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…

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

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…

Futures research: A neglected dimension in environmental policy and planning

Treesearch

David N. Bengston

2012-01-01

The need for strategic foresight in an increasingly complex and rapidly changing world poses a formidable challenge to environmental planners and policy makers. Th is paper introduces futures research as an under used but fruitful set of approaches to addressing this challenge. Futures research is a transdisciplinary social science that uses a wide range of methods to...

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.

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.

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.

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

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...

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.

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…

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...

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.

Teleretinal Imaging to Screen for Diabetic Retinopathy in the Veterans Health Administration

PubMed Central

Cavallerano, Anthony A.; Conlin, Paul R.

2008-01-01

Diabetes is the leading cause of adult vision loss in the United States and other industrialized countries. While the goal of preserving vision in patients with diabetes appears to be attainable, the process of achieving this goal poses a formidable challenge to health care systems. The large increase in the prevalence of diabetes presents practical and logistical challenges to providing quality care to all patients with diabetes. Given this challenge, the Veterans Health Administration (VHA) is increasingly using information technology as a means of improving the efficiency of its clinicians. The VHA has taken advantage of a mature computerized patient medical record system by integrating a program of digital retinal imaging with remote image interpretation (teleretinal imaging) to assist in providing eye care to the nearly 20% of VHA patients with diabetes. We describe this clinical pathway for accessing patients with diabetes in ambulatory care settings, evaluating their retinas for level of diabetic retinopathy with a teleretinal imaging system, and prioritizing their access into an eye and health care program in a timely and appropriate manner. PMID:19885175

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…

Is There a Critical Period for Semantics?

ERIC Educational Resources Information Center

Slabakova, Roumyana

2006-01-01

This article reviews recent research on the second language acquisition of meaning with a view of establishing whether there is a critical period for the acquisition of compositional semantics. It is claimed that the functional lexicon presents the most formidable challenge, while syntax and phrasal semantics pose less difficulty to learners.…

A repellent against the coffee berry borer (Coleoptera: Curculionidae: Scolytinae)

USDA-ARS?s Scientific Manuscript database

The coffee berry borer continues to pose a formidable challenge to coffee growers worldwide. Due to the cryptic life habit of the insect inside coffee berries, effective pest management strategies have been difficult to develop. A sesquiterpene, (E,E)-a-farnesene, produced by infested coffee berries...

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,…

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...

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…

Confirmation of the trials and tribulations of vaping.

PubMed

Budney, Alan J; Sargent, James D; Lee, Dustin C

2015-11-01

Responses to our article indicate consensus on the need for expedited scientific and regulatory action related to vaping of cannabis and other substances to curtail untoward public health impact and identify potential benefits. How to speed up science, increase knowledge and enact responsible regulatory policy poses a formidable challenge.

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.

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.

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.

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…

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 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

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.

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…

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…

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.

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.

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.

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

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.

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.

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

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

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

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.

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

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.

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

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

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.

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.

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…

The Fundamental Issues Study within the British BMD Review

DTIC Science & Technology

1998-02-01

also be considered. Nevertheless, how formidable a challenge is posed by the ascent release of submunitions is acknowledged by Richard Garwin on the...Arguably, the crunch came in February 1987 when Richard Perle, visiting London as US Assistant Secretary for Defense, extolled a strong SDI as the...resignation of Richard Perle. That year was also to see the departure from political office in the Pentagon of four other SDI stalwarts: Frank

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.

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.

Identification of high-level functional/system requirements for future civil transports

NASA Technical Reports Server (NTRS)

Swink, Jay R.; Goins, Richard T.

1992-01-01

In order to accommodate the rapid growth in commercial aviation throughout the remainder of this century, the Federal Aviation Administration (FAA) is faced with a formidable challenge to upgrade and/or modernize the National Airspace System (NAS) without compromising safety or efficiency. A recurring theme in both the Aviation System Capital Investment Plan (CIP), which has replaced the NAS Plan, and the new FAA Plan for Research, Engineering, and Development (RE&D) rely on the application of new technologies and a greater use of automation. Identifying the high-level functional and system impacts of such modernization efforts on future civil transport operational requirements, particularly in terms of cockpit functionality and information transfer, was the primary objective of this project. The FAA planning documents for the NAS of the 2005 era and beyond were surveyed; major aircraft functional capabilities and system components required for such an operating environment were identified. A hierarchical structured analysis of the information processing and flows emanating from such functional/system components were conducted and the results documented in graphical form depicting the relationships between functions and systems.

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.

A Computational Framework for Bioimaging Simulation.

PubMed

Watabe, Masaki; Arjunan, Satya N V; Fukushima, Seiya; Iwamoto, Kazunari; Kozuka, Jun; Matsuoka, Satomi; Shindo, Yuki; Ueda, Masahiro; Takahashi, Koichi

2015-01-01

Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units.

Statistical Teleodynamics: Toward a Theory of Emergence.

PubMed

Venkatasubramanian, Venkat

2017-10-24

The central scientific challenge of the 21st century is developing a mathematical theory of emergence that can explain and predict phenomena such as consciousness and self-awareness. The most successful research program of the 20th century, reductionism, which goes from the whole to parts, seems unable to address this challenge. This is because addressing this challenge inherently requires an opposite approach, going from parts to the whole. In addition, reductionism, by the very nature of its inquiry, typically does not concern itself with teleology or purposeful behavior. Modeling emergence, in contrast, requires the addressing of teleology. Together, these two requirements present a formidable challenge in developing a successful mathematical theory of emergence. In this article, I describe a new theory of emergence, called statistical teleodynamics, that addresses certain aspects of the general problem. Statistical teleodynamics is a mathematical framework that unifies three seemingly disparate domains-purpose-free entities in statistical mechanics, human engineered teleological systems in systems engineering, and nature-evolved teleological systems in biology and sociology-within the same conceptual formalism. This theory rests on several key conceptual insights, the most important one being the recognition that entropy mathematically models the concept of fairness in economics and philosophy and, equivalently, the concept of robustness in systems engineering. These insights help prove that the fairest inequality of income is a log-normal distribution, which will emerge naturally at equilibrium in an ideal free market society. Similarly, the theory predicts the emergence of the three classes of network organization-exponential, scale-free, and Poisson-seen widely in a variety of domains. Statistical teleodynamics is the natural generalization of statistical thermodynamics, the most successful parts-to-whole systems theory to date, but this generalization is only a modest step toward a more comprehensive mathematical theory of emergence.

An integrated real-time health monitoring and impact/collision detection system for bridges in cold remote regions.

DOT National Transportation Integrated Search

2015-03-01

This report presents a research examining the feasibility of creating an integrated structural health : monitoring and impact/collision detection system for bridges in remote cold regions, where in-person : inspection becomes formidable. The research...

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).

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.

Emerging infectious diseases in southeast Asia: regional challenges to control.

PubMed

Coker, Richard J; Hunter, Benjamin M; Rudge, James W; Liverani, Marco; Hanvoravongchai, Piya

2011-02-12

Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37,500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Examining the impact of succession management practices on organizational performance: A national study of U.S. hospitals.

PubMed

Groves, Kevin S

2017-08-03

Spearheaded by the industry's transition from volume- to value-based care, the health care reform movement has spurred both unprecedented challenges and opportunities for developing more effective and sustainable health care delivery organizations. Whereas the formidable challenges of leading hospitals and health systems have been widely discussed, including reimbursement degradation, the rapidly aging workforce, and the imminent wave of executive retirements, the opportunity to leverage succession management and talent development capabilities to overcome these challenges has been largely overlooked. To address this key research and practice need, this multiphase study develops and validates an assessment of succession management practices for health care organizations. Utilizing data collected from two national samples of hospital organizations, the results provide a 32-item succession management assessment comprising seven distinct sets of succession management practices. The results indicate that succession management practices are strongly associated with multiple hospital performance metrics, including patient satisfaction and Medicare Spending per Beneficiary, leadership bench strength, and internal/external placement rate for executive level positions. The author concludes this article with a discussion of several practical implications for health care executives and boards, including employing the succession management assessment for diagnosing development opportunities, benchmarking succession planning and talent development practices against similar hospitals or health systems, and elevating the profile of succession management as a strategic priority in today's increasingly uncertain health care landscape.

Presidents and health reform: from Franklin D. Roosevelt to Barack Obama.

PubMed

Morone, James A

2010-06-01

The health care reforms that President Barack Obama signed into law in March 2010 were seventy-five years in the making. Since Franklin D. Roosevelt, U.S. presidents have struggled to enact national health care reform; most failed. This article explores the highly charged political landscape in which Obama maneuvered and the skills he brought to bear. It contrasts his accomplishments with the experiences of his Oval Office predecessors. Going forward, implementation poses formidable challenges for Democrats, Republicans, and the political process itself.

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.

Human Response to Emergency Warning

NASA Astrophysics Data System (ADS)

Sorensen, J.

2009-12-01

Almost every day people evacuate from their homes, businesses or other sites, even ships, in response to actual or predicted threats or hazards. Evacuation is the primary protective action utilized in large-scale emergencies such as hurricanes, floods, tornados, tsunamis, volcanic eruptions, or wildfires. Although often precautionary, protecting human lives by temporally relocating populations before or during times of threat remains a major emergency management strategy. One of the most formidable challenges facing emergency officials is evacuating residents for a fast-moving and largely unpredictable event such as a wildfire or a local tsunami. How to issue effective warnings to those at risk in time for residents to take appropriate action is an on-going problem. To do so, some communities have instituted advanced communications systems that include reverse telephone call-down systems or other alerting systems to notify at-risk residents of imminent threats. This presentation examines the effectiveness of using reverse telephone call-down systems for warning San Diego residents of wildfires in the October of 2007. This is the first systematic study conducted on this topic and is based on interviews with 1200 households in the evacuation areas.

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

The evolution of sex roles in birds is related to adult sex ratio.

PubMed

Liker, András; Freckleton, Robert P; Székely, Tamás

2013-01-01

Sex-role reversal represents a formidable challenge for evolutionary biologists, since it is not clear which ecological, life-history or social factors facilitated conventional sex roles (female care and male-male competition for mates) to be reversed (male care and female-female competition). Classic theories suggested ecological or life-history predictors of role reversal, but most studies failed to support these hypotheses. Recent theory however predicts that sex-role reversal should be driven by male-biased adult sex ratio (ASR). Here we test this prediction for the first time using phylogenetic comparative analyses. Consistent with theory, both mating system and parental care are strongly related to ASR in shorebirds: conventional sex roles are exhibited by species with female-biased ASR, whereas sex-role reversal is associated with male-biased ASR. These results suggest that social environment has a strong influence on breeding systems and therefore revealing the causes of ASR variation in wild populations is essential for understanding sex role evolution.

Generation of iPS-derived model cells for analyses of hair shaft differentiation.

PubMed

Kido, Takumi; Horigome, Tomoatsu; Uda, Minori; Adachi, Naoki; Hirai, Yohei

2017-09-01

Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS). While Tet- BMP4-KRT31-Luc iPS cells could be maintained as stable iPS cells, the cells differentiated to produce luciferase luminescence in the presence of all-trans retinoic acid (RA) and doxycycline (Dox), and addition of a hair differentiation factor significantly increased luciferase fluorescence. Thus, this cell line may provide a reliable cell-based screening system to evaluate drug candidates for hair differentiation activity.

Getting into the brain: Potential of nanotechnology in the management of NeuroAIDS.

PubMed

Nair, Madhavan; Jayant, Rahul Dev; Kaushik, Ajeet; Sagar, Vidya

2016-08-01

In spite of significant advances in antiretroviral (ARV) therapy, the elimination of human immunodeficiency virus (HIV) reservoirs from the periphery and the central nervous system (CNS) remains a formidable task. The incapability of ARV to go across the blood-brain barrier (BBB) after systemic administration makes the brain one of the dominant HIV reservoirs. Thus, screening, monitoring, and elimination of HIV reservoirs from the brain remain a clinically daunting and key task. The practice and investigation of nanomedicine possesses potentials for therapeutics against neuroAIDS. This review highlights the advancements in nanoscience and nanotechnology to design and develop specific size therapeutic cargo for efficient navigation across BBB so as to recognize and eradicate HIV brain reservoirs. Different navigation and drug release strategies, their biocompatibility and efficacy with related challenges and future prospects are also discussed. This review would be an excellent platform to understand nano-enable multidisciplinary research to formulate efficient nanomedicine for the management of neuroAIDS. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Requirements for guidelines systems: implementation challenges and lessons from existing software-engineering efforts.

PubMed

Shah, Hemant; Allard, Raymond D; Enberg, Robert; Krishnan, Ganesh; Williams, Patricia; Nadkarni, Prakash M

2012-03-09

A large body of work in the clinical guidelines field has identified requirements for guideline systems, but there are formidable challenges in translating such requirements into production-quality systems that can be used in routine patient care. Detailed analysis of requirements from an implementation perspective can be useful in helping define sub-requirements to the point where they are implementable. Further, additional requirements emerge as a result of such analysis. During such an analysis, study of examples of existing, software-engineering efforts in non-biomedical fields can provide useful signposts to the implementer of a clinical guideline system. In addition to requirements described by guideline-system authors, comparative reviews of such systems, and publications discussing information needs for guideline systems and clinical decision support systems in general, we have incorporated additional requirements related to production-system robustness and functionality from publications in the business workflow domain, in addition to drawing on our own experience in the development of the Proteus guideline system (http://proteme.org). The sub-requirements are discussed by conveniently grouping them into the categories used by the review of Isern and Moreno 2008. We cite previous work under each category and then provide sub-requirements under each category, and provide example of similar work in software-engineering efforts that have addressed a similar problem in a non-biomedical context. When analyzing requirements from the implementation viewpoint, knowledge of successes and failures in related software-engineering efforts can guide implementers in the choice of effective design and development strategies.

Requirements for guidelines systems: implementation challenges and lessons from existing software-engineering efforts

PubMed Central

2012-01-01

Background A large body of work in the clinical guidelines field has identified requirements for guideline systems, but there are formidable challenges in translating such requirements into production-quality systems that can be used in routine patient care. Detailed analysis of requirements from an implementation perspective can be useful in helping define sub-requirements to the point where they are implementable. Further, additional requirements emerge as a result of such analysis. During such an analysis, study of examples of existing, software-engineering efforts in non-biomedical fields can provide useful signposts to the implementer of a clinical guideline system. Methods In addition to requirements described by guideline-system authors, comparative reviews of such systems, and publications discussing information needs for guideline systems and clinical decision support systems in general, we have incorporated additional requirements related to production-system robustness and functionality from publications in the business workflow domain, in addition to drawing on our own experience in the development of the Proteus guideline system (http://proteme.org). Results The sub-requirements are discussed by conveniently grouping them into the categories used by the review of Isern and Moreno 2008. We cite previous work under each category and then provide sub-requirements under each category, and provide example of similar work in software-engineering efforts that have addressed a similar problem in a non-biomedical context. Conclusions When analyzing requirements from the implementation viewpoint, knowledge of successes and failures in related software-engineering efforts can guide implementers in the choice of effective design and development strategies. PMID:22405400

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

With God on our side: Religious primes reduce the envisioned physical formidability of a menacing adversary.

PubMed

Holbrook, Colin; Fessler, Daniel M T; Pollack, Jeremy

2016-01-01

The imagined support of benevolent supernatural agents attenuates anxiety and risk perception. Here, we extend these findings to judgments of the threat posed by a potentially violent adversary. Conceptual representations of bodily size and strength summarize factors that determine the relative threat posed by foes. The proximity of allies moderates the envisioned physical formidability of adversaries, suggesting that cues of access to supernatural allies will reduce the envisioned physical formidability of a threatening target. Across two studies, subtle cues of both supernatural and earthly social support reduced the envisioned physical formidability of a violent criminal. These manipulations had no effect on the perceived likelihood of encountering non-conflictual physical danger, raising the possibility that imagined supernatural support leads participants to view themselves not as shielded from encountering perilous situations, but as protected should perils arise. Copyright © 2015 Elsevier B.V. All rights reserved.

A Computational Framework for Bioimaging Simulation

PubMed Central

Watabe, Masaki; Arjunan, Satya N. V.; Fukushima, Seiya; Iwamoto, Kazunari; Kozuka, Jun; Matsuoka, Satomi; Shindo, Yuki; Ueda, Masahiro; Takahashi, Koichi

2015-01-01

Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units. PMID:26147508

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.

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

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.

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.

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

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.

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.

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

Evolution from electrophysiologic to hemodynamic monitoring: the story of left atrial and pulmonary artery pressure monitors.

PubMed

Mooney, Deirdre M; Fung, Erik; Doshi, Rahul N; Shavelle, David M

2015-01-01

Heart failure (HF) is a costly, challenging and highly prevalent medical condition. Hospitalization for acute decompensation is associated with high morbidity and mortality. Despite application of evidence-based medical therapies and technologies, HF remains a formidable challenge for virtually all healthcare systems. Repeat hospitalizations for acute decompensated HF (ADHF) can have major financial impact on institutions and resources. Early and accurate identification of impending ADHF is of paramount importance yet there is limited high quality evidence or infrastructure to guide management in the outpatient setting. Historically, ADHF was identified by physical exam findings or invasive hemodynamic monitoring during a hospital admission; however, advances in medical microelectronics and the advent of device-based diagnostics have enabled long-term ambulatory monitoring of HF patients in the outpatient setting. These monitors have evolved from piggybacking on cardiac implantable electrophysiologic devices to standalone implantable hemodynamic monitors that transduce left atrial or pulmonary artery pressures as surrogate measures of left ventricular filling pressure. As technology evolves, devices will likely continue to miniaturize while their capabilities grow. An important, persistent challenge that remains is developing systems to translate the large volumes of real-time data, particularly data trends, into actionable information that leads to appropriate, safe and timely interventions without overwhelming outpatient cardiology and general medical practices. Future directions for implantable hemodynamic monitors beyond their utility in heart failure may include management of other major chronic diseases such as pulmonary hypertension, end stage renal disease and portal hypertension.

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.

The genetic pleiotropy of musculoskeletal aging

PubMed Central

Karasik, David; Cohen-Zinder, Miri

2012-01-01

Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than “compartmental,” problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the “norm” and “pathology,” which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its “neighboring” tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the “musculoskeleton.” Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a “holistic” genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health. PMID:22934054

Maintaining a Distributed File System by Collection and Analysis of Metrics

NASA Technical Reports Server (NTRS)

Bromberg, Daniel

1997-01-01

AFS(originally, Andrew File System) is a widely-deployed distributed file system product used by companies, universities, and laboratories world-wide. However, it is not trivial to operate: runing an AFS cell is a formidable task. It requires a team of dedicated and experienced system administratores who must manage a user base numbring in the thousands, rather than the smaller range of 10 to 500 faced by the typical system administrator.

Baseline Assessment and Prioritization Framework for IVHM Integrity Assurance Enabling Capabilities

NASA Technical Reports Server (NTRS)

Cooper, Eric G.; DiVito, Benedetto L.; Jacklin, Stephen A.; Miner, Paul S.

2009-01-01

Fundamental to vehicle health management is the deployment of systems incorporating advanced technologies for predicting and detecting anomalous conditions in highly complex and integrated environments. Integrated structural integrity health monitoring, statistical algorithms for detection, estimation, prediction, and fusion, and diagnosis supporting adaptive control are examples of advanced technologies that present considerable verification and validation challenges. These systems necessitate interactions between physical and software-based systems that are highly networked with sensing and actuation subsystems, and incorporate technologies that are, in many respects, different from those employed in civil aviation today. A formidable barrier to deploying these advanced technologies in civil aviation is the lack of enabling verification and validation tools, methods, and technologies. The development of new verification and validation capabilities will not only enable the fielding of advanced vehicle health management systems, but will also provide new assurance capabilities for verification and validation of current generation aviation software which has been implicated in anomalous in-flight behavior. This paper describes the research focused on enabling capabilities for verification and validation underway within NASA s Integrated Vehicle Health Management project, discusses the state of the art of these capabilities, and includes a framework for prioritizing activities.

Non-Fermi liquids in oxide heterostructures

NASA Astrophysics Data System (ADS)

Stemmer, Susanne; Allen, S. James

2018-06-01

Understanding the anomalous transport properties of strongly correlated materials is one of the most formidable challenges in condensed matter physics. For example, one encounters metal-insulator transitions, deviations from Landau Fermi liquid behavior, longitudinal and Hall scattering rate separation, a pseudogap phase, and bad metal behavior. These properties have been studied extensively in bulk materials, such as the unconventional superconductors and heavy fermion systems. Oxide heterostructures have recently emerged as new platforms to probe, control, and understand strong correlation phenomena. This article focuses on unconventional transport phenomena in oxide thin film systems. We use specific systems as examples, namely charge carriers in SrTiO3 layers and interfaces with SrTiO3, and strained rare earth nickelate thin films. While doped SrTiO3 layers appear to be a well behaved, though complex, electron gas or Fermi liquid, the rare earth nickelates are a highly correlated electron system that may be classified as a non-Fermi liquid. We discuss insights into the underlying physics that can be gained from studying the emergence of non-Fermi liquid behavior as a function of the heterostructure parameters. We also discuss the role of lattice symmetry and disorder in phenomena such as metal-insulator transitions in strongly correlated heterostructures.

Oxidation of ethane to ethanol by N2O in a metal-organic framework with coordinatively unsaturated iron(II) sites.

PubMed

Xiao, Dianne J; Bloch, Eric D; Mason, Jarad A; Queen, Wendy L; Hudson, Matthew R; Planas, Nora; Borycz, Joshua; Dzubak, Allison L; Verma, Pragya; Lee, Kyuho; Bonino, Francesca; Crocellà, Valentina; Yano, Junko; Bordiga, Silvia; Truhlar, Donald G; Gagliardi, Laura; Brown, Craig M; Long, Jeffrey R

2014-07-01

Enzymatic haem and non-haem high-valent iron-oxo species are known to activate strong C-H bonds, yet duplicating this reactivity in a synthetic system remains a formidable challenge. Although instability of the terminal iron-oxo moiety is perhaps the foremost obstacle, steric and electronic factors also limit the activity of previously reported mononuclear iron(IV)-oxo compounds. In particular, although nature's non-haem iron(IV)-oxo compounds possess high-spin S = 2 ground states, this electronic configuration has proved difficult to achieve in a molecular species. These challenges may be mitigated within metal-organic frameworks that feature site-isolated iron centres in a constrained, weak-field ligand environment. Here, we show that the metal-organic framework Fe2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate) and its magnesium-diluted analogue, Fe0.1Mg1.9(dobdc), are able to activate the C-H bonds of ethane and convert it into ethanol and acetaldehyde using nitrous oxide as the terminal oxidant. Electronic structure calculations indicate that the active oxidant is likely to be a high-spin S = 2 iron(IV)-oxo species.

New Approaches to HSCT Multidisciplinary Design and Optimization

NASA Technical Reports Server (NTRS)

Schrage, D. P.; Craig, J. I.; Fulton, R. E.; Mistree, F.

1996-01-01

The successful development of a capable and economically viable high speed civil transport (HSCT) is perhaps one of the most challenging tasks in aeronautics for the next two decades. At its heart it is fundamentally the design of a complex engineered system that has significant societal, environmental and political impacts. As such it presents a formidable challenge to all areas of aeronautics, and it is therefore a particularly appropriate subject for research in multidisciplinary design and optimization (MDO). In fact, it is starkly clear that without the availability of powerful and versatile multidisciplinary design, analysis and optimization methods, the design, construction and operation of im HSCT simply cannot be achieved. The present research project is focused on the development and evaluation of MDO methods that, while broader and more general in scope, are particularly appropriate to the HSCT design problem. The research aims to not only develop the basic methods but also to apply them to relevant examples from the NASA HSCT R&D effort. The research involves a three year effort aimed first at the HSCT MDO problem description, next the development of the problem, and finally a solution to a significant portion of the problem.

Nurturing Quality of Higher Education through National Ranking: A Potential Empowerment Model for Developing Countries

ERIC Educational Resources Information Center

Kusumastuti, Dyah; Idrus, Nirwan

2017-01-01

This paper reviews the recently introduced National Higher Education ranking system in Indonesia in order to evaluate its potential as a sustainable model to improve the quality of higher education in the country. It is a scaffold towards an established world-universities ranking system that may prove formidable for a developing country. This…

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.

A linear framework for time-scale separation in nonlinear biochemical systems.

PubMed

Gunawardena, Jeremy

2012-01-01

Cellular physiology is implemented by formidably complex biochemical systems with highly nonlinear dynamics, presenting a challenge for both experiment and theory. Time-scale separation has been one of the few theoretical methods for distilling general principles from such complexity. It has provided essential insights in areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors, ion channels, gene regulation and post-translational modification. In each case, internal molecular complexity has been eliminated, leading to rational algebraic expressions among the remaining components. This has yielded familiar formulas such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these calculations are all instances of a single graph-theoretic framework. Despite the biochemical nonlinearity to which it is applied, this framework is entirely linear, yet requires no approximation. We show that elimination of internal complexity is feasible when the relevant graph is strongly connected. The framework provides a new methodology with the potential to subdue combinatorial explosion at the molecular level.

Management of Lung Cancer Invading the Superior Sulcus.

PubMed

Kratz, Johannes R; Woodard, Gavitt; Jablons, David M

2017-05-01

Superior sulcus tumors have posed a formidable therapeutic challenge since their original description by Pancoast and Tobias in the early twentieth century. Initial therapeutic efforts with radiotherapy were associated with high rates of relapse and mortality. Bimodality therapy with complete surgical resection in the 1960s paved the way for trimodality therapy as the current standard of care in the treatment of superior sulcus tumors. The evolution of treatment approaches over time has provided outcomes that come increasingly closer to rivaling those of similarly staged nonapical lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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.

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.

Recent Perspectives in Ocular Drug Delivery

PubMed Central

Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

2015-01-01

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

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.

Learning Agents for Autonomous Space Asset Management (LAASAM)

NASA Astrophysics Data System (ADS)

Scally, L.; Bonato, M.; Crowder, J.

2011-09-01

Current and future space systems will continue to grow in complexity and capabilities, creating a formidable challenge to monitor, maintain, and utilize these systems and manage their growing network of space and related ground-based assets. Integrated System Health Management (ISHM), and in particular, Condition-Based System Health Management (CBHM), is the ability to manage and maintain a system using dynamic real-time data to prioritize, optimize, maintain, and allocate resources. CBHM entails the maintenance of systems and equipment based on an assessment of current and projected conditions (situational and health related conditions). A complete, modern CBHM system comprises a number of functional capabilities: sensing and data acquisition; signal processing; conditioning and health assessment; diagnostics and prognostics; and decision reasoning. In addition, an intelligent Human System Interface (HSI) is required to provide the user/analyst with relevant context-sensitive information, the system condition, and its effect on overall situational awareness of space (and related) assets. Colorado Engineering, Inc. (CEI) and Raytheon are investigating and designing an Intelligent Information Agent Architecture that will provide a complete range of CBHM and HSI functionality from data collection through recommendations for specific actions. The research leverages CEI’s expertise with provisioning management network architectures and Raytheon’s extensive experience with learning agents to define a system to autonomously manage a complex network of current and future space-based assets to optimize their utilization.

The right incentives enable ocean sustainability successes and provide hope for the future

PubMed Central

Lubchenco, Jane; Cerny-Chipman, Elizabeth B.; Reimer, Jessica N.; Levin, Simon A.

2016-01-01

Healthy ocean ecosystems are needed to sustain people and livelihoods and to achieve the United Nations Sustainable Development Goals. Using the ocean sustainably requires overcoming many formidable challenges: overfishing, climate change, ocean acidification, and pollution. Despite gloomy forecasts, there is reason for hope. New tools, practices, and partnerships are beginning to transform local fisheries, biodiversity conservation, and marine spatial planning. The challenge is to bring them to a global scale. We dissect recent successes using a complex adaptive-systems (CAS) framework, which acknowledges the interconnectedness of social and ecological systems. Understanding how policies and practices change the feedbacks in CASs by altering the behavior of different system components is critical for building robust, sustainable states with favorable emergent properties. Our review reveals that altering incentives—either economic or social norms, or both—can achieve positive outcomes. For example, introduction of well-designed rights-based or secure-access fisheries and ecosystem service accounting shifts economic incentives to align conservation and economic benefits. Modifying social norms can create conditions that incentivize a company, country, or individual to fish sustainably, curb illegal fishing, or create large marine reserves as steps to enhance reputation or self-image. In each example, the feedbacks between individual actors and emergent system properties were altered, triggering a transition from a vicious to a virtuous cycle. We suggest that evaluating conservation tools by their ability to align incentives of actors with broader goals of sustainability is an underused approach that can provide a pathway toward scaling sustainability successes. In short, getting incentives right matters. PMID:27911770

The right incentives enable ocean sustainability successes and provide hope for the future.

PubMed

Lubchenco, Jane; Cerny-Chipman, Elizabeth B; Reimer, Jessica N; Levin, Simon A

2016-12-20

Healthy ocean ecosystems are needed to sustain people and livelihoods and to achieve the United Nations Sustainable Development Goals. Using the ocean sustainably requires overcoming many formidable challenges: overfishing, climate change, ocean acidification, and pollution. Despite gloomy forecasts, there is reason for hope. New tools, practices, and partnerships are beginning to transform local fisheries, biodiversity conservation, and marine spatial planning. The challenge is to bring them to a global scale. We dissect recent successes using a complex adaptive-systems (CAS) framework, which acknowledges the interconnectedness of social and ecological systems. Understanding how policies and practices change the feedbacks in CASs by altering the behavior of different system components is critical for building robust, sustainable states with favorable emergent properties. Our review reveals that altering incentives-either economic or social norms, or both-can achieve positive outcomes. For example, introduction of well-designed rights-based or secure-access fisheries and ecosystem service accounting shifts economic incentives to align conservation and economic benefits. Modifying social norms can create conditions that incentivize a company, country, or individual to fish sustainably, curb illegal fishing, or create large marine reserves as steps to enhance reputation or self-image. In each example, the feedbacks between individual actors and emergent system properties were altered, triggering a transition from a vicious to a virtuous cycle. We suggest that evaluating conservation tools by their ability to align incentives of actors with broader goals of sustainability is an underused approach that can provide a pathway toward scaling sustainability successes. In short, getting incentives right matters.

The Browning of U.S. Higher Education

ERIC Educational Resources Information Center

Roach, Ronald

2009-01-01

The author reports the result of a population analysis released by scholars at the Tomas Rivera Policy Institute at the University of Southern California. The scholars say that changing student demographics may prove the most formidable ever for American colleges and universities as well as for public K-12 school systems. They have pointed to the…

Immobilization of single argon atoms in nano-cages of two-dimensional zeolite model systems.

PubMed

Zhong, Jian-Qiang; Wang, Mengen; Akter, Nusnin; Kestell, John D; Boscoboinik, Alejandro M; Kim, Taejin; Stacchiola, Dario J; Lu, Deyu; Boscoboinik, J Anibal

2017-07-17

The confinement of noble gases on nanostructured surfaces, in contrast to bulk materials, at non-cryogenic temperatures represents a formidable challenge. In this work, individual Ar atoms are trapped at 300 K in nano-cages consisting of (alumino)silicate hexagonal prisms forming a two-dimensional array on a planar surface. The trapping of Ar atoms is detected in situ using synchrotron-based ambient pressure X-ray photoelectron spectroscopy. The atoms remain in the cages upon heating to 400 K. The trapping and release of Ar is studied combining surface science methods and density functional theory calculations. While the frameworks stay intact with the inclusion of Ar atoms, the permeability of gasses (for example, CO) through them is significantly affected, making these structures also interesting candidates for tunable atomic and molecular sieves. These findings enable the study of individually confined noble gas atoms using surface science methods, opening up new opportunities for fundamental research.

