How to tell a new story about battering.

PubMed

Polletta, Francesca

2009-12-01

As Evan Stark observes, getting domestic violence against women recognized as coercive control will require a major effort of storytelling. Women's accounts of subjugation have to be narrated in a way that is both true to their experiences and capable of eliciting public understanding, sympathy, and action. This essay draws on an interdisciplinary literature on narrative to show why doing that poses such a formidable challenge. In lieu of the tragic form that has dominated battered women's storytelling, and in lieu of the quest and mystery forms that appear in Stark's own accounts, this article argues for using a rebirth story line.This genre, which has affinities with the fairytales Snow White and Sleeping Beauty, seems an unlikely vehicle for asserting battered women's combination of victimization and agency. Drawing on the stories told by battered women as part of a successful reform effort, however, this article shows how women have used the form effectively.

Ion specific correlations in bulk and at biointerfaces.

PubMed

Kalcher, I; Horinek, D; Netz, R R; Dzubiella, J

2009-10-21

Ion specific effects are ubiquitous in any complex colloidal or biological fluid in bulk or at interfaces. The molecular origins of these 'Hofmeister effects' are not well understood and their theoretical description poses a formidable challenge to the modeling and simulation community. On the basis of the combination of atomistically resolved molecular dynamics (MD) computer simulations and statistical mechanics approaches, we present a few selected examples of specific electrolyte effects in bulk, at simple neutral and charged interfaces, and on a short α-helical peptide. The structural complexity in these strongly Coulomb-correlated systems is highlighted and analyzed in the light of available experimental data. While in general the comparison of MD simulations to experiments often lacks quantitative agreement, mostly because molecular force fields and coarse-graining procedures remain to be optimized, the consensus as regards trends provides important insights into microscopic hydration and binding mechanisms.

Five Policy Levers To Meet The Value Challenge In Cancer Care.

PubMed

Callahan, Ryan; Darzi, Ara

2015-09-01

The burden of cancer on public finances is a serious concern for policy makers. More people are developing cancer, and as standards of care have risen, more are surviving and requiring longer-term care. Precision medicine promises better outcomes but demands commensurately higher payments for care. As both incidence and per case costs rise, we suggest that the task of expanding access to high-quality cancer care poses a "value challenge" that policies in many countries are inadequate to meet. Policy makers should respond with a new approach. We explore questions that policy makers will need to consider regarding objectives, barriers, and levers for policy development. We use transparency and accountability as cornerstones of a new approach to promote value-based decision making. Although barriers to advancing this agenda are formidable, we recommend that governments define common standards for value-based accounting; serve as information brokers for evidence development; pioneer value-based procurement of goods and services; engage in deliberative democracy in cancer care; and educate communities to facilitate knowledge sharing between communities of patients, their caretakers, and researchers. Project HOPE—The People-to-People Health Foundation, Inc.

Challenges in predicting climate and environmental effects on vector-borne disease episystems in a changing world.

PubMed

Tabachnick, W J

2010-03-15

Vector-borne pathogens cause enormous suffering to humans and animals. Many are expanding their range into new areas. Dengue, West Nile and Chikungunya have recently caused substantial human epidemics. Arthropod-borne animal diseases like Bluetongue, Rift Valley fever and African horse sickness pose substantial threats to livestock economies around the world. Climate change can impact the vector-borne disease epidemiology. Changes in climate will influence arthropod vectors, their life cycles and life histories, resulting in changes in both vector and pathogen distribution and changes in the ability of arthropods to transmit pathogens. Climate can affect the way pathogens interact with both the arthropod vector and the human or animal host. Predicting and mitigating the effects of future changes in the environment like climate change on the complex arthropod-pathogen-host epidemiological cycle requires understanding of a variety of complex mechanisms from the molecular to the population level. Although there has been substantial progress on many fronts the challenges to effectively understand and mitigate the impact of potential changes in the environment on vector-borne pathogens are formidable and at an early stage of development. The challenges will be explored using several arthropod-borne pathogen systems as illustration, and potential avenues to meet the challenges will be presented.

BI Project Success

ERIC Educational Resources Information Center

Tracey, Graham; Riha, James

2009-01-01

Managing business intelligence (BI) projects in higher education is a formidable responsibility that challenges even the most experienced technical project managers. Data source dependencies, uncertain data quality, changing information requirements, and urgency for actionable information are but a few examples among the multitude of challenges.…

Vinegar as a broadcast herbicide for spring-transplanted onions

USDA-ARS?s Scientific Manuscript database

The weed control challenges for onion production are formidable; however, these challenges are even greater for those considering organic crop production. Organic onion producers need additional organic herbicides that can effectively provide post-emergent weed control. Field research was conducted...

Bio-inspired nano tools for neuroscience.

PubMed

Das, Suradip; Carnicer-Lombarte, Alejandro; Fawcett, James W; Bora, Utpal

2016-07-01

Research and treatment in the nervous system is challenged by many physiological barriers posing a major hurdle for neurologists. The CNS is protected by a formidable blood brain barrier (BBB) which limits surgical, therapeutic and diagnostic interventions. The hostile environment created by reactive astrocytes in the CNS along with the limited regeneration capacity of the PNS makes functional recovery after tissue damage difficult and inefficient. Nanomaterials have the unique ability to interface with neural tissue in the nano-scale and are capable of influencing the function of a single neuron. The ability of nanoparticles to transcend the BBB through surface modifications has been exploited in various neuro-imaging techniques and for targeted drug delivery. The tunable topography of nanofibers provides accurate spatio-temporal guidance to regenerating axons. This review is an attempt to comprehend the progress in understanding the obstacles posed by the complex physiology of the nervous system and the innovations in design and fabrication of advanced nanomaterials drawing inspiration from natural phenomenon. We also discuss the development of nanomaterials for use in Neuro-diagnostics, Neuro-therapy and the fabrication of advanced nano-devices for use in opto-electronic and ultrasensitive electrophysiological applications. The energy efficient and parallel computing ability of the human brain has inspired the design of advanced nanotechnology based computational systems. However, extensive use of nanomaterials in neuroscience also raises serious toxicity issues as well as ethical concerns regarding nano implants in the brain. In conclusion we summarize these challenges and provide an insight into the huge potential of nanotechnology platforms in neuroscience. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries.

PubMed

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-04-08

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries

NASA Astrophysics Data System (ADS)

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-04-01

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries.

The Effectiveness of the Personality Assessment Inventory With Feigned PTSD: An Initial Investigation of Resnick's Model of Malingering.

PubMed

Wooley, Chelsea N; Rogers, Richard

2015-08-01

Malingered posttraumatic stress disorder (PTSD) poses a formidable clinical challenge because of the apparent ease in feigning PTSD. As an additional confound, some patients with genuine PTSD produce elevated profiles on feigning indicators that are difficult to distinguish from feigned PTSD. The current study utilized 109 inpatients from a trauma unit to examine whether the Personality Assessment Inventory and the Detailed Assessment of Posttraumatic Stress can effectively differentiate between genuine and feigned PTSD. As a primary focus, Resnick's model of malingered PTSD was evaluated with its three subtypes: pure malingering, partial malingering, and false imputation. They were tested on their ability to (a) effectively simulate PTSD and (b) avoid being classified as feigning. The partial malingering group proved to be the best feigning group in achieving these two goals. Overall, the Personality Assessment Inventory Malingering Index and Negative Distortion Scale were the most effective at identifying feigning. © The Author(s) 2014.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries

PubMed Central

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-01-01

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries. PMID:24710575

Self-organized cooperative swimming at low Reynolds numbers.

PubMed

Reinmüller, Alexander; Schöpe, Hans Joachim; Palberg, Thomas

2013-02-12

Investigations of swimming at low Reynolds numbers (Re < 10(-4)) so far have focused on individual or collectively moving autonomous microswimmers consisting of a single active building unit. Here we show that linear propulsion can also be reproducibly generated in a self-assembled dynamic complex formed from a granular, HCl-releasing particle settled on a charged quartz wall and a swarm of micrometer-sized negatively charged colloids. In isolation, none of the constituents shows motion beyond diffusion. When brought together, they self-assemble into a complex capable of directed swimming. It is stabilized by toroidal solvent flow centered about the granular particle. Propulsion is then launched by an asymmetric distribution of the colloids. Motion is self-stabilizing and continues for up to 25 min with velocities of 1-3 μm/s. Although the details of the mechanisms involved pose a formidable experimental and theoretical challenge, our observations offer a conceptually new, well-reproduced, versatile approach to swimming and transport at low Reynolds numbers.

Emergence of structured communities through evolutionary dynamics.

PubMed

Shtilerman, Elad; Kessler, David A; Shnerb, Nadav M

2015-10-21

Species-rich communities, in which many competing species coexist in a single trophic level, are quite frequent in nature, but pose a formidable theoretical challenge. In particular, it is known that complex competitive systems become unstable and unfeasible when the number of species is large. Recently, many studies have attributed the stability of natural communities to the structure of the interspecific interaction network, yet the nature of such structures and the underlying mechanisms responsible for them remain open questions. Here we introduce an evolutionary model, based on the generic Lotka-Volterra competitive framework, from which a stable, structured, diverse community emerges spontaneously. The modular structure of the competition matrix reflects the phylogeny of the community, in agreement with the hierarchial taxonomic classification. Closely related species tend to have stronger niche overlap and weaker fitness differences, as opposed to pairs of species from different modules. The competitive-relatedness hypothesis and the idea of emergent neutrality are discussed in the context of this evolutionary model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Understanding and managing organizational change: implications for public health management.

PubMed

Thompson, Jon M

2010-01-01

Managing organizational change has become a significant responsibility of managers. Managing the change process within public health organizations is important because appropriately and systematically managing change is linked to improved organizational performance. However, change is difficult and the change process poses formidable challenges for managers. Managers themselves face increased pressure to respond to environmental influences and provide the necessary leadership to their organizations in the change process. In fact, managing organizational change has become a key competency for healthcare managers. This article addresses the important topic of organizational change in public health organizations. It provides a conceptual foundation for understanding organizational change and its relationship to healthcare organizational performance, and then discusses the types and nature of change, using some examples and evidence from those organizations that have successfully managed change. A framework for guiding public health managers in the change management process is provided. The article concludes with suggested management competencies to establish a change-oriented organization with the culture and capacity for change.

Fluid-Structure Interaction Modeling of Parachutes with Disreefing and Modified Geometric Porosity and Separation Aerodynamics of a Cover Jettisoned to the Spacecraft Wake

NASA Astrophysics Data System (ADS)

Fritze, Matthew D.

Fluid-structure interaction (FSI) modeling of spacecraft parachutes involves a number of computational challenges. The canopy complexity created by the hundreds of gaps and slits and design-related modification of that geometric porosity by removal of some of the sails and panels are among the formidable challenges. Disreefing from one stage to another when the parachute is used in multiple stages is another formidable challenge. This thesis addresses the computational challenges involved in disreefing of spacecraft parachutes and fully-open and reefed stages of the parachutes with modified geometric porosity. The special techniques developed to address these challenges are described and the FSI computations are be reported. The thesis also addresses the modeling and computation challenges involved in very early stages, where the sudden separation of a cover jettisoned to the spacecraft wake needs to be modeled. Higher-order temporal representations used in modeling the separation motion are described, and the computed separation and wake-induced forces acting on the cover are reported.

Balancing data sharing requirements for analyses with data sensitivity

USGS Publications Warehouse

Jarnevich, C.S.; Graham, J.J.; Newman, G.J.; Crall, A.W.; Stohlgren, T.J.

2007-01-01

Data sensitivity can pose a formidable barrier to data sharing. Knowledge of species current distributions from data sharing is critical for the creation of watch lists and an early warning/rapid response system and for model generation for the spread of invasive species. We have created an on-line system to synthesize disparate datasets of non-native species locations that includes a mechanism to account for data sensitivity. Data contributors are able to mark their data as sensitive. This data is then 'fuzzed' in mapping applications and downloaded files to quarter-quadrangle grid cells, but the actual locations are available for analyses. We propose that this system overcomes the hurdles to data sharing posed by sensitive data. ?? 2006 Springer Science+Business Media B.V.

Impact of over-the-top broadcast applications of Racer® on onion weed control

USDA-ARS?s Scientific Manuscript database

The weed control challenges for onion production are formidable; however, these challenges are even greater for those considering organic crop production. Organic onion producers need organic herbicides that can effectively provide post-emergent weed control. Racer (registered trademark) is a poten...

Plural Societies and the Possibility of Shared Citizenship

ERIC Educational Resources Information Center

Merry, Michael S.

2012-01-01

As civilization pushes headlong into the twenty-first century, increasingly stringent demands for citizenship issue forth from governments around the world faced with a formidable assortment of challenges. Faced with these challenges, states are exploring ways to elicit civic attachments from their heterogeneous populations, but doing so is…

E-Learning and the Transformation of Social Interaction in Higher Education

ERIC Educational Resources Information Center

Slevin, James

2008-01-01

This article examines the way in which e-learning is transforming the nature of social interaction in higher education. In this new educational environment, radical societal transitions and the opportunities afforded by modern communication technologies together produce formidable challenges. Significant as these challenges may be, concentration…

Petrosectomies for invasive tumours: surgery and reconstruction.

PubMed

Malata, C M; Cooter, R D; Towns, G M; Batchelor, A G

1996-09-01

Tumours involving the temporal bone have historically carried a bad prognosis. The only prospect of cure is radical en bloc resection. Temporal bone resection for malignancies is, however, such a formidable undertaking that many centres label such tumours as unresectable. Additionally, the enormity of the surgical defect poses a major reconstructive challenge. A review of 14 petrosectomies (in 12 males and 2 females) performed for extensively invasive neoplasms in and around the ear is presented. All underwent immediate reconstruction, the majority (12/14) with free tissue transfers. 9 of the 14 patients (64%) are still alive after a mean follow-up of 70 months (range 4-8 years). With the use of free tissue transfers, an aggressive approach with regard to the resection margins can safely be adopted in the full knowledge that the eventual size of the defect need not compromise tumour clearance. Additionally, free flaps provided a reliable dural seal. This approach of radical en bloc resection with free flap reconstruction has decreased the mortality (compared to the literature), while largely reducing the morbidity to that of unavoidable cranial nerve resection.

HIV Infection among People Who Inject Drugs: The Challenge of Racial/Ethnic Disparities

ERIC Educational Resources Information Center

Des Jarlais, Don C.; McCarty, Dennis; Vega, William A.; Bramson, Heidi

2013-01-01

Racial/ethnic disparities in HIV infection, with minority groups typically having higher rates of infection, are a formidable public health challenge. In the United States, among both men and women who inject drugs, HIV infection rates are elevated among Hispanics and non-Hispanic Blacks. A meta-analysis of international research concluded that…

Metallized gelled monopropellants

NASA Technical Reports Server (NTRS)

Nieder, Erin G.; Harrod, Charles E.; Rodgers, Frederick C.; Rapp, Douglas C.; Palaszewski, Bryan A.

1992-01-01

Thermochemical calculations of seven metallized monopropellants were conducted to quantify theoretical specific impulse and density specific impulse performance. On the basis of theoretical performance, commercial availability of formulation constituents, and anticipated viscometric behavior, two metallized monopropellants were selected for formulation characterization: triethylene glycol dinitrate, ammonium perchlorate, aluminum and hydrogen peroxide, aluminum. Formulation goals were established, and monopropellant formulation compatibility and hazard sensitivity were experimentally determined. These experimental results indicate that the friction sensitivity, detonation susceptibility, and material handling difficulties of the elevated monopropellant formulations and their constituents pose formidable barriers to their future application as metallized monopropellants.

Visual control of prey-capture flight in dragonflies.

PubMed

Olberg, Robert M

2012-04-01

Interacting with a moving object poses a computational problem for an animal's nervous system. This problem has been elegantly solved by the dragonfly, a formidable visual predator on flying insects. The dragonfly computes an interception flight trajectory and steers to maintain it during its prey-pursuit flight. This review summarizes current knowledge about pursuit behavior and neurons thought to control interception in the dragonfly. When understood, this system has the potential for explaining how a small group of neurons can control complex interactions with moving objects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dressed to kill? Visible markers of coalitional affiliation enhance conceptualized formidability.

PubMed

Fessler, Daniel M T; Holbrook, Colin; Dashoff, David

2016-01-01

Displaying markers of coalitional affiliation is a common feature of contemporary life. In situations in which interaction with members of rival coalitions is likely, signaling coalitional affiliation may simultaneously constitute an implicit challenge to opponents and an objective commitment device, binding signalers to their coalitions. Individuals who invite conflict, and who cannot readily back out of conflict, constitute a greater threat than those who avoid conflict and preserve the option of feigning neutrality. As a consequence, the former should be viewed as more formidable than the latter. Recent research indicates that relative formidability is summarized using the envisioned physical size and strength of a potential antagonist. Thus, individuals who display markers of coalitional affiliation should be conceptualized as more physically imposing than those who do not. We tested this prediction in two experiments. In Study 1, conducted with U.S. university students, participants inspected images of sports fans' faces. In Study 2, conducted with U.S. Mechanical Turk workers, participants read vignettes depicting political partisans. In both studies, participants estimated the physical formidability of the target individuals and reported their own ability to defend themselves; in Study 2, participants estimated the target's aggressiveness. Consonant with predictions, targets depicted as signaling coalitional affiliation in situations of potential conflict were envisioned to be more physically formidable and more aggressive than were those not depicted as signaling thusly. Underscoring that the calculations at issue concern the possibility of violent conflict, participants' estimates of the protagonist's features were inversely correlated with their ability to defend themselves. © 2016 Wiley Periodicals, Inc.

A systematic way to assess compliance with human factors standards

DOT National Transportation Integrated Search

1996-01-01

Assessing the human factors : considerations associated : with the design or : evaluation of any major : new system can be a formidable challenge. : To make this more manageable, : the Federal Aviation Administrations : (FAA) Office of the Chief S...

Different Systems--Similar Challenges? Factors Impacting the Motivation of German and U.S. Teachers to become School Leaders

ERIC Educational Resources Information Center

Hancock, Dawson R.; Muller, Ulrich

2009-01-01

In the United States and Germany, effective school leadership is pivotal to a school's success. Yet in each country, attracting and retaining qualified school leaders is a formidable challenge. This study compares the influence of possible motivators and inhibitors that impact teachers' decisions to become principals in the two countries. Survey…

Seven Steps for Success: Selecting IT Consultants

ERIC Educational Resources Information Center

Moriarty, Daniel F.

2004-01-01

Information technology (IT) presents community colleges with both powerful opportunities and formidable challenges. The prospects of expedited and more efficient business processes, greater student access through distance learning, improved communication, and strengthened relationships with students can embolden the most hesitant college…

Rapid stabilization of thawing soils For enhanced vehicle mobility: a field demonstration project

DOT National Transportation Integrated Search

1999-02-01

Thawing soil presents a formidable challenge for vehicle operations cross-country and on unsurfaced roads. To mitigate the problem, a variety of stabilization techniques were evaluated for their suitability for rapid employment to enhance military ve...

A New Vision of Professional Development for University Teachers in Libya "It's Not an Event, It Is a Process"

ERIC Educational Resources Information Center

Suwaed, Hameda; Rahouma, Wesam

2015-01-01

Being a university teacher in the Libya is most of the time described as a challenge. In the case of the current unstable situation in Libya, the task is formidable in many cases. This paper investigates the challenges encountered by Alzawia university teachers in four colleges. It attempts to answer the following questions: what are the…

Evolutionary preferences for physical formidability in leaders.

PubMed

Murray, Gregg R

2014-01-01

This research uses evolutionary theory to evaluate followers' preferences for physically formidable leaders and to identify conditions that stimulate those preferences. It employs a population-based survey experiment (N ≥ 760), which offers the advantages to internal validity of experiments and external validity of a highly heterogeneous sample drawn from a nationally representative subject pool. The theoretical argument proffered here is followers tend to prefer leaders with greater physical formidability because of evolutionary adaptations derived from humans' violent ancestral environment. In this environment, individuals who allied with and ultimately followed physically powerful partners were more likely to acquire and retain important resources necessary for survival and reproduction because the presence of the physically powerful partner cued opponents to avoid a challenge for the resources or risk a costly confrontation. This argument suggests and the results indicate that threatening (war) and nonthreatening (peace, cooperation, and control) stimuli differentially motivate preferences for physically formidable leaders. In particular, the findings suggest threatening conditions lead to preferences for leaders with more powerful physical attributes, both anthropometric (i.e., weight, height, and body mass index) and perceptual (i.e., attributes of being "physically imposing or intimidating" and "physically strong"). Overall, this research offers a theoretical framework from which to understand this otherwise seemingly irrational phenomenon. Further, it advances the emerging but long-neglected investigation of biological effects on political behavior and has implications for a fundamental process in democratic society, leader selection.

Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

EPA Science Inventory

Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

Interactive Videodisc at California State University, Fullerton.

ERIC Educational Resources Information Center

Reisman, S.

In January 1987, California State University, Fullerton (CSUF), began to explore the potential of interactive videodisk (IVD) technology on its campus. The challenge of introducing an individualized instructional technology into a cost conscious and conventional teaching environment was formidable, considering the traditional orientation of…

Communicable disease surveillance and control in the context of conflict and mass displacement in Syria.

PubMed

Ismail, Sharif A; Abbara, Aula; Collin, Simon M; Orcutt, Miriam; Coutts, Adam P; Maziak, Wasim; Sahloul, Zaher; Dar, Osman; Corrah, Tumena; Fouad, Fouad M

2016-06-01

To describe trends in major communicable diseases in Syria during the ongoing conflict, and the challenges to communicable disease surveillance and control in the context of dynamic, large-scale population displacement, unplanned mass gatherings, and disruption to critical infrastructure. A rapid review of the peer-reviewed and non-peer-reviewed literature from 2005 to 2015 was performed, augmented by secondary analysis of monitoring data from two disease early warning systems currently operational in Syria, focusing mainly on three diseases: tuberculosis (TB), measles, and polio. Trend data show discrepancies in case report numbers between government and non-government controlled areas, especially for TB, but interpretation is hampered by uncertainties over sentinel surveillance coverage and base population numbers. Communicable disease control has been undermined by a combination of governance fragmentation, direct and indirect damage to facilities and systems, and health worker flight. Five years into the crisis, some progress has been made in disease surveillance, but governance and coordination problems, variable immunization coverage, and the dynamic and indiscriminate nature of the conflict continue to pose a serious threat to population health in Syria and surrounding countries. The risk of major cross-border communicable disease outbreaks is high, and challenges for health in a post-conflict Syria are formidable. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Antimicrobial Resistance Gene Transfer in Drug Resistant Acinetobacter Species

USDA-ARS?s Scientific Manuscript database

Abstract: Antibiotic resistance is rapidly developing into one of the most formidable challenges for healthcare providers and researchers alike. To combat the rapid evolution of resistance, it will be important to uncover different mechanisms that bacteria use to acquire drug resistance genes. Acine...

No Mickey Mouse Operation: Despite Cutting-Edge Technology, Free Book Delivery, and Bilingual Programming, Luring Users Is the Orange County Library's Greatest Challenge

ERIC Educational Resources Information Center

Rogers, Michael

2004-01-01

Living in the vast shadow cast by the spires of the Magic Kingdom presents special challenges for Orlando's Orange County Library System (OCLS), the most formidable of which is increasing its relatively small user base. The library additionally faces tension between the administration and staff, political strife on the board, and looming contract…

Some challenges in designing a lunar, Martian, or microgravity CELSS.

PubMed

Salisbury, F B

1992-01-01

The design of a bioregenerative life-support system (a Controlled Ecological Life-Support System or CELSS) for long-duration stays on the moon, Mars, or in a space craft poses formidable problems in engineering and in theory. Technological (hardware) problems include: (1) Creation and control of gas composition and pressure, temperature, light, humidity, and air circulation, especially in microgravity to 1/3 xg and in the vacuum of space. Light (energy demanding), CO2 levels, and the rooting media are special problems for plants. (2) Developing specialized equipment for food preparation. (3) Equipment development for waste recycling. (4) Development of computer systems for environmental monitoring and control as well as several other functions. Problems of theory (software) include: (1) Determining crop species and cultivars (some bred especially for CELSS). (2) Optimum environments and growing and harvesting techniques for each crop. (3) Best and most efficient food-preparation techniques and required equipment. (4) Best and most efficient waste-recycling techniques and equipment. This topic includes questions about the extent of closure, resupply, and waste storage. (5) How to achieve long-term stability. (6) How to avoid catastrophic failures--and how to recover from near-catastrophic failures (for example, plant diseases). Many problems must be solved.

Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion.

PubMed

Adeeb, Nimer; Griessenauer, Christoph J; Moore, Justin M; Foreman, Paul M; Shallwani, Hussain; Motiei-Langroudi, Rouzbeh; Gupta, Raghav; Baccin, Carlos E; Alturki, Abdulrahman; Harrigan, Mark R; Siddiqui, Adnan H; Levy, Elad I; Ogilvy, Christopher S; Thomas, Ajith J

2017-04-01

Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement. A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis. Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis. Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke. © 2017 American Heart Association, Inc.

All things rhabdoid and SMARC: An enigmatic exploration with Dr. Louis P. Dehner.

PubMed

Fuller, Christine E

2016-11-01

Over the past several decades, our understanding of malignant rhabdoid tumors (MRT) and the central nervous system equivalent atypical teratoid/rhabdoid tumor (ATRT) has undergone considerable refinement, particularly in terms of genetic characterization. MRT (both renal and extra-renal) and ATRT share phenotypic similarities and a common genetic signature, that being inactivating alterations of the SWI/SNF complex component SMARCB1 (or rarely SMARCA4). Unfortunately, a wide array of tumors bears significantly overlapping phenotypic characteristics to MRT/ATRT, posing a formidable diagnostic challenge. Likewise, the list of tumors bearing SMARC-related alterations has grown at a dizzying pace, and the original assumption that SMARCB1 alterations were unique to MRT/ATRT has been essentially negated. It should come as no surprise that Dr. Louis P. Dehner, no stranger to enigmatic lesions, participated significantly in this pathologic controversy, and the circuitous journey of entity discovery and clarification. This review aims to (1) summarize our current knowledge of MRT and ATRT with an emphasis on genetic characterization, (2) present insight into so-called "composite rhabdoid tumors" (CRTs), and (3) and provide an updated account of others tumors bearing SMARC alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Conductive Polymer Binder for High-Tap-Density Nanosilicon Material for Lithium-Ion Battery Negative Electrode Application.

PubMed

Zhao, Hui; Wei, Yang; Qiao, Ruimin; Zhu, Chenhui; Zheng, Ziyan; Ling, Min; Jia, Zhe; Bai, Ying; Fu, Yanbao; Lei, Jinglei; Song, Xiangyun; Battaglia, Vincent S; Yang, Wanli; Messersmith, Phillip B; Liu, Gao

2015-12-09

High-tap-density silicon nanomaterials are highly desirable as anodes for lithium ion batteries, due to their small surface area and minimum first-cycle loss. However, this material poses formidable challenges to polymeric binder design. Binders adhere on to the small surface area to sustain the drastic volume changes during cycling; also the low porosities and small pore size resulting from this material are detrimental to lithium ion transport. This study introduces a new binder, poly(1-pyrenemethyl methacrylate-co-methacrylic acid) (PPyMAA), for a high-tap-density nanosilicon electrode cycled in a stable manner with a first cycle efficiency of 82%-a value that is further improved to 87% when combined with graphite material. Incorporating the MAA acid functionalities does not change the lowest unoccupied molecular orbital (LUMO) features or lower the adhesion performance of the PPy homopolymer. Our single-molecule force microscopy measurement of PPyMAA reveals similar adhesion strength between polymer binder and anode surface when compared with conventional polymer such as homopolyacrylic acid (PAA), while being electronically conductive. The combined conductivity and adhesion afforded by the MAA and pyrene copolymer results in good cycling performance for the high-tap-density Si electrode.

Gene mutations in Mycobacterium tuberculosis: multidrug-resistant TB as an emerging global public health crisis.

PubMed

Mishra, Rahul; Shukla, Priyanka; Huang, Wei; Hu, Ning

2015-01-01

Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictive models for moving contact line flows

NASA Technical Reports Server (NTRS)

Rame, Enrique; Garoff, Stephen

2003-01-01

Modeling flows with moving contact lines poses the formidable challenge that the usual assumptions of Newtonian fluid and no-slip condition give rise to a well-known singularity. This singularity prevents one from satisfying the contact angle condition to compute the shape of the fluid-fluid interface, a crucial calculation without which design parameters such as the pressure drop needed to move an immiscible 2-fluid system through a solid matrix cannot be evaluated. Some progress has been made for low Capillary number spreading flows. Combining experimental measurements of fluid-fluid interfaces very near the moving contact line with an analytical expression for the interface shape, we can determine a parameter that forms a boundary condition for the macroscopic interface shape when Ca much les than l. This parameter, which plays the role of an "apparent" or macroscopic dynamic contact angle, is shown by the theory to depend on the system geometry through the macroscopic length scale. This theoretically established dependence on geometry allows this parameter to be "transferable" from the geometry of the measurement to any other geometry involving the same material system. Unfortunately this prediction of the theory cannot be tested on Earth.

Some challenges in designing a lunar, Martian, or microgravity CELSS

NASA Astrophysics Data System (ADS)

Salisbury, Frank B.

The design of a bioregenerative life-support system (a Controlled Ecological Life-Support System or CELSS) for long-duration stays on the moon, Mars, or in a space craft poses formidable problems in engineering and in theory. Technological (hardware) problems include: (1) Creation and control of gas composition and pressure, temperature, light, humidity, and air circulation, especially in microgravity to 1/3xg and in the vacuum of space. Light (energy demanding), CO 2 levels, and the rooting media are special problems for plants. (2) Developing specialized equipment for food preparation. (3) Equipment development for waste recycling. (4) Development of computer systems for environmental monitoring and control as well as several other functions. Problems of theory (software) include: (1) Determining crop species and cultivars (some bred especially for CELSS). (2) Optimum environments and growing and harvesting techniques for each crop. (3) Best and most efficient food-preparation techniques and required equipment. (4) Best and most efficient waste-recycling techniques and equipment. This topic includes questions about the extent of closure, resupply, and waste storage. (5) How to achieve long-term stability. (6) How to avoid catastrophic failures-and how to recover from near-catastrophic failures (for example, plant diseases). Many problems must be solved.

Progress in Computational Electron-Molecule Collisions

NASA Astrophysics Data System (ADS)

Rescigno, Tn

1997-10-01

The past few years have witnessed tremendous progress in the development of sophisticated ab initio methods for treating collisions of slow electrons with isolated small molecules. Researchers in this area have benefited greatly from advances in computer technology; indeed, the advent of parallel computers has made it possible to carry out calculations at a level of sophistication inconceivable a decade ago. But bigger and faster computers are only part of the picture. Even with today's computers, the practical need to study electron collisions with the kinds of complex molecules and fragments encountered in real-world plasma processing environments is taxing present methods beyond their current capabilities. Since extrapolation of existing methods to handle increasingly larger targets will ultimately fail as it would require computational resources beyond any imagined, continued progress must also be linked to new theoretical developments. Some of the techniques recently introduced to address these problems will be discussed and illustrated with examples of electron-molecule collision calculations we have carried out on some fairly complex target gases encountered in processing plasmas. Electron-molecule scattering continues to pose many formidable theoretical and computational challenges. I will touch on some of the outstanding open questions.

Linearized lattice Boltzmann method for micro- and nanoscale flow and heat transfer.

PubMed

Shi, Yong; Yap, Ying Wan; Sader, John E

2015-07-01

Ability to characterize the heat transfer in flowing gases is important for a wide range of applications involving micro- and nanoscale devices. Gas flows away from the continuum limit can be captured using the Boltzmann equation, whose analytical solution poses a formidable challenge. An efficient and accurate numerical simulation of the Boltzmann equation is thus highly desirable. In this article, the linearized Boltzmann Bhatnagar-Gross-Krook equation is used to develop a hierarchy of thermal lattice Boltzmann (LB) models based on half-space Gaussian-Hermite (GH) quadrature ranging from low to high algebraic precision, using double distribution functions. Simplified versions of the LB models in the continuum limit are also derived, and are shown to be consistent with existing thermal LB models for noncontinuum heat transfer reported in the literature. Accuracy of the proposed LB hierarchy is assessed by simulating thermal Couette flows for a wide range of Knudsen numbers. Effects of the underlying quadrature schemes (half-space GH vs full-space GH) and continuum-limit simplifications on computational accuracy are also elaborated. The numerical findings in this article provide direct evidence of improved computational capability of the proposed LB models for modeling noncontinuum flows and heat transfer at small length scales.

Urban Pest Management of Ants in California

USDA-ARS?s Scientific Manuscript database

Keeping pace with the dynamic and evolving landscape of invasive ants in California presents a formidable challenge to the pest management industry. Pest management professionals (PMPs) are on the frontlines when it comes to battling these exotic ant pests, and are often the first ones to intercept ...

Feasibility and Preliminary Outcomes of a Yoga and Mindfulness Intervention for School Teachers

ERIC Educational Resources Information Center

Ancona, Matthew R.; Mendelson, Tamar

2014-01-01

Many public school teachers face formidable challenges, including overcrowded classrooms, limited administrative resources, and high numbers of students with behavioral and emotional problems. Mindfulness-based strategies are a potentially promising means of reducing teachers' stress and enhancing their ability to handle job demands effectively.…

A Proposed Astronomy Learning Progression for Remote Telescope Observation

ERIC Educational Resources Information Center

Slater, Timothy F.; Burrows, Andrea C.; French, Debbie A.; Sanchez, Richard A.; Tatge, Coty B.

2014-01-01

Providing meaningful telescope observing experiences for students who are deeply urban or distantly rural place-bound--or even daylight time-bound--has consistently presented a formidable challenge for astronomy educators. For nearly 2 decades, the Internet has promised unfettered access for large numbers of students to conduct remote telescope…

Shared Geospatial Metadata Repository for Ontario University Libraries: Collaborative Approaches

ERIC Educational Resources Information Center

Forward, Erin; Leahey, Amber; Trimble, Leanne

2015-01-01

Successfully providing access to special collections of digital geospatial data in academic libraries relies upon complete and accurate metadata. Creating and maintaining metadata using specialized standards is a formidable challenge for libraries. The Ontario Council of University Libraries' Scholars GeoPortal project, which created a shared…

The Function of Phenomenal States: Supramodular Interaction Theory

ERIC Educational Resources Information Center

Morsella, Ezequiel

2005-01-01

Discovering the function of phenomenal states remains a formidable scientific challenge. Research on consciously penetrable conflicts (e.g., "pain-for-gain" scenarios) and impenetrable conflicts (as in the pupillary reflex, ventriloquism, and the McGurk effect [H. McGurk & J. MacDonald, 1976]) reveals that these states integrate diverse kinds of…

What Beginning Special Educators Need to Know about Conducting Functional Behavioral Assessments

ERIC Educational Resources Information Center

Lewis, Timothy J.; Hatton, Heather L.; Jorgenson, Courtney; Maynard, Deanna

2017-01-01

New--and often veteran--teachers find managing significant inappropriate student behavior a formidable challenge. Although more severe inappropriate behaviors, such as aggression, often receive attention in the professional literature, survey research has shown that the high frequency of milder inappropriate behaviors (e.g., disruptions,…

Teacher Training in Afghanistan: Intersections of Need and Reality

ERIC Educational Resources Information Center

Husting, Sheila; Intili, Jo Ann; Kissam, Edward

2008-01-01

As post-Taliban Afghanistan moves toward the establishment of a viable educational system, key stakeholders and donors are faced with the formidable challenge of how to most rapidly implement teacher training within an environment of diverse, changing, and largely unassessed training needs. The current article explores the dilemmas inherent in…

Management of Early Carcinoma of the Ovary

PubMed Central

Chapman, George W.

1988-01-01

Ovarian cancer represents a formidable challenge to physicians. Early symptoms are nonspecific, and are usually attributed to disorders of the upper gastrointestinal tract. Especially important is suspicion of this neoplasm in its early stage. This article discusses the epidemiology, clinical features, evaluation, and treatment of early carcinomas of the ovary. PMID:3071612

Restoring tropical forests on bauxite mined lands: lessons from the Brazilian Amazon

Treesearch

John A. Parrotta; Oliver H. Knowles

2001-01-01

Restoring self-sustaining tropical forest ecosystems on surface mined sites is a formidable challenge that requires the integration of proven reclamation techniques and reforestation strategies appropriate to specific site conditions, including landscape biodiversity patterns. Restorationists working in most tropical settings are usually hampered by lack of basic...

A systems approach for management of pests and pathogens of nursery crops

Treesearch

Jennifer L. Parke; Niklaus J. Grünwald

2012-01-01

Horticultural nurseries are heterogeneous and spatially complex agricultural systems, which present formidable challenges to management of diseases and pests. Moreover, nursery plants shipped interstate and internationally can serve as important vectors for pathogens and pests that threaten both agriculture and forestry. Current regulatory strategies to prevent this...

Axis I Screens and Suicide Risk in Jails: A Comparative Analysis

ERIC Educational Resources Information Center

Harrison, Kimberly S.; Rogers, Richard

2007-01-01

Mental health professionals conducting screenings in jail settings face formidable challenges in identifying inmates at risk for major depression and suicide. Psychologists often rely on correctional staff to provide initial appraisals of those inmates requiring further evaluation. In a sample of 100 jail detainees, the effectiveness of two…

Global burden of COPD.

PubMed

López-Campos, José Luis; Tan, Wan; Soriano, Joan B

2016-01-01

It is estimated that the world population will reach a record 7.3 billion in 2015, and the high burden of chronic conditions associated with ageing and smoking will increase further. Respiratory diseases in general receive little attention and funding in comparison with other major causes of global morbidity and mortality. In particular, chronic obstructive pulmonary disease (COPD) has been a major public health problem and will remain a challenge for clinicians within the 21st century. Worldwide, COPD is in the spotlight, since its high prevalence, morbidity and mortality create formidable challenges for health-care systems. This review emphasizes the magnitude of the COPD problem from a clinician's standpoint by drawing extensively from the new findings of the Global Burden of Disease study. Updated, distilled information on the population distribution of COPD is useful for the clinician to help provide an appreciation of the relative impact of COPD in daily practice compared with other chronic conditions, and to allocate minimum resources in anticipation of future needs in care. Despite recent trends in reduction of COPD standardized mortality rates and some recent successes in anti-smoking efforts in a number of Western countries, the overarching demographic impact of ageing in an ever-expanding world population, joined with other factors such as high rates of smoking and air pollution in Asia, will ensure that COPD will continue to pose an ever-increasing problem well into the 21st century. © 2015 Asian Pacific Society of Respirology.

Business strategies for conservation on private lands: Koa forestry as a case study

PubMed Central

Goldstein, Joshua H.; Daily, Gretchen C.; Friday, James B.; Matson, Pamela A.; Naylor, Rosamond L.; Vitousek, Peter

2006-01-01

Innovative financial instruments are being created to reward conservation on private, working lands. Major design challenges remain, however, to make investments in biodiversity and ecosystem services economically attractive and commonplace. From a business perspective, three key financial barriers for advancing conservation land uses must frequently be addressed: high up-front costs, long time periods with no revenue, and high project risk due to long time horizons and uncertainty. We explored ways of overcoming these barriers on grazing lands in Hawaii by realizing a suite of timber and conservation revenue streams associated with their (partial) reforestation. We calculated the financial implications of alternative strategies, focusing on Acacia koa (“koa”) forestry because of its high conservation and economic potential. Koa’s timber value alone creates a viable investment (mean net present value = $453/acre), but its long time horizon and poor initial cash flow pose formidable challenges for landowners. At present, subsidy payments from a government conservation program targeting benefits for biodiversity, water quality, and soil erosion have the greatest potential to move landowners beyond the tipping point in favor of investments in koa forestry, particularly when combined with future timber harvest (mean net present value = $1,661/acre). Creating financial mechanisms to capture diverse ecosystem service values through time will broaden opportunities for conservation land uses. Governments, nongovernmental organizations, and private investors have roles to play in catalyzing this transition by developing new revenue streams that can reach a broad spectrum of landowners. PMID:16782816

Bottom-Up and Top-Down Solid-State NMR Approaches for Bacterial Biofilm Matrix Composition

PubMed Central

Cegelski, Lynette

2015-01-01

The genomics and proteomics revolutions have been enormously successful in providing crucial “parts lists” for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this Perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The “sum-of-theparts” bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by E. coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in V. cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture. PMID:25797008

Bottom-up and top-down solid-state NMR approaches for bacterial biofilm matrix composition.

PubMed

Cegelski, Lynette

2015-04-01

The genomics and proteomics revolutions have been enormously successful in providing crucial "parts lists" for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The "sum-of-the-parts" bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by Escherichia coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in Vibrio cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture. Copyright © 2015 Elsevier Inc. All rights reserved.

Vulnerability of health to market forces.

PubMed

Brezis, Mayer; Wiist, William H

2011-03-01

This article reviews adverse influences of for-profit enterprises on health care and public health, and examines significance for public policy. Narrative review. For-profit health-care industries may increase costs and reduce quality, leading to market failure and contributing to the USA's unflattering position in international comparisons of health-care efficiency. Drug and device corporations use strategies such as making biased inferences, influencing scientists and physicians, marketing rather than informing the public, and lobbying to control their own industry regulations to create market advantage. Successful marketing leads to the increased use of costly profit-making drugs and procedures over cheaper, nonpatented therapies. Because resources are limited, the overuse of costly modalities contributes to expensive health care, which presents a challenge to universal coverage. The free market also fosters the proliferation of industries, such as tobacco, food, and chemicals, which externalize costs to maximize profits, seek to unduly influence research by paying experts and universities, and attempt to control the media and regulatory agencies. Most vulnerable to the cumulative harm of these tactics are children, the poor, the sick, and the least educated. The free market can harm health and health care. The corporate obligation to increase profits and ensure a return to shareholders affects public health. Such excesses of capitalism pose formidable challenges to social justice and public health. The recognition of the health risks entailed by corporation-controlled markets has important implications for public policy. Reforms are required to limit the power of corporations.

Business strategies for conservation on private lands: Koa forestry as a case study.

PubMed

Goldstein, Joshua H; Daily, Gretchen C; Friday, James B; Matson, Pamela A; Naylor, Rosamond L; Vitousek, Peter

2006-06-27

Innovative financial instruments are being created to reward conservation on private, working lands. Major design challenges remain, however, to make investments in biodiversity and ecosystem services economically attractive and commonplace. From a business perspective, three key financial barriers for advancing conservation land uses must frequently be addressed: high up-front costs, long time periods with no revenue, and high project risk due to long time horizons and uncertainty. We explored ways of overcoming these barriers on grazing lands in Hawaii by realizing a suite of timber and conservation revenue streams associated with their (partial) reforestation. We calculated the financial implications of alternative strategies, focusing on Acacia koa ("koa") forestry because of its high conservation and economic potential. Koa's timber value alone creates a viable investment (mean net present value = $453/acre), but its long time horizon and poor initial cash flow pose formidable challenges for landowners. At present, subsidy payments from a government conservation program targeting benefits for biodiversity, water quality, and soil erosion have the greatest potential to move landowners beyond the tipping point in favor of investments in koa forestry, particularly when combined with future timber harvest (mean net present value = $1,661/acre). Creating financial mechanisms to capture diverse ecosystem service values through time will broaden opportunities for conservation land uses. Governments, nongovernmental organizations, and private investors have roles to play in catalyzing this transition by developing new revenue streams that can reach a broad spectrum of landowners.

Application of science-based restoration planning to a desert river system.

PubMed

Laub, Brian G; Jimenez, Justin; Budy, Phaedra

2015-06-01

Persistence of many desert river species is threatened by a suite of impacts linked to water infrastructure projects that provide human water security where water is scarce. Many desert rivers have undergone regime shifts from spatially and temporally dynamic ecosystems to more stable systems dominated by homogenous physical habitat. Restoration of desert river systems could aid in biodiversity conservation, but poses formidable challenges due to multiple threats and the infeasibility of recovery to pre-development conditions. The challenges faced in restoring desert rivers can be addressed by incorporating scientific recommendations into restoration planning efforts at multiple stages, as demonstrated here through an example restoration project. In particular, use of a watershed-scale planning process can identify data gaps and irreversible constraints, which aid in developing achievable restoration goals and objectives. Site-prioritization focuses limited the resources for restoration on areas with the greatest potential to improve populations of target organisms. Investment in research to understand causes of degradation, coupled with adoption of a guiding vision is critical for identifying feasible restoration actions that can enhance river processes. Setting monitoring as a project goal, developing hypotheses for expected outcomes, and implementing restoration as an experimental design will facilitate adaptive management and learning from project implementation. Involvement of scientists and managers during all planning stages is critical for developing process-based restoration actions and an implementation plan to maximize learning. The planning process developed here provides a roadmap for use of scientific recommendations in future efforts to recover dynamic processes in imperiled riverine ecosystems.

Bottom-up and top-down solid-state NMR approaches for bacterial biofilm matrix composition

NASA Astrophysics Data System (ADS)

Cegelski, Lynette

2015-04-01

The genomics and proteomics revolutions have been enormously successful in providing crucial "parts lists" for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The "sum-of-the-parts" bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by Escherichia coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in Vibrio cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture.

Application of Science-Based Restoration Planning to a Desert River System

NASA Astrophysics Data System (ADS)

Laub, Brian G.; Jimenez, Justin; Budy, Phaedra

2015-06-01

Persistence of many desert river species is threatened by a suite of impacts linked to water infrastructure projects that provide human water security where water is scarce. Many desert rivers have undergone regime shifts from spatially and temporally dynamic ecosystems to more stable systems dominated by homogenous physical habitat. Restoration of desert river systems could aid in biodiversity conservation, but poses formidable challenges due to multiple threats and the infeasibility of recovery to pre-development conditions. The challenges faced in restoring desert rivers can be addressed by incorporating scientific recommendations into restoration planning efforts at multiple stages, as demonstrated here through an example restoration project. In particular, use of a watershed-scale planning process can identify data gaps and irreversible constraints, which aid in developing achievable restoration goals and objectives. Site-prioritization focuses limited the resources for restoration on areas with the greatest potential to improve populations of target organisms. Investment in research to understand causes of degradation, coupled with adoption of a guiding vision is critical for identifying feasible restoration actions that can enhance river processes. Setting monitoring as a project goal, developing hypotheses for expected outcomes, and implementing restoration as an experimental design will facilitate adaptive management and learning from project implementation. Involvement of scientists and managers during all planning stages is critical for developing process-based restoration actions and an implementation plan to maximize learning. The planning process developed here provides a roadmap for use of scientific recommendations in future efforts to recover dynamic processes in imperiled riverine ecosystems.

Application of science-based restoration planning to a desert river system

USGS Publications Warehouse

Laub, Brian G.; Jimenez, Justin; Budy, Phaedra

2015-01-01

Persistence of many desert river species is threatened by a suite of impacts linked to water infrastructure projects that provide human water security where water is scarce. Many desert rivers have undergone regime shifts from spatially and temporally dynamic ecosystems to more stable systems dominated by homogenous physical habitat. Restoration of desert river systems could aid in biodiversity conservation, but poses formidable challenges due to multiple threats and the infeasibility of recovery to pre-development conditions. The challenges faced in restoring desert rivers can be addressed by incorporating scientific recommendations into restoration planning efforts at multiple stages, as demonstrated here through an example restoration project. In particular, use of a watershed-scale planning process can identify data gaps and irreversible constraints, which aid in developing achievable restoration goals and objectives. Site-prioritization focuses limited the resources for restoration on areas with the greatest potential to improve populations of target organisms. Investment in research to understand causes of degradation, coupled with adoption of a guiding vision is critical for identifying feasible restoration actions that can enhance river processes. Setting monitoring as a project goal, developing hypotheses for expected outcomes, and implementing restoration as an experimental design will facilitate adaptive management and learning from project implementation. Involvement of scientists and managers during all planning stages is critical for developing process-based restoration actions and an implementation plan to maximize learning. The planning process developed here provides a roadmap for use of scientific recommendations in future efforts to recover dynamic processes in imperiled riverine ecosystems.

