhouette Method.
Ripple, Maureen O; Kim, Namjoon; Springett, Roger
2013-02-22
Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H(+)/2e(-)) but it has been suggested that stoichiometry may be 3H(+)/2e(-) based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD(+) and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc(1) complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H(+)/2e(-) in mouse and human cells at high and physiological proton motive force.
Rapid onset of decoherence in driven-dissipative Rydberg systems
NASA Astrophysics Data System (ADS)
Magnan, Eric; Boulier, Thomas; Bracamontes, Carlos; Maslek, James; Young, Jeremy; Gorshkov, Alexei; Porto, Trey; Rolston, Steven; JQI-Rubidium One Team
2017-04-01
Rydberg atoms have been strong candidates for the realization of quantum information processing and quantum simulation. Recently, however, there has been concerns about this approach due to the observation of a rapid onset of decoherence in large ensembles. In we provide experimental support for the hypothesis that this is due to the avalanche-like onset of exchange dipole interactions, fueled by blackbody transitions to nearby Rydberg states of opposite parity. Making a fully microscopic model has proven difficult as it requires beyond mean-field arguments, but the ubiquitousness of Rydberg-Rydberg blackbody transitions at room temperature and the always-resonant nature of dipole exchange interactions make it an interesting challenge, and argues for deeper study into the matter. In this poster, we present complementary measurements and analysis that confirm this mechanism. We also discuss several possibilities to reduce its impact on the system's coherence. This work was partially supported by NSF PIF, AFOSR, ARO, ARL-CDQI, and NSF PFC at JQI.
Alphabet soup: making sense of genetic testing in CMT.
Lawson, Victoria; Gharibshahi, Shahram
2010-09-01
The diagnosis of inherited neuropathies can be challenging in several ways. First, a hereditary neuropathy must be suspected. Although some family histories are clear with multiple members affected, other families require directed inquiry. Second, even when a hereditary neuropathy is clear, it can be difficult to make a genetic characterization. The field of genotyping is expanding so rapidly, it is difficult to know what tests to order. The authors share their guidelines for the diagnosis of inherited neuropathies. © Thieme Medical Publishers.
Experimental challenge of pregnant cattle with the putative abortifacient Waddlia chondrophila.
Wheelhouse, Nicholas; Flockhart, Allen; Aitchison, Kevin; Livingstone, Morag; Finlayson, Jeanie; Flachon, Virginie; Sellal, Eric; Dagleish, Mark P; Longbottom, David
2016-11-14
Waddlia chondrophila is a Gram-negative intracellular bacterial organism that is related to classical chlamydial species and has been implicated as a cause of abortion in cattle. Despite an increasing number of observational studies linking W. chondrophila infection to cattle abortion, little direct experimental evidence exists. Given this paucity of direct evidence the current study was carried out to investigate whether experimental challenge of pregnant cattle with W. chondrophila would result in infection and abortion. Nine pregnant Friesian-Holstein heifers received 2 × 10 8 inclusion forming units (IFU) W. chondrophila intravenously on day 105-110 of pregnancy, while four negative-control animals underwent mock challenge. Only one of the challenged animals showed pathogen-associated lesions, with the organism being detected in the diseased placenta. Importantly, the organism was re-isolated and its identity confirmed by whole genome sequencing, confirming Koch's third and fourth postulates. However, while infection of the placenta was observed, the experimental challenge in this study did not confirm the abortifacient potential of the organism.
ERIC Educational Resources Information Center
Hagen, Kenneth M.; Gutkin, Terry B.; Wilson, Caryll Palmer; Oats, Robert G.
1998-01-01
Investigates whether self-efficacy perceptions pertaining to working with difficult-to-teach children could be increased for preservice teachers using vicarious experience and verbal persuasion. Experimental group viewed a videotape demonstrating behavior management procedures while the control group viewed a placebo video. Experimental group…
Using Self-Experimentation and Single-Subject Methodology to Promote Critical Thinking
ERIC Educational Resources Information Center
Cowley, Brian J.; Lindgren, Ann; Langdon, David
2006-01-01
Critical thinking is often absent from classroom endeavor because it is hard to define (Gelder, 2005) or is difficult to assess (Bissell & Lemons, 2006). Critical thinking is defined as application, analysis, synthesis, and evaluation (Browne & Minnick, 2005). This paper shows how self-experimentation and single-subject methodology can be used to…
Presentation and Impact of Experimental Techniques in Chemistry
ERIC Educational Resources Information Center
Sojka, Zbigniew; Che, Michel
2008-01-01
Laboratory and practical courses, where students become familiar with experimental techniques and learn to interpret data and relate them to appropriate theory, play a vital role in chemical education. In the large panoply of currently available techniques, it is difficult to find a rational and easy way to classify the techniques in relation to…
NASA Astrophysics Data System (ADS)
Xing, Xi; Rey-de-Castro, Roberto; Rabitz, Herschel
2014-12-01
Optimally shaped femtosecond laser pulses can often be effectively identified in adaptive feedback quantum control experiments, but elucidating the underlying control mechanism can be a difficult task requiring significant additional analysis. We introduce landscape Hessian analysis (LHA) as a practical experimental tool to aid in elucidating control mechanism insights. This technique is applied to the dissociative ionization of CH2BrI using shaped fs laser pulses for optimization of the absolute yields of ionic fragments as well as their ratios for the competing processes of breaking the C-Br and C-I bonds. The experimental results suggest that these nominally complex problems can be reduced to a low-dimensional control space with insights into the control mechanisms. While the optimal yield for some fragments is dominated by a non-resonant intensity-driven process, the optimal generation of other fragments maa difficult task requiring significant additionaly be explained by a non-resonant process coupled to few level resonant dynamics. Theoretical analysis and modeling is consistent with the experimental observations.
Sanchez, Gaëtan; Lecaignard, Françoise; Otman, Anatole; Maby, Emmanuel; Mattout, Jérémie
2016-01-01
The relatively young field of Brain-Computer Interfaces has promoted the use of electrophysiology and neuroimaging in real-time. In the meantime, cognitive neuroscience studies, which make extensive use of functional exploration techniques, have evolved toward model-based experiments and fine hypothesis testing protocols. Although these two developments are mostly unrelated, we argue that, brought together, they may trigger an important shift in the way experimental paradigms are being designed, which should prove fruitful to both endeavors. This change simply consists in using real-time neuroimaging in order to optimize advanced neurocognitive hypothesis testing. We refer to this new approach as the instantiation of an Active SAmpling Protocol (ASAP). As opposed to classical (static) experimental protocols, ASAP implements online model comparison, enabling the optimization of design parameters (e.g., stimuli) during the course of data acquisition. This follows the well-known principle of sequential hypothesis testing. What is radically new, however, is our ability to perform online processing of the huge amount of complex data that brain imaging techniques provide. This is all the more relevant at a time when physiological and psychological processes are beginning to be approached using more realistic, generative models which may be difficult to tease apart empirically. Based upon Bayesian inference, ASAP proposes a generic and principled way to optimize experimental design adaptively. In this perspective paper, we summarize the main steps in ASAP. Using synthetic data we illustrate its superiority in selecting the right perceptual model compared to a classical design. Finally, we briefly discuss its future potential for basic and clinical neuroscience as well as some remaining challenges.
Cingulo-opercular activity affects incidental memory encoding for speech in noise.
Vaden, Kenneth I; Teubner-Rhodes, Susan; Ahlstrom, Jayne B; Dubno, Judy R; Eckert, Mark A
2017-08-15
Correctly understood speech in difficult listening conditions is often difficult to remember. A long-standing hypothesis for this observation is that the engagement of cognitive resources to aid speech understanding can limit resources available for memory encoding. This hypothesis is consistent with evidence that speech presented in difficult conditions typically elicits greater activity throughout cingulo-opercular regions of frontal cortex that are proposed to optimize task performance through adaptive control of behavior and tonic attention. However, successful memory encoding of items for delayed recognition memory tasks is consistently associated with increased cingulo-opercular activity when perceptual difficulty is minimized. The current study used a delayed recognition memory task to test competing predictions that memory encoding for words is enhanced or limited by the engagement of cingulo-opercular activity during challenging listening conditions. An fMRI experiment was conducted with twenty healthy adult participants who performed a word identification in noise task that was immediately followed by a delayed recognition memory task. Consistent with previous findings, word identification trials in the poorer signal-to-noise ratio condition were associated with increased cingulo-opercular activity and poorer recognition memory scores on average. However, cingulo-opercular activity decreased for correctly identified words in noise that were not recognized in the delayed memory test. These results suggest that memory encoding in difficult listening conditions is poorer when elevated cingulo-opercular activity is not sustained. Although increased attention to speech when presented in difficult conditions may detract from more active forms of memory maintenance (e.g., sub-vocal rehearsal), we conclude that task performance monitoring and/or elevated tonic attention supports incidental memory encoding in challenging listening conditions. Copyright © 2017 Elsevier Inc. All rights reserved.
Migrated esophageal stent posing a challenge for ventilation.
D'souza, Nita; Arbhi, Sachin; Dikshit, Amit; Ghadge, Murarji; Jha, Smriti
2017-01-01
Self-expandable esophageal stents are being commonly used for palliative treatment in advanced esophageal cancer patients to relieve dysphagia, prevent tracheoesophageal fistula, and facilitate symptomatic betterment. The modern covered stents reduce the ingrowth of the tumor but have seen an increase in the incidence of stent migrations. We report a rather complicated presentation of an esophageal stent for esophageal dilatation and a challenging management of a difficult tracheostomy.
Microworld Simulations: A New Dimension in Training Army Logistics Management Skills
2004-01-01
Providing effective training to Army personnelis always challenging, but the Army facessome new challenges in training its logisticsstaff managers in...soldiers are stationed and where materiel and services are readily available. The design and management of the Army’s Combat Ser- vice Support (CSS) large...scale logistics systems are increasingly important. The skills that are required to manage these systems are difficult to train. Large deployments
Challenges in adopting evidence-based school drug education programmes.
Cahill, Helen W
2007-11-01
The paper discusses the school-based challenges that may moderate the implementation of evidence-based drug education in schools. Knowledge about what constitutes an effective evidence-based drug education programme is discussed in relation to the challenge of delivery in the school setting. Research demonstrates that drug education should be engaging, incorporate interactive learning strategies, stimulate higher-order thinking, promote learning and be transferable to real life circumstances. This may difficult to accomplish in practice, as a range of contextual challenges and ideological assumptions may moderate the teacher's capacity to deliver a programme of this nature. Collaborative learning strategies are not the norm in schools and therefore teachers may find interactive drug education programmes difficult to adopt. Conflicting ideological assumptions about effective epistemological approaches to drug education may also direct the way in which teachers modify programmes in the local context. Teachers need professional training and support if they are to adopt successfully evidence-based school drug education programmes. This support may be enhanced if it includes whole school approaches to effective pedagogy and the development of pro-social classroom environments. Drug education research should take account of the complexities of implementation in the school setting and investigate further the professional and organisational support that teachers require in order to maintain high-quality provision in the school context.
2013-01-01
Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. Conclusions Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases. PMID:23735014
Rabies Virus Infection in Eptesicus fuscus Bats Born in Captivity (Naïve Bats)
Davis, April D.; Jarvis, Jodie A.; Pouliott, Craig; Rudd, Robert J.
2013-01-01
The study of rabies virus infection in bats can be challenging due to quarantine requirements, husbandry concerns, genetic differences among animals, and lack of medical history. To date, all rabies virus (RABV) studies in bats have been performed in wild caught animals. Determining the RABV exposure history of a wild caught bat based on the presence or absence of viral neutralizing antibodies (VNA) may be misleading. Previous studies have demonstrated that the presence of VNA following natural or experimental inoculation is often ephemeral. With this knowledge, it is difficult to determine if a seronegative, wild caught bat has been previously exposed to RABV. The influence of prior rabies exposure in healthy, wild caught bats is unknown. To investigate the pathogenesis of RABV infection in bats born in captivity (naïve bats), naïve bats were inoculated intramuscularly with one of two Eptesicus fuscus rabies virus variants, EfV1 or EfV2. To determine the host response to a heterologous RABV, a separate group of naïve bats were inoculated with a Lasionycteris noctivagans RABV (LnV1). Six months following the first inoculation, all bats were challenged with EfV2. Our results indicate that naïve bats may have some level of innate resistance to intramuscular RABV inoculation. Additionally, naïve bats inoculated with the LnV demonstrated the lowest clinical infection rate of all groups. However, primary inoculation with EfV1 or LnV did not appear to be protective against a challenge with the more pathogenic EfV2. PMID:23741396
Rabies virus infection in Eptesicus fuscus bats born in captivity (naïve bats).
Davis, April D; Jarvis, Jodie A; Pouliott, Craig; Rudd, Robert J
2013-01-01
The study of rabies virus infection in bats can be challenging due to quarantine requirements, husbandry concerns, genetic differences among animals, and lack of medical history. To date, all rabies virus (RABV) studies in bats have been performed in wild caught animals. Determining the RABV exposure history of a wild caught bat based on the presence or absence of viral neutralizing antibodies (VNA) may be misleading. Previous studies have demonstrated that the presence of VNA following natural or experimental inoculation is often ephemeral. With this knowledge, it is difficult to determine if a seronegative, wild caught bat has been previously exposed to RABV. The influence of prior rabies exposure in healthy, wild caught bats is unknown. To investigate the pathogenesis of RABV infection in bats born in captivity (naïve bats), naïve bats were inoculated intramuscularly with one of two Eptesicus fuscus rabies virus variants, EfV1 or EfV2. To determine the host response to a heterologous RABV, a separate group of naïve bats were inoculated with a Lasionycteris noctivagans RABV (LnV1). Six months following the first inoculation, all bats were challenged with EfV2. Our results indicate that naïve bats may have some level of innate resistance to intramuscular RABV inoculation. Additionally, naïve bats inoculated with the LnV demonstrated the lowest clinical infection rate of all groups. However, primary inoculation with EfV1 or LnV did not appear to be protective against a challenge with the more pathogenic EfV2.
Interrogating HIV integrase for compounds that bind- a SAMPL challenge
NASA Astrophysics Data System (ADS)
Peat, Thomas S.; Dolezal, Olan; Newman, Janet; Mobley, David; Deadman, John J.
2014-04-01
Tremendous gains and novel methods are often developed when people are challenged to do something new or difficult. This process is enhanced when people compete against each other-this can be seen in sport as well as in science and technology (e.g. the space race). The SAMPL challenges, like the CASP challenges, aim to challenge modellers and software developers to develop new ways of looking at molecular interactions so the community as a whole can progress in the accurate prediction of these interactions. In order for this challenge to occur, data must be supplied so the prospective test can be done. We have supplied unpublished data related to a drug discovery program run several years ago on HIV integrase for the SAMPL4 challenge. This paper describes the methods used to obtain these data and the chemistry involved.
Challenges in implementing electronic hand hygiene monitoring systems.
Conway, Laurie J
2016-05-02
Electronic hand hygiene (HH) monitoring systems offer the exciting prospect of a more precise, less biased measure of HH performance than direct observation. However, electronic systems are challenging to implement. Selecting a system that minimizes disruption to the physical infrastructure and to clinician workflow, and that fits with the organization's culture and budget, is challenging. Getting front-line workers' buy-in and addressing concerns about the accuracy of the system and how the data will be used are also difficult challenges. Finally, ensuring information from the system reaches front-line workers and is used by them to improve HH practice is a complex challenge. We describe these challenges in detail and suggests ways to overcome them. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
SU-F-T-419: Evaluation of PlanIQ Feasibility DVH as Planning Objectives for Skull Base SBRT Patients
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, W; Wang, H; Chi, P
2016-06-15
Purpose: PlanIQ(Sun Nuclear Corporation) can provide feasibility measures on organs-at-risk(OARs) around the target based on depth, local anatomy density and energy of radiation beam used. This study is to test and evaluate PlanIQ feasibility DVHs as optimization objectives in the treatment planning process, and to investigate the potential to use them in routine clinical cases to improve planning efficiency. Methods: Two to three arcs VMAT Treatment plans were generated in Pinnacle based on PlanIQ feasibility DVH for six skull base patients who previously treated with SBRT. The PlanIQ feasibility DVH for each OAR consists of four zones – impossible (atmore » 100% target coverage), difficult, challenging and probable. Constrains to achieve DVH in difficult zone were used to start plan optimization. Further adjustment was made to improve coverage. The plan DVHs were compared to PlanIQ feasibility DVH to assess the dose received by 0%(D0), 5%(D5), 10%(D10) and 50%(D50) of the OAR volumes. Results: A total of 90 OARs were evaluated for 6 patients (mean 15 OARs, range 11–18 OARs). We used >98% PTV coverage as planning goal since it’s difficult to achieve 100% target coverage. For the generated plans, 96.7% of the OARs achieved D0 or D5 within difficult zone or impossible zone (ipsilateral OARs 93.5%, contralateral OARs 100%), while 90% and 65.6% of the OARs achieved D10 and D50 within difficult zone, respectively. Seventeen of the contralateral and out of field OARs achieved DVHs in impossible zone. For OARs adjacent or overlapped with target volume, the D0 and D5 are challenging to be optimized into difficult zone. All plans were completed within 2–4 adjustments to improve target coverage and uniformity. Conclusion: PlanIQ feasibility tool has the potential to provide difficult but achievable initial optimization objectives and therefore reduce the planning time to obtain a well optimized plan.« less
Ferrada, Evandro; Vergara, Ismael A; Melo, Francisco
2007-01-01
The correct discrimination between native and near-native protein conformations is essential for achieving accurate computer-based protein structure prediction. However, this has proven to be a difficult task, since currently available physical energy functions, empirical potentials and statistical scoring functions are still limited in achieving this goal consistently. In this work, we assess and compare the ability of different full atom knowledge-based potentials to discriminate between native protein structures and near-native protein conformations generated by comparative modeling. Using a benchmark of 152 near-native protein models and their corresponding native structures that encompass several different folds, we demonstrate that the incorporation of close non-bonded pairwise atom terms improves the discriminating power of the empirical potentials. Since the direct and unbiased derivation of close non-bonded terms from current experimental data is not possible, we obtained and used those terms from the corresponding pseudo-energy functions of a non-local knowledge-based potential. It is shown that this methodology significantly improves the discrimination between native and near-native protein conformations, suggesting that a proper description of close non-bonded terms is important to achieve a more complete and accurate description of native protein conformations. Some external knowledge-based energy functions that are widely used in model assessment performed poorly, indicating that the benchmark of models and the specific discrimination task tested in this work constitutes a difficult challenge.
