BI Project Success

ERIC Educational Resources Information Center

Tracey, Graham; Riha, James

2009-01-01

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

Vinegar as a broadcast herbicide for spring-transplanted onions

USDA-ARS?s Scientific Manuscript database

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

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

NASA Astrophysics Data System (ADS)

Fritze, Matthew D.

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

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

USDA-ARS?s Scientific Manuscript database

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

Plural Societies and the Possibility of Shared Citizenship

ERIC Educational Resources Information Center

Merry, Michael S.

2012-01-01

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

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

ERIC Educational Resources Information Center

Slevin, James

2008-01-01

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

Strategies for Enhanced Drug Delivery to the Central Nervous System

PubMed Central

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

2008-01-01

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

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

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

Shiltsev, Vladimir

2016-11-15

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

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.

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.

A systematic way to assess compliance with human factors standards

DOT National Transportation Integrated Search

1996-01-01

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

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

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

ERIC Educational Resources Information Center

Hancock, Dawson R.; Muller, Ulrich

2009-01-01

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

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.

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.

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...

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.

Multiple Fault Isolation in Redundant Systems

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

Multiple Fault Isolation in Redundant Systems

NASA Technical Reports Server (NTRS)

Pattipati, Krishna R.

1997-01-01

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

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.

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

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.…

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…

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,…

Teacher Training in Afghanistan: Intersections of Need and Reality

ERIC Educational Resources Information Center

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

2008-01-01

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

Management of Early Carcinoma of the Ovary

PubMed Central

Chapman, George W.

1988-01-01

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

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

Treesearch

John A. Parrotta; Oliver H. Knowles

2001-01-01

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

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.

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.

The College Completion Agenda: State Policy Guide

ERIC Educational Resources Information Center

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

2010-01-01

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

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

ERIC Educational Resources Information Center

Hansen, Dee; Milligan, Sarah A.

2012-01-01

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

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

ERIC Educational Resources Information Center

Mystkowska-Wiertelak, Anna; Pietrzykowska, Agnieszka

2011-01-01

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

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

ERIC Educational Resources Information Center

Hockley, Lori White

2013-01-01

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

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…

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.

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

DTIC Science & Technology

1988-12-31

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

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

ERIC Educational Resources Information Center

Campbell, Merle Wayne

2013-01-01

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

"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…

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

ERIC Educational Resources Information Center

Shear, Linda

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

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

ERIC Educational Resources Information Center

Heystek, Jan

2015-01-01

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

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

ERIC Educational Resources Information Center

Duncan, Ravit Golan

2007-01-01

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

Orthostatic hypotension: epidemiology, pathophysiology and management

NASA Technical Reports Server (NTRS)

Jacob, G.; Robertson, D.

1995-01-01

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

Pursuing Peace in Chicago

ERIC Educational Resources Information Center

Schachter, Ron

2010-01-01

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

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.

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

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

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.

Catalog of 174 Binary Black Hole Simulations for Gravitational Wave Astronomy

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Toward a multiscale modeling framework for understanding serotonergic function

PubMed Central

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

2017-01-01

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

In Search of Grid Converged Solutions

NASA Technical Reports Server (NTRS)

Lockard, David P.

2010-01-01

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

File Formats Commonly Used in Mass Spectrometry Proteomics*

PubMed Central

Deutsch, Eric W.

2012-01-01

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

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

PubMed Central

GABBARD, GLEN O.

1995-01-01

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

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

PubMed

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

2013-12-13

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

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…

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)

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

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.

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.

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

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

ERIC Educational Resources Information Center

Bernstein, Larry; Edmunds, Julie; Fesler, Lily

2014-01-01

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

Team Problem Solving: Effects of Communication and Function Overlap

DTIC Science & Technology

1987-03-01

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

Coup Prevention: A Critical Ingredient of Nation-Building Operations

DTIC Science & Technology

2010-03-01

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

Virtual Surgical Planning in Craniofacial Surgery

PubMed Central

Chim, Harvey; Wetjen, Nicholas; Mardini, Samir

2014-01-01

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

Mental health services then and now.

PubMed

Mechanic, David

2007-01-01

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

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

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.

Developing a Viable Approach for Effective Tiered Systems

DTIC Science & Technology

2007-01-17

TERMS 16. SECURITY CLASSIFICATION OF: a. REPORT 19a. NAME OF RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (include area code ) b. ABSTRACT c. THIS PAGE 18...is changing the world. Now deal with it” (New Scientist 2006). If true, this significant message is one that would extend well beyond the realm of...system-of-systems poses formidable challenges for the acquisitions bureaucracy and the defense industries” (Dombrowski et al. 2002). “TRLs

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

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 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).

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.

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.

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.

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.

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.

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.

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.

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.

Challenging the ‘Big G’ measurement with atoms and light

NASA Astrophysics Data System (ADS)

Rosi, Gabriele

2016-10-01

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

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

PubMed

Lau, Y S

2006-10-01

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

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

PubMed Central

Plank, G; Prassl, AJ; Augustin, C

2014-01-01

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

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.

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.

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.

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 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.

Bodily attractiveness and egalitarianism are negatively related in males.

PubMed

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

2015-02-09

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

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

PubMed Central

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

2016-01-01

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

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.

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.

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

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.

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.

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

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.

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.

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

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.

Creating effective scholarly posters: a guide for DNP students.

PubMed

Christenbery, Thomas L; Latham, Tiffany G

2013-01-01

Dissemination of scholarly project outcomes is an essential component of Doctor of Nursing Practice (DNP) education. This article provides guidelines for professional poster development and presentation as well as suggestions for integrating poster development as part of the DNP curriculum. This article was prepared by reviewing both theoretical and research-based literature regarding professional poster development. Evidence indicates that poster presentations at professional conferences are an excellent venue for DNP students to successfully share the results of their scholarly projects. For posters to be both well perceived and received at conferences, certain guidelines must be followed regarding poster development. Guidelines include emphasizing a consistent message, clear focus, logical format, and esthetically pleasing design. Poster development guidelines and strategies need to be taught early and regularly throughout the DNP student's education. DNP scholarly projects provide forward-looking solutions to some of society's most formidable healthcare challenges. The dissemination of knowledge gleaned from the DNP scholarly projects is vital to 21st century global health. Effective poster presentations are critical to the dissemination of scholarly knowledge. ©2012 The Author(s) Journal compilation ©2012 American Association of Nurse Practitioners.

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.

SWOT analysis and revelation in traditional Chinese medicine internationalization.

PubMed

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

2018-01-01

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

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

NASA Technical Reports Server (NTRS)

Lynnes, Christopher; Walter, Jeff

2015-01-01

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

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...

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.

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

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.

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.

Census Data: Geographic Significance and Classroom Utility. NCGE Pacesetters in Geography Series. No. 2.

ERIC Educational Resources Information Center

Dent, Bordon D., Ed.

The volume contains essays and classroom activities on a variety of U. S. and Canadian census materials. Designed to present census data in a less formidable manner than it is usually presented, it is intended for social studies teachers and college professors who want to introduce census materials in their classrooms. Essays treat various…

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.

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

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.

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

PubMed Central

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

2006-01-01

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

Advancing our understanding of religion and spirituality in the context of behavioral medicine.

PubMed

Park, Crystal L; Masters, Kevin S; Salsman, John M; Wachholtz, Amy; Clements, Andrea D; Salmoirago-Blotcher, Elena; Trevino, Kelly; Wischenka, Danielle M

2017-02-01

Recognizing and understanding the potentially powerful roles that religiousness and spirituality (RS) may serve in the prevention and amelioration of disease, as well as symptom management and health related quality of life, significantly enhances research and clinical efforts across many areas of behavioral medicine. This article examines the knowledge established to date and suggests advances that remain to be made. We begin with a brief summary of the current knowledge regarding RS as related to three exemplary health conditions: (a) cardiovascular disease; (b) cancer; and, (c) substance abuse. We then focus on particular concerns for future investigations, emphasizing conceptual issues, possible mediators and moderators of relationships or effects, and methodology. Our discussion is framed by a conceptual model that may serve to guide and organize future investigations. This model highlights a number of important issues regarding the study of links between RS and health: (a) RS comprise many diverse constructs, (b) the mechanisms through which RS may influence health outcomes are quite diverse, and (c) a range of different types of health and health relevant outcomes may be influenced by RS. The multidimensional nature of RS and the complexity of related associations with different types of health relevant outcomes present formidable challenges to empirical study in behavioral medicine. These issues are referred to throughout our review and we suggest several solutions to the presented challenges in our summary. We end with a presentation of barriers to be overcome, along with strategies for doing so, and concluding thoughts.

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

PubMed

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

2006-06-27

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

Advancing our understanding of religion and spirituality in the context of behavioral medicine

PubMed Central

Masters, Kevin S.; Salsman, John M.; Wachholtz, Amy; Clements, Andrea D.; Salmoirago-Blotcher, Elena; Trevino, Kelly; Wischenka, Danielle M.

2016-01-01

Recognizing and understanding the potentially powerful roles that religiousness and spirituality (RS) may serve in the prevention and amelioration of disease, as well as symptom management and health related quality of life, significantly enhances research and clinical efforts across many areas of behavioral medicine. This article examines the knowledge established to date and suggests advances that remain to be made. We begin with a brief summary of the current knowledge regarding RS as related to three exemplary health conditions: (a) cardiovascular disease; (b) cancer; and, (c) substance abuse. We then focus on particular concerns for future investigations, emphasizing conceptual issues, possible mediators and moderators of relationships or effects, and methodology. Our discussion is framed by a conceptual model that may serve to guide and organize future investigations. This model highlights a number of important issues regarding the study of links between RS and health: (a) RS comprise many diverse constructs, (b) the mechanisms through which RS may influence health outcomes are quite diverse, and (c) a range of different types of health and health relevant outcomes may be influenced by RS. The multidimensional nature of RS and the complexity of related associations with different types of health relevant outcomes present formidable challenges to empirical study in behavioral medicine. These issues are referred to throughout our review and we suggest several solutions to the presented challenges in our summary. We end with a presentation of barriers to be overcome, along with strategies for doing so, and concluding thoughts. PMID:27342616

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.

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

NASA Astrophysics Data System (ADS)

Hauck Newman, Amy; Katz, Jonathan L.

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

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

PubMed

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

2018-03-02

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

Engaging the Unengaged: Using Visual Images to Enhance Students' "Poli Sci 101" Experience

ERIC Educational Resources Information Center

Ulbig, Stacy

2009-01-01

As the nation witnesses a distinct decline in civic engagement among young adults, political science instructors across the nation face the formidable task of engaging students in lower-level, general education courses outside students' primary domain of interest. The research presented here seeks to understand if visually enhanced lecture…

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

Adult Onset Leigh Syndrome in the Intensive Care Setting: A Novel Presentation of a C12orf65 Related Mitochondrial Disease.