Catalysis as an Enabling Science for Sustainable Polymers.

PubMed

Zhang, Xiangyi; Fevre, Mareva; Jones, Gavin O; Waymouth, Robert M

2018-01-24

The replacement of current petroleum-based plastics with sustainable alternatives is a crucial but formidable challenge for the modern society. Catalysis presents an enabling tool to facilitate the development of sustainable polymers. This review provides a system-level analysis of sustainable polymers and outlines key criteria with respect to the feedstocks the polymers are derived from, the manner in which the polymers are generated, and the end-of-use options. Specifically, we define sustainable polymers as a class of materials that are derived from renewable feedstocks and exhibit closed-loop life cycles. Among potential candidates, aliphatic polyesters and polycarbonates are promising materials due to their renewable resources and excellent biodegradability. The development of renewable monomers, the versatile synthetic routes to convert these monomers to polyesters and polycarbonate, and the different end-of-use options for these polymers are critically reviewed, with a focus on recent advances in catalytic transformations that lower the technological barriers for developing more sustainable replacements for petroleum-based plastics.

Immobilization of single argon atoms in nano-cages of two-dimensional zeolite model systems

DOE PAGES

Zhong, Jian-Qiang; Wang, Mengen; Akter, Nusnin; ...

2017-07-17

The confinement of noble gases on nanostructured surfaces, in contrast to bulk materials, at non-cryogenic temperatures represents a formidable challenge. Here, individual Ar atoms are trapped at 300 K in nano-cages consisting of (alumino)silicate hexagonal prisms forming a two-dimensional array on a planar surface. The trapping of Ar atoms is detected in situ using synchrotron-based ambient pressure X-ray photoelectron spectroscopy. The atoms remain in the cages upon heating to 400 K. The trapping and release of Ar is studied combining surface science methods and density functional theory calculations. While the frameworks stay intact with the inclusion of Ar atoms, themore » permeability of gasses (for example, CO) through them is significantly affected, making these structures also interesting candidates for tunable atomic and molecular sieves. Our findings enable the study of individually confined noble gas atoms using surface science methods, opening up new opportunities for fundamental research.« less

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

PubMed

Bode, Gerard H; Coué, Gregory; Freese, Christian; Pickl, Karin E; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F J; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J G; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M; Kirkpatrick, C James; Steinbusch, Harry W M; Frank, Hans-Georg; Unger, Ronald E; Martinez-Martinez, Pilar

2017-04-01

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Advances in surgical techniques for resection of childhood cerebellopontine angle ependymomas are key to survival.

PubMed

Sanford, Robert A; Merchant, Thomas E; Zwienenberg-Lee, Marike; Kun, Larry E; Boop, Frederick A

2009-10-01

Childhood cerebellopontine angle (CPA) ependymoma is an uncommon anatomical variant of posterior fossa ependymoma. In infants and young children, the tumor often goes undetected until it causes hydrocephalus. As CPA ependymomas grow, they distort the anatomy and encase cranial nerves and vessels, thereby making resection a formidable surgical challenge. The purpose of this paper is to describe the surgical technique used to achieve gross total resection (GTR) of CPA ependymomas and demonstrate improved survival in these patients. Surgical techniques used for GTR in 45 patients with CPA ependymoma treated from 1997 to 2008 are described. Results of those procedures are compared with data from 11 patients who previously underwent surgical resection (1985-1995). We achieved GTR in 43 (95.6%) patients and near-total resection in two (4.4%); the probability of progression-free survival was 53.8%, and that of overall survival was 64%. Our novel surgical techniques greatly improve central nervous system function and survival among pediatric patients with CPA ependymoma.

Immobilization of single argon atoms in nano-cages of two-dimensional zeolite model systems

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

Zhong, Jian-Qiang; Wang, Mengen; Akter, Nusnin

The confinement of noble gases on nanostructured surfaces, in contrast to bulk materials, at non-cryogenic temperatures represents a formidable challenge. Here, individual Ar atoms are trapped at 300 K in nano-cages consisting of (alumino)silicate hexagonal prisms forming a two-dimensional array on a planar surface. The trapping of Ar atoms is detected in situ using synchrotron-based ambient pressure X-ray photoelectron spectroscopy. The atoms remain in the cages upon heating to 400 K. The trapping and release of Ar is studied combining surface science methods and density functional theory calculations. While the frameworks stay intact with the inclusion of Ar atoms, themore » permeability of gasses (for example, CO) through them is significantly affected, making these structures also interesting candidates for tunable atomic and molecular sieves. Our findings enable the study of individually confined noble gas atoms using surface science methods, opening up new opportunities for fundamental research.« less

Urban science education: examining current issues through a historical lens

NASA Astrophysics Data System (ADS)

McLaughlin, Cheryl A.

2014-12-01

This paper reviews and synthesizes urban science education studies published between 2000 and 2013 with a view to identifying current challenges faced by both teachers and students in urban classrooms. Additionally, this paper considers the historical events that have shaped the conditions, bureaucracies, and interactions of urban institutions. When the findings from these urban science education studies were consolidated with the historical overview provided, it was revealed that the basic design and regulatory policies of urban schools have not substantively changed since their establishment in the nineteenth century. Teachers in urban science classrooms continue to face issues of inequality, poverty, and social injustice as they struggle to meet the needs of an increasingly diverse student population. Furthermore, persistent concerns of conflicting Discourses, cultural dissonance, and oppression create formidable barriers to science learning. Despite the many modifications in structure and organization, urban students are still subjugated and marginalized in systems that emphasize control and order over high-quality science education.

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.

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.

A novel method for measuring health care system performance: experience from QIDS in the Philippines.

PubMed

Solon, Orville; Woo, Kimberly; Quimbo, Stella A; Shimkhada, Riti; Florentino, Jhiedon; Peabody, John W

2009-05-01

Measuring and monitoring health system performance is important albeit controversial. Technical, logistic and financial challenges are formidable. We introduced a system of measurement, which we call Q, to measure the quality of hospital clinical performance across a range of facilities. This paper describes how Q was developed, implemented in hospitals in the Philippines and how it compares with typical measures. Q consists of measures of clinical performance, patient satisfaction and volume of physician services. We evaluate Q using experimental data from the Quality Improvement Demonstration Study (QIDS), a randomized policy experiment. We determined its responsiveness over time and to changes in structural measures such as staffing and supplies. We also examined the operational costs of implementing Q. Q was sustainable, minimally disruptive and readily grafted into existing routines in 30 hospitals in 10 provinces semi-annually for a period of 2(1/2) years. We found Q to be more responsive to immediate impacts of policy change than standard structural measures. The operational costs totalled USD2133 or USD305 per assessment per site. Q appears to be an achievable assessment tool that is a comprehensive and responsive measure of system level quality at a limited cost in resource-poor settings.

A novel method for measuring health care system performance: experience from QIDS in the Philippines

PubMed Central

Solon, Orville; Woo, Kimberly; Quimbo, Stella A; Shimkhada, Riti; Florentino, Jhiedon; Peabody, John W

2009-01-01

Objectives Measuring and monitoring health system performance is important albeit controversial. Technical, logistic and financial challenges are formidable. We introduced a system of measurement, which we call Q*, to measure the quality of hospital clinical performance across a range of facilities. This paper describes how Q* was developed, implemented in hospitals in the Philippines and how it compares with typical measures. Methods Q* consists of measures of clinical performance, patient satisfaction and volume of physician services. We evaluate Q* using experimental data from the Quality Improvement Demonstration Study (QIDS), a randomized policy experiment. We determined its responsiveness over time and to changes in structural measures such as staffing and supplies. We also examined the operational costs of implementing Q*. Results Q* was sustainable, minimally disruptive and readily grafted into existing routines in 30 hospitals in 10 provinces semi-annually for a period of 2½ years. We found Q* to be more responsive to immediate impacts of policy change than standard structural measures. The operational costs totalled US$2133 or US$305 per assessment per site. Conclusion Q* appears to be an achievable assessment tool that is a comprehensive and responsive measure of system level quality at a limited cost in resource-poor settings. PMID:19224955

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.

Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis.

PubMed

Forrey, Christopher; Saylor, David M; Silverstein, Joshua S; Douglas, Jack F; Davis, Eric M; Elabd, Yossef A

2014-10-14

Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.

Cultured meat from stem cells: challenges and prospects.

PubMed

Post, Mark J

2012-11-01

As one of the alternatives for livestock meat production, in vitro culturing of meat is currently studied. The generation of bio-artificial muscles from satellite cells has been ongoing for about 15 years, but has never been used for generation of meat, while it already is a great source of animal protein. In order to serve as a credible alternative to livestock meat, lab or factory grown meat should be efficiently produced and should mimic meat in all of its physical sensations, such as visual appearance, smell, texture and of course, taste. This is a formidable challenge even though all the technologies to create skeletal muscle and fat tissue have been developed and tested. The efficient culture of meat will primarily depend on culture conditions such as the source of medium and its composition. Protein synthesis by cultured skeletal muscle cells should further be maximized by finding the optimal combination of biochemical and physical conditions for the cells. Many of these variables are known, but their interactions are numerous and need to be mapped. This involves a systematic, if not systems, approach. Given the urgency of the problems that the meat industry is facing, this endeavor is worth undertaking. As an additional benefit, culturing meat may provide opportunities for production of novel and healthier products. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Grand Challenge for CMOS Scaling: Alternate Gate Dielectrics

NASA Astrophysics Data System (ADS)

Wallace, Robert M.

2001-03-01

Many materials systems are currently under consideration as potential replacements for SiO2 as the gate dielectric material for sub-0.13 um complementary metal oxide semiconductor (CMOS) technology. The prospect of replacing SiO2 is a formidable task because the alternate gate dielectric must provide many properties that are, at a minimum, comparable to those of SiO2 yet with a much higher permittivity. A systematic examination of the required performance of gate dielectrics suggests that the key properties to consider in the selection an alternative gate dielectric candidate are (a) permittivity, band gap and band alignment to silicon, (b) thermodynamic stability, (c) film morphology, (d) interface quality, (e) compatibility with the current or expected materials to be used in processing for CMOS devices, (f) process compatibility, and (g) reliability. Many dielectrics appear favorable in some of these areas, but very few materials are promising with respect to all of these guidelines. We will review the performance requirements for materials associated with CMOS scaling, the challenges associated with these requirements, and the state-of-the-art in current research for alternate gate dielectrics. The requirements for process integration compatibility are remarkably demanding, and any serious candidates will emerge only through continued, intensive investigation.

Control of Randomly Sampled Robotic Systems

DTIC Science & Technology

1989-05-01

task is so cumbersome and complicated that we would not be able to do without lots of mistakes. To avoid this formidable business , a Lisp program is...Artificial Inteligence Laboratory, 1972. PumA26O.c Ned Mar 8 17:51:04 1989 1 #include <rnath.h> #define real float #define mm 6 #define G 9.83. #define M6

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.

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.

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.

Fusion Materials Research at Oak Ridge National Laboratory in Fiscal Year 2015

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

Wiffen, F. W.; Katoh, Yutai; Melton, Stephanie G.

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 Oak Ridge National Laboratory (ORNL) fusion materials program is to provide the applied materials science support and understanding to underpin the ongoing Department of Energy (DOE) Office of Science fusion energy program while developing materials for fusionmore » power systems. In doing so the program continues to be integrated both with the larger United States (US) and international fusion materials communities, and with the international fusion design and technology communities.This document provides a summary of Fiscal Year (FY) 2015 activities supporting the Office of Science, Office of Fusion Energy Sciences Materials Research for Magnetic Fusion Energy (AT-60-20-10-0) carried out by ORNL. The organization of this report is mainly by material type, with sections on specific technical activities. Four projects selected in the Funding Opportunity Announcement (FOA) solicitation of late 2011 and funded in FY2012-FY2014 are identified by “FOA” in the titles. This report includes the final funded work of these projects, although ORNL plans to continue some of this work within the base program.« less

Tissue engineering: state of the art in oral rehabilitation

PubMed Central

SCHELLER, E. L.; KREBSBACH, P. H.; KOHN, D. H.

2009-01-01

SUMMARY More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering. PMID:19228277

Tissue engineering: state of the art in oral rehabilitation.

PubMed

Scheller, E L; Krebsbach, P H; Kohn, D H

2009-05-01

More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

State of the art and trends for digital pathology.

PubMed

García Rojo, Marcial

2012-01-01

Anatomic pathology is a medical specialty where both information management systems and digital images systems paly a most important role. Digital pathology is a new concept that considers all uses of this information, including diagnosis, biomedical research and education. Virtual microscopy or whole slide imaging, resulting in digital slides, is an outreaching technology in anatomic pathology. Limiting factors in the expansion of virtual microscopy are formidable storage dimension, scanning speed, quality of image and cultural change. Anatomic pathology data and images should be an important part of the patient electronic health records as well as of clinical data warehouse, epidemiological or biomedical research databases, and platforms dedicated to translational medicine. Integrating anatomic pathology to the "healthcare enterprise" can only be achieved using existing and emerging medical informatics standards like Digital Imaging and Communications in Medicine (DICOM®¹), Health Level Seven (HL7®), and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT®), following the recommendations of Integrating the Healthcare Enterprise (IHE®). The consequences of the full digitalization of pathology departments are hard to foresee, but short term issues have arisen that imply interesting challenges for health care standards bodies.

Oral Delivery of Nanoparticles Loaded With Ginger Active Compound, 6-Shogaol, Attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis.

PubMed

Zhang, Mingzhen; Xu, Changlong; Liu, Dandan; Han, Moon Kwon; Wang, Lixin; Merlin, Didier

2018-01-24

Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges. We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis. NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors. Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD]. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

PubMed

Li, Min; Zhang, John Zenghui; Xia, Fei

2016-04-12

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10,000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

Petascale Many Body Methods for Complex Correlated Systems

NASA Astrophysics Data System (ADS)

Pruschke, Thomas

2012-02-01

Correlated systems constitute an important class of materials in modern condensed matter physics. Correlation among electrons are at the heart of all ordering phenomena and many intriguing novel aspects, such as quantum phase transitions or topological insulators, observed in a variety of compounds. Yet, theoretically describing these phenomena is still a formidable task, even if one restricts the models used to the smallest possible set of degrees of freedom. Here, modern computer architectures play an essential role, and the joint effort to devise efficient algorithms and implement them on state-of-the art hardware has become an extremely active field in condensed-matter research. To tackle this task single-handed is quite obviously not possible. The NSF-OISE funded PIRE collaboration ``Graduate Education and Research in Petascale Many Body Methods for Complex Correlated Systems'' is a successful initiative to bring together leading experts around the world to form a virtual international organization for addressing these emerging challenges and educate the next generation of computational condensed matter physicists. The collaboration includes research groups developing novel theoretical tools to reliably and systematically study correlated solids, experts in efficient computational algorithms needed to solve the emerging equations, and those able to use modern heterogeneous computer architectures to make then working tools for the growing community.

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing.

PubMed

Wardrip, Nathaniel C; Arnusch, Christopher J

2016-02-13

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing

PubMed Central

Wardrip, Nathaniel C.; Arnusch, Christopher J.

2016-01-01

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.  PMID:26968008

Consideration of Optimal Input on Semi-Active Shock Control System

NASA Astrophysics Data System (ADS)

Kawashima, Takeshi

In press working, unidirectional transmission of mechanical energy is expected in order to maximize the life of the dies. To realize this transmission, the author has developed a shock control system based on the sliding mode control technique. The controller makes a collision-receiving object effectively deform plastically by adjusting the force of the actuator inserted between the colliding objects, while the deformation of the colliding object is held at the necessity minimum. However, the actuator has to generate a large force corresponding to the impulsive force. Therefore, development of such an actuator is a formidable challenge. The author has proposed a semi-active shock control system in which the impulsive force is adjusted by a brake mechanism, although the system exhibits inferior performance. Thus, the author has also designed an actuator using a friction device for semi-active shock control, and proposed an active seatbelt system as an application. The effectiveness has been confirmed by a numerical simulation and model experiment. In this study, the optimal deformation change of the colliding object is theoretically examined in the case that the collision-receiving object has perfect plasticity and the colliding object has perfect elasticity. As a result, the optimal input condition is obtained so that the ratio of the maximum deformation of the collision-receiving object to the maximum deformation of the colliding object becomes the maximum. Additionally, the energy balance is examined.

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.

Understanding Global Change (UGC) as a Unifying Conceptual Framework for Teaching Ecology: Using UGC in a High School Biology Program to Integrate Earth Science and Biology, and to Demonstrate the Value of Modeling Global Systems in Promoting Conceptual Learning

NASA Astrophysics Data System (ADS)

Levine, J.; Bean, J. R.

2017-12-01

Global change science is ideal for NGSS-informed teaching, but presents a serious challenge to K-12 educators because it is complex and interdisciplinary- combining earth science, biology, chemistry, and physics. Global systems are themselves complex. Adding anthropogenic influences on those systems creates a formidable list of topics - greenhouse effect, climate change, nitrogen enrichment, introduced species, land-use change among them - which are often presented as a disconnected "laundry list" of "facts." This complexity, combined with public and mass-media scientific illiteracy, leaves global change science vulnerable to misrepresentation and politicization, creating additional challenges to teachers in public schools. Ample stand-alone, one-off, online resources, many of them excellent, are (to date) underutilized by teachers in the high school science course taken by most students: biology. The Understanding Global Change project (UGC) from the UC Berkeley Museum of Paleontology has created a conceptual framework that organizes, connects, and explains global systems, human and non-human drivers of change in those systems, and measurable changes in those systems. This organization and framework employ core ideas, crosscutting concepts, structure/function relationships, and system models in a unique format that facilitates authentic understanding, rather than memorization. This system serves as an organizing framework for the entire ecology unit of a forthcoming mainstream high school biology program. The UGC system model is introduced up front with its core informational graphic. The model is elaborated, step by step, by adding concepts and processes as they are introduced and explained in each chapter. The informational graphic is thus used in several ways: to organize material as it is presented, to summarize topics in each chapter and put them in perspective, and for review and critical thinking exercises that supplement the usual end-of-chapter lists of key terms.

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.

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.

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.

Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges

PubMed Central

2017-01-01

Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases. PMID:28286767

Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges.

PubMed

Nii-Trebi, Nicholas Israel

2017-01-01

Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases.

The Complexity Trap

DTIC Science & Technology

2012-01-01

proactively and effectively to today’s international environment, prioritization is the key first step —and precisely the opposite reaction to the complacency...formidable than just endless grains of sand.”32 This is not to deny the possibility of nonlinear phenomena, butterfly effects, self-organizing systems...The first step is replac- ing the current reactive worship of complexity with proactive prioritization. To escape the complexity trap, let us dare

Multiyear Program Plan for the High Temperature Materials Laboratory

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

Arvid E. Pasto

2000-03-17

Recently, the U.S. Department of Energy's (DOE) Office of Heavy Vehicle Technologies (OHVT) prepared a Technology Roadmap describing the challenges facing development of higher fuel efficiency, less polluting sport utility vehicles, vans, and commercial trucks. Based on this roadmap, a multiyear program plan (MYPP) was also developed, in which approaches to solving the numerous challenges are enumerated. Additional planning has been performed by DOE and national laboratory staff, on approaches to solving the numerous challenges faced by heavy vehicle system improvements. Workshops and planning documents have been developed concerning advanced aerodynamics, frictional and other parasitic losses, and thermal management. Similarly,more » the Heavy Vehicle Propulsion Materials Program has developed its own multiyear program plan. The High Temperature Materials Laboratory, a major user facility sponsored by OHVT, has now developed its program plan, described herein. Information was gathered via participation in the development of OHVT's overall Technology Roadmap and MYPP, through personal contacts within the materials-user community, and from attendance at conferences and expositions. Major materials issues for the heavy vehicle industry currently center on trying to increase efficiency of (diesel) engines while at the same time reducing emissions (particularly NO{sub x} and particulates). These requirements dictate the use of increasingly stronger, higher-temperature capable and more corrosion-resistant materials of construction, as well as advanced catalysts, particulate traps, and other pollution-control devices. Exhaust gas recirculation (EGR) is a technique which will certainly be applied to diesel engines in the near future, and its use represents a formidable challenge, as will be described later. Energy-efficient, low cost materials processing methods and surface treatments to improve wear, fracture, and corrosion resistance are also required.« less

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Quantum chemical approaches in structure-based virtual screening and lead optimization

NASA Astrophysics Data System (ADS)

Cavasotto, Claudio N.; Adler, Natalia S.; Aucar, Maria G.

2018-05-01

Today computational chemistry is a consolidated tool in drug lead discovery endeavors. Due to methodological developments and to the enormous advance in computer hardware, methods based on quantum mechanics (QM) have gained great attention in the last 10 years, and calculations on biomacromolecules are becoming increasingly explored, aiming to provide better accuracy in the description of protein-ligand interactions and the prediction of binding affinities. In principle, the QM formulation includes all contributions to the energy, accounting for terms usually missing in molecular mechanics force-fields, such as electronic polarization effects, metal coordination, and covalent binding; moreover, QM methods are systematically improvable, and provide a greater degree of transferability. In this mini-review we present recent applications of explicit QM-based methods in small-molecule docking and scoring, and in the calculation of binding free-energy in protein-ligand systems. Although the routine use of QM-based approaches in an industrial drug lead discovery setting remains a formidable challenging task, it is likely they will increasingly become active players within the drug discovery pipeline.

Financial sustainability planning for immunization services in Cambodia.

PubMed

Soeung, Sann Chan; Grundy, John; Maynard, Jim; Brooks, Alan; Boreland, Marian; Sarak, Duong; Jenkinson, Karl; Biggs, Beverley-Ann

2006-07-01

The expanded programme of immunization was established in Cambodia in 1986. In 2002, 67% of eligible children were immunized, despite significant health sector and macro-economic financial constraints. A financial sustainability planning process for immunization was introduced in 2002, in order to mobilize national and international resources in support of the achievement of child health objectives. The aim of this paper is to outline this process, describe its early impact as an advocacy tool and recommend additional strategies for mobilizing additional resources for health. The methods of financial sustainability planning are described, including the advocacy strategies that were applied. Analysis of financial sustainability planning results indicates rising programme costs associated with new vaccine introduction and new technologies. Despite this, the national programme has demonstrated important early successes in using financial sustainability planning to advocate for increased mobilization of national and international sources of funding for immunization. The national immunization programme nevertheless faces formidable system and financial challenges in the coming years associated with rising costs, potentially diminishing sources of international assistance, and the developing role of sub-national authorities in programme management and financing.

Separation of prescribing and dispensing in Malaysia: the history and challenges.

PubMed

Tiong, John Jeh Lung; Mai, Chun Wai; Gan, Pou Wee; Johnson, James; Mak, Vivienne Sook Li

2016-08-01

This article serves as an update to the work by Shafie et al. (2012) which previously reviewed the benefits of policies separating prescribing and dispensing in various countries to advocate its implementation in Malaysia. This article seeks to strengthen the argument by highlighting not only the weaknesses of the Malaysian health care system from the historical, professional and economic viewpoints but also the shortcomings of both medical and pharmacy professions in the absence of separation of dispensing. It also provides a detailed insight into the ongoing initiatives taken to consolidate the role of pharmacists in the health care system in the advent of separation of dispensing. Under the two tier system in Malaysia at present, the separation of prescribing and dispensing is implemented only in government hospitals. The absence of this separation in the private practices has led to possible profit-oriented medical and pharmacy practices which hinder safe and cost-effective delivery of health services. The call for separation of dispensing has gained traction over the years despite various hurdles ranging from the formidable resistance from the medical fraternity to the public's scepticism towards the new policy. With historical testament and present evidence pointing towards the merits of a system in which doctors prescribe and pharmacists dispense, the implementation of this health care model is justified. © 2016 The Authors. IJPP © 2016 Royal Pharmaceutical Society.

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

Evaluating the Potential of Commercial GIS for Accelerator Configuration Management

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

T.L. Larrieu; Y.R. Roblin; K. White

2005-10-10

The Geographic Information System (GIS) is a tool used by industries needing to track information about spatially distributed assets. A water utility, for example, must know not only the precise location of each pipe and pump, but also the respective pressure rating and flow rate of each. In many ways, an accelerator such as CEBAF (Continuous Electron Beam Accelerator Facility) can be viewed as an ''electron utility''. Whereas the water utility uses pipes and pumps, the ''electron utility'' uses magnets and RF cavities. At Jefferson lab we are exploring the possibility of implementing ESRI's ArcGIS as the framework for buildingmore » an all-encompassing accelerator configuration database that integrates location, configuration, maintenance, and connectivity details of all hardware and software. The possibilities of doing so are intriguing. From the GIS, software such as the model server could always extract the most-up-to-date layout information maintained by the Survey & Alignment for lattice modeling. The Mechanical Engineering department could use ArcGIS tools to generate CAD drawings of machine segments from the same database. Ultimately, the greatest benefit of the GIS implementation could be to liberate operators and engineers from the limitations of the current system-by-system view of machine configuration and allow a more integrated regional approach. The commercial GIS package provides a rich set of tools for database-connectivity, versioning, distributed editing, importing and exporting, and graphical analysis and querying, and therefore obviates the need for much custom development. However, formidable challenges to implementation exist and these challenges are not only technical and manpower issues, but also organizational ones. The GIS approach would crosscut organizational boundaries and require departments, which heretofore have had free reign to manage their own data, to cede some control and agree to a centralized framework.« less

Challenges in Transitioning Research Data to Operations: The SPoRT Paradigm

NASA Technical Reports Server (NTRS)

Jedloved, Gary J.; Smith, Matt; McGrath, Kevin

2010-01-01

Established in 2002 to demonstrate the weather and forecasting application of real-time EOS measurements, the NASA Short-term Prediction Research and Transition (SPoRT) program has grown to be an end-to-end research to operations activity focused on the use of advanced NASA modeling and data assimilation approaches, nowcasting techniques, and unique high-resolution multispectral data from EOS satellites to improve short-term weather forecasts on a regional and local scale. With the ever-broadening application of real-time high resolution satellite data from current EOS and planned NPP, JPSS, and GOES-R sensors to weather forecast problems, significant challenges arise in the acquisition, delivery, and integration of the new capabilities into the decision making process of the operational weather community. For polar orbiting sensors such as MODIS, AIRS, VIIRS, and CRiS, the use of direct broadcast ground stations is key to the real-time delivery of the data and derived products in a timely fashion. With the ABI on the geostationary GOES-R satellite, the data volume will likely increase by a factor of 5- 10 from current data streams. However, the high data volume and limited bandwidth of end user facilities presents a formidable obstacle to timely access to the data. This challenge can be addressed through the use of subsetting techniques, innovative web services, and the judicious selection of data formats. Many of these approaches have been implemented by SPoRT for the delivery of real-time products to NWS forecast offices and other weather entities. Once available in decision support systems like AWIPS II, these new data and products must be integrated into existing and new displays that allow for the integration of the data with existing operational products in these systems. SPoRT is leading the way in demonstrating this enhanced capability. This paper will highlight the ways SPoRT is overcoming many of the challenges presented by the enormous data volumes of current and future satellite systems to get unique high quality research data into the operational weather environment.

Management of herbicide resistance in wheat cropping systems: learning from the Australian experience.

PubMed

Walsh, Michael J; Powles, Stephen B

2014-09-01

Herbicide resistance continues to escalate in weed populations infesting global wheat (Triticum aestivum L.) crops, threatening grain production and thereby food supply. Conservation wheat production systems are reliant on the use of efficient herbicides providing low-cost, selective weed control in intensive cropping systems. The resistance-driven loss of herbicide resources combined with limited potential for new herbicide molecules means greater emphasis must be placed on preserving existing herbicides. For more than two decades, since the initial recognition of the dramatic consequences of herbicide resistance, the challenge of introducing additional weed control strategies into herbicide-based weed management programmes has been formidable. Throughout this period, herbicide resistance has expanded unabated across the world's wheat production regions. However, in Australia, where herbicide resources have become desperately depleted, the adoption of harvest weed seed control is evidence, at last, of a successful approach to sustainable weed management in wheat production systems. Growers routinely including strategies to target weed seeds during crop harvest, as part of herbicide-based weed management programmes, are now realising significant weed control and crop production benefits. When combined with an attitude of zero weed tolerance, there is evidence of a sustainable weed control future for wheat production systems. The hard-learned lessons of Australian growers can now be viewed by global wheat producers as an example of how to stop the continual loss of herbicide resources in productive cropping systems. © 2013 Society of Chemical Industry.

College Choice Interrupted or Facilitated: A Qualitative Case Study Examining How Social Class and Schools Structure Opportunity for Students in Urban High Schools

ERIC Educational Resources Information Center

Reavis, Tangela Blakely

2017-01-01

Although college enrollment rates have expanded over the last several decades, low-income students and students of color continue to face formidable barriers as they seek entry into higher education. While the existence of these barriers are often viewed as macro-level roadblocks that are largely systemic, much of the literature around access to…

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.

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.

Don't blame the 'bio'--blame the 'ethics': varieties of (bio)ethics and the challenge of pluralism.

PubMed

Charlesworth, Max

2005-01-01

We tend to think that the difficulties in bioethics spring from the novel and alarming issues that arise due to discoveries in the new biosciences and biotechnologies. But many of the crucial difficulties in bioethics arise from the assumption we make about ethics. This paper offers a brief overview of bioethics, and relates ethical 'principlism' to 'ethical fundamentalism.' It then reviews some alternative approaches that have emerged during the second phase of bioethics and argues for a neo-Aristotelian approach. Misconceptions about ethical principles and ethical reasoning not only distort our views of the business of bioethics, but they also prevent us from facing up to the formidable problems posed by ethical pluralism in so-called liberal societies.

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

Transparent data service with multiple wireless access

NASA Technical Reports Server (NTRS)

Dean, Richard A.; Levesque, Allen H.

1993-01-01

The rapid introduction of digital wireless networks is an important part of the emerging digital communications scene. The introduction of Digital Cellular, LEO and GEO Satellites, and Personal Communications Services poses both a challenge and an opportunity for the data user. On the one hand wireless access will introduce significant new portable data services such as personal notebooks, paging, E-mail, and fax that will put the information age in the user's pocket. On the other hand the challenge of creating a seamless and transparent environment for the user in multiple access environments and across multiple network connections is formidable. A summary of the issues associated with developing techniques and standards that can support transparent and seamless data services is presented. The introduction of data services into the radio world represents a unique mix of RF channel problems, data protocol issues, and network issues. These problems require that experts from each of these disciplines fuse the individual technologies to support these services.

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.