3D variational brain tumor segmentation on a clustered feature set
NASA Astrophysics Data System (ADS)
Popuri, Karteek; Cobzas, Dana; Jagersand, Martin; Shah, Sirish L.; Murtha, Albert
2009-02-01
Tumor segmentation from MRI data is a particularly challenging and time consuming task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. Our work addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multi-dimensional feature set. Further, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this paper is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to the previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned inside and outside region voxel probabilities in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance, during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters in the ventricles to be in the tumor and hence better disambiguate the tumor from brain tissue. We show the performance of our method on real MRI scans. The experimental dataset includes MRI scans, from patients with difficult instances, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Our method shows good results on these test cases.
Smsynth: AN Imagery Synthesis System for Soil Moisture Retrieval
NASA Astrophysics Data System (ADS)
Cao, Y.; Xu, L.; Peng, J.
2018-04-01
Soil moisture (SM) is a important variable in various research areas, such as weather and climate forecasting, agriculture, drought and flood monitoring and prediction, and human health. An ongoing challenge in estimating SM via synthetic aperture radar (SAR) is the development of the retrieval SM methods, especially the empirical models needs as training samples a lot of measurements of SM and soil roughness parameters which are very difficult to acquire. As such, it is difficult to develop empirical models using realistic SAR imagery and it is necessary to develop methods to synthesis SAR imagery. To tackle this issue, a SAR imagery synthesis system based on the SM named SMSynth is presented, which can simulate radar signals that are realistic as far as possible to the real SAR imagery. In SMSynth, SAR backscatter coefficients for each soil type are simulated via the Oh model under the Bayesian framework, where the spatial correlation is modeled by the Markov random field (MRF) model. The backscattering coefficients simulated based on the designed soil parameters and sensor parameters are added into the Bayesian framework through the data likelihood where the soil parameters and sensor parameters are set as realistic as possible to the circumstances on the ground and in the validity range of the Oh model. In this way, a complete and coherent Bayesian probabilistic framework is established. Experimental results show that SMSynth is capable of generating realistic SAR images that suit the needs of a large amount of training samples of empirical models.
Ethical challenges related to elder care. High level decision-makers' experiences
Mamhidir, Anna-Greta; Kihlgren, Mona; Sorlie, Venke
2007-01-01
Background Few empirical studies have been found that explore ethical challenges among persons in high public positions that are responsible for elder care. The aim of this paper was to illuminate the meaning of being in ethically difficult situations related to elder care as experienced by high level decision-makers. Methods A phenomenological-hermeneutic method was used to analyse the eighteen interviews conducted with political and civil servant high level decision-makers at the municipality and county council level from two counties in Sweden. The participants worked at a planning and control as well as executive level and had both budget and quality of elder care responsibilities. Results Both ethical dilemmas and the meaning of being in ethically difficult situations related to elder care were revealed. No differences were seen between the politicians and the civil servants. The ethical dilemmas mostly concerned dealings with extensive care needs and working with a limited budget. The dilemmas were associated with a lack of good care and a lack of agreement concerning care such as vulnerable patients in inappropriate care settings, weaknesses in medical support, dissimilar focuses between the caring systems, justness in the distribution of care and deficient information. Being in ethically difficult situations was challenging. Associated with them were experiences of being exposed, having to be strategic and living with feelings such as aloneness and loneliness, uncertainty, lack of confirmation, the risk of being threatened or becoming a scapegoat and difficult decision avoidance. Conclusion Our paper provides further insight into the ethical dilemmas and ethical challenges met by high level decision-makers', which is important since the overall responsibility for elder care that is also ethically defensible rests with them. They have power and their decisions affect many stakeholders in elder care. Our results can be used to stimulate discussions between high level decision-makers and health care professionals concerning ways of dealing with ethical issues and the necessity of structures that facilitate dealing with them. Even if the high level decision-makers have learned to live with the ethical challenges that confronted them, it was obvious that they were not free from feelings of uncertainty, frustration and loneliness. Vulnerability was revealed regarding themselves and others. Their feelings of failure indicated that they felt something was at stake for the older adults in elder care and for themselves as well, in that there was the risk that important needs would go unmet. PMID:17419880
Ethical challenges related to elder care. High level decision-makers' experiences.
Mamhidir, Anna-Greta; Kihlgren, Mona; Sorlie, Venke
2007-04-10
Few empirical studies have been found that explore ethical challenges among persons in high public positions that are responsible for elder care. The aim of this paper was to illuminate the meaning of being in ethically difficult situations related to elder care as experienced by high level decision-makers. A phenomenological-hermeneutic method was used to analyse the eighteen interviews conducted with political and civil servant high level decision-makers at the municipality and county council level from two counties in Sweden. The participants worked at a planning and control as well as executive level and had both budget and quality of elder care responsibilities. Both ethical dilemmas and the meaning of being in ethically difficult situations related to elder care were revealed. No differences were seen between the politicians and the civil servants. The ethical dilemmas mostly concerned dealings with extensive care needs and working with a limited budget. The dilemmas were associated with a lack of good care and a lack of agreement concerning care such as vulnerable patients in inappropriate care settings, weaknesses in medical support, dissimilar focuses between the caring systems, justness in the distribution of care and deficient information. Being in ethically difficult situations was challenging. Associated with them were experiences of being exposed, having to be strategic and living with feelings such as aloneness and loneliness, uncertainty, lack of confirmation, the risk of being threatened or becoming a scapegoat and difficult decision avoidance. Our paper provides further insight into the ethical dilemmas and ethical challenges met by high level decision-makers', which is important since the overall responsibility for elder care that is also ethically defensible rests with them. They have power and their decisions affect many stakeholders in elder care. Our results can be used to stimulate discussions between high level decision-makers and health care professionals concerning ways of dealing with ethical issues and the necessity of structures that facilitate dealing with them. Even if the high level decision-makers have learned to live with the ethical challenges that confronted them, it was obvious that they were not free from feelings of uncertainty, frustration and loneliness. Vulnerability was revealed regarding themselves and others. Their feelings of failure indicated that they felt something was at stake for the older adults in elder care and for themselves as well, in that there was the risk that important needs would go unmet.
[Research status and prospects of DNA test on difficult specimens].
Dang, Hua-Wei; Mao, Jiong; Wang, Hui; Huang, Jiang-Ping; Bai, Xiao-Gang
2012-02-01
This paper reviews the advances of DNA detection on three types of difficult biological specimens including degraded samples, trace evidences and mixed samples. The source of different samples, processing methods and announcements were analyzed. New methods such as mitochondrial test system, changing the original experimental conditions, low-volume PCR amplification and new technologies such as whole genome amplification techniques, laser capture micro-dissection, and mini-STR technology in recent years are introduced.
Northern Shenandoah public mobility project evaluation
DOT National Transportation Integrated Search
2003-06-01
Developing new intelligent transportation systems to meet unusual challenges in rural areas where ITS implementation is limited is difficult in part because there are few similar examples to use as guides. In such situations, it is critical to conduc...
GEOSPATIAL DATA ACCURACY ASSESSMENT
The development of robust accuracy assessment methods for the validation of spatial data represent's a difficult scientific challenge for the geospatial science community. The importance and timeliness of this issue is related directly to the dramatic escalation in the developmen...
Validated questionnaires heighten detection of difficult asthma comorbidities.
Radhakrishna, Naghmeh; Tay, Tunn Ren; Hore-Lacy, Fiona; Stirling, Robert; Hoy, Ryan; Dabscheck, Eli; Hew, Mark
2017-04-01
Multiple extra-pulmonary comorbidities contribute to difficult asthma, but their diagnosis can be challenging and time consuming. Previous data on comorbidity detection have focused on clinical assessment, which may miss certain conditions. We aimed to locate relevant validated screening questionnaires to identify extra-pulmonary comorbidities that contribute to difficult asthma, and evaluate their performance during a difficult asthma evaluation. MEDLINE was searched to identify key extra-pulmonary comorbidities that contribute to difficult asthma. Screening questionnaires were chosen based on ease of use, presence of a cut-off score, and adequate validation to help systematically identify comorbidities. In a consecutive series of 86 patients referred for systematic evaluation of difficult asthma, questionnaires were administered prior to clinical consultation. Six difficult asthma comorbidities and corresponding screening questionnaires were found: sinonasal disease (allergic rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional breathing, obstructive sleep apnea, anxiety and depression, and gastro-oesophageal reflux disease. When the questionnaires were added to the referring clinician's impression, the detection of all six comorbidities was significantly enhanced. The average time for questionnaire administration was approximately 40 minutes. The use of validated screening questionnaires heightens detection of comorbidities in difficult asthma. The availability of data from a battery of questionnaires prior to consultation can save time and allow clinicians to systematically assess difficult asthma patients and to focus on areas of particular concern. Such an approach would ensure that all contributing comorbidities have been addressed before significant treatment escalation is considered.
Large eddy simulation applications in gas turbines.
Menzies, Kevin
2009-07-28
The gas turbine presents significant challenges to any computational fluid dynamics techniques. The combination of a wide range of flow phenomena with complex geometry is difficult to model in the context of Reynolds-averaged Navier-Stokes (RANS) solvers. We review the potential for large eddy simulation (LES) in modelling the flow in the different components of the gas turbine during a practical engineering design cycle. We show that while LES has demonstrated considerable promise for reliable prediction of many flows in the engine that are difficult for RANS it is not a panacea and considerable application challenges remain. However, for many flows, especially those dominated by shear layer mixing such as in combustion chambers and exhausts, LES has demonstrated a clear superiority over RANS for moderately complex geometries although at significantly higher cost which will remain an issue in making the calculations relevant within the design cycle.
Athermalization and achromatization of visible/SWIR optics using instantaneous Abbe number
NASA Astrophysics Data System (ADS)
Ramsey, J. L.
2017-11-01
With the move to more and more lightweight and cost-effective design, a move to multiband or multi-spectral optics is required. These systems are becoming more prevalent in the market as new detector technologies have been developed. However, the lens designs are only starting to be considered with the addition of new materials in the MWIR and the LWIR. For the VIS/SWIR region the designs have been possible, but a lack of detector technology has resulted in few designs being considered for actual manufacturing. These designs are also difficult due to changes in the Abbe number in the different wavebands. Where the glass map is robust in the visible region, there exists a lack of crown glasses in the SWIR, and one is left with mostly flint glasses. This proves challenging from a chromatic perspective. The challenge becomes even more difficult if one wants to incorporate athermalization.
2003-10-01
Toujours comparativement au placebo, les sujets ayant pris du zopiclone avaient eu moins de difficulté à s’endormir (p < 0,001), s’étaient réveillés...5 Multitask (MT)........................................................................... 6 Experimental Design Considerations...Experimental Design ............................................................................ 19 Statistical Analysis
Experimental Evaluation of the Drag Coefficient of Water Rockets by a Simple Free-Fall Test
ERIC Educational Resources Information Center
Barrio-Perotti, R.; Blanco-Marigorta, E. Arguelles-Diaz, K.; Fernandez-Oro, J.
2009-01-01
The flight trajectory of a water rocket can be reasonably calculated if the magnitude of the drag coefficient is known. The experimental determination of this coefficient with enough precision is usually quite difficult, but in this paper we propose a simple free-fall experiment for undergraduate students to reasonably estimate the drag…
Evaluation of tocopherol recovery through simulation of molecular distillation process.
Moraes, E B; Batistella, C B; Alvarez, M E Torres; Filho, Rubens Maciel; Maciel, M R Wolf
2004-01-01
DISMOL simulator was used to determine the best possible operating conditions to guide, in future studies, experimental works. This simulator needs several physical-chemical properties and often it is very difficult to determine them because of the complexity of the involved components. Their determinations must be made through correlations and/or predictions, in order to characterize the system and calculate it. The first try is to have simulation results of a system that later can be validated with experimental data. To implement, in the simulator, the necessary parameters of complex systems is a difficult task. In this work, we aimed to determe these properties in order to evaluate the tocopherol (vitamin E) recovery using a DISMOL simulator. The raw material used was the crude deodorizer distillate of soya oil. With this procedure, it is possible to determine the best operating conditions for experimental works and to evaluate the process in the separation of new systems, analyzing the profiles obtained from these simulations for the falling film molecular distillator.
Challenges in the Protection of US Critical Infrastructure in the Cyber Realm
2014-05-22
their nature and motivation and the need to differentiate attacks in case of individual attributions ( criminal , espionage, and hacktivist attack vs ...also difficult to distinguish between acts of war and criminal acts. For example, it is natural for the military to be ambiguous as to whether an...must be addressed. The resultant cyber security issues challenge everyone. This prompts the question, what is the nature of the US military
NASA Astrophysics Data System (ADS)
Ceccherini, S.; Colocci, M.; Gurioli, M.; Bogani, F.
1998-11-01
The distinction between the coherent and the incoherent component of the radiation emitted from resonantly excited material systems is difficult experimentally, particularly when ultra-short optical pulses are used for excitation. We propose an experimental procedure allowing an easy measurement of the two components. The method is completely general and applicable to any kind of physical system; its feasibility is demonstrated on the resonant emission from excitons in a semiconductor quantum well.
Jyotsna, S; Rajesh, G; Wadgave, Umesh; Sankeshwari, Banashree; Nayak, Sushma S; Vyas, Rashmi
2017-01-01
Introduction Preclinical dental education promotes development of competency and expertise before students work on patients, but this phase is devoid of exposure to real patients leading to challenges in teaching-learning. Aim The aim of this study was to explore the challenges faced by students during the process of learning preclinical prosthodontics. Materials and Methods Two Focus Group Discussions (FGDs) were conducted with two different groups of students and one FGD was held with prosthodontics faculty. The FGDs explored the student’s and faculty perceptions on the topics which were difficult for the students to understand and their suggestions on how these topics can be made easier to understand. The discussions were audio taped with prior consent and transcribed. Results The students and the faculty felt that the subject of prosthodontics is vast, difficult to visualize and also difficult to correlate theory with practical aspects. Lack of clinical exposure coupled with use of conventional methods of teaching were identified as reasons for difficulty in understanding the subject. Both students and faculty members suggested that use of simulation, demonstrations, and videos could augment the learning process for the students. Early clinical exposure will help solve many problems encountered during learning and contribute to a better understanding. Conclusion The students and faculty expressed a “need” for early clinical exposure to enhance the learner’s understanding of the preclinical aspects of the subject. The present study highlights the need for change in instruction methods to enhance the learning experiences in preclinical prosthodontics of dental undergraduate students in India. PMID:28969263
Li, Jin; Zheng, Le; Uchiyama, Akihiko; Bin, Lianghua; Mauro, Theodora M; Elias, Peter M; Pawelczyk, Tadeusz; Sakowicz-Burkiewicz, Monika; Trzeciak, Magdalena; Leung, Donald Y M; Morasso, Maria I; Yu, Peng
2018-06-13
A large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery. The heterogeneity of these data makes it difficult to consistently integrate them, slowing down the process of biological discovery. We introduce a data processing paradigm to identify key factors in biological processes via systematic collection of gene expression datasets, primary analysis of data, and evaluation of consistent signals. To demonstrate its effectiveness, our paradigm was applied to epidermal development and identified many genes that play a potential role in this process. Besides the known epidermal development genes, a substantial proportion of the identified genes are still not supported by gain- or loss-of-function studies, yielding many novel genes for future studies. Among them, we selected a top gene for loss-of-function experimental validation and confirmed its function in epidermal differentiation, proving the ability of this paradigm to identify new factors in biological processes. In addition, this paradigm revealed many key genes in cold-induced thermogenesis using data from cold-challenged tissues, demonstrating its generalizability. This paradigm can lead to fruitful results for studying molecular mechanisms in an era of explosive accumulation of publicly available biological data.
Improved ligand geometries in crystallographic refinement using AFITT in PHENIX
Janowski, Pawel A.; Moriarty, Nigel W.; Kelley, Brian P.; ...
2016-08-31
Modern crystal structure refinement programs rely on geometry restraints to overcome the challenge of a low data-to-parameter ratio. While the classical Engh and Huber restraints work well for standard amino-acid residues, the chemical complexity of small-molecule ligands presents a particular challenge. Most current approaches either limit ligand restraints to those that can be readily described in the Crystallographic Information File (CIF) format, thus sacrificing chemical flexibility and energetic accuracy, or they employ protocols that substantially lengthen the refinement time, potentially hindering rapid automated refinement workflows.PHENIX–AFITTrefinement uses a full molecular-mechanics force field for user-selected small-molecule ligands during refinement, eliminating the potentiallymore » difficult problem of finding or generating high-quality geometry restraints. It is fully integrated with a standard refinement protocol and requires practically no additional steps from the user, making it ideal for high-throughput workflows.PHENIX–AFITTrefinements also handle multiple ligands in a single model, alternate conformations and covalently bound ligands. Here, the results of combiningAFITTand thePHENIXsoftware suite on a data set of 189 protein–ligand PDB structures are presented. Refinements usingPHENIX–AFITTsignificantly reduce ligand conformational energy and lead to improved geometries without detriment to the fit to the experimental data. Finally, for the data presented,PHENIX–AFITTrefinements result in more chemically accurate models for small-molecule ligands.« less
Preclinical Magnetic Resonance Imaging and Systems Biology in Cancer Research
Albanese, Chris; Rodriguez, Olga C.; VanMeter, John; Fricke, Stanley T.; Rood, Brian R.; Lee, YiChien; Wang, Sean S.; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F.; Wang, Yue
2014-01-01
Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. PMID:23219428
Olsen, S. C.; Johnson, C.