The College Completion Agenda: State Policy Guide

ERIC Educational Resources Information Center

Stedron, Jennifer M.; Shah, Tajel; Bautsch, Brenda; Martin, Patricia; Deye, Sunny; Bailey, Lamar; Handel, Stephen J.; Vasavada, Natasha; Shen, Yilan; Exstrom, Michelle; Shelton, Sara; Santiago, Helen; Bell, Julie Davis; Quin, Bradley J.; Baum, Sandy; Bell, Julie Davis; Sturtevant, Anne; Bautsch, Brenda; Williams, Ronald; Kerouac, Pamela; Badolato, Vincent

2010-01-01

There are formidable challenges at every level of the system that confront students who aspire to enroll and succeed in college. In 2007, the College Board formed the Commission on Access, Admissions and Success in Higher Education to study the educational pipeline as a single continuum and identify solutions to increase the number of students who…

Aural Skills: At the Juncture of Research in Early Reading and Music Literacy

ERIC Educational Resources Information Center

Hansen, Dee; Milligan, Sarah A.

2012-01-01

Pressure on music educators to accommodate reading initiatives in their schools continues to challenge genuine music-learning experiences. Children are taken out of music classrooms for additional reading time, although mounting research informs us of the value of music as a formidable avenue for developing crucial auditory skills needed for…

L2 Willingness to Communicate (WTC) and International Posture in the Polish Educational Context

ERIC Educational Resources Information Center

Mystkowska-Wiertelak, Anna; Pietrzykowska, Agnieszka

2011-01-01

Speaking, the language skill whose mastering appears to be the ultimate aim of every attempt at learning a foreign language, constitutes a formidable challenge. Apart from involving the online interaction of complex processes of conceptualization, formulation, articulation and monitoring (Levelt, 1989), it appears prone to numerous psychological…

Dual Enrollment in Times of Financial Constraint: A Community College Perspective

ERIC Educational Resources Information Center

Hockley, Lori White

2013-01-01

Community college leaders today must contend with a formidable challenge: dwindling state funding and declining resources. Increased enrollments without proportional increases in state and local financial support have placed colleges in the unenviable position of needing to do more with less--or in some cases, simply do less. Despite the…

Fire management ramifications of Hurricane Hugo

Treesearch

J. M. Saveland; D. D. Wade

1991-01-01

Hurricane Hugo passed over the Francis Marion National Forest on September 22, 1989, removing almost 75 percent of the overstory. The radically altered fuel bed presented new and formidable challenges to fire managers. Tractor-plows, the mainstay of fire suppression, were rendered ineffective. The specter of wind-driven escaped burns with no effective means of ground...

Methicillin-Resistant "Staphylococcus aureus" on Campus: A New Challenge to College Health

ERIC Educational Resources Information Center

Weiner, H. Richard

2008-01-01

As new drugs to control bacterial pathogens are developed, the organisms evolve to survive. "Staphylococcus aureus", a common organism, has steadily developed resistance to antibiotics. For more than 40 years, resistant "S. aureus" presented a formidable problem to hospitalized patients; in the past decade, however, it has begun to appear outside…

Stimulation through Simulation? Motor Imagery and Functional Reorganization in Hemiplegic Stroke Patients

ERIC Educational Resources Information Center

Johnson-Frey, Scott H.

2004-01-01

A key factor influencing reorganization of function in damaged neural networks of the adult brain is stimulation. How to stimulate motor areas of patients with paralyses is a formidable challenge. One possibility is to use internal movement simulations, or motor imagery, as an alternative to conventional therapeutic interventions that require…

On the Analysis of Indirect Proofs: Contradiction and Contraposition

ERIC Educational Resources Information Center

Jourdan, Nicolas; Yevdokimov, Oleksiy

2016-01-01

The paper explores and clarifies the similarities and differences that exist between proof by contradiction and proof by contraposition. The paper also focuses on the concept of contradiction, and a general model for this method of proof is offered. The introduction of mathematical proof in the classroom remains a formidable challenge to students…

The College Completion Agenda: 2011 Progress Report. Latino Edition

ERIC Educational Resources Information Center

Lee, John Michael, Jr.; Contreras, Frances; McGuire, Keon M.; Flores-Ragade, Adriana; Rawls, Anita; Edwards, Kelcey; Menson, Roxanna

2011-01-01

When the Commission on Access, Admissions and Success in Higher Education (subsequently referred to as the commission) convened in fall 2008, the educational landscape was facing a number of issues that the commission's members recognized as formidable challenges to those students who aspire to enroll and succeed in college. Summarizing the…

Integrating the Study of the Holocaust: One School's Triumph

ERIC Educational Resources Information Center

Ruder, Robert

2005-01-01

Integrating the study of the Holocaust into the middle school curriculum is a formidable challenge. This article describes the approach taken by Whitwell Middle School in Tennessee: When teachers found that students were having a difficult time comprehending the number of Jews and others killed by the Nazis, they decided to have the students…

Peer Mentoring to Support First-Generation Low-Income College Students

ERIC Educational Resources Information Center

Plaskett, Sean; Bali, Diksha; Nakkula, Michael J.; Harris, John

2018-01-01

Transitioning from high school to college can be a formidable challenge, especially for students who are the first in their family to attend college (first-generation) and/or are from low-income backgrounds. The authors' qualitative investigation of a college mentoring program illuminates the potential value of relatable peer mentors in helping…

Human Exposure Estimates and Oral Equivalents of In Vitro Bioactivity for Prioritizing, Monitoring and Testing of Environmental Chemicals

EPA Science Inventory

High-throughput, lower-cost, in vitro toxicity testing is currently being evaluated for use in prioritization and eventually for predicting in vivo toxicity. Interpreting in vitro data in the context of in vivo human relevance remains a formidable challenge. A key component in us...

Promoting Student Transition Planning by Using a Self-Directed Summary of Performance

ERIC Educational Resources Information Center

Morgan, Robert L.; Kupferman, Scott; Jex, Eliza; Preece, Heidi; Williams, Shannon

2017-01-01

Youth and young adults with disabilities who make the transition out of secondary settings face formidable odds. For example, they confront challenges in regard to attaining employment and becoming involved in postsecondary education. In many cases, their efforts are unsuccessful. One way to support the transition from school to employment or…

Resilient Parenting of Preschool Children at Developmental Risk

ERIC Educational Resources Information Center

Ellingsen, R.; Baker, B. L.; Blacher, J.; Crnic, K.

2014-01-01

Background: Given the great benefits of effective parenting to child development under normal circumstances, and the even greater benefits in the face of risk, it is important to understand why some parents manage to be effective in their interactions with their child despite facing formidable challenges. This study examined factors that promoted…

Optimizing Burn Treatment in Developing Low-and Middle-Income Countries with Limited Health Care Resources (Part 2)

PubMed Central

Atiyeh, B.; Masellis, A.; Conte, C.

2009-01-01

Summary The present review of the literature aims at analysing the challenges facing burn management in low- and middleincome countries (LMICs) and exploring probable modalities to optimize burn management in these countries. In Part 1, the epidemiology of burn injuries and the formidable challenges for proper management due to limited resources and inaccessibility to sophisticated skills and technologies in LMICs were presented. Part II will discuss the actual state of burn injuries management in LMICs. PMID:21991180

Sites and Landforms: A Phase One Archaeological Sampling Survey at Camp Ripley, Morrison County, Minnesota

DTIC Science & Technology

1988-12-31

research of Obadiah StoutI Bennett, an entreprenuer at the Chippewa townsite with an obvious knack for selling undeveloped lots to young women . Dr. Elden...proved a formidable challenge to settlement and agriculture. I The belief that former pine lands were of no value for farming (Anonymous 1894:12) did...cause him to slur his words and lose his train of thought. His was a challenging interview but well worth the time. Among the topics of conversation

Decision-Making Amplification under Uncertainty: An Exploratory Study of Behavioral Similarity and Intelligent Decision Support Systems

ERIC Educational Resources Information Center

Campbell, Merle Wayne

2013-01-01

Intelligent decision systems have the potential to support and greatly amplify human decision-making across a number of industries and domains. However, despite the rapid improvement in the underlying capabilities of these "intelligent" systems, increasing their acceptance as decision aids in industry has remained a formidable challenge.…

Written Parental Consent and the Use of Incentives in a Youth Smoking Prevention Trial: A Case Study from Project SPLASH

ERIC Educational Resources Information Center

Leakey, Tricia; Lunde, Kevin B.; Koga, Karin; Glanz, Karen

2004-01-01

More Institutional Review Boards (IRBs) are requiring written parental consent in school health intervention trials. Because this requirement presents a formidable challenge in conducting large-scale research, it is vital for investigators to share effective strategies learned from completed trials. Investigators for the recently completed Project…

"Hiding Our Snickers": "Weekly Mail" Journalists' Indirect Resistance in Apartheid South Africa

ERIC Educational Resources Information Center

Trabold, Bryan

2006-01-01

In the mid- to late 1980s, the challenges facing the editors and journalists working for the South African antiapartheid newspaper, the "Weekly Mail," were formidable. In addition to the more than one hundred censorship laws already in place, the apartheid government had declared a series of states of emergency in a final and desperate…

How to Create "Thriller" PowerPoints[R] in the Classroom!

ERIC Educational Resources Information Center

Berk, Ronald A.

2012-01-01

PowerPoint[R] presentations in academia have a reputation for being less than engaging in this era of learner-centered teaching. The Net Generation also presents a formidable challenge to using PowerPoint[R]. Although the research on the basic elements is rather sparse, the multimedia elements of movement, music, and videos have a stronger…

Debating Life on Mars: The Knowledge Integration Environment (KIE) in Varied School Settings.

ERIC Educational Resources Information Center

Shear, Linda

Technology-enabled learning environments are beginning to come of age. Tools and frameworks are now available that have been shown to improve learning and are being deployed more widely in varied school settings. Teachers are now faced with the formidable challenge of integrating these promising new environments with the everyday context in which…

Principals' Perceptions of the Motivation Potential of Performance Agreements in Underperforming Schools

ERIC Educational Resources Information Center

Heystek, Jan

2015-01-01

A formidable challenge most school leaders in South Africa face is to improve the academic results in state schools. In terms of their contracts, principals are accountable for the academic results as reflected in examination and test results for their schools. The National Department of Education (currently the Department of Basic Education) has…

The Role of Domain-Specific Knowledge in Generative Reasoning about Complicated Multileveled Phenomena

ERIC Educational Resources Information Center

Duncan, Ravit Golan

2007-01-01

Promoting the ability to reason generatively about novel phenomena and problems students may encounter in their everyday lives is a major goal of science education. This goal proves to be a formidable challenge in domains, such as molecular genetics, for which the accumulated scientific understandings are daunting in both amount and complexity. To…

Orthostatic hypotension: epidemiology, pathophysiology and management

NASA Technical Reports Server (NTRS)

Jacob, G.; Robertson, D.

1995-01-01

Orthostatic hypotension is characterized by low upright blood pressure levels and symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is heterogeneous, correct pathophysiologic diagnosis is important because of therapeutic and prognostic considerations. Although therapy is not usually curative, it can be extraordinarily beneficial if it is individually tailored. Management of the Shy-Drager syndrome (multiple-system atrophy) remains a formidable challenge.

Pursuing Peace in Chicago

ERIC Educational Resources Information Center

Schachter, Ron

2010-01-01

He's patrolled the streets of Chicago, kept the local trains running on time and become a player in the highest echelons of City Hall. But at age 38, Ron Huberman--born in Israel and raised just outside of Chicago--is facing his most formidable challenge. The new Chicago Public Schools (CPS) CEO, who took over from Arne Duncan after President…

Targeted enzyme prodrug therapies.

PubMed

Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

2010-09-01

The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

Thermal transport in suspended silicon membranes measured by laser-induced transient gratings

DOE PAGES

Vega-Flick, A.; Duncan, R. A.; Eliason, J. K.; ...

2016-12-05

Studying thermal transport at the nanoscale poses formidable experimental challenges due both to the physics of the measurement process and to the issues of accuracy and reproducibility. The laser-induced transient thermal grating (TTG) technique permits non-contact measurements on nanostructured samples without a need for metal heaters or any other extraneous structures, offering the advantage of inherently high absolute accuracy. We present a review of recent studies of thermal transport in nanoscale silicon membranes using the TTG technique. An overview of the methodology, including an analysis of measurements errors, is followed by a discussion of new findings obtained from measurements onmore » both “solid” and nanopatterned membranes. The most important results have been a direct observation of non-diffusive phonon-mediated transport at room temperature and measurements of thickness-dependent thermal conductivity of suspended membranes across a wide thickness range, showing good agreement with first-principles-based theory assuming diffuse scattering at the boundaries. Measurements on a membrane with a periodic pattern of nanosized holes (135nm) indicated fully diffusive transport and yielded thermal diffusivity values in agreement with Monte Carlo simulations. Based on the results obtained to-date, we conclude that room-temperature thermal transport in membrane-based silicon nanostructures is now reasonably well understood.« less

Extra-metabolic energy use and the rise in human hyper-density

NASA Astrophysics Data System (ADS)

Burger, Joseph R.; Weinberger, Vanessa P.; Marquet, Pablo A.

2017-03-01

Humans, like all organisms, are subject to fundamental biophysical laws. Van Valen predicted that, because of zero-sum dynamics, all populations of all species in a given environment flux the same amount of energy on average. Damuth’s ’energetic equivalence rule’ supported Van Valen´s conjecture by showing a tradeoff between few big animals per area with high individual metabolic rates compared to abundant small species with low energy requirements. We use metabolic scaling theory to compare variation in densities and individual energy use in human societies to other land mammals. We show that hunter-gatherers occurred at densities lower than the average for a mammal of our size. Most modern humans, in contrast, concentrate in large cities at densities up to four orders of magnitude greater than hunter-gatherers, yet consume up to two orders of magnitude more energy per capita. Today, cities across the globe flux greater energy than net primary productivity on a per area basis. This is possible by importing enormous amounts of energy and materials required to sustain hyper-dense, modern humans. The metabolic rift with nature created by modern cities fueled largely by fossil energy poses formidable challenges for establishing a sustainable relationship on a rapidly urbanizing, yet finite planet.

Ad hoc posterior tibial vessels perforator propeller flaps for the reconstruction of lower third leg soft- tissue defects.

PubMed

Balakrishnan, Thalaivirithan Margabandu; Ramkumar, Jayagosh; Jaganmohan, Janardhanan

2017-01-01

Lower third leg soft tissue defects with anatomical and pathological constraints are posing formidable challenges to reconstructive surgeon. This retrospective study was conducted to assess the effectiveness of ad hoc posterior tibial vessels perforator-propeller flaps for the reconstruction of small and medium sized soft tissue defects in the lower third leg. 22 patients (16 were males and 6 were females) were involved in this study between period of January 2012 and December 2016.We followed the protocol of initial non delineating exploratory incision made to find out single best perforator in all patients. All the defects in leg reconstructed with adhoc posterior tibial vessel propeller flaps. All 22 flaps survived well. All in an average of 13 months follow up period, had pain free walking, with minimal scarring and acceptable aesthesis at the reconstruction sites with no need for any secondary procedure. With inability of preoperatively dopplering the perforators in the lower third leg region, the exploratory posterior nondelineating incision was used in all cases to secure the single best perforator for the propeller flaps. Thus adhoc posterior tibial vessel propeller flaps are dependable, easily adoptable for the reconstruction of soft tissue defects of the lower third leg region.

O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development.

PubMed

Radermacher, Pablo T; Myachina, Faina; Bosshardt, Fritz; Pandey, Rahul; Mariappa, Daniel; Müller, H-Arno J; Lehner, Christian F

2014-04-15

Effects of temperature on biological processes are complex. Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change.

Social Determinants of Infectious Diseases in South Asia

PubMed Central

Bishwajit, Ghose; Ide, Seydou; Ghosh, Sharmistha

2014-01-01

South Asian countries have developed infectious disease control programs such as routine immunization, vaccination, and the provision of essential drugs which are operating nationwide in cooperation with many local and foreign NGOs. Most South Asian countries have a relatively low prevalence of HIV/AIDS until now, but issues like poverty, food insecurity, illiteracy, poor sanitation, and social stigma around AIDS are widespread and are creating formidable challenges to prevention of further spread of this epidemic. Besides that, resurgence of tuberculosis along with the emergence of the drug resistant (MDR-TB and XDRTB) strains and the coepidemic of TB and HIV are posing ever-growing threats to the underdeveloped healthcare infrastructure. The countries are undergoing an epidemiological transition where the disease burden is gradually shifting to noncommunicable diseases, but the infectious diseases still account for almost half of the total disease burden. Despite this huge burden of infectious diseases in South Asia, which is second only to Africa, there is yet any study on the social determinants of infectious diseases in a local context. This paper examines various issues surrounding the social determinants of infectious diseases in South Asian countries with a special reference to HIV and tuberculosis. And, by doing so, it attempts to provide a framework for formulating more efficient prevention and intervention strategies for the future. PMID:27350969

Ad hoc posterior tibial vessels perforator propeller flaps for the reconstruction of lower third leg soft- tissue defects

PubMed Central

Balakrishnan, Thalaivirithan Margabandu; Ramkumar, Jayagosh; Jaganmohan, Janardhanan

2017-01-01

Introduction: Lower third leg soft tissue defects with anatomical and pathological constraints are posing formidable challenges to reconstructive surgeon. Aim: This retrospective study was conducted to assess the effectiveness of ad hoc posterior tibial vessels perforator-propeller flaps for the reconstruction of small and medium sized soft tissue defects in the lower third leg. Patients and Methods: 22 patients (16 were males and 6 were females) were involved in this study between period of January 2012 and December 2016.We followed the protocol of initial non delineating exploratory incision made to find out single best perforator in all patients. All the defects in leg reconstructed with adhoc posterior tibial vessel propeller flaps. Results: All 22 flaps survived well. All in an average of 13 months follow up period, had pain free walking, with minimal scarring and acceptable aesthesis at the reconstruction sites with no need for any secondary procedure. Conclusion: With inability of preoperatively dopplering the perforators in the lower third leg region, the exploratory posterior nondelineating incision was used in all cases to secure the single best perforator for the propeller flaps. Thus adhoc posterior tibial vessel propeller flaps are dependable, easily adoptable for the reconstruction of soft tissue defects of the lower third leg region. PMID:29618863

Conductive Polymer Binder for High-Tap-Density Nanosilicon Material for Lithium-Ion Battery Negative Electrode Application

DOE PAGES

Zhao, Hui; Wei, Yang; Qiao, Ruimin; ...

2015-11-24

High-tap-density silicon nanomaterials are highly desirable as anodes for lithium ion batteries, due to their small surface area and minimum first-cycle loss. However, this material poses formidable challenges to polymeric binder design. Binders adhere on to the small surface area to sustain the drastic volume changes during cycling; also the low porosities and small pore size resulting from this material are detrimental to lithium ion transport. This study introduces a new binder, poly(1-pyrenemethyl methacrylate-co-methacrylic acid) (PPyMAA), for a high-tap-density nanosilicon electrode cycled in a stable manner with a first cycle efficiency of 82%-a value that is further improved to 87%more » when combined with graphite material. Incorporating the MAA acid functionalities does not change the lowest unoccupied molecular orbital (LUMO) features or lower the adhesion performance of the PPy homopolymer. Our single-molecule force microscopy measurement of PPyMAA reveals similar adhesion strength between polymer binder and anode surface when compared with conventional polymer such as homopolyacrylic acid (PAA), while being electronically conductive. Finally, the combined conductivity and adhesion afforded by the MAA and pyrene copolymer results in good cycling performance for the high-tap-density Si electrode.« less

Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats

PubMed Central

Armour, John A. L.; Palla, Raquel; Zeeuwen, Patrick L. J. M.; den Heijer, Martin; Schalkwijk, Joost; Hollox, Edward J.

2007-01-01

Recent work has demonstrated an unexpected prevalence of copy number variation in the human genome, and has highlighted the part this variation may play in predisposition to common phenotypes. Some important genes vary in number over a high range (e.g. DEFB4, which commonly varies between two and seven copies), and have posed formidable technical challenges for accurate copy number typing, so that there are no simple, cheap, high-throughput approaches suitable for large-scale screening. We have developed a simple comparative PCR method based on dispersed repeat sequences, using a single pair of precisely designed primers to amplify products simultaneously from both test and reference loci, which are subsequently distinguished and quantified via internal sequence differences. We have validated the method for the measurement of copy number at DEFB4 by comparison of results from >800 DNA samples with copy number measurements by MAPH/REDVR, MLPA and array-CGH. The new Paralogue Ratio Test (PRT) method can require as little as 10 ng genomic DNA, appears to be comparable in accuracy to the other methods, and for the first time provides a rapid, simple and inexpensive method for copy number analysis, suitable for application to typing thousands of samples in large case-control association studies. PMID:17175532

Extra-metabolic energy use and the rise in human hyper-density.

PubMed

Burger, Joseph R; Weinberger, Vanessa P; Marquet, Pablo A

2017-03-02

Humans, like all organisms, are subject to fundamental biophysical laws. Van Valen predicted that, because of zero-sum dynamics, all populations of all species in a given environment flux the same amount of energy on average. Damuth's 'energetic equivalence rule' supported Van Valen´s conjecture by showing a tradeoff between few big animals per area with high individual metabolic rates compared to abundant small species with low energy requirements. We use metabolic scaling theory to compare variation in densities and individual energy use in human societies to other land mammals. We show that hunter-gatherers occurred at densities lower than the average for a mammal of our size. Most modern humans, in contrast, concentrate in large cities at densities up to four orders of magnitude greater than hunter-gatherers, yet consume up to two orders of magnitude more energy per capita. Today, cities across the globe flux greater energy than net primary productivity on a per area basis. This is possible by importing enormous amounts of energy and materials required to sustain hyper-dense, modern humans. The metabolic rift with nature created by modern cities fueled largely by fossil energy poses formidable challenges for establishing a sustainable relationship on a rapidly urbanizing, yet finite planet.

Drug-resistant tuberculosis: time for visionary political leadership.

PubMed

Abubakar, Ibrahim; Zignol, Matteo; Falzon, Dennis; Raviglione, Mario; Ditiu, Lucica; Masham, Susan; Adetifa, Ifedayo; Ford, Nathan; Cox, Helen; Lawn, Stephen D; Marais, Ben J; McHugh, Timothy D; Mwaba, Peter; Bates, Matthew; Lipman, Marc; Zijenah, Lynn; Logan, Simon; McNerney, Ruth; Zumla, Adam; Sarda, Krishna; Nahid, Payam; Hoelscher, Michael; Pletschette, Michel; Memish, Ziad A; Kim, Peter; Hafner, Richard; Cole, Stewart; Migliori, Giovanni Battista; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin

2013-06-01

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans. Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

Antiracism Education? A Study of an Antiracism Workshop in Finland

ERIC Educational Resources Information Center

Alemanji, Aminkeng Atabong; Mafi, Boby

2018-01-01

In doing antiracism education there is a risk that it can in effect reinforce the very racialisation it is supposed to fight against. This paradox becomes a formidable challenge given the ubiquity of race in contemporary ways of knowing and ways of being for both its subjects and its objects: more so in an era of "racism without race," a…

Using Speech Recognition Software to Improve Writing Skills

ERIC Educational Resources Information Center

Diaz, Felix

2014-01-01

Orthopedically impaired (OI) students face a formidable challenge during the writing process due to their limited or non-existing ability to use their hands to hold a pen or pencil or even to press the keys on a keyboard. While they may have a clear mental picture of what they want to write, the biggest hurdle comes well before having to tackle…

The Continuing Struggle: Civil Rights and the Clinton Administration. Report of the Citizens' Commission on Civil Rights.

ERIC Educational Resources Information Center

Yu, Corrine M., Ed.; Taylor, William L., Ed.

In 1993 the Citizens' Commission on Civil Rights concluded that the election of Bill Clinton as President presented a new opportunity to work toward equal opportunity. In 1995, at the midpoint of his first term, the Commission identified the new and often formidable challenges his administration was facing in dealing with issues of equal…

Free Your Mind. The Book for Gay, Lesbian, and Bisexual Youth--and Their Allies.

ERIC Educational Resources Information Center

Bass, Ellen; Kaufman, Kate

Gay, lesbian, and bisexual youth face formidable challenges, but are beginning to proclaim their worth and power and to assert their rightful places in the world. Being lesbian or gay means that a person's primary romantic, emotional, physical, and sexual attractions are with someone of the same sex. Bisexual people have these attractions to both…

A Superannuated Physicist's Attempts to Master Music Theory: Resolving Cognitive Conflicts and a Paradigm Clash

ERIC Educational Resources Information Center

Page-Shipp, Roy; van Niekerk, Caroline

2014-01-01

A sexagenarian retired physicist (the first author) set out, with the assistance of members of a university music department, to acquire some insight into Western music theory. For a lifelong singer and seasoned autodidact, this appeared to be a not too formidable challenge, yet he experienced significant difficulty in penetrating the music theory…

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

Shiltsev, Vladimir

The 2014 P5 report indicated the accelerator-based neutrino and rare decay physics research as a centerpiece of the US domestic HEP program. Operation, upgrade and development of the accelerators for the near-term and longer-term particle physics program at the Intensity Frontier face formidable challenges. Here we discuss key elements of the accelerator physics and technology R&D program toward future multi-MW proton accelerators.

Adoption of Geospatial Systems towards evolving Sustainable Himalayan Mountain Development

NASA Astrophysics Data System (ADS)

Murthy, M. S. R.; Bajracharya, B.; Pradhan, S.; Shestra, B.; Bajracharya, R.; Shakya, K.; Wesselmann, S.; Ali, M.; Bajracharya, S.; Pradhan, S.

2014-11-01

Natural resources dependence of mountain communities, rapid social and developmental changes, disaster proneness and climate change are conceived as the critical factors regulating sustainable Himalayan mountain development. The Himalayan region posed by typical geographic settings, diverse physical and cultural diversity present a formidable challenge to collect and manage data, information and understands varied socio-ecological settings. Recent advances in earth observation, near real-time data, in-situ measurements and in combination of information and communication technology have transformed the way we collect, process, and generate information and how we use such information for societal benefits. Glacier dynamics, land cover changes, disaster risk reduction systems, food security and ecosystem conservation are a few thematic areas where geospatial information and knowledge have significantly contributed to informed decision making systems over the region. The emergence and adoption of near-real time systems, unmanned aerial vehicles (UAV), board-scale citizen science (crowd-sourcing), mobile services and mapping, and cloud computing have paved the way towards developing automated environmental monitoring systems, enhanced scientific understanding of geophysical and biophysical processes, coupled management of socio-ecological systems and community based adaptation models tailored to mountain specific environment. There are differentiated capacities among the ICIMOD regional member countries with regard to utilization of earth observation and geospatial technologies. The region can greatly benefit from a coordinated and collaborative approach to capture the opportunities offered by earth observation and geospatial technologies. The regional level data sharing, knowledge exchange, and Himalayan GEO supporting geospatial platforms, spatial data infrastructure, unique region specific satellite systems to address trans-boundary challenges would go a long way in evolving sustainable Himalayan livelihoods.

Type 2 Diabetes Mellitus in Saudi Arabia: Major Challenges and Possible Solutions.

PubMed

Robert, Asirvatham Alwin; Al Dawish, Mohamed Abdulaziz; Braham, Rim; Musallam, Maha Ali; Al Hayek, Ayman Abdullah; Al Kahtany, Nasser Hazza

2017-01-01

The World Health Organization has ranked Saudi Arabia as having the second highest rate of diabetes in the Middle East (7th highest in the world) with an estimated population of 7 million living with diabetes and more than 3 million with pre-diabetes. This presents a pressing public health problem. Several challenges in diabetes management need to be tackled in Saudi Arabia, including the growing prevalence (chiefly among children and young adults), micro-and macrovascular complications, lifestyle changes, late diagnosis, poor awareness and high treatment costs. Over the last two decades, the Saudi population saw an increase in the expenses in healthcare and treatment of diabetes by more than 500%. In 2014, the health care budget was 180 billion (Saudi Riyal) of which 17 billion was spent on all Saudis, with an approximate 25 billion on the entire Saudi diabetic population. This implies that the direct expense of diabetes is costing Saudi Arabia around 13.9% of the total health expenditure. Therefore, unless a comprehensive epidemic control program/ multidisciplinary approach is stringently enforced, the diabetes mellitus burden on Saudi Arabia will probably increase to very serious levels. It is crucial to implement improved health and health-related quality of life of to those with diabetes, thus minimizing the social and personal expenses for diabetes care in Saudi Arabia. In this study we discuss the significant and major threats posed by diabetes mellitus to the Saudi population and recommend essential possible solutions to delay/ prevent this formidable issue. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advanced staring Si PIN visible sensor chip assembly for Bepi-Colombo mission to Mercury

NASA Astrophysics Data System (ADS)

Mills, R. E.; Drab, J. J.; Gin, A.

2009-08-01

The planet Mercury, by its near proximity to the sun, has always posed a formidable challenge to spacecraft. The Bepi-Colombo mission, coordinated by the European Space Agency, will be a pioneering effort in the investigation of this planet. Raytheon Vision Systems (RVS) has been given the opportunity to develop the radiation hardened, high operability, high SNR, advanced staring focal plane array (FPA) for the spacecraft destined (Fig. 1) to explore the planet Mercury. This mission will launch in 2013 on a journey lasting approximately 6 years. When it arrives at Mercury in August 2019, it will endure temperatures as high as 350°C as well as relatively high radiation environments during its 1 year data collection period from September 2019 until September 2020. To support this challenging goal, RVS has designed and produced a custom visible sensor based on a 2048 x 2048 (2k2) format with a 10 μm unit cell. This sensor will support both the High Resolution Imaging Camera (HRIC) and the Stereo Camera (STC) instruments. This dual purpose sensor was designed to achieve high sensitivity as well as low input noise (<100 e-) for space-based, low light conditions. It also must maintain performance parameters in a total ionizing dose environment up to 70 kRad (Si) as well as immunity to latch-up and singe event upset. This paper will show full sensor chip assembly data highlighting the performance parameters prior to irradiation. Radiation testing performance will be reported by an independent source in a subsequent paper.

When it rains, it pours: future climate extremes and health.

PubMed

Patz, Jonathan A; Grabow, Maggie L; Limaye, Vijay S

2014-01-01

The accelerating accumulation of greenhouse gases in the Earth's atmosphere is changing global environmental conditions in unprecedented and potentially irreversible ways. Climate change poses a host of challenges to the health of populations through complex direct and indirect mechanisms. The direct effects include an increased frequency of heat waves, rising sea levels that threaten low-lying communities, anticipated extremes in the global hydrologic cycle (droughts, floods, and intense storms), and adverse effects on agricultural production and fisheries due to environmental stressors and changes in land use. Indirectly, climate change is anticipated to threaten health by worsening urban air pollution and increasing rates of infectious (particularly waterborne and vector-borne) disease transmission. To provide a state-of-the-science review on the health consequences of a changing climate. Environmental public health researchers have concluded that, on balance, adverse health outcomes will dominate under these changed climatic conditions. The number of pathways through which climate change can affect the health of populations makes this environmental health threat one of the largest and most formidable of the new century. Geographic location plays an influential role the potential for adverse health effects caused by climate change, and certain regions and populations are more vulnerable than others to expected health effects. Two kinds of strategies are available for responding to climate change: mitigation policies (which aim to reduce greenhouse gas emissions) and adaptation measures (relating to preparedness for anticipated impacts). To better understand and address the complex nature of health risks posed by climate change, interdisciplinary collaboration is critical. Efforts to move beyond our current reliance on fossil fuels to cleaner, more sustainable energy sources may offer some of the greatest health opportunities in more than a century and cobenefits beyond the health sector. Because the nations least responsible for climate change are most vulnerable to its effects, the challenge to reduce greenhouse gas emissions is not merely technical, but also moral. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Optical medical imaging: from glass to man

NASA Astrophysics Data System (ADS)

Bradley, Mark

2016-11-01

A formidable challenge in modern respiratory healthcare is the accurate and timely diagnosis of lung infection and inflammation. The EPSRC Interdisciplinary Research Collaboration (IRC) `Proteus' seeks to address this challenge by developing an optical fibre based healthcare technology platform that combines physiological sensing with multiplexed optical molecular imaging. This technology will enable in situ measurements deep in the human lung allowing the assessment of tissue function and characterization of the unique signatures of pulmonary disease and is illustrated here with our in-man application of Optical Imaging SmartProbes and our first device Versicolour.

The adaptation challenge in the Arctic

NASA Astrophysics Data System (ADS)

Ford, James D.; McDowell, Graham; Pearce, Tristan

2015-12-01

It is commonly asserted that human communities in the Arctic are highly vulnerable to climate change, with the magnitude of projected impacts limiting their ability to adapt. At the same time, an increasing number of field studies demonstrate significant adaptive capacity. Given this paradox, we review climate change adaptation, resilience and vulnerability research to identify and characterize the nature and magnitude of the adaptation challenge facing the Arctic. We find that the challenge of adaptation in the Arctic is formidable, but suggest that drivers of vulnerability and barriers to adaptation can be overcome, avoided or reduced by individual and collective efforts across scales for many, if not all, climate change risks.

Achieving Medical Currency via Selected Staff Integration in Civilian and Veterans Administration Medical Facilities

DTIC Science & Technology

2012-10-01

medical license as long as care is delivered in a military facility.26 Hurdles—Liability Medical malpractice also presents a formidable challenge. In...AIR UNIVERSITY AIR WAR COLLEGE Achieving Medical Currency via Selected Staff Integration in Civilian and Veterans Administration... Medical Facilities THOMAS W. HARRELL Colonel, USAF, MC, SFS Air War College Maxwell Paper No. 68 Maxwell Air Force Base, Alabama

Performance of multiple docking and refinement methods in the pose prediction D3R prospective Grand Challenge 2016

NASA Astrophysics Data System (ADS)

Fradera, Xavier; Verras, Andreas; Hu, Yuan; Wang, Deping; Wang, Hongwu; Fells, James I.; Armacost, Kira A.; Crespo, Alejandro; Sherborne, Brad; Wang, Huijun; Peng, Zhengwei; Gao, Ying-Duo

2018-01-01

We describe the performance of multiple pose prediction methods for the D3R 2016 Grand Challenge. The pose prediction challenge includes 36 ligands, which represent 4 chemotypes and some miscellaneous structures against the FXR ligand binding domain. In this study we use a mix of fully automated methods as well as human-guided methods with considerations of both the challenge data and publicly available data. The methods include ensemble docking, colony entropy pose prediction, target selection by molecular similarity, molecular dynamics guided pose refinement, and pose selection by visual inspection. We evaluated the success of our predictions by method, chemotype, and relevance of publicly available data. For the overall data set, ensemble docking, visual inspection, and molecular dynamics guided pose prediction performed the best with overall mean RMSDs of 2.4, 2.2, and 2.2 Å respectively. For several individual challenge molecules, the best performing method is evaluated in light of that particular ligand. We also describe the protein, ligand, and public information data preparations that are typical of our binding mode prediction workflow.

Closing the Performance Gap: The Impact of the Early College High School Model on Underprepared Students

ERIC Educational Resources Information Center

Bernstein, Larry; Edmunds, Julie; Fesler, Lily

2014-01-01

Students entering high school in 9th grade face a formidable challenge. The transition to high school from 8th grade brings with it increased risks for all students. For example, students in 9th grade are anywhere from three to five times more likely to fail a class than students in any other grade. Similarly, ninth grade retention rates are…

Team Problem Solving: Effects of Communication and Function Overlap

DTIC Science & Technology

1987-03-01

group. At the very least, this concept helps to focus to some degree on the formidable complexity of the relationship between the available rosources... relationship with task load gains clarity, for a task load may be overwhelming to a group of limited capability, yet challenging or even gratifying to a...considered if othaer important resources were also missing. This behavior is consistent with predictions of social motivational theories such as

Coup Prevention: A Critical Ingredient of Nation-Building Operations

DTIC Science & Technology

2010-03-01

Mozambique, to name a few.7 Peace and Security Development Humanitarian Relief Peace Building Right to Protect Rights Based A greater challenge lies ...because it was based “on the drifting nature of Mian Nawaz Sharif’s administration that lacked political stability, contrasted with unlimited desire...Court validated the coup and imprisoned Mian Nawaz Sharif for 25 years and, in essence, provided a formidable amount of judicial legitimacy. 7

Virtual Surgical Planning in Craniofacial Surgery

PubMed Central

Chim, Harvey; Wetjen, Nicholas; Mardini, Samir

2014-01-01

The complex three-dimensional anatomy of the craniofacial skeleton creates a formidable challenge for surgical reconstruction. Advances in computer-aided design and computer-aided manufacturing technology have created increasing applications for virtual surgical planning in craniofacial surgery, such as preoperative planning, fabrication of cutting guides, and stereolithographic models and fabrication of custom implants. In this review, the authors describe current and evolving uses of virtual surgical planning in craniofacial surgery. PMID:25210509

Mental health services then and now.

PubMed

Mechanic, David

2007-01-01

Over the past twenty-five years, psychiatric services have shifted from hospital to community. Managed care reinforces this trend. Mental illness is better understood and less stigmatized, and services are more commonly used. But many in need do not receive care consistent with evidence-based standards, or at all. Challenges are greatest for people with serious and persistent mental illnesses who depend on generic health and welfare programs and integrated services. Evidence-based rehabilitative care is often unavailable. Failures in community care lead to arrest; jail diversion and treatment are required. Despite progress, implementing an effective, patient-centered care system remains a formidable challenge.

Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions

NASA Astrophysics Data System (ADS)

Li, Jianguo; Garg, Manju; Shah, Dhawal; Rajagopalan, Raj

2010-08-01

Experiments hold intriguing, circumstantial clues to the mechanisms behind arginine-mediated solubilization of small organic drugs and suppression of protein aggregation driven by hydrophobic or aromatic associations, but how exactly arginine's molecular structure and interactions contribute to its function remains unclear since attention has focused so far on the thermodynamics of the preferential exclusion or binding of arginine. Here, we examine, through molecular dynamics simulations, how arginine solubilizes nanoscale particles with hydrophobic surfaces or aromatic-ring-type surface interactions. We show that preferential, hydrophobic, and dispersion interactions of arginine's guanidinium group with the particles lead to a surfactant-like behavior of arginine around the particles and to a solvation layer with a protective polar mask creating a hydrophilic shell. Additionally, arginine-arginine association around the solvation layer further prevents aggregative contacts. The results shed some light on the mechanistic basis of arginine's function as a suppressant of protein aggregation, although the complex energy landscapes and kinetic pathways of aggregation are protein-dependent and pose formidable challenges to developing comprehensive mechanistic pictures. Our results suggest arginine's mode of interaction with hydrophobic patches and aromatic residues could reduce aggregation-prone intermediate states of proteins and shield protein-protein aggregative contacts. The approach used here offers a systematic way of exploring implications of other amino acid/excipient interactions by studying interactions of the excipient with particles grafted with amino acids.

Telomeres and NextGen CO-FISH: Directional Genomic Hybridization (Telo-dGH™).

PubMed

McKenna, Miles J; Robinson, Erin; Goodwin, Edwin H; Cornforth, Michael N; Bailey, Susan M

2017-01-01

The cytogenomics-based methodology of Directional Genomic Hybridization (dGH™) emerged from the concept of strand-specific hybridization, first made possible by Chromosome Orientation FISH (CO-FISH), the utility of which was demonstrated in a variety of early applications, often involving telomeres. Similar to standard whole chromosome painting (FISH), dGH™ is capable of identifying inter-chromosomal rearrangements (translocations between chromosomes), but its distinctive strength stems from its ability to detect intra-chromosomal rearrangements (inversions within chromosomes), and to do so at higher resolution than previously possible. dGH™ brings together the strand specificity and directionality of CO-FISH with sophisticated bioinformatics-based oligonucleotide probe design to unique sequences. dGH™ serves not only as a powerful discovery tool-capable of interrogating the entire genome at the megabase level-it can also be used for high-resolution targeted detection of known inversions, a valuable attribute in both research and clinical settings. Detection of chromosomal inversions, particularly small ones, poses a formidable challenge for more traditional cytogenetic approaches, especially when they occur near the ends or telomeric regions. Here, we describe Telo-dGH™, a strand-specific scheme that utilizes dGH™ in combination with telomere CO-FISH to differentiate between terminal exchange events, specifically terminal inversions, and an altogether different form of genetic recombination that often occurs near the telomere, namely sister chromatid exchange (SCE).

malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication

PubMed Central

2017-01-01

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination. PMID:29190291

A surface code quantum computer in silicon

PubMed Central

Hill, Charles D.; Peretz, Eldad; Hile, Samuel J.; House, Matthew G.; Fuechsle, Martin; Rogge, Sven; Simmons, Michelle Y.; Hollenberg, Lloyd C. L.

2015-01-01

The exceptionally long quantum coherence times of phosphorus donor nuclear spin qubits in silicon, coupled with the proven scalability of silicon-based nano-electronics, make them attractive candidates for large-scale quantum computing. However, the high threshold of topological quantum error correction can only be captured in a two-dimensional array of qubits operating synchronously and in parallel—posing formidable fabrication and control challenges. We present an architecture that addresses these problems through a novel shared-control paradigm that is particularly suited to the natural uniformity of the phosphorus donor nuclear spin qubit states and electronic confinement. The architecture comprises a two-dimensional lattice of donor qubits sandwiched between two vertically separated control layers forming a mutually perpendicular crisscross gate array. Shared-control lines facilitate loading/unloading of single electrons to specific donors, thereby activating multiple qubits in parallel across the array on which the required operations for surface code quantum error correction are carried out by global spin control. The complexities of independent qubit control, wave function engineering, and ad hoc quantum interconnects are explicitly avoided. With many of the basic elements of fabrication and control based on demonstrated techniques and with simulated quantum operation below the surface code error threshold, the architecture represents a new pathway for large-scale quantum information processing in silicon and potentially in other qubit systems where uniformity can be exploited. PMID:26601310

A surface code quantum computer in silicon.

PubMed

Hill, Charles D; Peretz, Eldad; Hile, Samuel J; House, Matthew G; Fuechsle, Martin; Rogge, Sven; Simmons, Michelle Y; Hollenberg, Lloyd C L

2015-10-01

The exceptionally long quantum coherence times of phosphorus donor nuclear spin qubits in silicon, coupled with the proven scalability of silicon-based nano-electronics, make them attractive candidates for large-scale quantum computing. However, the high threshold of topological quantum error correction can only be captured in a two-dimensional array of qubits operating synchronously and in parallel-posing formidable fabrication and control challenges. We present an architecture that addresses these problems through a novel shared-control paradigm that is particularly suited to the natural uniformity of the phosphorus donor nuclear spin qubit states and electronic confinement. The architecture comprises a two-dimensional lattice of donor qubits sandwiched between two vertically separated control layers forming a mutually perpendicular crisscross gate array. Shared-control lines facilitate loading/unloading of single electrons to specific donors, thereby activating multiple qubits in parallel across the array on which the required operations for surface code quantum error correction are carried out by global spin control. The complexities of independent qubit control, wave function engineering, and ad hoc quantum interconnects are explicitly avoided. With many of the basic elements of fabrication and control based on demonstrated techniques and with simulated quantum operation below the surface code error threshold, the architecture represents a new pathway for large-scale quantum information processing in silicon and potentially in other qubit systems where uniformity can be exploited.

HIV/AIDS, conflict and security in Africa: rethinking relationships

PubMed Central

2008-01-01

The effect of conflict on HIV transmission and regional and global security has been the subject of much recent discussion and debate. Many long held assumptions regarding these relationships are being reconsidered. Conflict has long been assumed to contribute significantly to the spread of HIV infection. However, new research is casting doubt on this assumption. Studies from Africa suggest that conflict does not necessarily predispose to HIV transmission and indeed, there is evidence to suggest that recovery in the "post-conflict" state is potentially dangerous from the standpoint of HIV transmission. As well, refugee populations have been previously considered as highly infected vectors of HIV transmission. But in light of new investigation this belief is also being reconsidered. There has additionally been concern that high rates of HIV infection among many of the militaries of sub-Saharan Africa poses a threat to regional security. However, data is lacking on both dramatically elevated prevalence amongst soldiers and a possible negative effect on regional security. Nevertheless, HIV/AIDS remain a serious threat to population health and economic well being in this region. These issues are of vital importance for HIV programming and health sector development in conflict and "post-conflict" societies and will constitute formidable challenges to the international community. Further research is required to better inform the discussion of HIV, conflict, and security in sub-Saharan Africa. PMID:19014653

Human Immunodeficiency Virus Vaccine Trials

PubMed Central

O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

2012-01-01

More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

Management of diabetic nephropathy: Recent progress and future perspective.

PubMed

Ahmad, Jamal

2015-01-01

Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD) affecting ∼20-30% diabetics, is associated with increased cardiovascular mortality. The progression of kidney disease in patients with diabetes can take many years. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk factors besides elevated serum lipids, smoking habits, and the amount of dietary proteins. Interventions such as glycaemic control, blood pressure control and inhibition of the renin-angiotensin-aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes that ultimately develop end-stage renal disease remains high. The treatment of DN, therefore, has posed a formidable challenge besides optimization of renin-angiotensin-aldosterone system blockade in patients with DN; additional investigation has focused on the potential of novel therapies that target various pathways upregulated by hyperglycaemia or other targets believed to promote the progression of DN such as oxidative stress, inflammation, endothelin system and vitamin D receptors. This review article addresses the pathogenesis and some of the well established principles regarding the progression and accepted management of DN, and also includes the perspectives of novel anti-DN agents and the future directions for the prevention of DN. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication.

PubMed

2017-11-01

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination.

Size, skills, and suffrage: Motivated distortions in perceived formidability of political leaders

PubMed Central

Blaker, Nancy M.; Pollet, Thomas V.