Entangling spin-spin interactions of ions in individually controlled potential wells

NASA Astrophysics Data System (ADS)

Wilson, Andrew; Colombe, Yves; Brown, Kenton; Knill, Emanuel; Leibfried, Dietrich; Wineland, David

2014-03-01

Physical systems that cannot be modeled with classical computers appear in many different branches of science, including condensed-matter physics, statistical mechanics, high-energy physics, atomic physics and quantum chemistry. Despite impressive progress on the control and manipulation of various quantum systems, implementation of scalable devices for quantum simulation remains a formidable challenge. As one approach to scalability in simulation, here we demonstrate an elementary building-block of a configurable quantum simulator based on atomic ions. Two ions are trapped in separate potential wells that can individually be tailored to emulate a number of different spin-spin couplings mediated by the ions' Coulomb interaction together with classical laser and microwave fields. We demonstrate deterministic tuning of this interaction by independent control of the local wells and emulate a particular spin-spin interaction to entangle the internal states of the two ions with 0.81(2) fidelity. Extension of the building-block demonstrated here to a 2D-network, which ion-trap micro-fabrication processes enable, may provide a new quantum simulator architecture with broad flexibility in designing and scaling the arrangement of ions and their mutual interactions. This research was funded by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), ONR, and the NIST Quantum Information Program.

Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

PubMed

Williams, Tim D; Turan, Nil; Diab, Amer M; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L; Hrydziuszko, Olga; Lyons, Brett P; Stentiford, Grant D; Herbert, John M; Abraham, Joseph K; Katsiadaki, Ioanna; Leaver, Michael J; Taggart, John B; George, Stephen G; Viant, Mark R; Chipman, Kevin J; Falciani, Francesco

2011-08-01

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach

PubMed Central

Williams, Tim D.; Turan, Nil; Diab, Amer M.; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L.; Hrydziuszko, Olga; Lyons, Brett P.; Stentiford, Grant D.; Herbert, John M.; Abraham, Joseph K.; Katsiadaki, Ioanna; Leaver, Michael J.; Taggart, John B.; George, Stephen G.; Viant, Mark R.; Chipman, Kevin J.; Falciani, Francesco

2011-01-01

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations. PMID:21901081

A space station Structures and Assembly Verification Experiment, SAVE

NASA Technical Reports Server (NTRS)

Russell, R. A.; Raney, J. P.; Deryder, L. J.

1986-01-01

The Space Station structure has been baselined to be a 5 M (16.4 ft) erectable truss. This structure will provide the overall framework to attach laboratory modules and other systems, subsystems and utilities. The assembly of this structure represents a formidable EVA challenge. To validate this capability the Space Station Structures/Dynamics Technical Integration Panel (TIP) met to develop the necessary data for an integrated STS structures flight experiment. As a result of this meeting, the Langley Research Center initiated a joint Langley/Boeing Aerospace Company study which supported the structures/dynamics TIP in developing the preliminary definition and design of a 5 M erectable space station truss and the resources required for a proposed flight experiment. The purpose of the study was to: (1) devise methods of truss assembly by astronauts; (2) define a specific test matrix for dynamic characterization; (3) identify instrumentation and data system requirements; (4) determine the power, propulsion and control requirements for the truss on-orbit for 3 years; (5) study the packaging of the experiment in the orbiter cargo bay; (6) prepare a preliminary cost estimate and schedule for the experiment; and (7) provide a list of potential follow-on experiments using the structure as a free flyer. The results of this three month study are presented.

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

NASA Astrophysics Data System (ADS)

Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

2015-06-01

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

How can the cystic fibrosis respiratory microbiome influence our clinical decision-making?

PubMed

Rogers, Geraint B; Bruce, Kenneth D; Hoffman, Lucas R

2017-11-01

Almost 15 years have now passed since bacterial community profiling techniques were first used to analyse respiratory samples from people with cystic fibrosis. Since then, many different analytical approaches have been used to try to better understand the contribution of the cystic fibrosis lung microbiota to disease, with varying degrees of success. We examine the extent to which cystic fibrosis respiratory microbiome research has been successful in informing clinical decision-making, and highlight areas that we believe have the potential to yield important insight. Recent research on the cystic fibrosis lung microbiome can be broadly divided into efforts to better characterize microbiota composition, particularly relative to key clinical events, and attempts to understand the cystic fibrosis lung microbiology as an interactive microbial system. The latter, in particular, has led to the development of a number of models in which microbiome-mediated processes precipitate clinical events. Growing technological sophistication is enabling increasingly detailed microbiological data to be generated from cystic fibrosis respiratory samples. However, translating these data into clinically useful measures that accurately predict outcomes and guide treatments remains a formidable challenge. The development of systems biology approaches that enable the integration of complex microbiome and host-derived data provide an exciting opportunity to address this goal.

Virtual reality: a reality for future military pilotage?

NASA Astrophysics Data System (ADS)

McIntire, John P.; Martinsen, Gary L.; Marasco, Peter L.; Havig, Paul R.

2009-05-01

Virtual reality (VR) systems provide exciting new ways to interact with information and with the world. The visual VR environment can be synthetic (computer generated) or be an indirect view of the real world using sensors and displays. With the potential opportunities of a VR system, the question arises about what benefits or detriments a military pilot might incur by operating in such an environment. Immersive and compelling VR displays could be accomplished with an HMD (e.g., imagery on the visor), large area collimated displays, or by putting the imagery on an opaque canopy. But what issues arise when, instead of viewing the world directly, a pilot views a "virtual" image of the world? Is 20/20 visual acuity in a VR system good enough? To deliver this acuity over the entire visual field would require over 43 megapixels (MP) of display surface for an HMD or about 150 MP for an immersive CAVE system, either of which presents a serious challenge with current technology. Additionally, the same number of sensor pixels would be required to drive the displays to this resolution (and formidable network architectures required to relay this information), or massive computer clusters are necessary to create an entirely computer-generated virtual reality with this resolution. Can we presently implement such a system? What other visual requirements or engineering issues should be considered? With the evolving technology, there are many technological issues and human factors considerations that need to be addressed before a pilot is placed within a virtual cockpit.

Recognition and categorization considerations for information assurance requirements development and speficication

NASA Astrophysics Data System (ADS)

Stytz, Martin R.; May, Michael; Banks, Sheila B.

2009-04-01

Department of Defense (DoD) Information Technology (IT) systems operate in an environment different from the commercial world, the differences arise from the differences in the types of attacks, the interdependencies between DoD software systems, and the reliance upon commercial software to provide basic capabilities. The challenge that we face is determining how to specify the information assurance requirements for a system without requiring changes to the commercial software and in light of the interdependencies between systems. As a result of the interdependencies and interconnections between systems introduced by the global information grid (GIG), an assessment of the IA requirements for a system must consider three facets of a system's IA capabilities: 1) the IA vulnerabilities of the system, 2) the ability of a system to repel IA attacks, and 3) the ability of a system to insure that any IA attack that penetrates the system is contained within the system and does not spread. Each facet should be assessed independently and the requirements should be derived independently from the assessments. In addition to the desired IA technology capabilities of the system, a complete assessment of the system's overall IA security technology readiness level cannot be accomplished without an assessment of the capabilities required of the system for its capability to recover from and remediate IA vulnerabilities and compromises. To allow us to accomplish these three formidable tasks, we propose a general system architecture designed to separate the system's IA capabilities from its other capability requirements; thereby allowing the IA capabilities to be developed and assessed separately from the other system capabilities. The architecture also enables independent requirements specification, implementation, assessment, measurement, and improvement of a system's IA capabilities without requiring modification of the underlying application software.

Recent (1999-2003) Canadian research on contemporary processes of river erosion and sedimentation, and river mechanics

NASA Astrophysics Data System (ADS)

de Boer, D. H.; Hassan, M. A.; MacVicar, B.; Stone, M.

2005-01-01

Contributions by Canadian fluvial geomorphologists between 1999 and 2003 are discussed under four major themes: sediment yield and sediment dynamics of large rivers; cohesive sediment transport; turbulent flow structure and sediment transport; and bed material transport and channel morphology. The paper concludes with a section on recent technical advances. During the review period, substantial progress has been made in investigating the details of fluvial processes at relatively small scales. Examples of this emphasis are the studies of flow structure, turbulence characteristics and bedload transport, which continue to form central themes in fluvial research in Canada. Translating the knowledge of small-scale, process-related research to an understanding of the behaviour of large-scale fluvial systems, however, continues to be a formidable challenge. Models play a prominent role in elucidating the link between small-scale processes and large-scale fluvial geomorphology, and, as a result, a number of papers describing models and modelling results have been published during the review period. In addition, a number of investigators are now approaching the problem by directly investigating changes in the system of interest at larger scales, e.g. a channel reach over tens of years, and attempting to infer what processes may have led to the result. It is to be expected that these complementary approaches will contribute to an increased understanding of fluvial systems at a variety of spatial and temporal scales. Copyright

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.

The Gravity of the Situation. Chapter 1

NASA Technical Reports Server (NTRS)

Paloski, William; Clement, Gilles; Bukley, Angie; Paloski, William

2006-01-01

Prolonged exposure in humans to a microgravity environment can lead to significant loss of bone and muscle mass, cardiovascular and sensory-motor deconditioning, and hormonal changes. These adaptive changes to weightlessness present a formidable obstacle to human exploration of space, particularly for missions requiring travel times of several months or more, such as on a trip to Mars. Countermeasures that address each of these body systems separately show only limited success. One possible remedy for this situation is artificial gravity, because it tackles all these systems across the board.

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.

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.

National Media Laboratory media testing results

NASA Technical Reports Server (NTRS)

Mularie, William

1993-01-01

The government faces a crisis in data storage, analysis, archive, and communication. The sheer quantity of data being poured into the government systems on a daily basis is overwhelming systems ability to capture, analyze, disseminate, and store critical information. Future systems requirements are even more formidable: with single government platforms having data rate of over 1 Gbit/sec, greater than Terabyte/day storage requirements, and with expected data archive lifetimes of over 10 years. The charter of the National Media Laboratory (NML) is to focus the resources of industry, government, and academia on government needs in the evaluation, development, and field support of advanced recording systems.

Manned Mars missions: A working group report

NASA Technical Reports Server (NTRS)

Duke, Michael B. (Editor); Keaton, Paul W. (Editor)

1986-01-01

The discussions of the Working Group (based in large part on working papers, which will shortly be published separately) are summarized. These papers cover a broad range of subjects which need to be addressed in the formulation of such a formidable enterprise as a manned Mars program. Science objective and operations; Mars surface infrastructure and activities; mission and system concepts and configurations; life sciences; impacts on the space infrastructure; and costs, schedules, and organizations are addressed.

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.

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.

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.

Dairy goat production systems: status quo, perspectives and challenges.

PubMed

Escareño, Luis; Salinas-Gonzalez, Homero; Wurzinger, Maria; Iñiguez, Luiz; Sölkner, Johann; Meza-Herrera, Cesar

2013-01-01

Goat production concentrated in developing countries (tropics, dry areas), contributes largely to the livelihoods of low and medium income farmers. Farming systems in these areas have evolved to cope with the formidable constraints imposed by harsh natural and economic conditions by adapting integrated crop/livestock production strategies. In Asia, Africa and Latin America, due to its almost exclusive extensive nature, goat production relies mainly on grazing on communal lands that hardly provide the minimum nutrient requirements due to overstocking and degradation. While some of these production systems are becoming semi-intensive, appropriate breeding strategies should be designed to promote conservation and improvement of their unique attributes, such as adaptability, water use efficiency and suitability under harsh climatic conditions. In Europe, dairy goat production is more common around the Mediterranean basin, where it is important from an economic, environmental and sociological perspective to the Mediterranean countries: Spain, France, Italy and Greece. Europe owns only 5.1 % of the world's dairy goat herds, but produces 15.6 % of the world's goat milk; this is the only continent where goat milk has such an economic importance and organization. In developing countries the dairy goat sector requires a systemic approach, whereby nutrition, animal health, breeding, know-how, inputs and technologies must be assembled. This would allow the optimization of natural and local resources and would promote the transition from a risk reduction strategy towards an increased productivity strategy. Such an increase would privilege production efficiency based on clean, green and ethical practices for responsible innovation.

Functions of an engineered barrier system for a nuclear waste repository in basalt

NASA Astrophysics Data System (ADS)

Coons, W. E.; Moore, E. L.; Smith, M. J.; Kaser, J. D.

1980-01-01

The functions of components selected for an engineered barrier system for a nuclear waste repository in basalt are defined providing a focal point for barrier material research and development by delineating the purpose and operative lifetime of each component of the engineered system. A five component system (comprised of waste form, canister, buffer, overpack, and tailored backfill) is discussed. Redundancy is provided by subsystems of physical and chemical barriers which act in concert with the geology to provide a formidable barrier to transport of hazardous materials to the biosphere. The barrier system is clarified by examples pertinent to storage in basalt, and a technical approach to barrier design and material selection is proposed.

Information Fusion Issues in the UK Environmental Science Community

NASA Astrophysics Data System (ADS)

Giles, J. R.

2010-12-01

The Earth is a complex, interacting system which cannot be neatly divided by discipline boundaries. To gain an holistic understanding of even a component of an Earth System requires researchers to draw information from multiple disciplines and integrate these to develop a broader understanding. But the barriers to achieving this are formidable. Research funders attempting to encourage the integration of information across disciplines need to take into account culture issues, the impact of intrusion of projects on existing information systems, ontologies and semantics, scale issues, heterogeneity and the uncertainties associated with combining information from diverse sources. Culture - There is a cultural dualism in the environmental sciences were information sharing is both rewarded and discouraged. Researchers who share information both gain new opportunities and risk reducing their chances of being first author in an high-impact journal. The culture of the environmental science community has to be managed to ensure that information fusion activities are encouraged. Intrusion - Existing information systems have an inertia of there own because of the intellectual and financial capital invested within them. Information fusion activities must recognise and seek to minimise the potential impact of their projects on existing systems. Low intrusion information fusions systems such as OGC web-service and the OpenMI Standard are to be preferred to whole-sale replacement of existing systems. Ontology and Semantics - Linking information across disciplines requires a clear understanding of the concepts deployed in the vocabulary used to describe them. Such work is a critical first step to creating routine information fusion. It is essential that national bodies, such as geological surveys organisations, document and publish their ontologies, semantics, etc. Scale - Environmental processes operate at scales ranging from microns to the scale of the Solar System and potentially beyond. The many different scales involved provide serious challenges to information fusion which need to be researched. Heterogeneity - Natural systems are heterogeneous, that is a system consisting of multiple components each of which may have considerable internal variation. Modelling Earth Systems requires recognition of the inherent complexity. Uncertainty - Understanding the uncertainties within a single information source can be difficult. Understanding the uncertainties across a system of linked models, each drawn from multiple information resources, represents a considerable challenge that must be addressed. The challenges to overcome appear insurmountable to individual research groups; but the potential rewards, in terms of a fuller scientific understanding of Earth Systems, are significant. A major international effort must be mounted to tackle these barriers and enable routine information fusion.

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.

Rift Valley fever virus infection in golden Syrian hamsters.

PubMed

Scharton, Dionna; Van Wettere, Arnaud J; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Siddharthan, Venkatraman; Gowen, Brian B

2015-01-01

Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

Swarming: flexible roaming plans.

PubMed

Partridge, Jonathan D; Harshey, Rasika M

2013-03-01

Movement over an agar surface via swarming motility is subject to formidable challenges not encountered during swimming. Bacteria display a great deal of flexibility in coping with these challenges, which include attracting water to the surface, overcoming frictional forces, and reducing surface tension. Bacteria that swarm on "hard" agar surfaces (robust swarmers) display a hyperflagellated and hyperelongated morphology. Bacteria requiring a "softer" agar surface (temperate swarmers) do not exhibit such a dramatic morphology. For polarly flagellated robust swarmers, there is good evidence that restriction of flagellar rotation somehow signals the induction of a large number of lateral flagella, but this scenario is apparently not relevant to temperate swarmers. Swarming bacteria can be further subdivided by their requirement for multiple stators (Mot proteins) or a stator-associated protein (FliL), secretion of essential polysaccharides, cell density-dependent gene regulation including surfactant synthesis, a functional chemotaxis signaling pathway, appropriate cyclic (c)-di-GMP levels, induction of virulence determinants, and various nutritional requirements such as iron limitation or nitrate availability. Swarming strategies are as diverse as the bacteria that utilize them. The strength of these numerous designs stems from the vantage point they offer for understanding mechanisms for effective colonization of surface niches, acquisition of pathogenic potential, and identification of environmental signals that regulate swarming. The signature swirling and streaming motion within a swarm is an interesting phenomenon in and of itself, an emergent behavior with properties similar to flocking behavior in diverse systems, including birds and fish, providing a convenient new avenue for modeling such behavior.

The challenges facing mental health programs for post-conflict and refugee communities.

PubMed

Silove, Derrick

2004-01-01

The majority of refugees and communities exposed to warfare and oppression live in low-income countries with few resources or special skills. Yet, epidemiological studies have identified high levels of traumatic stress reactions in such populations. These stress reactions can be intensified by harsh policies aimed at deterring survivors from seeking refuge in technologically advanced societies. The scale of the problem of mass violence and displacement creates formidable challenges for mental health professionals in their efforts to develop practical frameworks for responding to the extensive needs of displaced persons. In this article, a model is proposed for low-income, post-conflict countries, based on a two-tiered formulation. At the eco-social level, mental health professionals can play a supportive, but not a lead, role in facilitating recovery of core adaptive systems that hasten natural recovery from stress for the majority of the population. Where small-scale, community mental health services are established, the emphasis should be on assisting persons and their families who are at greatest survival and adaptive risk. Training and promotion of local workers to assume leadership in such programs are essential. In technologically advanced societies in which refugees are in a minority, torture and trauma services can focus more specifically on traumatic stress reactions, acculturation, and resettlement. In a historical epoch in which displaced persons are facing particularly harsh treatment, there is a pressing need for consensus amongst mental health professionals in advocating for their needs.

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.

Protecting Place Through Community Alliances: Haida Gwaii Responds to the Proposed Enbridge Northern Gateway Project

NASA Astrophysics Data System (ADS)

Crist, Valine

This research contributes to the emerging dialogue concerning power relationships and the alliances that are challenging current frameworks in an attempt to create positive change. Worldwide, local people in rural places are threatened by development paradigms and conflicting social, political, economic, and ecological values. Large-scale development, such as the Enbridge Northern Gateway Project (NGP), provide a tangible example of our failing systems and make the interplay of these elements palpable. Increasingly, communities are coalescing to challenge the current models and economically motivated agendas threatening Indigenous sovereignty and local lifeways. Central to these coalitions are Indigenous peoples who are aligning with non-Indigenous neighbours to renegotiate power relationships. This research examines these dynamic alliances and uses Haida Gwaii's resistance to the NGP as an example of the formidable strength of community coalitions mobilized by intersecting values. To contextualize the NGP within the broader discourse, I problematize Canada's environmental assessment process and consider how media portrays the growing resistance to the proposed project. Drawing on information presented through the environmental assessment, I analyze the main messages and shared values of Haida Gwaii citizens opposed to the NGP. This thesis focuses on this unanimous and galvanizing resistance, which is largely motivated by the reliance on local food sources and an embodied connection to Haida Gwaii shared by Island citizens. The continued denial of Aboriginal title and rights was inherent throughout this consideration and is an underlying theme throughout the analyses.

Swarming: Flexible Roaming Plans

PubMed Central

Partridge, Jonathan D.

2013-01-01

Movement over an agar surface via swarming motility is subject to formidable challenges not encountered during swimming. Bacteria display a great deal of flexibility in coping with these challenges, which include attracting water to the surface, overcoming frictional forces, and reducing surface tension. Bacteria that swarm on “hard” agar surfaces (robust swarmers) display a hyperflagellated and hyperelongated morphology. Bacteria requiring a “softer” agar surface (temperate swarmers) do not exhibit such a dramatic morphology. For polarly flagellated robust swarmers, there is good evidence that restriction of flagellar rotation somehow signals the induction of a large number of lateral flagella, but this scenario is apparently not relevant to temperate swarmers. Swarming bacteria can be further subdivided by their requirement for multiple stators (Mot proteins) or a stator-associated protein (FliL), secretion of essential polysaccharides, cell density-dependent gene regulation including surfactant synthesis, a functional chemotaxis signaling pathway, appropriate cyclic (c)-di-GMP levels, induction of virulence determinants, and various nutritional requirements such as iron limitation or nitrate availability. Swarming strategies are as diverse as the bacteria that utilize them. The strength of these numerous designs stems from the vantage point they offer for understanding mechanisms for effective colonization of surface niches, acquisition of pathogenic potential, and identification of environmental signals that regulate swarming. The signature swirling and streaming motion within a swarm is an interesting phenomenon in and of itself, an emergent behavior with properties similar to flocking behavior in diverse systems, including birds and fish, providing a convenient new avenue for modeling such behavior. PMID:23264580

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.

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.

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.

Perceptions, practices and health seeking behaviour constrain JE/AES interventions in high endemic district of North India.

PubMed

Chaturvedi, Sanjay; Sharma, Neha; Kakkar, Manish

2017-08-08

Acute Encephalitis Syndrome (AES) and Japanese Encephalitis (JE) stay as poorly understood phenomena in India. Multiple linkages to determinants such as poverty, socio-economic status, gender, environment, and population distribution, make it a greater developmental issue than just a zoonotic disease. A qualitative study was conducted to map knowledge, perceptions and practices of community and health systems level stakeholders. Seventeen interviews with utilizers of AES care, care givers from human and veterinary sectors, Non-governmental Organizations (NGOs), and pig owners and 4 Focused Group Discussions (FGDs) with farmers, community leaders, and students were conducted in an endemic north Indian district-Kushinagar. Core themes that emerged were: JE/AES been perceived as a deadly disease, but not a major health problem; filthy conditions, filthy water and mosquitoes seen to be associated with JE/AES; pigs not seen as a source of infection; minimal role of government health workers in the first-contact care of acute Illness; no social or cultural resistance to JE vaccination or mosquito control; no gender-based discrimination in the care of acute Illness; and non-utilization of funds available with local self govt. Serious challenges and systematic failures in delivery of care during acute illness, which can critically inform the health systems, were also identified. There is an urgent need for promotive interventions to address lack of awareness about the drivers of JE/AES. Delivery of care during acute illness suffers with formidable challenges and systematic failures. A large portion of mortality can be prevented by early institution of rational management at primary and secondary level, and by avoiding wastage of time and resources for investigations and medications that are not actually required.

Hydrologic and biogeochemical impacts of a period of elevated hurricane activity on the Pamlico Sound system, NC: The challenges for nutrient and habitat management

NASA Astrophysics Data System (ADS)

Paerl, H. W.; Peierls, B. L.; Hall, N. S.; Rossignol, K. L.; Wetz, M. S.

2008-12-01

Since the mid-1990's, US Coastal regions have experienced a sudden rise in hurricane and tropical storm landfalls; this elevated frequency is expected to continue for the next several decades. The North Carolina coast has been impacted by at least eight hurricanes and six tropical storms during this time. Each of these storms exhibited unique hydrologic and nutrient loading scenarios. This variability represents a formidable challenge to management of eutrophication and fisheries habitats of the Pamlico Sound system, the US's largest lagoonal ecosystem and a key fisheries resource. Different rainfall amounts among hurricanes led to variable freshwater and nutrient discharge and hence variable nutrient, organic matter, and sediment enrichment. These enrichments differentially affected physical-chemical properties (salinity, water residence time, transparency, stratification, dissolved oxygen), phytoplankton community production and composition. The contrasting effects were accompanied by biogeochemical perturbations (hypoxia, enhanced nutrient cycling), habitat alterations, and food web disturbances. Floodwaters from the two largest hurricanes, Fran (1996) and Floyd (1999), exerted multi-month to multi-annual hydrologic and biogeochemical effects. In contrast, relatively low rainfall coastal hurricanes like Isabel (2003) and Ophelia (2005) caused strong vertical mixing and storm surges, but relatively minor hydrologic, nutrient, and biotic impacts. Both hydrologic and wind forcing are important drivers and must be integrated with nutrient loading in assessing short- and long- term ecological impacts of these storms. These climatic forcings cannot be managed but must be considered when developing water quality and habitat management strategies for these and other large estuarine ecosystems faced with increasing frequencies and intensities of hurricanes.

Biomaterial-based technologies for brain anti-cancer therapeutics and imaging.

PubMed

Orive, G; Ali, O A; Anitua, E; Pedraz, J L; Emerich, D F

2010-08-01

Treating malignant brain tumors represents one of the most formidable challenges in oncology. Contemporary treatment of brain tumors has been hampered by limited drug delivery across the blood-brain barrier (BBB) to the tumor bed. Biomaterials are playing an increasingly important role in developing more effective brain tumor treatments. In particular, polymer (nano)particles can provide prolonged drug delivery directly to the tumor following direct intracerebral injection, by making them physiochemically able to cross the BBB to the tumor, or by functionalizing the material surface with peptides and ligands allowing the drug-loaded material to be systemically administered but still specifically target the tumor endothelium or tumor cells themselves. Biomaterials can also serve as targeted delivery devices for novel therapies including gene therapy, photodynamic therapy, anti-angiogenic and thermotherapy. Nanoparticles also have the potential to play key roles in the diagnosis and imaging of brain tumors by revolutionizing both preoperative and intraoperative brain tumor detection, allowing early detection of pre-cancerous cells, and providing real-time, longitudinal, non-invasive monitoring/imaging of the effects of treatment. Additional efforts are focused on developing biomaterial systems that are uniquely capable of delivering tumor-associated antigens, immunotherapeutic agents or programming immune cells in situ to identify and facilitate immune-mediated tumor cell killing. The continued translation of current research into clinical practice will rely on solving challenges relating to the pharmacology of nanoparticles but it is envisioned that novel biomaterials will ultimately allow clinicians to target tumors and introduce multiple, pharmaceutically relevant entities for simultaneous targeting, imaging, and therapy in a unique and unprecedented manner. Copyright 2010 Elsevier B.V. All rights reserved.

Analysing and Rationalising Molecular and Materials Databases Using Machine-Learning

NASA Astrophysics Data System (ADS)

de, Sandip; Ceriotti, Michele

Computational materials design promises to greatly accelerate the process of discovering new or more performant materials. Several collaborative efforts are contributing to this goal by building databases of structures, containing between thousands and millions of distinct hypothetical compounds, whose properties are computed by high-throughput electronic-structure calculations. The complexity and sheer amount of information has made manual exploration, interpretation and maintenance of these databases a formidable challenge, making it necessary to resort to automatic analysis tools. Here we will demonstrate how, starting from a measure of (dis)similarity between database items built from a combination of local environment descriptors, it is possible to apply hierarchical clustering algorithms, as well as dimensionality reduction methods such as sketchmap, to analyse, classify and interpret trends in molecular and materials databases, as well as to detect inconsistencies and errors. Thanks to the agnostic and flexible nature of the underlying metric, we will show how our framework can be applied transparently to different kinds of systems ranging from organic molecules and oligopeptides to inorganic crystal structures as well as molecular crystals. Funded by National Center for Computational Design and Discovery of Novel Materials (MARVEL) and Swiss National Science Foundation.

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.

Real-time geometry-aware augmented reality in minimally invasive surgery.

PubMed

Chen, Long; Tang, Wen; John, Nigel W

2017-10-01

The potential of augmented reality (AR) technology to assist minimally invasive surgery (MIS) lies in its computational performance and accuracy in dealing with challenging MIS scenes. Even with the latest hardware and software technologies, achieving both real-time and accurate augmented information overlay in MIS is still a formidable task. In this Letter, the authors present a novel real-time AR framework for MIS that achieves interactive geometric aware AR in endoscopic surgery with stereo views. The authors' framework tracks the movement of the endoscopic camera and simultaneously reconstructs a dense geometric mesh of the MIS scene. The movement of the camera is predicted by minimising the re-projection error to achieve a fast tracking performance, while the three-dimensional mesh is incrementally built by a dense zero mean normalised cross-correlation stereo-matching method to improve the accuracy of the surface reconstruction. The proposed system does not require any prior template or pre-operative scan and can infer the geometric information intra-operatively in real time. With the geometric information available, the proposed AR framework is able to interactively add annotations, localisation of tumours and vessels, and measurement labelling with greater precision and accuracy compared with the state-of-the-art approaches.

Special test equipment and fixturing for MSAT reflector assembly alignment

NASA Technical Reports Server (NTRS)

Young, Jeffrey A.; Zinn, Michael R.; Mccarten, David R.

1994-01-01

The MSAT Reflector Assembly is a state of the art subsystem for Mobile Satellite (MSAT), a geosynchronous-based commercial mobile telecommunication satellite program serving North America. The Reflector Assembly consisted of a deployable, three-hinge, folding-segment Boom, deployable 5.7 x 5.3-meter 16-rib Wrap-Rib Reflector, and a Reflector Pointing Mechanism (RPM). The MSAT spacecraft was based on a Hughes HS601 spacecraft bus carrying two Reflector Assemblies independently dedicated for L-band transmit and receive operations. Lockheed Missiles and Space Company (LMSC) designed and built the Reflector Assembly for MSAT under contract to SPAR Aerospace Ltd. Two MSAT satellites were built jointly by SPAR Aerospace Ltd. and Hughes Space and Communications Co. for this program, the first scheduled for launch in 1994. When scaled for wavelength, the assembly and alignment requirements for the Reflector Assembly were in many instances equivalent to or exceeded that of a diffraction-limited visible light optical system. Combined with logistical constraints inherent to large, compliant, lightweight structures; 'bolt-on' alignment; and remote, indirect spacecraft access; the technical challenges were formidable. This document describes the alignment methods, the special test equipment, and fixturing for Reflector Assembly assembly and alignment.

Advanced thermal management of high-power quantum cascade laser arrays for infrared countermeasures

NASA Astrophysics Data System (ADS)

Barletta, Philip; Diehl, Laurent; North, Mark T.; Yang, Bao; Baldasaro, Nick; Temple, Dorota

2017-10-01

Next-generation infrared countermeasure (IRCM) systems call for compact and lightweight high-power laser sources. Specifically, optical output power of tens of Watts in the mid-wave infrared (MWIR) is desired. Monolithically fabricated arrays of quantum cascade lasers (QCLs) have the potential to meet these requirements. Single MWIR QCL emitters operating in continuous wave at room temperature have demonstrated multi-Watt power levels with wall-plug efficiency of up to 20%. However, tens of Watts of output power from an array of QCLs translates into the necessity of removing hundreds of Watts per cm2, a formidable thermal management challenge. A potential thermal solution for such high-power QCL arrays is active cooling based on high-performance thin-film thermoelectric coolers (TFTECs), in conjunction with pumped porous-media heat exchangers. The use of active cooling via TFTECs makes it possible to not only pump the heat away, but also to lower the QCL junction temperature, thus improving the wall-plug efficiency of the array. TFTECs have shown the ability to pump >250W/cm2 at ΔT=0K, which is 25 times greater than that typically seen in commercially available bulk thermoelectric devices.

Microneedles for intradermal and transdermal delivery

PubMed Central

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2014-01-01

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

SPoRT: Transitioning NASA and NOAA Experimental Data to the Operational Weather Community

NASA Technical Reports Server (NTRS)

Jedlovec, Gary J.