PubMed

Wesolowska, Maria; Gorman, Grainne S; Alston, Charlotte L; Pajak, Aleksandra; Pyle, Angela; He, Langping; Griffin, Helen; Chinnery, Patrick F; Miller, James A L; Schaefer, Andrew M; Taylor, Robert W; Lightowlers, Robert N; Chrzanowska-Lightowlers, Zofia M

2015-10-07

Mitochondrial disease can present at any age, with dysfunction in almost any tissue making diagnosis a challenge. It can result from inherited or sporadic mutations in either the mitochondrial or the nuclear genome, many of which affect intraorganellar gene expression. The estimated prevalence of 1/4300 indicates these to be amongst the commonest inherited neuromuscular disorders, emphasising the importance of recognition of the diagnostic clinical features. Despite major advances in our understanding of the molecular basis of mitochondrial diseases, accurate and early diagnoses are critically dependent on the fastidious clinical and biochemical characterisation of patients. Here we describe a patient harbouring a previously reported homozygous mutation in C12orf65, a mitochondrial protein of unknown function, which does not adhere to the proposed distinct genotype-phenotype relationship. We performed clinical, biochemical and molecular analysis including whole exome sequencing on patient samples and cell lines. We report an extremely rare case of an adult presenting with Leigh-like disease, in intensive care, in the 5th decade of life, harbouring a recessively inherited mutation previously reported in children. A global reduction in intra-mitochondrial protein synthesis was observed despite normal or elevated levels of mt-RNA, leading to an isolated complex IV deficiency. All the reported C12orf65 mutations have shown an autosomal recessive pattern of inheritance. Mitochondrial disease causing mutations inherited in this manner are usually of early onset and associated with a severe, often fatal clinical phenotype. Presentations in adulthood are usually less severe. This patient's late adulthood presentation is in sharp contrast emphasising the clinical variability that is characteristic of mitochondrial disease and illustrates why making a definitive diagnosis remains a formidable challenge.

Black Women in the Academy: The Secrets to Success and Achievement.

ERIC Educational Resources Information Center

Gregory, Sheila T.

This book presents selected historical data focusing on three aspects in the lives of Black women: resilience of Black women and their families; strengths of the Black church and community; and formidable gains made by Black women in the workforce. The status and achievements of Black women professors and scholars in the academy are reviewed, with…

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

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.

Challenges for semilocal density functionals with asymptotically nonvanishing potentials

NASA Astrophysics Data System (ADS)

Aschebrock, Thilo; Armiento, Rickard; Kümmel, Stephan

2017-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Quantification of Soil Pore Structure Based on Minkowski-Functions

NASA Astrophysics Data System (ADS)

Vogel, H.; Weller, U.; Schlüter, S.

2009-05-01

The porous structure in soils and other geologic media is typically a complex 3-dimensional object. Most of the physical material properties including mechanical and hydraulic characteristics are immediately linked to this structure which can be directly observed using non-invasive techniques as e.g. X-ray tomography. It is an old dream and still a formidable challenge to related structural features of porous media to their physical properties. In this contribution we present a scale-invariant concept to quantify pore structure based on a limited set of meaningful morphological functions. They are based on d+1 Minkowski functionals as defined for d-dimensional bodies. These basic quantities are determined as a function of pore size obtained by filter procedures using mathematical morphology. The resulting Minkowski functions provide valuable information on pore size, pore surface area and pore topology having the potential to be linked to physical properties. The theoretical background and the related algorithms are presented and the approach is demonstrated for the structure of an arable topsoil obtained by X-ray micro tomography. We also discuss the fundamental problem of limited resolution which is critical for any attempt to quantify structural features at any scale.

Aggressive-antisocial boys develop into physically strong young men.

PubMed

Isen, Joshua D; McGue, Matthew K; Iacono, William G

2015-04-01

Young men with superior upper-body strength typically show a greater proclivity for physical aggression than their weaker male counterparts. The traditional interpretation of this phenomenon is that young men calibrate their attitudes and behaviors to their physical formidability. Physical strength is thus viewed as a causal antecedent of aggressive behavior. The present study is the first to examine this phenomenon within a developmental framework. We capitalized on the fact that physical strength is a male secondary sex characteristic. In two longitudinal cohorts of children, we estimated adolescent change in upper-body strength using the slope parameter from a latent growth model. We found that males' antisocial tendencies temporally precede their physical formidability. Boys, but not girls, with greater antisocial tendencies in childhood attained larger increases in physical strength between the ages of 11 and 17. These results support sexual selection theory, indicating an adaptive congruence between male-typical behavioral dispositions and subsequent physical masculinization during puberty. © The Author(s) 2015.

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.

Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans.

PubMed

Sanchez-Luque, Francisco J; Richardson, Sandra R; Faulkner, Geoffrey J

2016-01-01

Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.

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.

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.

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.

Fusion energy: Status and prospects

NASA Astrophysics Data System (ADS)

Salomaa, Rainer

A review of the present state of the international fusion research is given. In the largest tokamak devices (JET, TFTR, JT-60) fusion relevant temperatures are routinely obtained and the scientific feasibility of plasma confinement has been demonstrated. Plans concerning the next step are described. A critical view is presented on questions as to what extent the generic advantages of fusion (availability, sufficiency, safety, environmental acceptability, etc.) can be exploited in a practical power reactor where the formidable technological problems call for compromises.

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.

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.

Petrosectomies for invasive tumours: surgery and reconstruction.

PubMed

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

1996-09-01

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

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.

The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome.

PubMed

Kronewitter, Scott R; An, Hyun Joo; de Leoz, Maria Lorna; Lebrilla, Carlito B; Miyamoto, Suzanne; Leiserowitz, Gary S

2009-06-01

Annotation of the human serum N-linked glycome is a formidable challenge but is necessary for disease marker discovery. A new theoretical glycan library was constructed and proposed to provide all possible glycan compositions in serum. It was developed based on established glycobiology and retrosynthetic state-transition networks. We find that at least 331 compositions are possible in the serum N-linked glycome. By pairing the theoretical glycan mass library with a high mass accuracy and high-resolution MS, human serum glycans were effectively profiled. Correct isotopic envelope deconvolution to monoisotopic masses and the high mass accuracy instruments drastically reduced the amount of false composition assignments. The high throughput capacity enabled by this library permitted the rapid glycan profiling of large control populations. With the use of the library, a human serum glycan mass profile was developed from 46 healthy individuals. This paper presents a theoretical N-linked glycan mass library that was used for accurate high-throughput human serum glycan profiling. Rapid methods for evaluating a patient's glycome are instrumental for studying glycan-based markers.

Optoelectrical Cooling of Formaldehyde to Sub-Millikelvin Temperatures

NASA Astrophysics Data System (ADS)

Zeppenfeld, Martin

2016-05-01

Due to their strong long-range dipole-dipole interactions and large number of internal states, polar molecules cooled to ultracold temperatures enable fascinating applications ranging from ultracold chemistry to investigation of dipolar quantum gases. However, realizing a simple and general technique to cool molecules to ultracold temperatures, akin to laser cooling of atoms, has been a formidable challenge. We present results for opto-electrical Sisyphus cooling applied to formaldehyde (H2 CO). In this generally applicable cooling scheme, molecules repeatedly move up and down electric field gradients of a trapping potential in different rotational states to efficiently extract kinetic energy. A total of about 300,000 molecules are thereby cooled by a factor of 1000 to 400uK, resulting in a record-large ensemble of ultracold molecules. In addition to cooling of the motional degrees of freedom, optical pumping via a vibrational transition allows us to control the internal rotational state. We thereby achieve a purity of over 80% of formaldehyde molecules in a single rotational M-sublevel. Our experiment provides an excellent starting point for precision spectroscopy and investigation of ultracold collisions.

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.

From SEST to ALMA, from NTT to OWL: of vision, dreams and realities. Perspectives from the Directors General, past and present: Harry van der Laan, ESO Director General, 1988 - 1992

NASA Astrophysics Data System (ADS)

van der Laan, Harry

2002-09-01

ESO has come a long way since in 1987 the first rocks were blasted at the NTT site on La Silla. Those were exciting days, when SEST came online and soon after the VLT programme was getting up to speed upon its approval in December 1987. It was not an easy time for staff or management: taking up the role of main contractor for its own design and construction programme rather than finding an industrial consultant to do so was an enormous challenge. It was not obvious that it could be done, for more than ninety per cent of ESO's staff capacity was occupied with running La Silla, operating Headquarter services and constructing the NTT. The VLT Blue Book and the bag of money Council had allocated to its realization were necessary but by no means sufficient. For the new, formidable task, manpower had to be found and trained, manpower both reassigned and newly recruited.

Directional Solidification of Mercury Cadmium Telluride During the Second United States Microgravity Payload Mission (USMP-2)

NASA Technical Reports Server (NTRS)

Gillies, D. C.; Lehoczky, S. L.; Szofran, F. R.; Watring, D. A.; Alexander, H. A.; Jerman, G. A.

1996-01-01

As a solid solution semiconductor having, a large separation between liquidus and solidus, mercury cadmium telluride (MCT) presents a formidable challenge to crystal growers desiring an alloy of high compositional uniformity. To avoid constitutional supercooling during Bridgman crystal growth it is necessary to solidify slowly in a high temperature gradient region. The necessary translation rate of less than 1 mm/hr results in a situation where fluid flow induced by gravity on earth is a significant factor in material transport. The Advanced Automated Directional Solidification Furnace (AADSF) is equipped to provide the stable thermal environment with a high gradient, and the required slow translation rate needed. Ground based experiments in AADSF show clearly the dominance of flow driven transport. The first flight of AADSF in low gravity on USMP-2 provided an opportunity to test theories of fluid flow in MCT and showed several solidification regimes which are very different from those observed on earth. Residual acceleration vectors in the orbiter during the mission were measured by the Orbital Acceleration Research Experiment (OARE), and correlated well with observed compositional differences in the samples.

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.

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

Imagine Something Different: How a Group Approach to Scholarly Faculty Development Can Turn Joy-Stealing Competition Into Scholarly Productivity.