2017-01-01

Research shows that perception of physical size and status are positively associated. The current study was developed to replicate and extend earlier research on height perceptions of political leaders, indicating that supporters perceive their leaders as taller than non-supporters do, and winners are perceived as taller after the elections, while losers are perceived as shorter after the elections (winner/loser effects). Individuals use greater height and strength as indications of greater physical formidability. We hypothesized that in-group leaders’ height and strength, but not weight, would be overestimated more compared to out-group leaders’, and that this status-size association is not only driven by dominance, but also by prestige. We also tested whether previously found gender effects in estimates were due to using one’s own height as an anchor, and we used an improved methodological approach by relying on multiple measurements of physical formidability and a within-subject design for testing winner/loser effects. The results of a two-part longitudinal study (self-selected sample via voting advice website; NWave1 = 2,011; NWave2 = 322) suggest that estimated physical formidability of political leaders is affected by motivated perception, as prestige was positively associated with estimated formidability, and in-group leaders were estimated more formidable than out-group leaders. We conclude that distortions in judged formidability related to social status are the result of motivated social perception in order to promote group functioning and leadership. Although we did not replicate a winner-effect (greater estimations of formidability after winning the elections), we did find some evidence for a loser-effect. Earlier suggestions that men make larger estimations than women because of their own larger body size are not supported. Implications for theory and future research are discussed. PMID:29267275

Complex and biofluids: From Maxwell to nowadays

NASA Astrophysics Data System (ADS)

Misbah, Chaouqi

2009-11-01

Complex fluids are the rule in biology and in many industrial applications. Typical examples are blood, cartilage, and polymer solutions. Unlike water (as well as domestic oils, soft clear drinks, and so on), the law(s) describing the behavior of complex fluids are not yet fully established. The complexity arises from strong coupling between microscopic scales (like the motion of a red blood cell in the case of blood, or a polymer molecule for a polymer solution) and the global scale of the flow (say at the scale of a blood artery, or a channel in laboratory experiments). In this issue entitled Complex and Biofluids a large panel of experimental and theoretical problems of complex fluids is exposed. The topics range from dilute polymer solutions, food products, to biology (blood flow, cell and tissue mechanics). One of the earliest model put forward as an attempt to describe a complex fluid was suggested a long time ago by James Clerk Maxwell (in 1867). Other famous scientists, like Einstein (in 1906), and Taylor (in 1932) have made important contributions to the field, but the topic of complex fluids still continues to pose a formidable challenge to science. This field has known during the past decade an unbelievable upsurge of interest in many branches of science (physics, mechanics, chemistry, biology, medical science, mathematics, and so on). Understanding complex fluids is viewed as one of the biggest challenge of the present century. This synthesis will provide a simple introduction to the topic, summarize the main contribution of this issue, and list major open questions in this field. To cite this article: C. Misbah, C. R. Physique 10 (2009).

Who is bearing the financial burden of non-communicable diseases in Mongolia?

PubMed Central

Dugee, Otgontuya; Palam, Enkhtuya; Dorjsuren, Bayarsaikhan; Mahal, Ajay

2018-01-01

Background Non-communicable diseases (NCDs) pose a formidable health and development challenge for low- and middle-income countries (LMICs). However, translating this challenge into resource allocation is seriously constrained by a lack of country specific evidence on NCD financing and its distributional implications. This study estimated expenditures associated with NCDs in Mongolia and their distributions across socioeconomic groups, focusing especially on private out-of-pocket (OOP) spending on the major NCDs. Methods Secondary data analysis of multiple data sources on NCD related health service use and expenditures including detailed administrative data, World Health Organization STEPwise approach to Surveillance (STEPs) survey for Mongolia, and household surveys. Sample-weighted estimates of OOP expenditures for NCDs were constructed using STEPs data. OOP payments per discharge and per outpatient visit were estimated by condition and type of service provider, and survey data on utilization, after adjusting for utilization in administrative records. Results NCDs in Mongolia accounted for more than one-third of total health expenditures in 2013. A significant fraction of this expenditure was borne by households in the form of OOP spending. CVD-related health spending is the major driver of NCD-spending in Mongolia, accounting for about 24.2% of total health expenditure. OOP health payments, largely driven by outpatient diagnostics and drugs, were incurred disproportionately by the better-off, seeking more specialist services and better quality private care. Conclusion A high share of OOP spending for NCDs in Mongolia, which ostensibly enjoys universal health coverage, provides a cautionary tale for LMICs in a similar situation. Improvement in the quality of services at the primary care level and rural health care facilities, where the poor mainly attend, is desirable together with an effective exemption policy for user fees at higher level hospitals. PMID:29564086

Increasing drought and diminishing benefits of elevated carbon dioxide for soybean yields across the US Midwest.

PubMed

Jin, Zhenong; Ainsworth, Elizabeth A; Leakey, Andrew D B; Lobell, David B

2018-02-01

Elevated atmospheric CO 2 concentrations ([CO 2 ]) are expected to increase C3 crop yield through the CO 2 fertilization effect (CFE) by stimulating photosynthesis and by reducing stomatal conductance and transpiration. The latter effect is widely believed to lead to greater benefits in dry rather than wet conditions, although some recent experimental evidence challenges this view. Here we used a process-based crop model, the Agricultural Production Systems sIMulator (APSIM), to quantify the contemporary and future CFE on soybean in one of its primary production area of the US Midwest. APSIM accurately reproduced experimental data from the Soybean Free-Air CO 2 Enrichment site showing that the CFE declined with increasing drought stress. This resulted from greater radiation use efficiency (RUE) and above-ground biomass production at elevated [CO 2 ] that outpaced gains in transpiration efficiency (TE). Using an ensemble of eight climate model projections, we found that drought frequency in the US Midwest is projected to increase from once every 5 years currently to once every other year by 2050. In addition to directly driving yield loss, greater drought also significantly limited the benefit from rising [CO 2 ]. This study provides a link between localized experiments and regional-scale modeling to highlight that increased drought frequency and severity pose a formidable challenge to maintaining soybean yield progress that is not offset by rising [CO 2 ] as previously anticipated. Evaluating the relative sensitivity of RUE and TE to elevated [CO 2 ] will be an important target for future modeling and experimental studies of climate change impacts and adaptation in C3 crops. © 2017 John Wiley & Sons Ltd.

Current aspects in reconstructive surgery for nasal cavity and paranasal sinus cancer

NASA Astrophysics Data System (ADS)

Shtin, V. I.; Novikov, V. A.; Gjunter, V. E.; Choinzonov, E. L.; Ryabova, A. I.; Sirkashev, V. A.; Surkova, P. V.; Vasilev, R. V.; Menkova, E. N.

2017-09-01

Tumors of the nasal cavity and paranasal sinuses present a challenge to treat them. A combination of surgery and radiation therapy can improve treatment outcomes in 49-56% [1, 2] of the patients with locally advanced nasal cavity and paranasal sinus cancer. The midface reconstruction poses a formidable challenge to the reconstructive surgeon due to the region's complex skeletal and soft-tissue anatomy. The rehabilitation program including the reconstruction of the resected orbital walls using the porous and mesh implants from titanium nickelid (TiNi) was developed at the Cancer Research institute jointly with the Research Institute of Medical Materials. The technique was proven effective, allowing the natural position of the eye and visual function to be preserved in 90% [1-3] of the patients. A long period of reparative processes and risk of developing inflammation in the implant area, as well as the need to decrease length of surgery, contributed to the development of a novel approach to repairing the midface bone structures using the implant based on the microporous wire and TiNi mesh. Eighteen patients with nasal cavity and paranasal sinus cancer were treated using the combined thin implants. The novel technique allowed the time of the implant installation to be reduced to 5-10 min. The structure of the implant contributed to prevention of inflammatory processes in 97% [1, 2] of cases. Thus, the natural position of the eyeball and visual function were preserved in 100% [1, 3, 4] of patients. The use of the TiNi implants in reconstructive surgery for patients with nasal cavity and paranasal sinus cancer led to reduced time of surgery and rehabilitation, increased level of social adaptation of patients and improved cosmetic and functional results.

Investigation of the Feasibility of Using Laser Induced Fluorescence for Concentration Measurements by Diatomic Sulfur.

DTIC Science & Technology

1982-12-01

GEP/PH/82D-1O INVESTIGATION OF THE FEASIBILITY OF USING LASER INDUCED FLUORESCENCE FOR CONCENTRATION MEASUREMENTS OF DIATOMIC SULFUR THESIS AFIT/GEP...FEASIBILITY OF USING LASER INDUCED FLUORESCENCE FOR CONCENTRATION MEASUREMENTS OF DIATOMIC SULFUR THESIS Presented to the Faculty of the School of...December 1982 SPecial Approved for public release; distribution unlimited Preface This thesis presented a rare opportunity and a formidable challenge

The Social Functions of Iranian Education: An Historical Survey Related to the Current Political Crisis. 1979 World Education Monograph Series, Number Two.

ERIC Educational Resources Information Center

Woolman, David C.

Although the Shah of Iran should be admired for his efforts to use education to deal with formidable social challenges, his goal of producing a modern state in a single generation was unrealistic. Entrenched traditional values and unpredicted economic changes such as the need in 1977 to slow down Iran's rate of growth in the face of runaway…

Developing a Robust Strategy for Implementing a Water Resources Master Plan in Lima, Peru

NASA Astrophysics Data System (ADS)

Kalra, N.; Groves, D.; Bonzanigo, L.; Molina-Perez, E.

2015-12-01

Lima, the capital of Peru, faces significant water stress. It is the fifth largest metropolitan area in Latin America, and the second largest desert city in the world. The city has developed a Master Plan of major investment projects to improve water reliability until 2040. Yet key questions remain. Is the Master Plan sufficient for ensuring reliability in the face of deeply uncertain future climate change and demand? How do uncertain budget and project feasibility conditions shape Lima's options? How should the investments in the plan be prioritized, and can some be delayed? Lima is not alone in facing these planning challenges. Governments invest billions of dollars annually in long-term projects. Yet deep uncertainties pose formidable challenges to making near-term decisions that make long-term sense. The World Bank has spearheaded a community of practice on methods for Decision Making Under Deep Uncertainty (DMU). This pilot project in Peru is the first in-depth application of DMU techniques to water supply planning in a developing country. It builds on prior analysis done in New York, California, and for the Colorado River, yet shows how these methods can be applied in regions which do not have as advanced data or tools available. The project combines three methods in particular -- Robust Decision Making, Decision Scaling, and Adaptive Pathways -- to help Lima implement its Master Plan in a way that is robust, no-regret, and adaptive. It was done in close partnership with SEDAPAL, the water utility company in Lima, and in coordination with other national WRM and meteorological agencies. This talk will: Present the planning challenges Lima and other cities face, including climate change Describe DMU methodologies and how they were applied in collaboration with SEDAPAL Summarize recommendations for achieving long-term water reliability in Lima Suggest how these methodologies can benefit other investment projects in developing countries.

Using physics-based pose predictions and free energy perturbation calculations to predict binding poses and relative binding affinities for FXR ligands in the D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Athanasiou, Christina; Vasilakaki, Sofia; Dellis, Dimitris; Cournia, Zoe

2018-01-01

Computer-aided drug design has become an integral part of drug discovery and development in the pharmaceutical and biotechnology industry, and is nowadays extensively used in the lead identification and lead optimization phases. The drug design data resource (D3R) organizes challenges against blinded experimental data to prospectively test computational methodologies as an opportunity for improved methods and algorithms to emerge. We participated in Grand Challenge 2 to predict the crystallographic poses of 36 Farnesoid X Receptor (FXR)-bound ligands and the relative binding affinities for two designated subsets of 18 and 15 FXR-bound ligands. Here, we present our methodology for pose and affinity predictions and its evaluation after the release of the experimental data. For predicting the crystallographic poses, we used docking and physics-based pose prediction methods guided by the binding poses of native ligands. For FXR ligands with known chemotypes in the PDB, we accurately predicted their binding modes, while for those with unknown chemotypes the predictions were more challenging. Our group ranked #1st (based on the median RMSD) out of 46 groups, which submitted complete entries for the binding pose prediction challenge. For the relative binding affinity prediction challenge, we performed free energy perturbation (FEP) calculations coupled with molecular dynamics (MD) simulations. FEP/MD calculations displayed a high success rate in identifying compounds with better or worse binding affinity than the reference (parent) compound. Our studies suggest that when ligands with chemical precedent are available in the literature, binding pose predictions using docking and physics-based methods are reliable; however, predictions are challenging for ligands with completely unknown chemotypes. We also show that FEP/MD calculations hold predictive value and can nowadays be used in a high throughput mode in a lead optimization project provided that crystal structures of sufficiently high quality are available.

Optimizing Burn Treatment in Developing Low-and Middle-Income Countries with Limited Health Care Resources (Part 3)

PubMed Central

Atiyeh, B.; Masellis, A.; Conte, F.

2010-01-01

Summary The present review of the literature aims at analysing the challenges facing burn management in low- and middleincome countries and exploring probable modalities to optimize burn management in these countries. In Part I, epidemiology of burns injuries and the formidable challenges for proper management due to limited resources and inaccessibility to sophisticated skills and technologies in low- and middle income countries (LMICs) were presented. Part II discussed the actual state of burn injuries management in LMICs. In Part III of this review strategies for proper prevention and burn care in LMICs will be presented. PMID:21991190

Smart integrated microsystems: the energy efficiency challenge (Conference Presentation) (Plenary Presentation)

NASA Astrophysics Data System (ADS)

Benini, Luca

2017-06-01

The "internet of everything" envisions trillions of connected objects loaded with high-bandwidth sensors requiring massive amounts of local signal processing, fusion, pattern extraction and classification. From the computational viewpoint, the challenge is formidable and can be addressed only by pushing computing fabrics toward massive parallelism and brain-like energy efficiency levels. CMOS technology can still take us a long way toward this goal, but technology scaling is losing steam. Energy efficiency improvement will increasingly hinge on architecture, circuits, design techniques such as heterogeneous 3D integration, mixed-signal preprocessing, event-based approximate computing and non-Von-Neumann architectures for scalable acceleration.

The role of physical formidability in human social status allocation.

PubMed

Lukaszewski, Aaron W; Simmons, Zachary L; Anderson, Cameron; Roney, James R

2016-03-01

Why are physically formidable men willingly allocated higher social status by others in cooperative groups? Ancestrally, physically formidable males would have been differentially equipped to generate benefits for groups by providing leadership services of within-group enforcement (e.g., implementing punishment of free riders) and between-group representation (e.g., negotiating with other coalitions). Therefore, we hypothesize that adaptations for social status allocation are designed to interpret men's physical formidability as a cue to these leadership abilities, and to allocate greater status to formidable men on this basis. These hypotheses were supported in 4 empirical studies wherein young adults rated standardized photos of subjects (targets) who were described as being part of a white-collar business consultancy. In Studies 1 and 2, male targets' physical strength positively predicted ratings of their projected status within the organization, and this effect was mediated by perceptions that stronger men possessed greater leadership abilities of within-group enforcement and between-group representation. Moreover, (a) these same patterns held whether status was conceptualized as overall ascendancy, prestige-based status, or dominance-based status, and (b) strong men who were perceived as aggressively self-interested were not allocated greater status. Finally, 2 experiments established the causality of physical formidability's effects on status-related perceptions by manipulating targets' relative strength (Study 3) and height (Study 4). In interpreting our findings, we argue that adaptations for formidability-based status allocation may have facilitated the evolution of group cooperation in humans and other primates. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Silicate Inclusions in the Kodaikanal IIE Iron Meteorite

NASA Technical Reports Server (NTRS)

Kurat, G.; Varela, M. E.; Zinner, E.

2005-01-01

Silicate inclusions in iron meteorites display an astonishing chemical and mineralogical variety, ranging from chondritic to highly fractionated, silica- and alkali-rich assemblages. In spite of this, their origin is commonly considered to be a simple one: mixing of silicates, fractionated or unfractionated, with metal. The latter had to be liquid in order to accommodate the former in a pore-free way which all models accomplish by assuming shock melting. II-E iron meteorites are particularly interesting because they contain an exotic zoo of silicate inclusions, including some chemically strongly fractionated ones. They also pose a formidable conundrum: young silicates are enclosed by very old metal. This and many other incompatibilities between models and reality forced the formulation of an alternative genetic model for irons. Here we present preliminary findings in our study of Kodaikanal silicate inclusions.

On the simulation of indistinguishable fermions in the many-body Wigner formalism

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

Sellier, J.M., E-mail: jeanmichel.sellier@gmail.com; Dimov, I.

2015-01-01

The simulation of quantum systems consisting of interacting, indistinguishable fermions is an incredible mathematical problem which poses formidable numerical challenges. Many sophisticated methods addressing this problem are available which are based on the many-body Schrödinger formalism. Recently a Monte Carlo technique for the resolution of the many-body Wigner equation has been introduced and successfully applied to the simulation of distinguishable, spinless particles. This numerical approach presents several advantages over other methods. Indeed, it is based on an intuitive formalism in which quantum systems are described in terms of a quasi-distribution function, and highly scalable due to its Monte Carlo nature.more » In this work, we extend the many-body Wigner Monte Carlo method to the simulation of indistinguishable fermions. To this end, we first show how fermions are incorporated into the Wigner formalism. Then we demonstrate that the Pauli exclusion principle is intrinsic to the formalism. As a matter of fact, a numerical simulation of two strongly interacting fermions (electrons) is performed which clearly shows the appearance of a Fermi (or exchange–correlation) hole in the phase-space, a clear signature of the presence of the Pauli principle. To conclude, we simulate 4, 8 and 16 non-interacting fermions, isolated in a closed box, and show that, as the number of fermions increases, we gradually recover the Fermi–Dirac statistics, a clear proof of the reliability of our proposed method for the treatment of indistinguishable particles.« less

Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism

PubMed Central

Jing, Da; Zhai, Mingming; Tong, Shichao; Xu, Fei; Cai, Jing; Shen, Guanghao; Wu, Yan; Li, Xiaokang; Xie, Kangning; Liu, Juan; Xu, Qiaoling; Luo, Erping

2016-01-01

Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/β-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and β-catenin protein expressions. In vivo results via μCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/β-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/β-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect. PMID:27555216

An embodied view of octopus neurobiology.

PubMed

Hochner, Binyamin

2012-10-23

Octopuses have a unique flexible body and unusual morphology, but nevertheless they are undoubtedly a great evolutionary success. They compete successfully with vertebrates in their ecological niche using a rich behavioral repertoire more typical of an intelligent predator which includes extremely effective defensive behavior--fast escape swimming and an astonishing ability to adapt their shape and color to their environment. The most obvious characteristic feature of an octopus is its eight long and flexible arms, but these pose a great challenge for achieving the level of motor and sensory information processing necessary for their behaviors. First, coordinating motion is a formidable task because of the infinite degrees of freedom that have to be controlled; and second, it is hard to use body coordinates in this flexible animal to represent sensory information in a central control system. Here I will review experimental results suggesting that these difficulties, arising from the animal's morphology, have imposed the evolution of unique brain/body/behavior relationships best explained as intelligent behavior which emerges from the octopus's embodied organization. The term 'intelligent embodiment' comes from robotics and refers to an approach to designing autonomous robots in which the behavior emerges from the dynamic physical and sensory interactions of the agent's materials, morphology and environment. Consideration of the unusual neurobiology of the octopus in the light of its unique morphology suggests that similar embodied principles are instrumental for understanding the emergence of intelligent behavior in all biological systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparative cost-effectiveness of policy instruments for reducing the global burden of alcohol, tobacco and illicit drug use.

PubMed

Chisholm, Dan; Doran, Chris; Shibuya, Kenji; Rehm, Jürgen

2006-11-01

Alcohol, tobacco and illicit drug use together pose a formidable challenge to international public health. Building on earlier estimates of the demonstrated burden of alcohol, tobacco and illicit drug use at the global level, this review aims to consider the comparative cost-effectiveness of evidence-based interventions for reducing the global burden of disease from these three risk factors. Although the number of published cost-effectiveness studies in the addictions field is now extensive (reviewed briefly here) there are a series of practical problems in using them for sector-wide decision making, including methodological heterogeneity, differences in analytical reference point and the specificity of findings to a particular context. In response to these limitations, a more generalised form of cost-effectiveness analysis (CEA) is proposed, which enables like-with-like comparisons of the relative efficiency of preventive or individual-based strategies to be made, not only within but also across diseases or their risk factors. The application of generalised CEA to a range of personal and non-personal interventions for reducing the burden of addictive substances is described. While such a development avoids many of the obstacles that have plagued earlier attempts and in so doing opens up new opportunities to address important policy questions, there remain a number of caveats to population-level analysis of this kind, particularly when conducted at the global level. These issues are the subject of the final section of this review.

Herbivorous ecomorphology and specialization patterns in theropod dinosaur evolution.

PubMed

Zanno, Lindsay E; Makovicky, Peter J

2011-01-04

Interpreting key ecological parameters, such as diet, of extinct organisms without the benefit of direct observation or explicit fossil evidence poses a formidable challenge for paleobiological studies. To date, dietary categorizations of extinct taxa are largely generated by means of modern analogs; however, for many species the method is subject to considerable ambiguity. Here we present a refined approach for assessing trophic habits in fossil taxa and apply the method to coelurosaurian dinosaurs--a clade for which diet is particularly controversial. Our findings detect 21 morphological features that exhibit statistically significant correlations with extrinsic fossil evidence of coelurosaurian herbivory, such as stomach contents and a gastric mill. These traits represent quantitative, extrinsically founded proxies for identifying herbivorous ecomorphology in fossils and are robust despite uncertainty in phylogenetic relationships among major coelurosaurian subclades. The distribution of these features suggests that herbivory was widespread among coelurosaurians, with six major subclades displaying morphological evidence of the diet, and that contrary to previous thought, hypercarnivory was relatively rare and potentially secondarily derived. Given the potential for repeated, independent evolution of herbivory in Coelurosauria, we also test for repetitive patterns in the appearance of herbivorous traits within sublineages using rank concordance analysis. We find evidence for a common succession of increasing specialization to herbivory in the subclades Ornithomimosauria and Oviraptorosauria, perhaps underlain by intrinsic functional and/or developmental constraints, as well as evidence indicating that the early evolution of a beak in coelurosaurians correlates with an herbivorous diet.

Herbivorous ecomorphology and specialization patterns in theropod dinosaur evolution

PubMed Central

Zanno, Lindsay E.; Makovicky, Peter J.

2011-01-01

Interpreting key ecological parameters, such as diet, of extinct organisms without the benefit of direct observation or explicit fossil evidence poses a formidable challenge for paleobiological studies. To date, dietary categorizations of extinct taxa are largely generated by means of modern analogs; however, for many species the method is subject to considerable ambiguity. Here we present a refined approach for assessing trophic habits in fossil taxa and apply the method to coelurosaurian dinosaurs—a clade for which diet is particularly controversial. Our findings detect 21 morphological features that exhibit statistically significant correlations with extrinsic fossil evidence of coelurosaurian herbivory, such as stomach contents and a gastric mill. These traits represent quantitative, extrinsically founded proxies for identifying herbivorous ecomorphology in fossils and are robust despite uncertainty in phylogenetic relationships among major coelurosaurian subclades. The distribution of these features suggests that herbivory was widespread among coelurosaurians, with six major subclades displaying morphological evidence of the diet, and that contrary to previous thought, hypercarnivory was relatively rare and potentially secondarily derived. Given the potential for repeated, independent evolution of herbivory in Coelurosauria, we also test for repetitive patterns in the appearance of herbivorous traits within sublineages using rank concordance analysis. We find evidence for a common succession of increasing specialization to herbivory in the subclades Ornithomimosauria and Oviraptorosauria, perhaps underlain by intrinsic functional and/or developmental constraints, as well as evidence indicating that the early evolution of a beak in coelurosaurians correlates with an herbivorous diet. PMID:21173263

Δ98Δ, a minimalist model of antiparallel β-sheet proteins based on intestinal fatty acid binding protein

PubMed Central

Curto, Lucrecia María; Caramelo, Julio Javier; Franchini, Gisela Raquel; Delfino, José María

2009-01-01

The design of β-barrels has always been a formidable challenge for de novo protein design. For instance, a persistent problem is posed by the intrinsic tendency to associate given by free edges. From the opposite standpoint provided by the redesign of natural motifs, we believe that the intestinal fatty acid binding protein (IFABP) framework allows room for intervention, giving rise to abridged forms from which lessons on β-barrel architecture and stability could be learned. In this context, Δ98Δ (encompassing residues 29–126 of IFABP) emerges as a monomeric variant that folds properly, retaining functional activity, despite lacking extensive stretches involved in the closure of the β-barrel. Spectroscopic probes (fluorescence and circular dichroism) support the existence of a form preserving the essential determinants of the parent structure, albeit endowed with enhanced flexibility. Chemical and physical perturbants reveal cooperative unfolding transitions, with evidence of significant population of intermediate species in equilibrium, structurally akin to those transiently observed in IFABP. The recognition by the natural ligand oleic acid exerts a mild stabilizing effect, being of a greater magnitude than that found for IFABP. In summary, Δ98Δ adopts a monomeric state with a compact core and a loose periphery, thus pointing to the nonintuitive notion that the integrity of the β-barrel can indeed be compromised with no consequence on the ability to attain a native-like and functional fold. PMID:19309727

Strategies for Enhanced Drug Delivery to the Central Nervous System

PubMed Central

Dwibhashyam, V. S. N. M.; Nagappa, A. N.

2008-01-01

Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

FERMILAB ACCELERATOR R&D PROGRAM TOWARDS INTENSITY FRONTIER ACCELERATORS : STATUS AND PROGRESS

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

Shiltsev, Vladimir

2016-11-15

The 2014 P5 report indicated the accelerator-based neutrino and rare decay physics research as a centrepiece of the US domestic HEP program at Fermilab. Operation, upgrade and development of the accelerators for the near- term and longer-term particle physics program at the Intensity Frontier face formidable challenges. Here we discuss key elements of the accelerator physics and technology R&D program toward future multi-MW proton accelerators and present its status and progress. INTENSITY FRONTIER ACCELERATORS

Profiling of Sugar Nucleotides.

PubMed

Rejzek, Martin; Hill, Lionel; Hems, Edward S; Kuhaudomlarp, Sakonwan; Wagstaff, Ben A; Field, Robert A

2017-01-01

Sugar nucleotides are essential building blocks for the glycobiology of all living organisms. Detailed information on the types of sugar nucleotides present in a particular cell and how they change as a function of metabolic, developmental, or disease status is vital. The extraction, identification, and quantification of sugar nucleotides in a given sample present formidable challenges. In this chapter, currently used techniques for sugar nucleotide extraction from cells, separation from complex biological matrices, and detection by optical and mass spectrometry methods are discussed. © 2017 Elsevier Inc. All rights reserved.

Oral rehabilitation of the cancer patient: A formidable challenge.

PubMed

Petrovic, Ivana; Rosen, Evan B; Matros, Evan; Huryn, Joseph M; Shah, Jatin P

2018-05-03

Rehabilitation of oral functions following surgery on the jaws is a goal that is often difficult to achieve. Removable dentures supported by remaining teeth or gum are often unstable and seldom satisfactory. On the other hand, endosseous (dental) implants offer a mechanism to provide stability to the dentures. This review, discusses factors related to the tumor, patient, treatment, and physicians which impact upon the feasibility and success of dental implants in patients with oral cancer. © 2018 Wiley Periodicals, Inc.

Impact of Ultraviolet Light on Vitiligo.

PubMed

Singh, Rasnik K

2017-01-01

Vitiligo is a disorder of the melanocytes that results in a dynamic spectrum of skin depigmentation. Its etiology is complex and multifactorial, with data supporting several different hypotheses. Given its prominent phenotype, vitiligo has a significant negative impact on quality of life. Coupled with the chronic and incurable nature of the disease, this presents a formidable treatment challenge. Several treatment modalities have been instituted over the years, with varying efficacy. This chapter focuses on the use of ultraviolet light in vitiligo as an established therapeutic option.

Challenging the ‘Big G’ measurement with atoms and light

NASA Astrophysics Data System (ADS)

Rosi, Gabriele

2016-10-01

The measurement of the Newtonian gravity constant G is a formidable task. Starting from the first determination made by Henry Cavendish in 1798, several attempts have been made in order to improve knowledge of its value. Nevertheless, despite these efforts, its uncertainty has decreased only by a factor of ten per century. Cold atom interferometry represents a conceptually different technique to challenge the G measurement, a feature that is crucial in order to identify discrepancies among previous measurements. In this review paper, after a short introduction on the traditional measurement techniques, I will describe and discuss past and ongoing G determination based on atom interferometry, highlighting for each of them the most significant aspects.

An insight into burns in a developing country: a Sri Lankan experience.

PubMed

Lau, Y S

2006-10-01

Burn injuries represent a diverse and varied challenge to medical and paramedical staff. The management of burns and their sequelae in a well-equipped, modern burns unit remains demanding despite advances in surgical techniques and development of tissue-engineered biomaterials; in a developing country, these difficulties are amplified many times. Sri Lanka has a high incidence of burn-related injuries annually due to a combination of adverse social, economic and cultural factors. The management of burn injuries remains a formidable public health problem. The epidemiology of burns, challenges faced in their management and effective strategies specific to Sri Lanka, such as the Safe Bottle Lamp campaign, are highlighted in this paper.

COMPUTATIONAL CHALLENGES IN BUILDING MULTI-SCALE AND MULTI-PHYSICS MODELS OF CARDIAC ELECTRO-MECHANICS

PubMed Central

Plank, G; Prassl, AJ; Augustin, C

2014-01-01

Despite the evident multiphysics nature of the heart – it is an electrically controlled mechanical pump – most modeling studies considered electrophysiology and mechanics in isolation. In no small part, this is due to the formidable modeling challenges involved in building strongly coupled anatomically accurate and biophyically detailed multi-scale multi-physics models of cardiac electro-mechanics. Among the main challenges are the selection of model components and their adjustments to achieve integration into a consistent organ-scale model, dealing with technical difficulties such as the exchange of data between electro-physiological and mechanical model, particularly when using different spatio-temporal grids for discretization, and, finally, the implementation of advanced numerical techniques to deal with the substantial computational. In this study we report on progress made in developing a novel modeling framework suited to tackle these challenges. PMID:24043050

Bodily attractiveness and egalitarianism are negatively related in males.

PubMed

Price, Michael E; Brown, Stuart; Dukes, Amber; Kang, Jinsheng

2015-02-09

Ancestrally, relatively attractive individuals and relatively formidable males may have had reduced incentives to be egalitarian (i.e., to act in accordance with norms promoting social equality). If selection calibrated one's egalitarianism to one's attractiveness/formidability, then such people may exhibit reduced egalitarianism ("observed egalitarianism") and be perceived by others as less egalitarian ("perceived egalitarianism") in modern environments. To investigate, we created 3D body models of 125 participants to use both as a source of anthropometric measurements and as stimuli to obtain ratings of bodily attractiveness and perceived egalitarianism. We also measured observed egalitarianism (via an economic "dictator" game) and indices of political egalitarianism (preference for socialism over capitalism) and "equity sensitivity." Results indicated higher egalitarianism levels in women than in men, and moderate-to-strong negative relationships between (a) attractiveness and observed egalitarianism among men, (b) attractiveness and perceived egalitarianism among both sexes, and (c) formidability and perceived egalitarianism among men. We did not find support for two previously-reported findings: that observed egalitarianism and formidability are negatively related in men, and that wealth and formidability interact to explain variance in male egalitarianism. However, this lack of support may have been due to differences in variable measurement between our study and previous studies.

Global Antimicrobial Stewardship: A Closer Look at the Formidable Implementation Challenges

PubMed Central

Tiong, John J. L.; Loo, Jason S. E.; Mai, Chun-Wai

2016-01-01

Antimicrobial stewardship (AMS) has been touted as one of the key strategies required in tackling worldwide escalation of antibiotic resistance. Although AMS has optimized antibiotic usage and reduced the incidence of resistance development in some regions, its full global potential has been curtailed by various AMS-impeding factors. This article seeks to highlight in a detailed perspective, the key challenges that hamper global AMS endeavors, some of which include the paucity of effective implementation strategies that cater for the challenging settings of developing nations, the slow response of governments, uncoordinated AMS activities as well as implementation fragmentation across different sectors and countries. The authors of this article call upon all stakeholders to pay attention to these seemingly obvious but often under-addressed problems. If left unresolved, this may render all current and future AMS initiatives pointless. PMID:27899924

SWOT analysis and revelation in traditional Chinese medicine internationalization.

PubMed

Tang, Haitao; Huang, Wenlong; Ma, Jimei; Liu, Li

2018-01-01

Traditional Chinese medicine (TCM) is currently the best-preserved and most influential traditional medical system with the largest number of users worldwide. In recent years, the trend of TCM adoption has increased greatly, but the process of TCM internationalization has suffered from a series of setbacks for both internal and external reasons. Thus, the process of TCM internationalization faces formidable challenges, although it also has favourable opportunities. Using SWOT analysis, this paper investigates the strengths, weaknesses, opportunities and threats for TCM. These findings can serve as references for TCM enterprises with global ambitions.

Taming Big Data Variety in the Earth Observing System Data and Information System

NASA Technical Reports Server (NTRS)

Lynnes, Christopher; Walter, Jeff

2015-01-01

Although the volume of the remote sensing data managed by the Earth Observing System Data and Information System is formidable, an oft-overlooked challenge is the variety of data. The diversity in satellite instruments, science disciplines and user communities drives cost as much or more as the data volume. Several strategies are used to tame this variety: data allocation to distinct centers of expertise; a common metadata repository for discovery, data format standards and conventions; and services that further abstract the variations in data.

The Defense Science Board 1997 Summer Study Task Force on DoD Responses to Transnational Threats; Volume 1 - Final Report.

DTIC Science & Technology

1997-10-01

loss of human life - both theirs and ours - their initiatives present a formidable challenge to long-term national security. Even a small nation with...the chemical release killed a dozen people, well over 5,000 were injured and the release had the potential for far more devastating loss of life. In...individuals or groups to produce major damage and loss of life exists today. Events that we have already witnessed could well have resulted in far graver

On the Isothermality of Solar Plasmas

NASA Technical Reports Server (NTRS)

Landi, E.; Klimchuk, J. A.

2010-01-01

Recent measurements have shown that the quiet unstructured solar corona observed at the solar limb is close to isothermal, at a temperature that does not appear to change over wide areas or with time. Some in dividual active loop structures have also been found to be nearly iso thermal both along their axis and across their cross-section. Even a complex active region observed at the solar limb has been found to be composed of three distinct isothermal plasmas. If confirmed, these r esults would pose formidable challenges to the current theoretical understanding of the thermal structure and heating of the solar corona. For example, no current theoretical model can explain the excess dens ities and lifetimes of many observed loops if the loops are in fact i sothermal. All of these measurements are based on the so-called emiss ion measure (EM) diagnostic technique that is applied to a set of opt ically thin lines under the assumption of isothermal plasma. It provi des simultaneous measurement of both the temperature and EM. However, no study has ever been carried out to quantify the uncertainties in the technique and to rigorously assess its ability to discriminate bet ween isothermal and multithermal plasmas. Such a study is the topic o f the present work. We define a formal measure of the uncertainty in the EM diagnostic technique that can easily be applied to real data. We here apply it to synthetic data based on a variety of assumed plas ma thermal distributions, and develop a method to quantitatively asse ss the degree of multithermality of a plasma.

Joint Use of ERT, Tracer, and Numerical Techniques to Image Preferential Flow Paths in a Fractured Granite Aquifer

NASA Astrophysics Data System (ADS)

Sanaga, S.; Vijay, S.; Kbvn, P.; Peddinti, S. R.; P S L, S.

2017-12-01

Fractured geologic media poses formidable challenges to hydrogeologists due of the strenuous mapping of fracture-matrix system and quantification of flow and transport processes. In this research, we demonstrated the efficacy of tracer-ERT studies coupled with numerical simulations to delineate preferential flow paths in a fractured granite aquifer of Deccan traps in India. A series of natural gradient saline tracer experiments were conducted from a depth window of 18 to 22 m in an injection well located inside the IIT Hyderabad campus. Tracer migration was monitored in a time-lapse mode using two cross-sectional surface ERT profiles placed in the direction of flow gradient. Dynamic changes in sub-surface electrical properties inferred via resistivity anomalies were used to highlight preferential flow paths of the study area. ERT-derived tracer breakthrough curves were in agreement with geochemical sample measurements (R2=0.74). Fracture geometry and hydraulic properties derived from ERT and pumping tests were then used to evaluate two mathematical conceptualizations that are relevant to fractured aquifers. Results of numerical analysis conclude that a dual continuum model that combines matrix and fracture systems through a flow exchange term has outperformed equivalent continuum model in reproducing tracer concentrations at the monitoring wells (evident by decrease in RMSE from 199 mg/l to 65 mg/l). A sensitivity analysis of the model parameters reveals that spatial variability in hydraulic conductivity, local-scale dispersion, and flow exchange at fracture-matrix interface have a profound effect on model simulations. Keywords: saline tracer, ERT, fractured granite, groundwater, preferential flow, numerical simulation

The effects of alcohol-containing e-cigarettes on young adult smokers.

PubMed

Valentine, Gerald W; Jatlow, Peter I; Coffman, Marcedes; Nadim, Haleh; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-02-01

The liquids (e-liquids) used in an electronic cigarette (e-cigarette) contain myriad chemicals without adequate human inhalation safety data. Furthermore, the absence of e-liquid labeling requirements poses a formidable challenge to understanding how e-liquid constituents may promote nicotine addiction and/or have independent or synergistic biological effects when combined with nicotine. Ethyl alcohol is such a constituent, but has received little scientific interest in this context. Using a randomized, double blind, crossover design, acute changes in subjective drug effects, motor performance and biochemical measures of alcohol and nicotine intake were evaluated after directed and ad lib puffing from two commercially available e-liquids containing nicotine (8 mg/ml), vanilla flavor and either 23.5% (high) or 0.4% (trace) alcohol. While no differences in subjective drug effects were observed between alcohol conditions, performance on the Purdue Pegboard Dexterity Test (PPDT) improved under the trace, but not under the 23.5% alcohol condition. Although plasma alcohol levels remained undetectable during testing, urine ethyl glucuronide (EtG), an alcohol metabolite, became measurable in three participants after puffing from the 23.5% alcohol e-cigarette. Brief use of a widely available type of e-cigarette containing an e-liquid purchased from an internet vendor can negatively impact psychomotor performance and in some instances, produce detectable levels of a urine alcohol metabolite. Given the widespread and unregulated use of e-cigarettes, especially by youth and other vulnerable populations, further studies are needed to evaluate both the acute safety and long-term health risks of using alcohol-containing e-cigarettes. Published by Elsevier Ireland Ltd.

The Cannon: A data-driven approach to Stellar Label Determination

NASA Astrophysics Data System (ADS)

Ness, M.; Hogg, David W.; Rix, H.-W.; Ho, Anna. Y. Q.; Zasowski, G.

2015-07-01

New spectroscopic surveys offer the promise of stellar parameters and abundances (“stellar labels”) for hundreds of thousands of stars; this poses a formidable spectral modeling challenge. In many cases, there is a subset of reference objects for which the stellar labels are known with high(er) fidelity. We take advantage of this with The Cannon, a new data-driven approach for determining stellar labels from spectroscopic data. The Cannon learns from the “known” labels of reference stars how the continuum-normalized spectra depend on these labels by fitting a flexible model at each wavelength; then, The Cannon uses this model to derive labels for the remaining survey stars. We illustrate The Cannon by training the model on only 542 stars in 19 clusters as reference objects, with {T}{eff}, {log} g, and [{Fe}/{{H}}] as the labels, and then applying it to the spectra of 55,000 stars from APOGEE DR10. The Cannon is very accurate. Its stellar labels compare well to the stars for which APOGEE pipeline (ASPCAP) labels are provided in DR10, with rms differences that are basically identical to the stated ASPCAP uncertainties. Beyond the reference labels, The Cannon makes no use of stellar models nor any line-list, but needs a set of reference objects that span label-space. The Cannon performs well at lower signal-to-noise, as it delivers comparably good labels even at one-ninth the APOGEE observing time. We discuss the limitations of The Cannon and its future potential, particularly, to bring different spectroscopic surveys onto a consistent scale of stellar labels.

Assessment for Systems Learning: A Holistic Assessment Framework to Support Decision Making Across the Medical Education Continuum.

PubMed

Bowe, Constance M; Armstrong, Elizabeth

2017-05-01

Viewing health care from a systems perspective-that is, "a collection of different things which, working together, produce a result not achievable by the things alone"-raises awareness of the complex interrelationships involved in meeting society's goals for accessible, cost-effective, high-quality health care. This perspective also emphasizes the far-reaching consequences of changes in one sector of a system on other components' performance. Medical education promotes this holistic view of health care in its curricula and competency requirements for graduation at the undergraduate and graduate training levels. But how completely does medical education apply a systems lens to itself?The continuum of medical training has undergone a series of changes that have moved it more closely to a systems organizational model. Competency assessment criteria have been expanded and more explicitly defined for learners at all levels of training. Outcomes data, in multiple domains, are monitored by external reviewers for program accreditation. However, translating increasing amounts of individual outcomes into actionable intelligence for decision making poses a formidable information management challenge.Assessment in systems is designed to impart a "big picture" of overall system performance through the synthesis, analysis, and interpretation of outcomes data to provide actionable information for continuous systems improvement, innovation, and long-term planning. A systems-based framework is presented for use across the medical education continuum to facilitate timely improvements in individual curriculum components, continuous improvement in overall program performance, and program decision making on changes required to better address society's health care needs.

Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use

PubMed Central

Gudin, Jeffrey A.; Mogali, Shanthi; Jones, Jermaine D.; Comer, Sandra D.

2014-01-01

The concurrent use of opioids, benzodiazepines (BZDs), and/or alcohol poses a formidable challenge for clinicians who manage chronic pain. While the escalating use of opioid analgesics for the treatment of chronic pain and the concomitant rise in opioid-related abuse and misuse are widely recognized trends, the contribution of combination use of BZDs, alcohol, and/or other sedative agents to opioid-related morbidity and mortality is underappreciated, even when these agents are used appropriately. Patients with chronic pain who use opioid analgesics along with BZDs and/or alcohol are at higher risk for fatal/nonfatal overdose and have more aberrant behaviors. Few practice guidelines for BZD treatment are readily available, especially when they are combined clinically with opioid analgesics and other central nervous system–depressant agents. However, coadministration of these agents produces a defined increase in rates of adverse events, overdose, and death, warranting close monitoring and consideration when treating patients with pain. To improve patient outcomes, ongoing screening for aberrant behavior, monitoring of treatment compliance, documentation of medical necessity, and the adjustment of treatment to clinical changes are essential. In this article, we review the prevalence and pharmacologic consequences of BZDs and/or alcohol use among patients with pain on chronic opioid therapy, as well as the importance of urine drug testing, an indispensable tool for therapeutic drug monitoring, which helps to ensure the continued safety of patients. Regardless of risk or known aberrant drug-related behaviors, patients on chronic opioid therapy should periodically undergo urine drug testing to confirm adherence to the treatment plan. PMID:23933900

Beam tests of beampipe coatings for electron cloud mitigation in Fermilab Main Injector

DOE PAGES

Backfish, Michael; Eldred, Jeffrey; Tan, Cheng Yang; ...

2015-10-26

Electron cloud beam instabilities are an important consideration in virtually all high-energy particle accelerators and could pose a formidable challenge to forthcoming high-intensity accelerator upgrades. Dedicated tests have shown beampipe coatings dramatically reduce the density of electron cloud in particle accelerators. In this work, we evaluate the performance of titanium nitride, amorphous carbon, and diamond-like carbon as beampipe coatings for the mitigation of electron cloud in the Fermilab Main Injector. Altogether our tests represent 2700 ampere-hours of proton operation spanning five years. Three electron cloud detectors, retarding field analyzers, are installed in a straight section and allow a direct comparisonmore » between the electron flux in the coated and uncoated stainless steel beampipe. We characterize the electron flux as a function of intensity up to a maximum of 50 trillion protons per cycle. Each beampipe material conditions in response to electron bombardment from the electron cloud and we track the changes in these materials as a function of time and the number of absorbed electrons. Contamination from an unexpected vacuum leak revealed a potential vulnerability in the amorphous carbon beampipe coating. We measure the energy spectrum of electrons incident on the stainless steel, titanium nitride and amorphous carbon beampipes. We find the electron cloud signal is highly sensitive to stray magnetic fields and bunch-length over the Main Injector ramp cycle. In conclusion, we conduct a complete survey of the stray magnetic fields at the test station and compare the electron cloud signal to that in a field-free region.« less

Lessons learned in induced fit docking and metadynamics in the Drug Design Data Resource Grand Challenge 2

NASA Astrophysics Data System (ADS)

Baumgartner, Matthew P.; Evans, David A.

2018-01-01

Two of the major ongoing challenges in computational drug discovery are predicting the binding pose and affinity of a compound to a protein. The Drug Design Data Resource Grand Challenge 2 was developed to address these problems and to drive development of new methods. The challenge provided the 2D structures of compounds for which the organizers help blinded data in the form of 35 X-ray crystal structures and 102 binding affinity measurements and challenged participants to predict the binding pose and affinity of the compounds. We tested a number of pose prediction methods as part of the challenge; we found that docking methods that incorporate protein flexibility (Induced Fit Docking) outperformed methods that treated the protein as rigid. We also found that using binding pose metadynamics, a molecular dynamics based method, to score docked poses provided the best predictions of our methods with an average RMSD of 2.01 Å. We tested both structure-based (e.g. docking) and ligand-based methods (e.g. QSAR) in the affinity prediction portion of the competition. We found that our structure-based methods based on docking with Smina (Spearman ρ = 0.614), performed slightly better than our ligand-based methods (ρ = 0.543), and had equivalent performance with the other top methods in the competition. Despite the overall good performance of our methods in comparison to other participants in the challenge, there exists significant room for improvement especially in cases such as these where protein flexibility plays such a large role.

Security Planning and Policies to Meet the Challenges of Climate Change

DTIC Science & Technology

2010-07-01

Security Climate change poses challenges to societies and governments that go far beyond the alteration of our environment. The physical impacts of...capacity of governments to respond. In this sense, the growing likelihood of events such as mass migrations, crop failures, economic shocks, public...riots and violence, floods and other natural disasters, widespread epidemics, and competition for resources pose serious challenges for governments and

Prospective evaluation of shape similarity based pose prediction method in D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2016-09-01

Evaluation of ligand three-dimensional (3D) shape similarity is one of the commonly used approaches to identify ligands similar to one or more known active compounds from a library of small molecules. Apart from using ligand shape similarity as a virtual screening tool, its role in pose prediction and pose scoring has also been reported. We have recently developed a method that utilizes ligand 3D shape similarity with known crystallographic ligands to predict binding poses of query ligands. Here, we report the prospective evaluation of our pose prediction method through the participation in drug design data resource (D3R) Grand Challenge 2015. Our pose prediction method was used to predict binding poses of heat shock protein 90 (HSP90) and mitogen activated protein kinase kinase kinase kinase (MAP4K4) ligands and it was able to predict the pose within 2 Å root mean square deviation (RMSD) either as the top pose or among the best of five poses in a majority of cases. Specifically for HSP90 protein, a median RMSD of 0.73 and 0.68 Å was obtained for the top and the best of five predictions respectively. For MAP4K4 target, although the median RMSD for our top prediction was only 2.87 Å but the median RMSD of 1.67 Å for the best of five predictions was well within the limit for successful prediction. Furthermore, the performance of our pose prediction method for HSP90 and MAP4K4 ligands was always among the top five groups. Particularly, for MAP4K4 protein our pose prediction method was ranked number one both in terms of mean and median RMSD when the best of five predictions were considered. Overall, our D3R Grand Challenge 2015 results demonstrated that ligand 3D shape similarity with the crystal ligand is sufficient to predict binding poses of new ligands with acceptable accuracy.

Combining in silico and in cerebro approaches for virtual screening and pose prediction in SAMPL4.