2013-01-01

Established in 2002 to demonstrate the weather and forecasting application of real-time EOS measurements, the NASA Short-term Prediction Research and Transition (SPoRT) program has grown to be an end-to-end research to operations activity focused on the use of advanced NASA modeling and data assimilation approaches, nowcasting techniques, and unique high-resolution multispectral data from EOS satellites to improve short-term weather forecasts on a regional and local scale. With the ever-broadening application of real-time high resolution satellite data from current EOS, Suomi NPP, and planned JPSS and GOES-R sensors to weather forecast problems, significant challenges arise in the acquisition, delivery, and integration of the new capabilities into the decision making process of the operational weather community. For polar orbiting sensors such as MODIS, AIRS, VIIRS, and CRiS, the use of direct broadcast ground stations is key to the real-time delivery of the data and derived products in a timely fashion. With the ABI on the geostationary GOES-R satellite, the data volumes will likely increase by a factor of 5-10 from current data streams. However, the high data volume and limited bandwidth of end user facilities presents a formidable obstacle to timely access to the data. This challenge can be addressed through the use of subsetting techniques, innovative web services, and the judicious selection of data formats. Many of these approaches have been implemented by SPoRT for the delivery of real-time products to NWS forecast offices and other weather entities. Once available in decision support systems like AWIPS II, these new data and products must be integrated into existing and new displays that allow for the integration of the data with existing operational products in these systems. SPoRT is leading the way in demonstrating this enhanced capability. This paper will highlight the ways SPoRT is overcoming many of the challenges presented by the enormous data volumes of current and future satellite systems to get unique high quality research data into the operational weather environment.

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

Software Re-Engineering of the Human Factors Analysis and Classification System - (Maintenance Extension) Using Object Oriented Methods in a Microsoft Environment

DTIC Science & Technology

2001-09-01

replication) -- all from Visual Basic and VBA . In fact, we found that the SQL Server engine actually had a plethora of options, most formidable of...2002, the new SQL Server 2000 database engine, and Microsoft Visual Basic.NET. This thesis describes our use of the Spiral Development Model to...versions of Microsoft products? Specifically, the pending release of Microsoft Office 2002, the new SQL Server 2000 database engine, and Microsoft

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.

Efficient Computation of Info-Gap Robustness for Finite Element Models

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

Stull, Christopher J.; Hemez, Francois M.; Williams, Brian J.

2012-07-05

A recent research effort at LANL proposed info-gap decision theory as a framework by which to measure the predictive maturity of numerical models. Info-gap theory explores the trade-offs between accuracy, that is, the extent to which predictions reproduce the physical measurements, and robustness, that is, the extent to which predictions are insensitive to modeling assumptions. Both accuracy and robustness are necessary to demonstrate predictive maturity. However, conducting an info-gap analysis can present a formidable challenge, from the standpoint of the required computational resources. This is because a robustness function requires the resolution of multiple optimization problems. This report offers anmore » alternative, adjoint methodology to assess the info-gap robustness of Ax = b-like numerical models solved for a solution x. Two situations that can arise in structural analysis and design are briefly described and contextualized within the info-gap decision theory framework. The treatments of the info-gap problems, using the adjoint methodology are outlined in detail, and the latter problem is solved for four separate finite element models. As compared to statistical sampling, the proposed methodology offers highly accurate approximations of info-gap robustness functions for the finite element models considered in the report, at a small fraction of the computational cost. It is noted that this report considers only linear systems; a natural follow-on study would extend the methodologies described herein to include nonlinear systems.« less

Buccal drug delivery.

PubMed

Smart, John D

2005-05-01

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

Statistical physics of human cooperation

NASA Astrophysics Data System (ADS)

Perc, Matjaž; Jordan, Jillian J.; Rand, David G.; Wang, Zhen; Boccaletti, Stefano; Szolnoki, Attila

2017-05-01

Extensive cooperation among unrelated individuals is unique to humans, who often sacrifice personal benefits for the common good and work together to achieve what they are unable to execute alone. The evolutionary success of our species is indeed due, to a large degree, to our unparalleled other-regarding abilities. Yet, a comprehensive understanding of human cooperation remains a formidable challenge. Recent research in the social sciences indicates that it is important to focus on the collective behavior that emerges as the result of the interactions among individuals, groups, and even societies. Non-equilibrium statistical physics, in particular Monte Carlo methods and the theory of collective behavior of interacting particles near phase transition points, has proven to be very valuable for understanding counterintuitive evolutionary outcomes. By treating models of human cooperation as classical spin models, a physicist can draw on familiar settings from statistical physics. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among humans often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. The complexity of solutions therefore often surpasses that observed in physical systems. Here we review experimental and theoretical research that advances our understanding of human cooperation, focusing on spatial pattern formation, on the spatiotemporal dynamics of observed solutions, and on self-organization that may either promote or hinder socially favorable states.

Staged Inference using Conditional Deep Learning for energy efficient real-time smart diagnosis.

PubMed

Parsa, Maryam; Panda, Priyadarshini; Sen, Shreyas; Roy, Kaushik

2017-07-01

Recent progress in biosensor technology and wearable devices has created a formidable opportunity for remote healthcare monitoring systems as well as real-time diagnosis and disease prevention. The use of data mining techniques is indispensable for analysis of the large pool of data generated by the wearable devices. Deep learning is among the promising methods for analyzing such data for healthcare applications and disease diagnosis. However, the conventional deep neural networks are computationally intensive and it is impractical to use them in real-time diagnosis with low-powered on-body devices. We propose Staged Inference using Conditional Deep Learning (SICDL), as an energy efficient approach for creating healthcare monitoring systems. For smart diagnostics, we observe that all diagnoses are not equally challenging. The proposed approach thus decomposes the diagnoses into preliminary analysis (such as healthy vs unhealthy) and detailed analysis (such as identifying the specific type of cardio disease). The preliminary diagnosis is conducted real-time with a low complexity neural network realized on the resource-constrained on-body device. The detailed diagnosis requires a larger network that is implemented remotely in cloud and is conditionally activated only for detailed diagnosis (unhealthy individuals). We evaluated the proposed approach using available physiological sensor data from Physionet databases, and achieved 38% energy reduction in comparison to the conventional deep learning approach.

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.

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.

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

High-κ gate dielectrics: Current status and materials properties considerations

NASA Astrophysics Data System (ADS)

Wilk, G. D.; Wallace, R. M.; Anthony, J. M.

2001-05-01

Many materials systems are currently under consideration as potential replacements for SiO2 as the gate dielectric material for sub-0.1 μm complementary metal-oxide-semiconductor (CMOS) technology. A systematic consideration of the required properties of gate dielectrics indicates that the key guidelines for selecting an alternative gate dielectric are (a) permittivity, band gap, and band alignment to silicon, (b) thermodynamic stability, (c) film morphology, (d) interface quality, (e) compatibility with the current or expected materials to be used in processing for CMOS devices, (f) process compatibility, and (g) reliability. Many dielectrics appear favorable in some of these areas, but very few materials are promising with respect to all of these guidelines. A review of current work and literature in the area of alternate gate dielectrics is given. Based on reported results and fundamental considerations, the pseudobinary materials systems offer large flexibility and show the most promise toward successful integration into the expected processing conditions for future CMOS technologies, especially due to their tendency to form at interfaces with Si (e.g. silicates). These pseudobinary systems also thereby enable the use of other high-κ materials by serving as an interfacial high-κ layer. While work is ongoing, much research is still required, as it is clear that any material which is to replace SiO2 as the gate dielectric faces a formidable challenge. The requirements for process integration compatibility are remarkably demanding, and any serious candidates will emerge only through continued, intensive investigation.

Climate change mitigation through livestock system transitions.

PubMed

Havlík, Petr; Valin, Hugo; Herrero, Mario; Obersteiner, Michael; Schmid, Erwin; Rufino, Mariana C; Mosnier, Aline; Thornton, Philip K; Böttcher, Hannes; Conant, Richard T; Frank, Stefan; Fritz, Steffen; Fuss, Sabine; Kraxner, Florian; Notenbaert, An

2014-03-11

Livestock are responsible for 12% of anthropogenic greenhouse gas emissions. Sustainable intensification of livestock production systems might become a key climate mitigation technology. However, livestock production systems vary substantially, making the implementation of climate mitigation policies a formidable challenge. Here, we provide results from an economic model using a detailed and high-resolution representation of livestock production systems. We project that by 2030 autonomous transitions toward more efficient systems would decrease emissions by 736 million metric tons of carbon dioxide equivalent per year (MtCO2e⋅y(-1)), mainly through avoided emissions from the conversion of 162 Mha of natural land. A moderate mitigation policy targeting emissions from both the agricultural and land-use change sectors with a carbon price of US$10 per tCO2e could lead to an abatement of 3,223 MtCO2e⋅y(-1). Livestock system transitions would contribute 21% of the total abatement, intra- and interregional relocation of livestock production another 40%, and all other mechanisms would add 39%. A comparable abatement of 3,068 MtCO2e⋅y(-1) could be achieved also with a policy targeting only emissions from land-use change. Stringent climate policies might lead to reductions in food availability of up to 200 kcal per capita per day globally. We find that mitigation policies targeting emissions from land-use change are 5 to 10 times more efficient--measured in "total abatement calorie cost"--than policies targeting emissions from livestock only. Thus, fostering transitions toward more productive livestock production systems in combination with climate policies targeting the land-use change appears to be the most efficient lever to deliver desirable climate and food availability outcomes.

Climate change mitigation through livestock system transitions

PubMed Central

Havlík, Petr; Valin, Hugo; Herrero, Mario; Obersteiner, Michael; Schmid, Erwin; Rufino, Mariana C.; Mosnier, Aline; Thornton, Philip K.; Böttcher, Hannes; Conant, Richard T.; Frank, Stefan; Fritz, Steffen; Fuss, Sabine; Kraxner, Florian; Notenbaert, An

2014-01-01

Livestock are responsible for 12% of anthropogenic greenhouse gas emissions. Sustainable intensification of livestock production systems might become a key climate mitigation technology. However, livestock production systems vary substantially, making the implementation of climate mitigation policies a formidable challenge. Here, we provide results from an economic model using a detailed and high-resolution representation of livestock production systems. We project that by 2030 autonomous transitions toward more efficient systems would decrease emissions by 736 million metric tons of carbon dioxide equivalent per year (MtCO2e⋅y−1), mainly through avoided emissions from the conversion of 162 Mha of natural land. A moderate mitigation policy targeting emissions from both the agricultural and land-use change sectors with a carbon price of US$10 per tCO2e could lead to an abatement of 3,223 MtCO2e⋅y−1. Livestock system transitions would contribute 21% of the total abatement, intra- and interregional relocation of livestock production another 40%, and all other mechanisms would add 39%. A comparable abatement of 3,068 MtCO2e⋅y−1 could be achieved also with a policy targeting only emissions from land-use change. Stringent climate policies might lead to reductions in food availability of up to 200 kcal per capita per day globally. We find that mitigation policies targeting emissions from land-use change are 5 to 10 times more efficient—measured in “total abatement calorie cost”—than policies targeting emissions from livestock only. Thus, fostering transitions toward more productive livestock production systems in combination with climate policies targeting the land-use change appears to be the most efficient lever to deliver desirable climate and food availability outcomes. PMID:24567375

Scaling and systems biology for integrating multiple organs-on-a-chip.

PubMed

Wikswo, John P; Curtis, Erica L; Eagleton, Zachary E; Evans, Brian C; Kole, Ayeeshik; Hofmeister, Lucas H; Matloff, William J

2013-09-21

Coupled systems of in vitro microfabricated organs-on-a-chip containing small populations of human cells are being developed to address the formidable pharmacological and physiological gaps between monolayer cell cultures, animal models, and humans that severely limit the speed and efficiency of drug development. These gaps present challenges not only in tissue and microfluidic engineering, but also in systems biology: how does one model, test, and learn about the communication and control of biological systems with individual organs-on-chips that are one-thousandth or one-millionth of the size of adult organs, or even smaller, i.e., organs for a milliHuman (mHu) or microHuman (μHu)? Allometric scaling that describes inter-species variation of organ size and properties provides some guidance, but given the desire to utilize these systems to extend and validate human pharmacokinetic and pharmacodynamic (PK/PD) models in support of drug discovery and development, it is more appropriate to scale each organ functionally to ensure that it makes the suitable physiological contribution to the coupled system. The desire to recapitulate the complex organ-organ interactions that result from factors in the blood and lymph places a severe constraint on the total circulating fluid (~5 mL for a mHu and ~5 μL for a μHu) and hence on the pumps, valves, and analytical instruments required to maintain and study these systems. Scaling arguments also provide guidance on the design of a universal cell-culture medium, typically without red blood cells. This review presents several examples of scaling arguments and discusses steps that should ensure the success of this endeavour.

[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.

Beam Tests of Diamond-Like Carbon Coating for Mitigation of Electron Cloud

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

Eldred, Jeffrey; Backfish, Michael; Kato, Shigeki

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. Our results evaluate the efficacy of a diamond-like carbon (DLC) coating for the mitigation of electron in the Fermilab Main Injector. The interior surface of the beampipe conditions in response to electron bombardment from the electron cloud and we track the change in electron cloud flux over time in the DLC coated beampipe and uncoated stainless steel beampipe. The electron flux is measured by retarding field analyzers placed in a field-free region of the Mainmore » Injector. We find the DLC coating reduces the electron cloud signal to roughly 2\\% of that measured in the uncoated stainless steel beampipe.« less

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.

System Engineering on the Use for Ares I,V - the Simpler, the Better

NASA Technical Reports Server (NTRS)

Kelly, William; Greene, William D.; Greasley, Paul; Ackerman, Peter C.

2008-01-01

The Ares I and Ares V Vehicles will utilize the J-2X rocket engine developed for NASA by the Pratt & Whitney Rocketdyne Company. The J-2X is an improved higher power version of the original J-2 engine used during the Apollo program. With higher power and updated requirements for safety and performance, the J-2X becomes a new engine using state-of-the-art design methodology, materials and manufacturing processes. The implementation of Systems Engineering (SE) principles enables the rapid J-2X development program to remain aligned with the ARES I and V vehicle programs, Meeting the aggressive development schedule is a challenge. Coordinating the best expertise thai NASA and PWR have to offer requires effectively utilizing resources at multiple sites. This presents formidable communication challenges. SE allows honest and open discussions of issues and problems. This simple idea is often overlooked in large and complex SE programs. Regular and effective meetings linking SE objectives to component designs are used to voice differences of opinions with customer and contractor in attendance so that the best mutual decisions can be made on the shortest possible schedule. Regular technical interchange meetings on secure program wide computer networks and CM processes are effective,in the "Controlled Change" process that exemplifies good SE. Good communication is a key effective SE implementation. The System of Systems approach is the vision of the Orion program which facilitates the establishment of dynamic SE processes at all levels including the engine. SE enables requirements evolution by facilitating organizational and process agility. Flow down and distribution of requirements is controlled by Allocation Reports which breakdown numerical design objectives (weight, reliability, etc.) into quanta goals for each component area. Linked databases of design and verification requirements helps eliminate redundancy and potential mistakes inherent m separated systems. Another tool, the Architecture Design Description, is being used to control J-2X system architecture and effectively communicate configuration changes to those involved in the design process. But the proof is in successful program accomplishment. The SE is the methodology being used to meet the challenge of completing J-2X engine certification 2 years ahead of any engine program ever developed at PWR. The Ares I SE system of systems has delivered according to expectations thus far. All major design reviews (SRR. PDR, CDR) have been successfully conducted to satisfy overall program objectives using SE as the basis for accomplishment. The paper describes SE tools and techniques utilized to achieve this success.

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.

Comparative Studies to Be a Theme for the Joint Assembly in Montreal

NASA Astrophysics Data System (ADS)

Mendillo, Michael; Schubert, Gerald; Alexander, Joan; Strangeway, Robert

2004-02-01

To have a truly global view of geophysical systems, it helps to have a few globes to view. Our solar system offers a rich set of case studies on how environmental systems form and evolve. The temperature structures of atmospheres, their circulation patterns, and their optical emissions are governed by the same basic laws of physics and photochemistry, but with constituents and solar flux input values that vary dramatically over the span of the planets. The escape of gases from the Earth and those planets and moons with dense atmospheres involve processes rather different from those associated with sputtered gases from the far more abundant regoliths of rock and ice. The origins and dynamics of plasmas and magnetic fields, their interactions with the flowing solar wind and/or rapidly rotating planetary fields, and episodic ``space weather'' events provide additional areas of common science in remarkably different settings. The Earth and its companions thus comprise the only known set of experiments in planetary formation for which there is actual data to validate and to challenge theory and computer models. While observations are abundant for Earth, and beyond the ``discovery mode'' set for many of the planets and moons, there remain crucial gaps in our understanding and formidable problems to solve at each of these worlds. Coupling processes, perhaps most of all, from regions below and above the environmental systems being studied are at the forefront of current work, drawing attention to the need for advanced observational capabilities and breakthroughs in computer simulation techniques.

Trends and Challenges in Neuroengineering: Toward "Intelligent" Neuroprostheses through Brain-"Brain Inspired Systems" Communication.

PubMed

Vassanelli, Stefano; Mahmud, Mufti

2016-01-01

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term "neurobiohybrids" indicating all those systems where such interaction is established. We argue that achieving a "high-level" communication and functional synergy between natural and artificial neuronal networks in vivo , will allow the development of a heterogeneous world of neurobiohybrids, which will include "living robots" but will also embrace "intelligent" neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and more specifically, on how deeply it should be allowed that brain processing is affected by implanted "intelligent" artificial systems. Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a "community building" perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes.

AMORE: Applied Momentum for Orbital Refuse Elimination

NASA Astrophysics Data System (ADS)

Wolfson, M.

2014-09-01

The need for active orbital debris remediation has increasingly gained acceptance throughout the space community throughout the last decade as the threat to our assets has also increased. While there have been a wide variety of conceptual solutions proposed, a debris removal system has yet to be put in place. The challenges that stand in the way of action are formidable and range from technical to political to economic. The AMORE concept is a nascent technique that has the potential to address these challenges and bring active debris remediation into reality. It uses an on-orbit low energy neutral particle beam (~10 keV, TBD) to impart momentum onto medium (5mm 10 cm) debris objects in Low Earth Orbit (LEO), thereby reducing their kinetic energy and expediting their reentry. The advantage of this technique over other proposed concepts is that it does not require delta-V intensive rendezvous, has an effective range that allows daily access to hundreds of debris objects, and does not create policy concerns over violation of international treaties. In essence, AMORE would be a medium-sized high power satellite with one or more particle beams fed by a large propellant tank, and an on-board tracking sensor that provides beam control. The particle beam would be similar to existing Xenon Hall Effect thrusters being used today, with the addition of a beam lens that would focus and aim the beam. The primary technical challenge of this concept is the focusing, pointing, and closed loop control of the beam that is necessary to maintain effective momentum transfer at ranges up to 100 km. This effective range is critical in order to maximize daily access to debris objects. Even in the densely populated 800 km debris band, it can be expected that a single AMORE system would be within 100 km of a debris object less than an hour a day. Space is big, and range is critical for timely, cost effective debris removal. Initial analysis indicates that a single AMORE vehicle operating in the 800 km regime could lower the perigee of 100 pieces of 1 kg debris to a 25 year reentry orbit annually. The actual performance of a system would be highly dependent on the debris regime. An operational AMORE system would likely involve several vehicles operating autonomously for continuous mitigation of existing and future debris.

Creating a health care agenda for the Department of Homeland Security.

PubMed

Noji, Eric K

2003-11-01

The challenge before us at DHS--to optimize use of our resources to create an effective health response to terrorist incidents--is formidable. After spending several weeks in Baghdad and seeing all the problems that arise in establishing a new government, I found myself thinking, "This is going to take years." Then, when I returned to the United States, Surgeon General Vice Adam. Richard Carmona, MD, MPH, almost immediately assigned me to the new Department of Homeland Security, adding that the problems it faced were probably worse than those in Baghdad. "That is impossible," I thought. "There's no way this could present a greater logistical, organizational, cultural, and administrative challenge than establishing a new government in a country with no democratic tradition in its 5,000-year history!" Within two days of my appointment to the new department, however, I recognized the accuracy of the surgeon general's statement. We will, however, work diligently toward our goals. During the next couple of years, a major DHS priority will be state and local preparedness, which includes rapid identification of epidemics, improved training, the establishment of liaisons with other first responders such as fire, rescue, law enforcement, and emergency medical services teams, and implementing state-of-the-art communication, disease alert, and reporting systems. Table 2 constitutes a checklist for bioterrorism preparedness, from a public health perspective. Local response and coordination with federal authorities and the issues inherent in these efforts are discussed in depth in the presentations that begin on the following page of this publication.

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.

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

Application of satellite data in variational analysis for global cyclonic systems

NASA Technical Reports Server (NTRS)

Achtemeier, G. L.

1987-01-01

The research goal was a variational data assimilation method that incorporates as dynamical constraints, the primitive equations for a moist, convectively unstable atmosphere and the radiative transfer equation. Variables to be adjusted include the three-dimensional vector wind, height, temperature, and moisture from rawinsonde data, and cloud-wind vectors, moisture, and radiance from satellite data. This presents a formidable mathematical problem. In order to facilitate thorough analysis of each of the model components, four variational models that divide the problem naturally according to increasing complexity are defined. Each model is summarized.

Data access for scientific problem solving

NASA Technical Reports Server (NTRS)

Brown, James W.

1987-01-01

An essential ingredient in scientific work is data. In disciplines such as Oceanography, data sources are many and volumes are formidable. The full value of large stores of data cannot be realized unless careful thought is given to data access. JPL has developed the Pilot Ocean Data System to investigate techniques for archiving and accessing ocean data obtained from space. These include efficient storage and rapid retrieval of satellite data, an easy-to-use user interface, and a variety of output products which, taken together, permit researchers to extract and use data rapidly and conveniently.

Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

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

Acar, Handan; Samaeekia, Ravand; Schnorenberg, Mathew R.

Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are twomore » major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.« less

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.

Augmented reality for personalized nanomedicines.

PubMed

Lee, Yugyung; Lee, Chi H

As our understanding of onset and progress of diseases at the genetic and molecular level rapidly progresses, the potential of advanced technologies, such as 3D-printing, Socially-Assistive Robots (SARs) or augmented reality (AR), that are applied to personalized nanomedicines (PNMs) to alleviate pathological conditions, has become more prominent. Among advanced technologies, AR in particular has the greatest potential to address those challenges and facilitate the translation of PNMs into formidable clinical application of personalized therapy. As AR is about to adapt additional new methods, such as speech, voice recognition, eye tracing and motion tracking, to enable interaction with host response or biological systems in 3-D space, a combination of multiple approaches to accommodate varying environmental conditions, such as public noise and atmosphere brightness, will be explored to improve its therapeutic outcomes in clinical applications. For instance, AR glasses still being developed by Facebook or Microsoft will serve as new platform that can provide people with the health information they are interested in or various measures through which they can interact with medical services. This review has addressed the current progress and impact of AR on PNMs and its application to the biomedical field. Special emphasis is placed on the application of AR based PNMs to the treatment strategies against senior care, drug addiction and medication adherence. Published by Elsevier Inc.

Machine Learning-based Transient Brokers for Real-time Classification of the LSST Alert Stream

NASA Astrophysics Data System (ADS)

Narayan, Gautham; Zaidi, Tayeb; Soraisam, Monika; ANTARES Collaboration

2018-01-01

The number of transient events discovered by wide-field time-domain surveys already far outstrips the combined followup resources of the astronomical community. This number will only increase as we progress towards the commissioning of the Large Synoptic Survey Telescope (LSST), breaking the community's current followup paradigm. Transient brokers - software to sift through, characterize, annotate and prioritize events for followup - will be a critical tool for managing alert streams in the LSST era. Developing the algorithms that underlie the brokers, and obtaining simulated LSST-like datasets prior to LSST commissioning, to train and test these algorithms are formidable, though not insurmountable challenges. The Arizona-NOAO Temporal Analysis and Response to Events System (ANTARES) is a joint project of the National Optical Astronomy Observatory and the Department of Computer Science at the University of Arizona. We have been developing completely automated methods to characterize and classify variable and transient events from their multiband optical photometry. We describe the hierarchical ensemble machine learning algorithm we are developing, and test its performance on sparse, unevenly sampled, heteroskedastic data from various existing observational campaigns, as well as our progress towards incorporating these into a real-time event broker working on live alert streams from time-domain surveys.

Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery

PubMed Central

Haddad, Dana

2017-01-01

Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly via cell lysis, while leaving non-cancerous tissues unharmed. Several wild-type and genetically engineered vaccinia virus (VACV) strains have been tested in both preclinical and clinical trials with promising results. Greater understanding and advancements in molecular biology have enabled the generation of genetically engineered oncolytic viruses for safer and more efficacious treatment, including arming VACVs with cytokines and immunostimulatory molecules, anti-angiogenic agents, and enzyme prodrug therapy, in addition to combining VACVs with conventional external and systemic radiotherapy, chemotherapy, immunotherapy, and other virus strains. Furthermore, novel oncolytic vaccinia virus strains have been generated that express reporter genes for the tracking and imaging of viral therapy and monitoring of therapeutic response. Further study is needed to unlock VACVs’ full potential as part of the future of cancer therapy. PMID:28589082

Bearing fault diagnosis using a whale optimization algorithm-optimized orthogonal matching pursuit with a combined time-frequency atom dictionary

NASA Astrophysics Data System (ADS)

Zhang, Xin; Liu, Zhiwen; Miao, Qiang; Wang, Lei

2018-07-01

Condition monitoring and fault diagnosis of rolling element bearings are significant to guarantee the reliability and functionality of a mechanical system, production efficiency, and plant safety. However, this is almost invariably a formidable challenge because the fault features are often buried by strong background noises and other unstable interference components. To satisfactorily extract the bearing fault features, a whale optimization algorithm (WOA)-optimized orthogonal matching pursuit (OMP) with a combined time-frequency atom dictionary is proposed in this paper. Firstly, a combined time-frequency atom dictionary whose atom is a combination of Fourier dictionary atom and impact time-frequency dictionary atom is designed according to the properties of bearing fault vibration signal. Furthermore, to improve the efficiency and accuracy of signal sparse representation, the WOA is introduced into the OMP algorithm to optimize the atom parameters for best approximating the original signal with the dictionary atoms. The proposed method is validated through analyzing the bearing fault simulation signal and the real vibration signals collected from an experimental bearing and a wheelset bearing of high-speed trains. The comparisons with the respect to the state of the art in the field are illustrated in detail, which highlight the advantages of the proposed method.

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.

Big data from electronic health records for early and late translational cardiovascular research: challenges and potential.

PubMed

Hemingway, Harry; Asselbergs, Folkert W; Danesh, John; Dobson, Richard; Maniadakis, Nikolaos; Maggioni, Aldo; van Thiel, Ghislaine J M; Cronin, Maureen; Brobert, Gunnar; Vardas, Panos; Anker, Stefan D; Grobbee, Diederick E; Denaxas, Spiros

2018-04-21

Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research. We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium. We identified formidable challenges including: data quality, knowing what data exist, the legal and ethical framework for their use, data sharing, building and maintaining public trust, developing standards for defining disease, developing tools for scalable, replicable science and equipping the clinical and scientific work force with new inter-disciplinary skills. Opportunities claimed for big health record data include: richer profiles of health and disease from birth to death and from the molecular to the societal scale; accelerated understanding of disease causation and progression, discovery of new mechanisms and treatment-relevant disease sub-phenotypes, understanding health and diseases in whole populations and whole health systems and returning actionable feedback loops to improve (and potentially disrupt) existing models of research and care, with greater efficiency. In early translational research we identified exemplars including: discovery of fundamental biological processes e.g. linking exome sequences to lifelong electronic health records (EHR) (e.g. human knockout experiments); drug development: genomic approaches to drug target validation; precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive pharmacogenomics. In late translational research we identified exemplars including: learning health systems with outcome trials integrated into clinical care; citizen driven health with 24/7 multi-parameter patient monitoring to improve outcomes and population-based linkages of multiple EHR sources for higher resolution clinical epidemiology and public health. High volumes of inherently diverse ('big') EHR data are beginning to disrupt the nature of cardiovascular research and care. Such big data have the potential to improve our understanding of disease causation and classification relevant for early translation and to contribute actionable analytics to improve health and healthcare.

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.

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

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.

Anomalous Diffusion of Single Particles in Cytoplasm

PubMed Central

Regner, Benjamin M.; Vučinić, Dejan; Domnisoru, Cristina; Bartol, Thomas M.; Hetzer, Martin W.; Tartakovsky, Daniel M.; Sejnowski, Terrence J.

2013-01-01

The crowded intracellular environment poses a formidable challenge to experimental and theoretical analyses of intracellular transport mechanisms. Our measurements of single-particle trajectories in cytoplasm and their random-walk interpretations elucidate two of these mechanisms: molecular diffusion in crowded environments and cytoskeletal transport along microtubules. We employed acousto-optic deflector microscopy to map out the three-dimensional trajectories of microspheres migrating in the cytosolic fraction of a cellular extract. Classical Brownian motion (BM), continuous time random walk, and fractional BM were alternatively used to represent these trajectories. The comparison of the experimental and numerical data demonstrates that cytoskeletal transport along microtubules and diffusion in the cytosolic fraction exhibit anomalous (nonFickian) behavior and posses statistically distinct signatures. Among the three random-walk models used, continuous time random walk provides the best representation of diffusion, whereas microtubular transport is accurately modeled with fractional BM. PMID:23601312

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

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.

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

Scribner, R.A.

Sea-launched cruise missiles (SLCMs) present some particularly striking problems for both national security and arms control. These small, dual-purpose, difficult to detect weapons present some formidable challenges for verification in any scheme that attempts to limit rather than eliminate them. Conventionally armed SLCMs offer to the navies of both superpowers important offensive and defensive capabilities. Nuclear armed, long-range, land-attack SLCMs, on the other hand, seem to pose destabilizing threats and otherwise have questionable value, despite strong US support for extensive deployment of them. If these weapons are not constrained, their deployment could circumvent gains which might be made in agreementsmore » directly reducing of strategic nuclear weapons. This paper reviews the technology and planned deployments of SLCMs, the verification schemes which have been discussed and are being investigated to try to deal with the problem, and examines the proposed need for and possible uses of SLCMs. It presents an overview of the problem technically, militarily, and politically.« less

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.

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

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.

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.

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

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.

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

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.

Trends and Challenges in Neuroengineering: Toward “Intelligent” Neuroprostheses through Brain-“Brain Inspired Systems” Communication

PubMed Central

Vassanelli, Stefano; Mahmud, Mufti

2016-01-01

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term “neurobiohybrids” indicating all those systems where such interaction is established. We argue that achieving a “high-level” communication and functional synergy between natural and artificial neuronal networks in vivo, will allow the development of a heterogeneous world of neurobiohybrids, which will include “living robots” but will also embrace “intelligent” neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and more specifically, on how deeply it should be allowed that brain processing is affected by implanted “intelligent” artificial systems. Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a “community building” perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes. PMID:27721741

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

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.

The use of big data in transfusion medicine.