PubMed

Heinrich, Kathleen T

As academic institutions across the country raise the scholarly bar for retention, promotion, and tenure, academic leaders are being asked to scholar-ready nursing faculty. With the retirement of senior scholars and too few scholar-mentors to go around, leaders often find themselves squeezed between scholarly expectations on the rise and faculty groups less than ready to meet those expectations. Today's nursing faculty present a formidable scholarly development challenge. A diverse mix of master's-prepared clinicians and recent graduates from doctor of philosophy and doctor of nursing practice programs, they come with a broad range of scholarly learning needs. These inequities not only leave many faculty feeling like scholar-impostors but also they can breed competitions that erode collegial bonds and sow the seeds of incivilities that steal scholarly joy, slow scholarly progress, and stress academic workplaces. What if leaders began imagining something different for themselves and with faculty groups? This is what can happen when leaders expand their perspective on scholarly faculty development from individual challenge to collective responsibility. More essay than research paper, this article describes how scholarly joy-stealing patterns can infiltrate faculty groups, shares thought leaders' visions for supportive scholarly communities, and offers strategies leaders can use to invite faculty groups to co-create cultures of scholarly caring. Copyright © 2016 Elsevier Inc. All rights reserved.

Laser Absorption Measurements of Equivalence Ratios Studied Along With Their Coupling to Pressure Fluctuations in Lean Premixed Prevaporized (LPP) Combustion

NASA Technical Reports Server (NTRS)

Nguyen, Quang-Viet

2001-01-01

Concerns about damaging the Earth's ozone layer as a result of high levels of nitrogen oxides (known collectively as NOx) from high-altitude, high-speed aircraft have prompted the study of lean premixed prevaporized (LPP) combustion in aircraft engines. LPP combustion reduces NOx emissions principally by reducing the peak flame temperatures inside an engine. Recent advances in LPP technologies have realized exceptional reductions in pollutant emissions (single-digit ppm NOx for example). However, LPP combustion also presents major challenges: combustion instability and dynamic coupling effects between fluctuations in heat-release rate, dynamic pressure, and fuel pressure. These challenges are formidable and can literally shake an engine apart if uncontrolled. To better understand this phenomenon so that it can be controlled, we obtained real-time laser absorption measurements of the fuel vapor concentration (and equivalence ratio) simultaneously with the dynamic pressure, flame luminosity, and time-averaged gaseous emissions measurements in a research-type jet-A-fueled LPP combustor. The measurements were obtained in NASA Glenn Research Center's CE-5B optically accessible flame tube facility. The CE-5B facility provides inlet air temperatures and pressures similar to the actual operating conditions of real aircraft engines. The laser absorption measurements were performed using an infrared 3.39 micron HeNe laser in conjunction with a visible HeNe laser for liquid droplet scattering compensation.

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.

AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species

PubMed Central

Ruggeri, Francesco Simone; Habchi, Johnny; Cerreta, Andrea; Dietler, Giovanni

2016-01-01

Background A wide class of human diseases and neurodegenerative disorders, such as Alzheimer’s disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-β sheet amyloid aggregates. During the fibrillization, several coexisting species are formed, giving rise to a highly heterogeneous mixture. Despite its fundamental role in biological function and malfunction, the mechanism of protein self-assembly and the fundamental origins of the connection between aggregation, cellular toxicity and the biochemistry of neurodegeneration remains challenging to elucidate in molecular detail. In particular, the nature of the specific state of proteins that is most prone to cause cytotoxicity is not established. Methods: In the present review, we present the latest advances obtained by Atomic Force Microscopy (AFM) based techniques to unravel the biophysical properties of amyloid aggregates at the nanoscale. Unraveling amyloid single species biophysical properties still represents a formidable experimental challenge, mainly because of their nanoscale dimensions and heterogeneous nature. Bulk techniques, such as circular dichroism or infrared spectroscopy, are not able to characterize the heterogeneity and inner properties of amyloid aggregates at the single species level, preventing a profound investigation of the correlation between the biophysical properties and toxicity of the individual species. Conclusion: The information delivered by AFM based techniques could be central to study the aggregation pathway of proteins and to design molecules that could interfere with amyloid aggregation delaying the onset of misfolding diseases. PMID:27189600

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

PubMed

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

2014-12-19

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

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

PubMed

Rønningen, Kjersti S

2013-12-01

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

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

PubMed

Swanson, Jeffrey W; Felthous, Alan R

2015-06-01

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

Hematopoietic stem cell engineering at a crossroads.

PubMed

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

2012-02-02

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

Low-latency situational awareness for UxV platforms

NASA Astrophysics Data System (ADS)

Berends, David C.

2012-06-01

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

The Business of Trust.

PubMed

Frisse, Mark E

2016-04-01

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

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.

Applications of XPS in the characterization of Battery materials

DOE PAGES

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

2018-05-26

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

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

PubMed

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

2018-06-27

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

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

PubMed

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

2017-01-04

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

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

PubMed Central

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

2015-01-01

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

Applications of XPS in the characterization of Battery materials

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

Shutthanandan, Vaithiyalingam; Nandasiri, Manjula; Zheng, Jianming

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2018-04-01

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

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

Coupling EELS/EFTEM Imaging with Environmental Fluid Cell Microscopy

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

Unocic, Raymond R; Baggetto, Loic; Veith, Gabriel M

2012-01-01

Insight into dynamically evolving electrochemical reactions and mechanisms encountered in electrical energy storage (EES) and conversion technologies (batteries, fuel cells, and supercapacitors), materials science (corrosion and oxidation), and materials synthesis (electrodeposition) remains limited due to the present lack of in situ high-resolution characterization methodologies. Electrochemical fluid cell microscopy is an emerging in-situ method that allows for the direct, real-time imaging of electrochemical processes within a fluid environment. This technique is facilitated by the use of MEMS-based biasing microchip platforms that serve the purpose of sealing the highly volatile electrolyte between two electron transparent SiNx membranes and interfacing electrodes to anmore » external potentiostat for controlled nanoscale electrochemislly experiments [!]. In order to elucidate both stmctural and chemical changes during such in situ electrochemical experiments, it is impmtant to first improve upon the spatial resolution by utilizing energy-filtered transmission electron microscopy (EFTEM) (to minimize chromatic aben ation), then to detennine the chemical changes via electron energy loss spectroscopy (EELS). This presents a formidable challenge since the overall thickness through which electrons are scattered through the multiple layers of the cell can be on the order of hundreds of nanometers to microns, scattering through which has the deleterious effect of degrading image resolution and decreasing signal-to noise for spectroscopy [2].« less

Space-based Ornithology-Studying Bird Migration and Environmental Change in North America

NASA Technical Reports Server (NTRS)

Smith, James; Deppe, Jill

2008-01-01

Natural fluctuations in the availability of critical stopover sites coupled with anthropogenic destruction of wetlands, land-use change, and anticipated losses due to climate change present migratory birds with a formidable challenge. We have developed an individual-based, spatially explicit bird migration model that simulates the migration routes, timing and energy budgets of individual birds under dynamic weather and land surface conditions. Our model incorporates biophysical constraints, individual bird energy status, bird behavior, and flight aerodynamics. We model the speed, direction, and timing of individual birds moving through a user specified Lagrangian grid. The model incorporates environmental properties including wind speed and direction, topography, dynamic hydrologic properties of the landscape, and environmental suitability. The model is driven by important variables estimated from satellite observations of the land surface, by data assimilation products from weather and climate models, and biological field data. We illustrate the use of the model to study the impact of both short- and long-term environmental variatios, e.g. climate, drought, anthropogenic, on migration timing (phenology), spatial pattern, and fitness (survival and reproductive success). We present several theoretical simulations of the spring migration of Pectoral Sandpiper (Calidris melanotos) in North America with emphasis on the Central flyway from the Gulf of Mexico to Alaska.

Can post-eradication laboratory containment of wild polioviruses be achieved?

PubMed Central

Dowdle, Walter R.; Gary, Howard E.; Sanders, Raymond; van Loon, Anton M.

2002-01-01

The purpose of containment is to prevent reintroduction of wild polioviruses from laboratories into polio-free communities. In order to achieve global commitment to laboratory containment the rationale should be clear and compelling; the biosafety levels should be justified by the risks; and the objectives should be realistic. Absolute containment can never be assured. Questions of intentional or unintentional non-compliance can never be wholly eliminated. Effective laboratory containment is, however, a realistic goal. Prevention of virus transmission through contaminated laboratory materials is addressed by WHO standards for biosafety. The principal challenge is to prevent transmission through unrecognized infectious laboratory workers. Such transmission is possible only if the following conditions occur: infectious and potentially infectious materials carrying wild poliovirus are present in the laboratory concerned; a laboratory operation exposes a worker to poliovirus; a worker is susceptible to an infection that results in the shedding of poliovirus; and the community is susceptible to poliovirus infections. At present it is difficult to envisage the elimination of any of these conditions. However, the risks of the first three can be greatly reduced so as to create a formidable barrier against poliovirus transmission to the community. Final biosafety recommendations must await post-eradication immunization policies adopted by the international community. PMID:12075368

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.

In situ characterization of the brain-microdevice interface using Device Capture Histology

PubMed Central

Woolley, Andrew J.; Desai, Himanshi A.; Steckbeck, Mitchell A.; Patel, Neil K.; Otto, Kevin J.

2011-01-01

Accurate assessment of brain-implantable microdevice bio-integration remains a formidable challenge. Prevailing histological methods require device extraction prior to tissue processing, often disrupting and removing the tissue of interest which had been surrounding the device. The Device-Capture Histology method, presented here, overcomes many limitations of the conventional Device-Explant Histology method, by collecting the device and surrounding tissue intact for subsequent labeling. With the implant remaining in situ, accurate and precise imaging of the morphologically preserved tissue at the brain/microdevice interface can then be collected and quantified. First, this article presents the Device-Capture Histology method for obtaining and processing the intact, undisturbed microdevice-tissue interface, and images using fluorescent labeling and confocal microscopy. Second, this article gives examples of how to quantify features found in the captured peridevice tissue. We also share histological data capturing 1) the impact of microdevice implantation on tissue, 2) the effects of an experimental anti-inflammatory coating, 3) a dense grouping of cell nuclei encapsulating a long-term implant, and 4) atypical oligodendrocyte organization neighboring a longterm implant. Data sets collected using the Device-Capture Histology method are presented to demonstrate the significant advantages of processing the intact microdevice-tissue interface, and to underscore the utility of the method in understanding the effects of the brain-implantable microdevices on nearby tissue. PMID:21802446

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.

Hematopoietic stem cell engineering at a crossroads

PubMed Central

Rivière, Isabelle; Dunbar, Cynthia E.

2012-01-01

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

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

PubMed Central

Groysman, Stanislav; Holm, R. H.

2009-01-01

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

Validation of the Spanish SIRS with monolingual Hispanic outpatients.