PubMed

Voet, Arnout R D; Kumar, Ashutosh; Berenger, Francois; Zhang, Kam Y J

2014-04-01

The SAMPL challenges provide an ideal opportunity for unbiased evaluation and comparison of different approaches used in computational drug design. During the fourth round of this SAMPL challenge, we participated in the virtual screening and binding pose prediction on inhibitors targeting the HIV-1 integrase enzyme. For virtual screening, we used well known and widely used in silico methods combined with personal in cerebro insights and experience. Regular docking only performed slightly better than random selection, but the performance was significantly improved upon incorporation of additional filters based on pharmacophore queries and electrostatic similarities. The best performance was achieved when logical selection was added. For the pose prediction, we utilized a similar consensus approach that amalgamated the results of the Glide-XP docking with structural knowledge and rescoring. The pose prediction results revealed that docking displayed reasonable performance in predicting the binding poses. However, prediction performance can be improved utilizing scientific experience and rescoring approaches. In both the virtual screening and pose prediction challenges, the top performance was achieved by our approaches. Here we describe the methods and strategies used in our approaches and discuss the rationale of their performances.

Combining in silico and in cerebro approaches for virtual screening and pose prediction in SAMPL4

NASA Astrophysics Data System (ADS)

Voet, Arnout R. D.; Kumar, Ashutosh; Berenger, Francois; Zhang, Kam Y. J.

2014-04-01

The SAMPL challenges provide an ideal opportunity for unbiased evaluation and comparison of different approaches used in computational drug design. During the fourth round of this SAMPL challenge, we participated in the virtual screening and binding pose prediction on inhibitors targeting the HIV-1 integrase enzyme. For virtual screening, we used well known and widely used in silico methods combined with personal in cerebro insights and experience. Regular docking only performed slightly better than random selection, but the performance was significantly improved upon incorporation of additional filters based on pharmacophore queries and electrostatic similarities. The best performance was achieved when logical selection was added. For the pose prediction, we utilized a similar consensus approach that amalgamated the results of the Glide-XP docking with structural knowledge and rescoring. The pose prediction results revealed that docking displayed reasonable performance in predicting the binding poses. However, prediction performance can be improved utilizing scientific experience and rescoring approaches. In both the virtual screening and pose prediction challenges, the top performance was achieved by our approaches. Here we describe the methods and strategies used in our approaches and discuss the rationale of their performances.

Sustainable Materials Management (SMM) Web Academy Webinar: An Introduction to Lithium Batteries and the Challenges that they Pose to the Waste and Recycling Industry

EPA Pesticide Factsheets

This is a webinar page for the Sustainable Management of Materials (SMM) Web Academy webinar titled, An Introduction to Lithium Batteries and the Challenges that they Pose to the Waste and Recycling Industry.

Career Counseling and the Information Highway: Heeding the Road Signs.

ERIC Educational Resources Information Center

O'Halloran, Theresa M.; Fahr, Alicia V.; Keller, Jenny R.

2002-01-01

Traveling the "information highway" in the process of career counseling or providing career counseling services via the Internet pose additional challenges for counselors. The authors use current ethical guidelines to guide discussion of, and possible resolutions to, challenges posed by incorporating the Internet into career counseling. (Contains…

Preterm labor: one syndrome, many causes.

PubMed

Romero, Roberto; Dey, Sudhansu K; Fisher, Susan J

2014-08-15

Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. Copyright © 2014, American Association for the Advancement of Science.

Fusion Materials Research at Oak Ridge National Laboratory in Fiscal Year 2014

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

Wiffen, Frederick W.; Noe, Susan P.; Snead, Lance Lewis

2014-10-01

The realization of fusion energy is a formidable challenge with significant achievements resulting from close integration of the plasma physics and applied technology disciplines. Presently, the most significant technological challenge for the near-term experiments such as ITER, and next generation fusion power systems, is the inability of current materials and components to withstand the harsh fusion nuclear environment. The overarching goal of the ORNL fusion materials program is to provide the applied materials science support and understanding to underpin the ongoing DOE Office of Science fusion energy program while developing materials for fusion power systems. In doing so the programmore » continues to be integrated both with the larger U.S. and international fusion materials communities, and with the international fusion design and technology communities.« less

Multiple Fault Isolation in Redundant Systems

NASA Technical Reports Server (NTRS)

Pattipati, Krishna R.; Patterson-Hine, Ann; Iverson, David

1997-01-01

Fault diagnosis in large-scale systems that are products of modern technology present formidable challenges to manufacturers and users. This is due to large number of failure sources in such systems and the need to quickly isolate and rectify failures with minimal down time. In addition, for fault-tolerant systems and systems with infrequent opportunity for maintenance (e.g., Hubble telescope, space station), the assumption of at most a single fault in the system is unrealistic. In this project, we have developed novel block and sequential diagnostic strategies to isolate multiple faults in the shortest possible time without making the unrealistic single fault assumption.

Multiple Fault Isolation in Redundant Systems

NASA Technical Reports Server (NTRS)

Pattipati, Krishna R.

1997-01-01

Fault diagnosis in large-scale systems that are products of modem technology present formidable challenges to manufacturers and users. This is due to large number of failure sources in such systems and the need to quickly isolate and rectify failures with minimal down time. In addition, for fault-tolerant systems and systems with infrequent opportunity for maintenance (e.g., Hubble telescope, space station), the assumption of at most a single fault in the system is unrealistic. In this project, we have developed novel block and sequential diagnostic strategies to isolate multiple faults in the shortest possible time without making the unrealistic single fault assumption.

Bed Bug Epidemic: A Challenge to Public Health

ERIC Educational Resources Information Center

Ratnapradipa, Dhitinut; Ritzel, Dale O.; Haramis, Linn D.; Bliss, Kadi R.

2011-01-01

In recent years, reported cases of bed bug infestations in the U.S. and throughout the world have escalated dramatically, posing a global public health problem. Although bed bugs are not known to transmit disease to humans, they pose both direct and indirect public health challenges in terms of health effects, treatment, cost, and resource…

Family Planning in the Democratic Republic of the Congo: Encouraging Momentum, Formidable Challenges

PubMed Central

Kwete, Dieudonné; Binanga, Arsene; Mukaba, Thibaut; Nemuandjare, Théophile; Mbadu, Muanda Fidele; Kyungu, Marie-Thérèse; Sutton, Perri; Bertrand, Jane T

2018-01-01

Momentum for family planning in the Democratic Republic of the Congo (DRC) is evident in multiple ways: strong political will, increasing donor support, a growing number of implementing organizations, innovative family planning programming, and a cohesive family planning stakeholder group. Between 2013 and 2017, the modern contraceptive prevalence rate (mCPR) in the capital city of Kinshasa increased from 18.5% to 26.7% among married women, but as of 2013–14, it was only 7.8% at the national level. The National Multisectoral Strategic Plan for Family Planning: 2014–2020 calls for achieving an mCPR of 19.0% by 2020, an ambitious goal in light of formidable challenges to family planning in the DRC. Of the 16,465 health facilities reporting to the national health information system in 2017, only 40% offer family planning services. Key challenges include uncertainty over the political situation, difficulties of ensuring access to family planning services in a vast country with a weak transportation infrastructure, funding shortfalls for procuring adequate quantities of contraceptives, weak contraceptive logistics and supply chain management, strong cultural norms that favor large families, and low capacity of the population to pay for contraceptive services. This article describes promising initiatives designed to address these barriers, consistent with the World Health Organization's framework for health systems strengthening. For example, the national family planning coordinating mechanism is being replicated at the provincial level to oversee the expansion of family planning service delivery. Promising initiatives are being implemented to improve the supply and quality of services and generate demand for family planning, including social marketing of subsidized contraceptives at both traditional and non-traditional channels and strengthening of services in military health facilities. To expand contraceptive access, family planning is being institutionalized in nursing schools, allowing students to operate as community-based distributors. While major challenges remain, significant progress in family planning has been made in the DRC, which should be judged not in comparison with sub-Saharan African countries with high mCPR and mature programs, but rather with those starting from much further behind. PMID:29602865

Family Planning in the Democratic Republic of the Congo: Encouraging Momentum, Formidable Challenges.

PubMed

Kwete, Dieudonné; Binanga, Arsene; Mukaba, Thibaut; Nemuandjare, Théophile; Mbadu, Muanda Fidele; Kyungu, Marie-Thérèse; Sutton, Perri; Bertrand, Jane T

2018-03-21

Momentum for family planning in the Democratic Republic of the Congo (DRC) is evident in multiple ways: strong political will, increasing donor support, a growing number of implementing organizations, innovative family planning programming, and a cohesive family planning stakeholder group. Between 2013 and 2017, the modern contraceptive prevalence rate (mCPR) in the capital city of Kinshasa increased from 18.5% to 26.7% among married women, but as of 2013-14, it was only 7.8% at the national level. The National Multisectoral Strategic Plan for Family Planning: 2014-2020 calls for achieving an mCPR of 19.0% by 2020, an ambitious goal in light of formidable challenges to family planning in the DRC. Of the 16,465 health facilities reporting to the national health information system in 2017, only 40% offer family planning services. Key challenges include uncertainty over the political situation, difficulties of ensuring access to family planning services in a vast country with a weak transportation infrastructure, funding shortfalls for procuring adequate quantities of contraceptives, weak contraceptive logistics and supply chain management, strong cultural norms that favor large families, and low capacity of the population to pay for contraceptive services. This article describes promising initiatives designed to address these barriers, consistent with the World Health Organization's framework for health systems strengthening. For example, the national family planning coordinating mechanism is being replicated at the provincial level to oversee the expansion of family planning service delivery. Promising initiatives are being implemented to improve the supply and quality of services and generate demand for family planning, including social marketing of subsidized contraceptives at both traditional and non-traditional channels and strengthening of services in military health facilities. To expand contraceptive access, family planning is being institutionalized in nursing schools, allowing students to operate as community-based distributors. While major challenges remain, significant progress in family planning has been made in the DRC, which should be judged not in comparison with sub-Saharan African countries with high mCPR and mature programs, but rather with those starting from much further behind. © Kwete et al.

Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanized battalion during Operation Iraqi Freedom II.

PubMed

Gondusky, Joseph S; Reiter, Michael P

2005-06-01

Improvised explosive devices and mines pose a formidable threat to military convoys traveling in Iraq. This study evaluated battle injuries sustained by a mechanized battalion operating against this threat. The objective was to gain insight into injury profiles and prevention. In the period examined, 32 attacks injured 120 Marines, causing 188 injuries. Upper extremity and head injuries (70%) were common, whereas lower extremity injuries (11%) were rare (as expected, given the threat and the body areas exposed). Shoulder and axilla protectors may be beneficial, but lower arm and hand injuries remain difficult to combat. Ear injury was the most common single injury type (23%). Combat earplugs may reduce ear blast injuries. Eye injuries were uncommon (0.5%), likely because of ballistic eye protection. Injury to the torso (11%) was generally mild, because of body armor vests. The majority of wounds were minor, allowing > 80% of the injured Marines to return to duty.

Navigating a social world with robot partners: A quantitative cartography of the Uncanny Valley.

PubMed

Mathur, Maya B; Reichling, David B

2016-01-01

Android robots are entering human social life. However, human-robot interactions may be complicated by a hypothetical Uncanny Valley (UV) in which imperfect human-likeness provokes dislike. Previous investigations using unnaturally blended images reported inconsistent UV effects. We demonstrate an UV in subjects' explicit ratings of likability for a large, objectively chosen sample of 80 real-world robot faces and a complementary controlled set of edited faces. An "investment game" showed that the UV penetrated even more deeply to influence subjects' implicit decisions concerning robots' social trustworthiness, and that these fundamental social decisions depend on subtle cues of facial expression that are also used to judge humans. Preliminary evidence suggests category confusion may occur in the UV but does not mediate the likability effect. These findings suggest that while classic elements of human social psychology govern human-robot social interaction, robust UV effects pose a formidable android-specific problem. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Lessons about Climate Change Pose Many Challenges for Science Teachers

ERIC Educational Resources Information Center

Cavanagh, Sean

2007-01-01

This article reports on lessons about climate change which pose many challenges for science teachers. The natural world today offers a broad--and dire--catalog of scientific phenomena for teachers wanting to craft classroom lessons on the topic of climate change. As public concern about global warming increases, teachers are carving out a larger…

Ranking docking poses by graph matching of protein-ligand interactions: lessons learned from the D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

da Silva Figueiredo Celestino Gomes, Priscila; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

2018-01-01

A novel docking challenge has been set by the Drug Design Data Resource (D3R) in order to predict the pose and affinity ranking of a set of Farnesoid X receptor (FXR) agonists, prior to the public release of their bound X-ray structures and potencies. In a first phase, 36 agonists were docked to 26 Protein Data Bank (PDB) structures of the FXR receptor, and next rescored using the in-house developed GRIM method. GRIM aligns protein-ligand interaction patterns of docked poses to those of available PDB templates for the target protein, and rescore poses by a graph matching method. In agreement with results obtained during the previous 2015 docking challenge, we clearly show that GRIM rescoring improves the overall quality of top-ranked poses by prioritizing interaction patterns already visited in the PDB. Importantly, this challenge enables us to refine the applicability domain of the method by better defining the conditions of its success. We notably show that rescoring apolar ligands in hydrophobic pockets leads to frequent GRIM failures. In the second phase, 102 FXR agonists were ranked by decreasing affinity according to the Gibbs free energy of the corresponding GRIM-selected poses, computed by the HYDE scoring function. Interestingly, this fast and simple rescoring scheme provided the third most accurate ranking method among 57 contributions. Although the obtained ranking is still unsuitable for hit to lead optimization, the GRIM-HYDE scoring scheme is accurate and fast enough to post-process virtual screening data.

Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter

NASA Astrophysics Data System (ADS)

Hauck Newman, Amy; Katz, Jonathan L.

The dopamine transporter (DAT) has been a primary target for cocaine abuse/addiction medication discovery. However predicted addiction liability and limited clinical evaluation has provided a formidable challenge for development of these agents for human use. The unique and atypical pharmacological profile of the benztropine (BZT) class of dopamine uptake inhibitors, in preclinical models of cocaine effects and abuse, has encouraged further development of these agents. Moreover, in vivo studies have challenged the original DAT hypothesis and demonstrated that DAT occupancy and subsequent increases in dopamine produced by BZT analogues are significantly delayed and long lasting, as compared to cocaine. These important and distinctive elements are critical to the lack of abuse liability among BZT analogues, and improve their potential for development as treatments for cocaine abuse and possibly other neuropsychiatric disorders.

CAR T Cell Therapy for Glioblastoma: Recent Clinical Advances and Future Challenges.

PubMed

Bagley, Stephen J; Desai, Arati S; Linette, Gerald P; June, Carl H; O'Rourke, Donald M

2018-03-02

In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T cell therapy for glioblastoma. In addition, despite formidable barriers to T cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.

Optimizing care for the obese patient in interventional radiology

PubMed Central

Aberle, Dwight; Charles, Hearns; Hodak, Steven; O’Neill, Daniel; Oklu, Rahmi; Deipolyi, Amy R.

2017-01-01

With the rising epidemic of obesity, interventional radiologists are treating increasing numbers of obese patients, as comorbidities associated with obesity preclude more invasive treatments. These patients are at heightened risk of vascular and oncologic disease, both of which often require interventional radiology care. Obese patients pose unique challenges in imaging, technical feasibility, and periprocedural monitoring. This review describes the technical and clinical challenges posed by this population, with proposed methods to mitigate these challenges and optimize care. PMID:28082253

Evaluation of UDP-GlcN derivatives for selective labeling of 5-(hydroxymethyl)cytosine.

PubMed

Dai, Nan; Bitinaite, Jurate; Chin, Hang-Gyeong; Pradhan, Sriharsa; Corrêa, Ivan R

2013-11-04

5-(hydroxymethyl)cytosine (5-hmC) is a newly identified oxidative product of 5-methylcytosine (5-mC) in the mammalian genome, and is believed to be an important epigenetic marker influencing a variety of biological processes. In addition to its relatively low abundance, the fluctuation of 5-hmC levels over time during cell development poses a formidable challenge for its accurate mapping and quantification. Here we describe a specific chemoenzymatic approach to 5-hmC detection in DNA samples by using new uridine 5'-diphosphoglucosamine (UDP-GlcN) probes. Our approach requires modification of the glucose moiety of UDP-Glc with small amino groups and transfer of these glucose derivatives to the hydroxy moiety of 5-hmC by using T4 phage glucosyltransferases. We evaluated the transfer efficiencies of three glucosyltransferases (wild-type α- and β-GTs and a Y261L mutant β-GT) with five different UDP-Glc derivatives containing functionalized groups for subsequent bioconjugation and detection. Our results indicate that UDP-6-N3 -Glc, UDP-6-GlcN, and UDP-2-GlcN can be transferred by β-GT with efficiencies similar to that seen with the native UDP-Glc cofactor. 6-N3 -Glc- and 6-GlcN-containing oligonucleotides were selectively labeled with reactive fluorescent probes. In addition, a 2 kb DNA fragment modified with 2-GlcN groups was specifically detected by use of a commercially available antiglucosamine antibody. Alternative substrates for β-GT and correlated glycosyltransferases might prove useful for the study of the function and dynamics of 5-hmC and other modified nucleotides, as well as for multiplex analysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Global trends in molecular epidemiology of HIV-1 during 2000–2007

PubMed Central

Hemelaar, Joris; Gouws, Eleanor; Ghys, Peter D.; Osmanov, Saladin

2013-01-01

Objective To estimate the global and regional distribution of HIV-1 subtypes and recombinants between 2000 and 2007. Design Country-specific HIV-1 molecular epidemiology data were combined with estimates of the number of HIV-infected people in each country. Method Cross-sectional HIV-1 subtyping data were collected from 65913 samples in 109 countries between 2000 and 2007. The distribution of HIV-1 subtypes in individual countries was weighted according to the number of HIV-infected people in each country to generate estimates of regional and global HIV-1 subtype distribution for the periods 2000–2003 and 2004–2007. Results Analysis of the global distribution of HIV-1 subtypes and recombinants in the two time periods indicated a broadly stable distribution of HIV-1 subtypes worldwide with a notable increase in the proportion of circulating recombinant forms (CRFs), a decrease in unique recombinant forms (URFs), and an overall increase in recombinants. In 2004–2007, subtype C accounted for nearly half (48%) of all global infections, followed by subtypes A (12%) and B (11%), CRF02_AG (8%), CRF01_AE (5%), subtype G (5%) and D(2%). Subtypes F, H, J and K together cause fewer than 1% of infections worldwide. Other CRFs and URFs are each responsible for 4% of global infections, bringing the combined total of worldwide CRFs to 16% and all recombinants (CRFs plus URFs) to 20%. Conclusions The global and regional distributions of individual subtypes and recombinants are broadly stable, although CRFs may play an increasing role in the HIV pandemic. The global diversity of HIV-1 poses a formidable challenge to HIV vaccine development. PMID:21297424

Attomolar detection of proteins via cascade strand-displacement amplification and polystyrene nanoparticle enhancement in fluorescence polarization aptasensors.

PubMed

Huang, Yong; Liu, Xiaoqian; Huang, Huakui; Qin, Jian; Zhang, Liangliang; Zhao, Shulin; Chen, Zhen-Feng; Liang, Hong

2015-08-18

Extremely sensitive and accurate measurements of protein markers for early detection and monitoring of diseases pose a formidable challenge. Herein, we develop a new type of amplified fluorescence polarization (FP) aptasensor based on allostery-triggered cascade strand-displacement amplification (CSDA) and polystyrene nanoparticle (PS NP) enhancement for ultrasensitive detection of proteins. The assay system consists of a fluorescent dye-labeled aptamer hairpin probe and a PS NP-modified DNA duplex (assistant DNA/trigger DNA duplex) probe with a single-stranded part and DNA polymerase. Two probes coexist stably in the absence of target, and the dye exhibits relatively low FP background. Upon recognition and binding with a target protein, the stem of the aptamer hairpin probe is opened, after which the opened hairpin probe hybridizes with the single-stranded part in the PS NP-modified DNA duplex probe and triggers the CSDA reaction through the polymerase-catalyzed recycling of both target protein and trigger DNA. Throughout this CSDA process, numerous massive dyes are assembled onto PS NPs, which results in a substantial FP increase that provides a readout signal for the amplified sensing process. Our newly proposed amplified FP aptasensor enables the quantitative measurement of proteins with the detection limit in attomolar range, which is about 6 orders of magnitude lower than that of traditional homogeneous aptasensors. Moreover, this sensing method also exhibits high specificity for target proteins and can be performed in homogeneous solutions. In addition, the suitability of this method for the quantification of target protein in biological samples has also been shown. Considering these distinct advantages, the proposed sensing method can be expected to provide an ultrasensitive platform for the analysis of various types of target molecules.

Nicholas Metropolis Award for Outstanding Doctoral Thesis Work in Computational Physics Lecture: The Janus computer, a new window into spin-glass physics

NASA Astrophysics Data System (ADS)

Yllanes, David

2013-03-01

Spin glasses are a longstanding model for the sluggish dynamics that appears at the glass transition. They enjoy a privileged status in this context, as they provide the simplest model system both for theoretical and experimental studies of glassy dynamics. However, in spite of forty years of intensive investigation, spin glasses still pose a formidable challenge to theoretical, computational and experimental physics. The main difficulty lies in their incredibly slow dynamics. A recent breakthrough has been made possible by our custom-built computer, Janus, designed and built in a collaboration formed by five universities in Spain and Italy. By employing a purpose-driven architecture, capable of fully exploiting the parallelization possibilities intrinsic to these simulations, Janus outperforms conventional computers by several orders of magnitude. After a brief introduction to spin glasses, the talk will focus on the new physics unearthed by Janus. In particular, we recall our numerical study of the nonequilibrium dynamics of the Edwards-Anderson Ising Spin Glass, for a time that spans eleven orders of magnitude, thus approaching the experimentally relevant scale (i.e. seconds). We have also studied the equilibrium properties of the spin-glass phase, with an emphasis on the quantitative matching between non-equilibrium and equilibrium correlation functions, through a time-length dictionary. Last but not least, we have clarified the existence of a glass transition in the presence of a magnetic field for a finite-range spin glass (the so-called de Almeida-Thouless line). We will finally mention some of the currently ongoing work of the collaboration, such as the characterization of the non-equilibrium dynamics in a magnetic field and the existence of a statics-dynamics dictionary in these conditions.

Climate Change and Arctic Issues in the Marine and Environmental Science Curriculum at the U.S. Coast Guard Academy

NASA Astrophysics Data System (ADS)

Vlietstra, L.; McConnell, M. C.; Bergondo, D. L.; Mrakovcich, K. L.; Futch, V.; Stutzman, B. S.; Fleischmann, C. M.

2016-02-01

As global climate change becomes more evident, demand will likely increase for experts with a detailed understanding of the scientific basis of climate change, the ocean's role in the earth-atmosphere system, and forecasted impacts, especially in Arctic regions where effects may be most pronounced. As a result, programs in marine and environmental sciences are uniquely poised to prepare graduates for the formidable challenges posed by changing climates. Here we present research evaluating the prevalence and themes of courses focusing on anthropogenic climate change in 125 Marine Science and Environmental Science undergraduate programs at 86 institutions in the United States. These results, in addition to the increasing role of the Coast Guard in the Arctic, led to the development of two new courses in the curriculum. Climate Change Science, a one-credit seminar, includes several student-centered activities supporting key learning objectives. Polar Oceanography, a three-credit course, incorporates a major outreach component to Coast Guard units and members of the scientific community. Given the importance of climate change in Arctic regions in particular, we also propose six essential "Arctic Literacy Principles" around which courses or individual lesson plans may be organized. We show how these principles are incorporated into an additional new three-credit course, Model Arctic Council, which prepares students to participate in a week-long simulation exercise of Arctic Council meetings, held in Fairbanks, Alaska. Students examine the history and mission of the Arctic Council and explore some of the issues on which the council has deliberated. Special attention is paid to priorities of the current U.S. chairmanship of the Arctic Council which include climate change impacts on, and stewardship of, the Arctic Ocean.

Spectrum and outcome of pancreatic trauma.

PubMed

Kantharia, Chetan V; Prabhu, R Y; Dalvi, A N; Raut, Abhijit; Bapat, R D; Supe, Avinash N

2007-01-01

Pancreatic trauma is associated with high morbidity and mortality. Diagnosis is often difficult and surgery poses a formidable challenge. Data from 17 patients of pancreatic trauma gathered from a prospectively maintained database were analysed and the following parameters were considered: mode of injury, diagnostic modalities, associated injury, grade of pancreatic trauma and management. Pancreatic trauma was graded from I through IV, as per Modified Lucas Classification. The median age was 39 years (range 19-61). The aetiology of pancreatic trauma was blunt abdominal trauma in 14 patients and penetrating injury in 3. Associated bowel injury was present in 4 cases (3 penetrating injury and 1 blunt trauma) and 1 case had associated vascular injury. 5 patients had grade I, 3 had grade II, 7 had grade III and 2 had grade IV pancreatic trauma. Contrast enhanced computed tomography scan was used to diagnose pancreatic trauma in all patients with blunt abdominal injury. Immediate diagnosis could be reached in only 4 (28.5%) patients. 7 patients responded to conservative treatment. Of the 10 patients who underwent surgery, 6 required it for the pancreas and the duodenum. (distal pancreatectomy with splenectomy-3, pylorus preserving pancreatoduodenectomy-1, debridement with external drainage-1, associated injuries-duodenum-1). Pancreatic fistula, recurrent pancreatitis and pseudocyst formation were seen in 3 (17.05%), 2 (11.7%) and 1 (5.4%) patient respectively. Death occurred in 4 cases (23.5%), 2 each in grades III and IV pancreatic trauma. Contrast enhanced computed tomography scan is a useful modality for diagnosing, grading and following up patients with pancreatic trauma. Although a majority of cases with pancreatic trauma respond to conservative treatment, patients with penetrating trauma, and associated bowel injury and higher grade pancreatic trauma require surgical intervention and are also associated with higher morbidity and mortality.

An Outlook on Lithium Ion Battery Technology

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

Manthiram, Arumugam

Lithium ion batteries as a power source are dominating in portable electronics, penetrating the electric vehicle market, and on the verge of entering the utility market for grid-energy storage. Depending on the application, trade-offs among the various performance parameters—energy, power, cycle life, cost, safety, and environmental impact—are often needed, which are linked to severe materials chemistry challenges. The current lithium ion battery technology is based on insertion-reaction electrodes and organic liquid electrolytes. With an aim to increase the energy density or optimize the other performance parameters, new electrode materials based on both insertion reaction and dominantly conversion reaction along withmore » solid electrolytes and lithium metal anode are being intensively pursued. In conclusion, this article presents an outlook on lithium ion technology by providing first the current status and then the progress and challenges with the ongoing approaches. In light of the formidable challenges with some of the approaches, the article finally points out practically viable near-term strategies.« less

Space Shuttle Strategic Planning Status

NASA Technical Reports Server (NTRS)

Henderson, Edward M.; Norbraten, Gordon L.

2006-01-01

The Space Shuttle Program is aggressively planning the Space Shuttle manifest for assembling the International Space Station and servicing the Hubble Space Telescope. Implementing this flight manifest while concurrently transitioning to the Exploration architecture creates formidable challenges; the most notable of which is retaining critical skills within the Shuttle Program workforce. The Program must define a strategy that will allow safe and efficient fly-out of the Shuttle, while smoothly transitioning Shuttle assets (both human and facility) to support early flight demonstrations required in the development of NASA s Crew Exploration Vehicle (CEV) and Crew and Cargo Launch Vehicles (CLV). The Program must accomplish all of this while maintaining the current level of resources. Therefore, it will be necessary to initiate major changes in operations and contracting. Overcoming these challenges will be essential for NASA to fly the Shuttle safely, accomplish the President s "Vision for Space Exploration," and ultimately meet the national goal of maintaining a robust space program. This paper will address the Space Shuttle Program s strategy and its current status in meeting these challenges.

An Outlook on Lithium Ion Battery Technology

DOE PAGES

Manthiram, Arumugam

2017-09-07

Lithium ion batteries as a power source are dominating in portable electronics, penetrating the electric vehicle market, and on the verge of entering the utility market for grid-energy storage. Depending on the application, trade-offs among the various performance parameters—energy, power, cycle life, cost, safety, and environmental impact—are often needed, which are linked to severe materials chemistry challenges. The current lithium ion battery technology is based on insertion-reaction electrodes and organic liquid electrolytes. With an aim to increase the energy density or optimize the other performance parameters, new electrode materials based on both insertion reaction and dominantly conversion reaction along withmore » solid electrolytes and lithium metal anode are being intensively pursued. In conclusion, this article presents an outlook on lithium ion technology by providing first the current status and then the progress and challenges with the ongoing approaches. In light of the formidable challenges with some of the approaches, the article finally points out practically viable near-term strategies.« less

An Outlook on Lithium Ion Battery Technology

PubMed Central

2017-01-01

Lithium ion batteries as a power source are dominating in portable electronics, penetrating the electric vehicle market, and on the verge of entering the utility market for grid-energy storage. Depending on the application, trade-offs among the various performance parameters—energy, power, cycle life, cost, safety, and environmental impact—are often needed, which are linked to severe materials chemistry challenges. The current lithium ion battery technology is based on insertion-reaction electrodes and organic liquid electrolytes. With an aim to increase the energy density or optimize the other performance parameters, new electrode materials based on both insertion reaction and dominantly conversion reaction along with solid electrolytes and lithium metal anode are being intensively pursued. This article presents an outlook on lithium ion technology by providing first the current status and then the progress and challenges with the ongoing approaches. In light of the formidable challenges with some of the approaches, the article finally points out practically viable near-term strategies. PMID:29104922

Space Shuttle Strategic Planning Status

NASA Technical Reports Server (NTRS)

Norbraten, Gordon L.; Henderson, Edward M.

2007-01-01

The Space Shuttle Program is aggressively flying the Space Shuttle manifest for assembling the International Space Station and servicing the Hubble Space Telescope. Completing this flight manifest while concurrently transitioning to the Exploration architecture creates formidable challenges; the most notable of which is retaining critical skills within the Shuttle Program workforce. The Program must define a strategy that will allow safe and efficient fly-out of the Shuttle, while smoothly transitioning Shuttle assets (both human and facility) to support early flight demonstrations required in the development of NASA's Crew Exploration Vehicle (Orion) and Crew and Cargo Launch Vehicles (Ares I). The Program must accomplish all of this while maintaining the current level of resources. Therefore, it will be necessary to initiate major changes in operations and contracting. Overcoming these challenges will be essential for NASA to fly the Shuttle safely, accomplish the Vision for Space Exploration, and ultimately meet the national goal of maintaining a robust space program. This paper will address the Space Shuttle Program s strategy and its current status in meeting these challenges.

D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity predictions

NASA Astrophysics Data System (ADS)

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A.; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2016-09-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor.

D3R Grand Challenge 2015: Evaluation of Protein-Ligand Pose and Affinity Predictions

PubMed Central

Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.

2017-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (i) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (ii) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor. PMID:27696240

Pose-Invariant Face Recognition via RGB-D Images.

PubMed

Sang, Gaoli; Li, Jing; Zhao, Qijun

2016-01-01

Three-dimensional (3D) face models can intrinsically handle large pose face recognition problem. In this paper, we propose a novel pose-invariant face recognition method via RGB-D images. By employing depth, our method is able to handle self-occlusion and deformation, both of which are challenging problems in two-dimensional (2D) face recognition. Texture images in the gallery can be rendered to the same view as the probe via depth. Meanwhile, depth is also used for similarity measure via frontalization and symmetric filling. Finally, both texture and depth contribute to the final identity estimation. Experiments on Bosphorus, CurtinFaces, Eurecom, and Kiwi databases demonstrate that the additional depth information has improved the performance of face recognition with large pose variations and under even more challenging conditions.

Chronic disease management in rural and underserved populations: innovation and system improvement help lead to success.

PubMed

Bolin, Jane; Gamm, Larry; Kash, Bita; Peck, Mitchell

2005-03-01

Successful implementation of disease management (DM) is based on the ability of an organization to overcome a variety of barriers to deliver timely, appropriate care of chronic illnesses. Such programs initiate DM services to patient populations while initiating self-management education among medication-resistant patients who are chronically ill. Despite formidable challenges, rural health care providers have been successful in initiating DM programs and have discovered several ways in which these programs benefit their organizations. This research reports on six DM programs that serve large rural and underserved populations and have demonstrated that DM can be successfully implemented in such areas.

Managing Complexity in the MSL/Curiosity Entry, Descent, and Landing Flight Software and Avionics Verification and Validation Campaign

NASA Technical Reports Server (NTRS)

Stehura, Aaron; Rozek, Matthew

2013-01-01

The complexity of the Mars Science Laboratory (MSL) mission presented the Entry, Descent, and Landing systems engineering team with many challenges in its Verification and Validation (V&V) campaign. This paper describes some of the logistical hurdles related to managing a complex set of requirements, test venues, test objectives, and analysis products in the implementation of a specific portion of the overall V&V program to test the interaction of flight software with the MSL avionics suite. Application-specific solutions to these problems are presented herein, which can be generalized to other space missions and to similar formidable systems engineering problems.

File formats commonly used in mass spectrometry proteomics.

PubMed

Deutsch, Eric W

2012-12-01

The application of mass spectrometry (MS) to the analysis of proteomes has enabled the high-throughput identification and abundance measurement of hundreds to thousands of proteins per experiment. However, the formidable informatics challenge associated with analyzing MS data has required a wide variety of data file formats to encode the complex data types associated with MS workflows. These formats encompass the encoding of input instruction for instruments, output products of the instruments, and several levels of information and results used by and produced by the informatics analysis tools. A brief overview of the most common file formats in use today is presented here, along with a discussion of related topics.

Literacy in Brazil: from Rights to Reality

NASA Astrophysics Data System (ADS)

Ireland, Timothy D.

2008-11-01

At a time when some 24% of the Brazilian population of 182 million are functionally illiterate, the author shows how illiteracy is concentrated in traditionally poor and disadvantaged social and ethnic groups as well as in certain regions of the country. He surveys the changes in legislation, policies and attitudes relating to literacy over the past few decades and describes how literacy is increasingly seen as a continuous process rather than a short-term, low-cost intervention. While there is still a lack of a broad, coordinated policy and adequate funding in this area, and while the challenges remain formidable, the author concludes that Brazil is moving slowly in the right direction.

Aggregate measures of ecosystem services: Can we take the pulse of nature?

USGS Publications Warehouse

Meyerson, L.A.; Baron, Jill S.; Melillo, J.M.; Naiman, R.J.; O'Malley, R.I.; Orians, G.; Palmer, Margaret A.; Pfaff, Alexander S.P.; Running, S.W.; Sala, O.E.

2005-01-01

National scale aggregate indicators of ecosystem services are useful for stimulating and supporting a broad public discussion about trends in the provision of these services. There are important considerations involved in producing an aggregate indicator, including whether the scientific and technological capacity exists, how to address varying perceptions of the societal importance of different services, and how to communicate information about these services to both decision makers and the general public. Although the challenges are formidable, they are not insurmountable. Quantification of ecosystem services and dissemination of information to decision makers and the public is critical for the responsible and sustainable management of natural resources.

Varied presentations of missile emboli in military combat.

PubMed

Aidinian, Gilbert; Fox, Charles J; Rasmussen, Todd E; Gillespie, David L

2010-01-01

Fragment embolization is a rare phenomenon in trauma patients. Although surgical and endovascular management of vascular injuries have evolved significantly, the detection and management of fragment emboli remain a formidable challenge. We reviewed our experience with this entity from December 2001 to March 2008. During this time period, four (1.1%) of 346 US soldiers evacuated to Walter Reed with arterial or venous injuries were discovered to have suffered missile emboli. Venous emboli were treated with anticoagulation and arterial emboli were treated with standard embolectomy techniques with good result. The presentation, diagnosis, and surgical management of these cases are described. Published by Mosby, Inc.

Feminism and psychology: analysis of a half-century of research on women and gender.

PubMed

Eagly, Alice H; Eaton, Asia; Rose, Suzanna M; Riger, Stephanie; McHugh, Maureen C

2012-04-01

Starting in the 1960s, feminists argued that the discipline of psychology had neglected the study of women and gender and misrepresented women in its research and theories. Feminists also posed many questions worthy of being addressed by psychological science. This call for research preceded the emergence of a new and influential body of research on gender and women that grew especially rapidly during the period of greatest feminist activism. The descriptions of this research presented in this article derive from searches of the journal articles cataloged by PsycINFO for 1960-2009. These explorations revealed (a) a concentration of studies in basic research areas investigating social behavior and individual dispositions and in many applied areas, (b) differing trajectories of research on prototypical topics, and (c) diverse theoretical orientations that authors have not typically labeled as feminist. The considerable dissemination of this research is evident in its dispersion beyond gender-specialty journals into a wide range of other journals, including psychology's core review and theory journals, as well as in its coverage in introductory psychology textbooks. In this formidable body of research, psychological science has reflected the profound changes in the status of women during the last half-century and addressed numerous questions that these changes have posed. Feminism served to catalyze this research area, which grew beyond the bounds of feminist psychology to incorporate a very large array of theories, methods, and topics.

Vision Based SLAM in Dynamic Scenes

DTIC Science & Technology

2012-12-20

the correct relative poses between cameras at frame F. For this purpose, we detect and match SURF features between cameras in dilierent groups, and...all cameras in s uch a challenging case. For a compa rison, we disabled the ’ inte r-camera pose estimation’ and applied the ’ intra-camera pose esti

Dental caries and periodontal diseases in the ageing population: call to action to protect and enhance oral health and well-being as an essential component of healthy ageing - Consensus report of group 4 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases.

PubMed

Tonetti, Maurizio S; Bottenberg, Peter; Conrads, Georg; Eickholz, Peter; Heasman, Peter; Huysmans, Marie-Charlotte; López, Rodrigo; Madianos, Phoebus; Müller, Frauke; Needleman, Ian; Nyvad, Bente; Preshaw, Philip M; Pretty, Iain; Renvert, Stefan; Schwendicke, Falk; Trombelli, Leonardo; van der Putten, Gert-Jan; Vanobbergen, Jacques; West, Nicola; Young, Alix; Paris, Sebastian

2017-03-01

Over the last two decades, progress in prevention and treatment of caries and periodontal diseases has been translated to better oral health and improved tooth retention in the adult population. The ageing population and the increasing expectations of good oral health-related quality of life in older age pose formidable challenges to clinical care and healthcare systems. The objective of this workshop was to critically review scientific evidence and develop specific recommendations to: (i) prevent tooth loss and retain oral function through prevention and treatment of caries and periodontal diseases later in life and (ii) increase awareness of the health benefits of oral health as an essential component of healthy ageing. Discussions were initiated by three systematic reviews covering aspects of epidemiology of caries and periodontal diseases in elders, the impact of senescence on caries and periodontal diseases and the effectiveness of interventions. Recommendations were developed based on evidence from the systematic reviews and expert opinion. Key messages included: (i) the ageing population, trends in risk factors and improved tooth retention point towards an expected increase in the total burden of disease posed by caries and periodontal diseases in the older population; (ii) specific surveillance is required to monitor changes in oral health in the older population; (iii) senescence impacts oral health including periodontitis and possibly caries susceptibility; (iv) evidence indicates that caries and periodontal diseases can be prevented and treated also in older adults; (v) oral health and functional tooth retention later in life provides benefits both in terms of oral and general quality of life and in terms of preventing physical decline and dependency by fostering a healthy diet; (vi) oral healthcare professionals and individuals should not base decisions impacting tooth retention on chronological age but on level of dependency, life expectancy, frailty, comfort and quality of life; and (vii) health policy should remove barriers to oral health care for vulnerable elders. Consensus was reached on specific actionable priorities for public health officials, oral healthcare professionals, educators and workforce planners, caregivers and relatives as well as for the public and ageing patients. Some priorities have major implications for policymakers as health systems need to adapt to the challenge by systemwide changes to enable (promote) tooth retention later in life and management of deteriorating oral health in increasingly dependent elders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Commercial viability of CNS drugs: balancing the risk/reward profile.

PubMed

Johnson, Ginger S

2014-01-01

CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

Single crystal growth of 67%BiFeO 3 -33%BaTiO 3 solution by the floating zone method

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

Rong, Y.; Zheng, H.; Krogstad, M. J.

The growth conditions and the resultant grain morphologies and phase purities from floating-zone growth of 67%BiFeO3-33%BaTiO3 (BF-33BT) single crystals are reported. We find two formidable challenges for the growth. First, a low-melting point constituent leads to a pre-melt zone in the feed-rod that adversely affects growth stability. Second, constitutional super-cooling (CSC), which was found to lead to dendritic and columnar features in the grain morphology, necessitates slow traveling rates during growth. Both challenges were addressed by modifications to the floating-zone furnace that steepened the temperature gradient at the melt-solid interfaces. Slow growth was also required to counter the effects ofmore » CSC. Single crystals with typical dimensions of hundreds of microns have been obtained which possess high quality and are suitable for detailed structural studies.« less

Integrating cultural community psychology: activity settings and the shared meanings of intersubjectivity.

PubMed

O'Donnell, Clifford R; Tharp, Roland G

2012-03-01

Cultural and community psychology share a common emphasis on context, yet their leading journals rarely cite each other's articles. Greater integration of the concepts of culture and community within and across their disciplines would enrich and facilitate the viability of cultural community psychology. The contextual theory of activity settings is proposed as one means to integrate the concepts of culture and community in cultural community psychology. Through shared activities, participants develop common experiences that affect their psychological being, including their cognitions, emotions, and behavioral development. The psychological result of these experiences is intersubjectivity. Culture is defined as the shared meanings that people develop through their common historic, linguistic, social, economic, and political experiences. The shared meanings of culture arise through the intersubjectivity developed in activity settings. Cultural community psychology presents formidable epistemological challenges, but overcoming these challenges could contribute to the transformation and advancement of community psychology.

Pricing and reimbursement frameworks in Central Eastern Europe: a decision tool to support choices.

PubMed

Kolasa, Katarzyna; Kalo, Zoltan; Hornby, Edward

2015-02-01

Given limited financial resources in the Central Eastern European (CEE) region, challenges in obtaining access to innovative medical technologies are formidable. The objective of this research was to develop a decision tree that supports decision makers and drug manufacturers from CEE region in their search for optimal innovative pricing and reimbursement scheme (IPRSs). A systematic literature review was performed to search for published IPRSs, and then ten experts from the CEE region were interviewed to ascertain their opinions on these schemes. In total, 33 articles representing 46 unique IPRSs were analyzed. Based on our literature review and subsequent expert input, key decision nodes and branches of the decision tree were developed. The results indicate that outcome-based schemes are better suited to deal with uncertainties surrounding cost effectiveness, while non-outcome-based schemes are more appropriate for pricing and budget impact challenges.

Spectral signatures for RDX-based explosives in the 3 micron region

NASA Astrophysics Data System (ADS)

Osborn, Tabetha; Kaimal, Sindhu; Reeve, Scott W.; Burns, William

2008-04-01

Explosive compounds such as RDX, and HMX present significant challenges to optically based sensors. This difficulty is due in part to the low vapor pressures these compounds possess. One approach for sensing explosives that circumvents the low explosive vapor pressure problem, involves focusing on the trace amounts of relatively high vapor pressure impurities that will be present in the vapor signature. In order to effectively detect these volatile impurities, the spectral signature databases must be readily available. One of our goals therefore, is the generation of a database of high resolution spectral signatures for these volatile organic impurities. Some rather formidable spectroscopic measurement challenges have been encountered while working to extend the spectral signature effort to the 3 micron region. Here we will outline progress to date, with a focus on the volatile organic compounds formaldehyde, acetaldehyde, nitromethane, acetone, isobutene, and cyclohexanone.

Challenges for semilocal density functionals with asymptotically nonvanishing potentials

NASA Astrophysics Data System (ADS)

Aschebrock, Thilo; Armiento, Rickard; Kümmel, Stephan

2017-08-01

The Becke-Johnson model potential [A. D. Becke and E. R. Johnson, J. Chem. Phys. 124, 221101 (2006), 10.1063/1.2213970] and the potential of the AK13 functional [R. Armiento and S. Kümmel, Phys. Rev. Lett. 111, 036402 (2013), 10.1103/PhysRevLett.111.036402] have been shown to mimic features of the exact Kohn-Sham exchange potential, such as step structures that are associated with shell closings and particle-number changes. A key element in the construction of these functionals is that the potential has a limiting value far outside a finite system that is a system-dependent constant rather than zero. We discuss a set of anomalous features in these functionals that are closely connected to the nonvanishing asymptotic potential. The findings constitute a formidable challenge for the future development of semilocal functionals based on the concept of a nonvanishing asymptotic constant.

Single crystal growth of 67%BiFeO3-33%BaTiO3 solution by the floating zone method

NASA Astrophysics Data System (ADS)

Rong, Y.; Zheng, H.; Krogstad, M. J.; Mitchell, J. F.; Phelan, D.

2018-01-01

The growth conditions and the resultant grain morphologies and phase purities from floating-zone growth of 67%BiFeO3-33%BaTiO3 (BF-33BT) single crystals are reported. We find two formidable challenges for the growth. First, a low-melting point constituent leads to a pre-melt zone in the feed-rod that adversely affects growth stability. Second, constitutional super-cooling (CSC), which was found to lead to dendritic and columnar features in the grain morphology, necessitates slow traveling rates during growth. Both challenges were addressed by modifications to the floating-zone furnace that steepened the temperature gradient at the melt-solid interfaces. Slow growth was also required to counter the effects of CSC. Single crystals with typical dimensions of hundreds of microns have been obtained which possess high quality and are suitable for detailed structural studies.

Teachers Implementing Mathematical Problem Posing in the Classroom: Challenges and Strategies

ERIC Educational Resources Information Center

Leung, Shuk-kwan S.

2013-01-01

This paper reports a study about how a teacher educator shared knowledge with teachers when they worked together to implement mathematical problem posing (MPP) in the classroom. It includes feasible methods for getting practitioners to use research-based tasks aligned to the curriculum in order to encourage children to pose mathematical problems.…

DOCKSCORE: a webserver for ranking protein-protein docked poses.

PubMed

Malhotra, Sony; Mathew, Oommen K; Sowdhamini, Ramanathan

2015-04-24

Proteins interact with a variety of other molecules such as nucleic acids, small molecules and other proteins inside the cell. Structure-determination of protein-protein complexes is challenging due to several reasons such as the large molecular weights of these macromolecular complexes, their dynamic nature, difficulty in purification and sample preparation. Computational docking permits an early understanding of the feasibility and mode of protein-protein interactions. However, docking algorithms propose a number of solutions and it is a challenging task to select the native or near native pose(s) from this pool. DockScore is an objective scoring scheme that can be used to rank protein-protein docked poses. It considers several interface parameters, namely, surface area, evolutionary conservation, hydrophobicity, short contacts and spatial clustering at the interface for scoring. We have implemented DockScore in form of a webserver for its use by the scientific community. DockScore webserver can be employed, subsequent to docking, to perform scoring of the docked solutions, starting from multiple poses as inputs. The results, on scores and ranks for all the poses, can be downloaded as a csv file and graphical view of the interface of best ranking poses is possible. The webserver for DockScore is made freely available for the scientific community at: http://caps.ncbs.res.in/dockscore/ .

Friends shrink foes: the presence of comrades decreases the envisioned physical formidability of an opponent.

PubMed

Fessler, Daniel M T; Holbrook, Colin

2013-05-01

In situations of potential violent conflict, deciding whether to fight, flee, or try to negotiate entails assessing many attributes contributing to the relative formidability of oneself and one's opponent. Summary representations can usefully facilitate such assessments of multiple factors. Because physical size and strength are both phylogenetically ancient and ontogenetically recurrent contributors to the outcome of violent conflicts, these attributes provide plausible conceptual dimensions that may be used by the mind to summarize the relative formidability of opposing parties. Because the presence of allies is a vital factor in determining victory, we hypothesized that men accompanied by male companions would therefore envision a solitary foe as physically smaller and less muscular than would men who were alone. We document the predicted effect in two studies, one using naturally occurring variation in the presence of male companions and one employing experimental manipulation of this factor.