2011-01-01
A comparative study was conducted using data from naive bison (n = 45) and cattle (n = 46) from 8 and 6 studies, respectively, in which a standardized Brucella abortus strain 2308 experimental challenge was administered during midgestation. The incidence of abortion, fetal infection, uterine or mammary infection, or infection in maternal tissues after experimental challenge was greater (P < 0.05) in bison than in cattle. In animals that did abort, the time between experimental challenge and abortion was shorter (P < 0.05) for bison than for cattle. Brucella colonization of four target tissues and serologic responses on the standard tube agglutination test at the time of abortion did not differ (P > 0.05) between cattle and bison. The results of our study suggest that naive bison and cattle have similarities and differences after experimental exposure to a virulent B. abortus strain. Although our data suggest that bison may be more susceptible to infection with Brucella, some pathogenic characteristics of brucellosis were similar between bison and cattle. PMID:21976222
Public health in Canada: a difficult history.
Mowat, David L; Butler-Jones, David
2007-01-01
Although the outbreak of severe acute respiratory syndrome in 2003 was the event that focused attention on Canada's capacity in public health, there have been, and will be, many other public health challenges, not just in the form of outbreaks but of a diverse set of threats to health, both infectious and non-infectious. Like many other countries, Canada must face the challenge of building and sustaining the capacity to respond to this broad range of challenges. Recently, there has been an emphasis on strengthening the public health infrastructure, including inter-jurisdictional agreements, research, knowledge translation, information systems and the workforce.
Addressing Challenges in Studies of Behavioral Responses of Whales to Noise.
Cato, Douglas H; Dunlop, Rebecca A; Noad, Michael J; McCauley, Robert D; Kniest, Eric; Paton, David; Kavanagh, Ailbhe S
2016-01-01
Studying the behavioral response of whales to noise presents numerous challenges. In addition to the characteristics of the noise exposure, many factors may affect the response and these must be measured and accounted for in the analysis. An adequate sample size that includes matching controls is crucial if meaningful results are to be obtained. Field work is thus complicated, logistically difficult, and expensive. This paper discusses some of the challenges and how they are being met in a large-scale multiplatform project in which humpback whales are exposed to the noise of seismic air guns.
Challenging behaviour: a challenge to change.
van Berckelaer-Onnes, I A; van Loon, J; Peelen, A
2002-09-01
People with intellectual disability often exhibit severe behavioural problems. Treatment of these problems is frequently very difficult. In The Netherlands, parents, institutes, schools and others can request the services of an independent advisory team with a pool of professionals who have experience with individuals who exhibit challenging behaviour. In this article the methods of the team will be described using a 24-year-old man as an example. The process took almost 7 years. Finally, this man, who had been living full time in one room in total isolation from the rest of the world, fulfilled his heart's desire--visiting the UK by Hovercraft.
Premature ejaculation: challenging new and the old concepts
Kalejaiye, Odunayo; Almekaty, Khaled; Blecher, Gideon; Minhas, Suks
2017-01-01
Premature ejaculation remains a difficult condition to manage for patients, their partners, and the clinician. Whilst prevalence rates are estimated to be 20–40%, determining a diagnosis of premature ejaculation is difficult, as the definition remains both subjective and ill-defined in the clinical context. As our understanding of the ejaculatory pathway has improved, new opportunities to treat the condition have evolved with mixed results. In this review, we explore some of these controversies surrounding the aetiology, diagnosis, and treatment of this condition and discuss potential novel therapeutic options. PMID:29259775
[Difficult teenagers: the challenges of interdisciplinarity].
Saint-Andrté, Stéphane; Botbola, Michel
2013-01-01
The adolescents in great distress, because of ruptures in the course of their lives and of their chaotic family environment, need educational and social actions. The consensual point of view is that responding to the needs of the so called "difficult adolescents" implies the involvement of educational, therapeutic and judicial services. Nevertheless, the usual tendency to categorize the users with the idea it will permit to guide them to the appropriate skill field and the transgressive characteristic of these adolescents' behaviours lead all these services to reject them and send them to the two other services.
Rabiu, Taopheeq B; Fadare, Amos E
2012-03-01
Accessing and maintaining the airway in penetrating cervical spine injury is a challenge for anaesthetists globally. This is more so in resource-poor settings, where advanced techniques for intubation in difficult airway situations are unavailable. We describe a new, low-cost, easily adaptable method of managing the airway used in a middle-aged man who sustained screw driver injury to the cervical spine with C4 Brown-Séquard syndrome. The deployment of readily available and cheap materials led to successful anaesthesia management of the patient.
Measuring Distribution Performance? Benchmarking Warrants Your Attention
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ericson, Sean J; Alvarez, Paul
Identifying, designing, and measuring performance metrics is critical to securing customer value, but can be a difficult task. This article examines the use of benchmarks based on publicly available performance data to set challenging, yet fair, metrics and targets.
The Challenge of Interdisciplinary Research.
ERIC Educational Resources Information Center
Locker, Kitty O.
1994-01-01
Discusses what makes business communication research interdisciplinary and why interdisciplinary research is difficult yet desirable. Details the value of interdisciplinary concepts, methods, and perspectives. Notes how business communication research might be made interdisciplinary and points out the need for tolerance in interdisciplinary…
Physiological Disorders of Pear Shoot Cultures
USDA-ARS?s Scientific Manuscript database
Physiological disorders are some of the most difficult challenges in micropropagation. Little is known of the causes of plant growth disorders which include callus formation, hyperhydricity, shoot tip necrosis, leaf lesions, epinasty, fasciation and hypertrophy. During our study of mineral nutritio...
Prototype design for a predictive model to improve evacuation operations : technical report.
DOT National Transportation Integrated Search
2011-08-01
Mass evacuations of the Texas Gulf Coast remain a difficult challenge. These events are massive in scale, : highly complex, and entail an intricate, ever-changing conglomeration of technical and jurisdictional issues. : This project focused primarily...
NASA Astrophysics Data System (ADS)
Toman, Blaza; Nelson, Michael A.; Bedner, Mary
2017-06-01
Chemical measurement methods are designed to promote accurate knowledge of a measurand or system. As such, these methods often allow elicitation of latent sources of variability and correlation in experimental data. They typically implement measurement equations that support quantification of effects associated with calibration standards and other known or observed parametric variables. Additionally, multiple samples and calibrants are usually analyzed to assess accuracy of the measurement procedure and repeatability by the analyst. Thus, a realistic assessment of uncertainty for most chemical measurement methods is not purely bottom-up (based on the measurement equation) or top-down (based on the experimental design), but inherently contains elements of both. Confidence in results must be rigorously evaluated for the sources of variability in all of the bottom-up and top-down elements. This type of analysis presents unique challenges due to various statistical correlations among the outputs of measurement equations. One approach is to use a Bayesian hierarchical (BH) model which is intrinsically rigorous, thus making it a straightforward method for use with complex experimental designs, particularly when correlations among data are numerous and difficult to elucidate or explicitly quantify. In simpler cases, careful analysis using GUM Supplement 1 (MC) methods augmented with random effects meta analysis yields similar results to a full BH model analysis. In this article we describe both approaches to rigorous uncertainty evaluation using as examples measurements of 25-hydroxyvitamin D3 in solution reference materials via liquid chromatography with UV absorbance detection (LC-UV) and liquid chromatography mass spectrometric detection using isotope dilution (LC-IDMS).
van Ede, Freek; Maris, Eric
2016-01-01
Oscillatory neuronal activity is implicated in many cognitive functions, and its phase coupling between sensors may reflect networks of communicating neuronal populations. Oscillatory activity is often studied using extracranial recordings and compared between experimental conditions. This is challenging, because there is overlap between sensor-level activity generated by different sources, and this can obscure differential experimental modulations of these sources. Additionally, in extracranial data, sensor-level phase coupling not only reflects communicating populations, but can also be generated by a current dipole, whose sensor-level phase coupling does not reflect source-level interactions. We present a novel method, which is capable of separating and characterizing sources on the basis of their phase coupling patterns as a function of space, frequency and time (trials). Importantly, this method depends on a plausible model of a neurobiological rhythm. We present this model and an accompanying analysis pipeline. Next, we demonstrate our approach, using magnetoencephalographic (MEG) recordings during a cued tactile detection task as a case study. We show that the extracted components have overlapping spatial maps and frequency content, which are difficult to resolve using conventional pairwise measures. Because our decomposition also provides trial loadings, components can be readily contrasted between experimental conditions. Strikingly, we observed heterogeneity in alpha and beta sources with respect to whether their activity was suppressed or enhanced as a function of attention and performance, and this happened both in task relevant and irrelevant regions. This heterogeneity contrasts with the common view that alpha and beta amplitude over sensory areas are always negatively related to attention and performance. PMID:27336159
NASA Astrophysics Data System (ADS)
Collins, S.
2010-07-01
Populations can respond to environmental change over tens or hundreds of generations by shifts in phenotype that can be the result of a sustained physiological response, evolutionary (genetic) change, shifts in community composition, or some combination of these factors. Microbes evolve on human timescales, and evolution may contribute to marine phytoplankton responses to global change over the coming decades. However, it is still unknown whether evolutionary responses are likely to contribute significantly to phenotypic change in marine microbial communities under high pCO2 regimes or other aspects of global change. Recent work by Müller et al. (2010) highlights that long-term responses of marine microbes to global change must be empirically measured and the underlying cause of changes in phenotype explained. Here, I briefly discuss how tools from experimental microbial evolution may be used to detect and measure evolutionary responses in marine phytoplankton grown in high CO2 environments and other environments of interest. I outline why the particular biology of marine microbes makes conventional experimental evolution challenging right now and make a case that marine microbes are good candidates for the development of new model systems in experimental evolution. I suggest that "black box" frameworks that focus on partitioning phenotypic change, such as the Price equation, may be useful in cases where direct measurements of evolutionary responses alone are difficult, and that such approaches could be used to test hypotheses about the underlying causes of phenotypic shifts in marine microbe communities responding to global change.
Capriotti, Matthew R; Brandt, Bryan C; Turkel, Jennifer E; Lee, Han-Joo; Woods, Douglas W
2014-03-01
Tourette syndrome (TS) is marked by the chronic presence of motor and vocal tics that are usually accompanied by aversive sensory experiences called "premonitory urges." Phenomenological accounts suggest that these urges occur before tics and diminish following their occurrence. This has led some to suggest that tics are negatively reinforced by removal of premonitory urges. This hypothesis has proven difficult to test experimentally, however, due in part to challenges in measuring premonitory urge strength. We tested predictions of the negative reinforcement conceptualization of premonitory urges using novel experimental tactics within the context of the "tic detector" paradigm. We compared tic rates and ratings of premonitory urge strength exhibited by youth with TS or chronic tic disorder under free-to-tic baseline (BL), reinforced tic suppression (RTS), and reinforced tic suppression with escape (RTS + E) conditions. Results were consistent with previous research and hypotheses of the present study. Participants rated the strength of their premonitory urges as higher during RTS conditions than during BL conditions. Within RTS + E conditions, tic rates were higher during escape portions when the contingency supporting tic suppression was inactive than during components where the contingency was active, and ratings of urge strength were higher at the onset of break periods than at the offset. All participants engaged in some level of escape from reinforced suppression during the course of the experiment. Results of this study support the notion that tics may be negatively reinforced by removal of aversive premonitory urges. Future directions for basic and clinical research are discussed. © The Author(s) 2014.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mehmood, Faisal; General Dynamics Information Technology, Inc., Dayton, Ohio 45433; Pachter, Ruth, E-mail: ruth.pachter@us.af.mil
Prediction of the frequency-dependent dielectric function of thin films poses computational challenges, and at the same time experimental characterization by spectroscopic ellipsometry remains difficult to interpret because of changes in stoichiometry and surface morphology, temperature, thickness of the film, or substrate. In this work, we report calculations for titanium nitride (TiN), a promising material for plasmonic applications because of less loss and other practical advantages compared to noble metals. We investigated structural, electronic, and optical properties of stoichiometric bulk TiN, as well as of the TiN(100), TiN(110), and TiN(111) outermost surfaces. Density functional theory (DFT) and many-body GW methods (Green'smore » (G) function-based approximation with screened Coulomb interaction (W)) were used, ranging from G{sub 0}W{sub 0}, GW{sub 0} to partially self-consistent sc-GW{sub 0}, as well as the GW-BSE (Bethe-Salpeter equation) and time-dependent DFT (TDDFT) methods for prediction of the optical properties. Structural parameters and the band structure for bulk TiN were shown to be consistent with previous work. Calculated dielectric functions, plasma frequencies, reflectivity, and the electron energy loss spectrum demonstrated consistency with experiment at the GW{sub 0}-BSE level. Deviations from experimental data are expected due to varying experimental conditions. Comparison of our results to spectroscopic ellipsometry data for realistic nanostructures has shown that although TDDFT may provide a computationally feasible level of theory in evaluation of the dielectric function, application is subject to validation with GW-BSE calculations.« less
Experimental design and reporting standards for metabolomics studies of mammalian cell lines.
Hayton, Sarah; Maker, Garth L; Mullaney, Ian; Trengove, Robert D
2017-12-01
Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important.
NASA Astrophysics Data System (ADS)
Pathak, Anupam; Brei, Diann; Luntz, Jonathan; LaVigna, Chris; Kwatny, Harry
2008-03-01
In urban combat environments where it is common to have unsupported firing positions, wobble significantly decreases shooting accuracy reducing mission effectiveness and soldier survivability. The SMASH (SMA Stabilizing Handgrip) has been developed to cancel wobble using antagonistic SMA actuators which reduce weight and size relative to conventional actuation, but lead to interesting control challenges. This paper presents the specification and design of the SMA actuation system for the SMASH platform along with experimental validation of the actuation and cancellation authority on the benchtop and on an M16 platform. Analytical dynamic weapon models and shooter experiments were conducted to define actuation frequency and amplitude specifications. The SMASH, designed to meet these, was experimentally characterized from the bounding quasi-static case up to the 3 Hz range, successfully generating the +/-2 mm amplitude requirement. To effectively cancel wobble it is critical to produce the proper output functional shape which is difficult for SMA due to inherent nonlinearities, hysteresis, etc. Three distinct electrical heating input functions (square, ramp, and preheat) were investigated to shape the actuator output to produce smooth sinusoidal motion. The effect of each of these functions on the cancellation response of the SMASH applied to the M16 platform was experimentally studied across the wobble range (1-3 Hz) demonstrating significant cancellation, between 50-97% depending on the smoothing function and frequency. These results demonstrate the feasibility of a hand-held wobble cancellation device providing an important foundation for future work in overall system optimization and the development of physically based feed-forward signals for closed-loop control.
Morris, Melody K.; Saez-Rodriguez, Julio; Clarke, David C.; Sorger, Peter K.; Lauffenburger, Douglas A.
2011-01-01
Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone. PMID:21408212
Next Generation Models for Storage and Representation of Microbial Biological Annotation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Quest, Daniel J; Land, Miriam L; Brettin, Thomas S
2010-01-01
Background Traditional genome annotation systems were developed in a very different computing era, one where the World Wide Web was just emerging. Consequently, these systems are built as centralized black boxes focused on generating high quality annotation submissions to GenBank/EMBL supported by expert manual curation. The exponential growth of sequence data drives a growing need for increasingly higher quality and automatically generated annotation. Typical annotation pipelines utilize traditional database technologies, clustered computing resources, Perl, C, and UNIX file systems to process raw sequence data, identify genes, and predict and categorize gene function. These technologies tightly couple the annotation software systemmore » to hardware and third party software (e.g. relational database systems and schemas). This makes annotation systems hard to reproduce, inflexible to modification over time, difficult to assess, difficult to partition across multiple geographic sites, and difficult to understand for those who are not domain experts. These systems are not readily open to scrutiny and therefore not scientifically tractable. The advent of Semantic Web standards such as Resource Description Framework (RDF) and OWL Web Ontology Language (OWL) enables us to construct systems that address these challenges in a new comprehensive way. Results Here, we develop a framework for linking traditional data to OWL-based ontologies in genome annotation. We show how data standards can decouple hardware and third party software tools from annotation pipelines, thereby making annotation pipelines easier to reproduce and assess. An illustrative example shows how TURTLE (Terse RDF Triple Language) can be used as a human readable, but also semantically-aware, equivalent to GenBank/EMBL files. Conclusions The power of this approach lies in its ability to assemble annotation data from multiple databases across multiple locations into a representation that is understandable to researchers. In this way, all researchers, experimental and computational, will more easily understand the informatics processes constructing genome annotation and ultimately be able to help improve the systems that produce them.« less
Extreme-Scale Bayesian Inference for Uncertainty Quantification of Complex Simulations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Biros, George
Uncertainty quantification (UQ)—that is, quantifying uncertainties in complex mathematical models and their large-scale computational implementations—is widely viewed as one of the outstanding challenges facing the field of CS&E over the coming decade. The EUREKA project set to address the most difficult class of UQ problems: those for which both the underlying PDE model as well as the uncertain parameters are of extreme scale. In the project we worked on these extreme-scale challenges in the following four areas: 1. Scalable parallel algorithms for sampling and characterizing the posterior distribution that exploit the structure of the underlying PDEs and parameter-to-observable map. Thesemore » include structure-exploiting versions of the randomized maximum likelihood method, which aims to overcome the intractability of employing conventional MCMC methods for solving extreme-scale Bayesian inversion problems by appealing to and adapting ideas from large-scale PDE-constrained optimization, which have been very successful at exploring high-dimensional spaces. 2. Scalable parallel algorithms for construction of prior and likelihood functions based on learning methods and non-parametric density estimation. Constructing problem-specific priors remains a critical challenge in Bayesian inference, and more so in high dimensions. Another challenge is construction of likelihood functions that capture unmodeled couplings between observations and parameters. We will create parallel algorithms for non-parametric density estimation using high dimensional N-body methods and combine them with supervised learning techniques for the construction of priors and likelihood functions. 3. Bayesian inadequacy models, which augment physics models with stochastic models that represent their imperfections. The success of the Bayesian inference framework depends on the ability to represent the uncertainty due to imperfections of the mathematical model of the phenomena of interest. This is a central challenge in UQ, especially for large-scale models. We propose to develop the mathematical tools to address these challenges in the context of extreme-scale problems. 4. Parallel scalable algorithms for Bayesian optimal experimental design (OED). Bayesian inversion yields quantified uncertainties in the model parameters, which can be propagated forward through the model to yield uncertainty in outputs of interest. This opens the way for designing new experiments to reduce the uncertainties in the model parameters and model predictions. Such experimental design problems have been intractable for large-scale problems using conventional methods; we will create OED algorithms that exploit the structure of the PDE model and the parameter-to-output map to overcome these challenges. Parallel algorithms for these four problems were created, analyzed, prototyped, implemented, tuned, and scaled up for leading-edge supercomputers, including UT-Austin’s own 10 petaflops Stampede system, ANL’s Mira system, and ORNL’s Titan system. While our focus is on fundamental mathematical/computational methods and algorithms, we will assess our methods on model problems derived from several DOE mission applications, including multiscale mechanics and ice sheet dynamics.« less
Enhanced Communication Network Solution for Positive Train Control Implementation
NASA Technical Reports Server (NTRS)
Fatehi, M. T.; Simon, J.; Chang, W.; Chow, E. T.; Burleigh, S. C.