PubMed

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

2010-09-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2018-05-17

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

Numerical Simulation of Metallic Uranium Sintering

NASA Astrophysics Data System (ADS)

Berry, Bruce

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

Ethical issues when modelling brain disorders innon-human primates.

PubMed

Neuhaus, Carolyn P

2018-05-01

Non-human animal models of human diseases advance our knowledge of the genetic underpinnings of disease and lead to the development of novel therapies for humans. While mice are the most common model organisms, their usefulness is limited. Larger animals may provide more accurate and valuable disease models, but it has, until recently, been challenging to create large animal disease models. Genome editors, such as Clustered Randomised Interspersed Palindromic Repeat (CRISPR), meet some of these challenges and bring routine genome engineering of larger animals and non-human primates (NHPs) well within reach. There is growing interest in creating NHP models of brain disorders such as autism, depression and Alzheimer's, which are very difficult to model or study in other organisms, including humans. New treatments are desperately needed for this set of disorders. This paper is novel in asking: Insofar as NHPs are being considered for use as model organisms for brain disorders, can this be done ethically? The paper concludes that it cannot. Notwithstanding ongoing debate about NHPs' moral status, (1) animal welfare concerns, (2) the availability of alternative methods of studying brain disorders and (3) unmet expectations of benefit justify a stop on the creation of NHP model organisms to study brain disorders. The lure of using new genetic technologies combined with the promise of novel therapeutics presents a formidable challenge to those who call for slow, careful, and only necessary research involving NHPs. But researchers should not create macaques with social deficits or capuchin monkeys with memory deficits just because they can. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

NASA Space Exploration Logistics Workshop Proceedings

NASA Technical Reports Server (NTRS)

deWeek, Oliver; Evans, William A.; Parrish, Joe; James, Sarah

2006-01-01

As NASA has embarked on a new Vision for Space Exploration, there is new energy and focus around the area of manned space exploration. These activities encompass the design of new vehicles such as the Crew Exploration Vehicle (CEV) and Crew Launch Vehicle (CLV) and the identification of commercial opportunities for space transportation services, as well as continued operations of the Space Shuttle and the International Space Station. Reaching the Moon and eventually Mars with a mix of both robotic and human explorers for short term missions is a formidable challenge in itself. How to achieve this in a safe, efficient and long-term sustainable way is yet another question. The challenge is not only one of vehicle design, launch, and operations but also one of space logistics. Oftentimes, logistical issues are not given enough consideration upfront, in relation to the large share of operating budgets they consume. In this context, a group of 54 experts in space logistics met for a two-day workshop to discuss the following key questions: 1. What is the current state-of the art in space logistics, in terms of architectures, concepts, technologies as well as enabling processes? 2. What are the main challenges for space logistics for future human exploration of the Moon and Mars, at the intersection of engineering and space operations? 3. What lessons can be drawn from past successes and failures in human space flight logistics? 4. What lessons and connections do we see from terrestrial analogies as well as activities in other areas, such as U.S. military logistics? 5. What key advances are required to enable long-term success in the context of a future interplanetary supply chain? These proceedings summarize the outcomes of the workshop, reference particular presentations, panels and breakout sessions, and record specific observations that should help guide future efforts.

Pushing the size limit of de novo structure ensemble prediction guided by sparse SDSL-EPR restraints to 200 residues: The monomeric and homodimeric forms of BAX

PubMed Central

Fischer, Axel W.; Bordignon, Enrica; Bleicken, Stephanie; García-Sáez, Ana J.; Jeschke, Gunnar; Meiler, Jens

2016-01-01

Structure determination remains a challenge for many biologically important proteins. In particular, proteins that adopt multiple conformations often evade crystallization in all biologically relevant states. Although computational de novo protein folding approaches often sample biologically relevant conformations, the selection of the most accurate model for different functional states remains a formidable challenge, in particular, for proteins with more than about 150 residues. Electron paramagnetic resonance (EPR) spectroscopy can obtain limited structural information for proteins in well-defined biological states and thereby assist in selecting biologically relevant conformations. The present study demonstrates that de novo folding methods are able to accurately sample the folds of 192-residue long soluble monomeric Bcl-2-associated X protein (BAX). The tertiary structures of the monomeric and homodimeric forms of BAX were predicted using the primary structure as well as 25 and 11 EPR distance restraints, respectively. The predicted models were subsequently compared to respective NMR/X-ray structures of BAX. EPR restraints improve the protein-size normalized root-mean-square-deviation (RMSD100) of the most accurate models with respect to the NMR/crystal structure from 5.9 Å to 3.9 Å and from 5.7 Å to 3.3 Å, respectively. Additionally, the model discrimination is improved, which is demonstrated by an improvement of the enrichment from 5% to 15% and from 13% to 21%, respectively. PMID:27129417

Vulnerability of health to market forces.

PubMed

Brezis, Mayer; Wiist, William H

2011-03-01

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

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.

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

The Magsat magnetometer boom

NASA Technical Reports Server (NTRS)

Smola, J. F.; Radford, W. E.; Reitz, M. H.

1980-01-01

A lightweight extendable structure that can precisely position magnetically sensitive instruments safe distances from magnetic sources in a spacecraft is described as well as the major areas of concern that played dominant roles in its development. Weight, packaging volume, thermal distortion, mechanical misalignments, dimensional instability, launch environments, and low temperature functioning were areas that presented some formidable obstacles. The ways in which these obstacles were dealt with are examined for those involving the development of similar aerospace mechanisms with equally restrictive requirements.

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.

Space-based ornithology: studying bird migration and environmental change in North America

NASA Astrophysics Data System (ADS)

Smith, James A.; Deppe, Jill L.

2008-10-01

Natural fluctuations in the availability of critical stopover sites coupled with anthropogenic destruction of wetlands, land-use change, and anticipated losses due to climate change present migratory birds with a formidable challenge. Space based technology in concert with bird migration modeling and geographical information analysis yields new opportunities to shed light on the distribution and movement of organisms on the planet and their sensitivity to human disturbances and environmental changes. At the NASA Goddard Space Flight Center, we are creating ecological forecasting tools for science and application users to address the consequences of loss of wetlands, flooding, drought or other natural disasters such as hurricanes on avian biodiversity and bird migration. We use an individual-based bird biophysical migration model, driven by remotely sensed land surface data, climate and hydrologic data, and biological field observations to study migratory bird responses to environmental change in North America. Simulation allows us to study bird migration across multiple scales and can be linked to mechanistic processes describing the time and energy budget states of migrating birds. We illustrate our approach by simulating the spring migration of pectoral sandpipers from the Gulf of Mexico to Alaska. Mean stopover length and trajectory patterns are consistent with field observations.

Space-Based Ornithology - Studying Bird Migration and Environmental Change in North America

NASA Technical Reports Server (NTRS)

Smith, James A.; Deppe, Jill L.

2008-01-01

Natural fluctuations in the availability of critical stopover sites coupled with anthropogenic destruction of wetlands, land-use change, and anticipated losses due to climate change present migratory birds with a formidable challenge. Space based technology in concert with bird migration modeling and geographical information analysis yields new opportunities to shed light on the distribution and movement of organisms on the planet and their sensitivity to human disturbances and environmental changes. At the NASA Goddard Space Flight Center, we are creating ecological forecasting tools for science and application users to address the consequences of loss of wetlands, flooding, drought or other natural disasters such as hurricanes on avian biodiversity and bird migration. We use an individual-based bird biophysical migration model, driven by remotely sensed land surface data, climate and hydrologic data, and biological field observations to study migratory bird responses to environmental change in North America. Simulation allows us to study bird migration across multiple scales and can be linked to mechanistic processes describing the time and energy budget states of migrating birds. We illustrate our approach by simulating the spring migration of pectoral sandpipers from the Gulf of Mexico to Alaska. Mean stopover length and trajectory patterns are consistent with field observations.

Interventions for preventing and treating hyperthyroidism in pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2010-09-08

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 July 2010). We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Two review authors would have assessed trial eligibility and risk of bias, and extracted data. No trials were located. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

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.

Rational Combinations of Targeted Agents in AML

PubMed Central

Bose, Prithviraj; Grant, Steven

2015-01-01

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. PMID:26113989

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.

Progress in Computational Electron-Molecule Collisions

NASA Astrophysics Data System (ADS)

Rescigno, Tn

1997-10-01

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

Laboratory measurement of tip and global behavior for zero-toughness hydraulic fractures with circular and blade-shaped (PKN) geometry

NASA Astrophysics Data System (ADS)

Xing, Pengju; Yoshioka, Keita; Adachi, Jose; El-Fayoumi, Amr; Bunger, Andrew P.

2017-07-01

The tip behavior of hydraulic fractures is characterized by a rich nesting of asymptotic solutions, comprising a formidable challenge for the development of efficient and accurate numerical simulators. We present experimental validation of several theoretically-predicted asymptotic behaviors, namely for hydraulic fracture growth under conditions of negligible fracture toughness, with growth progressing from early-time radial geometry to large-time blade-like (PKN) geometry. Our experimental results demonstrate: 1) existence of a asymptotic solution of the form w ∼ s3/2 (LEFM) in the near tip region, where w is the crack opening and s is the distance from the crack tip, 2) transition to an asymptotic solution of the form w ∼ s2/3 away from the near-tip region, with the transition length scale also consistent with theory, 3) transition to an asymptotic solution of the form w ∼ s1/3 after the fracture attains blade-like (PKN) geometry, and 4) existence of a region near the tip of a blade-like (PKN) hydraulic fracture in which plane strain conditions persist, with the thickness of this region of the same order as the crack height.

Student Interpretations of Phylogenetic Trees in an Introductory Biology Course

PubMed Central

Dees, Jonathan; Niemi, Jarad; Montplaisir, Lisa

2014-01-01

Phylogenetic trees are widely used visual representations in the biological sciences and the most important visual representations in evolutionary biology. Therefore, phylogenetic trees have also become an important component of biology education. We sought to characterize reasoning used by introductory biology students in interpreting taxa relatedness on phylogenetic trees, to measure the prevalence of correct taxa-relatedness interpretations, and to determine how student reasoning and correctness change in response to instruction and over time. Counting synapomorphies and nodes between taxa were the most common forms of incorrect reasoning, which presents a pedagogical dilemma concerning labeled synapomorphies on phylogenetic trees. Students also independently generated an alternative form of correct reasoning using monophyletic groups, the use of which decreased in popularity over time. Approximately half of all students were able to correctly interpret taxa relatedness on phylogenetic trees, and many memorized correct reasoning without understanding its application. Broad initial instruction that allowed students to generate inferences on their own contributed very little to phylogenetic tree understanding, while targeted instruction on evolutionary relationships improved understanding to some extent. Phylogenetic trees, which can directly affect student understanding of evolution, appear to offer introductory biology instructors a formidable pedagogical challenge. PMID:25452489

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.