Novel GM animal technologies and their governance.

PubMed

Bruce, Ann; Castle, David; Gibbs, Corrina; Tait, Joyce; Whitelaw, C Bruce A

2013-08-01

Scientific advances in methods of producing genetically modified (GM) animals continue, yet few such animals have reached commercial production. Existing regulations designed for early techniques of genetic modification pose formidable barriers to commercial applications. Radically improved techniques for producing GM animals invite a re-examination of current regulatory regimes. We critically examine current GM animal regulations, with a particular focus on the European Union, through a framework that recognises the importance of interactions among regulatory regimes, innovation outcomes and industry sectors. The current focus on the regulation of risk is necessary but is unable to discriminate among applications and tends to close down broad areas of application rather than facilitate innovation and positive industry interactions. Furthermore, the fields of innovative animal biosciences appear to lack networks of organisations with co-ordinated future oriented actions. Such networks could drive coherent programmes of innovation towards particular visions and contribute actively to the development of regulatory systems for GM animals. The analysis presented makes the case for regulatory consideration of each animal bioscience related innovation on the basis of the nature of the product itself and not the process by which it was developed.

Analyzing the Impacts of Land Use Land Change on Near Shore Coastal Habitat

NASA Astrophysics Data System (ADS)

Lehman, R. D.; Ta, E.; Boyle, C.; Alwood, B.

2017-12-01

The natural beauty of the United States Virgin Islands (USVI) has continued to attract visitors and residents, which overtime has increased human development and impact. The resulting land use change increases sediment loads and the flow of pollutants into surrounding nearshore environments such as coral reefs, mangroves, and seagrass beds. Compounded with regional climate-related processes such as rising ocean temperatures and acidification, future land-use change poses a formidable threat to coral reefs and other susceptible marine environments. Without a healthy environment, the USVI economy also becomes endangered because it is mainly supported by tourism and recreation. Using Google Earth Engine, we created a tool to composite yearly Landsat 5 TM, Landsat 8 OLI/TIRS and Sentinel-2 MSI images identify changes from 1985 to present day. Using these land cover change maps we then analyzed trends at a watershed scale using hydrological data. We found there is a spatial relationship between development intensity and the health of coral reefs. Our work supports the existing knowledge of the link between land use and coastal ecosystem health.

Continuous centrifuge decelerator for polar molecules.

PubMed

Chervenkov, S; Wu, X; Bayerl, J; Rohlfes, A; Gantner, T; Zeppenfeld, M; Rempe, G

2014-01-10

Producing large samples of slow molecules from thermal-velocity ensembles is a formidable challenge. Here we employ a centrifugal force to produce a continuous molecular beam with a high flux at near-zero velocities. We demonstrate deceleration of three electrically guided molecular species, CH3F, CF3H, and CF3CCH, with input velocities of up to 200  m s(-1) to obtain beams with velocities below 15  m s(-1) and intensities of several 10(9)  mm(-2) s(-1). The centrifuge decelerator is easy to operate and can, in principle, slow down any guidable particle. It has the potential to become a standard technique for continuous deceleration of molecules.

Catalog of 174 Binary Black Hole Simulations for Gravitational Wave Astronomy

NASA Astrophysics Data System (ADS)

Mroué, Abdul H.; Scheel, Mark A.; Szilágyi, Béla; Pfeiffer, Harald P.; Boyle, Michael; Hemberger, Daniel A.; Kidder, Lawrence E.; Lovelace, Geoffrey; Ossokine, Serguei; Taylor, Nicholas W.; Zenginoğlu, Anıl; Buchman, Luisa T.; Chu, Tony; Foley, Evan; Giesler, Matthew; Owen, Robert; Teukolsky, Saul A.

2013-12-01

This Letter presents a publicly available catalog of 174 numerical binary black hole simulations following up to 35 orbits. The catalog includes 91 precessing binaries, mass ratios up to 8∶1, orbital eccentricities from a few percent to 10-5, black hole spins up to 98% of the theoretical maximum, and radiated energies up to 11.1% of the initial mass. We establish remarkably good agreement with post-Newtonian precession of orbital and spin directions for two new precessing simulations, and we discuss other applications of this catalog. Formidable challenges remain: e.g., precession complicates the connection of numerical and approximate analytical waveforms, and vast regions of the parameter space remain unexplored.

Toward a multiscale modeling framework for understanding serotonergic function

PubMed Central

Wong-Lin, KongFatt; Wang, Da-Hui; Moustafa, Ahmed A; Cohen, Jeremiah Y; Nakamura, Kae

2017-01-01

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin. PMID:28417684

In Search of Grid Converged Solutions

NASA Technical Reports Server (NTRS)

Lockard, David P.

2010-01-01

Assessing solution error continues to be a formidable task when numerically solving practical flow problems. Currently, grid refinement is the primary method used for error assessment. The minimum grid spacing requirements to achieve design order accuracy for a structured-grid scheme are determined for several simple examples using truncation error evaluations on a sequence of meshes. For certain methods and classes of problems, obtaining design order may not be sufficient to guarantee low error. Furthermore, some schemes can require much finer meshes to obtain design order than would be needed to reduce the error to acceptable levels. Results are then presented from realistic problems that further demonstrate the challenges associated with using grid refinement studies to assess solution accuracy.

File Formats Commonly Used in Mass Spectrometry Proteomics*

PubMed Central

Deutsch, Eric W.

2012-01-01

The application of mass spectrometry (MS) to the analysis of proteomes has enabled the high-throughput identification and abundance measurement of hundreds to thousands of proteins per experiment. However, the formidable informatics challenge associated with analyzing MS data has required a wide variety of data file formats to encode the complex data types associated with MS workflows. These formats encompass the encoding of input instruction for instruments, output products of the instruments, and several levels of information and results used by and produced by the informatics analysis tools. A brief overview of the most common file formats in use today is presented here, along with a discussion of related topics. PMID:22956731

Transference and Countertransference in the Psychotherapy of Therapists Charged With Sexual Misconduct

PubMed Central

GABBARD, GLEN O.

1995-01-01

When psychotherapists accused of sexual misconduct are referred for personal psychotherapy, formidable challenges are presented to the clinician designated as the psychotherapist. The author outlines common transference-countertransference themes and discusses them in terms of their psychodynamic underpinnings and optimal management. These themes include the therapist as a law enforcement agent, the therapist as a corruptible object, the therapist as a love object, the therapist as a rescuer and absolver, the therapist as an authoritarian parent, and the therapist as a voyeur. A common thread in all of these transference-counter-transference paradigms involves the discomfort experienced by the treating psychotherapists when they recognize aspects of themselves in the accused professional. PMID:22700209

Catalog of 174 binary black hole simulations for gravitational wave astronomy.

PubMed

Mroué, Abdul H; Scheel, Mark A; Szilágyi, Béla; Pfeiffer, Harald P; Boyle, Michael; Hemberger, Daniel A; Kidder, Lawrence E; Lovelace, Geoffrey; Ossokine, Serguei; Taylor, Nicholas W; Zenginoğlu, Anıl; Buchman, Luisa T; Chu, Tony; Foley, Evan; Giesler, Matthew; Owen, Robert; Teukolsky, Saul A

2013-12-13

This Letter presents a publicly available catalog of 174 numerical binary black hole simulations following up to 35 orbits. The catalog includes 91 precessing binaries, mass ratios up to 8∶1, orbital eccentricities from a few percent to 10(-5), black hole spins up to 98% of the theoretical maximum, and radiated energies up to 11.1% of the initial mass. We establish remarkably good agreement with post-Newtonian precession of orbital and spin directions for two new precessing simulations, and we discuss other applications of this catalog. Formidable challenges remain: e.g., precession complicates the connection of numerical and approximate analytical waveforms, and vast regions of the parameter space remain unexplored.

The Challenges of Career and Technical Education Concurrent Enrollment: An Administrative Perspective

ERIC Educational Resources Information Center

Haag, Patricia W.

2015-01-01

Career and technical education concurrent enrollment may pose unique challenges in programming and enrollment for program administrators, and this chapter describes the experiences and challenges of a CTE concurrent enrollment administrator.

Nanotechnology-based cancer therapeutics--promise and challenge--lessons learned through the NCI Alliance for Nanotechnology in Cancer.

PubMed

Farrell, Dorothy; Ptak, Krzysztof; Panaro, Nicholas J; Grodzinski, Piotr

2011-02-01

The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct design can result in enhanced drug efficacy at lower doses as compared to free drug treatment, wider therapeutic window, and lower side effects. Nanoparticle carriers can also address several drug delivery problems which could not be effectively solved in the past and include reduction of multi-drug resistance effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although challenges in understanding toxicity, biodistribution, and paving an effective regulatory path must be met, nanoscale devices carry a formidable promise to change ways cancer is diagnosed and treated. This article summarizes current developments in nanotechnology-based drug delivery and discusses path forward in this field. The discussion is done in context of research and development occurring within the NCI Alliance for Nanotechnology in Cancer program.

Improved pose and affinity predictions using different protocols tailored on the basis of data availability

NASA Astrophysics Data System (ADS)

Prathipati, Philip; Nagao, Chioko; Ahmad, Shandar; Mizuguchi, Kenji

2016-09-01

The D3R 2015 grand drug design challenge provided a set of blinded challenges for evaluating the applicability of our protocols for pose and affinity prediction. In the present study, we report the application of two different strategies for the two D3R protein targets HSP90 and MAP4K4. HSP90 is a well-studied target system with numerous co-crystal structures and SAR data. Furthermore the D3R HSP90 test compounds showed high structural similarity to existing HSP90 inhibitors in BindingDB. Thus, we adopted an integrated docking and scoring approach involving a combination of both pharmacophoric and heavy atom similarity alignments, local minimization and quantitative structure activity relationships modeling, resulting in the reasonable prediction of pose [with the root mean square deviation (RMSD) values of 1.75 Å for mean pose 1, 1.417 Å for the mean best pose and 1.85 Å for the mean all poses] and affinity (ROC AUC = 0.702 at 7.5 pIC50 cut-off and R = 0.45 for 180 compounds). The second protein, MAP4K4, represents a novel system with limited SAR and co-crystal structure data and little structural similarity of the D3R MAP4K4 test compounds to known MAP4K4 ligands. For this system, we implemented an exhaustive pose and affinity prediction protocol involving docking and scoring using the PLANTS software which considers side chain flexibility together with protein-ligand fingerprints analysis assisting in pose prioritization. This protocol through fares poorly in pose prediction (with the RMSD values of 4.346 Å for mean pose 1, 4.69 Å for mean best pose and 4.75 Å for mean all poses) and produced reasonable affinity prediction (AUC = 0.728 at 7.5 pIC50 cut-off and R = 0.67 for 18 compounds, ranked 1st among 80 submissions).

Groundwater and human development: challenges and opportunities in livelihoods and environment.

PubMed

Shah, T

2005-01-01

At less than 1000 km3/year, the world's annual use of groundwater is 1.5% of renewable water resource but contributes a lion's share of water-induced human welfare. Global groundwater use however has increased manifold in the past 50 years; and the human race has never had to manage groundwater use on such a large scale. Sustaining the massive welfare gains groundwater development has created without ruining the resource is a key water challenge facing the world today. In exploring this challenge, we have focused a good deal on conditions of resource occurrence but less so on resource use. I offer a typology of five groundwater demand systems as Groundwater Socio-ecologies (GwSE), each embodying a unique pattern of interactions between socio-economic and ecological variables, and each facing a distinct groundwater governance challenge. During the past century, a growing corpus of experiential knowledge has accumulated in the industrialized world on managing groundwater in various uses and contexts. A daunting global groundwater issue today is to apply this knowledge intelligently to by far the more formidable challenge that has arisen in developing regions of Asia and Africa, where groundwater irrigation has evolved into a colossal anarchy supporting billions of livelihoods but threatening the resource itself.

Cockpit Accommodation Assessment of the Bell 412CF Helicopter (Evaluation du Poste de Pilotage de l’Hellcoptere Bell 412CF)

DTIC Science & Technology

2009-12-01

Research, Ottawa , 1998 as issued jointly by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada...Flight Rules ) skills. Nine Bell 412CF helicopters were produced from existing CH-146 Griffons, which posed technical challenges. One such compromise was...IFR (Instrument Flight Rules ) skills. Nine Bell 412CF helicopters were produced from existing CH-146 Griffons, which posed technical challenges. One

The Dragonian Subsurface Abyss and Submarine Force’s Ability to Counter the Rising Threat

DTIC Science & Technology

2013-05-23

large expanse of the Pacific while helping to turn China’s navy into one of the world’s most formidable blue water forces. Planned reductions in...most formidable blue water forces. While the U.S. joint force operates many platforms that can contend with various elements of China’s anti...shores of Chinese claimed territory. With a long-term vision in mind, Beijing has openly affirmed intentions to shift to a global, blue -water navy

Single leg balancing in ballet: effects of shoe conditions and poses.

PubMed

Lobo da Costa, Paula H; Azevedo Nora, Fernanda G S; Vieira, Marcus Fraga; Bosch, Kerstin; Rosenbaum, Dieter

2013-03-01

The purpose of this study was to describe the effects of lower limb positioning and shoe conditions on stability levels of selected single leg ballet poses performed in demi-pointe position. Fourteen female non-professional ballet dancers (mean age of 18.4±2.8 years and mean body mass index of 21.5±2.8kg/m(2)) who had practiced ballet for at least seven years, without any musculoskeletal impairment volunteered to participate in this study. A capacitive pressure platform allowed for the assessment of center of pressure variables related to the execution of three single leg ballet poses in demi pointé position: attitude devant, attitude derriére, and attitude a la second. Peak pressures, contact areas, COP oscillation areas, anterior-posterior and medio-lateral COP oscillations and velocities were compared between two shoe conditions (barefoot versus slippers) and among the different poses. Barefoot performances produced more stable poses with significantly higher plantar contact areas, smaller COP oscillation areas and smaller anterior-posterior COP oscillations. COP oscillation areas, anterior-posterior COP oscillations and medio-lateral COP velocities indicated that attitude a la second is the least challenging and attitude derriére the most challenging pose. Copyright © 2012 Elsevier B.V. All rights reserved.

Global Climate Change and the Mitigation Challenge

EPA Science Inventory

Book edited by Frank Princiotta titled Global Climate Change--The Technology Challenge Transparent modeling tools and the most recent literature are used, to quantify the challenge posed by climate change and potential technological remedies. The chapter examines forces driving ...

Predicting the affinity of Farnesoid X Receptor ligands through a hierarchical ranking protocol: a D3R Grand Challenge 2 case study

NASA Astrophysics Data System (ADS)

Réau, Manon; Langenfeld, Florent; Zagury, Jean-François; Montes, Matthieu

2018-01-01

The Drug Design Data Resource (D3R) Grand Challenges are blind contests organized to assess the state-of-the-art methods accuracy in predicting binding modes and relative binding free energies of experimentally validated ligands for a given target. The second stage of the D3R Grand Challenge 2 (GC2) was focused on ranking 102 compounds according to their predicted affinity for Farnesoid X Receptor. In this task, our workflow was ranked 5th out of the 77 submissions in the structure-based category. Our strategy consisted in (1) a combination of molecular docking using AutoDock 4.2 and manual edition of available structures for binding poses generation using SeeSAR, (2) the use of HYDE scoring for pose selection, and (3) a hierarchical ranking using HYDE and MM/GBSA. In this report, we detail our pose generation and ligands ranking protocols and provide guidelines to be used in a prospective computer aided drug design program.

Will learning to solve one-step equations pose a challenge to 8th grade students?

NASA Astrophysics Data System (ADS)

Ngu, Bing Hiong; Phan, Huy P.

2017-08-01

Assimilating multiple interactive elements simultaneously in working memory to allow understanding to occur, while solving an equation, would impose a high cognitive load. Element interactivity arises from the interaction between elements within and across operational and relational lines. Moreover, operating with special features (e.g. negative pronumeral) poses additional challenge to master equation solving skills. In an experiment, 41 8th grade students (girls = 16, boys = 25) sat for a pre-test, attended a session about equation solving, completed an acquisition phase which constituted the main intervention and were tested again in a post-test. The results showed that at post-test, students performed better on one-step equations tapping low rather than high element interactivity knowledge. In addition, students performed better on those one-step equations that contained no special features. Thus, both the degree of element interactivity and the operation with special features affect the challenge posed to 8th grade students on learning how to solve one-step equations.

A review of cooperative and uncooperative spacecraft pose determination techniques for close-proximity operations

NASA Astrophysics Data System (ADS)

Opromolla, Roberto; Fasano, Giancarmine; Rufino, Giancarlo; Grassi, Michele

2017-08-01

The capability of an active spacecraft to accurately estimate its relative position and attitude (pose) with respect to an active/inactive, artificial/natural space object (target) orbiting in close-proximity is required to carry out various activities like formation flying, on-orbit servicing, active debris removal, and space exploration. According to the specific mission scenario, the pose determination task involves both theoretical and technological challenges related to the search for the most suitable algorithmic solution and sensor architecture, respectively. As regards the latter aspect, electro-optical sensors represent the best option as their use is compatible with mass and power limitation of micro and small satellites, and their measurements can be processed to estimate all the pose parameters. Overall, the degree of complexity of the challenges related to pose determination largely varies depending on the nature of the targets, which may be actively/passively cooperative, uncooperative but known, or uncooperative and unknown space objects. In this respect, while cooperative pose determination has been successfully demonstrated in orbit, the uncooperative case is still under study by universities, research centers, space agencies and private companies. However, in both the cases, the demand for space applications involving relative navigation maneuvers, also in close-proximity, for which pose determination capabilities are mandatory, is significantly increasing. In this framework, a review of state-of-the-art techniques and algorithms developed in the last decades for cooperative and uncooperative pose determination by processing data provided by electro-optical sensors is herein presented. Specifically, their main advantages and drawbacks in terms of achieved performance, computational complexity, and sensitivity to variability of pose and target geometry, are highlighted.

Docking pose selection by interaction pattern graph similarity: application to the D3R grand challenge 2015

NASA Astrophysics Data System (ADS)

Slynko, Inna; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

2016-09-01

High affinity ligands for a given target tend to share key molecular interactions with important anchoring amino acids and therefore often present quite conserved interaction patterns. This simple concept was formalized in a topological knowledge-based scoring function (GRIM) for selecting the most appropriate docking poses from previously X-rayed interaction patterns. GRIM first converts protein-ligand atomic coordinates (docking poses) into a simple 3D graph describing the corresponding interaction pattern. In a second step, proposed graphs are compared to that found from template structures in the Protein Data Bank. Last, all docking poses are rescored according to an empirical score (GRIMscore) accounting for overlap of maximum common subgraphs. Taking the opportunity of the public D3R Grand Challenge 2015, GRIM was used to rescore docking poses for 36 ligands (6 HSP90α inhibitors, 30 MAP4K4 inhibitors) prior to the release of the corresponding protein-ligand X-ray structures. When applied to the HSP90α dataset, for which many protein-ligand X-ray structures are already available, GRIM provided very high quality solutions (mean rmsd = 1.06 Å, n = 6) as top-ranked poses, and significantly outperformed a state-of-the-art scoring function. In the case of MAP4K4 inhibitors, for which preexisting 3D knowledge is scarce and chemical diversity is much larger, the accuracy of GRIM poses decays (mean rmsd = 3.18 Å, n = 30) although GRIM still outperforms an energy-based scoring function. GRIM rescoring appears to be quite robust with comparison to the other approaches competing for the same challenge (42 submissions for the HSP90 dataset, 27 for the MAP4K4 dataset) as it ranked 3rd and 2nd respectively, for the two investigated datasets. The rescoring method is quite simple to implement, independent on a docking engine, and applicable to any target for which at least one holo X-ray structure is available.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling

NASA Astrophysics Data System (ADS)

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling.

PubMed

Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

2018-01-01

Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

Recovery of large carnivores in Europe's modern human-dominated landscapes.

PubMed

Chapron, Guillaume; Kaczensky, Petra; Linnell, John D C; von Arx, Manuela; Huber, Djuro; Andrén, Henrik; López-Bao, José Vicente; Adamec, Michal; Álvares, Francisco; Anders, Ole; Balčiauskas, Linas; Balys, Vaidas; Bedő, Péter; Bego, Ferdinand; Blanco, Juan Carlos; Breitenmoser, Urs; Brøseth, Henrik; Bufka, Luděk; Bunikyte, Raimonda; Ciucci, Paolo; Dutsov, Alexander; Engleder, Thomas; Fuxjäger, Christian; Groff, Claudio; Holmala, Katja; Hoxha, Bledi; Iliopoulos, Yorgos; Ionescu, Ovidiu; Jeremić, Jasna; Jerina, Klemen; Kluth, Gesa; Knauer, Felix; Kojola, Ilpo; Kos, Ivan; Krofel, Miha; Kubala, Jakub; Kunovac, Saša; Kusak, Josip; Kutal, Miroslav; Liberg, Olof; Majić, Aleksandra; Männil, Peep; Manz, Ralph; Marboutin, Eric; Marucco, Francesca; Melovski, Dime; Mersini, Kujtim; Mertzanis, Yorgos; Mysłajek, Robert W; Nowak, Sabina; Odden, John; Ozolins, Janis; Palomero, Guillermo; Paunović, Milan; Persson, Jens; Potočnik, Hubert; Quenette, Pierre-Yves; Rauer, Georg; Reinhardt, Ilka; Rigg, Robin; Ryser, Andreas; Salvatori, Valeria; Skrbinšek, Tomaž; Stojanov, Aleksandar; Swenson, Jon E; Szemethy, László; Trajçe, Aleksandër; Tsingarska-Sedefcheva, Elena; Váňa, Martin; Veeroja, Rauno; Wabakken, Petter; Wölfl, Manfred; Wölfl, Sybille; Zimmermann, Fridolin; Zlatanova, Diana; Boitani, Luigi

2014-12-19

The conservation of large carnivores is a formidable challenge for biodiversity conservation. Using a data set on the past and current status of brown bears (Ursus arctos), Eurasian lynx (Lynx lynx), gray wolves (Canis lupus), and wolverines (Gulo gulo) in European countries, we show that roughly one-third of mainland Europe hosts at least one large carnivore species, with stable or increasing abundance in most cases in 21st-century records. The reasons for this overall conservation success include protective legislation, supportive public opinion, and a variety of practices making coexistence between large carnivores and people possible. The European situation reveals that large carnivores and people can share the same landscape. Copyright © 2014, American Association for the Advancement of Science.

Type 1 diabetes: prospective cohort studies for identification of the environmental trigger.

PubMed

Rønningen, Kjersti S

2013-12-01

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way-the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D.

Guns, Mental Illness, and the Law: Introduction to This Issue.

PubMed

Swanson, Jeffrey W; Felthous, Alan R

2015-06-01

Firearm violence is a top-tier public health problem in the U.S., killing 33,563 and injuring an additional 81,396 people in 2012 (Centers for Disease Control and Prevention, CDC, ). Given constitutional protection and the cultural entrenchment of private gun ownership in the U.S., it is likely that guns will remain widely accessible--and largely unrestricted--for the foreseeable future. Therefore, most policies and laws intended to reduce firearm violence focus selectively on preventing "dangerous people" from having access to guns. That is a formidable challenge. How do we think productively about guns and mental illness in this context, and about the role of law in lessening the toll of gun violence? Copyright © 2015 John Wiley & Sons, Ltd.

Hematopoietic stem cell engineering at a crossroads.

PubMed

Rivière, Isabelle; Dunbar, Cynthia E; Sadelain, Michel

2012-02-02

The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.

Low-latency situational awareness for UxV platforms

NASA Astrophysics Data System (ADS)

Berends, David C.

2012-06-01

Providing high quality, low latency video from unmanned vehicles through bandwidth-limited communications channels remains a formidable challenge for modern vision system designers. SRI has developed a number of enabling technologies to address this, including the use of SWaP-optimized Systems-on-a-Chip which provide Multispectral Fusion and Contrast Enhancement as well as H.264 video compression. Further, the use of salience-based image prefiltering prior to image compression greatly reduces output video bandwidth by selectively blurring non-important scene regions. Combined with our customization of the VLC open source video viewer for low latency video decoding, SRI developed a prototype high performance, high quality vision system for UxV application in support of very demanding system latency requirements and user CONOPS.

The Business of Trust.

PubMed

Frisse, Mark E

2016-04-01

New mobile devices, social networks, analytics, and communications technologies are emerging at an unparalleled rate. As a result, academic health centers will face both new opportunities and formidable challenges. Unlike previous transitions from paper-based systems to networked computer systems, these new technologies are the product of new entrepreneurial and commercial interests driven by consumers. As these new commercial products and services are more widely adopted, the likelihood grows that data will be used in unanticipated ways inconsistent with societal norms. Academic health centers will have to understand the implications of these technologies and engage more actively in processes governing the collection, aggregation, and use of health data produced in a new era of consumer-driven health care technology. Maintaining public trust should be a paramount concern.

Tuning near field radiative heat flux through surface excitations with a metal insulator transition.

PubMed

van Zwol, P J; Ranno, L; Chevrier, J

2012-06-08

The control of heat flow is a formidable challenge due to lack of good thermal insulators. Promising new opportunities for heat flow control were recently theoretically discovered for radiative heat flow in near field, where large heat flow contrasts may be achieved by tuning electronic excitations on surfaces. Here we show experimentally that the phase transition of VO2 entails a change of surface polariton states that significantly affects radiative heat transfer in near field. In all cases the Derjaguin approximation correctly predicted radiative heat transfer in near field, but it underestimated the far field limit. Our results indicate that heat flow contrasts can be realized in near field that can be larger than those obtained in far field.

Silver-Catalyzed [2+1] Cyclopropenation of Alkynes with Unstable Diazoalkanes: N-Nosylhydrazones as Room-Temperature Decomposable Diazo Surrogates.

PubMed

Liu, Zhaohong; Li, Qiangqiang; Liao, Peiqiu; Bi, Xihe

2017-04-06

The [2+1] cycloaddition of alkynes with diazo compounds represents one of the most powerful and reliable methods for the construction of cyclopropenes. However, it remains a formidable challenge to accomplish the cyclopropenation of alkynes with non-stabilized diazoalkanes, owing to the fact that such compounds are unstable and prone to detonation. Herein, we report a general silver-catalyzed cyclopropenation reaction of alkynes with unstable diazoalkanes, by for the first time the discovery and application of N-nosylhydrazones as room-temperature decomposiable diazo surrogates. This method allows for the efficient assembly a wide variety of cyclopropene derivatives that are otherwise difficult to access by conventional methods. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adult Literacy in Africa: The Push and Pull Factors

NASA Astrophysics Data System (ADS)

Omolewa, Michael

2008-11-01

This paper examines the question of why Africa has made such slow progress towards the goal of eradicating illiteracy, and why it remains an exceptionally disadvantaged region in this respect. The article surveys the history of the development of literacy in Africa from colonial times to the present day, focusing on the role of adult education in pursuing the goal of universal literacy. The author seeks to identify both the "push" factors (those favouring the pursuit of this goal) and the "pull" factors (the obstacles and hindrances), examining these factors at the local, national and international levels. The author concludes that, while the literacy challenge in Africa remains a formidable one, there are examples of successful initiatives that give hope for the future.

Stray light rejection in giant externally-occulted solar coronagraphs: experimental developments

NASA Astrophysics Data System (ADS)

Venet, M.; Bazin, C.; Koutchmy, S.; Lamy, P.

2017-11-01

The advent of giant, formation-flight, externally-occulted solar coronagraphs such as ASPIICS (Association de Satellites Pour l'Imagerie et l'Interférométrie de la Couronne Solaire [1,2,3,4]) selected by the European Space Agency (ESA) for its third PROBA (Project for On-Board Autonomy) mission of formation flying demonstration (presently in phase B) and Hi-RISE proposed in the framework of ESA Cosmic Vision program, presents formidable challenges for the study and calibration of instrumental stray light. With distances between the external occulter (EO) and the optical pupil (OP) exceeding hundred meters and occulter sizes larger than a meter, it becomes impossible to perform tests at the real scale. The requirement to limit the over-occultation to less than 1.05 Rsun, orders of magnitude to what has been achieved so far in past coronagraphs, further adds to the challenge. We are approaching the problem experimentally using reduced scale simulators and present below a progress report of our work.

Applications of XPS in the characterization of Battery materials

DOE PAGES

Shutthanandan, Vaithiyalingam; Nandasiri, Manjula; Zheng, Jianming; ...

2018-05-26

In this study, technological development requires reliable power sources where energy storage devices are emerging as a critical component. Wide range of energy storage devices, Redox-flow batteries (RFB), Lithium ion based batteries (LIB), and Lithium-sulfur (LSB) batteries are being developed for various applications ranging from grid-scale level storage to mobile electronics. Material complexities associated with these energy storage devices with unique electrochemistry are formidable challenge which needs to be address for transformative progress in this field. X-ray photoelectron spectroscopy (XPS) - a powerful surface analysis tool - has been widely used to study these energy storage materials because of itsmore » ability to identify, quantify and image the chemical distribution of redox active species. However, accessing the deeply buried solid-electrolyte interfaces (which dictates the performance of energy storage devices) has been a challenge in XPS usage. Herein we report our recent efforts to utilize the XPS to gain deep insight about these interfaces under realistic conditions with varying electrochemistry involving RFB, LIB and LSB.« less

Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis.

PubMed

Williams, Alex H; Kim, Tony Hyun; Wang, Forea; Vyas, Saurabh; Ryu, Stephen I; Shenoy, Krishna V; Schnitzer, Mark; Kolda, Tamara G; Ganguli, Surya

2018-06-27

Perceptions, thoughts, and actions unfold over millisecond timescales, while learned behaviors can require many days to mature. While recent experimental advances enable large-scale and long-term neural recordings with high temporal fidelity, it remains a formidable challenge to extract unbiased and interpretable descriptions of how rapid single-trial circuit dynamics change slowly over many trials to mediate learning. We demonstrate a simple tensor component analysis (TCA) can meet this challenge by extracting three interconnected, low-dimensional descriptions of neural data: neuron factors, reflecting cell assemblies; temporal factors, reflecting rapid circuit dynamics mediating perceptions, thoughts, and actions within each trial; and trial factors, describing both long-term learning and trial-to-trial changes in cognitive state. We demonstrate the broad applicability of TCA by revealing insights into diverse datasets derived from artificial neural networks, large-scale calcium imaging of rodent prefrontal cortex during maze navigation, and multielectrode recordings of macaque motor cortex during brain machine interface learning. Copyright © 2018 Elsevier Inc. All rights reserved.

Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects.

PubMed

Kublin, James G; Mikolajczak, Sebastian A; Sack, Brandon K; Fishbaugher, Matt E; Seilie, Annette; Shelton, Lisa; VonGoedert, Tracie; Firat, Melike; Magee, Sara; Fritzen, Emma; Betz, Will; Kain, Heather S; Dankwa, Dorender A; Steel, Ryan W J; Vaughan, Ashley M; Noah Sather, D; Murphy, Sean C; Kappe, Stefan H I

2017-01-04

Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52 - /p36 - /sap1 - ). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain. Copyright © 2017, American Association for the Advancement of Science.

Facile synthesis of ultrahigh-surface-area hollow carbon nanospheres for enhanced adsorption and energy storage

PubMed Central

Xu, Fei; Tang, Zhiwei; Huang, Siqi; Chen, Luyi; Liang, Yeru; Mai, Weicong; Zhong, Hui; Fu, Ruowen; Wu, Dingcai

2015-01-01

Exceptionally large surface area and well-defined nanostructure are both critical in the field of nanoporous carbons for challenging energy and environmental issues. The pursuit of ultrahigh surface area while maintaining definite nanostructure remains a formidable challenge because extensive creation of pores will undoubtedly give rise to the damage of nanostructures, especially below 100 nm. Here we report that high surface area of up to 3,022 m2 g−1 can be achieved for hollow carbon nanospheres with an outer diameter of 69 nm by a simple carbonization procedure with carefully selected carbon precursors and carbonization conditions. The tailor-made pore structure of hollow carbon nanospheres enables target-oriented applications, as exemplified by their enhanced adsorption capability towards organic vapours, and electrochemical performances as electrodes for supercapacitors and sulphur host materials for lithium–sulphur batteries. The facile approach may open the doors for preparation of highly porous carbons with desired nanostructure for numerous applications. PMID:26072734

Applications of XPS in the characterization of Battery materials

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

Shutthanandan, Vaithiyalingam; Nandasiri, Manjula; Zheng, Jianming

In this study, technological development requires reliable power sources where energy storage devices are emerging as a critical component. Wide range of energy storage devices, Redox-flow batteries (RFB), Lithium ion based batteries (LIB), and Lithium-sulfur (LSB) batteries are being developed for various applications ranging from grid-scale level storage to mobile electronics. Material complexities associated with these energy storage devices with unique electrochemistry are formidable challenge which needs to be address for transformative progress in this field. X-ray photoelectron spectroscopy (XPS) - a powerful surface analysis tool - has been widely used to study these energy storage materials because of itsmore » ability to identify, quantify and image the chemical distribution of redox active species. However, accessing the deeply buried solid-electrolyte interfaces (which dictates the performance of energy storage devices) has been a challenge in XPS usage. Herein we report our recent efforts to utilize the XPS to gain deep insight about these interfaces under realistic conditions with varying electrochemistry involving RFB, LIB and LSB.« less

A research agenda for aging in China in the 21st century

PubMed Central

Fang, Evandro Fei; Scheibye-Knudsen, Morten; Jahn, Heiko J.; Li, Juan; Ling, Li; Guo, Hongwei; Zhu, Xinqiang; Preedy, Victor; Lu, Huiming; Bohr, Vilhelm A.; Chan, Wai Yee; Liu, Yuanli; Ng, Tzi Bun

2016-01-01

China is encountering formidable healthcare challenges brought about by the problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+, 150 million of whom will be 80+. The undesirable consequences of the one-child policy, rural-to-urban migration, and expansion of the population of ‘empty nest ’ elders are eroding the traditional family care of the elders, further exacerbating the burden borne by the current public healthcare system. The challenges of geriatric care demand prompt attention by proposing strategies for improvement in several key areas. Major diseases of the elderly that need more attention include chronic non-communicable diseases and mental health disorders. We suggest the establishment of a home care-dominated geriatric care system, and a proactive role for researchers on aging in reforming geriatric care through policy dialogs. We propose ideas for preparation of the impending aging burden and the creation of a nurturing environment conducive to healthy aging in China. PMID:26304837

Localizing Global Medicine: Challenges and Opportunities in Cervical Screening in an Indigenous Community in Ecuador.

PubMed

Nugus, Peter; Désalliers, Julie; Morales, Juana; Graves, Lisa; Evans, Andrea; Macaulay, Ann C

2018-04-01

This participatory research study examines the tensions and opportunities in accessing allopathic medicine, or biomedicine, in the context of a cervical cancer screening program in a rural indigenous community of Northern Ecuador. Focusing on the influence of social networks, the article extends research on "re-appropriation" of biomedicine. It does so by recognizing two competing tensions expressed through social interactions: suspicion of allopathic medicine and the desire to maximize one's health. Semistructured individual interviews and focus groups were conducted with 28 women who had previously participated in a government-sponsored cervical screening program. From inductive thematic analysis, the article traces these women's active agency in navigating coherent paths of health. Despite drawing on social networks to overcome formidable challenges, the participants faced enduring system obstacles-the organizational effects of the networks of allopathic medicine. Such obstacles need to be understood to reconcile competing knowledge systems and improve health care access in underresourced communities.

Plant-based FRET biosensor discriminates enviornmental zinc levels

USDA-ARS?s Scientific Manuscript database

Heavy metal accumulation in the environment poses great risks to flora and fauna. However, monitoring sites prone to accumulation poses scale and economic challenges. In this study, we present and test a method for monitoring these sites using fluorescent resonance energy transfer (FRET) change in r...

Security, development and human rights: normative, legal and policy challenges for the international drug control system.

PubMed

Barrett, Damon

2010-03-01

This commentary addresses some of the challenges posed by the broader normative, legal and policy framework of the United Nations for the international drug control system. The 'purposes and principles' of the United Nations are presented and set against the threat based rhetoric of the drug control system and the negative consequences of that system. Some of the challenges posed by human rights law and norms to the international drug control system are also described, and the need for an impact assessment of the current system alongside alternative policy options is highlighted as a necessary consequence of these analyses. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Leadership challenges in multinational medical peacekeeping operations: Lessons from UNIFIL Hospital.

PubMed

Datta, Rakesh; Khanna, Sangeeta

2017-10-01

Commanding a military multinational and multilingual healthcare facility can be a formidable task with very little margin for error. The authors were in leadership positions of UNIFIL Hospital, unique in its diversity of both staff and clientele. Experience about the challenges faced and methods adopted to overcome them will be shared. Troops from diverse backgrounds differ in their competency, and also in their attitudinal approach to situations. It is imperative for the medical commanders to identify these differences, and work towards harnessing individual strengths to form a cohesive unit. Frequent rotation of team members and thereby difficulty in adapting to new environment makes the tasks more challenging. Challenges can be broadly categorized in those dealing with functional roles (providing medical support) and command and control issues. Linguistic challenges especially in situations where professionals have to work as a coordinated unit remains a major challenge. The threat of medical errors arising out of misunderstandings is very real. Gender sensitization is essential to avoid potential unpleasant situations. Interpersonal conflict can easily go out of hand. The leadership has to be more direct and deliberate relying less on hierarchy and more on direct communication. A strict enforcement of UN standards for equipment and competence, frequent joint medical drills help to overcome interoperability issues and develop mutual confidence. Leadership in multinational UN hospitals is a demanding task with its peculiar set of challenges. A systematic and deliberate approach focused on mutual respect, flexibility and direct leadership can help medical commanders in such situations.

Intercollegiate Athletics Today and Tomorrow: The President's Challenge

ERIC Educational Resources Information Center

Hanford, George H.

1977-01-01

Colleges and university presidents must come to terms with the challenges posed by intercollegiate athletics. The author offers concrete ideas and suggestions aimed at breaking through the confusion surrounding intercollegiate athletics. (Editor/LBH)

Strategies to improve learning of all students in a class

NASA Astrophysics Data System (ADS)

Suraishkumar, G. K.

2018-05-01

The statistical distribution of the student learning abilities in a typical undergraduate engineering class poses a significant challenge to simultaneously improve the learning of all the students in the class. With traditional instruction styles, the students with significantly high learning abilities are not satisfied due to a feeling of unfulfilled potential, and the students with significantly low learning abilities feel lost. To address the challenge in an undergraduate core/required course on 'transport phenomena in biological systems', a combination of learning strategies such as active learning including co-operative group learning, challenge exercises, and others were employed in a pro-advising context. The short-term and long-term impacts were evaluated through student course performances and input, respectively. The results show that it is possible to effectively address the challenge posed by the distribution of student learning abilities in a class.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Feasibility of Applying Clean Development Mechanism and GHGs Emission Reductions in the Gold Mining Industry: A Case of Thailand

NASA Astrophysics Data System (ADS)

Kittipongvises, Suthirat

2015-12-01

There is presently overwhelming scientific consensus that global climate change is indeed occurring, and that human activities are the primary driver. An increasingly resource and carbon constrained world will continue to pose formidable challenges to major industries, including mining. Understanding the implications of climate change mitigation for the mining industry, however, remains limited. This paper presents the results of a feasibility study on the implementation of a clean development mechanism and greenhouse gases (GHGs) emission reductions in the gold mining industry. It draws upon and extends the analysis of a case study conducted on gold mining operations in Thailand. The results from the case study indicated that total GHGs emissions by company A were approximately 36,886 tons carbon dioxide equivalents (tCO2e) per annual gold production capacity that meet the eligibility criteria for small-scaled clean development mechanism (CDM) projects. The electrostatic separation process was found to release the lowest amount of GHGs, whereas comminution (i.e. crushing and grinding) generated the highest GHGs emissions. By scope, the emission from purchased electricity (scope 2) is the most significant source. Opportunities for CDM projects implementation in the gold mining sector can be found in employing energy efficiency measures. Through innovation, some technical efficiency and technological development in gold processing (i.e. high pressure grinding rolls (HPGR), vertical roller mills (VRM), gravity pre-concentration and microwave heating technologies) that have the potential to reduce energy use and also lower carbon footprint of the gold mining were further discussed. The evidence reviews found that HPGR and VRM abatement technologies have shown energy and climate benefits as electricity savings and CO2 reduction of about 8-25.93 kWh/ton ore processed and 1.8-26.66 kgCO2/ton ore processed, respectively. Implications for further research and practice were finally raised.

A cDNA Immunization Strategy to Generate Nanobodies against Membrane Proteins in Native Conformation

PubMed Central

Eden, Thomas; Menzel, Stephan; Wesolowski, Janusz; Bergmann, Philine; Nissen, Marion; Dubberke, Gudrun; Seyfried, Fabienne; Albrecht, Birte; Haag, Friedrich; Koch-Nolte, Friedrich

2018-01-01

Nanobodies (Nbs) are soluble, versatile, single-domain binding modules derived from the VHH variable domain of heavy-chain antibodies naturally occurring in camelids. Nbs hold huge promise as novel therapeutic biologics. Membrane proteins are among the most interesting targets for therapeutic Nbs because they are accessible to systemically injected biologics. In order to be effective, therapeutic Nbs must recognize their target membrane protein in native conformation. However, raising Nbs against membrane proteins in native conformation can pose a formidable challenge since membrane proteins typically contain one or more hydrophobic transmembrane regions and, therefore, are difficult to purify in native conformation. Here, we describe a highly efficient genetic immunization strategy that circumvents these difficulties by driving expression of the target membrane protein in native conformation by cells of the immunized camelid. The strategy encompasses ballistic transfection of skin cells with cDNA expression plasmids encoding one or more orthologs of the membrane protein of interest and, optionally, other costimulatory proteins. The plasmid is coated onto 1 µm gold particles that are then injected into the shaved and depilated skin of the camelid. A gene gun delivers a helium pulse that accelerates the DNA-coated particles to a velocity sufficient to penetrate through multiple layers of cells in the skin. This results in the exposure of the extracellular domains of the membrane protein on the cell surface of transfected cells. Repeated immunization drives somatic hypermutation and affinity maturation of target-specific heavy-chain antibodies. The VHH/Nb coding region is PCR-amplified from B cells obtained from peripheral blood or a lymph node biopsy. Specific Nbs are selected by phage display or by screening of Nb-based heavy-chain antibodies expressed as secretory proteins in transfected HEK cells. Using this strategy, we have successfully generated agonistic and antagonistic Nbs against several cell surface ecto-enzymes and ligand-gated ion channels. PMID:29410663

Interventions to significantly improve service uptake and retention of HIV-positive pregnant women and HIV-exposed infants along the prevention of mother-to-child transmission continuum of care: systematic review.

PubMed

Vrazo, Alexandra C; Firth, Jacqueline; Amzel, Anouk; Sedillo, Rebecca; Ryan, Julia; Phelps, B Ryan

2018-02-01

Despite the success of Prevention of Mother-to-Child Transmission of HIV (PMTCT) programmes, low uptake of services and poor retention pose a formidable challenge to achieving the elimination of vertical HIV transmission in low- and middle-income countries. This systematic review summarises interventions that demonstrate statistically significant improvements in service uptake and retention of HIV-positive pregnant and breastfeeding women and their infants along the PMTCT cascade. Databases were systematically searched for peer-reviewed studies. Outcomes of interest included uptake of services, such as antiretroviral therapy (ART) such as initiation, early infant diagnostic testing, and retention of HIV-positive pregnant and breastfeeding women and their infants. Interventions that led to statistically significant outcomes were included and mapped to the PMTCT cascade. An eight-item assessment tool assessed study rigour. CRD42017063816. Of 686 citations reviewed, 11 articles met inclusion criteria. Ten studies detailed maternal outcomes and seven studies detailed infant outcomes in PMTCT programmes. Interventions to increase access to antenatal care (ANC) and ART services (n = 4) and those using lay cadres (n = 3) were most common. Other interventions included quality improvement (n = 2), mHealth (n = 1), and counselling (n = 1). One study described interventions in an Option B+ programme. Limitations included lack of HIV testing and counselling and viral load monitoring outcomes, small sample size, geographical location, and non-randomized assignment and selection of participants. Interventions including ANC/ART integration, family-centred approaches, and the use of lay healthcare providers are demonstrably effective in increasing service uptake and retention of HIV-positive mothers and their infants in PMTCT programmes. Future studies should include control groups and assess whether interventions developed in the context of earlier 'Options' are effective in improving outcomes in Option B+ programmes. © 2017 John Wiley & Sons Ltd.

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury. PMID:27830790

D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies

NASA Astrophysics Data System (ADS)

Gaieb, Zied; Liu, Shuai; Gathiaka, Symon; Chiu, Michael; Yang, Huanwang; Shao, Chenghua; Feher, Victoria A.; Walters, W. Patrick; Kuhn, Bernd; Rudolph, Markus G.; Burley, Stephen K.; Gilson, Michael K.; Amaro, Rommie E.

2018-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.

Promises and challenges in solid-state lighting

NASA Astrophysics Data System (ADS)

Schubert, Fred

2010-03-01

Lighting technologies based on semiconductor light-emitting diodes (LEDs) offer unprecedented promises that include three major benefits: (i) Gigantic energy savings enabled by efficient conversion of electrical energy to optical energy; (ii) Substantial positive contributions to sustainability through reduced emissions of global-warming gases, acid-rain gases, and toxic substances such as mercury; and (iii) The creation of new paradigms in lighting driven by the unique controllability of solid-state lighting sources. Due to the powerful nature of these benefits, the transition from conventional lighting sources to solid-state lighting is virtually assured. This presentation will illustrate the new world of lighting and illustrate the pervasive changes to be expected in lighting, displays, communications, and biotechnology. The presentation will also address the formidable challenges that must be addressed to continue the further advancement of solid-state lighting technology. These challenges offer opportunities for research and innovation. Specific challenges include light management, carrier transport, and optical design. We will present some innovative approaches in order to solve known technical challenges faced by solid-state lighting. These approaches include the demonstration and use of new optical thin-film materials with a continuously tunable refractive index. These approaches also include the use of polarization-matched structures that reduce the polarization fields in GaInN LEDs and the hotly debated efficiency droop, that is, the decreasing LED efficiency at high currents.

Application of infrared thermography in computer aided diagnosis

NASA Astrophysics Data System (ADS)

Faust, Oliver; Rajendra Acharya, U.; Ng, E. Y. K.; Hong, Tan Jen; Yu, Wenwei

2014-09-01

The invention of thermography, in the 1950s, posed a formidable problem to the research community: What is the relationship between disease and heat radiation captured with Infrared (IR) cameras? The research community responded with a continuous effort to find this crucial relationship. This effort was aided by advances in processing techniques, improved sensitivity and spatial resolution of thermal sensors. However, despite this progress fundamental issues with this imaging modality still remain. The main problem is that the link between disease and heat radiation is complex and in many cases even non-linear. Furthermore, the change in heat radiation as well as the change in radiation pattern, which indicate disease, is minute. On a technical level, this poses high requirements on image capturing and processing. On a more abstract level, these problems lead to inter-observer variability and on an even more abstract level they lead to a lack of trust in this imaging modality. In this review, we adopt the position that these problems can only be solved through a strict application of scientific principles and objective performance assessment. Computing machinery is inherently objective; this helps us to apply scientific principles in a transparent way and to assess the performance results. As a consequence, we aim to promote thermography based Computer-Aided Diagnosis (CAD) systems. Another benefit of CAD systems comes from the fact that the diagnostic accuracy is linked to the capability of the computing machinery and, in general, computers become ever more potent. We predict that a pervasive application of computers and networking technology in medicine will help us to overcome the shortcomings of any single imaging modality and this will pave the way for integrated health care systems which maximize the quality of patient care.