2011-01-01
The commuter and freight railroad industry is required to implement Positive Train Control (PTC) by 2015 (2012 for Metrolink), a challenging network communications problem. This paper will discuss present technologies developed by the National Aeronautics and Space Administration (NASA) to overcome comparable communication challenges encountered in deep space mission operations. PTC will be based on a new cellular wireless packet Internet Protocol (IP) network. However, ensuring reliability in such a network is difficult due to the "dead zones" and transient disruptions we commonly experience when we lose calls in commercial cellular networks. These disruptions make it difficult to meet PTC s stringent reliability (99.999%) and safety requirements, deployment deadlines, and budget. This paper proposes innovative solutions based on space-proven technologies that would help meet these challenges: (1) Delay Tolerant Networking (DTN) technology, designed for use in resource-constrained, embedded systems and currently in use on the International Space Station, enables reliable communication over networks in which timely data acknowledgments might not be possible due to transient link outages. (2) Policy-Based Management (PBM) provides dynamic management capabilities, allowing vital data to be exchanged selectively (with priority) by utilizing alternative communication resources. The resulting network may help railroads implement PTC faster, cheaper, and more reliably.
2017-03-24
for Design and Control of Adaptive Stochastic Complex Systems John Baillieul∗ Contents 1 Executive Summary 2 2 Introduction and Issues to Be Addressed...difficult of real-world Systems-of-Systems challenges is the design and operational control of medical treatment networks that support forces operating...This report describes a brief research project on foundartional aspects of systems-of-systems design and operation. The overarching goal of the
Collective Protection (ColPro) Field Testing
2011-09-28
It is recommended that methyl salicylate (MeS) or similar simulants that are not difficult to decontaminate should be used for this purpose. 4.4.3...ce nt ra tio n (m g/ m 3 ) Figure 3. Analysis of ppbRAE® and Solid Sorbent Tube (SST) Data, Methyl Salicylate (MeS) Challenge to the Interior of...the Vehicle. Figure 4. Gasmet™ Analysis of the Methyl Salicylate (MeS) Challenge in the Simulant- Exposure Area (SEA). TOP 08-2-198 28 September
Quantum computing and probability.
Ferry, David K
2009-11-25
Over the past two decades, quantum computing has become a popular and promising approach to trying to solve computationally difficult problems. Missing in many descriptions of quantum computing is just how probability enters into the process. Here, we discuss some simple examples of how uncertainty and probability enter, and how this and the ideas of quantum computing challenge our interpretations of quantum mechanics. It is found that this uncertainty can lead to intrinsic decoherence, and this raises challenges for error correction.
ERIC Educational Resources Information Center
Tierney, William G., Ed.; Colyar, Julia E., Ed.
2006-01-01
This book documents a year in the life of five adolescents preparing for college. The text examines the different pathways that brought these students to where they are: living in poverty, attending overcrowded schools, and the pressure to be the first in their families to attend college are just a few of the challenges these students must battle…
1983-02-01
blow-off stability and fractional conversion was evaluated for design of an experimental study of these phenomena. The apparatus designed will be...the development of an array of experimental methods and test strategies designed to unravel a complex process that is very difficult to observe directly...this effort of lead field theoretic analysis as a design basis has made that possible. The experimental phase of the effort has three major
Teaching Physics for Conceptual Understanding Exemplified for Einstein's Special Relativity
NASA Astrophysics Data System (ADS)
Undreiu, Lucian M.
2006-12-01
In most liberal arts colleges the prerequisites for College Physics, Introductory or Calculus based, are strictly related to Mathematics. As a state of fact, the majorities of the students perceive Physics as a conglomerate of mathematical equations, a collection of facts to be memorized and they regard Physics as one of the most difficult subjects. A change of this attitude towards Physics, and Science in general, is intrinsically connected with the promotion of conceptual understanding and stimulation of critical thinking. In such an environment, the educators are facilitators, rather than the source of knowledge. One good way of doing this is to challenge the students to think about what they see around them and to connect physics with the real world. Motivation occurs when students realize that what was learned is interesting and relevant. Visual teaching aids such as educational videos or computer simulations, as well as computer-assisted experiments, can greatly enhance the effectiveness of a science lecture or laboratory. Difficult topics can be discussed through animated analogies. Special Relativity is recognized as a challenging topic and is probably one of the most misunderstood theories of Physics. While understanding Special Relativity requires a detachment from ordinary perception and every day life notions, animated analogies can prove to be very successful in making difficult topics accessible.
The mGA1.0: A common LISP implementation of a messy genetic algorithm
NASA Technical Reports Server (NTRS)
Goldberg, David E.; Kerzic, Travis
1990-01-01
Genetic algorithms (GAs) are finding increased application in difficult search, optimization, and machine learning problems in science and engineering. Increasing demands are being placed on algorithm performance, and the remaining challenges of genetic algorithm theory and practice are becoming increasingly unavoidable. Perhaps the most difficult of these challenges is the so-called linkage problem. Messy GAs were created to overcome the linkage problem of simple genetic algorithms by combining variable-length strings, gene expression, messy operators, and a nonhomogeneous phasing of evolutionary processing. Results on a number of difficult deceptive test functions are encouraging with the mGA always finding global optima in a polynomial number of function evaluations. Theoretical and empirical studies are continuing, and a first version of a messy GA is ready for testing by others. A Common LISP implementation called mGA1.0 is documented and related to the basic principles and operators developed by Goldberg et. al. (1989, 1990). Although the code was prepared with care, it is not a general-purpose code, only a research version. Important data structures and global variations are described. Thereafter brief function descriptions are given, and sample input data are presented together with sample program output. A source listing with comments is also included.
Student Teachers' Approaches to Teaching Biological Evolution
ERIC Educational Resources Information Center
Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert
2015-01-01
Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution…
Documenting Public Values for River Ecosystem Services
The value to society of environmental changes is difficult to assess, and thus challenging to include in environmental management decisions. This presentation will first provide an overview of how framing these values in an ecosystem services perspective can facilitate the proces...
Panama Canal : a new course for the canal
DOT National Transportation Integrated Search
1999-01-01
While the Panama Canal provides significant time savings, passage through this narrow waterway presents a host of challenges. Soon all canal pilots will have a new tool in their efforts to safely guide vessels through this difficult canal: a Communic...
Mathematical Sciences in Australia
ERIC Educational Resources Information Center
Thomas, Jan; Muchatuta, Michelle; Wood, Leigh
2009-01-01
This article investigates enrolment trends in mathematical sciences in Australian universities. Data has been difficult to extract and the coding for mathematical disciplines has made investigation challenging. We show that the number of mathematics major undergraduates in Australia is steadily declining though the number studying…
Machinability of nickel based alloys using electrical discharge machining process
NASA Astrophysics Data System (ADS)
Khan, M. Adam; Gokul, A. K.; Bharani Dharan, M. P.; Jeevakarthikeyan, R. V. S.; Uthayakumar, M.; Thirumalai Kumaran, S.; Duraiselvam, M.
2018-04-01
The high temperature materials such as nickel based alloys and austenitic steel are frequently used for manufacturing critical aero engine turbine components. Literature on conventional and unconventional machining of steel materials is abundant over the past three decades. However the machining studies on superalloy is still a challenging task due to its inherent property and quality. Thus this material is difficult to be cut in conventional processes. Study on unconventional machining process for nickel alloys is focused in this proposed research. Inconel718 and Monel 400 are the two different candidate materials used for electrical discharge machining (EDM) process. Investigation is to prepare a blind hole using copper electrode of 6mm diameter. Electrical parameters are varied to produce plasma spark for diffusion process and machining time is made constant to calculate the experimental results of both the material. Influence of process parameters on tool wear mechanism and material removal are considered from the proposed experimental design. While machining the tool has prone to discharge more materials due to production of high energy plasma spark and eddy current effect. The surface morphology of the machined surface were observed with high resolution FE SEM. Fused electrode found to be a spherical structure over the machined surface as clumps. Surface roughness were also measured with surface profile using profilometer. It is confirmed that there is no deviation and precise roundness of drilling is maintained.
The Locus analytical framework for indoor localization and tracking applications
NASA Astrophysics Data System (ADS)
Segou, Olga E.; Thomopoulos, Stelios C. A.
2015-05-01
Obtaining location information can be of paramount importance in the context of pervasive and context-aware computing applications. Many systems have been proposed to date, e.g. GPS that has been proven to offer satisfying results in outdoor areas. The increased effect of large and small scale fading in indoor environments, however, makes localization a challenge. This is particularly reflected in the multitude of different systems that have been proposed in the context of indoor localization (e.g. RADAR, Cricket etc). The performance of such systems is often validated on vastly different test beds and conditions, making performance comparisons difficult and often irrelevant. The Locus analytical framework incorporates algorithms from multiple disciplines such as channel modeling, non-uniform random number generation, computational geometry, localization, tracking and probabilistic modeling etc. in order to provide: (a) fast and accurate signal propagation simulation, (b) fast experimentation with localization and tracking algorithms and (c) an in-depth analysis methodology for estimating the performance limits of any Received Signal Strength localization system. Simulation results for the well-known Fingerprinting and Trilateration algorithms are herein presented and validated with experimental data collected in real conditions using IEEE 802.15.4 ZigBee modules. The analysis shows that the Locus framework accurately predicts the underlying distribution of the localization error and produces further estimates of the system's performance limitations (in a best-case/worst-case scenario basis).
Thermodynamic stability of boron: the role of defects and zero point motion.
van Setten, Michiel J; Uijttewaal, Matthé A; de Wijs, Gilles A; de Groot, Robert A
2007-03-07
Its low weight, high melting point, and large degree of hardness make elemental boron a technologically interesting material. The large number of allotropes, mostly containing over a hundred atoms in the unit cell, and their difficult characterization challenge both experimentalists and theoreticians. Even the ground state of this element is still under discussion. For over 30 years, scientists have attempted to determine the relative stability of alpha- and beta-rhombohedral boron. We use density functional calculations in the generalized gradient approximation to study a broad range of possible beta-rhombohedral structures containing interstitial atoms and partially occupied sites within a 105 atoms framework. The two most stable structures are practically degenerate in energy and semiconducting. One contains the experimental 320 atoms in the hexagonal unit cell, and the other contains 106 atoms in the triclinic unit cell. When populated with the experimental 320 electrons, the 106 atom structure exhibits a band gap of 1.4 eV and an in-gap hole trap at 0.35 eV above the valence band, consistent with known experiments. The total energy of these two structures is 23 meV/B lower than the original 105 atom framework, but it is still 1 meV/B above the alpha phase. Adding zero point energies finally makes the beta phase the ground state of elemental boron by 3 meV/B. At finite temperatures, the difference becomes even larger.
Epileptogenesis in experimental models.
Pitkänen, Asla; Kharatishvili, Irina; Karhunen, Heli; Lukasiuk, Katarzyna; Immonen, Riikka; Nairismägi, Jaak; Gröhn, Olli; Nissinen, Jari
2007-01-01
Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.
Peak provoked craving: an alternative to smoking cue-reactivity.
Sayette, Michael A; Tiffany, Stephen T
2013-06-01
Smoking cue-exposure research has provided a powerful tool for examining cravings in the laboratory. A key attraction of this method is that tightly controlled experimental procedures can model craving experiences that are presumed to relate to addiction. Despite its appeal, key assumptions underlying the clinical relevance of smoking cue-reactivity studies have been questioned recently. For both conceptual and methodological reasons it may be difficult to tease apart cue-based and abstinence-based cravings. Moreover, conventional cue-reactivity procedures typically generate levels of craving with only minimal clinical relevance. We argue here that sometimes it is unfeasible-and in some instances conceptually misguided-to disentangle abstinence-based and cued components of cigarette cravings. In light of the challenges associated with cue-reactivity research, we offer an alternative approach to smoking cue-exposure experimental research focusing on peak provoked craving (PPC) states. The PPC approach uses nicotine-deprived smokers and focuses on urges during smoking cue-exposure without subtracting out urge ratings during control cue or baseline assessments. This design relies on two factors found in many cue-exposure studies-nicotine deprivation and exposure to explicit smoking cues-which, when combined, can create powerful craving states. The PPC approach retains key aspects of the cue-exposure method, and in many circumstances may be a viable design for studies examining robust laboratory-induced cravings. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.
Maatz, Anke; Wainwright, Megan; Russell, Andrew J; Macnaughton, Jane; Yiannakou, Yan
2016-11-01
The term 'difficult' is pervasively used in relation to medically unexplained symptoms (MUS) and patients with MUS. This article scrutinises the use of the term by analysing interview data from a study of secondary care specialists' experiences with and attitudes towards patients suffering from MUS. Qualitative design employing semi-structured open-ended interviews systematically analysed in three stages: first, data were analysed according to the principles of content analysis. The analysis subsequently focused on the use of the term 'difficult'. Iterations of the term were extracted by summative analysis and thematic coding revealed its different meanings. Finally, alternative expressions were explored. Three NHS trust secondary care hospitals in North-East England. 17 senior clinicians from seven medical and two surgical specialities. Unsolicited use of the term 'difficult' was common. 'Difficult' was rarely used as a patient characteristic or to describe the therapeutic relationship. Participants used 'difficult' to describe their experience of diagnosing, explaining, communicating and managing these conditions and their own emotional reactions. Health care system deficits and the conceptual basis for MUS were other facets of 'difficult'. Participants also reported experiences that were rewarding and positive. This study shows that blanket statements such as 'difficult patients' mask the complexity of doctors' experiences in the context of MUS. Our nuanced analysis of the use of 'difficult' challenges preconceived attitudes. This can help counter the unreflexive perpetuation of negative evaluations that stigmatize patients with MUS, encourage greater acknowledgement of doctors' emotions, and lead to more appropriate conceptualizations and management of MUS. Copyright © 2016 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Tesfay, Hayelom D.
Bio-ceramics are those engineered materials that find their applications in the field of biomedical engineering or medicine. They have been widely used in dental restorations, repairing bones, joint replacements, pacemakers, kidney dialysis machines, and respirators. etc. due to their physico-chemical properties, such as excellent corrosion resistance, good biocompatibility, high strength and high wear resistance. Because of their inherent brittleness and hardness nature they are difficult to machine to exact sizes and dimensions. Abrasive machining processes such as grinding is one of the most widely used manufacturing processes for bioceramics. However, the principal technical challenge resulted from these machining is edge chipping. Edge chipping is a common edge failure commonly observed during the machining of bio-ceramic materials. The presence of edge chipping on bio-ceramic products affects dimensional accuracy, increases manufacturing cost, hider their industrial applications and causes potential failure during service. To overcome these technological challenges, a new ultrasonic vibration-assisted grinding (UVAG) manufacturing method has been developed and employed in this research. The ultimate aim of this study is to develop a new cost-effective manufacturing process relevant to eliminate edge chippings in grinding of bio-ceramic materials. In this dissertation, comprehensive investigations will be carried out using experimental, theoretical, and numerical approaches to evaluate the effect of ultrasonic vibrations on edge chipping of bioceramics. Moreover, effects of nine input variables (static load, vibration frequency, grinding depth, spindle speed, grinding distance, tool speed, grain size, grain number, and vibration amplitude) on edge chipping will be studied based on the developed models. Following a description of previous research and existing approaches, a series of experimental tests on three bio-ceramic materials (Lava, partially fired Lava, and Alumina) were conducted. Based on the experimental results, analytical models for UVAG and CG (conventional grinding without ultrasonic vibration) processes were developed. As for the numerical study, an extended finite element method (XFEM) based on Virtual Crack Closure Technique (VCCT) in ABAQUS was used to model the formation of edge chippings both for UVAG and CG processes. The experimental results are compared against the numerical FEA and the analytical models. The experimental, theoretical, and computational simulation results revealed that the edge chipping size of bioceramics can be significantly reduced with the assistance of ultrasonic vibration. The investigation procedures and the results obtained in this dissertation would be used as a reference and practical guidance for choosing reasonable process variables as well as designing mathematical (analytical and numerical) models in manufacturing industries and academic institutions when the edge chippings of brittle materials are expected to be controlled.