PubMed

Pendry, K

2015-06-01

'Big data' refers to the huge quantities of digital information now available that describe much of human activity. The science of data management and analysis is rapidly developing to enable organisations to convert data into useful information and knowledge. Electronic health records and new developments in Pathology Informatics now support the collection of 'big laboratory and clinical data', and these digital innovations are now being applied to transfusion medicine. To use big data effectively, we must address concerns about confidentiality and the need for a change in culture and practice, remove barriers to adopting common operating systems and data standards and ensure the safe and secure storage of sensitive personal information. In the UK, the aim is to formulate a single set of data and standards for communicating test results and so enable pathology data to contribute to national datasets. In transfusion, big data has been used for benchmarking, detection of transfusion-related complications, determining patterns of blood use and definition of blood order schedules for surgery. More generally, rapidly available information can monitor compliance with key performance indicators for patient blood management and inventory management leading to better patient care and reduced use of blood. The challenges of enabling reliable systems and analysis of big data and securing funding in the restrictive financial climate are formidable, but not insurmountable. The promise is that digital information will soon improve the implementation of best practice in transfusion medicine and patient blood management globally. © 2015 British Blood Transfusion Society.

Implementing clinical governance in English primary care groups/trusts: reconciling quality improvement and quality assurance.

PubMed

Campbell, S M; Sheaff, R; Sibbald, B; Marshall, M N; Pickard, S; Gask, L; Halliwell, S; Rogers, A; Roland, M O

2002-03-01

To investigate the concept of clinical governance being advocated by primary care groups/trusts (PCG/Ts), approaches being used to implement clinical governance, and potential barriers to its successful implementation in primary care. Qualitative case studies using semi-structured interviews and documentation review. Twelve purposively sampled PCG/Ts in England. Fifty senior staff including chief executives, clinical governance leads, mental health leads, and lay board members. Participants' perceptions of the role of clinical governance in PCG/Ts. PCG/Ts recognise that the successful implementation of clinical governance in general practice will require cultural as well as organisational changes, and the support of practices. They are focusing their energies on supporting practices and getting them involved in quality improvement activities. These activities include, but move beyond, conventional approaches to quality assessment (audit, incentives) to incorporate approaches which emphasise corporate and shared learning. PCG/Ts are also engaged in setting up systems for monitoring quality and for dealing with poor performance. Barriers include structural barriers (weak contractual levers to influence general practices), resource barriers (perceived lack of staff or money), and cultural barriers (suspicion by practice staff or problems overcoming the perceived blame culture associated with quality assessment). PCG/Ts are focusing on setting up systems for implementing clinical governance which seek to emphasise developmental and supportive approaches which will engage health professionals. Progress is intentionally incremental but formidable challenges lie ahead, not least reconciling the dual role of supporting practices while monitoring (and dealing with poor) performance.

Spun-wrapped aligned nanofiber (SWAN) lithography for fabrication of micro/nano-structures on 3D objects

NASA Astrophysics Data System (ADS)

Ye, Zhou; Nain, Amrinder S.; Behkam, Bahareh

2016-06-01

Fabrication of micro/nano-structures on irregularly shaped substrates and three-dimensional (3D) objects is of significant interest in diverse technological fields. However, it remains a formidable challenge thwarted by limited adaptability of the state-of-the-art nanolithography techniques for nanofabrication on non-planar surfaces. In this work, we introduce Spun-Wrapped Aligned Nanofiber (SWAN) lithography, a versatile, scalable, and cost-effective technique for fabrication of multiscale (nano to microscale) structures on 3D objects without restriction on substrate material and geometry. SWAN lithography combines precise deposition of polymeric nanofiber masks, in aligned single or multilayer configurations, with well-controlled solvent vapor treatment and etching processes to enable high throughput (>10-7 m2 s-1) and large-area fabrication of sub-50 nm to several micron features with high pattern fidelity. Using this technique, we demonstrate whole-surface nanopatterning of bulk and thin film surfaces of cubes, cylinders, and hyperbola-shaped objects that would be difficult, if not impossible to achieve with existing methods. We demonstrate that the fabricated feature size (b) scales with the fiber mask diameter (D) as b1.5 ~ D. This scaling law is in excellent agreement with theoretical predictions using the Johnson, Kendall, and Roberts (JKR) contact theory, thus providing a rational design framework for fabrication of systems and devices that require precisely designed multiscale features.Fabrication of micro/nano-structures on irregularly shaped substrates and three-dimensional (3D) objects is of significant interest in diverse technological fields. However, it remains a formidable challenge thwarted by limited adaptability of the state-of-the-art nanolithography techniques for nanofabrication on non-planar surfaces. In this work, we introduce Spun-Wrapped Aligned Nanofiber (SWAN) lithography, a versatile, scalable, and cost-effective technique for fabrication of multiscale (nano to microscale) structures on 3D objects without restriction on substrate material and geometry. SWAN lithography combines precise deposition of polymeric nanofiber masks, in aligned single or multilayer configurations, with well-controlled solvent vapor treatment and etching processes to enable high throughput (>10-7 m2 s-1) and large-area fabrication of sub-50 nm to several micron features with high pattern fidelity. Using this technique, we demonstrate whole-surface nanopatterning of bulk and thin film surfaces of cubes, cylinders, and hyperbola-shaped objects that would be difficult, if not impossible to achieve with existing methods. We demonstrate that the fabricated feature size (b) scales with the fiber mask diameter (D) as b1.5 ~ D. This scaling law is in excellent agreement with theoretical predictions using the Johnson, Kendall, and Roberts (JKR) contact theory, thus providing a rational design framework for fabrication of systems and devices that require precisely designed multiscale features. Electronic supplementary information (ESI) available: SWAN lithography on silicon; comparison of SWAN lithography and state-of-the-art nanopatterning methods; replica molding using SWAN lithography fabricated template; PDMS nanofluidic device, gold nanopattern characterization. See DOI: 10.1039/c6nr03323g

Bioterror events: preemptive strategies for healthcare executives.

PubMed

Zinkovich, Lisa; Malvey, Donna; Hamby, Eileen; Fottler, Myron

2005-01-01

Today's healthcare executives face challenges that their predecessors have never known: bioterror events. To prepare their organizations to cope with new and emerging strategic threats of bioterrorism, these executives must consider preemptive strategies. The authors present courses of action to assist executives' internal, external, and cross-sectional organizational preparedness. For example, stakeholder groups, internal resources, and competencies that combine and align efforts efficiently are identified. Twelve preemptive strategies are provided to guide healthcare executives in meeting these formidable and unprecedented challenges. The reputation of the healthcare organization (HCO) is at risk if a bioterror event is not properly handled, resulting in severe disadvantages for future operations. Justifiably, healthcare executives are contemplating the value of prioritizing bioterror preparedness, taking into account the immediate realities of decreasing reimbursement, increasing numbers of uninsured patients, and staffing shortages. Resources must be focused on the most valid concerns and must maximize the return on investment. Healthcare organizations can reap the benefits of a win-win approach by optimizing available resources, planning, and training. Bioterror preparedness will transcend the boundaries of bioterrorism and prepare for myriad mass healthcare incidents such as the looming potential for an avian (bird) influenza pandemic.

Beyond flexible batteries: aesthetically versatile, printed rechargeable power sources for smart electronics

NASA Astrophysics Data System (ADS)

Lee, Sang-Young

2017-05-01

Forthcoming wearable/flexible electronics with compelling shape diversity and mobile usability have garnered significant attention as a kind of disruptive technology to drastically change our daily lives. From a power source point of view, conventional rechargeable batteries (represented by lithium-ion batteries) with fixed shapes and dimensions are generally fabricated by winding (or stacking) cell components (such as anodes, cathodes and separator membranes) and then packaging them with (cylindrical-/rectangular-shaped) metallic canisters or pouch films, finally followed by injection of liquid electrolytes. In particular, the use of liquid electrolytes gives rise to serious concerns in cell assembly, because they require strict packaging materials to avoid leakage problems and also separator membranes to prevent electrical contact between electrodes. For these reasons, the conventional cell assembly and materials have pushed the batteries to lack of variety in form factors, thus imposing formidable challenges on their integration into versatile-shaped electronic devices. Here, as a facile and efficient strategy to address the aforementioned longstanding challenge, we demonstrate a new class of printed solid-state Li-ion batteries and also all-inkjet-printed solid-state supercapacitors with exceptional shape conformability and aesthetic versatility which lie far beyond those achievable with conventional battery technologies.

Scalable production of mechanically tunable block polymers from sugar

PubMed Central

Xiong, Mingyong; Schneiderman, Deborah K.; Bates, Frank S.; Hillmyer, Marc A.; Zhang, Kechun

2014-01-01

Development of sustainable and biodegradable materials is essential for future growth of the chemical industry. For a renewable product to be commercially competitive, it must be economically viable on an industrial scale and possess properties akin or superior to existing petroleum-derived analogs. Few biobased polymers have met this formidable challenge. To address this challenge, we describe an efficient biobased route to the branched lactone, β-methyl-δ-valerolactone (βMδVL), which can be transformed into a rubbery (i.e., low glass transition temperature) polymer. We further demonstrate that block copolymerization of βMδVL and lactide leads to a new class of high-performance polyesters with tunable mechanical properties. Key features of this work include the creation of a total biosynthetic route to produce βMδVL, an efficient semisynthetic approach that employs high-yielding chemical reactions to transform mevalonate to βMδVL, and the use of controlled polymerization techniques to produce well-defined PLA–PβMδVL–PLA triblock polymers, where PLA stands for poly(lactide). This comprehensive strategy offers an economically viable approach to sustainable plastics and elastomers for a broad range of applications. PMID:24912182

Green turtle fibropapillomatosis: challenges to assessing the role of environmental cofactors.

PubMed Central

Herbst, L H; Klein, P A

1995-01-01

Green turtle fibropapillomatosis (GTFP) is a growing threat to the survival of green turtle (Chelonia mydas) populations worldwide. Recent transmission studies point to an infectious etiology. Several field studies suggest that high GTFP prevalence is associated with marine habitats that have been impacted by agricultural, industrial, or urban development. Environmental contaminants could be involved in GTFP through several plausible mechanisms including cocarcinogenesis and contaminant-induced immune suppression. However, an association of contaminants with GTFP has not been established. A broader perspective is needed when studying infectious diseases such as GTFP in complex ecosystems. Alternative explanations for high GTFP prevalence in some near-shore habitats include the following: a) these habitats provide an optimum physical environment for survival and transmission of the infectious agent; b) these habitats attract a high density of susceptible turtles or harbor a higher density of potential vectors, facilitating transmission of the pathogen in a density-dependent fashion; and c) these habitats may contain other stressors that render turtles more susceptible to GTFP. Application of scientifically rigorous criteria in the epizootiology of GTFP in free-ranging populations remains a formidable challenge. Images Figure 1. PMID:7556020

A case of a power failure in the operating room.

PubMed

Yasny, Jeffrey; Soffer, Robert

2005-01-01

In the operating room, safely administering anesthesia amidst a major power failure can instantly present one with a formidable challenge. A case is presented involving a 23-year-old healthy woman who underwent a complex oral and maxillofacial surgery to correct a dentofacial deformity. Three hours into the case and with the patient's maxilla downfractured, the overhead surgical lights blacked out, and there was an apparent loss of the anesthesia machine's ability to function. Providing adequate oxygenation, ventilation, anesthesia levels, monitoring of vital signs, and transportation of the patient were some of the challenges faced, and the response to this unexpected event is recounted. The importance of one's familiarity with an anesthesia machine's backup battery supply, routinely checking machinery, ensuring that appropriate and sufficient supplies are readily available, exercising calm leadership with clear communication, and formulating a clear plan with backup alternatives are discussed. Various recommendations are proposed with respect to the preparation for and the prevention of a power failure in the operating room. This report's account of events is aimed to "shed some light" on this topic, serve as a check of one's own preparedness, and facilitate the optimal management of a similarly unexpected incident.

Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges

PubMed Central

Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C.

2016-01-01

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of non-small cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify two major lessons from the outcomes of these trials: 1) The antioxidant hypothesis was tested in wrong subjects or patient populations. 2) The selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to re-vitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials. PMID:26595411

Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges.

PubMed

Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C

2016-01-01

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of nonsmall cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify 2 major lessons from the outcomes of these trials: 1) the antioxidant hypothesis was tested in wrong subjects or patient populations, and 2) the selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to revitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials.

Physics and technological aspects of nanofluidics.

PubMed

Bocquet, Lyderic; Tabeling, Patrick

2014-09-07

From a physical perspective, nanofluidics represents an extremely rich domain. It hosts many mechanisms acting on the nanoscale, which combine together or interact with the confinement to generate new phenomena. Superfast flows in carbon nanotubes, nonlinear electrokinetic transport, slippage over smooth surfaces, nanobubble stability, etc. are the most striking phenomena that have been unveiled over the past few years, and some of them are still awaiting an explanation. One may anticipate that new nanofluidic effects will be discovered in the future, but at the moment, the technological barrier is high. Fabrication of nanochannels is most often a tour de force, slow and costly. However, with the accumulation of technological skills along with the use of new nanofluidic materials (like nanotubes), nanofluidics is becoming increasingly accessible to experimentalists. Among the technological challenges faced by the field, fabricating devices mimicking natural nanometric systems, such as aquaporins, ionic pumps or kidney osmotic filtering, seems the most demanding in terms of groundbreaking ideas. Nanoflow characterization remains delicate, although considerable progress has been achieved over the past years. The targeted application of nanofluidics is not only in the field of genomics and membrane science--with disruptive developments to be expected for water purification, desalination, and energy harvesting--but also for oil and gas production from unconventional reservoirs. Today, in view of the markets that are targeted, nanofluidics may well impact the industry more than microfluidics; this would represent an unexpected paradox. These successes rely on using a variety of materials and technologies, using state-of-the-art nanofabrication, or low-tech inexpensive approaches. As a whole, nanofluidics is a fascinating field that is facing considerable challenges today. It possesses a formidable potential and offers much space for creative groundbreaking ideas.

Challenges to the global control of tuberculosis.

PubMed

Chiang, Chen-Yuan; Van Weezenbeek, Catharina; Mori, Toru; Enarson, Donald A

2013-05-01

Diagnosis and treatment of tuberculosis (TB) will likely navigate a historical turning point in the 2010s with a new management paradigm emerging. However, global control of TB remains a formidable challenge for the decades to come. The estimated case detection rate of TB globally was 66%, and there were 310 000 estimated multidrug-resistant TB (MDR-TB) cases among the 6.2 million TB patients notified in 2011. Although new tools are being introduced for the diagnosis of MDR-TB, there are operational and cost issues related to their use that require urgent attention, so that the poor and vulnerable can benefit. World Health Organization (WHO) estimated that globally, 3.7% of new cases and 20% of previously treated cases have MDR-TB. However, the scale-up of programmatic management of drug-resistant TB is slow, with only 60 000 MDR-TB cases notified to WHO in 2011. The overall proportion of treatment success of MDR-TB notified globally in 2009 was 48%, far below the global target of 75% success rate. Although new tools and drugs have the potential to significantly improve both case detection and treatment outcome, adequate health systems and human resources are needed for rapid uptake and proper implementation to have the impact required to eliminate TB. Hence, the global TB community should broaden its scope, seek intersectoral collaboration and advocate for cost reduction of new tools, while ensuring that the basics of TB control are implemented to reduce the TB burden through the current 'prevention through case management' paradigm. Respirology © 2013 Asian Pacific Society of Respirology. The World Health Organization retains copyright and all other rights in the manuscript as submitted for publication and has granted the Publisher permission for the reproduction of this article.

Abraham Lincoln and the global economy.

PubMed

Hormats, Robert D

2003-08-01

Abraham Lincoln would have well understood the challenges facing many modern emerging nations. In Lincoln's America, as in many developing nations today, sweeping economic change threatened older industries, traditional ways of living, and social and national cohesion by exposing economies and societies to new and powerful competitive forces. Yet even in the midst of the brutal and expensive American Civil war--and in part because of it--Lincoln and the Republican Congress enacted bold legislation that helped create a huge national market, a strong and unified economy governed by national institutions, and a rising middle class of businessmen and property owners. Figuring out how to maximize the benefits of globalization while minimizing its disruptions is a formidable challenge for policy makers. How do you expand opportunities for the talented and the lucky while making sure the rest of society doesn't fall behind? It may be helpful to look at the principles that informed the policies that Lincoln and the Republican Congress instituted after they came to power in 1861: Facilitate the upward mobility of low- and middle-income groups to give them a significant stake in the country. Emphasize the good of the national economy over regional interests. Affirm the need for sound government institutions to temper the dynamics of the free enterprise system. Tailor policies to the national situation. Realize that a period of turmoil may present a unique opportunity for reform. These principles drove the reforms that helped Americans cope with and benefit from rapid technological advances and the fast integration of the American economy in the nineteenth century. They may be instructive to today's policy makers who are struggling to help their own citizens integrate into the fast-changing global economy of the twenty-first century.

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.

Is rangeland agriculture sustainable?

PubMed

Heitschmidt, R K; Vermeire, L T; Grings, E E

2004-01-01

The objective of this paper is to examine the sustainability of rangeland agriculture (i.e., managed grazing) on a world-wide basis, with a focus on North America. Sustainability is addressed on three fronts: 1) ecological, 2) economic, and 3) social acceptance. Based on previous and on-going research, we suggest that employment of science-based rangeland grazing management strategies and tactics can ensure ecological sustainability. The formidable challenge in employing such technology centers around the need to balance efficiency of solar energy capture and subsequent harvest efficiencies across an array of highly spatially and temporally variable vegetation growing conditions using animals that graze selectively. Failure to meet this fundamental challenge often accelerates rangeland desertification processes, and in some instances, enhances rate and extent of the invasion of noxious weeds. We also suggest that the fundamental reason that ecologically sound grazing management technologies are often not employed in the management of grazed ecological systems is because social values drive management decisions more so than ecological science issues. This is true in both well-developed societies with substantial economic resources and in less-developed societies with few economic resources. However, the social issues driving management are often entirely different, ranging from multiple-use issues in developed countries to human day-to-day survival issues in poorly developed countries. We conclude that the long-term sustainability of rangeland agriculture in 1) developed societies depends on the ability of rangeland agriculturalists to continually respond in a dynamic, positive, proactive manner to ever-changing social values and 2) less-developed societies on their ability to address the ecological and social consequences arising from unsustainable human populations before the adoption of science-based sustainable rangeland management technologies.

A Fundamental Study of Inorganic Clathrate and Other Open-Framework Materials

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

Nolas, George

Due to formidable synthetic challenges, many materials of scientific and technological interest are first obtained as microcrystalline powders. High purity, high yield processing techniques are often lacking and thus care must be taken in interpretation of the observed structural, chemical, and physical properties of powder or polycrystalline materials, which can be strongly influenced by extrinsic properties. Furthermore, the preparation of high-quality single crystals for many materials by traditional techniques can be especially challenging in cases where the elemental constituents have greatly differing melting points and/or vapor pressures, when the desired compound is thermodynamically metastable, or where growth with participation ofmore » the melt is generally not possible. New processing techniques are therefore imperative in order to investigate the intrinsic properties of these materials and elucidate their fundamental physical properties. Intermetallic clathrates constitute one such class of materials. The complex crystal structures of intermetallic clathrates are characterized by mainly group 14 host frameworks encapsulating guest-ions in polyhedral cages. The unique features of clathrate structures are intimately related to their physical properties, offering ideal systems for the study of structure-property relationships in crystalline solids. Moreover, intermetallic clathrates are being actively investigated due to their potential for application in thermoelectrics, photovoltaics and opto-electronics, superconductivity, and magnetocaloric technologies. We have developed different processing techniques in order to synthesize phase-pure high yield clathrates reproducibly, as well as grow single crystals for the first time. We also employed these techniques to synthesize new “open-framework” compounds. These advances in materials processing and crystal growth allowed for the investigation of the physical properties of a variety of different clathrate compositions for the first time.« less

Skylab food system

NASA Technical Reports Server (NTRS)

Bush, W. H.

1974-01-01

The Skylab food program was a major effort involving a complex spectrum of activities necessary for the preparation of a crew feeding system. Approximately 17,000 individual food packages and support items, weighing more than 1225 kg, were launched into space as a single unit on board the orbital workshop. This unit provided the three (three-man) Skylab crews with nourishing foods and beverages for a total of 156 days, as well as with eating utensils and accessory items. Additionally, provisions for 5 days (15 man-days) were provided in each of the three command and service modules in a manner similar to that of the Apollo flights. The Skylab food system not only provided the crew with a palatable balanced diet in a familiar and acceptable manner but also supported the formidable mineral balance medical experiment series (M070).

A method for evaluating nanoparticle transport through the blood-brain barrier in vitro.

PubMed

Guarnieri, Daniela; Muscetti, Ornella; Netti, Paolo A

2014-01-01

Blood-brain barrier (BBB) represents a formidable barrier for many therapeutic drugs to enter the brain tissue. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous system (CNS) diseases. In this context, nanoparticles are an emerging class of drug delivery systems that can be easily tailored to deliver drugs to various compartments of the body, including the brain. To identify, characterize, and validate novel nanoparticles applicable to brain delivery, in vitro BBB model systems have been developed. In this work, we describe a method to screen nanoparticles with variable size and surface functionalization in order to define the physicochemical characteristics underlying the design of nanoparticles that are able to efficiently cross the BBB.

Data acquisition using the 168/E. [CERN ISR

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

Carroll, J.T.; Cittolin, S.; Demoulin, M.

1983-03-01

Event sizes and data rates at the CERN anti p p collider compose a formidable environment for a high level trigger. A system using three 168/E processors for experiment UA1 real-time event selection is described. With 168/E data memory expanded to 512K bytes, each processor holds a complete event allowing a FORTRAN trigger algorithm access to data from the entire detector. A smart CAMAC interface reads five Remus branches in parallel transferring one word to the target processor every 0.5 ..mu..s. The NORD host computer can simultaneously read an accepted event from another processor.

Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.

PubMed

Oscherwitz, Jon; Feldman, Daniel; Yu, Fen; Cease, Kemp B

2015-01-09

Anthrax represents a formidable bioterrorism threat for which new, optimized vaccines are required. We previously demonstrated that epitope-focused multiple antigenic peptides or a recombinant protein in Freund's adjuvant can elicit Ab against the loop neutralizing determinant (LND), a cryptic linear neutralizing epitope in the 2ß2-2ß3 loop of protective antigen from Bacillus anthracis, which mediated protection of rabbits from inhalation challenge with B. anthracis Ames strain. However, demonstration of efficacy using human-use adjuvants is required before proceeding with further development of an LND vaccine for testing in non-human primates and humans. To optimize the LND immunogen, we first evaluated the protective efficacy and immune correlates associated with immunization of rabbits with mixtures containing two molecular variants of multiple antigenic peptides in Freunds adjuvant, termed BT-LND(2) and TB-LND(2). TB-LND(2) was then further evaluated for protective efficacy in rabbits employing human-use adjuvants. Immunization of rabbits with TB-LND(2) in human-use adjuvants elicited protection from Ames strain spore challenge which was statistically indistinguishable from that elicited through immunization with protective antigen. All TB-LND(2) rabbits with any detectable serum neutralization prior to challenge were protected from aerosolized spore exposure. Remarkably, rabbits immunized with TB-LND(2) in Alhydrogel/CpG had significant anamnestic increases in post-challenge LND-specific Ab and neutralization titers despite little evidence of spore germination in these rabbits. An LND-specific epitope-focused vaccine may complement PA-based vaccines and may represent a complementary stand-alone vaccine for anthrax. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decolonizing Strategies for Mentoring American Indians and Alaska Natives in HIV and Mental Health Research

PubMed Central

Simoni, Jane M.

2009-01-01

American Indian and Alaska Native (AIAN) scholars in the fields of mental health and HIV face formidable barriers to scientific success. These include justifiable mistrust of historically oppressive educational systems, educational disparities, role burdens within academe, the devaluation and marginalization of their research interests, and outright discrimination. Research partners can work to dismantle these barriers by embracing indigenous worldviews, engaging in collaborative research partnerships, building research capacity within universities and tribal communities, changing reward systems, and developing mentoring programs. At the individual level, aspiring AIAN scholars must build coalitions, reject internalized colonial messages, and utilize indigenous ethical frames. The creation of a cadre of AIAN researchers is crucial to improving the health of AIAN peoples. PMID:19246668

High Data Rate Architecture (HiDRA)

NASA Technical Reports Server (NTRS)

Hylton, Alan; Raible, Daniel

2016-01-01

One of the greatest challenges in developing new space technology is in navigating the transition from ground based laboratory demonstration at Technology Readiness Level 6 (TRL-6) to conducting a prototype demonstration in space (TRL-7). This challenge is com- pounded by the relatively low availability of new spacecraft missions when compared with aeronautical craft to bridge this gap, leading to the general adoption of a low-risk stance by mission management to accept new, unproven technologies into the system. Also in consideration of risk, the limited selection and availability of proven space-grade components imparts a severe limitation on achieving high performance systems by current terrestrial technology standards. Finally from a space communications point of view the long duration characteristic of most missions imparts a major constraint on the entire space and ground network architecture, since any new technologies introduced into the system would have to be compliant with the duration of the currently deployed operational technologies, and in some cases may be limited by surrounding legacy capabilities. Beyond ensuring that the new technology is verified to function correctly and validated to meet the needs of the end users the formidable challenge then grows to additionally include: carefully timing the maturity path of the new technology to coincide with a feasible and accepting future mission so it flies before its relevancy has passed, utilizing a limited catalog of available components to their maximum potential to create meaningful and unprecedented new capabilities, designing and ensuring interoperability with aging space and ground infrastructures while simultaneously providing a growth path to the future. The International Space Station (ISS) is approaching 20 years of age. To keep the ISS relevant, technology upgrades are continuously taking place. Regarding communications, the state-of-the-art communication system upgrades underway include high-rate laser terminals. These must interface with the existing, aging data infrastructure. The High Data Rate Architecture (HiDRA) project is designed to provide networked store, carry, and forward capability to optimize data flow through both the existing radio frequency (RF) and new laser communications terminal. The networking capability is realized through the Delay Tolerant Networking (DTN) protocol, and is used for scheduling data movement as well as optimizing the performance of existing RF channels. HiDRA is realized as a distributed FPGA memory and interface controller that is itself controlled by a local computer running DTN software. Thus HiDRA is applicable to other arenas seeking to employ next-generation communications technologies, e.g. deep space. In this paper, we describe HiDRA and its far-reaching research implications.

Observing copepods through a genomic lens

PubMed Central

2011-01-01

Background Copepods outnumber every other multicellular animal group. They are critical components of the world's freshwater and marine ecosystems, sensitive indicators of local and global climate change, key ecosystem service providers, parasites and predators of economically important aquatic animals and potential vectors of waterborne disease. Copepods sustain the world fisheries that nourish and support human populations. Although genomic tools have transformed many areas of biological and biomedical research, their power to elucidate aspects of the biology, behavior and ecology of copepods has only recently begun to be exploited. Discussion The extraordinary biological and ecological diversity of the subclass Copepoda provides both unique advantages for addressing key problems in aquatic systems and formidable challenges for developing a focused genomics strategy. This article provides an overview of genomic studies of copepods and discusses strategies for using genomics tools to address key questions at levels extending from individuals to ecosystems. Genomics can, for instance, help to decipher patterns of genome evolution such as those that occur during transitions from free living to symbiotic and parasitic lifestyles and can assist in the identification of genetic mechanisms and accompanying physiological changes associated with adaptation to new or physiologically challenging environments. The adaptive significance of the diversity in genome size and unique mechanisms of genome reorganization during development could similarly be explored. Genome-wide and EST studies of parasitic copepods of salmon and large EST studies of selected free-living copepods have demonstrated the potential utility of modern genomics approaches for the study of copepods and have generated resources such as EST libraries, shotgun genome sequences, BAC libraries, genome maps and inbred lines that will be invaluable in assisting further efforts to provide genomics tools for copepods. Summary Genomics research on copepods is needed to extend our exploration and characterization of their fundamental biological traits, so that we can better understand how copepods function and interact in diverse environments. Availability of large scale genomics resources will also open doors to a wide range of systems biology type studies that view the organism as the fundamental system in which to address key questions in ecology and evolution. PMID:21933388

Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Li, Dongdong; Xu, Fan; Wu, Aihua; Wang, Jinyu; Huang, Yongzhuo

2017-01-01

Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences. Even assisting by targeting ligands, protein brain delivery still remains challenging because of the synthesis difficulties of ligand-modified proteins. Herein, we propose a rocket-like, multistage booster delivery system of a protein toxin, trichosanthin (TCS), for antiglioma treatment. TCS is a ribosome-inactivating protein with the potent activity against various solid tumors but lack of specific action and cell penetration ability. To overcome the challenge of its poor druggability and site-specific modification, intein-mediated ligation was applied, by which a gelatinase-cleavable peptide and cell-penetrating peptide (CPP)-fused recombinant TCS toxin can be site-specifically conjugated to lactoferrin (LF), thus constructing a BBB-penetrating, gelatinase-activatable cell-penetrating nanohybrid TCS toxin. This nanohybrid TCS system is featured by the multistage booster strategy for glioma dual-targeting delivery. First, LF can target to the BBB-overexpressing low-density lipoprotein receptor-related protein-1 (LRP-1), and assist with BBB penetration. Second, once reaching the tumor site, the gelatinase-cleavable peptide acts as a separator responsive to the glioma-associated matrix metalloproteinases (MMPs), thus releasing to the CPP-fused toxin. Third, CPP mediates intratumoral and intracellular penetration of TCS toxin, thereby enhancing its antitumor activity. The BBB penetration and MMP-2-activability of this delivery system were demonstrated. The antiglioma activity was evaluated in the subcutaneous and orthotopic animal models. Our work provides a useful protocol for improving the druggability of such class of protein toxins and promoting their in-vivo application for targeted cancer therapy. PMID:28912890

Hidden weapons of microbial destruction in plant genomes

PubMed Central

Manners, John M

2007-01-01

Recent bioinformatic analyses of sequenced plant genomes reveal a previously unrecognized abundance of genes encoding antimicrobial cysteine-rich peptides, representing a formidable and dynamic defense arsenal against plant pests and pathogens. PMID:17903311

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus.

PubMed

Guerra, Fermin E; Borgogna, Timothy R; Patel, Delisha M; Sward, Eli W; Voyich, Jovanka M

2017-01-01

Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages. Staphylococcus aureus ( S. aureus ) is a prevalent Gram-positive bacterium that is a common commensal and causes a wide range of diseases from skin infections to endocarditis. Since its discovery, S. aureus has been a formidable neutrophil foe that has challenged the efficacy of this professional assassin. Indeed, proper clearance of S. aureus by neutrophils is essential to positive infection outcome, and S. aureus has developed mechanisms to evade neutrophil killing. Herein, we will review mechanisms used by S. aureus to modulate and evade neutrophil bactericidal mechanisms including priming, activation, chemotaxis, production of reactive oxygen species, and resolution of infection. We will also highlight how S. aureus uses sensory/regulatory systems to tailor production of virulence factors specifically to the triggering signal, e.g., neutrophils and defensins. To conclude, we will provide an overview of therapeutic approaches that may potentially enhance neutrophil antimicrobial functions.