Tissue polarimetry: concepts, challenges, applications, and outlook.

PubMed

Ghosh, Nirmalya; Vitkin, I Alex

2011-11-01

Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.

Manufacturing and Security Challenges in 3D Printing

NASA Astrophysics Data System (ADS)

Zeltmann, Steven Eric; Gupta, Nikhil; Tsoutsos, Nektarios Georgios; Maniatakos, Michail; Rajendran, Jeyavijayan; Karri, Ramesh

2016-07-01

As the manufacturing time, quality, and cost associated with additive manufacturing (AM) continue to improve, more and more businesses and consumers are adopting this technology. Some of the key benefits of AM include customizing products, localizing production and reducing logistics. Due to these and numerous other benefits, AM is enabling a globally distributed manufacturing process and supply chain spanning multiple parties, and hence raises concerns about the reliability of the manufactured product. In this work, we first present a brief overview of the potential risks that exist in the cyber-physical environment of additive manufacturing. We then evaluate the risks posed by two different classes of modifications to the AM process which are representative of the challenges that are unique to AM. The risks posed are examined through mechanical testing of objects with altered printing orientation and fine internal defects. Finite element analysis and ultrasonic inspection are also used to demonstrate the potential for decreased performance and for evading detection. The results highlight several scenarios, intentional or unintentional, that can affect the product quality and pose security challenges for the additive manufacturing supply chain.

Subclinical Primary Psychopathy, but Not Physical Formidability or Attractiveness, Predicts Conversational Dominance in a Zero-Acquaintance Situation

PubMed Central

Manson, Joseph H.; Gervais, Matthew M.; Fessler, Daniel M. T.; Kline, Michelle A.

2014-01-01

The determinants of conversational dominance are not well understood. We used videotaped triadic interactions among unacquainted same-sex American college students to test predictions drawn from the theoretical distinction between dominance and prestige as modes of human status competition. Specifically, we investigated the effects of physical formidability, facial attractiveness, social status, and self-reported subclinical psychopathy on quantitative (proportion of words produced), participatory (interruptions produced and sustained), and sequential (topic control) dominance. No measure of physical formidability or attractiveness was associated with any form of conversational dominance, suggesting that the characteristics of our study population or experimental frame may have moderated their role in dominance dynamics. Primary psychopathy was positively associated with quantitative dominance and (marginally) overall triad talkativeness, and negatively associated (in men) with affect word use, whereas secondary psychopathy was unrelated to conversational dominance. The two psychopathy factors had significant opposing effects on quantitative dominance in a multivariate model. These latter findings suggest that glibness in primary psychopathy may function to elicit exploitable information from others in a relationally mobile society. PMID:25426962

Subclinical primary psychopathy, but not physical formidability or attractiveness, predicts conversational dominance in a zero-acquaintance situation.

PubMed

Manson, Joseph H; Gervais, Matthew M; Fessler, Daniel M T; Kline, Michelle A

2014-01-01

The determinants of conversational dominance are not well understood. We used videotaped triadic interactions among unacquainted same-sex American college students to test predictions drawn from the theoretical distinction between dominance and prestige as modes of human status competition. Specifically, we investigated the effects of physical formidability, facial attractiveness, social status, and self-reported subclinical psychopathy on quantitative (proportion of words produced), participatory (interruptions produced and sustained), and sequential (topic control) dominance. No measure of physical formidability or attractiveness was associated with any form of conversational dominance, suggesting that the characteristics of our study population or experimental frame may have moderated their role in dominance dynamics. Primary psychopathy was positively associated with quantitative dominance and (marginally) overall triad talkativeness, and negatively associated (in men) with affect word use, whereas secondary psychopathy was unrelated to conversational dominance. The two psychopathy factors had significant opposing effects on quantitative dominance in a multivariate model. These latter findings suggest that glibness in primary psychopathy may function to elicit exploitable information from others in a relationally mobile society.

Extraterrestrial Intelligence: What Would it Mean?

NASA Astrophysics Data System (ADS)

Impey, Chris

2015-04-01

Results from NASA's Kepler mission imply a hundred million Earth-like habitable worlds in the Milky Way galaxy, many of which formed billions of years before the Earth. Each of these worlds is likely to have all of the ingredients needed for biology. The real estate of time and space for the evolution of intelligent life is formidable, begging the question of whether or not we are alone in the universe. The implications of making contact have been explored extensively in science fiction and the popular culture, but less frequently in the serious scientific literature. Astronomers have carried out searches for extraterrestrial intelligence for over half a century, with no success so far. In practice, it is easier to search for alien technology than to discern intelligence of unknown function and form. In this talk, the modes of technology that can currently be detected are summarized, along with the implications of a timing argument than any detected civilization is likely to be much more advanced than ours. Fermi's famous question ``Where Are They?'' is as well posed now as it was sixty years ago. The existence of extraterrestrial intelligence would have profound practical, cultural, and religious implications for humanity.

Hyper-Parallel Tempering Monte Carlo Method and It's Applications

NASA Astrophysics Data System (ADS)

Yan, Qiliang; de Pablo, Juan

2000-03-01

A new generalized hyper-parallel tempering Monte Carlo molecular simulation method is presented for study of complex fluids. The method is particularly useful for simulation of many-molecule complex systems, where rough energy landscapes and inherently long characteristic relaxation times can pose formidable obstacles to effective sampling of relevant regions of configuration space. The method combines several key elements from expanded ensemble formalisms, parallel-tempering, open ensemble simulations, configurational bias techniques, and histogram reweighting analysis of results. It is found to accelerate significantly the diffusion of a complex system through phase-space. In this presentation, we demonstrate the effectiveness of the new method by implementing it in grand canonical ensembles for a Lennard-Jones fluid, for the restricted primitive model of electrolyte solutions (RPM), and for polymer solutions and blends. Our results indicate that the new algorithm is capable of overcoming the large free energy barriers associated with phase transitions, thereby greatly facilitating the simulation of coexistence properties. It is also shown that the method can be orders of magnitude more efficient than previously available techniques. More importantly, the method is relatively simple and can be incorporated into existing simulation codes with minor efforts.

Trade-off between aerobic capacity and locomotor capability in an Antarctic pteropod

PubMed Central

Rosenthal, Joshua J. C.; Seibel, Brad A.; Dymowska, Agnieszka; Bezanilla, Francisco

2009-01-01

At −1.8 °C, the waters of Antarctica pose a formidable physiological barrier for most ectotherms. The few taxa that inhabit this zone have presumably made specific adjustments to their neuromuscular function and have enhanced their metabolic capacity. However, support for this assertion is equivocal and the details of specific compensations are largely unknown. This can generally be attributed to the fact that most Antarctic organisms are either too distantly related to their temperate relatives to permit direct comparisons (e.g., notothenioid fishes) or because they are not amenable to neuromuscular recording. Here, as a comparative model, we take advantage of 2 pelagic molluscs in the genus Clione to conduct a broadly integrative investigation on neuromuscular adaptation to the extreme cold. We find that for the Antarctic congener aerobic capacity is enhanced, but at a cost. To support a striking proliferation of mitochondria, the Antarctic species has shed a 2-gear swim system and the associated specialized neuromuscular components, resulting in greatly reduced scope for locomotor activity. These results suggest that polar animals have undergone substantial tissue-level reorganizations to accommodate their environment, which may reduce their capacity to acclimate to a changing climate. PMID:19325127

Application of MSCTA combined with VRT in the operation of cervical dumbbell tumors

PubMed Central

Wang, Wan; Lin, Jia; Knosp, Engelbert; Zhao, Yuanzheng; Xiu, Dianhui; Guo, Yongchuan

2015-01-01

Cervical dumbbell tumor poses great difficulties for neurosurgical treatment and incurs remarkable local recurrence rate as the formidable problem for neurosurgery. However, as the routine preoperative evaluation scheme, MRI and CT failed to reveal the mutual three-dimensional relationships between tumor and adjacent structures. Here, we report the clinical application of MSCTA and VRT in three-dimensional reconstruction of cervical dumbbell tumors. From January 2012 to July 2014, 24 patients diagnosed with cervical dumbbell tumor were retrospectively analyzed. All patients enrolled were indicated for preoperative MSCTA/VRT image reconstruction to explore the three-dimensional stereoscopic anatomical relationships among neuroma, spinal cord and vertebral artery to achieve optimal surgical approach from multiple configurations and surgical practice. Three-dimensional mutual anatomical relationships among tumor, adjacent vessels and vertebrae were vividly reconstructed by MSCTA/VRT in all patients in accordance with intraoperative findings. Multiple configurations for optimal surgical approach contribute to total resection of tumor, minimal damage to vessels and nerves, and maximal maintenance of cervical spine stability. Preoperative MSCTA/VRT contributes to reconstruction of three-dimensional stereoscopic anatomical relationships between cervical dumbbell tumor and adjacent structures for optimal surgical approach by multiple configurations and reduction of intraoperative damages and postoperative complications. PMID:26550385

Application of MSCTA combined with VRT in the operation of cervical dumbbell tumors.

PubMed

Wang, Wan; Lin, Jia; Knosp, Engelbert; Zhao, Yuanzheng; Xiu, Dianhui; Guo, Yongchuan

2015-01-01

Cervical dumbbell tumor poses great difficulties for neurosurgical treatment and incurs remarkable local recurrence rate as the formidable problem for neurosurgery. However, as the routine preoperative evaluation scheme, MRI and CT failed to reveal the mutual three-dimensional relationships between tumor and adjacent structures. Here, we report the clinical application of MSCTA and VRT in three-dimensional reconstruction of cervical dumbbell tumors. From January 2012 to July 2014, 24 patients diagnosed with cervical dumbbell tumor were retrospectively analyzed. All patients enrolled were indicated for preoperative MSCTA/VRT image reconstruction to explore the three-dimensional stereoscopic anatomical relationships among neuroma, spinal cord and vertebral artery to achieve optimal surgical approach from multiple configurations and surgical practice. Three-dimensional mutual anatomical relationships among tumor, adjacent vessels and vertebrae were vividly reconstructed by MSCTA/VRT in all patients in accordance with intraoperative findings. Multiple configurations for optimal surgical approach contribute to total resection of tumor, minimal damage to vessels and nerves, and maximal maintenance of cervical spine stability. Preoperative MSCTA/VRT contributes to reconstruction of three-dimensional stereoscopic anatomical relationships between cervical dumbbell tumor and adjacent structures for optimal surgical approach by multiple configurations and reduction of intraoperative damages and postoperative complications.

SMEs and their E-Commerce: Implications for Training in Wellington, New Zealand

ERIC Educational Resources Information Center

Beal, Tim; Abdullah, Moha Asri

2005-01-01

One of the greatest challenges facing traditional small and medium-sized enterprises (SMEs) throughout the world is that posed by the Internet. While the Internet offers great potential to SMEs, from improving and cheapening production processes through to reaching global customers, it also poses great problems. SMEs' resources, human and…

The Marihuana Dilemma: Challenge to Commanders.

DTIC Science & Technology

The marihuana dilemma poses a major challenge to commanders in the US Army today. The problem was analyzed as to the characteristics of the drug...available to commanders to meet the challenge. The essay concludes that marihuana should not be legalized; drug users or former drug users should not be

Student Media Production to Meet Challenges in Climate Change Science Education

ERIC Educational Resources Information Center

Rooney-Varga, Juliette N.; Brisk, Angelica Allende; Adams, Elizabeth; Shuldman, Elizabeth; Rath, Kenneth

2014-01-01

While the need for effective climate change education is growing, this area of geoscience also poses unique educational challenges. These challenges include the politicization of climate change, the psychological and affective responses it elicits, and common misconceptions, which can all create barriers to learning. Here, we present an…

Transforming Teaching Challenges into Learning Opportunities: Interdisciplinary Reflective Collaboration

ERIC Educational Resources Information Center

Callaghan, Ronel

2015-01-01

Teaching in higher education poses unique sets of challenges, especially for academics in the engineering, built sciences and information science education disciplines. This article focuses on how reflective collaboration can support academics in their quest to find unique solutions to challenges in different academic contexts. A reflective…

In-the-wild facial expression recognition in extreme poses

NASA Astrophysics Data System (ADS)

Yang, Fei; Zhang, Qian; Zheng, Chi; Qiu, Guoping

2018-04-01

In the computer research area, facial expression recognition is a hot research problem. Recent years, the research has moved from the lab environment to in-the-wild circumstances. It is challenging, especially under extreme poses. But current expression detection systems are trying to avoid the pose effects and gain the general applicable ability. In this work, we solve the problem in the opposite approach. We consider the head poses and detect the expressions within special head poses. Our work includes two parts: detect the head pose and group it into one pre-defined head pose class; do facial expression recognize within each pose class. Our experiments show that the recognition results with pose class grouping are much better than that of direct recognition without considering poses. We combine the hand-crafted features, SIFT, LBP and geometric feature, with deep learning feature as the representation of the expressions. The handcrafted features are added into the deep learning framework along with the high level deep learning features. As a comparison, we implement SVM and random forest to as the prediction models. To train and test our methodology, we labeled the face dataset with 6 basic expressions.

Docking pose selection by interaction pattern graph similarity: application to the D3R grand challenge 2015.

PubMed

Slynko, Inna; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

2016-09-01

High affinity ligands for a given target tend to share key molecular interactions with important anchoring amino acids and therefore often present quite conserved interaction patterns. This simple concept was formalized in a topological knowledge-based scoring function (GRIM) for selecting the most appropriate docking poses from previously X-rayed interaction patterns. GRIM first converts protein-ligand atomic coordinates (docking poses) into a simple 3D graph describing the corresponding interaction pattern. In a second step, proposed graphs are compared to that found from template structures in the Protein Data Bank. Last, all docking poses are rescored according to an empirical score (GRIMscore) accounting for overlap of maximum common subgraphs. Taking the opportunity of the public D3R Grand Challenge 2015, GRIM was used to rescore docking poses for 36 ligands (6 HSP90α inhibitors, 30 MAP4K4 inhibitors) prior to the release of the corresponding protein-ligand X-ray structures. When applied to the HSP90α dataset, for which many protein-ligand X-ray structures are already available, GRIM provided very high quality solutions (mean rmsd = 1.06 Å, n = 6) as top-ranked poses, and significantly outperformed a state-of-the-art scoring function. In the case of MAP4K4 inhibitors, for which preexisting 3D knowledge is scarce and chemical diversity is much larger, the accuracy of GRIM poses decays (mean rmsd = 3.18 Å, n = 30) although GRIM still outperforms an energy-based scoring function. GRIM rescoring appears to be quite robust with comparison to the other approaches competing for the same challenge (42 submissions for the HSP90 dataset, 27 for the MAP4K4 dataset) as it ranked 3rd and 2nd respectively, for the two investigated datasets. The rescoring method is quite simple to implement, independent on a docking engine, and applicable to any target for which at least one holo X-ray structure is available.

Efficient computation of hashes

NASA Astrophysics Data System (ADS)

Lopes, Raul H. C.; Franqueira, Virginia N. L.; Hobson, Peter R.

2014-06-01

The sequential computation of hashes at the core of many distributed storage systems and found, for example, in grid services can hinder efficiency in service quality and even pose security challenges that can only be addressed by the use of parallel hash tree modes. The main contributions of this paper are, first, the identification of several efficiency and security challenges posed by the use of sequential hash computation based on the Merkle-Damgard engine. In addition, alternatives for the parallel computation of hash trees are discussed, and a prototype for a new parallel implementation of the Keccak function, the SHA-3 winner, is introduced.

A case of severe and rigid congenital thoracolumbar lordoscoliosis with diastematomyelia presenting with type 2 respiratory failure: managed by staged correction with controlled axial traction.

PubMed

Kanagaraju, Vijayanth; Chhabra, H S; Srivastava, Abhishek; Mahajan, Rajat; Kaul, Rahul; Bhatia, Pallav; Tandon, Vikas; Nanda, Ankur; Sangondimath, Gururaj; Patel, Nishit

2016-10-01

Congenital lordoscoliosis is an uncommon pathology and its management poses formidable challenge especially in the presence of type 2 respiratory failure and intraspinal anomalies. In such patients standard management protocols are not applicable and may require multistage procedure to minimize risk and optimize results. A 15-year-old girl presented in our hospital emergency services with severe breathing difficulty. She had a severe and rapidly progressing deformity in her back, noted since 6 years of age, associated with severe respiratory distress requiring oxygen and BiPAP support. She was diagnosed to have a severe and rigid congenital right thoracolumbar lordoscoliosis (coronal Cobb's angle: 105° and thoracic lordosis -10°) with type 1 split cord malformation with bony septum extending from T11 to L3. This leads to presentation of restrictive lung disease with type 2 respiratory failure. As her lung condition did not allow for any major procedure, we did a staged procedure rather than executing in a single stage. Controlled axial traction by halogravity was applied initially followed by halo-femoral traction. Four weeks later, this was replaced by halo-pelvic distraction device after a posterior release procedure with asymmetric pedicle substraction osteotomies at T7 and T10. Halo-pelvic distraction continued for 4 more weeks to optimize and correct the deformity. Subsequently definitive posterior stabilization and fusion was done. The detrimental effect of diastematomyelia resection in such cases is clearly evident from literature, so it was left unresected. A good scoliotic correction with improved respiratory function was achieved. Three years follow-up showed no loss of deformity correction, no evidence of pseudarthrosis and a good clinical outcome with reasonably balanced spine. The management of severe and rigid congenital lordoscoliotic deformities with intraspinal anomalies is challenging. Progressive reduction in respiratory volume in untreated cases can lead to acute respiratory failure. Such patients have a high rate of intraoperative and postoperative morbidity and mortality. Hence a staged procedure is recommended. Initially a less invasive procedure like halo traction helps to improve their respiratory function with simultaneous correction of the deformity, while allowing for monitoring of neurological deficit. Subsequently spinal osteotomies and combined halo traction helps further improve the correction, following which definitive instrumented fusion can be done.

Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.

PubMed

Sharma, Rishi; Kim, Soo-Young; Sharma, Anjali; Zhang, Zhi; Kambhampati, Siva Pramodh; Kannan, Sujatha; Kannan, Rangaramanujam M

2017-11-15

Brain-related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood-brain barrier (BBB) and potency. Despite its potential in the clinic and in preclinical models, the high doses needed to affect a positive therapeutic response have led to side effects. Targeted delivery of minocycline to the injured site and injured cells in the brain can be highly beneficial. Systemically administered hydroxyl poly(amidoamine) (PAMAM) generation-6 (G6) dendrimers have a longer blood circulation time and have been shown to cross the impaired BBB. We have successfully prepared and characterized the in vitro efficacy and in vivo targeting ability of hydroxyl-G6 PAMAM dendrimer-9-amino-minocycline conjugate (D-mino). Minocycline is a challenging drug to carry out chemical transformations due to its inherent instability. We used a combination of a highly efficient and mild copper catalyzed azide-alkyne click reaction (CuAAC) along with microwave energy to conjugate 9-amino-minocycline (mino) to the dendrimer surface via enzyme responsive linkages. D-mino was further evaluated for anti-inflammatory and antioxidant activity in lipopolysaccharides-activated murine microglial cells. D-mino conjugates enhanced the intracellular availability of the drug due to their rapid uptake, suppressed inflammatory cytokine tumor necrosis factor α (TNF-α) production, and reduced oxidative stress by suppressing nitric oxide production, all significantly better than the free drug. Fluorescently labeled dendrimer conjugate (Cy5-D-mino) was systematically administered (intravenous, 55 mg/kg) on postnatal day 1 to rabbit kits with a clinically relevant phenotype of cerebral palsy. The in vivo imaging study indicates that Cy5-D-mino crossed the impaired blood-brain barrier and co-localized with activated microglia at the periventricular white matter areas, including the corpus callosum and the angle of the lateral ventricle, with significant implications for positive therapeutic outcomes. The enhanced efficacy of D-mino, when combined with the inherent neuroinflammation-targeting capability of the PAMAM dendrimers, may provide new opportunities for targeted drug delivery to treat neurological disorders.

Head pose estimation in computer vision: a survey.

PubMed

Murphy-Chutorian, Erik; Trivedi, Mohan Manubhai

2009-04-01

The capacity to estimate the head pose of another person is a common human ability that presents a unique challenge for computer vision systems. Compared to face detection and recognition, which have been the primary foci of face-related vision research, identity-invariant head pose estimation has fewer rigorously evaluated systems or generic solutions. In this paper, we discuss the inherent difficulties in head pose estimation and present an organized survey describing the evolution of the field. Our discussion focuses on the advantages and disadvantages of each approach and spans 90 of the most innovative and characteristic papers that have been published on this topic. We compare these systems by focusing on their ability to estimate coarse and fine head pose, highlighting approaches that are well suited for unconstrained environments.

Hematopoietic stem cell engineering at a crossroads

PubMed Central

Rivière, Isabelle; Dunbar, Cynthia E.

2012-01-01

The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead. PMID:22096239

Biomimetic Chemistry of Iron, Nickel, Molybdenum, and Tungsten in Sulfur-Ligated Protein Sites†

PubMed Central

Groysman, Stanislav; Holm, R. H.

2009-01-01

Biomimetic inorganic chemistry has as its primary goal the synthesis of molecules that approach or achieve the structures, oxidation states, and electronic and reactivity features of native metal-containing sites of variant nuclearity. Comparison of properties of accurate analogues and these sites ideally provides insight into the influence of protein structure and environment on intrinsic properties as represented by the analogue. For polynuclear sites in particular, the goal provides a formidable challenge for, with the exception of iron-sulfur clusters, all such site structures have never been achieved and few even closely approximated by chemical synthesis. This account describes the current status of the synthetic analogue approach as applied to the mononuclear sites in certain molybdoenzymes and the polynuclear sites in hydrogenases, nitrogenase, and carbon monoxide dehydrogenases. PMID:19206188

Validation of the Spanish SIRS with monolingual Hispanic outpatients.

PubMed

Correa, Amor A; Rogers, Richard; Hoersting, Raquel

2010-09-01

Psychologists are faced with formidable challenges in making their assessment methods relevant to growing numbers of Hispanic clients for whom English is not the primary or preferred language. Among other clinical issues, the determination of malingering has profound consequences for clients. In this investigation, we evaluated a Spanish translation of the Structured Interview of Reported Symptoms (SIRS; Rogers, Bagby, & Dickens, 1992) with 80 Spanish-speaking Hispanic American outpatients. Using a between-subjects simulation design, the Spanish SIRS was found to produce reliable results with small standard errors of measurement. Regarding validity, very large effect sizes (mean Cohen's d= 2.00) were observed between feigners and honest responders for the SIRS primary scales. We consider the potential role of the Spanish SIRS with reference to Spanish translations for other assessment instruments.

Blood brain barrier: a challenge for effectual therapy of brain tumors.

PubMed

Bhowmik, Arijit; Khan, Rajni; Ghosh, Mrinal Kanti

2015-01-01

Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier.

Polymer waveguides for electro-optical integration in data centers and high-performance computers.

PubMed

Dangel, Roger; Hofrichter, Jens; Horst, Folkert; Jubin, Daniel; La Porta, Antonio; Meier, Norbert; Soganci, Ibrahim Murat; Weiss, Jonas; Offrein, Bert Jan

2015-02-23

To satisfy the intra- and inter-system bandwidth requirements of future data centers and high-performance computers, low-cost low-power high-throughput optical interconnects will become a key enabling technology. To tightly integrate optics with the computing hardware, particularly in the context of CMOS-compatible silicon photonics, optical printed circuit boards using polymer waveguides are considered as a formidable platform. IBM Research has already demonstrated the essential silicon photonics and interconnection building blocks. A remaining challenge is electro-optical packaging, i.e., the connection of the silicon photonics chips with the system. In this paper, we present a new single-mode polymer waveguide technology and a scalable method for building the optical interface between silicon photonics chips and single-mode polymer waveguides.

Moving Contact Lines: Linking Molecular Dynamics and Continuum-Scale Modeling.

PubMed

Smith, Edward R; Theodorakis, Panagiotis E; Craster, Richard V; Matar, Omar K

2018-05-17

Despite decades of research, the modeling of moving contact lines has remained a formidable challenge in fluid dynamics whose resolution will impact numerous industrial, biological, and daily life applications. On the one hand, molecular dynamics (MD) simulation has the ability to provide unique insight into the microscopic details that determine the dynamic behavior of the contact line, which is not possible with either continuum-scale simulations or experiments. On the other hand, continuum-based models provide a link to the macroscopic description of the system. In this Feature Article, we explore the complex range of physical factors, including the presence of surfactants, which governs the contact line motion through MD simulations. We also discuss links between continuum- and molecular-scale modeling and highlight the opportunities for future developments in this area.

Numerical Simulation of Metallic Uranium Sintering

NASA Astrophysics Data System (ADS)

Berry, Bruce

Conventional ceramic oxide nuclear fuels are limited in their thermal and life-cycle properties. The desire to operate at higher burnups as is required by current utility economics has proven a formidable challenge for oxide fuel designs. Metallic formulations have superior thermal performance but are plagued by volumetric swelling due to fission gas buildup. In this study, we consider a number of specific microstructure configurations that have been experimentally shown to exhibit considerable resistance to porosity loss. Specifically, a void sizing that is bimodally distributed was shown to resist early pore loss and could provide collection sites for fission gas buildup. We employ the phase field model of Cahn and Hilliard, solved via the finite element method using the open source Multi-User Object Oriented Simulation Environment (MOOSE) developed by INL.

Development of vaccines for bio-warfare agents.

PubMed

Rosenthal, S R; Clifford, J C M

2002-01-01

There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations.

PubMed

Liu, Kai; Watanabe, Etsurou; Kokubo, Hironori

2017-02-01

The binding mode prediction is of great importance to structure-based drug design. The discrimination of various binding poses of ligand generated by docking is a great challenge not only to docking score functions but also to the relatively expensive free energy calculation methods. Here we systematically analyzed the stability of various ligand poses under molecular dynamics (MD) simulation. First, a data set of 120 complexes was built based on the typical physicochemical properties of drug-like ligands. Three potential binding poses (one correct pose and two decoys) were selected for each ligand from self-docking in addition to the experimental pose. Then, five independent MD simulations for each pose were performed with different initial velocities for the statistical analysis. Finally, the stabilities of ligand poses under MD were evaluated and compared with the native one from crystal structure. We found that about 94% of the native poses were maintained stable during the simulations, which suggests that MD simulations are accurate enough to judge most experimental binding poses as stable properly. Interestingly, incorrect decoy poses were maintained much less and 38-44% of decoys could be excluded just by performing equilibrium MD simulations, though 56-62% of decoys were stable. The computationally-heavy binding free energy calculation can be performed only for these survived poses.

NASA Space Rocket Logistics Challenges

NASA Technical Reports Server (NTRS)

Bramon, Chris; Neeley, James R.; Jones, James V.; Watson, Michael D.; Inman, Sharon K.; Tuttle, Loraine

2014-01-01

The Space Launch System (SLS) is the new NASA heavy lift launch vehicle in development and is scheduled for its first mission in 2017. SLS has many of the same logistics challenges as any other large scale program. However, SLS also faces unique challenges. This presentation will address the SLS challenges, along with the analysis and decisions to mitigate the threats posed by each.

Communicating about smoke from wildland fire: challenges and ways to address them

Treesearch

Christine S. Olsen; Danielle K. Mazzotta; Eric Toman; A. Paige Fischer

2014-01-01

Wildland fire and associated management efforts are dominant topics in natural resource fields. Smoke from fires can be a nuisance and pose serious health risks and aggravate pre-existing health conditions. When it results in reduced visibility near roadways, smoke can also pose hazardous driving conditions and reduce the scenic value of vistas. Communicating about...

Tracking the Careers of Graduates: A New Agenda for Graduate Schools

ERIC Educational Resources Information Center

Stewart, Debra W.

2013-01-01

As candidates in the 2012 election debated issues raised by the state of the US economy, unemployment statistics and job creation took center stage. The problems under discussion posed (and continue to pose) a particularly clear and pressing challenge to the nation's graduate schools. While the US enjoys a reputation for having the most dynamic…

A Problem Posing-Based Practicing Strategy for Facilitating Students' Computer Programming Skills in the Team-Based Learning Mode

ERIC Educational Resources Information Center

Wang, Xiao-Ming; Hwang, Gwo-Jen

2017-01-01

Computer programming is a subject that requires problem-solving strategies and involves a great number of programming logic activities which pose challenges for learners. Therefore, providing learning support and guidance is important. Collaborative learning is widely believed to be an effective teaching approach; it can enhance learners' social…

Binding pose and affinity prediction in the 2016 D3R Grand Challenge 2 using the Wilma-SIE method

NASA Astrophysics Data System (ADS)

Hogues, Hervé; Sulea, Traian; Gaudreault, Francis; Corbeil, Christopher R.; Purisima, Enrico O.

2018-01-01

The Farnesoid X receptor (FXR) exhibits significant backbone movement in response to the binding of various ligands and can be a challenge for pose prediction algorithms. As part of the D3R Grand Challenge 2, we tested Wilma-SIE, a rigid-protein docking method, on a set of 36 FXR ligands for which the crystal structures had originally been blinded. These ligands covered several classes of compounds. To overcome the rigid protein limitations of the method, we used an ensemble of publicly available structures for FXR from the PDB. The use of the ensemble allowed Wilma-SIE to predict poses with average and median RMSDs of 2.3 and 1.4 Å, respectively. It was quite clear, however, that had we used a single structure for the receptor the success rate would have been much lower. The most successful predictions were obtained on chemical classes for which one or more crystal structures of the receptor bound to a molecule of the same class was available. In the absence of a crystal structure for the class, observing a consensus binding mode for the ligands of the class using one or more receptor structures of other classes seemed to be indicative of a reasonable pose prediction. Affinity prediction proved to be more challenging with generally poor correlation with experimental IC50s (Kendall tau 0.3). Even when the 36 crystal structures were used the accuracy of the predicted affinities was not appreciably improved. A possible cause of difficulty is the internal energy strain arising from conformational differences in the receptor across complexes, which may need to be properly estimated and incorporated into the SIE scoring function.

Incorporating Qualitative Evidence in Systematic Reviews: Strategies and Challenges

ERIC Educational Resources Information Center

Caracelli, Valerie J.; Cooksy, Leslie J.

2013-01-01

The quality of mixed methods systematic reviews relies on the quality of primary-level studies. The synthesis of qualitative evidence and the recent development of synthesizing mixed methods studies hold promise, but also pose challenges to evidence synthesis.

Variation in Transpiration Efficiency in Sorghum

USDA-ARS?s Scientific Manuscript database

Declining freshwater resources, increasing population, and growing demand for biofuels pose new challenges for agriculture research. To meet these challenges, the concept "Blue Revolution" (more crop per drop) was proposed to improve water productivity in agriculture. We have identified several so...

The Challenge of Teacher Retention in Urban Schools: Evidence of Variation from a Cross-Site Analysis

ERIC Educational Resources Information Center

Papay, John P.; Bacher-Hicks, Andrew; Page, Lindsay C.; Marinell, William H.

2017-01-01

Substantial teacher turnover poses a challenge to staffing public schools with effective teachers. The scope of the teacher retention challenge across school districts, however, remains poorly defined. Applying consistent data practices and analytical techniques to administrative data sets from 16 urban districts, we document substantial…

The Enduring Challenges in Public Management: Surviving and Excelling in a Changing World.

ERIC Educational Resources Information Center

Halachmi, Arie, Ed.; Bouckaert, Geert, Ed.

This book addresses in different ways the prospect of improving the performance of government and nonprofit organizations. The chapters are clustered around enduring management challenges that may influence productivity in the public sector. Fifteen chapters discuss the challenges to productivity posed by immediate and distant changes in the…

Influenza Vaccines: Challenges and Solutions

PubMed Central

Houser, Katherine; Subbarao, Kanta

2015-01-01

Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

A study on facial expressions recognition

NASA Astrophysics Data System (ADS)

Xu, Jingjing

2017-09-01

In terms of communication, postures and facial expressions of such feelings like happiness, anger and sadness play important roles in conveying information. With the development of the technology, recently a number of algorithms dealing with face alignment, face landmark detection, classification, facial landmark localization and pose estimation have been put forward. However, there are a lot of challenges and problems need to be fixed. In this paper, a few technologies have been concluded and analyzed, and they all relate to handling facial expressions recognition and poses like pose-indexed based multi-view method for face alignment, robust facial landmark detection under significant head pose and occlusion, partitioning the input domain for classification, robust statistics face formalization.

Human pose tracking from monocular video by traversing an image motion mapped body pose manifold

NASA Astrophysics Data System (ADS)

Basu, Saurav; Poulin, Joshua; Acton, Scott T.

2010-01-01

Tracking human pose from monocular video sequences is a challenging problem due to the large number of independent parameters affecting image appearance and nonlinear relationships between generating parameters and the resultant images. Unlike the current practice of fitting interpolation functions to point correspondences between underlying pose parameters and image appearance, we exploit the relationship between pose parameters and image motion flow vectors in a physically meaningful way. Change in image appearance due to pose change is realized as navigating a low dimensional submanifold of the infinite dimensional Lie group of diffeomorphisms of the two dimensional sphere S2. For small changes in pose, image motion flow vectors lie on the tangent space of the submanifold. Any observed image motion flow vector field is decomposed into the basis motion vector flow fields on the tangent space and combination weights are used to update corresponding pose changes in the different dimensions of the pose parameter space. Image motion flow vectors are largely invariant to style changes in experiments with synthetic and real data where the subjects exhibit variation in appearance and clothing. The experiments demonstrate the robustness of our method (within +/-4° of ground truth) to style variance.

RECRUITMENT STRATEGIES FOR AN EXPOSURE MEASUREMENT STUDY OF PRESCHOOL CHILDREN

EPA Science Inventory

Recruiting study participants is always a challenge for researchers. It poses an even bigger challenge for researchers to recruit participants for a study involving intrusive, burdensome data collection activities. A study of preschool children's exposure to persistent organic ...

Sustainable Materials Management (SMM) Web Academy Webinar: Management Challenges for Lithium Batteries at Electronics Recyclers

EPA Pesticide Factsheets

This is a webinar page for the Sustainable Management of Materials (SMM) Web Academy webinar titled, An Introduction to Lithium Batteries and the Challenges that they Pose to the Waste and Recycling Industry.

SU-D-210-04: Using Radiotherapy Biomaterials to Brand and Track Deadly Cancer Cells

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

Altundal, Y; Sajo, E; Ngwa, W

Purpose: Metastasis accounts for over 90% of all cancer associated suffering and death and arguably presents the most formidable challenges in cancer management. The detection of metastatic or rare circulating tumor cells (CTCs) in blood or lymph nodes remains a formidable technological challenge. In this study, we investigated the time needed to label each cancer cell in-situ (right at the source tumor) with sufficient number of GNPs that will allow enhanced non-invasive detection via photoacoustic imaging in the lymph nodes. Such in-situ labeling can be achieved via sustained release of the GNPs from Radiotherapy (RT) biomaterials (e.g. fiducials, spacers) coated/loadedmore » with the GNP. Methods: The minimum concentration (1000 GNPs/cell for 50nm GNPs) to detect GNPs with photoacoustic imaging method was experimentally measured by Mallidi et al. and fixed at the tumor sub-volume periphery. In this work, the GNPs were assumed to diffuse from a point source, placed in the middle of a 2–3cm tumor, with an initial concentration of 7–30 mg/g. The time required to label the cells with GNPs was calculated by solving the three dimensional diffusion-reaction equation analytically. The diffusion coefficient of 10nm GNPs was experimentally determined previously. Stokes-Einstein equation was used to calculate the diffusion coefficients for other sizes (2–50nm) of GNPs. The cellular uptake rate constants for several sizes of GNPs were experimentally measured by Jin et al. Results: The time required to label the cells was found 0.635–15.91 days for 2–50nm GNPs with an initial concentration of 7 mg/g GNPs in a 2 cm tumor; 1.379–34.633 days for 2–50nm GNPs with an initial concentration of 30 mg/g GNPs in a 3cm tumor. Conclusion: Our results highlight new potential for labeling CTCs with GNPs released from smart RT biomaterials (i.e. fiducials or spacers loaded with the GNP) towards enhanced non-invasive imaging/detection via photoacoustic imaging.« less

“You’re dealing with an emotionally charged individual…”: an industry perspective on the challenges posed by medical tourists’ informal caregiver-companions

PubMed Central

2013-01-01

Background Patients engage in medical tourism when they privately obtain a medical care abroad. Previous research shows that many medical tourists travel abroad with friends and family members who provide support and assistance. Meanwhile, very little is known about this important stakeholder group, referred to here as caregiver-companions. In this article we examine the challenges that can be posed by caregiver-companions and the overall practice of informal caregiving in medical tourism from an industry perspective. Specifically, we report on the findings of interviews conducted with international patient coordinators (IPCs) who work at destination facilities. IPCs come into regular contact with caregiver-companions in their professional positions and thus are ideally suited to comment on trends they have observed among this stakeholder group as well as the challenges they can pose to medical tourists, health workers, and facilities. Methods We conducted 20 semi-structured interviews with 21 IPCs from 16 different facilities across nine countries. Topics probed in the interviews included caregiver-companion roles, IPCs’ and others’ interaction with caregiver-companions, and potential health and safety risks posed to medical tourists and caregiver-companions. Thematic analysis of the verbatim transcripts was employed. Results Although most participants encouraged medical tourists to travel with a caregiver-companion, many challenges associated with caregiver-companions were identified. Three themes best characterize the challenges that emerged: (1) caregiver-companions require time, attention and resources; (2) caregiver-companions can disrupt the provision of quality care; and (3) caregiver-companions can be exposed to risks. IPCs pointed out that caregiver-companions may, for example, have a negative impact on the patient through cost of accompaniment or inadequate care provision. Caregiver-companions may also create unanticipated or extra work for IPCs, as additional clients and by ignoring established organizational rules, routines, and expectations. Furthermore, caregiver-companions may be susceptible to stresses and health and safety risks, which would further deteriorate their own abilities to offer the patient quality care. Conclusions Although caregiver-companions can pose challenges to medical tourists, health workers, and medical tourism facilities, they can also assist in enhancing best care and offering meaningful support to medical tourists. If caregiver-companions are open to collaboration with IPCs, and particularly in the form of information sharing, then their experience abroad can be safer and less stressful for themselves and, by extension, for the accompanied patients and facility staff. PMID:23889860

"You're dealing with an emotionally charged individual...": an industry perspective on the challenges posed by medical tourists' informal caregiver-companions.

PubMed

Casey, Victoria; Crooks, Valorie A; Snyder, Jeremy; Turner, Leigh

2013-07-26

Patients engage in medical tourism when they privately obtain a medical care abroad. Previous research shows that many medical tourists travel abroad with friends and family members who provide support and assistance. Meanwhile, very little is known about this important stakeholder group, referred to here as caregiver-companions. In this article we examine the challenges that can be posed by caregiver-companions and the overall practice of informal caregiving in medical tourism from an industry perspective. Specifically, we report on the findings of interviews conducted with international patient coordinators (IPCs) who work at destination facilities. IPCs come into regular contact with caregiver-companions in their professional positions and thus are ideally suited to comment on trends they have observed among this stakeholder group as well as the challenges they can pose to medical tourists, health workers, and facilities. We conducted 20 semi-structured interviews with 21 IPCs from 16 different facilities across nine countries. Topics probed in the interviews included caregiver-companion roles, IPCs' and others' interaction with caregiver-companions, and potential health and safety risks posed to medical tourists and caregiver-companions. Thematic analysis of the verbatim transcripts was employed. Although most participants encouraged medical tourists to travel with a caregiver-companion, many challenges associated with caregiver-companions were identified. Three themes best characterize the challenges that emerged: (1) caregiver-companions require time, attention and resources; (2) caregiver-companions can disrupt the provision of quality care; and (3) caregiver-companions can be exposed to risks. IPCs pointed out that caregiver-companions may, for example, have a negative impact on the patient through cost of accompaniment or inadequate care provision. Caregiver-companions may also create unanticipated or extra work for IPCs, as additional clients and by ignoring established organizational rules, routines, and expectations. Furthermore, caregiver-companions may be susceptible to stresses and health and safety risks, which would further deteriorate their own abilities to offer the patient quality care. Although caregiver-companions can pose challenges to medical tourists, health workers, and medical tourism facilities, they can also assist in enhancing best care and offering meaningful support to medical tourists. If caregiver-companions are open to collaboration with IPCs, and particularly in the form of information sharing, then their experience abroad can be safer and less stressful for themselves and, by extension, for the accompanied patients and facility staff.

Curriculum Integration: Helping Career and Technical Education Students Truly Develop College and Career Readiness

ERIC Educational Resources Information Center

Park, Travis; Pearson, Donna; Richardson, George B.

2017-01-01

All students need to learn how to read, write, solve mathematics problems, and understand and apply scientific principles to succeed in college and/or careers. The challenges posed by entry-level career fields are no less daunting than those posed by college-level study. Thus, career and technical education students must learn effective math,…

National Security and Global Climate Change

DTIC Science & Technology

2008-01-01

The uncertainty, confusion, and speculation about the causes, effects, and implications of global climate change (GCC) often paralyze serious...against scientific indications of global climate change , but to consider how it would pose challenges to national security, explore options for facing...generals and admirals, released a report concluding that projected climate change poses a serious threat to America’s national security. This article

Understanding the Formidable Nail Barrier: A Review of the Nail Microstructure, Composition and Diseases

PubMed Central

Baswan, Sudhir; Kasting, Gerald B.; Li, S. Kevin; Wickett, Randy; Adams, Brian; Eurich, Sean; Schamper, Ryan

2016-01-01

The topical treatment of nail fungal infections has been a focal point of nail research in the past few decades as it offers a much safer and focused alternative to conventional oral therapy. Although the current focus remains on exploring the ways of enhancing permeation through the formidable nail barrier, the understanding of the nail microstructure and composition is far from complete. This article reviews our current understanding of the nail microstructure, composition and diseases. A few of the parameters affecting the nail permeability and potential causes of the recurrence of fungal nail infection are also discussed. PMID:28098391

Understanding the formidable nail barrier: A review of the nail microstructure, composition and diseases.

PubMed

Baswan, Sudhir; Kasting, Gerald B; Li, S Kevin; Wickett, Randy; Adams, Brian; Eurich, Sean; Schamper, Ryan

2017-05-01

The topical treatment of nail fungal infections has been a focal point of nail research in the past few decades as it offers a much safer and focused alternative to conventional oral therapy. Although the current focus remains on exploring the ways of enhancing permeation through the formidable nail barrier, the understanding of the nail microstructure and composition is far from complete. This article reviews our current understanding of the nail microstructure, composition and diseases. A few of the parameters affecting the nail permeability and potential causes of the recurrence of fungal nail infection are also discussed. © 2017 Blackwell Verlag GmbH.

Racial bias in judgments of physical size and formidability: From size to threat.

PubMed

Wilson, John Paul; Hugenberg, Kurt; Rule, Nicholas O

2017-07-01

Black men tend to be stereotyped as threatening and, as a result, may be disproportionately targeted by police even when unarmed. Here, we found evidence that biased perceptions of young Black men's physical size may play a role in this process. The results of 7 studies showed that people have a bias to perceive young Black men as bigger (taller, heavier, more muscular) and more physically threatening (stronger, more capable of harm) than young White men. Both bottom-up cues of racial prototypicality and top-down information about race supported these misperceptions. Furthermore, this racial bias persisted even among a target sample from whom upper-body strength was controlled (suggesting that racial differences in formidability judgments are a product of bias rather than accuracy). Biased formidability judgments in turn promoted participants' justifications of hypothetical use of force against Black suspects of crime. Thus, perceivers appear to integrate multiple pieces of information to ultimately conclude that young Black men are more physically threatening than young White men, believing that they must therefore be controlled using more aggressive measures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Sizing up the threat: the envisioned physical formidability of terrorists tracks their leaders' failures and successes.

PubMed

Holbrook, Colin; Fessler, Daniel M T

2013-04-01

Victory in modern intergroup conflict derives from complex factors, including weaponry, economic resources, tactical outcomes, and leadership. We hypothesize that the mind summarizes such factors into simple metaphorical representations of physical size and strength, concrete dimensions that have determined the outcome of combat throughout both ontogenetic and phylogenetic experience. This model predicts that in the aftermath of tactical victories (e.g., killing an enemy leader), members of defeated groups will be conceptualized as less physically formidable. Conversely, reminders that groups possess effective leadership should lead their members to be envisioned as more physically formidable. Consonant with these predictions, in both an opportunistic study conducted immediately after Osama bin Laden's death was announced (Study 1) and a follow-up experiment conducted approximately a year later (Study 2), Americans for whom the killing was salient estimated a purported Islamic terrorist to be physically smaller/weaker. In Studies 3 and 4, primes of victorious terrorist leaders led to inflated estimates of terrorists' physical attributes. These findings elucidate how the mind represents contemporary military power, and may help to explain how even largely symbolic victories can influence reasoning about campaigns of coalitional aggression. Copyright © 2012 Elsevier B.V. All rights reserved.

A Rare Terminal Dinitrogen Complex of Chromium

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

Mock, Michael T.; Chen, Shentan; Rousseau, Roger J.

The reduction of dinitrogen to ammonia from N2 and H2 is currently carried out by the Haber-Bosch process, an energy intensive process that requires high pressures and high temperatures and accounts for the production of millions of tons of ammonia per year. The development of a catalytic, energy-efficient process for N2 reduction is of great interest and remains a formidable challenge. In this communication, we are reporting the preparation, characterization and computational electronic structure analysis of a rare 'Chatt-type' ((P-P)2M(N2)2, P-P = diphosphine ligand) complex of chromium, cis-[Cr(N2)2(PPh2NBn2)2] and its reactivity with CO. This complex is supported by the diphosphinemore » ligand PPh2NBn2, containing non-coordinating pendant amine bases, to serve as proton relays. Future studies for this complex are aimed at answering fundamental questions regarding the role of proton relays in the second coordination sphere in their ability to facilitate proton movement from an external acid to metal-bound dinitrogen ligands in the challenging multi-proton/electron reduction of N2 to ammonia.« less

An alternative animal protein source: cultured beef.

PubMed

Post, Mark J

2014-11-01

Alternative sources of animal proteins are needed that can be produced efficiently, thereby providing food security with diminished ecological burden. It is feasible to culture beef from bovine skeletal muscle stem cells, but the technology is still under development. The aim is to create a beef mimic with equivalent taste, texture, and appearance and with the same nutritional value as livestock-produced beef. More specifically, there is a need for optimization of protein content and fat content. In addition, scalability of production requires modification of current small-scale bioreactors to the largest possible scale. The necessary steps and current progress suggest that this aim is achievable, but formal evidence is still required. Similarly, we can be optimistic about consumer acceptance based on initial data, but detailed studies are needed to gain more insight into potential psychological obstacles that could lead to rejection. These challenges are formidable but likely surmountable. The severity of upcoming food-security threats warrants serious research and development efforts to address the challenges that come with bringing cultured beef to the market. © 2014 New York Academy of Sciences.