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.

Protein 3D Structure Computed from Evolutionary Sequence Variation

PubMed Central

Sheridan, Robert; Hopf, Thomas A.; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

2011-01-01

The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing. In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy. We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues., including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7–4.8 Å Cα-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein structures, new strategies in protein and drug design, and the identification of functional genetic variants in normal and disease genomes. PMID:22163331

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.

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

Multi-Fluid Block-Adaptive-Tree Solar Wind Roe-Type Upwind Scheme: Magnetospheric Composition and Dynamics During Geomagnetic Storms, Initial Results

NASA Technical Reports Server (NTRS)

Gkocer, A.; Toth, G.; Ma, Y.; Gombosi, T.; Zhang, J. C.; Kistler, L. M.

2010-01-01

The magnetosphere contains a significant amount of ionospheric O{+}, particularly during geomagnetically active times. The presence of ionospheric plasma in the magnetosphere has a notable impact on magnetospheric composition and processes. We present a new multifluid MHD version of the BATS-R-US model of the magnetosphere to track the fate and consequences of ionospheric outflow. The multi-fluid MHD equations are presented as are the novel techniques for overcoming the formidable challenges associated with solving them. Our new model is then applied to the May 4, 1998 and March 31, 2001 geomagnetic storms. The results are juxtaposed with traditional single- fluid MHD and multispecies MHD simulations from a previous study, thereby allowing us to assess the benefits of using a more complex model with additional physics. We find that our multi-fluid MHD model (with outflow) gives comparable results to the multi-species MHD model (with outflow), including a more strongly negative Dst, reduced CPCP, and a drastically improved magnetic field at geosynchronous orbit, as compared to single-fluid MHD with no outflow. Significant differences in composition and magnetic field are found between the multi-species and multi-fluid approach further away from the Earth. We further demonstrate the ability to explore pressure and bulk velocity differences between H{+} and O(+}, which is not possible when utilizing the other techniques considered.

Multifluid Block-Adaptive-Tree Solar Wind Roe-Type Upwind Scheme: Magnetospheric Composition and Dynamics During Geomagnetic Storms-Initial Results

NASA Technical Reports Server (NTRS)

Glocer, A.; Toth, G.; Ma, Y.; Gombosi, T.; Zhang, J.-C.; Kistler, L. M.

2009-01-01

The magnetosphere contains a significant amount of ionospheric O+, particularly during geomagnetically active times. The presence of ionospheric plasma in the magnetosphere has a notable impact on magnetospheric composition and processes. We present a new multifluid MHD version of the Block-Adaptive-Tree Solar wind Roe-type Upwind Scheme model of the magnetosphere to track the fate and consequences of ionospheric outflow. The multifluid MHD equations are presented as are the novel techniques for overcoming the formidable challenges associated with solving them. Our new model is then applied to the May 4, 1998 and March 31, 2001 geomagnetic storms. The results are juxtaposed with traditional single-fluid MHD and multispecies MHD simulations from a previous study, thereby allowing us to assess the benefits of using a more complex model with additional physics. We find that our multifluid MHD model (with outflow) gives comparable results to the multispecies MHD model (with outflow), including a more strongly negative Dst, reduced CPCP, and a drastically improved magnetic field at geosynchronous orbit, as compared to single-fluid MHD with no outflow. Significant differences in composition and magnetic field are found between the multispecies and multifluid approach further away from the Earth. We further demonstrate the ability to explore pressure and bulk velocity differences between H+ and O+, which is not possible when utilizing the other techniques considered

Meet-U: Educating through research immersion.

PubMed

Abdollahi, Nika; Albani, Alexandre; Anthony, Eric; Baud, Agnes; Cardon, Mélissa; Clerc, Robert; Czernecki, Dariusz; Conte, Romain; David, Laurent; Delaune, Agathe; Djerroud, Samia; Fourgoux, Pauline; Guiglielmoni, Nadège; Laurentie, Jeanne; Lehmann, Nathalie; Lochard, Camille; Montagne, Rémi; Myrodia, Vasiliki; Opuu, Vaitea; Parey, Elise; Polit, Lélia; Privé, Sylvain; Quignot, Chloé; Ruiz-Cuevas, Maria; Sissoko, Mariam; Sompairac, Nicolas; Vallerix, Audrey; Verrecchia, Violaine; Delarue, Marc; Guérois, Raphael; Ponty, Yann; Sacquin-Mora, Sophie; Carbone, Alessandra; Froidevaux, Christine; Le Crom, Stéphane; Lespinet, Olivier; Weigt, Martin; Abboud, Samer; Bernardes, Juliana; Bouvier, Guillaume; Dequeker, Chloé; Ferré, Arnaud; Fuchs, Patrick; Lelandais, Gaëlle; Poulain, Pierre; Richard, Hugues; Schweke, Hugo; Laine, Elodie; Lopes, Anne

2018-03-01

We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4-5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes "coopetition," as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master's students in bioinformatics and modeling, with protein-protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org.

Probability of survival during accidental immersion in cold water.

PubMed

Wissler, Eugene H

2003-01-01

Estimating the probability of survival during accidental immersion in cold water presents formidable challenges for both theoreticians and empirics. A number of theoretical models have been developed assuming that death occurs when the central body temperature, computed using a mathematical model, falls to a certain level. This paper describes a different theoretical approach to estimating the probability of survival. The human thermal model developed by Wissler is used to compute the central temperature during immersion in cold water. Simultaneously, a survival probability function is computed by solving a differential equation that defines how the probability of survival decreases with increasing time. The survival equation assumes that the probability of occurrence of a fatal event increases as the victim's central temperature decreases. Generally accepted views of the medical consequences of hypothermia and published reports of various accidents provide information useful for defining a "fatality function" that increases exponentially with decreasing central temperature. The particular function suggested in this paper yields a relationship between immersion time for 10% probability of survival and water temperature that agrees very well with Molnar's empirical observations based on World War II data. The method presented in this paper circumvents a serious difficulty with most previous models--that one's ability to survive immersion in cold water is determined almost exclusively by the ability to maintain a high level of shivering metabolism.

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.

Ab initio Investigation of Helium in Vanadium Oxide Nanoclusters

NASA Astrophysics Data System (ADS)

Danielson, Thomas; Tea, Eric; Hin, Celine

Nanostructured ferritic alloys (NFAs) are strong candidate materials for the next generation of fission reactors and future fusion reactors. They are characterized by a large number density of oxide nanoclusters dispersed throughout a BCC iron matrix, where current oxide nanoclusters are primarily comprised of Y-Ti-O compounds. The oxide nanoclusters provide the alloy with high resistance to neutron irradiation, high yield strength and high creep strength at the elevated temperatures of a reactor environment. In addition, the oxide nanoclusters serve as trapping sites for transmutation product helium providing substantially increased resistance to catastrophic cracking and embrittlement. Although the mechanical properties and radiation resistance of the existing NFAs is promising, the problem of forming large scale reactor components continues to present a formidable challenge due to the high hardness and unpredictable fracture behavior of the alloys. An alternative alloy has been previously proposed and fabricated where vanadium is added in order to form vanadium oxide nanoclusters that serve as deflection sites for crack propagation. Although experiments have shown evidence that the fracture behavior of the alloys is improved, it is unknown whether or not the vanadium oxide nanoclusters are effective trapping sites for helium. We present results obtained using density functional theory investigating the thermodynamic stability of helium with the vanadium oxide matrix to make a comparison of trapping effectiveness to traditional Y-Ti-O compounds.

Maximally resolved anharmonic OH vibrational spectrum of the water/ZnO(101 \\xAF 0) interface from a high-dimensional neural network potential

NASA Astrophysics Data System (ADS)

Quaranta, Vanessa; Hellström, Matti; Behler, Jörg; Kullgren, Jolla; Mitev, Pavlin D.; Hermansson, Kersti

2018-06-01

Unraveling the atomistic details of solid/liquid interfaces, e.g., by means of vibrational spectroscopy, is of vital importance in numerous applications, from electrochemistry to heterogeneous catalysis. Water-oxide interfaces represent a formidable challenge because a large variety of molecular and dissociated water species are present at the surface. Here, we present a comprehensive theoretical analysis of the anharmonic OH stretching vibrations at the water/ZnO(101 ¯ 0) interface as a prototypical case. Molecular dynamics simulations employing a reactive high-dimensional neural network potential based on density functional theory calculations have been used to sample the interfacial structures. In the second step, one-dimensional potential energy curves have been generated for a large number of configurations to solve the nuclear Schrödinger equation. We find that (i) the ZnO surface gives rise to OH frequency shifts up to a distance of about 4 Å from the surface; (ii) the spectrum contains a number of overlapping signals arising from different chemical species, with the frequencies decreasing in the order ν(adsorbed hydroxide) > ν(non-adsorbed water) > ν(surface hydroxide) > ν(adsorbed water); (iii) stretching frequencies are strongly influenced by the hydrogen bond pattern of these interfacial species. Finally, we have been able to identify substantial correlations between the stretching frequencies and hydrogen bond lengths for all species.

Meet-U: Educating through research immersion

PubMed Central

Abdollahi, Nika; Albani, Alexandre; Anthony, Eric; Baud, Agnes; Cardon, Mélissa; Clerc, Robert; Czernecki, Dariusz; David, Laurent; Delaune, Agathe; Djerroud, Samia; Fourgoux, Pauline; Guiglielmoni, Nadège; Laurentie, Jeanne; Lehmann, Nathalie; Lochard, Camille; Montagne, Rémi; Myrodia, Vasiliki; Opuu, Vaitea; Parey, Elise; Polit, Lélia; Privé, Sylvain; Quignot, Chloé; Ruiz-Cuevas, Maria; Sissoko, Mariam; Vallerix, Audrey; Delarue, Marc; Guérois, Raphael; Ponty, Yann; Sacquin-Mora, Sophie; Froidevaux, Christine; Lespinet, Olivier; Weigt, Martin; Abboud, Samer; Ferré, Arnaud; Lelandais, Gaëlle; Poulain, Pierre; Lopes, Anne

2018-01-01

We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4–5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes "coopetition," as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master’s students in bioinformatics and modeling, with protein–protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org. PMID:29543809

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.

[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

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

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

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

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

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

Kong, Lingping; Liu, Gang; Gong, Jue

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

On the Unruly Power of Pain in Middle English Drama.