DISENTANGLING THE ICL WITH THE CHEFs: ABELL 2744 AS A CASE STUDY

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

Jiménez-Teja, Y.; Dupke, R., E-mail: yojite@iaa.es

Measurements of the intracluster light (ICL) are still prone to methodological ambiguities, and there are multiple techniques in the literature to address them, mostly based on the binding energy, the local density distribution, or the surface brightness. A common issue with these methods is the a priori assumption of a number of hypotheses on either the ICL morphology, its surface brightness level, or some properties of the brightest cluster galaxy (BCG). The discrepancy in the results is high, and numerical simulations just place a boundary on the ICL fraction in present-day galaxy clusters in the range 10%–50%. We developed amore » new algorithm based on the Chebyshev–Fourier functions to estimate the ICL fraction without relying on any a priori assumption about the physical or geometrical characteristics of the ICL. We are able to not only disentangle the ICL from the galactic luminosity but mark out the limits of the BCG from the ICL in a natural way. We test our technique with the recently released data of the cluster Abell 2744, observed by the Frontier Fields program. The complexity of this multiple merging cluster system and the formidable depth of these images make it a challenging test case to prove the efficiency of our algorithm. We found a final ICL fraction of 19.17 ± 2.87%, which is very consistent with numerical simulations.« less

Silver iodide microstructures of a uniform towerlike shape: morphology purification via a chemical dissolution, simultaneously boosted catalytic durability, and enhanced catalytic performances.

PubMed

Lei, Bin; Zhu, Mingshan; Chen, Penglei; Chen, Chuncheng; Ma, Wanhong; Li, Tiesheng; Liu, Minghua

2014-03-26

The fabrication of microstructures/nanostructures of a uniform yet well-defined morphology has attracted broad interest from a variety of fields of advanced functional materials, especially catalysts. Most of the conventional methods generally suffer from harsh synthesis conditions, requirement of bulky apparatus, or incapability of scalable production, etc. To meet these formidable challenges, it is strongly desired to develop a facile, cost-effective, scalable method to fulfill a morphology purification. By a precipitation reaction between AgNO3 and KI, we report that irregular AgI structures, or their mixture with towerlike AgI architectures could be fabricated. Compared to the former, the mixed structures exhibit enhanced catalytic reactivity toward the photodegradation of Methyl Orange pollutant. However, its catalytic durability, which is one of the most crucial criteria that are required by superior catalysts, is poor. We further show that the irregular structures could be facilely removed from the mixture via a KI-assisted chemical dissolution, producing AgI of a uniform towerlike morphology. Excitingly, after such simple morphology purification, our towerlike AgI displays not only a boosted catalytic durability but also an enhanced catalytic reactivity. Our chemical dissolution-based morphology purification protocol might be extended to other systems, wherein high-quality advanced functional materials of desired properties might be developed.

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.

An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh

PubMed Central

Mohammad Fazle Akbar, Sheikh; chandra Podder, Dulal; Kumar Saha, Paban; Jahan, Munira; Begum, Lovely; Afrose, Tanjina; chowdhury, Farzana; Rahman, Salimur

2014-01-01

ABSTRACT A total of 45 patients with acute hepatitis were detected in a medical facility of Bangladesh over a period of 6 months. All of them were physicians, nurses, students or employees of the hospital. About 50% of these patients suffered from acute hepatitis within a period of 2 months. All of them had clinical and biochemical evidences of acute hepatitis. All of them shared common working places as well as common dining and cooking facilities. Although the disease was supposed to be caused by hepatitis viruses, none of them were expressing IgM type antibody to hepatitis B core antigen (IgM anti-HBc) or hepatitis C virus (IgM anti-HCV). IgM type antibody to hepatitis A virus (IgM HAV) was detected in one patient and IgM type antibody to hepatitis E virus (anti-HEV IgM) were found in 14 patients. In conclusion, diagnosis of etiological agent of viral acute hepatitis constitutes a formidable challenge to the existing health care delivery system in developing countries as available serological and routine screening fails to find the proper etiological agent. How to cite this article: Mahtab MA, Akbar SMF, Podder DC, Saha PK, Jahan M, Begum L, Afrose T, Chowdhury F, Rahman S. An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(1):66-67. PMID:29264325

An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh.

PubMed

Al Mahtab, Mamun; Mohammad Fazle Akbar, Sheikh; Chandra Podder, Dulal; Kumar Saha, Paban; Jahan, Munira; Begum, Lovely; Afrose, Tanjina; Chowdhury, Farzana; Rahman, Salimur

2014-01-01

A total of 45 patients with acute hepatitis were detected in a medical facility of Bangladesh over a period of 6 months. All of them were physicians, nurses, students or employees of the hospital. About 50% of these patients suffered from acute hepatitis within a period of 2 months. All of them had clinical and biochemical evidences of acute hepatitis. All of them shared common working places as well as common dining and cooking facilities. Although the disease was supposed to be caused by hepatitis viruses, none of them were expressing IgM type antibody to hepatitis B core antigen (IgM anti-HBc) or hepatitis C virus (IgM anti-HCV). IgM type antibody to hepatitis A virus (IgM HAV) was detected in one patient and IgM type antibody to hepatitis E virus (anti-HEV IgM) were found in 14 patients. In conclusion, diagnosis of etiological agent of viral acute hepatitis constitutes a formidable challenge to the existing health care delivery system in developing countries as available serological and routine screening fails to find the proper etiological agent. How to cite this article: Mahtab MA, Akbar SMF, Podder DC, Saha PK, Jahan M, Begum L, Afrose T, Chowdhury F, Rahman S. An Outbreak of Acute Hepatitis in a Medical Facility of Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(1):66-67.

Characterizing Protein Complexes with UV absorption, Light Scattering, and Refractive Index Detection.

NASA Astrophysics Data System (ADS)

Trainoff, Steven

2009-03-01

Many modern pharmaceuticals and naturally occurring biomolecules consist of complexes of proteins and polyethylene glycol or carbohydrates. In the case of vaccine development, these complexes are often used to induce or amplify immune responses. For protein therapeutics they are used to modify solubility and function, or to control the rate of degradation and elimination of a drug from the body. Characterizing the stoichiometry of these complexes is an important industrial problem that presents a formidable challenge to analytical instrument designers. Traditional analytical methods, such as using florescent tagging, chemical assays, and mass spectrometry perturb the system so dramatically that the complexes are often destroyed or uncontrollably modified by the measurement. A solution to this problem consists of fractionating the samples and then measuring the fractions using sequential non-invasive detectors that are sensitive to different components of the complex. We present results using UV absorption, which is primarily sensitive to the protein fraction, Light Scattering, which measures the total weight average molar mass, and Refractive Index detection, which measures the net concentration. We also present a solution of the problem inter-detector band-broadening problem that has heretofore made this approach impractical. Presented will be instrumentation and an analysis method that overcome these obstacles and make this technique a reliable and robust way of non-invasively characterizing these industrially important compounds.

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus

PubMed Central

Guerra, Fermin E.; Borgogna, Timothy R.; Patel, Delisha M.; Sward, Eli W.; Voyich, Jovanka M.

2017-01-01

Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages. Staphylococcus aureus (S. aureus) is a prevalent Gram-positive bacterium that is a common commensal and causes a wide range of diseases from skin infections to endocarditis. Since its discovery, S. aureus has been a formidable neutrophil foe that has challenged the efficacy of this professional assassin. Indeed, proper clearance of S. aureus by neutrophils is essential to positive infection outcome, and S. aureus has developed mechanisms to evade neutrophil killing. Herein, we will review mechanisms used by S. aureus to modulate and evade neutrophil bactericidal mechanisms including priming, activation, chemotaxis, production of reactive oxygen species, and resolution of infection. We will also highlight how S. aureus uses sensory/regulatory systems to tailor production of virulence factors specifically to the triggering signal, e.g., neutrophils and defensins. To conclude, we will provide an overview of therapeutic approaches that may potentially enhance neutrophil antimicrobial functions. PMID:28713774

Classification of hydrological parameter sensitivity and evaluation of parameter transferability across 431 US MOPEX basins

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

Ren, Huiying; Hou, Zhangshuan; Huang, Maoyi

The Community Land Model (CLM) represents physical, chemical, and biological processes of the terrestrial ecosystems that interact with climate across a range of spatial and temporal scales. As CLM includes numerous sub-models and associated parameters, the high-dimensional parameter space presents a formidable challenge for quantifying uncertainty and improving Earth system predictions needed to assess environmental changes and risks. This study aims to evaluate the potential of transferring hydrologic model parameters in CLM through sensitivity analyses and classification across watersheds from the Model Parameter Estimation Experiment (MOPEX) in the United States. The sensitivity of CLM-simulated water and energy fluxes to hydrologicalmore » parameters across 431 MOPEX basins are first examined using an efficient stochastic sampling-based sensitivity analysis approach. Linear, interaction, and high-order nonlinear impacts are all identified via statistical tests and stepwise backward removal parameter screening. The basins are then classified accordingly to their parameter sensitivity patterns (internal attributes), as well as their hydrologic indices/attributes (external hydrologic factors) separately, using a Principal component analyses (PCA) and expectation-maximization (EM) –based clustering approach. Similarities and differences among the parameter sensitivity-based classification system (S-Class), the hydrologic indices-based classification (H-Class), and the Koppen climate classification systems (K-Class) are discussed. Within each S-class with similar parameter sensitivity characteristics, similar inversion modeling setups can be used for parameter calibration, and the parameters and their contribution or significance to water and energy cycling may also be more transferrable. This classification study provides guidance on identifiable parameters, and on parameterization and inverse model design for CLM but the methodology is applicable to other models. Inverting parameters at representative sites belonging to the same class can significantly reduce parameter calibration efforts.« less

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

Assessing the impacts of canopy openness and flight parameters on detecting a sub-canopy tropical invasive plant using a small unmanned aerial system

NASA Astrophysics Data System (ADS)

Perroy, Ryan L.; Sullivan, Timo; Stephenson, Nathan

2017-03-01

Small unmanned aerial systems (sUAS) have great potential to facilitate the early detection and management of invasive plants. Here we show how very high-resolution optical imagery, collected from small consumer-grade multirotor UAS platform at altitudes of 30-120 m above ground level (agl), can be used to detect individual miconia (Miconia calvescens) plants in a highly invaded tropical rainforest environment on the island of Hawai'i. The central aim of this research was to determine how overstory vegetation cover, imagery resolution, and camera look-angle impact the aerial detection of known individual miconia plants. For our finest resolution imagery (1.37 cm ground sampling distance collected at 30 m agl), we obtained a 100% detection rate for sub-canopy plants with above-crown openness values >40% and a 69% detection rate for those with >20% openness. We were unable to detect any plants with <10% above crown openness. Detection rates progressively declined with coarser spatial resolution imagery, ending in a 0% detection rate for the 120 m agl flights (ground sampling distance of 5.31 cm). The addition of forward-looking oblique imagery improved detection rates for plants below overstory vegetation, though this effect decreased with increasing flight altitude. While dense overstory canopy cover, limited flight times, and visual line of sight regulations present formidable obstacles for detecting miconia and other invasive plant species, we show that sUAS platforms carrying optical sensors can be an effective component of an integrated management plan within challenging subcanopy forest environments.

Implementing clinical governance in English primary care groups/trusts: reconciling quality improvement and quality assurance

PubMed Central

Campbell, S; Sheaff, R; Sibbald, B; Marshall, M; Pickard, S; Gask, L; Halliwell, S; Rogers, A; Roland, M

2002-01-01

Objectives: To investigate the concept of clinical governance being advocated by primary care groups/trusts (PCG/Ts), approaches being used to implement clinical governance, and potential barriers to its successful implementation in primary care. Design: Qualitative case studies using semi-structured interviews and documentation review. Setting: Twelve purposively sampled PCG/Ts in England. Participants: Fifty senior staff including chief executives, clinical governance leads, mental health leads, and lay board members. Main outcome measures: Participants' perceptions of the role of clinical governance in PCG/Ts. Results: PCG/Ts recognise that the successful implementation of clinical governance in general practice will require cultural as well as organisational changes, and the support of practices. They are focusing their energies on supporting practices and getting them involved in quality improvement activities. These activities include, but move beyond, conventional approaches to quality assessment (audit, incentives) to incorporate approaches which emphasise corporate and shared learning. PCG/Ts are also engaged in setting up systems for monitoring quality and for dealing with poor performance. Barriers include structural barriers (weak contractual levers to influence general practices), resource barriers (perceived lack of staff or money), and cultural barriers (suspicion by practice staff or problems overcoming the perceived blame culture associated with quality assessment). Conclusion: PCG/Ts are focusing on setting up systems for implementing clinical governance which seek to emphasise developmental and supportive approaches which will engage health professionals. Progress is intentionally incremental but formidable challenges lie ahead, not least reconciling the dual role of supporting practices while monitoring (and dealing with poor) performance. PMID:12078380

Shedding genomic light on Aristotle's lantern.

PubMed

Sodergren, Erica; Shen, Yufeng; Song, Xingzhi; Zhang, Lan; Gibbs, Richard A; Weinstock, George M

2006-12-01

Sea urchins have proved fascinating to biologists since the time of Aristotle who compared the appearance of their bony mouth structure to a lantern in The History of Animals. Throughout modern times it has been a model system for research in developmental biology. Now, the genome of the sea urchin Strongylocentrotus purpuratus is the first echinoderm genome to be sequenced. A high quality draft sequence assembly was produced using the Atlas assembler to combine whole genome shotgun sequences with sequences from a collection of BACs selected to form a minimal tiling path along the genome. A formidable challenge was presented by the high degree of heterozygosity between the two haplotypes of the selected male representative of this marine organism. This was overcome by use of the BAC tiling path backbone, in which each BAC represents a single haplotype, as well as by improvements in the Atlas software. Another innovation introduced in this project was the sequencing of pools of tiling path BACs rather than individual BAC sequencing. The Clone-Array Pooled Shotgun Strategy greatly reduced the cost and time devoted to preparing shotgun libraries from BAC clones. The genome sequence was analyzed with several gene prediction methods to produce a comprehensive gene list that was then manually refined and annotated by a volunteer team of sea urchin experts. This latter annotation community edited over 9000 gene models and uncovered many unexpected aspects of the sea urchin genetic content impacting transcriptional regulation, immunology, sensory perception, and an organism's development. Analysis of the basic deuterostome genetic complement supports the sea urchin's role as a model system for deuterostome and, by extension, chordate development.

Integrative evaluation for sustainable decisions of urban wastewater system management under uncertainty

NASA Astrophysics Data System (ADS)

Hadjimichael, A.; Corominas, L.; Comas, J.

2017-12-01

With sustainable development as their overarching goal, urban wastewater system (UWS) managers need to take into account multiple social, economic, technical and environmental facets related to their decisions. In this complex decision-making environment, uncertainty can be formidable. It is present both in the ways the system is interpreted stochastically, but also in its natural ever-shifting behavior. This inherent uncertainty suggests that wiser decisions would be made under an adaptive and iterative decision-making regime. No decision-support framework has been presented in the literature to effectively addresses all these needs. The objective of this work is to describe such a conceptual framework to evaluate and compare alternative solutions for various UWS challenges within an adaptive management structure. Socio-economic aspects such as externalities are taken into account, along with other traditional criteria as necessary. Robustness, reliability and resilience analyses test the performance of the system against present and future variability. A valuation uncertainty analysis incorporates uncertain valuation assumptions in the decision-making process. The framework is demonstrated with an application to a case study presenting a typical problem often faced by managers: poor river water quality, increasing population, and more stringent water quality legislation. The application of the framework made use of: i) a cost-benefit analysis including monetized environmental benefits and damages; ii) a robustness analysis of system performance against future conditions; iii) reliability and resilience analyses of the system given contextual variability; and iv) a valuation uncertainty analysis of model parameters. The results suggest that the installation of bigger volumes would give rise to increased benefits despite larger capital costs, as well as increased robustness and resilience. Population numbers appear to affect the estimated benefits most, followed by electricity prices and climate change projections. The presented framework is expected to be a valuable tool for the next generation of UWS decision-making and the application demonstrates a novel and valuable integration of metrics and methods for UWS analysis.

Improved proton CT imaging using a bismuth germanium oxide scintillator.

PubMed

Tanaka, Sodai; Nishio, Teiji; Tsuneda, Masato; Matsushita, Keiichiro; Kabuki, Shigeto; Uesaka, Mitsuru

2018-02-02

Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera. The current method is based on a previous detection system that used a plastic scintillator, and implements improved image processing techniques. In the new system, the scintillation light intensity is integrated along the proton beam path by the BGO scintillator, and acquired as a two-dimensional distribution with the CCD camera. The range of a penetrating proton is derived from the integrated light intensity using a light-to-range conversion table, and a pCT image can be reconstructed. The proton range in the BGO scintillator is shorter than in the plastic scintillator, so errors due to extended proton ranges can be reduced. To demonstrate the feasibility of the pCT system, an experiment was performed using a 70 MeV proton beam created by the AVF930 cyclotron at the National Institute of Radiological Sciences. The accuracy of the light-to-range conversion table, which is susceptible to errors due to its spatial dependence, was investigated, and the errors in the acquired pixel values were less than 0.5 mm. Images of various materials were acquired, and the pixel-value errors were within 3.1%, which represents an improvement over previous results. We also obtained a pCT image of an edible chicken piece, the first of its kind for a biological material, and internal structures approximately one millimeter in size were clearly observed. This pCT imaging system is fast and simple, and based on these findings, we anticipate that we can acquire 200 MeV pCT images using the BGO scintillator system.

Constraint based scheduling for the Goddard Space Flight Center distributed Active Archive Center's data archive and distribution system

NASA Technical Reports Server (NTRS)

Short, Nick, Jr.; Bedet, Jean-Jacques; Bodden, Lee; Boddy, Mark; White, Jim; Beane, John

1994-01-01

The Goddard Space Flight Center (GSFC) Distributed Active Archive Center (DAAC) has been operational since October 1, 1993. Its mission is to support the Earth Observing System (EOS) by providing rapid access to EOS data and analysis products, and to test Earth Observing System Data and Information System (EOSDIS) design concepts. One of the challenges is to ensure quick and easy retrieval of any data archived within the DAAC's Data Archive and Distributed System (DADS). Over the 15-year life of EOS project, an estimated several Petabytes (10(exp 15)) of data will be permanently stored. Accessing that amount of information is a formidable task that will require innovative approaches. As a precursor of the full EOS system, the GSFC DAAC with a few Terabits of storage, has implemented a prototype of a constraint-based task and resource scheduler to improve the performance of the DADS. This Honeywell Task and Resource Scheduler (HTRS), developed by Honeywell Technology Center in cooperation the Information Science and Technology Branch/935, the Code X Operations Technology Program, and the GSFC DAAC, makes better use of limited resources, prevents backlog of data, provides information about resources bottlenecks and performance characteristics. The prototype which is developed concurrently with the GSFC Version 0 (V0) DADS, models DADS activities such as ingestion and distribution with priority, precedence, resource requirements (disk and network bandwidth) and temporal constraints. HTRS supports schedule updates, insertions, and retrieval of task information via an Application Program Interface (API). The prototype has demonstrated with a few examples, the substantial advantages of using HTRS over scheduling algorithms such as a First In First Out (FIFO) queue. The kernel scheduling engine for HTRS, called Kronos, has been successfully applied to several other domains such as space shuttle mission scheduling, demand flow manufacturing, and avionics communications scheduling.

Improved proton CT imaging using a bismuth germanium oxide scintillator

NASA Astrophysics Data System (ADS)

Tanaka, Sodai; Nishio, Teiji; Tsuneda, Masato; Matsushita, Keiichiro; Kabuki, Shigeto; Uesaka, Mitsuru

2018-02-01

Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera. The current method is based on a previous detection system that used a plastic scintillator, and implements improved image processing techniques. In the new system, the scintillation light intensity is integrated along the proton beam path by the BGO scintillator, and acquired as a two-dimensional distribution with the CCD camera. The range of a penetrating proton is derived from the integrated light intensity using a light-to-range conversion table, and a pCT image can be reconstructed. The proton range in the BGO scintillator is shorter than in the plastic scintillator, so errors due to extended proton ranges can be reduced. To demonstrate the feasibility of the pCT system, an experiment was performed using a 70 MeV proton beam created by the AVF930 cyclotron at the National Institute of Radiological Sciences. The accuracy of the light-to-range conversion table, which is susceptible to errors due to its spatial dependence, was investigated, and the errors in the acquired pixel values were less than 0.5 mm. Images of various materials were acquired, and the pixel-value errors were within 3.1%, which represents an improvement over previous results. We also obtained a pCT image of an edible chicken piece, the first of its kind for a biological material, and internal structures approximately one millimeter in size were clearly observed. This pCT imaging system is fast and simple, and based on these findings, we anticipate that we can acquire 200 MeV pCT images using the BGO scintillator system.

A deep etching mechanism for trench-bridging silicon nanowires

NASA Astrophysics Data System (ADS)

Tasdemir, Zuhal; Wollschläger, Nicole; Österle, Werner; Leblebici, Yusuf; Erdem Alaca, B.

2016-03-01

Introducing a single silicon nanowire with a known orientation and dimensions to a specific layout location constitutes a major challenge. The challenge becomes even more formidable, if one chooses to realize the task in a monolithic fashion with an extreme topography, a characteristic of microsystems. The need for such a monolithic integration is fueled by the recent surge in the use of silicon nanowires as functional building blocks in various electromechanical and optoelectronic applications. This challenge is addressed in this work by introducing a top-down, silicon-on-insulator technology. The technology provides a pathway for obtaining well-controlled silicon nanowires along with the surrounding microscale features up to a three-order-of-magnitude scale difference. A two-step etching process is developed, where the first shallow etch defines a nanoscale protrusion on the wafer surface. After applying a conformal protection on the protrusion, a deep etch step is carried out forming the surrounding microscale features. A minimum nanowire cross-section of 35 nm by 168 nm is demonstrated in the presence of an etch depth of 10 μm. Nanowire cross-sectional features are characterized via transmission electron microscopy and linked to specific process steps. The technology allows control on all dimensional aspects along with the exact location and orientation of the silicon nanowire. The adoption of the technology in the fabrication of micro and nanosystems can potentially lead to a significant reduction in process complexity by facilitating direct access to the nanowire during surface processes such as contact formation and doping.

A deep etching mechanism for trench-bridging silicon nanowires.

PubMed

Tasdemir, Zuhal; Wollschläger, Nicole; Österle, Werner; Leblebici, Yusuf; Alaca, B Erdem

2016-03-04

Introducing a single silicon nanowire with a known orientation and dimensions to a specific layout location constitutes a major challenge. The challenge becomes even more formidable, if one chooses to realize the task in a monolithic fashion with an extreme topography, a characteristic of microsystems. The need for such a monolithic integration is fueled by the recent surge in the use of silicon nanowires as functional building blocks in various electromechanical and optoelectronic applications. This challenge is addressed in this work by introducing a top-down, silicon-on-insulator technology. The technology provides a pathway for obtaining well-controlled silicon nanowires along with the surrounding microscale features up to a three-order-of-magnitude scale difference. A two-step etching process is developed, where the first shallow etch defines a nanoscale protrusion on the wafer surface. After applying a conformal protection on the protrusion, a deep etch step is carried out forming the surrounding microscale features. A minimum nanowire cross-section of 35 nm by 168 nm is demonstrated in the presence of an etch depth of 10 μm. Nanowire cross-sectional features are characterized via transmission electron microscopy and linked to specific process steps. The technology allows control on all dimensional aspects along with the exact location and orientation of the silicon nanowire. The adoption of the technology in the fabrication of micro and nanosystems can potentially lead to a significant reduction in process complexity by facilitating direct access to the nanowire during surface processes such as contact formation and doping.

Predicting protein structures with a multiplayer online game.

PubMed

Cooper, Seth; Khatib, Firas; Treuille, Adrien; Barbero, Janos; Lee, Jeehyung; Beenen, Michael; Leaver-Fay, Andrew; Baker, David; Popović, Zoran; Players, Foldit

2010-08-05

People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully 'crowd-sourced' through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.

Chandra mission scheduling on-orbit experience

NASA Astrophysics Data System (ADS)

Bucher, Sabina; Williams, Brent; Pendexter, Misty; Balke, David

2008-07-01

Scheduling observatory time to maximize both day-to-day science target integration time and the lifetime of the observatory is a formidable challenge. Furthermore, it is not a static problem. Of course, every schedule brings a new set of observations, but the boundaries of the problem change as well. As spacecraft ages, its capabilities may degrade. As in-flight experience grows, capabilities may expand. As observing programs are completed, the needs and expectations of the science community may evolve. Changes such as these impact the rules by which a mission scheduled. In eight years on orbit, the Chandra X-Ray Observatory Mission Planning process has adapted to meet the challenge of maximizing day-to-day and mission lifetime science return, despite a consistently evolving set of scheduling constraints. The success of the planning team has been achieved, not through the use of complex algorithms and optimization routines, but through processes and home grown tools that help individuals make smart short term and long term Mission Planning decisions. This paper walks through the processes and tools used to plan and produce mission schedules for the Chandra X-Ray Observatory. Nominal planning and scheduling, target of opportunity response, and recovery from on-board autonomous safing actions are all addressed. Evolution of tools and processes, best practices, and lessons learned are highlighted along the way.

Exercise and Diabetes: A Narrative Review.

PubMed

Jenkins, David W; Jenks, Alexander

Persons with diabetes might experience significant benefits through regular exercise. Not unlike the general population, those with diabetes could also lack motivation to participate in an exercise program. Often, those treating persons with diabetes lack training and/or interest in exercise prescription and are therefore unable to provide the needed information and encouragement. In many cases, reluctance to exercise could result from an inability to find an enjoyable exercise activity. Attempts to find activities that, not only provide effective aerobic challenges, but are also enjoyable to participate in are fraught with difficulty. Three electronic databases were searched in January 2017. Evidence for the merits of exercise for those with diabetes was robust. Numerous reports have addressed the degree of noncompliance to exercise recommendations and the barriers reported for this nonadherence. Additional studies concluded that most medical providers are deficient in formal training in the prescription of an exercise program. Newer studies are evaluating the effects of exercise and vitamin D supplementation and their interplay with diabetic peripheral neuropathy and ulceration. Exercise confers remarkable benefits to those with diabetes; however, the challenges to compelling patients with diabetes to exercise are formidable. An improved focus on exercise prescription and related motivation during provider training must be undertaken. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Assessing Omitted Confounder Bias in Multilevel Mediation Models.

PubMed

Tofighi, Davood; Kelley, Ken

2016-01-01

To draw valid inference about an indirect effect in a mediation model, there must be no omitted confounders. No omitted confounders means that there are no common causes of hypothesized causal relationships. When the no-omitted-confounder assumption is violated, inference about indirect effects can be severely biased and the results potentially misleading. Despite the increasing attention to address confounder bias in single-level mediation, this topic has received little attention in the growing area of multilevel mediation analysis. A formidable challenge is that the no-omitted-confounder assumption is untestable. To address this challenge, we first analytically examined the biasing effects of potential violations of this critical assumption in a two-level mediation model with random intercepts and slopes, in which all the variables are measured at Level 1. Our analytic results show that omitting a Level 1 confounder can yield misleading results about key quantities of interest, such as Level 1 and Level 2 indirect effects. Second, we proposed a sensitivity analysis technique to assess the extent to which potential violation of the no-omitted-confounder assumption might invalidate or alter the conclusions about the indirect effects observed. We illustrated the methods using an empirical study and provided computer code so that researchers can implement the methods discussed.

Generating carbon finance through avoided deforestation and its potential to create climatic, conservation and human development benefits.

PubMed

Ebeling, Johannes; Yasué, Maï

2008-05-27

Recent proposals to compensate developing countries for reducing emissions from deforestation (RED) under forthcoming climate change mitigation regimes are receiving increasing attention. Here we demonstrate that if RED credits were traded on international carbon markets, even moderate decreases in deforestation rates could generate billions of Euros annually for tropical forest conservation. We also discuss the main challenges for a RED mechanism that delivers real climatic benefits. These include providing sufficient incentives while only rewarding deforestation reductions beyond business-as-usual scenarios, addressing risks arising from forest degradation and international leakage, and ensuring permanence of emission reductions. Governance may become a formidable challenge for RED because some countries with the highest RED potentials score poorly on governance indices. In addition to climate mitigation, RED funds could help achieve substantial co-benefits for biodiversity conservation and human development. However, this will probably require targeted additional support because the highest biodiversity threats and human development needs may exist in countries that have limited income potentials from RED. In conclusion, how successfully a market-based RED mechanism can contribute to climate change mitigation, conservation and development will strongly depend on accompanying measures and carefully designed incentive structures involving governments, business, as well as the conservation and development communities.

An overview of the regulation of influenza vaccines in the United States.

PubMed

Weir, Jerry P; Gruber, Marion F

2016-09-01

Influenza virus vaccines are unique among currently licensed viral vaccines. The vaccines designed to protect against seasonal influenza illness must be updated periodically in an effort to match the vaccine strain with currently circulating viruses, and the vaccine manufacturing timeline includes multiple, overlapping processes with a very limited amount of flexibility. In the United States (U.S.), over 150 million doses of seasonal trivalent and quadrivalent vaccine are produced annually, a mammoth effort, particularly in the context of a vaccine with components that usually change on a yearly basis. In addition, emergence of an influenza virus containing an HA subtype that has not recently circulated in humans is an ever present possibility. Recently, pandemic influenza vaccines have been licensed, and the pathways for licensure of pandemic vaccines and subsequent strain updating have been defined. Thus, there are formidable challenges for the regulation of currently licensed influenza vaccines, as well as for the regulation of influenza vaccines under development. This review describes the process of licensing influenza vaccines in the U.S., the process and steps involved in the annual updating of seasonal influenza vaccines, and some recent experiences and regulatory challenges faced in development and evaluation of novel influenza vaccines. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Crash test for the Copenhagen problem.

PubMed

Nagler, Jan

2004-06-01

The Copenhagen problem is a simple model in celestial mechanics. It serves to investigate the behavior of a small body under the gravitational influence of two equally heavy primary bodies. We present a partition of orbits into classes of various kinds of regular motion, chaotic motion, escape and crash. Collisions of the small body onto one of the primaries turn out to be unexpectedly frequent, and their probability displays a scale-free dependence on the size of the primaries. The analysis reveals a high degree of complexity so that long term prediction may become a formidable task. Moreover, we link the results to chaotic scattering theory and the theory of leaking Hamiltonian systems.

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.

Improving wheat to remove coeliac epitopes but retain functionality

PubMed Central

Shewry, Peter R.; Tatham, Arthur S.