Relating Climate and Enviornmental Stress to Conflict... or Cooperation?

NASA Astrophysics Data System (ADS)

Kelley, C. P.

2016-12-01

There are many factors which contribute to social unrest, including governance, economy, access to resources and others. As global climate change progresses, many regions and nations, particularly those that are most vulnerable and least resilient, will face increasing challenges with respect to water and food scarcity. Increasing population and demand for water, combined with declining access to groundwater, will greatly increase exisiting vulnerability. Syria, Yemen and other countries serve as examples of nations that have experienced increasing both environmental stress and conflict. The Syria case in particular has had clear global repercussions, most notably contributing to a global refugee crisis. However, there are also examples of nations that have experienced increasing environmental stress that instead demonstrated transboundary water cooperation rather than conflict. An important and emerging body of work is that which seeks to better understand and characterize real-time resilience and vulnerability in order to better mitigate the consequences of future regional climate change. Prediction of potential conflict is a formidable challenge, one that is highly complex and multivariate, operating on many different temporal and spatial scales.

Science education as a pathway to teaching language literacy: a critical book review

NASA Astrophysics Data System (ADS)

Tolbert, Sara

2011-03-01

In this paper, I present a critical review of the recent book, Science Education as a Pathway to Teaching Language Literacy, edited by Alberto J. Rodriguez. This volume is a timely collection of essays in which the authors bring to attention both the successes and challenges of integrating science instruction with literacy instruction (and vice versa). Although several themes in the book merit further attention, a central unifying issue throughout all of the chapters is the task of designing instruction which (1) gives students access to the dominant Discourses in science and literacy, (2) builds on students' lived experiences, and (3) connects new material to socially and culturally relevant contexts in both science and literacy instruction— all within the high stakes testing realities of teachers and students in public schools. In this review, I illustrate how the authors of these essays effectively address this formidable challenge through research that `ascends to the concrete'. I also discuss where we could build on the work of the authors to integrate literacy and science instruction with the purpose of `humanizing and democratizing' science education in K-12 classrooms.

FATIGUE OF BIOMATERIALS: HARD TISSUES

PubMed Central

Arola, D.; Bajaj, D.; Ivancik, J.; Majd, H.; Zhang, D.

2009-01-01

The fatigue and fracture behavior of hard tissues are topics of considerable interest today. This special group of organic materials comprises the highly mineralized and load-bearing tissues of the human body, and includes bone, cementum, dentin and enamel. An understanding of their fatigue behavior and the influence of loading conditions and physiological factors (e.g. aging and disease) on the mechanisms of degradation are essential for achieving lifelong health. But there is much more to this topic than the immediate medical issues. There are many challenges to characterizing the fatigue behavior of hard tissues, much of which is attributed to size constraints and the complexity of their microstructure. The relative importance of the constituents on the type and distribution of defects, rate of coalescence, and their contributions to the initiation and growth of cracks, are formidable topics that have not reached maturity. Hard tissues also provide a medium for learning and a source of inspiration in the design of new microstructures for engineering materials. This article briefly reviews fatigue of hard tissues with shared emphasis on current understanding, the challenges and the unanswered questions. PMID:20563239

The Development of Questioning as a Means of Framing Problems and Posing Challenges.

ERIC Educational Resources Information Center

Feigenbaum, Peter

When a person encounters a problem, the character, form, and content of his or her response provides psychologists with useful and interesting information about processes of challenge and their relationship to intellectual development. In essence, challenge is a developing relationship that is defined on the one hand by objective factors (a person…

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…

When Bible and Science Interact: Teachers' Pedagogic and Value Challenges in Teaching Religious Minority Students in Higher Education Settings

ERIC Educational Resources Information Center

Novis-Deutsch, Nurit; Lifshitz, Chen

2016-01-01

The integration of highly religious minority students into institutions of higher education poses significant pedagogical and value challenges for students and teachers alike. We offer a framework for analyzing such challenges, distinguishing between practical concerns, identity issues and value conflicts. By contrasting a deficit perspective to…

The Real Challenge of ESD

ERIC Educational Resources Information Center

Jackson, M. G.

2011-01-01

Between the Inter-governmental Conference on Environmental Education at Tbilisi in 1977 and the Fourth International Conference on Environmental Education at Ahmedabad in 2007, our conception of the challenge posed by the global crises of climate change, environmental destruction, social disintegration, poverty, natural resources exhaustion and…

DEVELOPMENT, DESIGN AND CONSUMER TESTING OF MARKETABLE RESIDENTIAL LED LIGHT LUMINAIRES

EPA Science Inventory

Developing marketable LED luminaires poses challenges, even though LEDs are energy-efficient and an ecological alternative to conventionally lighting. Challenges include: perceptions that the color rendition of LEDs is unacceptable to the public; numbers of LEDs must be grou...

Variation in transpiration efficiency in sorghum

USDA-ARS?s Scientific Manuscript database

Declining freshwater resources, increasing population, and growing demand for biofuels pose new challenges for agriculture research. To meet these challenges, the concept “Blue Revolution” was proposed to improve water productivity in agriculture--“More Crop per Drop”. Sorghum is the fifth most imp...

Variation of Transpiration Efficiency in Sorghum

USDA-ARS?s Scientific Manuscript database

Declining freshwater resources, increasing population, and growing demand for biofuels pose new challenges for agriculture research. To meet these challenges, the concept “Blue Revolution” was proposed to improve water productivity in agriculture--“More Crop per Drop”. Sorghum is the fifth most imp...

Comparative assessment of techniques for initial pose estimation using monocular vision

NASA Astrophysics Data System (ADS)

Sharma, Sumant; D`Amico, Simone

2016-06-01

This work addresses the comparative assessment of initial pose estimation techniques for monocular navigation to enable formation-flying and on-orbit servicing missions. Monocular navigation relies on finding an initial pose, i.e., a coarse estimate of the attitude and position of the space resident object with respect to the camera, based on a minimum number of features from a three dimensional computer model and a single two dimensional image. The initial pose is estimated without the use of fiducial markers, without any range measurements or any apriori relative motion information. Prior work has been done to compare different pose estimators for terrestrial applications, but there is a lack of functional and performance characterization of such algorithms in the context of missions involving rendezvous operations in the space environment. Use of state-of-the-art pose estimation algorithms designed for terrestrial applications is challenging in space due to factors such as limited on-board processing power, low carrier to noise ratio, and high image contrasts. This paper focuses on performance characterization of three initial pose estimation algorithms in the context of such missions and suggests improvements.

Robust head pose estimation via supervised manifold learning.

PubMed

Wang, Chao; Song, Xubo

2014-05-01

Head poses can be automatically estimated using manifold learning algorithms, with the assumption that with the pose being the only variable, the face images should lie in a smooth and low-dimensional manifold. However, this estimation approach is challenging due to other appearance variations related to identity, head location in image, background clutter, facial expression, and illumination. To address the problem, we propose to incorporate supervised information (pose angles of training samples) into the process of manifold learning. The process has three stages: neighborhood construction, graph weight computation and projection learning. For the first two stages, we redefine inter-point distance for neighborhood construction as well as graph weight by constraining them with the pose angle information. For Stage 3, we present a supervised neighborhood-based linear feature transformation algorithm to keep the data points with similar pose angles close together but the data points with dissimilar pose angles far apart. The experimental results show that our method has higher estimation accuracy than the other state-of-art algorithms and is robust to identity and illumination variations. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Personality disorders, psychopathy and serial killers].

PubMed

Morana, Hilda C P; Stone, Michael H; Abdalla-Filho, Elias

2006-10-01

To illustrate the basic characteristics of several specific personality disorders, focusing mainly in antisocial personality disorder. The differences between antisocial personality disorder and psychopathy are highlighted. Serial killers and its psychopathic aspects are also discussed. A bibliographic review was completed in order to outline convergences and divergences among different authors about this controversial issue, especially those concerning the possibility of treatment. While anti-social personality disorder is a medical diagnosis, the term "psychopathy" (which belongs to the sphere of forensic psychiatry) may be understood as a "legal diagnosis". It is not still possible to identify an effective treatment for serial killers. Personality disorders, especially of the antisocial type, still represent a formidable challenge to forensic psychiatry today. Questions as yet unanswered include the best and most humane place for patients with this condition and the nature of a standardised treatment recommendation.

phMRI: methodological considerations for mitigating potential confounding factors

PubMed Central

Bourke, Julius H.; Wall, Matthew B.

2015-01-01

Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome. PMID:25999812

Thermodynamics of quantum information scrambling

NASA Astrophysics Data System (ADS)

Campisi, Michele; Goold, John

2017-06-01

Scrambling of quantum information can conveniently be quantified by so-called out-of-time-order correlators (OTOCs), i.e., correlators of the type <[Wτ,V ] †[Wτ,V ] > , whose measurements present a formidable experimental challenge. Here we report on a method for the measurement of OTOCs based on the so-called two-point measurement scheme developed in the field of nonequilibrium quantum thermodynamics. The scheme is of broader applicability than methods employed in current experiments and provides a clear-cut interpretation of quantum information scrambling in terms of nonequilibrium fluctuations of thermodynamic quantities, such as work and heat. Furthermore, we provide a numerical example on a spin chain which highlights the utility of our thermodynamic approach when understanding the differences between integrable and ergodic behaviors. We also discuss how the method can be used to extend the reach of current experiments.

Participant satisfaction with the vocational rehabilitation process: a micro perspective of relationship dimensions.

PubMed

Scovotti, Carol; Peltier, James W

2005-01-01

This article is the last in a series of two that examines participant satisfaction with the vocational rehabilitation (VR) process. Disabled individuals face formidable challenges when entering the workforce. The VR process involves a complex series of interactions and relationships among participants, counselors, training professionals, ancillary service providers, and employers to help participants prepare for and find employment. In the first article, we identified six relationship dimensions that influence overall satisfaction with vocational training services and presented a highly reliable survey instrument. In part two, we look at the items within each dimension and identify those with the greatest impact on participant satisfaction. The findings show that the level of caring or concern demonstrated by the counselor, an element of the interpersonal social bond dimension, has the greatest affect on participant satisfaction with the entire VR process.

Carbon Condensation during High Explosive Detonation with Time Resolved Small Angle X-ray Scattering

NASA Astrophysics Data System (ADS)

Hammons, Joshua; Bagge-Hansen, Michael; Nielsen, Michael; Lauderbach, Lisa; Hodgin, Ralph; Bastea, Sorin; Fried, Larry; May, Chadd; Sinclair, Nicholas; Jensen, Brian; Gustavsen, Rick; Dattelbaum, Dana; Watkins, Erik; Firestone, Millicent; Ilavsky, Jan; van Buuren, Tony; Willey, Trevor; Lawrence Livermore National Lab Collaboration; Los Alamos National Laboratory Collaboration; Washington State University/Advanced Photon Source Team

Carbon condensation during high-energy detonations occurs under extreme conditions and on very short time scales. Understanding and manipulating soot formation, particularly detonation nanodiamond, has attracted the attention of military, academic and industrial research. An in-situ characterization of these nanoscale phases, during detonation, is highly sought after and presents a formidable challenge even with today's instruments. Using the high flux available with synchrotron X-rays, pink beam small angle X-ray scattering is able to observe the carbon phases during detonation. This experimental approach, though powerful, requires careful consideration and support from other techniques, such as post-mortem TEM, EELS and USAXS. We present a comparative survey of carbon condensation from different CHNO high explosives. This work was performed under the auspices of the US DOE by LLNL under Contract DE-AC52-07NA27344.

The social dilemma of autonomous vehicles.

PubMed

Bonnefon, Jean-François; Shariff, Azim; Rahwan, Iyad

2016-06-24

Autonomous vehicles (AVs) should reduce traffic accidents, but they will sometimes have to choose between two evils, such as running over pedestrians or sacrificing themselves and their passenger to save the pedestrians. Defining the algorithms that will help AVs make these moral decisions is a formidable challenge. We found that participants in six Amazon Mechanical Turk studies approved of utilitarian AVs (that is, AVs that sacrifice their passengers for the greater good) and would like others to buy them, but they would themselves prefer to ride in AVs that protect their passengers at all costs. The study participants disapprove of enforcing utilitarian regulations for AVs and would be less willing to buy such an AV. Accordingly, regulating for utilitarian algorithms may paradoxically increase casualties by postponing the adoption of a safer technology. Copyright © 2016, American Association for the Advancement of Science.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

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

Kong, Lingping; Liu, Gang; Gong, Jue

The organic-inorganic hybrid lead trihalide perovskites have been emerging as the most attractive photovoltaic materials. As regulated by Shockley-Queisser theory, a formidable materials science challenge for improvement to the next level requires further band-gap narrowing for broader absorption in solar spectrum, while retaining or even synergistically prolonging the carrier lifetime, a critical factor responsible for attaining the near-band-gap photovoltage. Herein, by applying controllable hydrostatic pressure, we have achieved unprecedented simultaneous enhancement in both band-gap narrowing and carrier-lifetime prolongation (up to 70% to -100% increase) under mild pressures at -0.3 GPa. The pressure-induced modulation on pure hybrid perovskites without introducing anymore » adverse chemical or thermal effect clearly demonstrates the importance of band edges on the photon-electron interaction and maps a pioneering route toward a further increase in their photovoltaic performance.« less

On the Unruly Power of Pain in Middle English Drama.

PubMed

Nakley, Susan

2015-01-01

Late medieval culture tends to value pain highly and positively. Accordingly, much medievalist scholarship links pain with fear and emphasizes their usefulness in the period's philosophy, literature, visual art, and drama. Yet, key moments in The York Play of the Crucifixion, The Second Shepherds' Play, and The Tretise of Miraclis Pleyinge trouble the significance of pain and its relationships with punishment and performance; these works admit the unreliability of pain and fear, even as they harness the formidable power pain holds throughout Middle English literature. This essay analyzes passages from all three texts to demonstrate their deep skepticism about the signifying power of pain alongside their abiding investments in pain's utility. I argue that these texts ultimately challenge Middle English drama's dominant discourses of patriarchy and empire by way of their representations of pain.

A reagent-controlled SN2-glycosylation for the direct synthesis of β-linked 2-deoxy-sugars.

PubMed

Issa, John Paul; Bennett, Clay S

2014-04-16

The efficient and stereoselective construction of glycosidic linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as β-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce β-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an α-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an SN2-pathway.

Predictors of High Level of Hostility among Homeless Men on Parole

PubMed Central

Nyamathi, Adeline; Salem, Benissa; Farabee, David; Hall, Elizabeth; Zhang, Sheldon; Khalilifard, Farinaz; Faucette, Mark; Leake, Barbara

2014-01-01

High levels of hostility present a formidable challenge among homeless ex-offenders. This cross-sectional study assessed correlates of high levels of hostility using baseline data collected on recently-released male parolees (N=472; age 18-60) participating in a randomized trial focused on prevention of illicit drug use and recidivism. Predictors of high levels of hostility included greater depressive symptomatology, lower self-esteem, having a mother who was treated for alcohol/drugs, belonging to a gang, more tangible support, having used methamphetamine and having a history of cognitive difficulties. These findings highlight the need to understand predictors of hostility among recently released homeless men and how these predictors may relate to recidivism. Research implications are discussed as these findings will shape future nurse-led harm reduction and community-based interventions. PMID:25083121

Observations give us CLUES to Cosmic Flows' origins

NASA Astrophysics Data System (ADS)

Sorce, Jenny; Courtois, H.; Gottloeber, S.; Hoffman, Y.; Pomarede, D.; Tully, R. B.; Flows, Cosmic; CLUES

2014-01-01

In an era where the wealth of telescope-data and the development of computer superclusters keep increasing, the knowledge of Large Scale Structures' formation and evolution constitutes a tremendous challenge. Within this context the project Cosmic Flows has recently produced a catalog of peculiar velocities up to 150 Mpc. These velocities, obtained from direct distance measurements, are ideal markers of the underlying gravitational potential. They form a fantastic input to perform constrained simulations of the Local Universe within the CLUES project. A new method has recently been elaborated to achieve these simulations which prove to be excellent replicas of our neighborhood. The Wiener-Filter, the Reverse Zel'dovich Approximation and the Constrained Realization techniques are combined to build Initial Conditions. The resulting second generation of constrained simulations presents us the formidable history of the Great Attractor's and nearby supercluster's formation.

Ethics and Research with Undergraduates

ERIC Educational Resources Information Center

Richman, Kenneth A.; Alexander, Leslie B.

2006-01-01

Ethicists, researchers and policy makers have paid increasing attention to the ethical conduct of research, especially research involving human beings. Research performed with and by undergraduates poses a specific set of ethical challenges. These challenges are often overlooked by the research community because it is assumed that undergraduate…

Jesuit "Eloquentia Perfecta" and Theotropic Logology

ERIC Educational Resources Information Center

Mailloux, Steven

2015-01-01

This essay takes a rhetorical pragmatist perspective on current questions concerning educational goals and pedagogical practices. It begins by considering some challenges to rhetorical approaches to education, placing those challenges in the theoretical context of their posing. The essay then describes one current rhetorical approach--based on…

Challenges for PISA

ERIC Educational Resources Information Center

Schleicher, Andreas

2016-01-01

The OECD Programme for International Student Assessment (PISA) provides a framework in which over 80 countries collaborate to build advanced global metrics to assess the knowledge, skills and character attributes of the students. The design of assessments poses major conceptual and technical challenges, as successful learning. Beyond a sound…

Regenerative medicine in Brazil: small but innovative.

PubMed

McMahon, Dominique S; Singer, Peter A; Daar, Abdallah S; Thorsteinsdóttir, Halla

2010-11-01

Although Brazil has received attention for conducting one of the world's largest stem cell clinical trials for heart disease, little has been published regarding Brazil's regenerative medicine (RM) sector. Here we present a comprehensive case study of RM in Brazil, including analysis of the current activity, the main motivations for engaging in RM and the remaining challenges to development in this field. Our case study is primarily based on semi-structured interviews with experts on RM in Brazil, including researchers, policymakers, clinicians, representatives of firms and regulators. Driven by domestic health needs and strategic government support, Brazil is producing innovative RM research, particularly for clinical research in cardiology, orthopedics, diabetes and neurology. We describe the main RM research currently taking place in Brazil, as well as some of the economic, regulatory and policy events that have created a favorable environment for RM development. Brazilian RM researchers need to overcome several formidable challenges to research: research funding is inconsistent, importation of materials is costly and slow, and weak linkages between universities, hospitals and industry impede translational research. Although Brazil's contribution to the RM sector is small, its niche emphasis on clinical applications may become of global importance, particularly if Brazil manages to address the challenges currently impinging on RM innovation.

Challenges of Conducting Research With Young Offenders With Traumatic Brain Injury.

PubMed

OʼRourke, Conall; Templeton, Michelle; Cohen, Miriam H; Linden, Mark A

2018-05-31

The purpose of this commentary is to highlight the challenges encountered when conducting research with young offenders. This is drawn from the first-hand experience of 3 researchers working on separate projects within this environment. Young offenders present as a complex clinical population with high levels of illiteracy, substance abuse, and mental health issues. Significant planning is therefore required before working with this group. Consideration must be given to the heterogeneity of prison populations alongside the potential limitations of datacollection methods, in particular, reliance on self-report. The capacity of young offenders to comprehend and effectively engage with research is also of concern, posing issues of both a practical and ethical nature. The absence of a consistent "research culture" within prison environments poses further practical challenges, potentially also placing significant burden on both researchers and prison resources. The challenges discussed in this article may help inform future studies in the area and emphasize the need for greater critical reflection among researchers conducting work of this type.

Bisphenol A and Risk Management Ethics

PubMed Central

Resnik, David B.; Elliot, Kevin C.

2013-01-01

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. PMID:24471646

Bisphenol A and risk management ethics.

PubMed

Resnik, David B; Elliott, Kevin C

2015-03-01

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. © 2014 John Wiley & Sons Ltd.

The challenges associated with developing science-based landscape scale management plans.

Treesearch

Robert C. Szaro; Douglas A. Jr. Boyce; Thomas Puchlerz

2005-01-01

Planning activities over large landscapes poses a complex of challenges when trying to balance the implementation of a conservation strategy while still allowing for a variety of consumptive and nonconsumptive uses. We examine a case in southeast Alaska to illustrate the breadth of these challenges and an approach to developing a science-based resource plan. Not only...

Intelligent Tutoring Systems for Literacy: Existing Technologies and Continuing Challenges

ERIC Educational Resources Information Center

Jacovina, Matthew E.; McNamara, Danielle S.

2017-01-01

In this chapter, we describe several intelligent tutoring systems (ITSs) designed to support student literacy through reading comprehension and writing instruction and practice. Although adaptive instruction can be a powerful tool in the literacy domain, developing these technologies poses significant challenges. For example, evaluating the…

THE DNAPL REMEDIATION CHALLENGE: IS THERE A CASE FOR SOURCE DEPLETION?

EPA Science Inventory

Releases of Dense Non-Aqueous Phase Liquids (DNAPLs) at a large number of public and private sector sites in the United States pose significant challenges in site remediation and long-term site management. Extensive contamination of groundwater occurs as a result of significant ...

Social Risk Takers: Understanding Bilingualism in Mathematical Discussions

ERIC Educational Resources Information Center

Dominguez, Higinio

2017-01-01

The teaching and research communities in mathematics education agree that mathematical discussions pose challenges in elementary classrooms. These challenges continue to motivate research on mathematical discussions, with a focus on how students use talk in discussions. This study addresses the question, "What can teachers and researchers…

LIFE CYCLE ASSESSMENT (LCA) AS A FRAMEWORK FOR ADDRESSING THE SUSTAINABILITY OF CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFOS)

EPA Science Inventory

The challenges Concentrated Animal Feeding Operations (CAFOs) directly pose to sustainability include their impact on human health, receiving water bodies, groundwater, and air quality. These challenges result from the large quantities of macronutrients (carbon, nitrogen, and pho...

The Threat or Challenge of Accountability

ERIC Educational Resources Information Center

Rosenberg, Marvin L.; Brody, Ralph

1974-01-01

Social service agencies can improve accountability to their clients in specific ways. These techniques borrow some of the language and principles of management science and can be applied successfully only if social workers accept the challenge posed by accountability and view these concepts as compatible with professional values. (Author)

Exploration Design Challenge 2014

NASA Image and Video Library

2014-04-25

Team Lore poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Lore was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

Exploration Design Challenge 2014

NASA Image and Video Library

2014-04-25

Team Aegis poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Aegis was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

Food Aversions and Cravings during Pregnancy on Yasawa Island, Fiji.

PubMed

McKerracher, Luseadra; Collard, Mark; Henrich, Joseph

2016-09-01

Women often experience novel food aversions and cravings during pregnancy. These appetite changes have been hypothesized to work alongside cultural strategies as adaptive responses to the challenges posed by pregnancy (e.g., maternal immune suppression). Here, we report a study that assessed whether data from an indigenous population in Fiji are consistent with the predictions of this hypothesis. We found that aversions focus predominantly on foods expected to exacerbate the challenges of pregnancy. Cravings focus on foods that provide calories and micronutrients while posing few threats to mothers and fetuses. We also found that women who experience aversions to specific foods are more likely to crave foods that meet nutritional needs similar to those provided by the aversive foods. These findings are in line with the predictions of the hypothesis. This adds further weight to the argument that appetite changes may function in parallel with cultural mechanisms to solve pregnancy challenges.

Climate Change and Health in the Urban Context: The Experience of Barcelona.

PubMed

Villalbí, Joan R; Ventayol, Irma

2016-07-01

Climate change poses huge challenges for public health, and cities are at the forefront of this process. The purpose of this paper is to present the issues climate change poses for public health in the city of Barcelona, how they are being addressed, and what are the current major challenges, trying to contribute to the development of a baseline understanding of the status of adaptation in cities from a public health perspective. The major issues related to climate change faced by the city are common to other urban centers in a Mediterranean climate: heat waves, water availability and quality, air quality, and diseases transmitted by vectors, and all are reviewed in detail with empirical data. They are not a potential threat for the future, but have actually challenged the city services and infrastructure over the last years, requiring sustainable responses and rigorous planning. © The Author(s) 2016.

Inhalable Microorganisms in Beijing’s PM2.5 and PM10 Pollutants during a Severe Smog Event

PubMed Central

2014-01-01

Particulate matter (PM) air pollution poses a formidable public health threat to the city of Beijing. Among the various hazards of PM pollutants, microorganisms in PM2.5 and PM10 are thought to be responsible for various allergies and for the spread of respiratory diseases. While the physical and chemical properties of PM pollutants have been extensively studied, much less is known about the inhalable microorganisms. Most existing data on airborne microbial communities using 16S or 18S rRNA gene sequencing to categorize bacteria or fungi into the family or genus levels do not provide information on their allergenic and pathogenic potentials. Here we employed metagenomic methods to analyze the microbial composition of Beijing’s PM pollutants during a severe January smog event. We show that with sufficient sequencing depth, airborne microbes including bacteria, archaea, fungi, and dsDNA viruses can be identified at the species level. Our results suggested that the majority of the inhalable microorganisms were soil-associated and nonpathogenic to human. Nevertheless, the sequences of several respiratory microbial allergens and pathogens were identified and their relative abundance appeared to have increased with increased concentrations of PM pollution. Our findings may serve as an important reference for environmental scientists, health workers, and city planners. PMID:24456276

Narrating consciousness: language, media and embodiment.

PubMed

Hayles, N Katherine; Pulizzi, James J

2010-01-01

Although there has long been a division in studies of consciousness between a focus on neuronal processes or conversely an emphasis on the ruminations of a conscious self, the long-standing split between mechanism and meaning within the brain was mirrored by a split without, between information as a technical term and the meanings that messages are commonly thought to convey. How to heal this breach has posed formidable problems to researchers. Working through the history of cybernetics, one of the historical sites where Claude Shannon's information theory quickly became received doctrine, we argue that the cybernetic program as it developed through second-order cybernetics and autopoietic theory remains incomplete. In this article, we return to fundamental questions about pattern and noise, context and meaning, to forge connections between consciousness, narrative and media. The thrust of our project is to reintroduce context and narrative as crucial factors in the processes of meaning-making. The project proceeds along two fronts: advancing a theoretical framework within which context plays its property central role; and demonstrating the importance of context by analyzing two fictions, Stanislaw Lem's "His Master's Voice" and Joseph McElroy's "Plus," in which context has been deformed by being wrenched away from normal human environments, with radical consequences for processes of meaning-making.

The future water environment--using scenarios to explore the significant water management challenges in England and Wales to 2050.

PubMed

Henriques, C; Garnett, K; Weatherhead, E K; Lickorish, F A; Forrow, D; Delgado, J

2015-04-15

Society gets numerous benefits from the water environment. It is crucial to ensure that water management practices deliver these benefits over the long-term in a sustainable and cost-effective way. Currently, hydromorphological alterations and nutrient enrichment pose the greatest challenges in European water bodies. The rapidly changing climatic and socio-economic boundary conditions pose further challenges to water management decisions and the achievement of policy goals. Scenarios are a strategic tool useful in conducting systematic investigations of future uncertainties pertaining to water management. In this study, the use of scenarios revealed water management challenges for England and Wales to 2050. A set of existing scenarios relevant to river basin management were elaborated through stakeholder workshops and interviews, relying on expert knowledge to identify drivers of change, their interdependencies, and influence on system dynamics. In a set of four plausible alternative futures, the causal chain from driving forces through pressures to states, impacts and responses (DPSIR framework) was explored. The findings suggest that scenarios driven by short-term economic growth and competitiveness undermine current environmental legislative requirements and exacerbate the negative impacts of climate change, producing a general deterioration of water quality and physical habitats, as well as reduced water availability with adverse implications for the environment, society and economy. Conversely, there are substantial environmental improvements under the scenarios characterised by long-term sustainability, though achieving currently desired environmental outcomes still poses challenges. The impacts vary across contrasting generic catchment types that exhibit distinct future water management challenges. The findings suggest the need to address hydromorphological alterations, nutrient enrichment and nitrates in drinking water, which are all likely to be exacerbated in the future. Future-proofing river basin management measures that deal with these challenges is crucial moving forward. The use of scenarios to future-proof strategy, policy and delivery mechanisms is discussed to inform next steps. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of group size on the success of wolves hunting bison.

PubMed

MacNulty, Daniel R; Tallian, Aimee; Stahler, Daniel R; Smith, Douglas W

2014-01-01

An intriguing aspect of social foraging behaviour is that large groups are often no better at capturing prey than are small groups, a pattern that has been attributed to diminished cooperation (i.e., free riding) in large groups. Although this suggests the formation of large groups is unrelated to prey capture, little is known about cooperation in large groups that hunt hard-to-catch prey. Here, we used direct observations of Yellowstone wolves (Canis lupus) hunting their most formidable prey, bison (Bison bison), to test the hypothesis that large groups are more cooperative when hunting difficult prey. We quantified the relationship between capture success and wolf group size, and compared it to previously reported results for Yellowstone wolves hunting elk (Cervus elaphus), a prey that was, on average, 3 times easier to capture than bison. Whereas improvement in elk capture success levelled off at 2-6 wolves, bison capture success levelled off at 9-13 wolves with evidence that it continued to increase beyond 13 wolves. These results are consistent with the hypothesis that hunters in large groups are more cooperative when hunting more formidable prey. Improved ability to capture formidable prey could therefore promote the formation and maintenance of large predator groups, particularly among predators that specialize on such prey.

Influence of Group Size on the Success of Wolves Hunting Bison

PubMed Central

MacNulty, Daniel R.; Tallian, Aimee; Stahler, Daniel R.; Smith, Douglas W.

2014-01-01

An intriguing aspect of social foraging behaviour is that large groups are often no better at capturing prey than are small groups, a pattern that has been attributed to diminished cooperation (i.e., free riding) in large groups. Although this suggests the formation of large groups is unrelated to prey capture, little is known about cooperation in large groups that hunt hard-to-catch prey. Here, we used direct observations of Yellowstone wolves (Canis lupus) hunting their most formidable prey, bison (Bison bison), to test the hypothesis that large groups are more cooperative when hunting difficult prey. We quantified the relationship between capture success and wolf group size, and compared it to previously reported results for Yellowstone wolves hunting elk (Cervus elaphus), a prey that was, on average, 3 times easier to capture than bison. Whereas improvement in elk capture success levelled off at 2–6 wolves, bison capture success levelled off at 9–13 wolves with evidence that it continued to increase beyond 13 wolves. These results are consistent with the hypothesis that hunters in large groups are more cooperative when hunting more formidable prey. Improved ability to capture formidable prey could therefore promote the formation and maintenance of large predator groups, particularly among predators that specialize on such prey. PMID:25389760

A fragment-based approach to the SAMPL3 Challenge

NASA Astrophysics Data System (ADS)

Kulp, John L.; Blumenthal, Seth N.; Wang, Qiang; Bryan, Richard L.; Guarnieri, Frank

2012-05-01

The success of molecular fragment-based design depends critically on the ability to make predictions of binding poses and of affinity ranking for compounds assembled by linking fragments. The SAMPL3 Challenge provides a unique opportunity to evaluate the performance of a state-of-the-art fragment-based design methodology with respect to these requirements. In this article, we present results derived from linking fragments to predict affinity and pose in the SAMPL3 Challenge. The goal is to demonstrate how incorporating different aspects of modeling protein-ligand interactions impact the accuracy of the predictions, including protein dielectric models, charged versus neutral ligands, ΔΔGs solvation energies, and induced conformational stress. The core method is based on annealing of chemical potential in a Grand Canonical Monte Carlo (GC/MC) simulation. By imposing an initially very high chemical potential and then automatically running a sequence of simulations at successively decreasing chemical potentials, the GC/MC simulation efficiently discovers statistical distributions of bound fragment locations and orientations not found reliably without the annealing. This method accounts for configurational entropy, the role of bound water molecules, and results in a prediction of all the locations on the protein that have any affinity for the fragment. Disregarding any of these factors in affinity-rank prediction leads to significantly worse correlation with experimentally-determined free energies of binding. We relate three important conclusions from this challenge as applied to GC/MC: (1) modeling neutral ligands—regardless of the charged state in the active site—produced better affinity ranking than using charged ligands, although, in both cases, the poses were almost exactly overlaid; (2) simulating explicit water molecules in the GC/MC gave better affinity and pose predictions; and (3) applying a ΔΔGs solvation correction further improved the ranking of the neutral ligands. Using the GC/MC method under a variety of parameters in the blinded SAMPL3 Challenge provided important insights to the relevant parameters and boundaries in predicting binding affinities using simulated annealing of chemical potential calculations.

Comparison of Student and Instructor Perceptions of Social Presence

ERIC Educational Resources Information Center

Mathieson, Kathleen; Leafman, Joan S.

2014-01-01

As enrollment in online courses continues to grow and online education is increasingly recognized as an established instructional mode, the unique challenges posed by this learning environment should be addressed. A primary challenge for virtual educators is developing social presence such that participants feel a sense of human connection with…

Prediction, Error, and Adaptation during Online Sentence Comprehension

ERIC Educational Resources Information Center

Fine, Alex Brabham

2013-01-01

A fundamental challenge for human cognition is perceiving and acting in a world in which the statistics that characterize available sensory data are non-stationary. This thesis focuses on this problem specifically in the domain of sentence comprehension, where linguistic variability poses computational challenges to the processes underlying…

Entrepreneurship Education Can Business Schools Meet the Challenge

ERIC Educational Resources Information Center

Kirby, David A.

2004-01-01

Examines the characteristics and role of the entrepreneur and the challenges for business schools posed by the need to develop more enterprising individuals. Argues that the traditional education system stultifies rather than develops the requisite attributes and skills to produce entrepreneurs, and proposes that if entrepreneurs are to be…

Quantitative Approaches to Group Research: Suggestions for Best Practices

ERIC Educational Resources Information Center

McCarthy, Christopher J.; Whittaker, Tiffany A.; Boyle, Lauren H.; Eyal, Maytal

2017-01-01

Rigorous scholarship is essential to the continued growth of group work, yet the unique nature of this counseling specialty poses challenges for quantitative researchers. The purpose of this proposal is to overview unique challenges to quantitative research with groups in the counseling field, including difficulty in obtaining large sample sizes…

Adoption of Internet2 in a Southwestern University: Human Resources Concerns

ERIC Educational Resources Information Center

Mendoza-Diaz, Noemi V.; Dooley, Larry M.; Dooley, Kim E.

2007-01-01

Human Resources are often times challenged by the integration of new technologies (Benson, Johnson, & Kichinke, 2002). Universities pose a unique challenge since they reluctantly adapt to changes (Torraco & Hoover, 2005; Watkins 2005). This is a dissertation study of the human resource concerns about adopting Internet2 in a…

A Perkins Challenge: Assessing Technical Skills in CTE

ERIC Educational Resources Information Center

Stone, James R., III

2009-01-01

Federal law requires state to develop performance measures and data-collection systems for secondary and postsecondary technical-skill attainment. This poses many challenges, such as defining a technical skills, measurement and when to assess students. In this article, the author outlines various assessment models and looks at the challenges…

Military Children and Families: Strengths and Challenges during Peace and War

ERIC Educational Resources Information Center

Park, Nansook

2011-01-01

Throughout history, military children and families have shown great capacity for adaptation and resilience. However, in recent years, unprecedented lengthy and multiple combat deployments of service members have posed multiple challenges for U.S. military children and families. Despite needs to better understand the impact of deployment on…

Intergenerational Challenges in Australian Jewish School Education

ERIC Educational Resources Information Center

Gross, Zehavit; Rutland, Suzanne D.

2014-01-01

The aim of this research is to investigate the intergenerational changes that have occurred in Australian Jewish day schools and the challenges these pose for religious and Jewish education. Using a grounded theory approach according to the constant comparative method (Strauss 1987), data from three sources (interviews [296], observations [27],…

Insights into the polerovirus-plant interactome revealed by co-immunoprecipitation and mass spectrometry

USDA-ARS?s Scientific Manuscript database

The identification of host proteins that interact with virus proteins is a major challenge for the field of virology. Phloem-limited viruses pose extraordinary challenges for in vivo protein interaction experiments because these viruses are localized in very few and highly specialized host cells. ...

Evaluation Options for Family Resource Centers.

ERIC Educational Resources Information Center

Horsch, Karen, Ed.; Weiss, Heather B., Ed.

Family resource centers (FRC) are emerging as a promising program approach to solving urgent social problems. Evaluation plays an important role in learning how these programs work, what their impact is, and whether they should be expanded. However, FRCs pose unique challenges to evaluation. This report considers the challenges to evaluating FRCs,…

Many Faces Have I.

ERIC Educational Resources Information Center

Zilliox, Joseph T.; Lowery, Shannon G.

1997-01-01

Describes an extended investigation of polygons and polyhedra which was conducted in response to a challenge posed in Focus, a newsletter from the Mathematical Association of America (MAA). Students were challenged to construct a polyhedron with faces that measure more than 13 inches to a side. Outlines the process, including the questions posed…

Relative Clauses in Cantonese-English Bilingual Children: Typological Challenges and Processing Motivations

ERIC Educational Resources Information Center

Yip, Virginia; Matthews, Stephen

2007-01-01

Findings from a longitudinal study of bilingual children acquiring Cantonese and English pose a challenge to the noun phrase accessibility hierarchy (NPAH; Keenan & Comrie, 1977), which predicts that object relatives should not be acquired before subject relatives. In the children's Cantonese, object relatives emerged earlier than or…

A Self-Adaptive Multi-Agent System Approach for Collaborative Mobile Learning

ERIC Educational Resources Information Center

de la Iglesia, Didac Gil; Calderon, Juan Felipe; Weyns, Danny; Milrad, Marcelo; Nussbaum, Miguel

2015-01-01

Mobile technologies have emerged as facilitators in the learning process, extending traditional classroom activities. However, engineering mobile learning applications for outdoor usage poses severe challenges. The requirements of these applications are challenging, as many different aspects need to be catered, such as resource access and sharing,…

Big Data Goes Personal: Privacy and Social Challenges

ERIC Educational Resources Information Center

Bonomi, Luca

2015-01-01

The Big Data phenomenon is posing new challenges in our modern society. In addition to requiring information systems to effectively manage high-dimensional and complex data, the privacy and social implications associated with the data collection, data analytics, and service requirements create new important research problems. First, the high…

Science, Sport and Technology--A Contribution to Educational Challenges

ERIC Educational Resources Information Center

O'Hara, Kelly; Reis, Paula; Esteves, Dulce; Bras, Rui; Branco, Luisa

2011-01-01

Improve students' ability to link knowledge with real life practice, through enhancing children or teenagers' ability to think critically by way of making observations, posing questions, drawing up hypotheses, planning and carrying out investigations, analysing data and therefore improve their decision making is an educational challenge. Learning…

Challenging Anti-Immigration Discourses in School and Community Contexts

ERIC Educational Resources Information Center

Allexsaht-Snider, Martha; Buxton, Cory A.; Harman, Ruth

2012-01-01

Rapid migration shifts, anti-immigrant discourses in the public sphere, and harsh immigration policies have posed daunting challenges for immigrant students, their families, their teachers, and their communities in the 21st century. Trends in public discourse and law enforcement in the United States mirror developments in European countries with…

The architecture challenge: Future artificial-intelligence systems will require sophisticated architectures, and knowledge of the brain might guide their construction.

PubMed

Baldassarre, Gianluca; Santucci, Vieri Giuliano; Cartoni, Emilio; Caligiore, Daniele

2017-01-01

In this commentary, we highlight a crucial challenge posed by the proposal of Lake et al. to introduce key elements of human cognition into deep neural networks and future artificial-intelligence systems: the need to design effective sophisticated architectures. We propose that looking at the brain is an important means of facing this great challenge.

Challenges and climate of business environment and resources to support pediatric device development.

PubMed

Iqbal, Corey W; Wall, James; Harrison, Michael R

2015-06-01

The incidence of pediatric disease conditions pales in comparison to adult disease. Consequently, many pediatric disorders are considered orphan diseases. Resources for the development of devices targeting orphan diseases are scarce and this poses a unique challenge to the development of pediatric devices. This article outlines these challenges and offers solutions. Copyright © 2015 Elsevier Inc. All rights reserved.

Thesis Writing Challenges for Non-Native MA Students

ERIC Educational Resources Information Center

Sadeghi, Karim; Shirzad Khajepasha, Arash

2015-01-01

Writing in a second (L2)/foreign language is generally a challenging activity, and writing an MA thesis, as an example of academic enterprise, can be daunting when done in a language in which the writer is not fully competent. The challenge such a genre of writing poses for L2 writers has not been properly addressed. To fill in the gap in this…

Exploration Design Challenge 2014

NASA Image and Video Library

2014-04-25

Team Titan Shielding Systems poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Titan Shielding Systems was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

Exploring the Stability of Ligand Binding Modes to Proteins by Molecular Dynamics Simulations: A Cross-docking Study.

PubMed

Liu, Kai; Kokubo, Hironori

2017-10-23

Docking has become an indispensable approach in drug discovery research to predict the binding mode of a ligand. One great challenge in docking is to efficiently refine the correct pose from various putative docking poses through scoring functions. We recently examined the stability of self-docking poses under molecular dynamics (MD) simulations and showed that equilibrium MD simulations have some capability to discriminate between correct and decoy poses. Here, we have extended our previous work to cross-docking studies for practical applications. Three target proteins (thrombin, heat shock protein 90-alpha, and cyclin-dependent kinase 2) of pharmaceutical interest were selected. Three comparable poses (one correct pose and two decoys) for each ligand were then selected from the docking poses. To obtain the docking poses for the three target proteins, we used three different protocols, namely: normal docking, induced fit docking (IFD), and IFD against the homology model. Finally, five parallel MD equilibrium runs were performed on each pose for the statistical analysis. The results showed that the correct poses were generally more stable than the decoy poses under MD. The discrimination capability of MD depends on the strategy. The safest way was to judge a pose as being stable if any one run among five parallel runs was stable under MD. In this case, 95% of the correct poses were retained under MD, and about 25-44% of the decoys could be excluded by the simulations for all cases. On the other hand, if we judge a pose as being stable when any two or three runs were stable, with the risk of incorrectly excluding some correct poses, approximately 31-53% or 39-56% of the two decoys could be excluded by MD, respectively. Our results suggest that simple equilibrium simulations can serve as an effective filter to exclude decoy poses that cannot be distinguished by docking scores from the computationally expensive free-energy calculations.

DHS S&T First Responders Group and NATO Counter UAS Proposal Interest Response.

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

Salton, Jonathan R.

The capability, speed, size, and widespread availability of small unmanned aerial systems (sUAS) makes them a serious security concern. The enabling technologies for sUAS are rapidly evolving and so too are the threats they pose to national security. Potential threat vehicles have a small cross-section, and are difficult to reliably detect using purely ground-based systems (e.g. radar or electro-optical) and challenging to target using conventional anti-aircraft defenses. Ground-based sensors are static and suffer from interference with the earth, vegetation and other man-made structures which obscure objects at low altitudes. Because of these challenges, sUAS pose a unique and rapidly evolvingmore » threat to national security.« less

An infant with chronic severe neutropenia

PubMed Central

Bhat, Ramesh Y; Varma, Chaitanya P V; Bhatt, Sonia

2014-01-01

Neutropenia in infancy and childhood poses a diagnostic challenge as the aetiology ranges from acute life-threatening conditions to chronic benign diseases. Chronic benign neutropenia of infancy is a rare disorder occurring in 1:100 000. The neutrophil count continues to be low for a prolonged period until spontaneous resolution by the age of 3–4 years. Such infants are having higher incidences of minor infections requiring treatment with antibiotics and rare incidences of meningitis and sepsis. The authors describe an infant presenting with fever and cervical lymphadenitis, who was found to have isolated severe neutropenia and its persistence posing a diagnostic challenge. The prolonged course with minor infections and absence of serious underlying conditions finally confirmed chronic benign neutropenia of infancy. PMID:24711472

A qualitative exploration of district nurses' care of patients with advanced cancer: the challenges of supporting families within the home.

PubMed

Wilson, Charlotte; Griffiths, Jane; Ewing, Gail; Connolly, Michael; Grande, Gunn

2014-01-01

In the United Kingdom, district nurses (DNs) support patients with advanced cancer in their homes. Although evidence suggests that DNs emphasize the distinctiveness of home rather than hospital settings, little is known about the specific challenges of delivering care in family-home settings. The objective of this study was to explore DNs' experiences of supporting patients within families. Focus groups were conducted with 40 DNs from 4 areas in the United Kingdom. The groups were digitally recorded and facilitated by researchers using a flexible topic guide. Verbatim transcripts were analyzed using thematic content analysis. Case-load complexity (household volatility) and family dynamics posed distinct challenges for nurses supporting patients. Many family members struggled with accepting the patients' prognosis and were complicit in withholding information. At times, this foreclosed a consideration of palliative options. Carers provide a great deal of positive supportive care within the home. However, for some, the home is characterized by conflict rather than consensus. Complexities surrounding family relationships pose a distinctive and challenging environment for DNs. Education and training of DNs should be designed to address the challenges of supporting patients within the family-home setting.

A multimode electromechanical parametric resonator array

PubMed Central

Mahboob, I.; Mounaix, M.; Nishiguchi, K.; Fujiwara, A.; Yamaguchi, H.

2014-01-01

Electromechanical resonators have emerged as a versatile platform in which detectors with unprecedented sensitivities and quantum mechanics in a macroscopic context can be developed. These schemes invariably utilise a single resonator but increasingly the concept of an array of electromechanical resonators is promising a wealth of new possibilities. In spite of this, experimental realisations of such arrays have remained scarce due to the formidable challenges involved in their fabrication. In a variation to this approach, we identify 75 harmonic vibration modes in a single electromechanical resonator of which 7 can also be parametrically excited. The parametrically resonating modes exhibit vibrations with only 2 oscillation phases which are used to build a binary information array. We exploit this array to execute a mechanical byte memory, a shift-register and a controlled-NOT gate thus vividly illustrating the availability and functionality of an electromechanical resonator array by simply utilising higher order vibration modes. PMID:24658349

Secondary HIV prevention among kothi-identified MSM in Chennai, India.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali

2008-05-01

This study explored experiences and contexts of HIV risk and prevention among HIV-positive kothi-identified men in Chennai, India. In-depth, semi-structured interviews were conducted with 10 HIV-positive men and three service providers, recruited using purposive sampling. Interviews were audio-taped, transcribed in Tamil and translated into English. Data were analysed using a narrative thematic approach and constant comparative method. Misconceptions about HIV transmission; cultural taboos around discussing sexual behaviour and HIV; stigma related to same-sex behaviour; harassment; and the criminalization of consensual sex between men present formidable challenges to HIV prevention. Frank and open discussion about male-to-male sexual behaviour and living with HIV, which may support health and HIV prevention, may be dangerous in the context of pervasive risks due to stigmatization, violence and criminalization. Instead, culturally appropriate, multi-level interventions developed in collaboration with community stakeholders are needed to support HIV prevention among kothi-identified men in South India.

Dementia in intellectual disability: a review of diagnostic challenges.