Shapiro, Johanna; Rakhra, Pavandeep; Wong, Adrianne
2016-10-01
Physicians have long had patients whom they have labeled "difficult", but little is known about how medical students perceive difficult encounters with patients. In this study, we analyzed 134 third year medical students' reflective essays written over an 18-month period about difficult student-patient encounters. We used a qualitative computerized software program, Atlas.ti to analyze students' observations and reflections. Main findings include that students described patients who were angry and upset; noncompliant with treatment plans; discussed "nonmedical" problems; fearful, worried, withdrawn, or "disinterested" in their health. Students often described themselves as anxious, uncertain, confused, and frustrated. Nevertheless, they saw themselves behaving in empathic and patient-centered ways while also taking refuge in "standard" behaviors not necessarily appropriate to the circumstances. Students rarely mentioned receiving guidance from attendings regarding how to manage these challenging interactions. These third-year medical students recognized the importance of behaving empathically in difficult situations and often did so. However, they often felt overwhelmed and frustrated, resorting to more reductive behaviors that did not match the needs of the patient. Students need more guidance from attending physicians in order to approach difficult interactions with specific problem-solving skills while maintaining an empathic, patient-centered context.
Pastor, M Carmen; Rehbein, Maimu Alissa; Junghöfer, Markus; Poy, Rosario; López, Raul; Moltó, Javier
2015-01-01
Several challenges make it difficult to simultaneously investigate central and autonomous nervous system correlates of conditioned stimulus (CS) processing in classical conditioning paradigms. Such challenges include, for example, the discrepant requirements of electroencephalography (EEG) and electrodermal activity (EDA) recordings with regard to multiple repetitions of conditions and sufficient trial duration. Here, we propose a MultiCS conditioning set-up, in which we increased the number of CSs, decreased the number of learning trials, and used trials of short and long durations for meeting requirements of simultaneous EEG-EDA recording in a differential aversive conditioning task. Forty-eight participants underwent MultiCS conditioning, in which four neutral faces (CS+) were paired four times each with aversive electric stimulation (unconditioned stimulus) during acquisition, while four different neutral faces (CS-) remained unpaired. When comparing after relative to before learning measurements, EEG revealed an enhanced centro-posterior positivity to CS+ vs. CS- during 368-600 ms, and subjective ratings indicated CS+ to be less pleasant and more arousing than CS-. Furthermore, changes in CS valence and arousal were strong enough to bias subjective ratings when faces of CS+/CS- identity were displayed with different emotional expression (happy, angry) in a post-experimental behavioral task. In contrast to a persistent neural and evaluative CS+/CS- differentiation that sustained multiple unreinforced CS presentations, electrodermal differentiation was rapidly extinguished. Current results suggest that MultiCS conditioning provides a promising paradigm for investigating pre-post-learning changes under minimal influences of extinction and overlearning of simple stimulus features. Our data also revealed methodological pitfalls, such as the possibility of occurring artifacts when combining different acquisition systems for central and peripheral psychophysiological measures.
NASA Astrophysics Data System (ADS)
Yalçınkaya, Eylem; Taştan-Kırık, Özgecan; Boz, Yezdan; Yıldıran, Demet
2012-07-01
Background: Case-based learning (CBL) is simply teaching the concept to the students based on the cases. CBL involves a case, which is a scenario based on daily life, and study questions related to the case, which allows students to discuss their ideas. Chemical kinetics is one of the most difficult concepts for students in chemistry. Students have generally low levels of conceptual understanding and many alternative conceptions regarding it. Purpose: This study aimed to explore the effect of CBL on dealing with students' alternative conceptions about chemical kinetics. Sample: The sample consists of 53 high school students from one public high school in Turkey. Design and methods : Nonequivalent pre-test and post-test control group design was used. Reaction Rate Concept Test and semi-structured interviews were used for data collection. Convenience sampling technique was followed. For data analysis, the independent samples t-test and ANOVA was performed. Results : Both concept test and interview results showed that students instructed with cases had better understanding of core concepts of chemical kinetics and had less alternative conceptions related to the subject matter compared to the control group students, despite the fact that it was impossible to challenge all the alternative conceptions in the experimental group. Conclusions: CBL is an effective teaching method for challenging students' alternative conceptions in the context of chemical kinetics. Since using cases in small groups and whole class discussions has been found to be an effective way to cope with the alternative conceptions, it can be applied to other subjects and grade levels in high schools with a higher sample size. Furthermore, the effect of this method on academic achievement, motivation and critical thinking skills are other variables that can be investigated for future studies in the subject area of chemistry.
Sedimentary Geology Context and Challenges for Cyberinfrastructure Data Management
NASA Astrophysics Data System (ADS)
Chan, M. A.; Budd, D. A.
2014-12-01
A cyberinfrastructure data management system for sedimentary geology is crucial to multiple facets of interdisciplinary Earth science research, as sedimentary systems form the deep-time framework for many geoscience communities. The breadth and depth of the sedimentary field spans research on the processes that form, shape and affect the Earth's sedimentary crust and distribute resources such as hydrocarbons, coal, and water. The sedimentary record is used by Earth scientists to explore questions such as the continental crust evolution, dynamics of Earth's past climates and oceans, evolution of the biosphere, and the human interface with Earth surface processes. Major challenges to a data management system for sedimentary geology are the volume and diversity of field, analytical, and experimental data, along with many types of physical objects. Objects include rock samples, biological specimens, cores, and photographs. Field data runs the gamut from discrete location and spatial orientation to vertical records of bed thickness, textures, color, sedimentary structures, and grain types. Ex situ information can include geochemistry, mineralogy, petrophysics, chronologic, and paleobiologic data. All data types cover multiple order-of-magnitude scales, often requiring correlation of the multiple scales with varying degrees of resolution. The stratigraphic framework needs dimensional context with locality, time, space, and depth relationships. A significant challenge is that physical objects represent discrete values at specific points, but measured stratigraphic sections are continuous. In many cases, field data is not easily quantified, and determining uncertainty can be difficult. Despite many possible hurdles, the sedimentary community is anxious to embrace geoinformatic resources that can provide better tools to integrate the many data types, create better search capabilities, and equip our communities to conduct high-impact science at unprecedented levels.
The Impact of Self-Narratives of Motherhood for Mothers of Children with Autism
Trzebiński, Jerzy; Wołowicz-Ruszkowska, Agnieszka; Wójcik, Adrian Dominik
2016-01-01
The main goal of this study was to identify the impact of a narrative construction of a life challenge - discovering to have a child with autism - on the meaning of life and on resources for coping depending on the challenge’s novelty, i.e., the number of years from the diagnosis. Three hundred and sixty four mothers of children with autism participated in a long-term 3 × 2 experiment. Half of the mothers had children with autism at the age of 9–12 years. For the remaining half, having children with autism was a new and stressful life situation. Their children were 2–3 years old and just diagnosed by a medical center as having autism spectrum disorder. The mothers were assigned to one of three study conditions: they were either asked to write stories of their motherhood or to describe their children’s behavior on a questionnaire or they did not participate in any tasks. One month and then 4 months after this task the participants completed measures of meaning of life and several well-being scales. The results indicated that following the narrative writing the participants had the highest scores on the meaning of life and well-being scales. This affect was sustained over 4 months and was significant only for mothers with older children. The mediation analysis showed that the effects of the experimental conditions on different well-being scales were mediated by the changes in perceived meaning of life. The results suggest that construction of self-narratives of difficult ongoing challenges facilitates meaning making and subsequently strengthens resources for coping. However, it seems that a meaning-making construction of such self-story may be blocked by the uncertainty and stress caused by novelty of the challenging situation. PMID:27994568
Toddler’s Self-Regulation Strategies in a Challenge Context are Nap-Dependent
Miller, Alison L.; Seifer, Ronald; Crossin, Rebecca; LeBourgeois, Monique K.
2015-01-01
SUMMARY Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one’s behavior, attention, and emotion when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers’ self-regulation. Healthy children (n=12; 4 males; 30–36 months (33.9±1.7) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a Nap and a No-Nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the No-Nap versus the Nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in skepticism (d=0.77; 7% change), negative self-appraisal (d=0.92; 5% change), and increases in physical self-soothing (d=0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d=0.50; 9% change), and insistence on completing the unsolvable puzzle (d=0.91; 10% change). Results suggest sleep serves an important role in the way toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to effectively engage in a difficult task and reverted to less mature self-regulation strategies, than when they were well-rested. Over time, chronically missed sleep may impair young children’s self-regulation abilities, resulting in risk for social-emotional, behavioral, and school problems. PMID:25394169
Toddler's self-regulation strategies in a challenge context are nap-dependent.
Miller, Alison L; Seifer, Ronald; Crossin, Rebecca; Lebourgeois, Monique K
2015-06-01
Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers' self-regulation. Healthy children (n = 12; four males; aged 30-36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no-nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the no-nap versus the nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self-appraisal (d = 0.92; 5% change) and increases in physical self-soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self-regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self-regulation abilities, resulting in risk for social-emotional, behavioural and school problems. © 2014 European Sleep Research Society.
Fasani, Rick A; Livi, Carolina B; Choudhury, Dipanwita R; Kleensang, Andre; Bouhifd, Mounir; Pendse, Salil N; McMullen, Patrick D; Andersen, Melvin E; Hartung, Thomas; Rosenberg, Michael
2015-01-01
The Human Toxome Project is part of a long-term vision to modernize toxicity testing for the 21st century. In the initial phase of the project, a consortium of six academic, commercial, and government organizations has partnered to map pathways of toxicity, using endocrine disruption as a model hazard. Experimental data is generated at multiple sites, and analyzed using a range of computational tools. While effectively gathering, managing, and analyzing the data for high-content experiments is a challenge in its own right, doing so for a growing number of -omics technologies, with larger data sets, across multiple institutions complicates the process. Interestingly, one of the most difficult, ongoing challenges has been the computational collaboration between the geographically separate institutions. Existing solutions cannot handle the growing heterogeneous data, provide a computational environment for consistent analysis, accommodate different workflows, and adapt to the constantly evolving methods and goals of a research project. To meet the needs of the project, we have created and managed The Human Toxome Collaboratorium, a shared computational environment hosted on third-party cloud services. The Collaboratorium provides a familiar virtual desktop, with a mix of commercial, open-source, and custom-built applications. It shares some of the challenges of traditional information technology, but with unique and unexpected constraints that emerge from the cloud. Here we describe the problems we faced, the current architecture of the solution, an example of its use, the major lessons we learned, and the future potential of the concept. In particular, the Collaboratorium represents a novel distribution method that could increase the reproducibility and reusability of results from similar large, multi-omic studies.
Pastor, M. Carmen; Rehbein, Maimu Alissa; Junghöfer, Markus; Poy, Rosario; López, Raul; Moltó, Javier
2015-01-01
Several challenges make it difficult to simultaneously investigate central and autonomous nervous system correlates of conditioned stimulus (CS) processing in classical conditioning paradigms. Such challenges include, for example, the discrepant requirements of electroencephalography (EEG) and electrodermal activity (EDA) recordings with regard to multiple repetitions of conditions and sufficient trial duration. Here, we propose a MultiCS conditioning set-up, in which we increased the number of CSs, decreased the number of learning trials, and used trials of short and long durations for meeting requirements of simultaneous EEG–EDA recording in a differential aversive conditioning task. Forty-eight participants underwent MultiCS conditioning, in which four neutral faces (CS+) were paired four times each with aversive electric stimulation (unconditioned stimulus) during acquisition, while four different neutral faces (CS−) remained unpaired. When comparing after relative to before learning measurements, EEG revealed an enhanced centro-posterior positivity to CS+ vs. CS− during 368–600 ms, and subjective ratings indicated CS+ to be less pleasant and more arousing than CS−. Furthermore, changes in CS valence and arousal were strong enough to bias subjective ratings when faces of CS+/CS− identity were displayed with different emotional expression (happy, angry) in a post-experimental behavioral task. In contrast to a persistent neural and evaluative CS+/CS− differentiation that sustained multiple unreinforced CS presentations, electrodermal differentiation was rapidly extinguished. Current results suggest that MultiCS conditioning provides a promising paradigm for investigating pre–post-learning changes under minimal influences of extinction and overlearning of simple stimulus features. Our data also revealed methodological pitfalls, such as the possibility of occurring artifacts when combining different acquisition systems for central and peripheral psychophysiological measures. PMID:26106318
ERIC Educational Resources Information Center
Stuart, Shannon
2012-01-01
Schools have struggled for decades to provide expensive augmentative and alternative communication (AAC) resources for autistic students with communication challenges. Clunky voice output devices, often included in students' individualized education plans, cost about $8,000, a difficult expense to cover in hard times. However, mobile technology is…
Habitat degradation and loss as key drivers of regional population extinction
Habitat quality is a fundamental driver of species distributions and population outcomes but is often difficult to measure. Further, habitat quality can be abstract, multi-faceted and challenging to compare alongside measures of habitat amount and fragmentation. Consequently, hab...
ISSUES AND CHALLENGES IN MODELING CHILDREN'S LONGITUDINAL EXPOSURES: AN OZONE STUDY
Modeling children's exposures is a complicated, data-intensive process. Modeling longitudinal exposures, which are important for regulatory decision making, especially for most air toxics, adds another level of complexity and data requirements. Because it is difficult to model in...
Student Goals: Psychological Perspectives
ERIC Educational Resources Information Center
Muirhead, Brent; Little, Jennifer
2008-01-01
The paper will discuss research insights into student academic goals. Cognitive psychologists have found that effective goal setting procedures involves establishing specific and challenging learning objectives. Students who set difficult goals must be persistent while facing the risk of potential failure that could diminish their intrinsic…
Describing Acupuncture: A New Challenge for Technical Communicators.
ERIC Educational Resources Information Center
Karanikas, Marianthe
1997-01-01
Considers acupuncture as an increasingly popular alternative medical therapy, but difficult to describe in technical communication. Notes that traditional Chinese medical explanations of acupuncture are unscientific, and that scientific explanations of acupuncture are inconclusive. Finds that technical communicators must translate acupuncture for…
Inspiring us to inspire others.
2004-07-01
All nurses who genuinely care about older people will have encountered difficult situations that necessitate understanding, help and support. At times like this, good leaders can be crucial. They can make the difference between us mustering resources to overcome the challenges, and being overwhelmed by them.
ERIC Educational Resources Information Center
Jones, Joseph; Vari, T. J.
2017-01-01
The idea of conversations around performance reviews, and even more challenging improvement plans, is daunting. Even though the goal is to improve the employee's performance, difficult conversations don't automatically stimulate an environment and culture of continual growth. Establishing and systematizing professional dialogue in the workplace…
A review of stormwater management in karst
USDA-ARS?s Scientific Manuscript database
Stormwater management can be a challenge in any environment, but it is especially difficult in karst terrain. The characteristic dissolution of bedrock creates depressions in topography as well as voids in the subsurface, resulting in problems such as collapse sinkhole development, groundwater cont...
Soil mixing design methods and construction techniques for use in high organic soils.
DOT National Transportation Integrated Search
2015-06-01
Organic soils present a difficult challenge for roadway designers and construction due to the high : compressibility of the soil structure and the often associated high water table and moisture content. For : other soft or loose inorganic soils, stab...
Thomas, Frank; Carpenter, Judi; Rhoades, Carol; Holleran, Renee; Snow, Gregory
2010-04-01
This exploratory study examined novice intubators and the effect difficult airway factors have on pre- and posttraining oral-tracheal simulation intubation success rates. Using a two-level, full-factorial design of experimentation (DOE) involving a combination of six airway factors (curved vs. straight laryngoscope blade, trismus, tongue edema, laryngeal spasm, pharyngeal obstruction, or cervical immobilization), 64 airway scenarios were prospectively randomized to 12 critical care nurses to evaluate pre- and posttraining first-pass intubation success rates on a simulator. Scenario variables and intubation outcomes were analyzed using a generalized linear mixed-effects model to determine two-way main and interactive effects. Interactive effects between the six study factors were nonsignificant (p = 0.69). For both pre- and posttraining, main effects showed the straight blade (p = 0.006), tongue edema (p = 0.0001), and laryngeal spasm (p = 0.004) significantly reduced success rates, while trismus (p = 0.358), pharyngeal obstruction (p = 0.078), and cervical immobilization did not significantly change the success rate. First-pass intubation success rate on the simulator significantly improved (p = 0.005) from pre- (19%) to posttraining (36%). Design of experimentation is useful in analyzing the effect difficult airway factors and training have on simulator intubation success rates. Future quality improvement DOE simulator research studies should be performed to help clarify the relationship between simulator factors and patient intubation rates.
Biswas, Animesh; Dalal, Koustuv; Abdullah, Abu Sayeed Md; Gifford, Mervyn; Halim, M A
2016-01-01
Background: Maternal complications contribute to maternal deaths in developing countries. Bangladesh still has a high prevalence of maternal mortality, which is often preventable. There are some geographically challenging and hard to reach rural districts in Bangladesh and it is difficult to get information about maternal complications in these areas. In this study, we examined the community lay knowledge of possible pregnancy complications. We also examined the common practices associated with complications and we discuss the challenges for the community. Methods: The study was conducted in Moulvibazar of north east Bangladesh, a geographically challenged, difficult to reach district. Qualitative methods were used to collect the information. Pregnant women, mothers who had recently delivered, their guardians and traditional birth attendants participated in focus group discussions. Additionally, in-depth interviews were conducted with the family members. Thematic analyses were performed. Results: The study revealed that there is a lack of knowledge of maternal complications. In the majority of cases, the mothers did not receive proper treatment for maternal complications. There are significant challenges that these rural societies need to address: problems of ignorance, traditional myths and family restrictions on seeking better treatment. Moreover, traditional birth attendants and village doctors also have an important role in assuring appropriate, effective and timely treatment. Conclusions: The rural community lacks adequate knowledge on maternal complications. Reduction of the societal barriers including barriers within the family can improve overall practices. Moreover, dissemination of adequate information to the traditional birth attendant and village doctors may improve the overall situation, which would eventually help to reduce maternal deaths.