2016-01-01

Coeliac disease is an intolerance triggered by the ingestion of wheat gluten proteins. It is of increasing concern to consumers and health professionals as its incidence appears to be increasing. The amino acid sequences in gluten proteins that are responsible for triggering responses in sensitive individuals have been identified showing that they vary in distribution among and between different groups of gluten proteins. Conventional breeding may therefore be used to select for gluten protein fractions with lower contents of coeliac epitopes. Molecular breeding approaches can also be used to specifically down-regulate coeliac-toxic proteins or mutate coeliac epitopes within individual proteins. A combination of these approaches may therefore be used to develop a “coeliac-safe” wheat. However, this remains a formidable challenge due to the complex multigenic control of gluten protein composition. Furthermore, any modified wheats must retain acceptable properties for making bread and other processed foods. Not surprisingly, such coeliac-safe wheats have not yet been developed despite over a decade of research. PMID:26937068

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

Cho, Eun Seon; Ruminski, Anne M.; Aloni, Shaul

Interest in hydrogen fuel is growing for automotive applications; however, safe, dense, solid-state hydrogen storage remains a formidable scientific challenge. Metal hydrides offer ample storage capacity and do not require cryogens or exceedingly high pressures for operation. However, hydrides have largely been abandoned because of oxidative instability and sluggish kinetics. We report a new, environmentally stable hydrogen storage material constructed of Mg nanocrystals encapsulated by atomically thin and gas-selective reduced graphene oxide (rGO) sheets. This material, protected from oxygen and moisture by the rGO layers, exhibits exceptionally dense hydrogen storage (6.5 wt% and 0.105 kg H 2 per litre inmore » the total composite). As rGO is atomically thin, this approach minimizes inactive mass in the composite, while also providing a kinetic enhancement to hydrogen sorption performance. In conclusion, these multilaminates of rGO-Mg are able to deliver exceptionally dense hydrogen storage and provide a material platform for harnessing the attributes of sensitive nanomaterials in demanding environments.« less

Graphene oxide/metal nanocrystal multilaminates as the atomic limit for safe and selective hydrogen storage.

PubMed

Cho, Eun Seon; Ruminski, Anne M; Aloni, Shaul; Liu, Yi-Sheng; Guo, Jinghua; Urban, Jeffrey J

2016-02-23

Interest in hydrogen fuel is growing for automotive applications; however, safe, dense, solid-state hydrogen storage remains a formidable scientific challenge. Metal hydrides offer ample storage capacity and do not require cryogens or exceedingly high pressures for operation. However, hydrides have largely been abandoned because of oxidative instability and sluggish kinetics. We report a new, environmentally stable hydrogen storage material constructed of Mg nanocrystals encapsulated by atomically thin and gas-selective reduced graphene oxide (rGO) sheets. This material, protected from oxygen and moisture by the rGO layers, exhibits exceptionally dense hydrogen storage (6.5 wt% and 0.105 kg H2 per litre in the total composite). As rGO is atomically thin, this approach minimizes inactive mass in the composite, while also providing a kinetic enhancement to hydrogen sorption performance. These multilaminates of rGO-Mg are able to deliver exceptionally dense hydrogen storage and provide a material platform for harnessing the attributes of sensitive nanomaterials in demanding environments.

Rural-urban differences in the prevalence of chronic disease in northeast China.

PubMed

Wang, Shibin; Kou, Changgui; Liu, Yawen; Li, Bo; Tao, Yuchun; D'Arcy, Carl; Shi, Jieping; Wu, Yanhua; Liu, Jianwei; Zhu, Yingli; Yu, Yaqin

2015-05-01

Rural-urban differences in the prevalence of chronic diseases in the adult population of northeast China are examined. The Jilin Provincial Chronic Disease Survey used personal interviews and physical measures to research the presence of a range of chronic diseases among a large sample of rural and urban provincial residents aged 18 to 79 years (N = 21 435). Logistic regression analyses were used. After adjusting for age and gender, rural residents had higher prevalence of hypertension, chronic ischemic heart disease, cerebrovascular disease, chronic low back pain, arthritis, chronic gastroenteritis/peptic ulcer, chronic cholecystitis/gallstones, and chronic lower respiratory disease. Low education, low income, and smoking increased the risk of chronic diseases in rural areas. Reducing rural-urban differences in chronic disease presents a formidable public health challenge for China. The solution requires focusing attention on issues endemic to rural areas such as poverty, lack of chronic disease knowledge, and the inequality in access to primary care. © 2014 APJPH.

From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms

PubMed Central

Pierce, Christopher G.; Srinivasan, Anand; Ramasubramanian, Anand K.; López-Ribot, José L.

2015-01-01

Fungal infections constitute a major threat to an escalating number of critically ill patients. Fungi are eukaryotic organisms and, as such, there is a limited armamentarium of antifungal drugs, leading to high mortality rates. Moreover, fungal infections are often associated with the formation of biofilms, which contribute to virulence and further complicate treatment due to the high level of antifungal drug resistance displayed by sessile cells within these microbial communities. Thus, the treatment of fungal infections associated with a biofilm aetiology represents a formidable and unmet clinical challenge. The increasing importance and awareness of fungal biofilms is reflected by the fact that this is now an area of very active research. Studies in the last decade have provided important insights into fungal biofilm biology, physiology and pathology, as well as into the molecular basis of biofilm resistance. Here we discuss how this accumulated knowledge may inform the development of new anti-biofilm strategies and therapeutics that are urgently needed. PMID:26185082

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.

Treatment of Nonunion of Scaphoid Waist with Ni-Ti Shape-Memory Alloy Connector and Iliac Bone Graft

NASA Astrophysics Data System (ADS)

Cao, Lie-Hu; Xu, Shuo-Gui; Wu, Ya-Le; Zhang, Chun-Cai

2011-07-01

After fracture, the unique anatomy and blood supply of the scaphoid itself predisposes to nonunion. Scaphoid nonunion presents a formidable challenge to surgeons because of the difficulties for fixation, and the high failure rate after treatment. The Ni-Ti shape-memory alloy can provide compressive stress at the nonunion site, which is the key point for bone healing. Hence, we designed a shape-memory bone connector named arched shape-memory connector (ASC). We conducted a retrospective study looking at the union rate and complications and correlating the outcome of treatment with this device. The study reviewed a cohort of six consecutive patients presenting with scaphoid waist nonunion, who were treated with ASC and iliac cancellous bone grafting at our center from August 2002 to December 2007. The patients with nonunion achieved a 100% union rate. All the patients who achieved union had good pain relief and improved function. Our study demonstrates that scaphoid waist nonunions can be successfully treated by ASC and iliac bone grafting.

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

Electrical 2π phase control of infrared light in a 350-nm footprint using graphene plasmons

NASA Astrophysics Data System (ADS)

Woessner, Achim; Gao, Yuanda; Torre, Iacopo; Lundeberg, Mark B.; Tan, Cheng; Watanabe, Kenji; Taniguchi, Takashi; Hillenbrand, Rainer; Hone, James; Polini, Marco; Koppens, Frank H. L.

2017-07-01

Modulating the amplitude and phase of light is at the heart of many applications such as wavefront shaping, transformation optics, phased arrays, modulators and sensors. Performing this task with high efficiency and small footprint is a formidable challenge. Metasurfaces and plasmonics are promising, but metals exhibit weak electro-optic effects. Two-dimensional materials, such as graphene, have shown great performance as modulators with small drive voltages. Here, we show a graphene plasmonic phase modulator that is capable of tuning the phase between 0 and 2π in situ. The device length of 350 nm is more than 30 times shorter than the 10.6 μm free-space wavelength. The modulation is achieved by spatially controlling the plasmon phase velocity in a device where the spatial carrier density profile is tunable. We provide a scattering theory for plasmons propagating through spatial density profiles. This work constitutes a first step towards two-dimensional transformation optics for ultracompact modulators and biosensing.

Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.

PubMed

Perera, Reshani H; Wu, Hanping; Peiris, Pubudu; Hernandez, Christopher; Burke, Alan; Zhang, Helen; Exner, Agata A

2017-01-01

The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N,N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2±25.2nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoglycemia in type 2 diabetes: Standpoint of an experts’ committee (India hypoglycemia study group)

PubMed Central

Viswanathan, Mohan; Joshi, Shashank R.; Bhansali, Anil

2012-01-01

The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority. Despite compelling evidence that tight glycemic control is crucial for delaying disease progression, increased risk of hypoglycemia associated with such control underscore the complexity of diabetes management. In most cases, hypoglycemia results from an excess of insulin, either absolute or relative to the available glucose substrate and the factors perhaps exacerbating the risk are pharmacokinetic imperfections, behavioral, co-morbidities etc. Additionally, many patients remain undiagnosed, and many diagnosed patients are not treated appropriately. In this article, the challenges of hypoglycemia, confronting health care providers and their patients with diabetes, are discussed for making treatment decisions that will help minimize risk of hypoglycemia and eventually overcome formidable barriers to optimal diabetes management. Strategies to treat and minimize the frequency and severity of hypoglycemia without compromising on glycemic goals are also presented. PMID:23226632

Cereal-Based Gluten-Free Food: How to Reconcile Nutritional and Technological Properties of Wheat Proteins with Safety for Celiac Disease Patients

PubMed Central

Lamacchia, Carmela; Camarca, Alessandra; Picascia, Stefania; Di Luccia, Aldo; Gianfrani, Carmen

2014-01-01

The gluten-free diet is, to date, the only efficacious treatment for patients with Celiac Disease. In recent years, the impressive rise of Celiac Disease incidence, dramatically prompted changes in the dietary habit of an increasingly large population, with a rise in demand of gluten-free products. The formulation of gluten-free bakery products presents a formidable challenge to cereal technologists. As wheat gluten contributes to the formation of a strong protein network, that confers visco-elasticity to the dough and allows the wheat flour to be processed into a wide range of products, the preparation of cereal-based gluten-free products is a somehow difficult process. This review focuses on nutritional and technological quality of products made with gluten-free cereals available on the market. The possibility of using flour from naturally low toxic ancient wheat species or detoxified wheat for the diet of celiacs is also discussed. PMID:24481131

A practical review of prognostic correlations of molecular biomarkers in glioblastoma.

PubMed

Karsy, Michael; Neil, Jayson A; Guan, Jian; Mahan, Mark A; Mark, Mahan A; Colman, Howard; Jensen, Randy L

2015-03-01

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

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.

The complexity of rural contexts experienced by community disability workers in three southern African countries

PubMed Central

van Pletzen, Ermien; Lorenzo, Theresa

2015-01-01

An understanding of rural communities is fundamental to effective community-based rehabilitation work with persons with disabilities. By removing barriers to community participation, persons with disabilities are enabled to satisfy their fundamental human needs. However, insufficient attention has been paid to the challenges that rural community disability workers (CDWs) face in trying to realise these objectives. This qualitative interpretive study, involving in-depth interviews with 16 community disability workers in Botswana, Malawi and South Africa, revealed the complex ways in which poverty, inappropriately used power and negative attitudes of service providers and communities combine to create formidable barriers to the inclusion of persons with disabilities in families and rural communities. The paper highlights the importance of understanding and working with the concept of ‘disability’ from a social justice and development perspective. It stresses that by targeting attitudes, actions and relationships, community disability workers can bring about social change in the lives of persons with disabilities and the communities in which they live. PMID:28730029

Market value of asteroidal precious metals in an age of diminishing terrestrial resources

USGS Publications Warehouse

Kargel, Jeffrey S.; ,

1996-01-01

In the next century Mankind may have to choose from two options for our supply and usage of some nonrenewable natural resources, such as gold, platinum metals, and fossil fuels: learn to live with diminishing supplies of these materials obtained at ever increasing economic and environmental cost, or reach into difficult places and develop new technologies to give us what we need to sustain economic growth. Either prospect faces formidable technological and economic challenges. Exploitation of asteroids for precious and strategic metals is a possible environmentally friendly remedy for impending shortages of some resources. Certain types of asteroids could completely replace terrestrial sources of platinum metals. Asteroid metal mining may become a 21st-century space industry worth ten to fifty billion dollars annually (1995 dollars). Asteroids could make the United States and other countries self sufficient in many strategic metals, and it could usher new technologies and increase our applications of existing technologies that depend on these metals.

Remote C-H Activation of Quinolines through Copper-Catalyzed Radical Cross-Coupling.

PubMed

Xu, Jun; Shen, Chao; Zhu, Xiaolei; Zhang, Pengfei; Ajitha, Manjaly J; Huang, Kuo-Wei; An, Zhongfu; Liu, Xiaogang

2016-03-18

Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C-H bonds at the C5 position of 8-aminoquinoline through copper-catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single-electron-transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C-S cross-coupling. Importantly, our copper-catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C-O, C-Br, C-N, C-C, and C-I. These findings provide a fundamental insight into the activation of remote C-H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Broken Mirror: A Self Psychological Treatment Perspective for Relationship Violence

PubMed Central

Wexler, David B.

1999-01-01

Clinicians face formidable challenges in working with male perpetrators of domestic violence. Many treatment programs use a confrontational approach that emphasizes male entitlement and patriarchal societal attitudes, without honoring the genuine psychological pain of the abusive male. Although some men with strong psychopathic tendencies are almost impossible to treat, the majority of spouse-abusing males respond best to an empathic, client-centered, self psychological approach that also includes education about sociocultural issues and specific skill building. Understanding the deprivations in mirroring selfobject functions from which these men typically suffer facilitates clinical treatment response. While insisting that men take full responsibility for their abusive behavior, treatment approaches can still be most effective by addressing inherent psychological issues. Group leaders who can offer respect for perpetrators' history, their experience of powerlessness, and their emotional injuries in primary relationships are more likely to make an impact.(The Journal of Psychotherapy Practice and Research 1999; 8:129–141) PMID:10079460

Calculating the weight of evidence in low-template forensic DNA casework.

PubMed

Lohmueller, Kirk E; Rudin, Norah

2013-01-01

Interpreting and assessing the weight of low-template DNA evidence presents a formidable challenge in forensic casework. This report describes a case in which a similar mixed DNA profile was obtained from four different bloodstains. The defense proposed that the low-level minor profile came from an alternate suspect, the defendant's mistress. The strength of the evidence was assessed using a probabilistic approach that employed likelihood ratios incorporating the probability of allelic drop-out. Logistic regression was used to model the probability of drop-out using empirical validation data from the government laboratory. The DNA profile obtained from the bloodstain described in this report is at least 47 billion times more likely if, in addition to the victim, the alternate suspect was the minor contributor, than if another unrelated individual was the minor contributor. This case illustrates the utility of the probabilistic approach for interpreting complex low-template DNA profiles. © 2012 American Academy of Forensic Sciences.

Arthroscopic Triple Labral Repair in an Adolescent.

PubMed

Cotter, Eric J; Frank, Rachel M; Trenhaile, Scott W

2017-10-01

Traumatic glenohumeral dislocations often result in significant injury to the anterior-inferior labrum, most commonly leading to recurrent anterior instability. While in skeletally immature patients, shoulder trauma more commonly results in fracture versus a true dislocation, shoulder instability does occur and can be difficult to manage in the setting of open physes. In any event, the goal of treatment is to reduce the risk of recurrence and allow full participation in activities, including sports. Arthroscopic stabilization has been shown to be an effective treatment option for young patients, with good return to sport rates; however, the vast majority of literature on shoulder instability in the youth patient population focuses on anterior instability. Concomitant lesions of the anterior, posterior, and superior labrum have been rarely described in youth athletes and present a formidable clinical challenge, particularly in skeletally immature patients. In this Technical Note, we describe the authors' preferred technique for arthroscopic repair of a traumatic triple labral tear, including anterior, posterior, and type IV SLAP components, in adolescent patients.

Modelling of thermal behaviour of iron oxide layers on boiler tubes

NASA Astrophysics Data System (ADS)

Angelo, J. D.; Bennecer, A.; Kaczmarczyk, S.; Picton, P.

2016-05-01

Slender boiler tubes are subject to localised swelling when they are expose to excessive heat. The latter is due to the formation of an oxide layer, which acts as an insulation barrier. This excessive heat can lead to microstructural changes in the material that would reduce the mechanical strength and would eventually lead to critical and catastrophic failure. Detecting such creep damage remains a formidable challenge for boiler operators. It involves a costly process of shutting down the plant, performing electromagnetic and ultrasonic non-destructive inspection, repairing or replacing damaged tubes and finally restarting the plant to resume its service. This research explores through a model developed using a finite element computer simulation platform the thermal behaviour of slender tubes under constant temperature exceeding 723 °K. Our simulation results demonstrate that hematite layers up to 15 μm thickness inside the tubes do not act as insulation. They clearly show the process of long term overheating on the outside of boiler tubes which in turn leads to initiation of flaws.

Magnetic field enhanced photothermal effect of Fe3O4 nanoparticles

NASA Astrophysics Data System (ADS)

Pan, Pengfei; Lin, Yawen; Gan, Zhixing; Luo, Xiaobin; Zhou, Weiping; Zhang, Ning

2018-03-01

Photothermal and magnetothermal effects are promising in hyperthermia for cancer therapy. However, the development of safe treatments with limited side-effects requires a relatively-high thermal efficiency triggered by mild near-infrared (NIR) light and alternating magnetic field (HAC), which remains a formidable challenge. In this work, a magnetic field enhanced photothermal effect (MFEP) of Fe3O4 nanoparticles is proposed and investigated systematically. The results suggest remarkable temperature increments of 9.59 to 36.90 °C under irradiation of NIR with different light power densities (808 nm, 0-6.98 W/cm2) combined with a certain magnetic field (HAC = 1.5 kA/m at 90 kHz). The rise of temperature induced by MFEP is substantially larger than the sum of isolated photothermal and magnetothermal effects, which is attributed to the hot-phonon bottleneck effect. The MFEP of Fe3O4 nanoparticles could serve as an effective treatment for cancer therapy in the future.

The use of computer-aided design/manufacturing (CAD/CAM) technology to aid in the reconstruction of congenitally deficient pediatric mandibles: A case series.

PubMed

Gougoutas, Alexander J; Bastidas, Nicholas; Bartlett, Scott P; Jackson, Oksana

2015-12-01

Microvascular reconstruction of the pediatric mandible, particularly when necessitated by severe, congenital hypoplasia, presents a formidable challenge. Complex cases, however, may be simplified by computer-aided design/computer-aided manufacturing (CAD/CAM) assisted surgical planning. This series represents the senior authors' preliminary experiences with CAD/CAM assisted, microvascular reconstruction of the pediatric mandible. Presented are two patients with hemifacial/bifacial microsomia, both with profound mandibular hypoplasia, who underwent CAD/CAM assisted reconstruction of their mandibles with vascularized fibula flaps. Surgical techniques, CAD/CAM routines employed, complications, and long-term outcomes are reported. Successful mandibular reconstructions were achieved in both patients with centralization of their native mandibles and augmentation of deficient mandibular subunits. No long-term complications were observed. CAD/CAM technology can be utilized in pediatric mandibular reconstruction, and is particularly beneficial in cases of profound, congenital hypoplasia requiring extensive, multi-planar, bony reconstructions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Heat-labile Enterotoxins as Adjuvants or Anti-Inflammatory Agents

PubMed Central

Liang, Shuang; Hajishengallis, George

2010-01-01

Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases. PMID:20461887

Heat-labile enterotoxins as adjuvants or anti-inflammatory agents.

PubMed

Liang, Shuang; Hajishengallis, George

2010-01-01

Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins, which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases.

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.

Shaping van der Waals nanoribbons via torsional constraints: Scrolls, folds and supercoils

NASA Astrophysics Data System (ADS)

Shahabi, Alireza; Wang, Hailong; Upmanyu, Moneesh

2014-11-01

Interplay between structure and function in atomically thin crystalline nanoribbons is sensitive to their conformations yet the ability to prescribe them is a formidable challenge. Here, we report a novel paradigm for controlled nucleation and growth of scrolled and folded shapes in finite-length nanoribbons. All-atom computations on graphene nanoribbons (GNRs) and experiments on macroscale magnetic thin films reveal that decreasing the end distance of torsionally constrained ribbons below their contour length leads to formation of these shapes. The energy partitioning between twisted and bent shapes is modified in favor of these densely packed soft conformations due to the non-local van der Waals interactions in these 2D crystals; they subvert the formation of supercoils that are seen in their natural counterparts such as DNA and filamentous proteins. The conformational phase diagram is in excellent agreement with theoretical predictions. The facile route can be readily extended for tailoring the soft conformations of crystalline nanoscale ribbons, and more general self-interacting filaments.

Treatment of acute bacterial rhinosinusitis caused by antimicrobial-resistant Streptococcus pneumoniae.

PubMed

Anon, Jack B

2004-08-02

Acute bacterial rhinosinusitis (ABRS) is a secondary bacterial infection of the nose and paranasal sinuses, usually preceded by a viral upper respiratory infection or allergy, with symptoms that have not improved after 10 days or that have worsened after 5 to 7 days. Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of ABRS in adults. Increasing rates of antimicrobial resistance among S. pneumoniae and beta-lactamase production among H. influenzae are formidable challenges to the successful treatment of infections caused by these organisms. To this end, various formulations of amoxicillin-clavulanate have been developed, the most recent of which is pharmacokinetically enhanced and provides a total daily dose of 4,000 mg of amoxicillin and 250 mg of clavulanate. This formulation has been shown to be safe and effective in the treatment of infections caused by penicillin-resistant S. pneumoniae (minimum inhibitory concentration 2 microg/mL); the clavulanate component provides adequate coverage of beta-lactamase-producing pathogens.

Optimized Materials From First Principles Simulations: Are We There Yet?

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

Galli, G; Gygi, F

2005-07-26

In the past thirty years, the use of scientific computing has become pervasive in all disciplines: collection and interpretation of most experimental data is carried out using computers, and physical models in computable form, with various degrees of complexity and sophistication, are utilized in all fields of science. However, full prediction of physical and chemical phenomena based on the basic laws of Nature, using computer simulations, is a revolution still in the making, and it involves some formidable theoretical and computational challenges. We illustrate the progress and successes obtained in recent years in predicting fundamental properties of materials in condensedmore » phases and at the nanoscale, using ab-initio, quantum simulations. We also discuss open issues related to the validation of the approximate, first principles theories used in large scale simulations, and the resulting complex interplay between computation and experiment. Finally, we describe some applications, with focus on nanostructures and liquids, both at ambient and under extreme conditions.« less

Entering the New Millennium: Dilemmas in Arms Control

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

BROWN,JAMES

The end of the Cold War finds the international community no longer divided into two opposing blocks. The concerns that the community now faces are becoming more fluid, less focused, and, in many ways, much less predictable. Issues of religion, ethnicity, and nationalism; the possible proliferation of Weapons of Mass Destruction; and the diffusion of technology and information processing throughout the world community have greatly changed the international security landscape in the last decade. Although our challenges appear formidable, the United Nations, State Parties, nongovernmental organizations, and the arms control community are moving to address and lessen these concerns throughmore » both formal and informal efforts. Many of the multilateral agreements (e.g., NPT, BWC, CWC, CTBT, MTCR), as well as the bilateral efforts that are taking place between Washington and Moscow employ confidence-building and transparency measures. These measures along with on-site inspection and other verification procedures lessen suspicion and distrust and reduce uncertainty, thus enhancing stability, confidence, and cooperation.« less

Hippocampome.org: a knowledge base of neuron types in the rodent hippocampus.

PubMed

Wheeler, Diek W; White, Charise M; Rees, Christopher L; Komendantov, Alexander O; Hamilton, David J; Ascoli, Giorgio A

2015-09-24

Hippocampome.org is a comprehensive knowledge base of neuron types in the rodent hippocampal formation (dentate gyrus, CA3, CA2, CA1, subiculum, and entorhinal cortex). Although the hippocampal literature is remarkably information-rich, neuron properties are often reported with incompletely defined and notoriously inconsistent terminology, creating a formidable challenge for data integration. Our extensive literature mining and data reconciliation identified 122 neuron types based on neurotransmitter, axonal and dendritic patterns, synaptic specificity, electrophysiology, and molecular biomarkers. All ∼3700 annotated properties are individually supported by specific evidence (∼14,000 pieces) in peer-reviewed publications. Systematic analysis of this unprecedented amount of machine-readable information reveals novel correlations among neuron types and properties, the potential connectivity of the full hippocampal circuitry, and outstanding knowledge gaps. User-friendly browsing and online querying of Hippocampome.org may aid design and interpretation of both experiments and simulations. This powerful, simple, and extensible neuron classification endeavor is unique in its detail, utility, and completeness.

A Novel Architecture for Carbon Nanotube Membranes towards Fast and Efficient Oil/water Separation.

PubMed

Saththasivam, Jayaprakash; Yiming, Wubulikasimu; Wang, Kui; Jin, Jian; Liu, Zhaoyang

2018-05-09

Carbon nanotubes (CNT) are robust and proven as promising building blocks for oil/water separating membranes. However, according to classic fluid dynamic theory, achieving high permeation flux without sacrificing other membrane properties is a formidable challenge for CNT membranes, because of the trade-off nature among key membrane parameters. Herein, to relieve the trade-off between permeation fluxes, oil rejection rate, and membrane thickness, we present a new concept to engineer CNT membranes with a three-dimensional (3D) architecture. Apart from achieving high oil separation efficiency (>99.9%), these new oil/water separating membranes can achieve water flux as high as 5,500 L/m 2 .h.bar, which is one order of magnitude higher than pristine CNT membranes. Most importantly, these outstanding properties can be achieved without drastically slashing membrane thickness down to nanoscale. The present study sheds a new light for the adoption of CNT-based membranes in oil/water separation industry.

A Formidable Foe is Sabotaging Your Results: What You Should Know about Biofilms and Wound Healing

PubMed Central

Barker, Jenny C; Khansa, Ibrahim; Gordillo, Gayle M

2017-01-01

Learning Objectives After reading this article, the participant should be able to: 1. Describe biofilm pathogenesis as it relates to problem wounds, 2. Understand the pre-clinical and clinical evidence implicating biofilm in problem wounds, 3. Explain the diagnostic and treatment challenges that biofilms create for problem wounds, 4. Demonstrate a basic understanding of emerging strategies aimed at counteracting these processes. Summary Biofilm represents a protected mode of growth for bacteria, allowing them to evade standard diagnostic techniques and avoid eradication by standard therapies. Though only recently discovered, biofilm has existed for millennia and complicates nearly every aspect of medicine. Biofilm impacts wound healing by allowing bacteria to evade immune responses, prolonging inflammation and disabling skin barrier function. It is important to understand why problem wounds persist despite state-of-the-art treatment, why they are difficult to accurately diagnose, and why they recur. The aim of this article is to focus on current gaps in knowledge related to problem wounds, specifically, biofilm infection. PMID:28445380

Optoelectronically probing the density of nanowire surface trap states to the single state limit

NASA Astrophysics Data System (ADS)

Dan, Yaping

2015-02-01

Surface trap states play a dominant role in the optoelectronic properties of nanoscale devices. Understanding the surface trap states allows us to properly engineer the device surfaces for better performance. But characterization of surface trap states at nanoscale has been a formidable challenge using the traditional capacitive techniques. Here, we demonstrate a simple but powerful optoelectronic method to probe the density of nanowire surface trap states to the single state limit. In this method, we choose to tune the quasi-Fermi level across the bandgap of a silicon nanowire photoconductor, allowing for capture and emission of photogenerated charge carriers by surface trap states. The experimental data show that the energy density of nanowire surface trap states is in a range from 109 cm-2/eV at deep levels to 1012 cm-2/eV near the conduction band edge. This optoelectronic method allows us to conveniently probe trap states of ultra-scaled nano/quantum devices at extremely high precision.

Transforming the practice of medicine using genomics

PubMed Central

Ginsburg, Geoffrey S.; Ginsburg, Geoffrey S.; J. McCarthy, Jeanette

2009-01-01

Recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in complex diseases. Such studies herald the future for genomic medicine and the opportunity for personalized prognosis in a variety of clinical contexts that utilize genomescale molecular information. Several key areas represent logical and critical next steps in the use of complex genomic profiling data towards the goal of personalized medicine. First, analyses should be geared toward the development of molecular profiles that predict future events – such as major clinical events or the response, resistance, or adverse reaction to therapy. Secondly, these must move into actual clinical practice by forming the basis for the next generation of clinical trials that will employ these methodologies to stratify patients. Lastly, there remain formidable challenges is in the translation of genomic technologies into clinical medicine that will need to be addressed: professional and public education, health outcomes research, reimbursement, regulatory oversight and privacy protection. PMID:22461094

Rational material design for ultrafast rechargeable lithium-ion batteries.

PubMed

Tang, Yuxin; Zhang, Yanyan; Li, Wenlong; Ma, Bing; Chen, Xiaodong

2015-10-07

Rechargeable lithium-ion batteries (LIBs) are important electrochemical energy storage devices for consumer electronics and emerging electrical/hybrid vehicles. However, one of the formidable challenges is to develop ultrafast charging LIBs with the rate capability at least one order of magnitude (>10 C) higher than that of the currently commercialized LIBs. This tutorial review presents the state-of-the-art developments in ultrafast charging LIBs by the rational design of materials. First of all, fundamental electrochemistry and related ionic/electronic conduction theories identify that the rate capability of LIBs is kinetically limited by the sluggish solid-state diffusion process in electrode materials. Then, several aspects of the intrinsic materials, materials engineering and processing, and electrode materials architecture design towards maximizing both ionic and electronic conductivity in the electrode with a short diffusion length are deliberated. Finally, the future trends and perspectives for the ultrafast rechargeable LIBs are discussed. Continuous rapid progress in this area is essential and urgent to endow LIBs with ultrafast charging capability to meet huge demands in the near future.

Surgical Management of the Thick-Skinned Nose.

PubMed

Davis, Richard E; Hrisomalos, Emily N

2018-02-01

When executed properly, open structure rhinoplasty can dramatically improve the consistency, durability, and quality of the cosmetic surgical outcome. Moreover, in expert hands, dramatic transformations in skeletal architecture can be accomplished with minimal risk and unparalleled control, all while preserving nasal airway function. While skeletal enhancements have become increasingly more controlled and precise, the outer skin-soft tissue envelope (SSTE) often presents a formidable obstacle to a satisfactory cosmetic result. In noses with unusually thick skin, excessive skin volume and characteristically hostile healing responses frequently combine to obscure or sometimes even negate cosmetic skeletal modifications and taint the surgical outcome. For this challenging patient subgroup, care must be taken to optimize the SSTE using a graduated treatment strategy directed at minimizing skin thickness and controlling unfavorable healing responses. When appropriate efforts are implemented to manage thick nasal skin, cosmetic outcomes are often substantially improved, sometimes even negating the ill-effects of thick skin altogether. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multiwavelength Observations of Blazars

NASA Technical Reports Server (NTRS)

Sambruna, Rita

2007-01-01

The last decade has seen formidable progress in our understanding of blazar jets, thanks to the advent of several higher-sensitivity observatories. I will review the status of the art for blazar jets focusing especially on the latest multiwavelength campaigns.

Meaningful use of health information technology: evidence suggests benefits and challenges lie ahead.