PubMed

Nagdee, M

2011-07-01

The evaluation of dementia in individuals with intellectual disability (ID), which will guide subsequent intervention, care and management depends on the systematic review of a number of factors: (1) the individual historical context, obtained from multiple sources, (2) evaluation of the pre-existing cognitive, behavioural, psychiatric, medical and adaptive skill profile, (3) the constellation, and pattern of evolution, of presenting signs and symptoms, (4) results of focused investigations, and (5) refinement of the differential diagnosis. In patients with ID, standard clinical methods need to be supplemented by careful, longitudinal behavioural observations, and individually tailored assessment techniques. Co-morbidity, multiple biological, psychological and socioenvironmental factors, and complex interactions among events, are the reality for many ageing people with ID. Determining the various influences is often a formidable clinical task, but should be systematically carried out using medical, cognitive, behavioural, neuropsychiatric and psycho-social frameworks.

Symbolic Computation of Strongly Connected Components Using Saturation

NASA Technical Reports Server (NTRS)

Zhao, Yang; Ciardo, Gianfranco

2010-01-01

Finding strongly connected components (SCCs) in the state-space of discrete-state models is a critical task in formal verification of LTL and fair CTL properties, but the potentially huge number of reachable states and SCCs constitutes a formidable challenge. This paper is concerned with computing the sets of states in SCCs or terminal SCCs of asynchronous systems. Because of its advantages in many applications, we employ saturation on two previously proposed approaches: the Xie-Beerel algorithm and transitive closure. First, saturation speeds up state-space exploration when computing each SCC in the Xie-Beerel algorithm. Then, our main contribution is a novel algorithm to compute the transitive closure using saturation. Experimental results indicate that our improved algorithms achieve a clear speedup over previous algorithms in some cases. With the help of the new transitive closure computation algorithm, up to 10(exp 150) SCCs can be explored within a few seconds.

Harnessing the genome for characterization of GPCRs in cancer pathogenesis

PubMed Central

Feigin, Michael E.

2014-01-01

G-protein coupled receptors (GPCRs) mediate numerous physiological processes and represent the targets for a vast array of therapeutics for diseases ranging from depression to hypertension to reflux. Despite the recognition that GPCRs can act as oncogenes and tumor suppressors by regulating oncogenic signaling networks, few drugs targeting GPCRs are utilized in cancer therapy. Recent large-scale genome-wide analyses of multiple human tumors have uncovered novel GPCRs altered in cancer. However, the work of determining which GPCRs from these lists are drivers of tumorigenesis, and hence valid therapeutic targets, remains a formidable challenge. In this review I will highlight recent studies providing evidence that GPCRs are relevant targets for cancer therapy through their effects on known cancer signaling pathways, tumor progression, invasion and metastasis, and the microenvironment. Furthermore, I will explore how genomic analysis is beginning to shine a light on GPCRs as therapeutic targets in the age of personalized medicine. PMID:23927072

Site-Directed Synthesis of Cobalt Oxide Clusters in a Metal–Organic Framework

DOE PAGES

Peters, Aaron W.; Otake, Kenichi; Platero-Prats, Ana E.; ...

2018-04-19

Here, direct control over structure and location of catalytic species deposited on amorphous supports represents a formidable challenge in heterogeneous catalysis. In contrast, a structurally well-defined, crystalline metal–organic framework (MOF) can be rationally designed using post-synthetic techniques to allow for desired structural or locational changes of deposited metal ions. Herein, naphthalene dicarboxylate linkers are incorporated in the MOF, NU-1000, to block the small cavities where few-atom clusters of cobalt oxide preferentially grow, inducing catalyst deposition towards hither-to ill-favored grafting sites orientated toward NU-1000’s mesoporous channels. Despite the different cobalt oxide location, the resulting material is still an active propane oxidativemore » dehydrogenation catalyst at low temperature, reaching a turnover frequency of 0.68 ± 0.05 h –1 at 230 °C and confirming the utility of MOFs as crystalline supports to guide rational design of catalysts.« less

Environmental Trigger(s) of Type 1 Diabetes: Why So Difficult to Identify?

PubMed Central

2015-01-01

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease has increased two- to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself so that, in a very specific and targeted way, it destroys the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will focus on factors which have to be evaluated and decision to take before starting a new prospective cohort study. Considering all the large ongoing prospective studies, new and more conclusive data than that obtained so far should instead come from international collaboration on the ongoing cohort studies. PMID:25883954

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

Wilkerson, Andrea M.; McCullough, Jeffrey J.

The Yuma Sector Border Patrol Area is a high flux lighting application in a high temperature environment, presenting a formidable challenge for light-emitting diodes (LEDs). This retrofit is an Energy Savings Performance Contract ENABLE project under the U.S. Department of Energy (DOE) Federal Energy Management Program. If high flux LED technology performs well in a region with high ambient temperature and solar radiation, it can perform well in most outdoor environments. The design process for the Yuma retrofit has already provided valuable knowledge to CBP and DOE. The LED lighting system selected for the retrofit is expected to reduce energymore » consumption 69% compared to the incumbent quartz metal halide (QMH) lighting system. If the LED lighting system is installed, GATEWAY will continue to document and disseminate information regarding the installation and long-term performance so that others may also gain valuable knowledge from the Yuma Sector Border Patrol Area lighting retrofit.« less

PubMed

2009-03-10

Warming up: recovery sister and Territorial Army (TA) nurse Zayne Crow is undertaking a 151-mile race this month across part of the Sahara Desert. Ms Crow, who works at the King Edward VII's Hospital, London, and is an emergency nurse at the TA's City of London Field Hospital, is competing in the formidable Marathon des Sables, in Morocco. This is described as the world's toughest foot race, in which competitors run the equivalent of five and a half marathons in six days while carrying all of their kit, in temperatures of up to 50°C. Ms Crow said: 'The extreme temperatures and the weight I will be carrying will make it an immense challenge but, in terms of physical and mental fitness, I am in peak condition.' Ms Crow is raising funds for the wounded service personnel charity, Help for Heroes. ►For more information, go to www.justgiving.com/zaynecrow.

Complexity and Competition in Appetitive and Aversive Neural Circuits

PubMed Central

Barberini, Crista L.; Morrison, Sara E.; Saez, Alex; Lau, Brian; Salzman, C. Daniel

2012-01-01

Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two brain areas that process appetitive and aversive stimuli, reveals a dynamic relationship between appetitive and aversive circuits. Specifically, the relationship between signaling in appetitive and aversive circuits in these areas shifts as a function of learning. Furthermore, although appetitive and aversive circuits may often drive opposite behaviors – approaching or avoiding reinforcement depending upon its valence – these circuits can also drive similar behaviors, such as enhanced arousal or attention; these processes also may influence choice behavior. These data highlight the formidable challenges ahead in dissecting how appetitive and aversive neural circuits interact to produce a complex and nuanced range of behaviors. PMID:23189037

Kidney regeneration by xeno-embryonic nephrogenesis.

PubMed

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Kawamura, Tetsuya

2008-03-01

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

Progress on Updating the 1961-1990 National Solar Radiation Database

NASA Technical Reports Server (NTRS)

Renne, D.; Wilcox, S.; Marion, B.; George, R.; Myers, D.

2003-01-01

The 1961-1990 National Solar Radiation Data Base (NSRDB) provides a 30-year climate summary and solar characterization of 239 locations throughout the United States. Over the past several years, the National Renewable Energy Laboratory (NREL) has received numerous inquiries from a range of constituents as to whether an update of the database to include the 1990s will be developed. However, there are formidable challenges to creating an update of the serially complete station-specific database for the 1971-2000 period. During the 1990s, the National Weather Service changed its observational procedures from a human-based to an automated system, resulting in the loss of important input variables to the model used to complete the 1961-1990 NSRDB. As a result, alternative techniques are required for an update that covers the 1990s. This paper examines several alternative approaches for creating this update and describes preliminary NREL plans for implementing the update.

Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer

PubMed Central

Kim, Yunee; Jeon, Jouhyun; Mejia, Salvador; Yao, Cindy Q; Ignatchenko, Vladimir; Nyalwidhe, Julius O; Gramolini, Anthony O; Lance, Raymond S; Troyer, Dean A; Drake, Richard R; Boutros, Paul C; Semmes, O. John; Kislinger, Thomas

2016-01-01

Biomarkers are rapidly gaining importance in personalized medicine. Although numerous molecular signatures have been developed over the past decade, there is a lack of overlap and many biomarkers fail to validate in independent patient cohorts and hence are not useful for clinical application. For these reasons, identification of novel and robust biomarkers remains a formidable challenge. We combine targeted proteomics with computational biology to discover robust proteomic signatures for prostate cancer. Quantitative proteomics conducted in expressed prostatic secretions from men with extraprostatic and organ-confined prostate cancers identified 133 differentially expressed proteins. Using synthetic peptides, we evaluate them by targeted proteomics in a 74-patient cohort of expressed prostatic secretions in urine. We quantify a panel of 34 candidates in an independent 207-patient cohort. We apply machine-learning approaches to develop clinical predictive models for prostate cancer diagnosis and prognosis. Our results demonstrate that computationally guided proteomics can discover highly accurate non-invasive biomarkers. PMID:27350604

Electrophilicity: the "dark-side" of indole chemistry.

PubMed

Bandini, Marco

2013-08-28

Indole is by far one of the most popular heterocyclic scaffolds in nature. The intriguing and challenging molecular architectures of polycyclic, naturally occurring indolyl compounds constitute a continuous stimulus for development in organic synthesis. The field had a formidable boom across the new millennium when catalysis started revolutionizing the chemistry of indole, providing always more convincing and sustainable solutions to the selective "decoration" of this pharmacophore. A common guideline of these approaches relies on the intrinsic overexpression of electron density of the indole core. Despite less diffusion, the "dark-side" of indole reactivity, electrophilicity, has been also elegantly documented with direct applications towards the realization of specific interatomic connections that would be difficult to obtain by means of conventional indole reactivity. The present Perspective article summarizes the major findings that brought the research area from the pioneering findings of the 60s to the state of the art.

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants

PubMed Central

Beletsky, Leo; Ciccarone, Daniel

2018-01-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis’ trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions. PMID:29267060

Mergers involving academic health centers: a formidable challenge.

PubMed

Pellegrini, V D

2001-10-01

Escalating economic pressures on the clinical enterprise threaten the missions of education and research in many of the most prestigious academic health centers. Following the model of industry, mergers of the healthcare delivery systems of teaching hospitals and clinics held promise for economies of scale and an improved operating margin. Failure to follow business principles in constructing the merged entity, differences in organizational governance and culture, and inability of physician leadership to prioritize, downsize, and consolidate clinical programs to optimize operational efficiencies all compromise the success of such mergers in academic medicine. Academic institutions and their respective governing boards need to exercise greater discipline in financial analysis and a willingness to make difficult decisions that show favor to one parent institution over another if mergers are to be effective in this setting. To date, an example of a vibrant and successful merger of academic health centers remains to be found.

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles

PubMed Central

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L.; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-01-01

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi2Ta2O9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction–relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes. PMID:28194017

Mechanical stimulation in the engineering of heart muscle.

PubMed

Liaw, Norman Yu; Zimmermann, Wolfram-Hubertus

2016-01-15

Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. Copyright © 2015. Published by Elsevier B.V.

Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective.

PubMed

Khurana, Surender

2018-04-27

Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.

The Centauri project: Manned interstellar travel

NASA Technical Reports Server (NTRS)

Ciesla, Thomas M.

1990-01-01

The development of antimatter engines for spacecraft propulsion will allow man to expand to the nearest stellar neighbors such as the Alpha Centuri system. Compared to chemically powered rockets like the Apollo mission class which would take 50,000 years to reach the Centauri system, antimatter propulsion would reduce one way trip time to 30 years or less. The challenges encountered by manned interstellar travel are formidable. The spacecraft must be a combination of sublight speed transportation system and a traveling microplanet serving an expanding population. As the population expands from the initial 100 people to approximately 300, the terraformed asteroid, enclosed by a man-made shell will allow for expansion over its surface in the fashion of a small terrestrial town. All aspects of human life - birth; death; physical, emotional, and educational needs; and government and law must be met by the structure, systems, and institutions on-board.

Synthesis and Stereochemical Assignment of Crypto-Optically Active (2) H6 -Neopentane.

PubMed

Masarwa, Ahmad; Gerbig, Dennis; Oskar, Liron; Loewenstein, Aharon; Reisenauer, Hans Peter; Lesot, Philippe; Schreiner, Peter R; Marek, Ilan

2015-10-26

The determination of the absolute configuration of chiral molecules is at the heart of asymmetric synthesis. Here we probe the spectroscopic limits for chiral discrimination with NMR spectroscopy in chiral aligned media and with vibrational circular dichroism spectroscopy of the sixfold-deuterated chiral neopentane. The study of this compound presents formidable challenges since its stereogenicity is only due to small mass differences. For this purpose, we selectively prepared both enantiomers of (2) H6 -1 through a concise synthesis utilizing multifunctional intermediates. While NMR spectroscopy in chiral aligned media could be used to characterize the precursors to (2) H6 -1, the final assignment could only be accomplished with VCD spectroscopy, despite the fleetingly small dichroic properties of 1. Both enantiomers were assigned by matching the VCD spectra with those computed with density functional theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidative 1,2-carboamination of alkenes with alkyl nitriles and amines toward γ-amino alkyl nitriles

NASA Astrophysics Data System (ADS)

Liu, Yan-Yun; Yang, Xu-Heng; Song, Ren-Jie; Luo, Shenglian; Li, Jin-Heng

2017-04-01

Difunctionalization of alkenes has become a powerful tool for quickly increasing molecular complexity in synthesis. Despite significant progress in the area of alkene difunctionalization involving the incorporation of a nitrogen atom across the C-C double bonds, approaches for the direct 1,2-carboamination of alkenes to produce linear N-containing molecules are scarce and remain a formidable challenge. Here we describe a radical-mediated oxidative intermolecular 1,2-alkylamination of alkenes with alkyl nitriles and amines involving C(sp3)-H oxidative functionalization catalysed by a combination of Ag2CO3 with iron Lewis acids. This three-component alkene 1,2-alkylamination method is initiated by the C(sp3)-H oxidative radical functionalization, which enables one-step formation of two new chemical bonds, a C-C bond and a C-N bond, to selectively produce γ-amino alkyl nitriles.

Molecular recognition using receptor-free nanomechanical infrared spectroscopy based on a quantum cascade laser

PubMed Central

Kim, Seonghwan; Lee, Dongkyu; Liu, Xunchen; Van Neste, Charles; Jeon, Sangmin; Thundat, Thomas

2013-01-01

Speciation of complex mixtures of trace explosives presents a formidable challenge for sensors that rely on chemoselective interfaces due to the unspecific nature of weak intermolecular interactions. Nanomechanical infrared (IR) spectroscopy provides higher selectivity in molecular detection without using chemoselective interfaces by measuring the photothermal effect of adsorbed molecules on a thermally sensitive microcantilever. In addition, unlike conventional IR spectroscopy, the detection sensitivity is drastically enhanced by increasing the IR laser power, since the photothermal signal comes from the absorption of IR photons and nonradiative decay processes. By using a broadly tunable quantum cascade laser for the resonant excitation of molecules, we increased the detection sensitivity by one order of magnitude compared to the use of a conventional IR monochromator. Here, we demonstrate the successful speciation and quantification of picogram levels of ternary mixtures of similar explosives (trinitrotoluene (TNT), cyclotrimethylene trinitramine (RDX), and pentaerythritol tetranitrate (PETN)) using nanomechanical IR spectroscopy. PMID:23346368

Relaxation dynamics of dysprosium(III) single molecule magnets.

PubMed

Guo, Yun-Nan; Xu, Gong-Feng; Guo, Yang; Tang, Jinkui

2011-10-21

Over the past decade, lanthanide compounds have become of increasing interest in the field of Single Molecule Magnets (SMMs) due to the large inherent anisotropy of the metal ions. Heavy lanthanide metal systems, in particular those containing the dysprosium(III) ion, have been extensively employed to direct the formation of a series of SMMs. Although remarkable progress is being made regarding the synthesis and characterization of lanthanide-based SMMs, the understanding and control of the relaxation dynamics of strongly anisotropic systems represents a formidable challenge, since the dynamic behaviour of lanthanide-based SMMs is significantly more complex than that of transition metal systems. This perspective paper describes illustrative examples of pure dysprosium(III)-based SMMs, published during the past three years, showing new and fascinating phenomena in terms of magnetic relaxation, aiming at shedding light on the features relevant to modulating relaxation dynamics of polynuclear lanthanide SMMs. This journal is © The Royal Society of Chemistry 2011

A plasmonic nanorod that walks on DNA origami

PubMed Central

Zhou, Chao; Duan, Xiaoyang; Liu, Na

2015-01-01

In nano-optics, a formidable challenge remains in precise transport of a single optical nano-object along a programmed and routed path toward a predefined destination. Molecular motors in living cells that can walk directionally along microtubules have been the inspiration for realizing artificial molecular walkers. Here we demonstrate an active plasmonic system, in which a plasmonic nanorod can execute directional, progressive and reverse nanoscale walking on two or three-dimensional DNA origami. Such a walker comprises an anisotropic gold nanorod as its ‘body' and discrete DNA strands as its ‘feet'. Specifically, our walker carries optical information and can in situ optically report its own walking directions and consecutive steps at nanometer accuracy, through dynamic coupling to a plasmonic stator immobilized along its walking track. Our concept will enable a variety of smart nanophotonic platforms for studying dynamic light–matter interaction, which requires controlled motion at the nanoscale well below the optical diffraction limit. PMID:26303016

Simultaneous band-gap narrowing and carrier-lifetime prolongation of organic–inorganic trihalide perovskites

PubMed Central

Kong, Lingping; Liu, Gang; Gong, Jue; Hu, Qingyang; Schaller, Richard D.; Dera, Przemyslaw; Zhang, Dongzhou; Liu, Zhenxian; Yang, Wenge; Zhu, Kai; Tang, Yuzhao; Wang, Chuanyi; Wei, Su-Huai; Xu, Tao; Mao, Ho-kwang

2016-01-01

The organic–inorganic hybrid lead trihalide perovskites have been emerging as the most attractive photovoltaic materials. As regulated by Shockley–Queisser theory, a formidable materials science challenge for improvement to the next level requires further band-gap narrowing for broader absorption in solar spectrum, while retaining or even synergistically prolonging the carrier lifetime, a critical factor responsible for attaining the near-band-gap photovoltage. Herein, by applying controllable hydrostatic pressure, we have achieved unprecedented simultaneous enhancement in both band-gap narrowing and carrier-lifetime prolongation (up to 70% to ∼100% increase) under mild pressures at ∼0.3 GPa. The pressure-induced modulation on pure hybrid perovskites without introducing any adverse chemical or thermal effect clearly demonstrates the importance of band edges on the photon–electron interaction and maps a pioneering route toward a further increase in their photovoltaic performance. PMID:27444014

Concepts: Integrating population survey data from different spatial scales, sampling methods, and species

USGS Publications Warehouse

Dorazio, Robert; Delampady, Mohan; Dey, Soumen; Gopalaswamy, Arjun M.; Karanth, K. Ullas; Nichols, James D.

2017-01-01

Conservationists and managers are continually under pressure from the public, the media, and political policy makers to provide “tiger numbers,” not just for protected reserves, but also for large spatial scales, including landscapes, regions, states, nations, and even globally. Estimating the abundance of tigers within relatively small areas (e.g., protected reserves) is becoming increasingly tractable (see Chaps. 9 and 10), but doing so for larger spatial scales still presents a formidable challenge. Those who seek “tiger numbers” are often not satisfied by estimates of tiger occupancy alone, regardless of the reliability of the estimates (see Chaps. 4 and 5). As a result, wherever tiger conservation efforts are underway, either substantially or nominally, scientists and managers are frequently asked to provide putative large-scale tiger numbers based either on a total count or on an extrapolation of some sort (see Chaps. 1 and 2).

Wilhelm Heinrich Erb, M.D. (1840 to 1921): a historical perspective on Erb's palsy.

PubMed

Watt, Andrew J; Niederbichler, Andreas D; Yang, Lynda J-S; Chung, Kevin C

2007-06-01

Erb's palsy is well known to physicians across medical specialties, and its clinical manifestations present a formidable challenge to reconstructive surgeons. Although the condition is well established, knowledge pertaining to its namesake, Wilhelm Heinrich Erb, is rather obscure in the existing scientific literature. Erb was influential not only through his description of classic brachial plexus palsy involving the superior (or upper) roots, but also by his indelible contributions to our understanding of peripheral nerve physiology, deep tendon reflexes, and the muscular dystrophies. Erb's contributions to medicine transcend specialty boundaries. In this article, the authors seek to convey his scientific achievements and the character of the man through translation of his German manuscripts. These texts, complemented by the existing English literature, provide a unique perspective on Wilhelm Heinrich Erb's contribution to medicine. The authors will also emphasize his role in describing and clarifying the nature of Erb's palsy.

Moving beyond the stigma: systematic review of video games and their potential to combat obesity.

PubMed

Guy, Stacey; Ratzki-Leewing, Alexandria; Gwadry-Sridhar, Femida

2011-01-01

Increasing epidemic proportions of overweight children in the United States presents formidable challenges for education and healthcare. Given the popularity and pervasiveness of video gaming culture in North American children, the perfect opportunity arises to investigate the potential of video games to promote healthful behaviour. Our objective was to systematically review the literature for possible benefits of active and educational video games targeting diet and physical activity in children. A review of English-language journal articles from 1998 to 2011 using EMBASE and PubMed was conducted. Thirty-four studies concerned with children, video games, physical, and/or nutritional outcomes were included. Results of these studies that showed some benefit (increased physical activity and nutritional knowledge as a result of gaming) demonstrate the possibility of video games to combat childhood obesity-looking beyond the stigma attached to gaming.

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles

NASA Astrophysics Data System (ADS)

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L.; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-02-01

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi2Ta2O9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction-relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes.

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles.

PubMed

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-02-13

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi 2 Ta 2 O 9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction-relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes.

SBROME: a scalable optimization and module matching framework for automated biosystems design.

PubMed

Huynh, Linh; Tsoukalas, Athanasios; Köppe, Matthias; Tagkopoulos, Ilias

2013-05-17

The development of a scalable framework for biodesign automation is a formidable challenge given the expected increase in part availability and the ever-growing complexity of synthetic circuits. To allow for (a) the use of previously constructed and characterized circuits or modules and (b) the implementation of designs that can scale up to hundreds of nodes, we here propose a divide-and-conquer Synthetic Biology Reusable Optimization Methodology (SBROME). An abstract user-defined circuit is first transformed and matched against a module database that incorporates circuits that have previously been experimentally characterized. Then the resulting circuit is decomposed to subcircuits that are populated with the set of parts that best approximate the desired function. Finally, all subcircuits are subsequently characterized and deposited back to the module database for future reuse. We successfully applied SBROME toward two alternative designs of a modular 3-input multiplexer that utilize pre-existing logic gates and characterized biological parts.

Frequency domain optical parametric amplification

PubMed Central

Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

2014-01-01

Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

Novel Solid Electrolytes for Li-Ion Batteries: A Perspective from Electron Microscopy Studies

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

Ma, Cheng; Chi, Miaofang

2016-06-08

Solid electrolytes can simultaneously overcome two of the most formidable challenges of Li-ion batteries: the severe safety issues and insufficient energy densities. However, before they can be implemented in actual batteries, the ionic conductivity needs to be improved and the interface with electrodes must be optimized. The prerequisite for addressing these issues is a thorough understanding of the material’s behavior at the microscopic and/or the atomic level. (Scanning) transmission electron microscopy is a powerful tool for this purpose, as it can reach an ultrahigh spatial resolution. Here, we review recent electron microscopy investigations on the ion transport behavior in solidmore » electrolytes and their interfaces. Specifically, three aspects will be highlighted: the influence of grain interior atomic configuration on ionic conductivity, the contribution of grain boundaries, and the behavior of solid electrolyte/electrode interfaces. In conclusion, based on this, the perspectives for future research will be discussed.« less

A fast key generation method based on dynamic biometrics to secure wireless body sensor networks for p-health.

PubMed

Zhang, G H; Poon, Carmen C Y; Zhang, Y T

2010-01-01

Body sensor networks (BSNs) have emerged as a new technology for healthcare applications, but the security of communication in BSNs remains a formidable challenge yet to be resolved. The paper discusses the typical attacks faced by BSNs and proposes a fast biometric based approach to generate keys for ensuing confidentiality and authentication in BSN communications. The approach was tested on 900 segments of electrocardiogram. Each segment was 4 seconds long and used to generate a 128-bit key. The results of the study found that entropy of 96% of the keys were above 0.95 and 99% of the hamming distances calculated from any two keys were above 50 bits. Based on the randomness and distinctiveness of these keys, it is concluded that the fast biometric based approach has great potential to be used to secure communication in BSNs for health applications.

The dynamics of insight: mathematical discovery as a phase transition.

PubMed

Stephen, Damian G; Boncoddo, Rebecca A; Magnuson, James S; Dixon, James A

2009-12-01

In recent work in cognitive science, it has been proposed that cognition is a self-organizing, dynamical system. However, capturing the real-time dynamics of cognition has been a formidable challenge. Furthermore, it has been unclear whether dynamics could effectively address the emergence of abstract concepts (e.g., language, mathematics). Here, we provide evidence that a quintessentially cognitive phenomenon-the spontaneous discovery of a mathematical relation-emerges through self-organization. Participants solved a series of gear-system problems while we tracked their eye movements. They initially solved the problems by manually simulating the forces of the gears but then spontaneously discovered a mathematical solution. We show that the discovery of the mathematical relation was predicted by changes in entropy and changes in power-law behavior, two hallmarks of phase transitions. Thus, the present study demonstrates the emergence of higher order cognitive phenomena through the nonlinear dynamics of self-organization.

Security Hardened Cyber Components for Nuclear Power Plants: Phase I SBIR Final Technical Report

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

Franusich, Michael D.

SpiralGen, Inc. built a proof-of-concept toolkit for enhancing the cyber security of nuclear power plants and other critical infrastructure with high-assurance instrumentation and control code. The toolkit is based on technology from the DARPA High-Assurance Cyber Military Systems (HACMS) program, which has focused on applying the science of formal methods to the formidable set of problems involved in securing cyber physical systems. The primary challenges beyond HACMS in developing this toolkit were to make the new technology usable by control system engineers and compatible with the regulatory and commercial constraints of the nuclear power industry. The toolkit, packaged as amore » Simulink add-on, allows a system designer to assemble a high-assurance component from formally specified and proven blocks and generate provably correct control and monitor code for that subsystem.« less

Principles of nanoparticle design for overcoming biological barriers to drug delivery

PubMed Central

Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

2016-01-01

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

Site-Directed Synthesis of Cobalt Oxide Clusters in a Metal–Organic Framework

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

Peters, Aaron W.; Otake, Kenichi; Platero-Prats, Ana E.

Here, direct control over structure and location of catalytic species deposited on amorphous supports represents a formidable challenge in heterogeneous catalysis. In contrast, a structurally well-defined, crystalline metal–organic framework (MOF) can be rationally designed using post-synthetic techniques to allow for desired structural or locational changes of deposited metal ions. Herein, naphthalene dicarboxylate linkers are incorporated in the MOF, NU-1000, to block the small cavities where few-atom clusters of cobalt oxide preferentially grow, inducing catalyst deposition towards hither-to ill-favored grafting sites orientated toward NU-1000’s mesoporous channels. Despite the different cobalt oxide location, the resulting material is still an active propane oxidativemore » dehydrogenation catalyst at low temperature, reaching a turnover frequency of 0.68 ± 0.05 h –1 at 230 °C and confirming the utility of MOFs as crystalline supports to guide rational design of catalysts.« less

Anatomy of quantum critical wave functions in dissipative impurity problems

NASA Astrophysics Data System (ADS)

Blunden-Codd, Zach; Bera, Soumya; Bruognolo, Benedikt; Linden, Nils-Oliver; Chin, Alex W.; von Delft, Jan; Nazir, Ahsan; Florens, Serge

2017-02-01

Quantum phase transitions reflect singular changes taking place in a many-body ground state; however, computing and analyzing large-scale critical wave functions constitutes a formidable challenge. Physical insights into the sub-Ohmic spin-boson model are provided by the coherent-state expansion (CSE), which represents the wave function by a linear combination of classically displaced configurations. We find that the distribution of low-energy displacements displays an emergent symmetry in the absence of spontaneous symmetry breaking while experiencing strong fluctuations of the order parameter near the quantum critical point. Quantum criticality provides two strong fingerprints in critical low-energy modes: an algebraic decay of the average displacement and a constant universal average squeezing amplitude. These observations, confirmed by extensive variational matrix-product-state (VMPS) simulations and field theory arguments, offer precious clues into the microscopics of critical many-body states in quantum impurity models.

Moving Beyond the Stigma: Systematic Review of Video Games and Their Potential to Combat Obesity

PubMed Central

Guy, Stacey; Ratzki-Leewing, Alexandria; Gwadry-Sridhar, Femida

2011-01-01

Increasing epidemic proportions of overweight children in the United States presents formidable challenges for education and healthcare. Given the popularity and pervasiveness of video gaming culture in North American children, the perfect opportunity arises to investigate the potential of video games to promote healthful behaviour. Our objective was to systematically review the literature for possible benefits of active and educational video games targeting diet and physical activity in children. A review of English-language journal articles from 1998 to 2011 using EMBASE and PubMed was conducted. Thirty-four studies concerned with children, video games, physical, and/or nutritional outcomes were included. Results of these studies that showed some benefit (increased physical activity and nutritional knowledge as a result of gaming) demonstrate the possibility of video games to combat childhood obesity—looking beyond the stigma attached to gaming. PMID:21629863

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants.

PubMed

Dasgupta, Nabarun; Beletsky, Leo; Ciccarone, Daniel

2018-02-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis' trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions.

Quasiparticle Approach to Molecules Interacting with Quantum Solvents.

PubMed

Lemeshko, Mikhail

2017-03-03

Understanding the behavior of molecules interacting with superfluid helium represents a formidable challenge and, in general, requires approaches relying on large-scale numerical simulations. Here, we demonstrate that experimental data collected over the last 20 years provide evidence that molecules immersed in superfluid helium form recently predicted angulon quasiparticles [Phys. Rev. Lett. 114, 203001 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.203001]. Most important, casting the many-body problem in terms of angulons amounts to a drastic simplification and yields effective molecular moments of inertia as straightforward analytic solutions of a simple microscopic Hamiltonian. The outcome of the angulon theory is in good agreement with experiment for a broad range of molecular impurities, from heavy to medium-mass to light species. These results pave the way to understanding molecular rotation in liquid and crystalline phases in terms of the angulon quasiparticle.

Pose estimation of industrial objects towards robot operation

NASA Astrophysics Data System (ADS)

Niu, Jie; Zhou, Fuqiang; Tan, Haishu; Cao, Yu

2017-10-01

With the advantages of wide range, non-contact and high flexibility, the visual estimation technology of target pose has been widely applied in modern industry, robot guidance and other engineering practices. However, due to the influence of complicated industrial environment, outside interference factors, lack of object characteristics, restrictions of camera and other limitations, the visual estimation technology of target pose is still faced with many challenges. Focusing on the above problems, a pose estimation method of the industrial objects is developed based on 3D models of targets. By matching the extracted shape characteristics of objects with the priori 3D model database of targets, the method realizes the recognition of target. Thus a pose estimation of objects can be determined based on the monocular vision measuring model. The experimental results show that this method can be implemented to estimate the position of rigid objects based on poor images information, and provides guiding basis for the operation of the industrial robot.

Robust Head-Pose Estimation Based on Partially-Latent Mixture of Linear Regressions.

PubMed

Drouard, Vincent; Horaud, Radu; Deleforge, Antoine; Ba, Sileye; Evangelidis, Georgios

2017-03-01

Head-pose estimation has many applications, such as social event analysis, human-robot and human-computer interaction, driving assistance, and so forth. Head-pose estimation is challenging, because it must cope with changing illumination conditions, variabilities in face orientation and in appearance, partial occlusions of facial landmarks, as well as bounding-box-to-face alignment errors. We propose to use a mixture of linear regressions with partially-latent output. This regression method learns to map high-dimensional feature vectors (extracted from bounding boxes of faces) onto the joint space of head-pose angles and bounding-box shifts, such that they are robustly predicted in the presence of unobservable phenomena. We describe in detail the mapping method that combines the merits of unsupervised manifold learning techniques and of mixtures of regressions. We validate our method with three publicly available data sets and we thoroughly benchmark four variants of the proposed algorithm with several state-of-the-art head-pose estimation methods.

3D ocular ultrasound using gaze tracking on the contralateral eye: a feasibility study.

PubMed

Afsham, Narges; Najafi, Mohammad; Abolmaesumi, Purang; Rohling, Robert

2011-01-01

A gaze-deviated examination of the eye with a 2D ultrasound transducer is a common and informative ophthalmic test; however, the complex task of the pose estimation of the ultrasound images relative to the eye affects 3D interpretation. To tackle this challenge, a novel system for 3D image reconstruction based on gaze tracking of the contralateral eye has been proposed. The gaze fixates on several target points and, for each fixation, the pose of the examined eye is inferred from the gaze tracking. A single camera system has been developed for pose estimation combined with subject-specific parameter identification. The ultrasound images are then transformed to the coordinate system of the examined eye to create a 3D volume. Accuracy of the proposed gaze tracking system and the pose estimation of the eye have been validated in a set of experiments. Overall system error, including pose estimation and calibration, are 3.12 mm and 4.68 degrees.

Predicting binding poses and affinities for protein - ligand complexes in the 2015 D3R Grand Challenge using a physical model with a statistical parameter estimation

NASA Astrophysics Data System (ADS)

Grudinin, Sergei; Kadukova, Maria; Eisenbarth, Andreas; Marillet, Simon; Cazals, Frédéric

2016-09-01

The 2015 D3R Grand Challenge provided an opportunity to test our new model for the binding free energy of small molecules, as well as to assess our protocol to predict binding poses for protein-ligand complexes. Our pose predictions were ranked 3-9 for the HSP90 dataset, depending on the assessment metric. For the MAP4K dataset the ranks are very dispersed and equal to 2-35, depending on the assessment metric, which does not provide any insight into the accuracy of the method. The main success of our pose prediction protocol was the re-scoring stage using the recently developed Convex-PL potential. We make a thorough analysis of our docking predictions made with AutoDock Vina and discuss the effect of the choice of rigid receptor templates, the number of flexible residues in the binding pocket, the binding pocket size, and the benefits of re-scoring. However, the main challenge was to predict experimentally determined binding affinities for two blind test sets. Our affinity prediction model consisted of two terms, a pairwise-additive enthalpy, and a non pairwise-additive entropy. We trained the free parameters of the model with a regularized regression using affinity and structural data from the PDBBind database. Our model performed very well on the training set, however, failed on the two test sets. We explain the drawback and pitfalls of our model, in particular in terms of relative coverage of the test set by the training set and missed dynamical properties from crystal structures, and discuss different routes to improve it.

Gravitational Wave Science: Challenges for Numerical Relativistic Astrophysics

NASA Technical Reports Server (NTRS)

Cenrella, Joan

2005-01-01

Gravitational wave detectors on earth and in space will open up a new observational window on the universe. The new information about astrophysics and fundamental physics these observations will bring is expected to pose exciting challenges. This talk will provide an overview of this emerging area of gravitational wave science, with a focus on the challenges it will bring for numerical relativistic astrophysics and a look at some recent results.

Exploration Design Challenge 2014

NASA Image and Video Library

2014-04-25

Team ARES poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team ARES was the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winning team was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

Web-Scale Search-Based Data Extraction and Integration

DTIC Science & Technology

2011-10-17

differently, posing challenges for aggregating this information. For example, for the task of finding population for cities in Benin, we were faced with...merged record. Our GeoMerging algorithm attempts to address various ambiguity challenges : • For name: The name of a hospital is not a unique...departments in the same building. For agent-extractor results from structured sources, our GeoMerging algorithm overcomes these challenges using a two

Green Flight Challenge

NASA Image and Video Library

2011-09-28

e-Genius Aircraft Pilot Klaus Ohlmann poses for a photograph during the 2011 Green Flight Challenge, sponsored by Google, held at the Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. on Thursday, Sept. 29, 2011. NASA and the Comparative Aircraft Flight Efficiency (CAFE) Foundation are having the challenge with the goal to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Green Flight Challenge

NASA Image and Video Library

2011-09-28

e-Genius Aircraft Pilot Eric Raymond poses for a photograph during the 2011 Green Flight Challenge, sponsored by Google, held at the Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. on Thursday, Sept. 29, 2011. NASA and the Comparative Aircraft Flight Efficiency (CAFE) Foundation are having the challenge with the goal to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Green Flight Challenge

NASA Image and Video Library

2011-09-28

PhoEnix Aircraft Co-Pilot Jeff Shingleton poses for a photograph during the 2011 Green Flight Challenge, sponsored by Google, held at the Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. on Thursday, Sept. 29, 2011. NASA and the Comparative Aircraft Flight Efficiency (CAFE) Foundation are having the challenge with the goal to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Green Flight Challenge

NASA Image and Video Library

2011-09-28

PhoEnix Aircraft Pilot Jim Lee poses for a photograph during the 2011 Green Flight Challenge, sponsored by Google, held at the Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. on Thursday, Sept. 29, 2011. NASA and the Comparative Aircraft Flight Efficiency (CAFE) Foundation are having the challenge with the goal to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

Green Flight Challenge

NASA Image and Video Library

2011-09-28

EcoEagle Aircraft Pilot Mikhael Ponso poses for a photograph during the 2011 Green Flight Challenge, sponsored by Google, held at the Charles M. Schulz Sonoma County Airport in Santa Rosa, Calif. on Thursday, Sept. 29, 2011. NASA and the Comparative Aircraft Flight Efficiency (CAFE) Foundation are having the challenge with the goal to advance technologies in fuel efficiency and reduced emissions with cleaner renewable fuels and electric aircraft. Photo Credit: (NASA/Bill Ingalls)

A Donor-Focused Fundraising Model: An Essential Tool in Community College Foundations' Toolkit

ERIC Educational Resources Information Center

Carter, Linnie S.

2011-01-01

The increased focus on private fundraising poses challenges for community colleges (Jackson & Glass, 2000). A challenge is a lack of fundraising experience within community colleges and their foundations. There now exists a donor-focused fundraising model for community colleges to use to enhance their fundraising initiatives and increase the…

"How Can I Help?": Practicing Familial Support through Simulation

ERIC Educational Resources Information Center

Coughlin, April B.; Dotger, Benjamin H.

2016-01-01

Teachers face numerous challenges in daily practice, including situations that involve the health, safety, and well-being of students and families. When harassment and physical abuse impact K-12 students, these situations pose unexpected challenges to novice teachers working to support their students. In this article, the authors report on a study…

A Strategy to Support Educational Leaders in Developing Countries to Manage Contextual Challenges

ERIC Educational Resources Information Center

Wolhuter, Charl; van der Walt, Hannes; Steyn, Hennie

2016-01-01

The central theoretical argument of this paper is that educational leadership and organisational development and change in educational institutions in developing countries will not be effective unless school leaders are aware of the challenges posed by contextual factors that might have an impact on their professional activities. The article…

Experimental Evidence for Diagramming Benefits in Science Writing

ERIC Educational Resources Information Center

Barstow, Brendan; Fazio, Lisa; Schunn, Christian; Ashley, Kevin

2017-01-01

Arguing for the need for a scientific research study (i.e. writing an introduction to a research paper) poses significant challenges for students. When faced with these challenges, students often generate overly safe replications (i.e. fail to find and include opposition to their hypothesis) or in contrast include no strong support for their…

Places to Go: Challenges to Multicultural Art Education in a Global Economy

ERIC Educational Resources Information Center

Desai, Dipti

2005-01-01

This article examines the relationship between globalization and postmodern multicultural art education. The questions that drive my investigation are: What is the role of postmodern multiculturalism in this current phase of globalization and what challenges does globalization pose for multiculturalism? I explore the shifts in the field of art…

A Systematic Approach to Faculty Development--Capability Improvement for Blended Learning

ERIC Educational Resources Information Center

Badawood, Ashraf; Steenkamp, Annette Lerine; Al-Werfalli, Daw

2013-01-01

Blended learning (BL) provides an efficient and effective instructional experience. However, adopting a BL approach poses some challenges to faculty; the most important obstacle found in this research is faculty's lack of knowledge regarding the use of technology in their teaching. This challenge prompted the research project focused on improving…

Governing during an Institutional Crisis: 10 Fundamental Principles

ERIC Educational Resources Information Center

White, Lawrence

2012-01-01

In today's world, managing a campus crisis poses special challenges for an institution's governing board, which may operate some distance removed from the immediate events giving rise to the crisis. In its most challenging form, a campus crisis--a shooting, a natural disaster, a fraternity hazing death, the arrest of a prominent campus…

Teaching Caribbean Students: Research on Social Issues in the Caribbean and Abroad.

ERIC Educational Resources Information Center

Bastick, Tony, Ed.; Ezenne, Austin, Ed.

The issues and findings in the research essays in this collection focus on two main themes: the identification of challenges in preparing Caribbean students for the new global network and the isolation of the challenges posed in developing these global relations. Part 1, "Socially Sensitive Pedagogies," contains: (1) "Domain-Specific Modern…

Using Testimonial Response to Frame the Challenges and Possibilities of Risky Historical Texts

ERIC Educational Resources Information Center

Damico, James; Apol, Laura

2008-01-01

Literature that vividly and explicitly describes (often in the form of testimonies from one or more characters) traumatic and/or catastrophic events of human history poses particular challenges for readers. This article proposes testimonial response as one approach to responding to these "risky historical texts." By way of introducing "testimonial…

Investigating Factors Affecting Group Processes in Virtual Learning Environments

ERIC Educational Resources Information Center

Hazari, Sunil; Thompson, Sandra

2015-01-01

With the widespread popularity of distance learning, there is a need to investigate elements of online courses that continue to pose significant challenges for educators. One of the challenges relates to creating and managing group projects. This study investigated business students' perceptions of group work in online classes. The constructs of…

Using Facebook to Engage Learners in a Large Introductory Course

ERIC Educational Resources Information Center

Dougherty, Kevin D.; Andercheck, Brita

2014-01-01

Classes of hundreds pose special challenges for teaching and learning. Notable among these challenges is the tendency for students to feel like anonymous spectators rather than active, collaborative participants. To combat this tendency, we used the popular social networking site Facebook to cultivate a sense of community among 200-plus students…

Using System Dynamics as an Evaluation Tool: Experience from a Demonstration Program

ERIC Educational Resources Information Center

Fredericks, Kimberly A.; Deegan, Michael; Carman, Joanne G.

2008-01-01

Evaluators are often faced with many challenges in the design and implementation of a program's evaluation. Because programs are entangled in complex networks of structures and stakeholders, they can be challenging to understand, and they often pose issues of competing and conflicting goals. However, by using a systems mapping approach to…

The Dynamics of Multicultural NPD Teams in Virtual Environments

ERIC Educational Resources Information Center

Fain, Nusa; Kline, Miro

2013-01-01

Changes in the business environment, responses of companies to these changes and the available information and communication technologies (ICT) pose a number of challenges to present and future product developers, as well as to educational institutions. An appropriate response to these challenges is to create a solid basis for strategies to combat…

Review of Federal Motor Vehicle Safety Standards (FMVSS) for Automated Vehicles : Identifying Potential Barriers and Challenges for the Certification of Automated Vehicles Using Existing FMVSS

DOT National Transportation Integrated Search

2016-03-11

The purpose of this work is to identify instances where the existing Federal Motor Vehicle Safety Standards may pose challenges to the introduction of automated vehicles. It identifies standards requiring further review - both to ensure that existing...

Planning the future's forests with assisted migration

Treesearch

Mary I. Williams; R. Kasten Dumroese

2014-01-01

Studies show that changes in climate may exceed plant adaptation and migration. The mismatch in rates between climate change and plant adaptation and migration will pose significant challenges for practitioners that select, grow, and outplant native tree species. Native tree species and populations that are planted today must meet the climatic challenges that they will...

Managing Welfare Reform in Five States: The Challenge of Devolution.

ERIC Educational Resources Information Center

Liebschutz, Sarah F., Ed.

This book analyzes the responses of five states (Florida, Mississippi, New York, Washington, and Wisconsin) to challenges posed by the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 to alter state welfare programs and management systems. Using case studies, the book highlights similarities and differences in the states'…

Reading Desire: From Empathy to Estrangement, from Enlightenment to Implication

ERIC Educational Resources Information Center

Taylor, Lisa K.

2007-01-01

The imperial hubris, insecurities and indifference of our bloody new millennium pose profound challenges to feminist anti-racist and anti-colonial educators. For those of us who turn to literature education to create spaces of sustained moral reflection, there is a particular challenge to think through the kinds of reading practices which might…

Responding to the Mental Health and Well-Being Agenda in Adult Community Learning

ERIC Educational Resources Information Center

Lewis, Lydia

2014-01-01

In the United Kingdom, changes in the policy, funding and commissioning landscape for mental health and well-being are posing opportunities and challenges for adult community learning (ACL). Opportunities include increased recognition of, and funding for, the "wider benefits" of learning, whereas challenges include the risks of ACL…

Muslim Learners in English Schools: A Challenge for School Leaders

ERIC Educational Resources Information Center

Shah, Saeeda

2009-01-01

Faith identity is emerging as significant for Muslim students in the post 9/11 scenario, with implications for their education and wider social cohesion. This poses challenges to school leaders, raising issues not only linked to student achievement and performance, but also with regard to students' identity constructions and their educational…

Automating a Massive Online Course with Cluster Computing

ERIC Educational Resources Information Center

Haas, Timothy C.

2016-01-01

Before massive numbers of students can take online courses for college credit, the challenges of providing tutoring support, answers to student-posed questions, and the control of cheating will need to be addressed. These challenges are taken up here by developing an online course delivery system that runs in a cluster computing environment and is…

Ethical Challenges of In-The-Field Training: A Surgical Perspective

ERIC Educational Resources Information Center

Bernstein, Mark; Knifed, Eva

2007-01-01

The teaching of professions in which technical and manual acts combined with excellent judgment are used to enhance the safety of people, poses challenges to educators. Book learning combined with mock or simulated situations goes a long way, but ultimately "in-the-field" instruction and learning is necessary to qualify trainees for many…

Towards a Clearer Understanding of Student Disadvantage in Higher Education: Problematising Deficit Thinking

ERIC Educational Resources Information Center

Smit, Renee

2012-01-01

The increased diversity in the student body resulting from massification poses particular challenges to higher education. This article engages the uncritical use of the "disadvantage" discourse and its effect on pedagogy. It explores some of the challenges of coping with student diversity, with particular reference to the South African…

From a Semiotic Perspective: Inference Formation and the Critical Comprehension of Television Advertising.

ERIC Educational Resources Information Center

Langrehr, Don

2003-01-01

Outlines a study in which television advertising supplied the text that college students were challenged to interpret. Explains that the language and images of this advertising posed a complex, cognitive challenge--even to these students at advanced levels of education. Concludes that information processing of television advertising presents a…

Challenges to Common Core State Standards Implementation: Views from Six States

ERIC Educational Resources Information Center

Smith, Joanna; Thier, Michael

2017-01-01

The implementation of the Common Core State Standards has posed a number of challenges for school leaders. This study applies a policy implementation conceptual framework to analyze data gathered from 46 interviews in six states. Findings suggest the existence of multiple barriers to Common Core State Standards implementation. To promote…

US EPA - A*Star Partnership - Accelerating the Acceptance of Next-Generation Sciences and Their Application to Regulatory Risk Assessment (A*Star Symposium, Singapore)

EPA Science Inventory

The path for incorporating new alternative methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. Some of these challenges include development of relevant and predictive test systems and computational models to integrate...