Recent Transonic Flutter Investigations for Wings and External Stores
1983-01-01
and difficult method? In the early days of high-speed air- craft design . the aeroelastician realized that non -compressible aerodynamic theory and... experimental aeroelastic model program that would provide insight into the effects of Reynolds number and angle of attack on various airfoil designs regarding...investigation is carried out both experimentally and analytically. The analytic modelling will be described in a later section. The flutter calculations
Development of a new photocatalytic oxidation air filter for aircraft cabin.
Ginestet, A; Pugnet, D; Rowley, J; Bull, K; Yeomans, H
2005-10-01
A new photocatalytic oxidation air filter (PCO unit) has been designed for aircraft cabin applications. The PCO unit is designed as a regenerable VOC removal system in order to improve the quality of the recirculated air entering the aircraft cabin. The PCO was designed to be a modular unit, with four UV lamps sandwiched between two interchangeable titanium dioxide coated panels. Performances of the PCO unit has been measured in a single pass mode test rig in order to show the ability of the unit to decrease the amount of VOCs (toluene, ethanol, and acetone) entering it (VOCs are fed separately), and in a multipass mode test rig in order to measure the ability of the unit to clean the air of an experimental room polluted with the same VOCs (fed separately). Triangular cell panels have been chosen instead of the wire mesh panels because they have higher efficiency. The efficiency of the PCO unit depends on the type of VOCs that challenges it, toluene being the most difficult one to oxidise. The efficiency of the PCO unit decreases when the air flow rate increases. The multipass mode test results show that the VOCs are oxidized but additional testing time would be necessary in order to show if they can be fully oxidized. The intermediate reaction products are mainly acetaldehyde and formaldehyde whose amount depends on the challenge VOC. The intermediate reaction products are also oxidized and additional testing time would be necessary in order to show if they can be fully oxidized. The development of this new photocatalytic air filter is still going on. The VOC/odor removing adsorbers are available for only a small proportion of aircraft currently in service. The photocatalytic oxidation (PCO) technique has appeared to be a promising solution to odors problems met in aircraft. This article reports the test results of a new photocatalytic oxidation air filter (PCO unit) designed for aircraft cabin applications. The overall efficiency of the PCO unit is function of the compound (toluene, ethanol, and acetone) that challenges the unit and toluene appears to be the most difficult compound to oxidize. Test results have shown the influence of the design of the PCO unit, the air flow rate and the type of UV on the efficiency of the PCO unit. The results obtained in this study represent a first attempt on the way to design a filter for VOC removal in cabin aircraft applications. The PCO technique used by the tested prototype unit is able to partially oxidized the challenge VOCs but one has to be aware that some harmful intermediate reaction products (mainly formaldehyde and acetaldehyde) are produced during the oxidation process before being partially oxidized too.
Case study: a health check-up for the corporate IT department.
Clark, Frank; Kimmerly, William
2004-01-01
As advances such as the electronic charting, closed-loop medication safety, physician order entry, consumer portals, electronic collaboration, and wireless access become the norm, central IS organizations are finding it difficult to keep pace. This challenge is exacerbated by declining margins, severe cost pressures, increased regulation, and added public scrutiny. Is your centralized IS organization healthy enough to meet the challenges presented by today's complex, demanding, dynamic healthcare delivery environments? How do you know? What factors do you consider?
Employee vs independent contractor.
Kolender, Ellen
2012-01-01
Finding qualified personnel for the cancer registry department has become increasingly difficult, as experienced abstractors retire and cancer diagnoses increase. Faced with hiring challenges, managers turn to teleworkers to fill positions and accomplish work in a timely manner. Suddenly, the hospital hires new legal staff and all telework agreements are disrupted. The question arises: Are teleworkers employees or independent contractors? Creating telework positions requires approval from the legal department and human resources. Caught off-guard in the last quarter of the year, I found myself again faced with hiring challenges.
2012-07-01
modification, we changed the script such that the confederate not only exhibits the target skills but also a range of challenging responses that may make...implementation of the target skills more difficult. By including these challenging responses during the role-plays, the parents and tutors are...that may be recommended during the installation. d. VLC Player: i. Open the VLC installer. Under installation type select “recommended.” e. K-Lite
Current Challenges in the Management of Prolactinomas.
Maiter, Dominique
2015-04-01
Although the diagnosis of prolactinoma is often straightforward and the treatment strategy has been well defined in recent guidelines, several challenging issues persist in their management. The differential diagnosis of a large pituitary tumour with moderately elevated prolactin (PRL) concentrations is sometimes difficult, and prolonged treatment with a dopamine agonist may be inappropriate when the diagnosis of a prolactinoma is not sufficiently well substantiated. Also, timely withdrawal of dopamine agonist treatment and the remaining indications of transsphenoidal surgery are still matters of debate. Last but not least, the management of resistant or aggressive prolactinomas remains a challenge for the clinician, especially when they occur in young patients.
Current Challenges in the Management of Prolactinomas
2015-01-01
Summary Although the diagnosis of prolactinoma is often straightforward and the treatment strategy has been well defined in recent guidelines, several challenging issues persist in their management. The differential diagnosis of a large pituitary tumour with moderately elevated prolactin (PRL) concentrations is sometimes difficult, and prolonged treatment with a dopamine agonist may be inappropriate when the diagnosis of a prolactinoma is not sufficiently well substantiated. Also, timely withdrawal of dopamine agonist treatment and the remaining indications of transsphenoidal surgery are still matters of debate. Last but not least, the management of resistant or aggressive prolactinomas remains a challenge for the clinician, especially when they occur in young patients. PMID:29632566
Strategies and Challenges in Simultaneous Augmentation Mastopexy.
Spring, Michelle A; Hartmann, Emily C; Stevens, W Grant
2015-10-01
Simultaneous breast augmentation and mastopexy is a common procedure often considered to be one of the most difficult cosmetic breast surgeries. One-stage augmentation mastopexy was initially described more than 50 years ago. The challenge lies in the fact that the surgery has multiple opposing goals: to increasing the volume of a breast, enhance the shape, and simultaneously decrease the skin envelope. Successful outcomes in augmentation can be expected with proper planning, technique, and patient education. This article focuses on common indications for simultaneous augmentation mastopexy, techniques for safe and effective combined procedures, challenges of the procedure, and potential complications. Copyright © 2015 Elsevier Inc. All rights reserved.
Multiwavelength Challenges in the Fermi Era
NASA Technical Reports Server (NTRS)
Thompson, D. J.
2010-01-01
The gamma-ray surveys of the sky by AGILE and the Fermi Gamma-ray Space Telescope offer both opportunities and challenges for multiwavelength and multi-messenger studies. Gamma-ray bursts, pulsars, binary sources, flaring Active Galactic Nuclei, and Galactic transient sources are all phenomena that can best be studied with a wide variety of instruments simultaneously or contemporaneously. From the gamma-ray side, a principal challenge is the latency from the time of an astrophysical event to the recognition of this event in the data. Obtaining quick and complete multiwavelength coverage of gamma-ray sources of interest can be difficult both in terms of logistics and in terms of generating scientific interest.
In-Situ monitoring and modeling of metal additive manufacturing powder bed fusion
NASA Astrophysics Data System (ADS)
Alldredge, Jacob; Slotwinski, John; Storck, Steven; Kim, Sam; Goldberg, Arnold; Montalbano, Timothy
2018-04-01
One of the major challenges in metal additive manufacturing is developing in-situ sensing and feedback control capabilities to eliminate build errors and allow qualified part creation without the need for costly and destructive external testing. Previously, many groups have focused on high fidelity numerical modeling and true temperature thermal imaging systems. These approaches require large computational resources or costly hardware that requires complex calibration and are difficult to integrate into commercial systems. In addition, due to the rapid change in the state of the material as well as its surface properties, getting true temperature is complicated and difficult. Here, we describe a different approach where we implement a low cost thermal imaging solution allowing for relative temperature measurements sufficient for detecting unwanted process variability. We match this with a faster than real time qualitative model that allows the process to be rapidly modeled during the build. The hope is to combine these two, allowing for the detection of anomalies in real time, enabling corrective action to potentially be taken, or parts to be stopped immediately after the error, saving material and time. Here we describe our sensor setup, its costs and abilities. We also show the ability to detect in real time unwanted process deviations. We also show that the output of our high speed model agrees qualitatively with experimental results. These results lay the groundwork for our vision of an integrated feedback and control scheme that combines low cost, easy to use sensors and fast modeling for process deviation monitoring.
A toolbox and record for scientific models
NASA Technical Reports Server (NTRS)
Ellman, Thomas
1994-01-01
Computational science presents a host of challenges for the field of knowledge-based software design. Scientific computation models are difficult to construct. Models constructed by one scientist are easily misapplied by other scientists to problems for which they are not well-suited. Finally, models constructed by one scientist are difficult for others to modify or extend to handle new types of problems. Construction of scientific models actually involves much more than the mechanics of building a single computational model. In the course of developing a model, a scientist will often test a candidate model against experimental data or against a priori expectations. Test results often lead to revisions of the model and a consequent need for additional testing. During a single model development session, a scientist typically examines a whole series of alternative models, each using different simplifying assumptions or modeling techniques. A useful scientific software design tool must support these aspects of the model development process as well. In particular, it should propose and carry out tests of candidate models. It should analyze test results and identify models and parts of models that must be changed. It should determine what types of changes can potentially cure a given negative test result. It should organize candidate models, test data, and test results into a coherent record of the development process. Finally, it should exploit the development record for two purposes: (1) automatically determining the applicability of a scientific model to a given problem; (2) supporting revision of a scientific model to handle a new type of problem. Existing knowledge-based software design tools must be extended in order to provide these facilities.
Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.
Kivelevitch, Dario; Frieder, Jillian; Watson, Ian; Paek, So Yeon; Menter, M Alan
2018-04-01
Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. Expert opinion: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.
REDUCING AMBIGUITY IN THE FUNCTIONAL ASSESSMENT OF PROBLEM BEHAVIOR
Rooker, Griffin W.; DeLeon, Iser G.; Borrero, Carrie S. W.; Frank-Crawford, Michelle A.; Roscoe, Eileen M.
2015-01-01
Severe problem behavior (e.g., self-injury and aggression) remains among the most serious challenges for the habilitation of persons with intellectual disabilities and is a significant obstacle to community integration. The current standard of behavior analytic treatment for problem behavior in this population consists of a functional assessment and treatment model. Within that model, the first step is to assess the behavior–environment relations that give rise to and maintain problem behavior, a functional behavioral assessment. Conventional methods of assessing behavioral function include indirect, descriptive, and experimental assessments of problem behavior. Clinical investigators have produced a rich literature demonstrating the relative effectiveness for each method, but in clinical practice, each can produce ambiguous or difficult-to-interpret outcomes that may impede treatment development. This paper outlines potential sources of variability in assessment outcomes and then reviews the evidence on strategies for avoiding ambiguous outcomes and/or clarifying initially ambiguous results. The end result for each assessment method is a set of best practice guidelines, given the available evidence, for conducting the initial assessment. PMID:26236145
Laboratory automation: a challenge for the 1990s.
Mordini, C
1994-01-01
THERE IS TREMENDOUS PRESSURE ON INDUSTRY AND LABORATORIES TO DEVELOP INCREASINGLY COMPLEX PROCUCTS: for example catalysts, chiral chemicals, drugs and ceramics; conform to regulations; cope with increasingly severe competition; and meet steadily increasing costs. It is difficult, in this situation, to remain productive and competitive. It is vital to be equipped with, and be able to use appropriately, all the suitable methodologies and technologies. Working methods and personnel have to be appropriate. The future depends on three interdependent domains: automation in the broadest sense of the word, instrumentation and information systems. The easy work has already been done. Between 1984 and 1990, it was a question of going from nothing to something; now, it is necessary to increase and optimize.THEREFORE, THE CRUCIAL QUESTION IS NOW: 'how can we go quicker in experimentation and acquire more knowledge, while spending less money?' One solution is to use all the aspects of automation (robotics, instrumentation, data). Successful laboratory automation depends.on: shortened time to market; improved efficiency/cost ratio; motivation/competence/ expertise; communication; and knowledge acquisition. This paper examines some of the major technological areas of application.
Laboratory automation: a challenge for the 1990s
Mordini, Claude
1994-01-01
There is tremendous pressure on industry and laboratories to develop increasingly complex procucts: for example catalysts, chiral chemicals, drugs and ceramics; conform to regulations; cope with increasingly severe competition; and meet steadily increasing costs. It is difficult, in this situation, to remain productive and competitive. It is vital to be equipped with, and be able to use appropriately, all the suitable methodologies and technologies. Working methods and personnel have to be appropriate. The future depends on three interdependent domains: automation in the broadest sense of the word, instrumentation and information systems. The easy work has already been done. Between 1984 and 1990, it was a question of going from nothing to something; now, it is necessary to increase and optimize. Therefore, the crucial question is now: ‘how can we go quicker in experimentation and acquire more knowledge, while spending less money?’ One solution is to use all the aspects of automation (robotics, instrumentation, data). Successful laboratory automation depends.on: shortened time to market; improved efficiency/cost ratio; motivation/competence/ expertise; communication; and knowledge acquisition. This paper examines some of the major technological areas of application. PMID:18924998
Distinguishing between microscale gaseous bubbles and liquid drops
NASA Astrophysics Data System (ADS)
Tan, Beng Hau; An, Hongjie; Chan, Chon U.; Ohl, Claus-Dieter
2015-11-01
In recent years, there has been strong research interest in decorating surfaces with tiny bubbles and drops due to their potential applications in reducing slippage in micro and nanofluidic devices. Both nanobubbles and nanodrops are typically nucleated by exchanging fluids over a suitable substrate. However, the nucleation experiments present many challenges, such as reproducibility and the possibility of contamination. The use of one-use plastic syringes and needle cannulas in nucleation experiments can introduce polymeric contamination. A contaminated experiment may nucleate bubbles, drops or both. Moreover, it is surprisingly difficult to distinguish between bubbles and drops under the usual atomic force microscopy or optical techniques. Here we present an experimental study comparing bubbles and oil (PDMS) drops on an atomically smooth surface (HOPG). Instead of nucleating the objects via solvent exchange, we directly introduced bubbles via electrolysis, and oil drops by injecting a dilute solution. Contrary to previous reports, we find that under careful AFM characterisation, liquid drops and gaseous bubbles respond differently to a change in imaging force, and moreover present different characteristic force curves.
The Mechanisms of Aberrant Protein Aggregation
NASA Astrophysics Data System (ADS)
Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas
2012-02-01
We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.
Naqvi, S A; Naseer, M; Kazi, A; Pethani, A; Naeem, I; Zainab, S; Fatmi, Z
2012-06-01
Six towns of Karachi, Pakistan. 1) To strengthen the capacity of general practitioners (GPs) in providing tuberculosis (TB) treatment through DOTS; and 2) to enhance collaboration between the public and private sectors in TB management and case reporting. A quasi-experimental study design was adopted to ensure enrolment of TB patients through trained GPs with the support of laboratory networks and to improve the case detection rate. The following challenges were faced during implementation of the model in urban settings: no systematic list of GPs was available; the majority of the GPs were untrained health practitioners working in squatter settlements, where formally trained GPs are most needed; the motivation of GPs with high patient loads is very low; and access to a laboratory is difficult. Of 35 patients enrolled in the first quarter (third quarter 2009), 87% completed their treatment successfully. Public-private mix (PPM) DOTS is feasible in the cities of Pakistan. However, the cost, time and effort required to establish the programme is higher than in many other developing countries.
NASA Astrophysics Data System (ADS)
Ward, Matthew J.; Rupar, Paul A.; Murphy, Michael W.; Yiu, Yun-Mui; Baines, Kim M.; Sham, Tsun-Kong
2013-04-01
Digermene, the germanium analogue of ethylene, has a multiple bonding motif that differs greatly from that of alkenes and exhibits no pure σ or π type bonds. The electronic structure of digermenes is difficult to study experimentally due to their reactivity, and is computationally challenging because of their shallow potential energy surfaces. Using X-ray absorption near edge structures at both the germanium K and L edges we have been able to directly probe the unoccupied electronic states, or the lowest unoccupied molecular orbital (LUMO), and LUMO+ etc. in the Ge=Ge bond of tetramesityldigermene. We have demonstrated that the LUMO, LUMO+, etc. are composed of hybrid Ge 4s and 4p orbitals. Additionally, our data suggest that the LUMO exhibits relatively more Ge 4s character, whereas the LUMO+ and LUMO+2 exhibit relatively more Ge 4p character. An X-ray excited optical luminescence study of Ge2Mes4 revealed one broad optical emission band at 620 nm, which is significantly red shifted compared to the known energy gap of this molecular germanium compound.
Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology
Salazar, Brittany M.; Balczewski, Emily A.; Ung, Choong Yong; Zhu, Shizhen
2016-01-01
Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring “big data” applications in pediatric oncology. Computational strategies derived from big data science–network- and machine learning-based modeling and drug repositioning—hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which “big data” and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases. PMID:28035989
Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology.