PubMed

Nakley, Susan

2015-01-01

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

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

PubMed

Issa, John Paul; Bennett, Clay S

2014-04-16

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

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.

RiboFACSeq: A new method for investigating metabolic and transport pathways in bacterial cells by combining a riboswitch-based sensor, fluorescence-activated cell sorting and next-generation sequencing

PubMed Central

Li, Yingfu

2017-01-01

The elucidation of the cellular processes involved in vitamin and cofactor biosynthesis is a challenging task. The conventional approaches to these investigations rely on the discovery and purification of the products (i.e proteins and metabolites) of a particular transport or biosynthetic pathway, prior to their subsequent analysis. However, the purification of low-abundance proteins or metabolites is a formidable undertaking that presents considerable technical challenges. As a solution, we present an alternative approach to such studies that circumvents the purification step. The proposed approach takes advantage of: (1) the molecular detection capabilities of a riboswitch-based sensor to detect the cellular levels of its cognate molecule, as a means to probe the integrity of the transport and biosynthetic pathways of the target molecule in cells, (2) the high-throughput screening ability of fluorescence-activated cell sorters to isolate cells in which only these specific pathways are disrupted, and (3) the ability of next-generation sequencing to quickly identify the genes of the FACS-sorted populations. This approach was named “RiboFACSeq”. Following their identification by RiboFACSeq, the role of these genes in the presumed pathway needs to be verified through appropriate functional assays. To demonstrate the utility of our approach, an adenosylcobalamin (AdoCbl)-responsive riboswitch-based sensor was used in this study to demonstrate that RiboFACSeq can be used to track and sort cells carrying genetic mutations in known AdoCbl transport and biosynthesis genes with desirable sensitivity and specificity. This method could potentially be used to elucidate any pathway of interest, as long as a suitable riboswitch-based sensor can be created. We believe that RiboFACSeq would be especially useful for the elucidation of biological pathways in which the proteins and/or their metabolites are present at very low physiological concentrations in cells, as is the case with vitamin and cofactor biosynthesis. PMID:29211762

Adoption of Geospatial Systems towards evolving Sustainable Himalayan Mountain Development

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

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

PubMed

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

2017-01-01

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

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

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.

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.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

PubMed Central

Giri, Tapan Kumar; Choudhary, Chhatrapal; Ajazuddin; Alexander, Amit; Badwaik, Hemant; Tripathi, Dulal Krishna

2012-01-01

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active. PMID:23960828

An accurate and efficient laser-envelope solver for the modeling of laser-plasma accelerators

DOE PAGES

Benedetti, C.; Schroeder, C. B.; Geddes, C. G. R.; ...

2017-10-17

Detailed and reliable numerical modeling of laser-plasma accelerators (LPAs), where a short and intense laser pulse interacts with an underdense plasma over distances of up to a meter, is a formidably challenging task. This is due to the great disparity among the length scales involved in the modeling, ranging from the micron scale of the laser wavelength to the meter scale of the total laser-plasma interaction length. The use of the time-averaged ponderomotive force approximation, where the laser pulse is described by means of its envelope, enables efficient modeling of LPAs by removing the need to model the details ofmore » electron motion at the laser wavelength scale. Furthermore, it allows simulations in cylindrical geometry which captures relevant 3D physics at 2D computational cost. A key element of any code based on the time-averaged ponderomotive force approximation is the laser envelope solver. In this paper we present the accurate and efficient envelope solver used in the code INF & RNO (INtegrated Fluid & paRticle simulatioN cOde). The features of the INF & RNO laser solver enable an accurate description of the laser pulse evolution deep into depletion even at a reasonably low resolution, resulting in significant computational speed-ups.« 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.

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

DOE PAGES

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

2016-12-05

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

Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations

PubMed Central

Prieto, Gorka; Fullaondo, Asier; Rodríguez, Jose A.

2016-01-01

Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation, and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC), and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus. PMID:27174732

Distinguishing Emotional Co-Regulation From Co-Dysregulation: An Investigation of Emotional Dynamics and Body-Weight in Romantic Couples

PubMed Central

Reed, Rebecca G.; Barnard, Kobus; Butler, Emily A.

2015-01-01

Well-regulated emotions, both within people and between relationship partners, play a key role in facilitating health and well-being. The present study examined 39 heterosexual couples’ joint weight status (both partners are healthy-weight, both overweight, one healthy-weight and one overweight) as a predictor of two interpersonal emotional patterns during a discussion of their shared lifestyle choices. The first pattern, co-regulation, is one in which partners’ coupled emotions show a dampening pattern over time and ultimately return to homeostatic levels. The second, co-dysregulation, is one in which partners’ coupled emotions are amplified away from homeostatic balance. We demonstrate how a coupled linear oscillator (CLO) model (Butner, Amazeen, & Mulvey, 2005) can be used to distinguish co-regulation from co-dysregulation. As predicted, healthy-weight couples and mixed-weight couples in which the man was heavier than the woman displayed co-regulation, but overweight couples and mixed-weight couples in which the woman was heavier showed co-dysregulation. These results suggest that heterosexual couples in which the woman is overweight may face formidable co-regulatory challenges that could undermine both partners’ well-being. The results also demonstrate the importance of distinguishing between various interpersonal emotional dynamics for understanding connections between interpersonal emotions and health. PMID:25664951

Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

PubMed

Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

2016-01-01

The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling.

An Enhanced Method for Scheduling Observations of Large Sky Error Regions for Finding Optical Counterparts to Transients

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

Rana, Javed; Singhal, Akshat; Gadre, Bhooshan

2017-04-01

The discovery and subsequent study of optical counterparts to transient sources is crucial for their complete astrophysical understanding. Various gamma-ray burst (GRB) detectors, and more notably the ground-based gravitational wave detectors, typically have large uncertainties in the sky positions of detected sources. Searching these large sky regions spanning hundreds of square degrees is a formidable challenge for most ground-based optical telescopes, which can usually image less than tens of square degrees of the sky in a single night. We present algorithms for better scheduling of such follow-up observations in order to maximize the probability of imaging the optical counterpart, basedmore » on the all-sky probability distribution of the source position. We incorporate realistic observing constraints such as the diurnal cycle, telescope pointing limitations, available observing time, and the rising/setting of the target at the observatory’s location. We use simulations to demonstrate that our proposed algorithms outperform the default greedy observing schedule used by many observatories. Our algorithms are applicable for follow-up of other transient sources with large positional uncertainties, such as Fermi -detected GRBs, and can easily be adapted for scheduling radio or space-based X-ray follow-up.« less

Risk-based decision making for staggered bioterrorist attacks : resource allocation and risk reduction in "reload" scenarios.

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

Lemaster, Michelle Nicole; Gay, David M.; Ehlen, Mark Andrew

2009-10-01

Staggered bioterrorist attacks with aerosolized pathogens on population centers present a formidable challenge to resource allocation and response planning. The response and planning will commence immediately after the detection of the first attack and with no or little information of the second attack. In this report, we outline a method by which resource allocation may be performed. It involves probabilistic reconstruction of the bioterrorist attack from partial observations of the outbreak, followed by an optimization-under-uncertainty approach to perform resource allocations. We consider both single-site and time-staggered multi-site attacks (i.e., a reload scenario) under conditions when resources (personnel and equipment whichmore » are difficult to gather and transport) are insufficient. Both communicable (plague) and non-communicable diseases (anthrax) are addressed, and we also consider cases when the data, the time-series of people reporting with symptoms, are confounded with a reporting delay. We demonstrate how our approach develops allocations profiles that have the potential to reduce the probability of an extremely adverse outcome in exchange for a more certain, but less adverse outcome. We explore the effect of placing limits on daily allocations. Further, since our method is data-driven, the resource allocation progressively improves as more data becomes available.« less

Sequencing and assembly of the 22-gb loblolly pine genome.

PubMed

Zimin, Aleksey; Stevens, Kristian A; Crepeau, Marc W; Holtz-Morris, Ann; Koriabine, Maxim; Marçais, Guillaume; Puiu, Daniela; Roberts, Michael; Wegrzyn, Jill L; de Jong, Pieter J; Neale, David B; Salzberg, Steven L; Yorke, James A; Langley, Charles H

2014-03-01

Conifers are the predominant gymnosperm. The size and complexity of their genomes has presented formidable technical challenges for whole-genome shotgun sequencing and assembly. We employed novel strategies that allowed us to determine the loblolly pine (Pinus taeda) reference genome sequence, the largest genome assembled to date. Most of the sequence data were derived from whole-genome shotgun sequencing of a single megagametophyte, the haploid tissue of a single pine seed. Although that constrained the quantity of available DNA, the resulting haploid sequence data were well-suited for assembly. The haploid sequence was augmented with multiple linking long-fragment mate pair libraries from the parental diploid DNA. For the longest fragments, we used novel fosmid DiTag libraries. Sequences from the linking libraries that did not match the megagametophyte were identified and removed. Assembly of the sequence data were aided by condensing the enormous number of paired-end reads into a much smaller set of longer "super-reads," rendering subsequent assembly with an overlap-based assembly algorithm computationally feasible. To further improve the contiguity and biological utility of the genome sequence, additional scaffolding methods utilizing independent genome and transcriptome assemblies were implemented. The combination of these strategies resulted in a draft genome sequence of 20.15 billion bases, with an N50 scaffold size of 66.9 kbp.

Interventions for preventing and treating hyperthyroidism in pregnancy

PubMed Central

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2014-01-01

Background Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. Objectives To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010). Selection criteria We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Data collection and analysis Two review authors would have assessed trial eligibility and risk of bias, and extracted data. Main results No trials were located. Authors’ conclusions As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil. PMID:20824882

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

PubMed Central

Carroll, Karen C.

2013-01-01

SUMMARY Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile. This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians. PMID:23824374

Meshed doped silicon photonic crystals for manipulating near-field thermal radiation

NASA Astrophysics Data System (ADS)

Elzouka, Mahmoud; Ndao, Sidy

2018-01-01

The ability to control and manipulate heat flow is of great interest to thermal management and thermal logic and memory devices. Particularly, near-field thermal radiation presents a unique opportunity to enhance heat transfer while being able to tailor its characteristics (e.g., spectral selectivity). However, achieving nanometric gaps, necessary for near-field, has been and remains a formidable challenge. Here, we demonstrate significant enhancement of the near-field heat transfer through meshed photonic crystals with separation gaps above 0.5 μm. Using a first-principle method, we investigate the meshed photonic structures numerically via finite-difference time-domain technique (FDTD) along with the Langevin approach. Results for doped-silicon meshed structures show significant enhancement in heat transfer; 26 times over the non-meshed corrugated structures. This is especially important for thermal management and thermal rectification applications. The results also support the premise that thermal radiation at micro scale is a bulk (rather than a surface) phenomenon; the increase in heat transfer between two meshed-corrugated surfaces compared to the flat surface (8.2) wasn't proportional to the increase in the surface area due to the corrugations (9). Results were further validated through good agreements between the resonant modes predicted from the dispersion relation (calculated using a finite-element method), and transmission factors (calculated from FDTD).