PubMed

Furukawa, Michael F; Poon, Eric

2011-12-01

Less than 3 years into the passage of the Health Information Technology for Economic and Clinical Health (HITECH) provisions of the American Recovery and Reinvestment Act of 2009, measurable results are emerging. For example, in the first 11 months during which healthcare providers ("eligible professionals") and acute care hospitals ("eligible hospitals") had the opportunity to demonstrate stage 1 "Meaningful Use" of Healthcare Information Technology (HIT), more than 20,000 "eligible professionals" and 750 "eligible hospitals" have done so. In the current issue of The American Journal of Managed Care, we showcase examples of HITECH's potential impact, as well as illustrate the opportunities and challenges ahead. Two studies in this issue illustrate how HIT can improve the capacity of our healthcare system to manage chronic illnesses. The study by Vollmer et al describes how an interactive voice recognition system can improve adherence to inhaled corticosteroids among individuals with asthma in a large health maintenance organization. Shelley's study shows that the combination of electronic medical records, clinical decision support, and performance feedback can improve the rate of blood pressure control in patients with hypertension who receive care in community health centers. Together, these studies provide hope that the nation's investment in HIT could one day yield clinical dividends. Three other studies in this issue suggest that success for HIT will require attention to both technological and sociological factors. The study by Millery et al attributes the success of an HIT-based intervention to a multi-faceted approach that involves a combination of decision support tools, systematic provider feedback, implementation support, and leadership. Results from Abramson's study suggest that the full error-reduction potential of e-prescribing may only be reached with the combination of on-line clinical decision support and support for clinicians. The study by Dimitropoulos et al further illustrates that a broad spectrum of healthcare consumers needs to be engaged to allay their privacy and security concerns about Health Information Exchange. To be sure, the challenges that lie ahead remain formidable. The survey results reported by Jha et al warn us that in spite of the broad-based enthusiasm for the HITECH program among US hospitals, certain required functionalities remain challenging to implement. Attainment of the HITECH objectives is by no means certain. The HITECH legislation represents a once-in-a-generation opportunity to deploy tools that could address many of the problems underlying the US healthcare system. While the healthcare community appears to be making good progress toward making these tools available to clinicians, these tools will mean little unless we leverage them to redesign healthcare to be safe, effective, patient-centered, timely, efficient, and equitable.

ISLE: Intelligent Selection of Loop Electronics. A CLIPS/C++/INGRES integrated application

NASA Technical Reports Server (NTRS)

Fischer, Lynn; Cary, Judson; Currie, Andrew

1990-01-01

The Intelligent Selection of Loop Electronics (ISLE) system is an integrated knowledge-based system that is used to configure, evaluate, and rank possible network carrier equipment known as Digital Loop Carrier (DLC), which will be used to meet the demands of forecasted telephone services. Determining the best carrier systems and carrier architectures, while minimizing the cost, meeting corporate policies and addressing area service demands, has become a formidable task. Network planners and engineers use the ISLE system to assist them in this task of selecting and configuring the appropriate loop electronics equipment for future telephone services. The ISLE application is an integrated system consisting of a knowledge base, implemented in CLIPS (a planner application), C++, and an object database created from existing INGRES database information. The embedibility, performance, and portability of CLIPS provided us with a tool with which to capture, clarify, and refine corporate knowledge and distribute this knowledge within a larger functional system to network planners and engineers throughout U S WEST.

Taking Control Of Compliance

PubMed Central

KOBER, SCOTT

2007-01-01

The cost of biologic therapies adds urgency to the need to develop realistic compliance strategies. By engaging and educating both the physician and patient, some MCOs are working hard to address at what has always been a complicated and formidable issue. PMID:23319920

Far-field photostable optical nanoscopy (PHOTON) for real-time super-resolution single-molecular imaging of signaling pathways of single live cells

NASA Astrophysics Data System (ADS)

Huang, Tao; Browning, Lauren M.; Xu, Xiao-Hong Nancy

2012-04-01

Cellular signaling pathways play crucial roles in cellular functions and design of effective therapies. Unfortunately, study of cellular signaling pathways remains formidably challenging because sophisticated cascades are involved, and a few molecules are sufficient to trigger signaling responses of a single cell. Here we report the development of far-field photostable-optical-nanoscopy (PHOTON) with photostable single-molecule-nanoparticle-optical-biosensors (SMNOBS) for mapping dynamic cascades of apoptotic signaling pathways of single live cells in real-time at single-molecule (SM) and nanometer (nm) resolutions. We have quantitatively imaged single ligand molecules (tumor necrosis factor α, TNFα) and their binding kinetics with their receptors (TNFR1) on single live cells; tracked formation and internalization of their clusters and their initiation of intracellular signaling pathways in real-time; and studied apoptotic signaling dynamics and mechanisms of single live cells with sufficient temporal and spatial resolutions. This study provides new insights into complex real-time dynamic cascades and molecular mechanisms of apoptotic signaling pathways of single live cells. PHOTON provides superior imaging and sensing capabilities and SMNOBS offer unrivaled biocompatibility and photostability, which enable probing of signaling pathways of single live cells in real-time at SM and nm resolutions.Cellular signaling pathways play crucial roles in cellular functions and design of effective therapies. Unfortunately, study of cellular signaling pathways remains formidably challenging because sophisticated cascades are involved, and a few molecules are sufficient to trigger signaling responses of a single cell. Here we report the development of far-field photostable-optical-nanoscopy (PHOTON) with photostable single-molecule-nanoparticle-optical-biosensors (SMNOBS) for mapping dynamic cascades of apoptotic signaling pathways of single live cells in real-time at single-molecule (SM) and nanometer (nm) resolutions. We have quantitatively imaged single ligand molecules (tumor necrosis factor α, TNFα) and their binding kinetics with their receptors (TNFR1) on single live cells; tracked formation and internalization of their clusters and their initiation of intracellular signaling pathways in real-time; and studied apoptotic signaling dynamics and mechanisms of single live cells with sufficient temporal and spatial resolutions. This study provides new insights into complex real-time dynamic cascades and molecular mechanisms of apoptotic signaling pathways of single live cells. PHOTON provides superior imaging and sensing capabilities and SMNOBS offer unrivaled biocompatibility and photostability, which enable probing of signaling pathways of single live cells in real-time at SM and nm resolutions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr11739h

Search for organising principles: understanding in systems biology.

PubMed

Mesarovic, M D; Sreenath, S N; Keene, J D

2004-06-01

Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non-numerical mathematical tools are appropriate for the task. Such a categorical perspective led us to propose that the core of understanding in systems biology depends on the search for organising principles rather than solely on construction of predictive descriptions (i.e. models) that exactly outline the evolution of systems in space and time. The search for organising principles requires an identification/discovery of new concepts and hypotheses. Some of them, such as coordination motifs for transcriptional regulatory networks and bounded autonomy of levccels in a hierarchy, are outlined in this article. Experimental designs are outlined to help verify the applicability of the interaction balance principle of coordination to transcriptional and posttranscriptional networks.

Artificial transmembrane ion channels from self-assembling peptide nanotubes

NASA Astrophysics Data System (ADS)

Ghadiri, M. Reza; Granja, Juan R.; Buehler, Lukas K.

1994-05-01

NATURALLY occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secon-dary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and produc-tion of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules1, the design and synthesis of artificial systems that can mimic the bio-logical function of natural compounds remains a formidable task2-12. Here we present a simple strategy for the design of artifi-cial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture13. Our systems-essentially stacks of peptide rings-display good channel-mediated ion-transport activ-ity with rates exceeding 107 ions s-1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

Preventing HIV among adolescents with oral PrEP: observations and challenges in the United States and South Africa

PubMed Central

Hosek, Sybil; Celum, Connie; Wilson, Craig M; Kapogiannis, Bill; Delany-Moretlwe, Sinead; Bekker, Linda-Gail

2016-01-01

Introduction Adolescents and young adults aged <25 are a key population in the HIV epidemic, with very high HIV incidence rates in many geographic settings and a large number who have limited access to prevention services. Thus, any biomedical HIV prevention approach should prepare licensure and implementation strategies for young populations. Oral pre-exposure prophylaxis (PrEP) is the first antiretroviral-based prevention intervention with proven efficacy across many settings and populations, and regulatory and policy approvals at global and national levels are occurring rapidly. We discuss available data from studies in the United States and South Africa on the use of oral PrEP for HIV prevention in adolescent minors, along with some of the implementation challenges. Discussion Ongoing studies in the United States and South Africa among youth under the age of 18 should provide the safety data needed by the end of 2016 to contribute to licensure of Truvada as daily PrEP in adolescents. The challenges of completing these studies as well as foreseeable broader challenges highlighted by this work are presented. Adherence to daily PrEP is a greater challenge for younger populations, and poor adherence was associated with decreased efficacy in all PrEP trials. Individual-level barriers include limited familiarity with antiretroviral-based prevention, stigma, product storage, and social support. Structural challenges include healthcare financing for PrEP, clinician acceptability and comfort with PrEP delivery, and the limited youth-friendly health services available. These challenges are discussed in the context of the work done to date in the United States and South Africa, but will likely be magnified in the setting of limited resources in many other countries that are heavily impacted by HIV. Conclusions Adolescent populations are particularly vulnerable to HIV, and oral PrEP in these populations is likely to have an impact on population-level HIV incidence. The challenges of disseminating an HIV biomedical prevention tool requiring daily usage in adolescents are formidable, but addressing these issues and starting dialogues will lay the groundwork for the many other HIV prevention tools now being developed and tested. PMID:27760684

Using Conventional Hydropower to Help Alleviate Variable Resource Grid Integration Challenges in the Western U.S

NASA Astrophysics Data System (ADS)

Veselka, T. D.; Poch, L.

2011-12-01

Integrating high penetration levels of wind and solar energy resources into the power grid is a formidable challenge in virtually all interconnected systems due to the fact that supply and demand must remain in balance at all times. Since large scale electricity storage is currently not economically viable, generation must exactly match electricity demand plus energy losses in the system as time unfolds. Therefore, as generation from variable resources such as wind and solar fluctuate, production from generating resources that are easier to control and dispatch need to compensate for these fluctuations while at the same time respond to both instantaneous change in load and follow daily load profiles. The grid in the Western U.S. is not exempt to grid integration challenges associated with variable resources. However, one advantage that the power system in the Western U.S. has over many other regional power systems is that its footprint contains an abundance of hydropower resources. Hydropower plants, especially those that have reservoir water storage, can physically change electricity production levels very quickly both via a dispatcher and through automatic generation control. Since hydropower response time is typically much faster than other dispatchable resources such as steam or gas turbines, it is well suited to alleviate variable resource grid integration issues. However, despite an abundance of hydropower resources and the current low penetration of variable resources in the Western U.S., problems have already surfaced. This spring in the Pacific Northwest, wetter than normal hydropower conditions in combination with transmission constraints resulted in controversial wind resource shedding. This action was taken since water spilling would have increased dissolved oxygen levels downstream of dams thereby significantly degrading fish habitats. The extent to which hydropower resources will be able to contribute toward a stable and reliable Western grid is currently being studied. Typically these studies consider the inherent flexibility of hydropower technologies, but tend to fall short on details regarding grid operations, institutional arrangements, and hydropower environmental regulations. This presentation will focus on an analysis that Argonne National Laboratory is conducting in collaboration with the Western Area Power Administration (Western). The analysis evaluates the extent to which Western's hydropower resources may help with grid integration challenges via a proposed Energy Imbalance Market. This market encompasses most of the Western Electricity Coordinating Council footprint. It changes grid operations such that the real-time dispatch would be, in part, based on a 5-minute electricity market. The analysis includes many factors such as site-specific environmental considerations at each of its hydropower facilities, long-term firm purchase agreements, and hydropower operating objectives and goals. Results of the analysis indicate that site-specific details significantly affect the ability of hydropower plant to respond to grid needs in a future which will have a high penetration of variable resources.

Sensor Selection and Optimization for Health Assessment of Aerospace Systems

NASA Technical Reports Server (NTRS)

Maul, William A.; Kopasakis, George; Santi, Louis M.; Sowers, Thomas S.; Chicatelli, Amy

2007-01-01

Aerospace systems are developed similarly to other large-scale systems through a series of reviews, where designs are modified as system requirements are refined. For space-based systems few are built and placed into service. These research vehicles have limited historical experience to draw from and formidable reliability and safety requirements, due to the remote and severe environment of space. Aeronautical systems have similar reliability and safety requirements, and while these systems may have historical information to access, commercial and military systems require longevity under a range of operational conditions and applied loads. Historically, the design of aerospace systems, particularly the selection of sensors, is based on the requirements for control and performance rather than on health assessment needs. Furthermore, the safety and reliability requirements are met through sensor suite augmentation in an ad hoc, heuristic manner, rather than any systematic approach. A review of the current sensor selection practice within and outside of the aerospace community was conducted and a sensor selection architecture is proposed that will provide a justifiable, dependable sensor suite to address system health assessment requirements.

Sensor Selection and Optimization for Health Assessment of Aerospace Systems

NASA Technical Reports Server (NTRS)

Maul, William A.; Kopasakis, George; Santi, Louis M.; Sowers, Thomas S.; Chicatelli, Amy

2008-01-01

Aerospace systems are developed similarly to other large-scale systems through a series of reviews, where designs are modified as system requirements are refined. For space-based systems few are built and placed into service these research vehicles have limited historical experience to draw from and formidable reliability and safety requirements, due to the remote and severe environment of space. Aeronautical systems have similar reliability and safety requirements, and while these systems may have historical information to access, commercial and military systems require longevity under a range of operational conditions and applied loads. Historically, the design of aerospace systems, particularly the selection of sensors, is based on the requirements for control and performance rather than on health assessment needs. Furthermore, the safety and reliability requirements are met through sensor suite augmentation in an ad hoc, heuristic manner, rather than any systematic approach. A review of the current sensor selection practice within and outside of the aerospace community was conducted and a sensor selection architecture is proposed that will provide a justifiable, defendable sensor suite to address system health assessment requirements.

Toward an electrical power utility for space exploration

NASA Technical Reports Server (NTRS)

Bercaw, Robert W.

1989-01-01

Plans for space exploration depend on today's technology programs addressing the novel requirements of space-based enterprise. The requirements for electrical power will be formidable: megawatts in magnitude, reliability for multi-year missions and the flexibility to adapt to needs unanticipated at design time. The reasons for considering the power management and distribution in the various systems from a total mission perspective, rather than simply extrapolating current spacecraft design practice, are discussed. A utility approach to electric power being developed at the Lewis Research Center is described. It integrates requirements from a broad selection of current development programs with studies in which both space and terrestrial technologies are conceptually applied to exploration mission scenarios.

Women as a resource for the flexibility required for high technology innovation

NASA Technical Reports Server (NTRS)

Marlaire, Ruth Dasso

1994-01-01

What do women scientists need to know for career advancement into senior level positions? Our declining economic conditions have been the cause for major political and technological changes. The U.S. Congress is turning toward technology to increase our competitive edge in the world. Allowing women scientists, and women engineers in particular, more voice in the decision making process may be an innovative alternative for the diversity and flexibility needed for the unknown technological problems of the future. But first women scientists need to know how the system measures scientific achievement and how to identify the processes needed to increase our technological capability in order for them to formidably compete and win higher ranking positions.

Instrumentation and control upgrade plan for Browns Ferry nuclear plant

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

Belew, M.R.; Langley, D.T.; Torok, R.C.

1992-01-01

A comprehensive upgrade of the instrumentation and control (I C) systems at a power plant represents a formidable project for any utility. For a nuclear plant, the extra safety and reliability requirements along with regulatory constraints add further complications and cost. The need for the upgrade must, therefore, be very compelling, and the process must be well planned from the start. This paper describes the steps taken to initiate the I C upgrade process for Tennessee Valley Authority's (TVA's) Browns Ferry 2 nuclear plant. It explains the impetus for the upgrade, the expected benefits, and the process by which systemmore » upgrades will be selected and implemented.« less

JPRS Report, China.

DTIC Science & Technology

1993-06-08

size, with some of its industrial wares entering international markets. Overall, however, because of the shortage of capital and some irrational ...time. Japan’s exuberance makes it a formidable adversary of the United States and the USSR in the scientific and high technology fields. The grim

The Mediterranean: Geostrategic Study and Evaluation.

DTIC Science & Technology

1988-05-04

for more than sixty years. In it have participated the * 7 -.-. - national bourgeoisies that intended a synthesis between tradition and technological...a formidable barrier against the penetration of marxism . In this environment, what role does Spain play? To begin with, it represents together with

Urbanization in Bangladesh: some contemporary observations.

PubMed

Laskar, S I

1996-01-01

The author analyzes "levels and trends of urbanization in Bangladesh. It also makes an attempt to elucidate the implications of urbanization.... The...analysis corroborates that although the overall level of urbanization remained low, the sheer magnitude of total urban population has become formidable." excerpt

The Impact of Biotechnology on Pharmaceutics.

ERIC Educational Resources Information Center

Block, Lawrence H.

1990-01-01

The emergence of bioactive peptides and proteins as new drug species poses formidable problems for the pharmaceutical scientist. Implications for revision or change in undergraduate and graduate pharmaceutics curricula derive from the biopharmaceutical, pharmacokinetic, and physiochemical aspects of the new drug species, which differ from…

Foodborne viruses

USDA-ARS?s Scientific Manuscript database

Testing for human pathogenic viruses in foods represents a formidable task requiring the extraction, concentration, and assay of a host of viruses from a wide range of food matrices. The enteric viruses, particularly genogroup I and II (GI and GII) noroviruses and hepatitis A virus, are the princip...

Using natural selection and optimization for smarter vegetation models - challenges and opportunities

NASA Astrophysics Data System (ADS)

Franklin, Oskar; Han, Wang; Dieckmann, Ulf; Cramer, Wolfgang; Brännström, Åke; Pietsch, Stephan; Rovenskaya, Elena; Prentice, Iain Colin

2017-04-01

Dynamic global vegetation models (DGVMs) are now indispensable for understanding the biosphere and for estimating the capacity of ecosystems to provide services. The models are continuously developed to include an increasing number of processes and to utilize the growing amounts of observed data becoming available. However, while the versatility of the models is increasing as new processes and variables are added, their accuracy suffers from the accumulation of uncertainty, especially in the absence of overarching principles controlling their concerted behaviour. We have initiated a collaborative working group to address this problem based on a 'missing law' - adaptation and optimization principles rooted in natural selection. Even though this 'missing law' constrains relationships between traits, and therefore can vastly reduce the number of uncertain parameters in ecosystem models, it has rarely been applied to DGVMs. Our recent research have shown that optimization- and trait-based models of gross primary production can be both much simpler and more accurate than current models based on fixed functional types, and that observed plant carbon allocations and distributions of plant functional traits are predictable with eco-evolutionary models. While there are also many other examples of the usefulness of these and other theoretical principles, it is not always straight-forward to make them operational in predictive models. In particular on longer time scales, the representation of functional diversity and the dynamical interactions among individuals and species presents a formidable challenge. Here we will present recent ideas on the use of adaptation and optimization principles in vegetation models, including examples of promising developments, but also limitations of the principles and some key challenges.

Directly measuring single-molecule heterogeneity using force spectroscopy

PubMed Central

Hinczewski, Michael; Thirumalai, D.

2016-01-01

One of the most intriguing results of single-molecule experiments on proteins and nucleic acids is the discovery of functional heterogeneity: the observation that complex cellular machines exhibit multiple, biologically active conformations. The structural differences between these conformations may be subtle, but each distinct state can be remarkably long-lived, with interconversions between states occurring only at macroscopic timescales, fractions of a second or longer. Although we now have proof of functional heterogeneity in a handful of systems—enzymes, motors, adhesion complexes—identifying and measuring it remains a formidable challenge. Here, we show that evidence of this phenomenon is more widespread than previously known, encoded in data collected from some of the most well-established single-molecule techniques: atomic force microscopy or optical tweezer pulling experiments. We present a theoretical procedure for analyzing distributions of rupture/unfolding forces recorded at different pulling speeds. This results in a single parameter, quantifying the degree of heterogeneity, and also leads to bounds on the equilibration and conformational interconversion timescales. Surveying 10 published datasets, we find heterogeneity in 5 of them, all with interconversion rates slower than 10 s−1. Moreover, we identify two systems where additional data at realizable pulling velocities is likely to find a theoretically predicted, but so far unobserved crossover regime between heterogeneous and nonheterogeneous behavior. The significance of this regime is that it will allow far more precise estimates of the slow conformational switching times, one of the least understood aspects of functional heterogeneity. PMID:27317744

The community FabLab platform: applications and implications in biomedical engineering.

PubMed

Stephenson, Makeda K; Dow, Douglas E

2014-01-01

Skill development in science, technology, engineering and math (STEM) education present one of the most formidable challenges of modern society. The Community FabLab platform presents a viable solution. Each FabLab contains a suite of modern computer numerical control (CNC) equipment, electronics and computing hardware and design, programming, computer aided design (CAD) and computer aided machining (CAM) software. FabLabs are community and educational resources and open to the public. Development of STEM based workforce skills such as digital fabrication and advanced manufacturing can be enhanced using this platform. Particularly notable is the potential of the FabLab platform in STEM education. The active learning environment engages and supports a diversity of learners, while the iterative learning that is supported by the FabLab rapid prototyping platform facilitates depth of understanding, creativity, innovation and mastery. The product and project based learning that occurs in FabLabs develops in the student a personal sense of accomplishment, self-awareness, command of the material and technology. This helps build the interest and confidence necessary to excel in STEM and throughout life. Finally the introduction and use of relevant technologies at every stage of the education process ensures technical familiarity and a broad knowledge base needed for work in STEM based fields. Biomedical engineering education strives to cultivate broad technical adeptness, creativity, interdisciplinary thought, and an ability to form deep conceptual understanding of complex systems. The FabLab platform is well designed to enhance biomedical engineering education.

Simulation of MEMS for the Next Generation Space Telescope

NASA Technical Reports Server (NTRS)

Mott, Brent; Kuhn, Jonathan; Broduer, Steve (Technical Monitor)

2001-01-01

The NASA Goddard Space Flight Center (GSFC) is developing optical micro-electromechanical system (MEMS) components for potential application in Next Generation Space Telescope (NGST) science instruments. In this work, we present an overview of the electro-mechanical simulation of three MEMS components for NGST, which include a reflective micro-mirror array and transmissive microshutter array for aperture control for a near infrared (NIR) multi-object spectrometer and a large aperture MEMS Fabry-Perot tunable filter for a NIR wide field camera. In all cases the device must operate at cryogenic temperatures with low power consumption and low, complementary metal oxide semiconductor (CMOS) compatible, voltages. The goal of our simulation efforts is to adequately predict both the performance and the reliability of the devices during ground handling, launch, and operation to prevent failures late in the development process and during flight. This goal requires detailed modeling and validation of complex electro-thermal-mechanical interactions and very large non-linear deformations, often involving surface contact. Various parameters such as spatial dimensions and device response are often difficult to measure reliably at these small scales. In addition, these devices are fabricated from a wide variety of materials including surface micro-machined aluminum, reactive ion etched (RIE) silicon nitride, and deep reactive ion etched (DRIE) bulk single crystal silicon. The above broad set of conditions combine to be a formidable challenge for space flight qualification analysis. These simulations represent NASA/GSFC's first attempts at implementing a comprehensive strategy to address complex MEMS structures.

New views on global child health: global solutions for care of vulnerable children in the United States.

PubMed

Uwemedimo, Omolara T; Arora, Gitanjli; Russ, Christiana M

2016-10-01

This paper provides a brief overview of the current landscape of global child health and the impact of social determinants on the world's children. In the United States (US), global child health (GCH) has increasingly been highlighted as a priority area by national organizations, such as the National Academy of Medicine and American Academy of Pediatrics, as well as individual pediatricians committed to ensuring the health of all children regardless of geographic location. Although GCH is commonly used to refer to the health of children outside of the US, here, we highlight the recent call for GCH to also include care of US vulnerable children. Many of the lessons learned from abroad can be applied to pediatrics domestically by addressing social determinants that contribute to health disparities. Using the 'three-delay' framework, effective global health interventions target delays in seeking, accessing, and/or receiving adequate care. In resource-limited, international settings, novel health system strengthening approaches, such as peer groups, community health workers, health vouchers, cultural humility training, and provision of family-centered care, can mitigate barriers to healthcare and improve access to medical services. The creative use of limited resources for pediatric care internationally may offer insight into effective strategies to address health challenges that children face here in the US. The growing number of child health providers with clinical experience in resource-limited, low-income countries can serve as an unforeseen yet formidable resource for improving pediatric care in underserved US communities.

Exponential rise of dynamical complexity in quantum computing through projections.

PubMed

Burgarth, Daniel Klaus; Facchi, Paolo; Giovannetti, Vittorio; Nakazato, Hiromichi; Pascazio, Saverio; Yuasa, Kazuya

2014-10-10

The ability of quantum systems to host exponentially complex dynamics has the potential to revolutionize science and technology. Therefore, much effort has been devoted to developing of protocols for computation, communication and metrology, which exploit this scaling, despite formidable technical difficulties. Here we show that the mere frequent observation of a small part of a quantum system can turn its dynamics from a very simple one into an exponentially complex one, capable of universal quantum computation. After discussing examples, we go on to show that this effect is generally to be expected: almost any quantum dynamics becomes universal once 'observed' as outlined above. Conversely, we show that any complex quantum dynamics can be 'purified' into a simpler one in larger dimensions. We conclude by demonstrating that even local noise can lead to an exponentially complex dynamics.

Sub-4 nm PtZn Intermetallic Nanoparticles for Enhanced Mass and Specific Activities in Catalytic Electrooxidation Reaction

DOE PAGES

Qi, Zhiyuan; Xiao, Chaoxian; Liu, Cong; ...

2017-03-08

Atomically ordered intermetallic nanoparticles (iNPs) have sparked considerable interest in fuel cell applications by virtue of their exceptional electronic and structural properties. However, the synthesis of small iNPs in a controllable manner remains a formidable challenge because of the high temperature generally required in the formation of intermetallic phases. Here in this paper we report a general method for the synthesis of PtZn iNPs (3.2 ± 0.4 nm) on multiwalled carbon nanotubes (MWNT) via a facile and capping agent free strategy using a sacrificial mesoporous silica (mSiO 2) shell. The as-prepared PtZn iNPs exhibited ca. 10 times higher mass activitymore » in both acidic and basic solution toward the methanol oxidation reaction (MOR) compared to larger PtZn iNPs synthesized on MWNT without the mSiO 2 shell. Density functional theory (DFT) calculations predict that PtZn systems go through a “non-CO” pathway for MOR because of the stabilization of the OH* intermediate by Zn atoms, while a pure Pt system forms highly stable COH* and CO* intermediates, leading to catalyst deactivation. Experimental studies on the origin of the backward oxidation peak of MOR coincide well with DFT predictions. Moreover, the calculations demonstrate that MOR on smaller PtZn iNPs is energetically more favorable than larger iNPs, due to their high density of corner sites and lower-lying energetic pathway. Therefore, smaller PtZn iNPs not only increase the number but also enhance the activity of the active sites in MOR compared with larger ones. This work opens a new avenue for the synthesis of small iNPs with more undercoordinated and enhanced active sites for fuel cell applications.« less

Utility of AIRS Retrievals for Climate Studies

NASA Technical Reports Server (NTRS)

Molnar, Guyla I.; Susskind, Joel

2007-01-01

Satellites provide an ideal platform to study the Earth-atmosphere system on practically all spatial and temporal scales. Thus, one may expect that their rapidly growing datasets could provide crucial insights not only for short-term weather processes/predictions but into ongoing and future climate change processes as well. Though Earth-observing satellites have been around for decades, extracting climatically reliable information from their widely varying datasets faces rather formidable challenges. AIRS/AMSU is a state of the art infrared/microwave sounding system that was launched on the EOS Aqua platform on May 4, 2002, and has been providing operational quality measurements since September 2002. In addition to temperature and atmospheric constituent profiles, outgoing longwave radiation and basic cloud parameters are also derived from the AIRS/AMSU observations. However, so far the AIRS products have not been rigorously evaluated and/or validated on a large scale. Here we present preliminary assessments of monthly and 8-day mean AIRS "Version 4.0" retrieved products (available to the public through the DAAC at NASA/GSFC) to assess their utility for climate studies. First we present "consistency checks" by evaluating the time series of means, and "anomalies" (relative to the first 4 full years' worth of AIRS "climate statistics") of several climatically important retrieved parameters. Finally, we also present preliminary results regarding interrelationships of some of these geophysical variables, to assess to what extent they are consistent with the known physics of climate variability/change. In particular, we find at least one observed relationship which contradicts current general circulation climate (GCM) model results: the global water vapor climate feedback which is expected to be strongly positive is deduced to be slightly negative (shades of the "Lindzen effect"?). Though the current AIRS climatology covers only -4.5 years, it will hopefully extend much further into the future.

Exchange Coupling Interactions from the Density Matrix Renormalization Group and N-Electron Valence Perturbation Theory: Application to a Biomimetic Mixed-Valence Manganese Complex.

PubMed

Roemelt, Michael; Krewald, Vera; Pantazis, Dimitrios A

2018-01-09

The accurate description of magnetic level energetics in oligonuclear exchange-coupled transition-metal complexes remains a formidable challenge for quantum chemistry. The density matrix renormalization group (DMRG) brings such systems for the first time easily within reach of multireference wave function methods by enabling the use of unprecedentedly large active spaces. But does this guarantee systematic improvement in predictive ability and, if so, under which conditions? We identify operational parameters in the use of DMRG using as a test system an experimentally characterized mixed-valence bis-μ-oxo/μ-acetato Mn(III,IV) dimer, a model for the oxygen-evolving complex of photosystem II. A complete active space of all metal 3d and bridge 2p orbitals proved to be the smallest meaningful starting point; this is readily accessible with DMRG and greatly improves on the unrealistic metal-only configuration interaction or complete active space self-consistent field (CASSCF) values. Orbital optimization is critical for stabilizing the antiferromagnetic state, while a state-averaged approach over all spin states involved is required to avoid artificial deviations from isotropic behavior that are associated with state-specific calculations. Selective inclusion of localized orbital subspaces enables probing the relative contributions of different ligands and distinct superexchange pathways. Overall, however, full-valence DMRG-CASSCF calculations fall short of providing a quantitative description of the exchange coupling owing to insufficient recovery of dynamic correlation. Quantitatively accurate results can be achieved through a DMRG implementation of second order N-electron valence perturbation theory (NEVPT2) in conjunction with a full-valence metal and ligand active space. Perspectives for future applications of DMRG-CASSCF/NEVPT2 to exchange coupling in oligonuclear clusters are discussed.

Climatic Evolution and Habitability of Terrestrial Planets: Perspectives from Coupled Atmosphere-Mantle Systems

NASA Astrophysics Data System (ADS)

Basu Sarkar, D.; Moore, W. B.

2016-12-01

A multitude of factors including the distance from the host star and the stage of planetary evolution affect planetary climate and habitability. The complex interactions between the atmosphere and dynamics of the deep interior of the planets along with stellar fluxes present a formidable challenge. This work employs simplified approaches to address these complex issues in a systematic way. To be specific, we are investigating the coupled evolution of atmosphere and mantle dynamics. The overarching goal here is to simulate the evolutionary history of the terrestrial planets, for example Venus, Earth and Mars. This research also aims at deciphering the history of Venus-like runaway greenhouse and thus explore the possibility of cataclysmic shifts in climate of Earth-like planets. We focus on volatile cycling within the solid planets to understand the role of carbon/water in climatic and tectonic outcomes of such planets. In doing so, we are considering the feedbacks in the coupled mantle-atmosphere system. The primary feedback between the atmosphere and mantle is the surface temperature established by the greenhouse effect, which regulates the temperature gradient that drives the mantle convection and controls the rate at which volatiles are exchanged through weathering. We start our models with different initial assumptions to determine the final climate outcomes within a reasonable parameter space. Currently, there are very few planetary examples, to sample the climate outcomes, however this will soon change as exoplanets are discovered and examined. Therefore, we will be able to work with a significant number of potential candidates to answer questions like this one: For every Earth is there one Venus? ten? a thousand?