Salazar, Brittany M; Balczewski, Emily A; Ung, Choong Yong; Zhu, Shizhen
2016-12-27
Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring "big data" applications in pediatric oncology. Computational strategies derived from big data science-network- and machine learning-based modeling and drug repositioning-hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which "big data" and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.
An improved finite element modeling of the cerebrospinal fluid layer in the head impact analysis.
Wu, John Z; Pan, Christopher S; Wimer, Bryan M; Rosen, Charles L
2017-01-01
The finite element (FE) method has been widely used to investigate the mechanism of traumatic brain injuries (TBIs), because it is technically difficult to quantify the responses of the brain tissues to the impact in experiments. One of technical challenges to build a FE model of a human head is the modeling of the cerebrospinal fluid (CSF) of the brain. In the current study, we propose to use membrane elements to construct the CSF layer. Using the proposed approach, we demonstrate that a head model can be built by using existing meshes available in commercial databases, without using any advanced meshing software tool, and with the sole use of native functions of the FE package Abaqus. The calculated time histories of the intracranial pressures at frontal, posterior fossa, parietal, and occipital positions agree well with the experimental data and the simulations in the literature, indicating that the physical effects of the CSF layer have been accounted for in the proposed modeling approach. The proposed modeling approach would be useful for bioengineers to solve practical problems.
Time-Lapse, in Situ Imaging of Ice Crystal Growth Using Confocal Microscopy
2016-01-01
Ice crystals nucleate and grow when a water solution is cooled below its freezing point. The growth velocities and morphologies of the ice crystals depend on many parameters, such as the temperature of ice growth, the melting temperature, and the interactions of solutes with the growing crystals. Three types of morphologies may appear: dendritic, cellular (or fingerlike), or the faceted equilibrium form. Understanding and controlling which type of morphology is formed is essential in several domains, from biology to geophysics and materials science. Obtaining, in situ, three dimensional observations without introducing artifacts due to the experimental technique is nevertheless challenging. Here we show how we can use laser scanning confocal microscopy to follow in real-time the growth of smoothed and faceted ice crystals in zirconium acetate solutions. Both qualitative and quantitative observations can be made. In particular, we can precisely measure the lateral growth velocity of the crystals, a measure otherwise difficult to obtain. Such observations should help us understand the influence of the parameters that control the growth of ice crystals in various systems. PMID:27917410
An evolutionary firefly algorithm for the estimation of nonlinear biological model parameters.
Abdullah, Afnizanfaizal; Deris, Safaai; Anwar, Sohail; Arjunan, Satya N V
2013-01-01
The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.
An Evolutionary Firefly Algorithm for the Estimation of Nonlinear Biological Model Parameters
Abdullah, Afnizanfaizal; Deris, Safaai; Anwar, Sohail; Arjunan, Satya N. V.
2013-01-01
The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test. PMID:23469172
Mathematical modeling for novel cancer drug discovery and development.
Zhang, Ping; Brusic, Vladimir
2014-10-01
Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments. This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silico discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine.
NASA Astrophysics Data System (ADS)
Feng, Shou; Fu, Ping; Zheng, Wenbin
2018-03-01
Predicting gene function based on biological instrumental data is a complicated and challenging hierarchical multi-label classification (HMC) problem. When using local approach methods to solve this problem, a preliminary results processing method is usually needed. This paper proposed a novel preliminary results processing method called the nodes interaction method. The nodes interaction method revises the preliminary results and guarantees that the predictions are consistent with the hierarchy constraint. This method exploits the label dependency and considers the hierarchical interaction between nodes when making decisions based on the Bayesian network in its first phase. In the second phase, this method further adjusts the results according to the hierarchy constraint. Implementing the nodes interaction method in the HMC framework also enhances the HMC performance for solving the gene function prediction problem based on the Gene Ontology (GO), the hierarchy of which is a directed acyclic graph that is more difficult to tackle. The experimental results validate the promising performance of the proposed method compared to state-of-the-art methods on eight benchmark yeast data sets annotated by the GO.
Set-free Markov state model building
NASA Astrophysics Data System (ADS)
Weber, Marcus; Fackeldey, Konstantin; Schütte, Christof
2017-03-01
Molecular dynamics (MD) simulations face challenging problems since the time scales of interest often are much longer than what is possible to simulate; and even if sufficiently long simulations are possible the complex nature of the resulting simulation data makes interpretation difficult. Markov State Models (MSMs) help to overcome these problems by making experimentally relevant time scales accessible via coarse grained representations that also allow for convenient interpretation. However, standard set-based MSMs exhibit some caveats limiting their approximation quality and statistical significance. One of the main caveats results from the fact that typical MD trajectories repeatedly re-cross the boundary between the sets used to build the MSM which causes statistical bias in estimating the transition probabilities between these sets. In this article, we present a set-free approach to MSM building utilizing smooth overlapping ansatz functions instead of sets and an adaptive refinement approach. This kind of meshless discretization helps to overcome the recrossing problem and yields an adaptive refinement procedure that allows us to improve the quality of the model while exploring state space and inserting new ansatz functions into the MSM.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Webb-Robertson, Bobbie-Jo M.
Accurate identification of peptides is a current challenge in mass spectrometry (MS) based proteomics. The standard approach uses a search routine to compare tandem mass spectra to a database of peptides associated with the target organism. These database search routines yield multiple metrics associated with the quality of the mapping of the experimental spectrum to the theoretical spectrum of a peptide. The structure of these results make separating correct from false identifications difficult and has created a false identification problem. Statistical confidence scores are an approach to battle this false positive problem that has led to significant improvements in peptidemore » identification. We have shown that machine learning, specifically support vector machine (SVM), is an effective approach to separating true peptide identifications from false ones. The SVM-based peptide statistical scoring method transforms a peptide into a vector representation based on database search metrics to train and validate the SVM. In practice, following the database search routine, a peptides is denoted in its vector representation and the SVM generates a single statistical score that is then used to classify presence or absence in the sample« less
Signal decomposition for surrogate modeling of a constrained ultrasonic design space
NASA Astrophysics Data System (ADS)
Homa, Laura; Sparkman, Daniel; Wertz, John; Welter, John; Aldrin, John C.
2018-04-01
The U.S. Air Force seeks to improve the methods and measures by which the lifecycle of composite structures are managed. Nondestructive evaluation of damage - particularly internal damage resulting from impact - represents a significant input to that improvement. Conventional ultrasound can detect this damage; however, full 3D characterization has not been demonstrated. A proposed approach for robust characterization uses model-based inversion through fitting of simulated results to experimental data. One challenge with this approach is the high computational expense of the forward model to simulate the ultrasonic B-scans for each damage scenario. A potential solution is to construct a surrogate model using a subset of simulated ultrasonic scans built using a highly accurate, computationally expensive forward model. However, the dimensionality of these simulated B-scans makes interpolating between them a difficult and potentially infeasible problem. Thus, we propose using the chirplet decomposition to reduce the dimensionality of the data, and allow for interpolation in the chirplet parameter space. By applying the chirplet decomposition, we are able to extract the salient features in the data and construct a surrogate forward model.
Medusa: A Scalable MR Console Using USB
Stang, Pascal P.; Conolly, Steven M.; Santos, Juan M.; Pauly, John M.; Scott, Greig C.
2012-01-01
MRI pulse sequence consoles typically employ closed proprietary hardware, software, and interfaces, making difficult any adaptation for innovative experimental technology. Yet MRI systems research is trending to higher channel count receivers, transmitters, gradient/shims, and unique interfaces for interventional applications. Customized console designs are now feasible for researchers with modern electronic components, but high data rates, synchronization, scalability, and cost present important challenges. Implementing large multi-channel MR systems with efficiency and flexibility requires a scalable modular architecture. With Medusa, we propose an open system architecture using the Universal Serial Bus (USB) for scalability, combined with distributed processing and buffering to address the high data rates and strict synchronization required by multi-channel MRI. Medusa uses a modular design concept based on digital synthesizer, receiver, and gradient blocks, in conjunction with fast programmable logic for sampling and synchronization. Medusa is a form of synthetic instrument, being reconfigurable for a variety of medical/scientific instrumentation needs. The Medusa distributed architecture, scalability, and data bandwidth limits are presented, and its flexibility is demonstrated in a variety of novel MRI applications. PMID:21954200
Review of heat transfer problems associated with magnetically-confined fusion reactor concepts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hoffman, M.A.; Werner, R.W.; Carlson, G.A.
1976-04-01
Conceptual design studies of possible fusion reactor configurations have revealed a host of interesting and sometimes extremely difficult heat transfer problems. The general requirements imposed on the coolant system for heat removal of the thermonuclear power from the reactor are discussed. In particular, the constraints imposed by the fusion plasma, neutronics, structure and magnetic field environment are described with emphasis on those aspects which are unusual or unique to fusion reactors. Then the particular heat transfer characteristics of various possible coolants including lithium, flibe, boiling alkali metals, and helium are discussed in the context of these general fusion reactor requirements.more » Some specific areas where further experimental and/or theoretical work is necessary are listed for each coolant along with references to the pertinent research already accomplished. Specialized heat transfer problems of the plasma injection and removal systems are also described. Finally, the challenging heat transfer problems associated with the superconducting magnets are reviewed, and once again some of the key unsolved heat transfer problems are enumerated.« less
Pesticide residue quantification analysis by hyperspectral imaging sensors
NASA Astrophysics Data System (ADS)
Liao, Yuan-Hsun; Lo, Wei-Sheng; Guo, Horng-Yuh; Kao, Ching-Hua; Chou, Tau-Meu; Chen, Junne-Jih; Wen, Chia-Hsien; Lin, Chinsu; Chen, Hsian-Min; Ouyang, Yen-Chieh; Wu, Chao-Cheng; Chen, Shih-Yu; Chang, Chein-I.
2015-05-01
Pesticide residue detection in agriculture crops is a challenging issue and is even more difficult to quantify pesticide residue resident in agriculture produces and fruits. This paper conducts a series of base-line experiments which are particularly designed for three specific pesticides commonly used in Taiwan. The materials used for experiments are single leaves of vegetable produces which are being contaminated by various amount of concentration of pesticides. Two sensors are used to collected data. One is Fourier Transform Infrared (FTIR) spectroscopy. The other is a hyperspectral sensor, called Geophysical and Environmental Research (GER) 2600 spectroradiometer which is a batteryoperated field portable spectroradiometer with full real-time data acquisition from 350 nm to 2500 nm. In order to quantify data with different levels of pesticide residue concentration, several measures for spectral discrimination are developed. Mores specifically, new measures for calculating relative power between two sensors are particularly designed to be able to evaluate effectiveness of each of sensors in quantifying the used pesticide residues. The experimental results show that the GER is a better sensor than FTIR in the sense of pesticide residue quantification.
Statistical characterization of the optical interaction at a supercavitating interface
NASA Astrophysics Data System (ADS)
Walters, Gage; Kane, Tim; Jefferies, Rhett; Antonelli, Lynn
2016-05-01
The optical characteristics of an air/water interface have been widely studied for natural interface formations. However, the creation and management of artificial cavities creates a complicated interaction of gas and liquid that makes optical sensing and communication through the interface challenging. A ventilated cavity can reduce friction in underwater vehicles, but the resulting bubble drastically impedes optical and acoustic communication propagation. The complicated interaction at the air/water boundary yields surface waves and turbulence that make modeling and compensating of the optical properties difficult. Our experimental approach uses a narrow laser beam to probe the surface of the interface and measure the beam deflection and lensing effects. Using a vehicle model with a cavitator in a water tunnel, a laser beam is propagated outward from the model through the boundary and projected onto a target grid. The beam projection is captured using a high-speed camera, allowing us to measure and analyze beam shape and deflection. This approach has enabled us to quantify the temporal and spatial periodic variations in the beam propagation through the cavity boundary and fluid.
Microscopic Evolution of Laboratory Volcanic Hybrid Earthquakes
Ghaffari, H. O.; Griffith, W. A.; Benson, P. M.
2017-01-01
Characterizing the interaction between fluids and microscopic defects is one of the long-standing challenges in understanding a broad range of cracking processes, in part because they are so difficult to study experimentally. We address this issue by reexamining records of emitted acoustic phonon events during rock mechanics experiments under wet and dry conditions. The frequency spectrum of these events provides direct information regarding the state of the system. Such events are typically subdivided into high frequency (HF) and low frequency (LF) events, whereas intermediate “Hybrid” events, have HF onsets followed by LF ringing. At a larger scale in volcanic terranes, hybrid events are used empirically to predict eruptions, but their ambiguous physical origin limits their diagnostic use. By studying acoustic phonon emissions from individual microcracking events we show that the onset of a secondary instability–related to the transition from HF to LF–occurs during the fast equilibration phase of the system, leading to sudden increase of fluid pressure in the process zone. As a result of this squeezing process, a secondary instability akin to the LF event occurs. This mechanism is consistent with observations of hybrid earthquakes. PMID:28074878
Road Lane Detection Robust to Shadows Based on a Fuzzy System Using a Visible Light Camera Sensor
Hoang, Toan Minh; Baek, Na Rae; Cho, Se Woon; Kim, Ki Wan; Park, Kang Ryoung
2017-01-01
Recently, autonomous vehicles, particularly self-driving cars, have received significant attention owing to rapid advancements in sensor and computation technologies. In addition to traffic sign recognition, road lane detection is one of the most important factors used in lane departure warning systems and autonomous vehicles for maintaining the safety of semi-autonomous and fully autonomous systems. Unlike traffic signs, road lanes are easily damaged by both internal and external factors such as road quality, occlusion (traffic on the road), weather conditions, and illumination (shadows from objects such as cars, trees, and buildings). Obtaining clear road lane markings for recognition processing is a difficult challenge. Therefore, we propose a method to overcome various illumination problems, particularly severe shadows, by using fuzzy system and line segment detector algorithms to obtain better results for detecting road lanes by a visible light camera sensor. Experimental results from three open databases, Caltech dataset, Santiago Lanes dataset (SLD), and Road Marking dataset, showed that our method outperformed conventional lane detection methods. PMID:29143764
SocialRAD: an infrastructure for a secure, cooperative, asynchronous teleradiology system.
Figueiredo, João Filho Matos; Motta, Gustavo Henrique Matos Bezerra
2013-01-01
The popularity of teleradiology services has enabled a major advance in the provision of health services to areas with difficult geographical access. However, this potential has also brought with it a number of challenges: the large volume of data, characteristic of imaging tests, and security requirements designed to ensure confidentiality and integrity. Moreover, there is also a number of ethical questions involving the dominant model on the market, whereby this service is outsourced to private companies, and is not directly undertaken by professional radiologists. Therefore, the present paper proposes a cooperative model of teleradiology, where health professionals interact directly with the hospitals providing patient care. This has involved the integration of a wide range of technologies, such as the interconnection models Peer-to-Peer, Cloud Computing, Dynamic DNS, RESTful Web Services, as well as security and interoperability standards, with the aim of promoting a secure, collaborative asynchronous environment. The developed model is currently being used on an experimental basis, providing teleradiology support to cities in the north-eastern hinterland of Brazil, and is fulfilling all expectations.
Electronic Structure at Electrode/Electrolyte Interfaces in Magnesium based Batteries
NASA Astrophysics Data System (ADS)
Balachandran, Janakiraman; Siegel, Donald
2015-03-01
Magnesium is a promising multivalent element for use in next generation electrochemical energy storage systems. However, a wide range of challenges such as low coulombic efficiency, low/varying capacity and cyclability need to be resolved in order to realize Mg based batteries. Many of these issues can be related to interfacial phenomena between the Mg anode and common electrolytes. Ab-initio based computational models of these interfaces can provide insights on the interfacial interactions that can be difficult to probe experimentally. In this work we present ab-initio computations of common electrolyte solvents (THF, DME) in contact with two model electrode surfaces namely -- (i) an ``SEI-free'' electrode based on Mg metal and, (ii) a ``passivated'' electrode consisting of MgO. We perform GW calculations to predict the reorganization of the molecular orbitals (HOMO/LUMO) upon contact with the these surfaces and their alignment with respect to the Fermi energy of the electrodes. These computations are in turn compared with more efficient GGA (PBE) & Hybrid (HSE) functional calculations. The results obtained from these computations enable us to qualitatively describe the stability of these solvent molecules at electrode-electrolyte interfaces
Controlling Tensegrity Robots Through Evolution
NASA Technical Reports Server (NTRS)
Iscen, Atil; Agogino, Adrian; SunSpiral, Vytas; Tumer, Kagan
2013-01-01
Tensegrity structures (built from interconnected rods and cables) have the potential to offer a revolutionary new robotic design that is light-weight, energy-efficient, robust to failures, capable of unique modes of locomotion, impact tolerant, and compliant (reducing damage between the robot and its environment). Unfortunately robots built from tensegrity structures are difficult to control with traditional methods due to their oscillatory nature, nonlinear coupling between components and overall complexity. Fortunately this formidable control challenge can be overcome through the use of evolutionary algorithms. In this paper we show that evolutionary algorithms can be used to efficiently control a ball-shaped tensegrity robot. Experimental results performed with a variety of evolutionary algorithms in a detailed soft-body physics simulator show that a centralized evolutionary algorithm performs 400 percent better than a hand-coded solution, while the multi-agent evolution performs 800 percent better. In addition, evolution is able to discover diverse control solutions (both crawling and rolling) that are robust against structural failures and can be adapted to a wide range of energy and actuation constraints. These successful controls will form the basis for building high-performance tensegrity robots in the near future.
Ripple, Maureen O.; Kim, Namjoon; Springett, Roger
2013-01-01
Mitochondrial complex I couples electron transfer between matrix NADH and inner-membrane ubiquinone to the pumping of protons against a proton motive force. The accepted proton pumping stoichiometry was 4 protons per 2 electrons transferred (4H+/2e−) but it has been suggested that stoichiometry may be 3H+/2e− based on the identification of only 3 proton pumping units in the crystal structure and a revision of the previous experimental data. Measurement of proton pumping stoichiometry is challenging because, even in isolated mitochondria, it is difficult to measure the proton motive force while simultaneously measuring the redox potentials of the NADH/NAD+ and ubiquinol/ubiquinone pools. Here we employ a new method to quantify the proton motive force in living cells from the redox poise of the bc1 complex measured using multiwavelength cell spectroscopy and show that the correct stoichiometry for complex I is 4H+/2e− in mouse and human cells at high and physiological proton motive force. PMID:23306206
Time-Lapse, in Situ Imaging of Ice Crystal Growth Using Confocal Microscopy.
Marcellini, Moreno; Noirjean, Cecile; Dedovets, Dmytro; Maria, Juliette; Deville, Sylvain
2016-11-30
Ice crystals nucleate and grow when a water solution is cooled below its freezing point. The growth velocities and morphologies of the ice crystals depend on many parameters, such as the temperature of ice growth, the melting temperature, and the interactions of solutes with the growing crystals. Three types of morphologies may appear: dendritic, cellular (or fingerlike), or the faceted equilibrium form. Understanding and controlling which type of morphology is formed is essential in several domains, from biology to geophysics and materials science. Obtaining, in situ, three dimensional observations without introducing artifacts due to the experimental technique is nevertheless challenging. Here we show how we can use laser scanning confocal microscopy to follow in real-time the growth of smoothed and faceted ice crystals in zirconium acetate solutions. Both qualitative and quantitative observations can be made. In particular, we can precisely measure the lateral growth velocity of the crystals, a measure otherwise difficult to obtain. Such observations should help us understand the influence of the parameters that control the growth of ice crystals in various systems.
ERIC Educational Resources Information Center
Yelamarthi, Kumar
2012-01-01
Multidisciplinary projects involving electrical engineering (EE), mechanical engineering (ME), and computer engineering (CE) students are both exciting and difficult to conceptualize. Answering this challenge, this paper presents a multidisciplinary educational platform on radio frequency identification-based assistive devices. The combination of…
Making Homework More Meaningful
ERIC Educational Resources Information Center
Wieman, Rob; Arbaugh, Fran
2014-01-01
Parents in the United States expect their students to have homework; and students, especially in middle school and high school, expect daily homework assignments from their teachers. However, it is difficult to create effective homework assignments. Despite the challenges involved, the authors believe that homework "can" be an important…
ERIC Educational Resources Information Center
Hammond, Ormond W.; Onikama, Denise L.
This paper examines research on risk factors affecting teachers, noting that teachers encounter daily challenges and stresses in working with today's students. Risk is difficult to define. Consequences of risk can include stress and burnout, absenteeism, and attrition. Research shows that everyday events, even positive ones, cause stress, and…
Finding Creativity in an Artificial Artist
ERIC Educational Resources Information Center
Norton, David; Heath, Derrall; Ventura, Dan
2013-01-01
Creativity is an important component of human intelligence, and imbuing artificially intelligent systems with creativity is an interesting challenge. In particular, it is difficult to quantify (or even qualify) creativity. Recently, it has been suggested that conditions for attributing creativity to a system include: appreciation, imagination, and…
Providing Students with Formative Audio Feedback
ERIC Educational Resources Information Center
Brearley, Francis Q.; Cullen, W. Rod
2012-01-01
The provision of timely and constructive feedback is increasingly challenging for busy academics. Ensuring effective student engagement with feedback is equally difficult. Increasingly, studies have explored provision of audio recorded feedback to enhance effectiveness and engagement with feedback. Few, if any, of these focus on purely formative…
STEAM INJECTION REMEDIATION IN FRACTURED BEDROCK AT LORING AIR FORCE BASE
Contaminated groundwater occurs at many Superfund, RCRA, and Brownfields sites. Chlorinated solvents which can form a dense nonaqueous phase (DNAPL) when released to the subsurface can pose an extreme challenge for remediation, as DNAPLs are often difficult to locate and even ha...
Censorproofing School Library Collections: The Fallacy and Futility.
ERIC Educational Resources Information Center
Schrader, Alvin M.
1996-01-01
Discusses why challenges to materials in school libraries cannot be avoided. Demonstrates how reader response theory, the multiple readings of text, makes self-censorship difficult. Explains how "censorproofing" by title, author/artist, and subject ignores reader unpredictability and maturity levels. Finds all school libraries vulnerable…
Three types of rescue can avert extinction in a changing environment
USDA-ARS?s Scientific Manuscript database
Setting aside high quality, large areas of habitat to protect threatened populations is becoming increasingly difficult as humans fragment and degrade the environment. Biologists and managers therefore must determine the best way to shepherd small populations through the dual challenges of reduction...
ERIC Educational Resources Information Center
Rumberger, Russell
Job loss through technological advancement, particularly technologies based on microelectronics, is increasing for all economic sectors in a nation already hard challenged in world and domestic markets for goods and services. But assessing technology's employment impact remains difficult not only because of its direct and indirect effects and…
FROM ASSESSMENT TO POLICY--LESSONS LEARNED FROM THE U.S. NATIONAL ASSESSMENT (Journal Article)
The process of translating scientific information into timely and useful insights that inform policy and resource management decisions, despite the existence of uncertainties, is a difficult and challenging task. Policy-focused assessment is one approach to achieving this end. ...
FROM ASSESSMENT TO POLICY: LESSONS LEARNED FROM THE U.S. NATIONAL ASSESSMENT
The process of translating scientific information into timely and useful insights that inform policy and resource management decisions, despite the existence of uncertainties, is a difficult and challenging task. Policy-focused assessment is one approach to achieving this end. I...
A Different Method of Hepaticojejunostomy for Proximal Biliary Injuries
Schaefer, Glennon
1996-01-01
The management of proximal biliary injuries presents a surgical challenge. Anastomoses can be difficult to perform and can have poor results. We describe a method of hepaticojejunostomy done from within the Roux-en-Y loop, which can be utilized in this situation. PMID:9184866
The role of future scenarios to understand deep uncertainty for air quality management.
The environment and its interaction with human systems (economic, social and political) is complex and dynamic. Key drivers may disrupt systemdynamics in unforeseen ways, making it difficult to predict future conditions precisely. This kind of deep uncertainty presents a challeng...
Grandparent Education: Raising Grandchildren
ERIC Educational Resources Information Center
Strom, Paris S.; Strom, Robert D.
2011-01-01
Grandparent-headed households are increasing in the United States. Most caregivers believe their role will be permanent. The responsibilities are more difficult because previous parenting experiences do not apply to some current challenges, and there are no paradigms to provide guidance. Accordingly, caregivers want to know the goals that…
Recreating History with Archimedes and Pi
ERIC Educational Resources Information Center
Santucci, Lora C.
2011-01-01
Using modern technology to examine classical mathematics problems at the high school level can reduce difficult computations and encourage generalizations. When teachers combine historical context with access to technology, they challenge advanced students to think deeply, spark interest in students whose primary interest is not mathematics, and…
The Effects of Atmosphere on the Sintering of Ultrafine-Grained Tungsten with Ti
NASA Astrophysics Data System (ADS)
Ren, Chai; Koopman, Mark; Fang, Z. Zak; Zhang, Huan
2016-11-01
Tungsten (W) is a brittle material at room temperature making it very difficult to fabricate. Although the lack of ductility remains a difficult challenge, nano-sized and ultrafine-grained (UFG) structures offer the potential to overcome tungsten's room-temperature brittleness. One way to manufacture UFG W is to compact and sinter nano-sized W powder. It is challenging, however, to control grain growth during sintering. As one method to inhibit grain growth, the effect of Ti-based additives on the densification and grain growth of nano-W powders was investigated in this study. Addition of 1% Ti into tungsten led to more than a 63% decrease in average grain size of sintered samples at comparable density levels. It was found that sintering in Ar yielded a finer grain size than sintering in H2 at similar densities. The active diffusion mechanisms during sintering were different for W-1% Ti nano powders sintered in Ar and H2.
Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.
2014-01-01
Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494
Dental Pulp and Dentin Tissue Engineering and Regeneration – Advancement and Challenge
Huang, George T.-J.
2012-01-01
Hard tissue is difficult to repair especially dental structures. Tooth enamel is incapable of self-repairing whereas dentin and cememtum can regenerate with limited capacity. Enamel and dentin are commonly under the attack by caries. Extensive forms of caries destroy enamel and dentin and can lead to dental pulp infection. Entire pulp amputation followed by the pulp space disinfection and filled with an artificial rubber-like material is employed to treat the infection --commonly known as root canal or endodontic therapy. Regeneration of dentin relies on having vital pulps; however, regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. With the advent of modern tissue engineering concept and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the recent endeavor on pulp and dentin tissue engineering and regeneration. The prospective outcome of the current advancement and challenge in this line of research will be discussed. PMID:21196351
Challenges in Discerning Atmospheric Composition in Directly Imaged Planets
NASA Technical Reports Server (NTRS)
Marley, Mark S.
2017-01-01
One of the justifications motivating efforts to detect and characterize young extrasolar giant planets has been to measure atmospheric composition for comparison with that of the primary star. If the enhancement of heavy elements in the atmospheres of extrasolar giant planets, like it is for their solar system analogs, is inversely proportional to mass, then it is likely that these worlds formed by core accretion. However in practice it has been very difficult to constrain metallicity because of the complex effect of clouds. Cloud opacity varies both vertically and, in some cases, horizontally through the atmosphere. Particle size and composition, both of which impact opacity, are difficult challenges both for forward modeling and retrieval studies. In my presentation I will discuss systematic efforts to improve cloud studies to enable more reliable determinations of atmospheric composition. These efforts are relevant both to discerning composition of directly imaged young planets from ground based telescopes and future space based missions, such as WFIRST and LUVOIR.
Meyer, Annika; Gross, Neil; Teng, Marita
2018-01-01
Head and neck surgeons are commonly faced with surgical patients who have underlying medical problems requiring antithrombotic therapy. It is difficult to achieve a balance between minimizing the risk of thromboembolism and hemorrhage in the perioperative period. Data from randomized, controlled trials are limited, and procedure-specific bleed rates are also difficult to pinpoint. The decision is made more difficult when patients with moderate-to-high risk for thromboembolic events undergo procedures that are high risk for bleeding. This is true for many head and neck oncologic surgeries. Furthermore, although elective procedures may be delayed for optimization of antithrombotic medication, emergent procedures cannot. Head and neck surgery often represents the most challenging of all these circumstances, given the potential risk of airway compromise from bleeding after head and neck surgery. © 2017 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Reuter, Matthew; Tschudi, Stephen
When investigating the electrical response properties of molecules, experiments often measure conductance whereas computation predicts transmission probabilities. Although the Landauer-Büttiker theory relates the two in the limit of coherent scattering through the molecule, a direct comparison between experiment and computation can still be difficult. Experimental data (specifically that from break junctions) is statistical and computational results are deterministic. Many studies compare the most probable experimental conductance with computation, but such an analysis discards almost all of the experimental statistics. In this work we develop tools to decipher the Landauer-Büttiker transmission function directly from experimental statistics and then apply them to enable a fairer comparison between experimental and computational results.
Markazi, Ashley D; Perez, Victor; Sifri, Mamduh; Shanmugasundaram, Revathi; Selvaraj, Ramesh K
2017-07-01
Three separate experiments were conducted to study the effects of whole yeast cell product supplementation in pullets and layer hens. Body weight gain, fecal and intestinal coccidial oocyst counts, cecal microflora species, cytokine mRNA amounts, and CD4+ and CD8+ T-cell populations in the cecal tonsils were analyzed following an experimental coccidial infection. In Experiment I, day-old Leghorn layer chicks were fed 3 experimental diets with 0, 0.1, or 0.2% whole yeast cell product (CitriStim®, ADM, Decatur, IL). At 21 d of age, birds were challenged with 1 × 105 live coccidial oocysts. Supplementation with whole yeast cell product decreased the fecal coccidial oocyst count at 7 (P = 0.05) and 8 (P < 0.01) d post-challenge. In Experiment II, 27-week old Leghorn layer hens were fed 3 experimental diets with 0, 0.05 or 0.1% whole yeast cell product and challenged with 1 × 105 live coccidial oocysts on d 25 of whole yeast cell product feeding. Supplementation with whole yeast cell product decreased the coccidial oocyst count in the intestinal content (P < 0.01) at 5, 13, and 38 d post-coccidial challenge. Supplementation with whole yeast cell product increased relative proportion of Lactobacillus (P < 0.01) in the cecal tonsils 13 d post-coccidial challenge. Supplementation with whole yeast cell product decreased CD8+ T cell percentages (P < 0.05) in the cecal tonsils at 5 d post-coccidial challenge. In Experiment III, 32-week-old Leghorn layer hens were fed 3 experimental diets with 0, 0.1, or 0.2% whole yeast cell product and challenged with 1 × 105 live coccidial oocysts on d 66 of whole yeast cell product feeding. At 5 d post-coccidial challenge, whole yeast cell product supplementation down-regulated (P = 0.01) IL-10 mRNA amount. It could be concluded that supplementing whole yeast cell product can help minimize coccidial infection in both growing pullets and layer chickens. © 2017 Poultry Science Association Inc.
A Structured Career Intervention Program for Academically Challenged Students
ERIC Educational Resources Information Center
Salleh, Amla; Abdullah, Syed Mohamad; Mahmud, Zuria; Ghavifekr, Simin; Ishak, Noriah
2013-01-01
A study was carried out to test the effects of a 2-week structured intervention program on academically challenged students' career development. A quasi-experimental study was designed using pre-tests, post-tests, and a control group approach to examine the effects of the intervention program. Data were collected from both the experimental and…
Nelson, Michelle; Salguero, Francisco J; Dean, Rachel E; Ngugi, Sarah A; Smither, Sophie J; Atkins, Timothy P; Lever, Mark S
2014-12-01
Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 10(8) cfu Burkholderia pseudomallei within 22-85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 10(2) cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 10(2) cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures. © 2014 Crown copyright. International Journal of Experimental Pathology © 2014 Company of the International Journal of Experimental Pathology (CIJEP).
Smith, R Scott; Kay, Bruce D
2012-03-15
Experimental measurements of the properties of supercooled liquids at temperatures near their glass transition temperatures, Tg, are requisite for understanding the behavior of glasses and amorphous solids. Unfortunately, many supercooled molecular liquids rapidly crystallize at temperatures far above their Tg, making such measurements difficult to nearly impossible. In this Perspective, we discuss some recent alternative approaches to obtain experimental data in the temperature regime near Tg. These new approaches may yield the additional experimental data necessary to test current theoretical models of the dynamical slowdown that occurs in supercooled liquids approaching the glass transition.
Observations on the use of acoustic Doppler velocimeters over rough beds with suspended sediment
USDA-ARS?s Scientific Manuscript database
Acoustic Doppler velocimeters provide a means for measuring velocities and turbulence in challenging circumstances, such as in flows with suspended particles, which are difficult or impossible with laser-based techniques. The relatively non-intrusive measurement resulting from the offset sampling v...
Concepts for Telephone-Based Health Education
ERIC Educational Resources Information Center
Brouse, Corey H.; Basch, Charles E.
2004-01-01
A key challenge facing cancer educators is the extent to which effective programmes can be widely disseminated and implemented. Differences between target populations with respect to social, psychological, and educational characteristics, as well as the social and economic context make it difficult to replicate "cookbook" approaches. Tailoring of…
ERIC Educational Resources Information Center
Van Der Werf, Martin
2007-01-01
As the number of American students studying overseas increases, it will be difficult for colleges to establish or find enough adequate programs with challenging curricula. Students desire ever more remote locations, and colleges are being pushed to support the extremely adventurous. With more students studying abroad, and amid heightened fears…
Ethical Decisions in Turbulent Times
ERIC Educational Resources Information Center
Shapiro, Joan Poliner; Gross, Steven Jay; Shapiro, Susan H.
2008-01-01
Education leaders make difficult ethical decisions each day. Using the story of a preschool director in lower Manhattan on September 11, 2001, the authors detail a series of paradigms to help educational leaders navigate rationally through challenging and complex circumstances when they are under considerable emotional stress. One approach which…
Sufficiently elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-media constructs driven by a unique set of site-specific data. The ensuing challenge of examining ever more complex, integrated, higher-ord...
Cyberbullying: A Review of the Legal Issues Facing Educators
ERIC Educational Resources Information Center
Hinduja, Sameer; Patchin, Justin W.
2011-01-01
School districts are often given the challenging task of addressing problematic online behaviors committed by students while simultaneously protecting themselves from civil liability by not overstepping their authority. This is difficult, because the law concerning these behaviors is ambiguous and continuously evolving, and little consensus has…
Spiritual Development with Youth
ERIC Educational Resources Information Center
Ponds, Kenneth T.
2014-01-01
Research on positive psychology indicates that spiritual strengths can be important in helping individuals overcome crisis and loss. Encounters with difficult challenges of life inspire people to think more deeply about their spiritual and religious beliefs and the meaning of life. Spirituality, faith, and religious roots have been shown to be…
ERIC Educational Resources Information Center
Garcia, Michelle
2009-01-01
There's a lot wrong with the diversity training that goes on in the nation's schools. There are programs that offer shortcuts for communication across racial and ethnic lines, too often drawing on stereotypes rather than challenging them. There are dialogue programs that usher in difficult conversations about racism, prejudice and bias, sometimes…
Science, Religion and Difficult Dialectics
ERIC Educational Resources Information Center
Long, David E.
2010-01-01
Discussing themes from my paper "Scientists at play in a field of the Lord," three forum participants identify and discuss continuing social and epistemological issues which continue to challenge effective evolution education. I extend these themes and further amplify the vexing nature of an effective dialectic regarding evolution, especially for…