An accurate and efficient laser-envelope solver for the modeling of laser-plasma accelerators

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

Benedetti, C.; Schroeder, C. B.; Geddes, C. G. R.

Detailed and reliable numerical modeling of laser-plasma accelerators (LPAs), where a short and intense laser pulse interacts with an underdense plasma over distances of up to a meter, is a formidably challenging task. This is due to the great disparity among the length scales involved in the modeling, ranging from the micron scale of the laser wavelength to the meter scale of the total laser-plasma interaction length. The use of the time-averaged ponderomotive force approximation, where the laser pulse is described by means of its envelope, enables efficient modeling of LPAs by removing the need to model the details ofmore » electron motion at the laser wavelength scale. Furthermore, it allows simulations in cylindrical geometry which captures relevant 3D physics at 2D computational cost. A key element of any code based on the time-averaged ponderomotive force approximation is the laser envelope solver. In this paper we present the accurate and efficient envelope solver used in the code INF & RNO (INtegrated Fluid & paRticle simulatioN cOde). The features of the INF & RNO laser solver enable an accurate description of the laser pulse evolution deep into depletion even at a reasonably low resolution, resulting in significant computational speed-ups.« less

An accurate and efficient laser-envelope solver for the modeling of laser-plasma accelerators

NASA Astrophysics Data System (ADS)

Benedetti, C.; Schroeder, C. B.; Geddes, C. G. R.; Esarey, E.; Leemans, W. P.

2018-01-01

Detailed and reliable numerical modeling of laser-plasma accelerators (LPAs), where a short and intense laser pulse interacts with an underdense plasma over distances of up to a meter, is a formidably challenging task. This is due to the great disparity among the length scales involved in the modeling, ranging from the micron scale of the laser wavelength to the meter scale of the total laser-plasma interaction length. The use of the time-averaged ponderomotive force approximation, where the laser pulse is described by means of its envelope, enables efficient modeling of LPAs by removing the need to model the details of electron motion at the laser wavelength scale. Furthermore, it allows simulations in cylindrical geometry which captures relevant 3D physics at 2D computational cost. A key element of any code based on the time-averaged ponderomotive force approximation is the laser envelope solver. In this paper we present the accurate and efficient envelope solver used in the code INF&RNO (INtegrated Fluid & paRticle simulatioN cOde). The features of the INF&RNO laser solver enable an accurate description of the laser pulse evolution deep into depletion even at a reasonably low resolution, resulting in significant computational speed-ups.

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.

Robust and effective methodologies for cryopreservation and DNA extraction from anaerobic gut fungi.

PubMed

Solomon, Kevin V; Henske, John K; Theodorou, Michael K; O'Malley, Michelle A

2016-04-01

Cell storage and DNA isolation are essential to developing an expanded suite of microorganisms for biotechnology. However, many features of non-model microbes, such as an anaerobic lifestyle and rigid cell wall, present formidable challenges to creating strain repositories and extracting high quality genomic DNA. Here, we establish accessible, high efficiency, and robust techniques to store lignocellulolytic anaerobic gut fungi long term without specialized equipment. Using glycerol as a cryoprotectant, gut fungal isolates were preserved for a minimum of 23 months at -80 °C. Unlike previously reported approaches, this improved protocol is non-toxic and rapid, with samples surviving twice as long with negligible growth impact. Genomic DNA extraction for these isolates was optimized to yield samples compatible with next generation sequencing platforms (e.g. Illumina, PacBio). Popular DNA isolation kits and precipitation protocols yielded preps that were unsuitable for sequencing due to carbohydrate contaminants from the chitin-rich cell wall and extensive energy reserves of gut fungi. To address this, we identified a proprietary method optimized for hardy plant samples that rapidly yielded DNA fragments in excess of 10 kb with minimal RNA, protein or carbohydrate contamination. Collectively, these techniques serve as fundamental tools to manipulate powerful biomass-degrading gut fungi and improve their accessibility among researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiscale methods for gore curvature calculations from FSI modeling of spacecraft parachutes

NASA Astrophysics Data System (ADS)

Takizawa, Kenji; Tezduyar, Tayfun E.; Kolesar, Ryan; Boswell, Cody; Kanai, Taro; Montel, Kenneth

2014-12-01

There are now some sophisticated and powerful methods for computer modeling of parachutes. These methods are capable of addressing some of the most formidable computational challenges encountered in parachute modeling, including fluid-structure interaction (FSI) between the parachute and air flow, design complexities such as those seen in spacecraft parachutes, and operational complexities such as use in clusters and disreefing. One should be able to extract from a reliable full-scale parachute modeling any data or analysis needed. In some cases, however, the parachute engineers may want to perform quickly an extended or repetitive analysis with methods based on simplified models. Some of the data needed by a simplified model can very effectively be extracted from a full-scale computer modeling that serves as a pilot. A good example of such data is the circumferential curvature of a parachute gore, where a gore is the slice of the parachute canopy between two radial reinforcement cables running from the parachute vent to the skirt. We present the multiscale methods we devised for gore curvature calculation from FSI modeling of spacecraft parachutes. The methods include those based on the multiscale sequentially-coupled FSI technique and using NURBS meshes. We show how the methods work for the fully-open and two reefed stages of the Orion spacecraft main and drogue parachutes.

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

Symbolic Computation of Strongly Connected Components Using Saturation

NASA Technical Reports Server (NTRS)

Zhao, Yang; Ciardo, Gianfranco

2010-01-01

Finding strongly connected components (SCCs) in the state-space of discrete-state models is a critical task in formal verification of LTL and fair CTL properties, but the potentially huge number of reachable states and SCCs constitutes a formidable challenge. This paper is concerned with computing the sets of states in SCCs or terminal SCCs of asynchronous systems. Because of its advantages in many applications, we employ saturation on two previously proposed approaches: the Xie-Beerel algorithm and transitive closure. First, saturation speeds up state-space exploration when computing each SCC in the Xie-Beerel algorithm. Then, our main contribution is a novel algorithm to compute the transitive closure using saturation. Experimental results indicate that our improved algorithms achieve a clear speedup over previous algorithms in some cases. With the help of the new transitive closure computation algorithm, up to 10(exp 150) SCCs can be explored within a few seconds.

Harnessing the genome for characterization of GPCRs in cancer pathogenesis

PubMed Central

Feigin, Michael E.

2014-01-01

G-protein coupled receptors (GPCRs) mediate numerous physiological processes and represent the targets for a vast array of therapeutics for diseases ranging from depression to hypertension to reflux. Despite the recognition that GPCRs can act as oncogenes and tumor suppressors by regulating oncogenic signaling networks, few drugs targeting GPCRs are utilized in cancer therapy. Recent large-scale genome-wide analyses of multiple human tumors have uncovered novel GPCRs altered in cancer. However, the work of determining which GPCRs from these lists are drivers of tumorigenesis, and hence valid therapeutic targets, remains a formidable challenge. In this review I will highlight recent studies providing evidence that GPCRs are relevant targets for cancer therapy through their effects on known cancer signaling pathways, tumor progression, invasion and metastasis, and the microenvironment. Furthermore, I will explore how genomic analysis is beginning to shine a light on GPCRs as therapeutic targets in the age of personalized medicine. PMID:23927072

Site-Directed Synthesis of Cobalt Oxide Clusters in a Metal–Organic Framework

DOE PAGES

Peters, Aaron W.; Otake, Kenichi; Platero-Prats, Ana E.; ...

2018-04-19

Here, direct control over structure and location of catalytic species deposited on amorphous supports represents a formidable challenge in heterogeneous catalysis. In contrast, a structurally well-defined, crystalline metal–organic framework (MOF) can be rationally designed using post-synthetic techniques to allow for desired structural or locational changes of deposited metal ions. Herein, naphthalene dicarboxylate linkers are incorporated in the MOF, NU-1000, to block the small cavities where few-atom clusters of cobalt oxide preferentially grow, inducing catalyst deposition towards hither-to ill-favored grafting sites orientated toward NU-1000’s mesoporous channels. Despite the different cobalt oxide location, the resulting material is still an active propane oxidativemore » dehydrogenation catalyst at low temperature, reaching a turnover frequency of 0.68 ± 0.05 h –1 at 230 °C and confirming the utility of MOFs as crystalline supports to guide rational design of catalysts.« less

Environmental Trigger(s) of Type 1 Diabetes: Why So Difficult to Identify?

PubMed Central

2015-01-01

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease has increased two- to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself so that, in a very specific and targeted way, it destroys the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will focus on factors which have to be evaluated and decision to take before starting a new prospective cohort study. Considering all the large ongoing prospective studies, new and more conclusive data than that obtained so far should instead come from international collaboration on the ongoing cohort studies. PMID:25883954

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

Kidney regeneration by xeno-embryonic nephrogenesis.

PubMed

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Kawamura, Tetsuya

2008-03-01

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

Progress on Updating the 1961-1990 National Solar Radiation Database

NASA Technical Reports Server (NTRS)

Renne, D.; Wilcox, S.; Marion, B.; George, R.; Myers, D.

2003-01-01

The 1961-1990 National Solar Radiation Data Base (NSRDB) provides a 30-year climate summary and solar characterization of 239 locations throughout the United States. Over the past several years, the National Renewable Energy Laboratory (NREL) has received numerous inquiries from a range of constituents as to whether an update of the database to include the 1990s will be developed. However, there are formidable challenges to creating an update of the serially complete station-specific database for the 1971-2000 period. During the 1990s, the National Weather Service changed its observational procedures from a human-based to an automated system, resulting in the loss of important input variables to the model used to complete the 1961-1990 NSRDB. As a result, alternative techniques are required for an update that covers the 1990s. This paper examines several alternative approaches for creating this update and describes preliminary NREL plans for implementing the update.

Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer

PubMed Central

Kim, Yunee; Jeon, Jouhyun; Mejia, Salvador; Yao, Cindy Q; Ignatchenko, Vladimir; Nyalwidhe, Julius O; Gramolini, Anthony O; Lance, Raymond S; Troyer, Dean A; Drake, Richard R; Boutros, Paul C; Semmes, O. John; Kislinger, Thomas

2016-01-01

Biomarkers are rapidly gaining importance in personalized medicine. Although numerous molecular signatures have been developed over the past decade, there is a lack of overlap and many biomarkers fail to validate in independent patient cohorts and hence are not useful for clinical application. For these reasons, identification of novel and robust biomarkers remains a formidable challenge. We combine targeted proteomics with computational biology to discover robust proteomic signatures for prostate cancer. Quantitative proteomics conducted in expressed prostatic secretions from men with extraprostatic and organ-confined prostate cancers identified 133 differentially expressed proteins. Using synthetic peptides, we evaluate them by targeted proteomics in a 74-patient cohort of expressed prostatic secretions in urine. We quantify a panel of 34 candidates in an independent 207-patient cohort. We apply machine-learning approaches to develop clinical predictive models for prostate cancer diagnosis and prognosis. Our results demonstrate that computationally guided proteomics can discover highly accurate non-invasive biomarkers. PMID:27350604

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants

PubMed Central

Beletsky, Leo; Ciccarone, Daniel

2018-01-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis’ trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions. PMID:29267060

Mergers involving academic health centers: a formidable challenge.

PubMed

Pellegrini, V D

2001-10-01

Escalating economic pressures on the clinical enterprise threaten the missions of education and research in many of the most prestigious academic health centers. Following the model of industry, mergers of the healthcare delivery systems of teaching hospitals and clinics held promise for economies of scale and an improved operating margin. Failure to follow business principles in constructing the merged entity, differences in organizational governance and culture, and inability of physician leadership to prioritize, downsize, and consolidate clinical programs to optimize operational efficiencies all compromise the success of such mergers in academic medicine. Academic institutions and their respective governing boards need to exercise greater discipline in financial analysis and a willingness to make difficult decisions that show favor to one parent institution over another if mergers are to be effective in this setting. To date, an example of a vibrant and successful merger of academic health centers remains to be found.

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles

PubMed Central

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L.; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-01-01

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi2Ta2O9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction–relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes. PMID:28194017

Mechanical stimulation in the engineering of heart muscle.

PubMed

Liaw, Norman Yu; Zimmermann, Wolfram-Hubertus

2016-01-15

Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. Copyright © 2015. Published by Elsevier B.V.

Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective.

PubMed

Khurana, Surender

2018-04-27

Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.

The Centauri project: Manned interstellar travel

NASA Technical Reports Server (NTRS)

Ciesla, Thomas M.

1990-01-01

The development of antimatter engines for spacecraft propulsion will allow man to expand to the nearest stellar neighbors such as the Alpha Centuri system. Compared to chemically powered rockets like the Apollo mission class which would take 50,000 years to reach the Centauri system, antimatter propulsion would reduce one way trip time to 30 years or less. The challenges encountered by manned interstellar travel are formidable. The spacecraft must be a combination of sublight speed transportation system and a traveling microplanet serving an expanding population. As the population expands from the initial 100 people to approximately 300, the terraformed asteroid, enclosed by a man-made shell will allow for expansion over its surface in the fashion of a small terrestrial town. All aspects of human life - birth; death; physical, emotional, and educational needs; and government and law must be met by the structure, systems, and institutions on-board.

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.

Relaxation dynamics of dysprosium(III) single molecule magnets.

PubMed

Guo, Yun-Nan; Xu, Gong-Feng; Guo, Yang; Tang, Jinkui

2011-10-21

Over the past decade, lanthanide compounds have become of increasing interest in the field of Single Molecule Magnets (SMMs) due to the large inherent anisotropy of the metal ions. Heavy lanthanide metal systems, in particular those containing the dysprosium(III) ion, have been extensively employed to direct the formation of a series of SMMs. Although remarkable progress is being made regarding the synthesis and characterization of lanthanide-based SMMs, the understanding and control of the relaxation dynamics of strongly anisotropic systems represents a formidable challenge, since the dynamic behaviour of lanthanide-based SMMs is significantly more complex than that of transition metal systems. This perspective paper describes illustrative examples of pure dysprosium(III)-based SMMs, published during the past three years, showing new and fascinating phenomena in terms of magnetic relaxation, aiming at shedding light on the features relevant to modulating relaxation dynamics of polynuclear lanthanide SMMs. This journal is © The Royal Society of Chemistry 2011

A plasmonic nanorod that walks on DNA origami

PubMed Central

Zhou, Chao; Duan, Xiaoyang; Liu, Na

2015-01-01

In nano-optics, a formidable challenge remains in precise transport of a single optical nano-object along a programmed and routed path toward a predefined destination. Molecular motors in living cells that can walk directionally along microtubules have been the inspiration for realizing artificial molecular walkers. Here we demonstrate an active plasmonic system, in which a plasmonic nanorod can execute directional, progressive and reverse nanoscale walking on two or three-dimensional DNA origami. Such a walker comprises an anisotropic gold nanorod as its ‘body' and discrete DNA strands as its ‘feet'. Specifically, our walker carries optical information and can in situ optically report its own walking directions and consecutive steps at nanometer accuracy, through dynamic coupling to a plasmonic stator immobilized along its walking track. Our concept will enable a variety of smart nanophotonic platforms for studying dynamic light–matter interaction, which requires controlled motion at the nanoscale well below the optical diffraction limit. PMID:26303016

Simultaneous band-gap narrowing and carrier-lifetime prolongation of organic–inorganic trihalide perovskites

PubMed Central

Kong, Lingping; Liu, Gang; Gong, Jue; Hu, Qingyang; Schaller, Richard D.; Dera, Przemyslaw; Zhang, Dongzhou; Liu, Zhenxian; Yang, Wenge; Zhu, Kai; Tang, Yuzhao; Wang, Chuanyi; Wei, Su-Huai; Xu, Tao; Mao, Ho-kwang

2016-01-01

The organic–inorganic hybrid lead trihalide perovskites have been emerging as the most attractive photovoltaic materials. As regulated by Shockley–Queisser theory, a formidable materials science challenge for improvement to the next level requires further band-gap narrowing for broader absorption in solar spectrum, while retaining or even synergistically prolonging the carrier lifetime, a critical factor responsible for attaining the near-band-gap photovoltage. Herein, by applying controllable hydrostatic pressure, we have achieved unprecedented simultaneous enhancement in both band-gap narrowing and carrier-lifetime prolongation (up to 70% to ∼100% increase) under mild pressures at ∼0.3 GPa. The pressure-induced modulation on pure hybrid perovskites without introducing any adverse chemical or thermal effect clearly demonstrates the importance of band edges on the photon–electron interaction and maps a pioneering route toward a further increase in their photovoltaic performance. PMID:27444014

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles

NASA Astrophysics Data System (ADS)

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L.; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-02-01

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi2Ta2O9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction-relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes.

In situ study on atomic mechanism of melting and freezing of single bismuth nanoparticles.

PubMed

Li, Yingxuan; Zang, Ling; Jacobs, Daniel L; Zhao, Jie; Yue, Xiu; Wang, Chuanyi

2017-02-13

Experimental study of the atomic mechanism in melting and freezing processes remains a formidable challenge. We report herein on a unique material system that allows for in situ growth of bismuth nanoparticles from the precursor compound SrBi 2 Ta 2 O 9 under an electron beam within a high-resolution transmission electron microscope (HRTEM). Simultaneously, the melting and freezing processes within the nanoparticles are triggered and imaged in real time by the HRTEM. The images show atomic-scale evidence for point defect induced melting, and a freezing mechanism mediated by crystallization of an intermediate ordered liquid. During the melting and freezing, the formation of nucleation precursors, nucleation and growth, and the relaxation of the system, are directly observed. Based on these observations, an interaction-relaxation model is developed towards understanding the microscopic mechanism of the phase transitions, highlighting the importance of cooperative multiscale processes.

SBROME: a scalable optimization and module matching framework for automated biosystems design.

PubMed

Huynh, Linh; Tsoukalas, Athanasios; Köppe, Matthias; Tagkopoulos, Ilias

2013-05-17

The development of a scalable framework for biodesign automation is a formidable challenge given the expected increase in part availability and the ever-growing complexity of synthetic circuits. To allow for (a) the use of previously constructed and characterized circuits or modules and (b) the implementation of designs that can scale up to hundreds of nodes, we here propose a divide-and-conquer Synthetic Biology Reusable Optimization Methodology (SBROME). An abstract user-defined circuit is first transformed and matched against a module database that incorporates circuits that have previously been experimentally characterized. Then the resulting circuit is decomposed to subcircuits that are populated with the set of parts that best approximate the desired function. Finally, all subcircuits are subsequently characterized and deposited back to the module database for future reuse. We successfully applied SBROME toward two alternative designs of a modular 3-input multiplexer that utilize pre-existing logic gates and characterized biological parts.

Frequency domain optical parametric amplification

PubMed Central

Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

2014-01-01

Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

Novel Solid Electrolytes for Li-Ion Batteries: A Perspective from Electron Microscopy Studies

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

Ma, Cheng; Chi, Miaofang

2016-06-08

Solid electrolytes can simultaneously overcome two of the most formidable challenges of Li-ion batteries: the severe safety issues and insufficient energy densities. However, before they can be implemented in actual batteries, the ionic conductivity needs to be improved and the interface with electrodes must be optimized. The prerequisite for addressing these issues is a thorough understanding of the material’s behavior at the microscopic and/or the atomic level. (Scanning) transmission electron microscopy is a powerful tool for this purpose, as it can reach an ultrahigh spatial resolution. Here, we review recent electron microscopy investigations on the ion transport behavior in solidmore » electrolytes and their interfaces. Specifically, three aspects will be highlighted: the influence of grain interior atomic configuration on ionic conductivity, the contribution of grain boundaries, and the behavior of solid electrolyte/electrode interfaces. In conclusion, based on this, the perspectives for future research will be discussed.« less

A fast key generation method based on dynamic biometrics to secure wireless body sensor networks for p-health.

PubMed

Zhang, G H; Poon, Carmen C Y; Zhang, Y T

2010-01-01

Body sensor networks (BSNs) have emerged as a new technology for healthcare applications, but the security of communication in BSNs remains a formidable challenge yet to be resolved. The paper discusses the typical attacks faced by BSNs and proposes a fast biometric based approach to generate keys for ensuing confidentiality and authentication in BSN communications. The approach was tested on 900 segments of electrocardiogram. Each segment was 4 seconds long and used to generate a 128-bit key. The results of the study found that entropy of 96% of the keys were above 0.95 and 99% of the hamming distances calculated from any two keys were above 50 bits. Based on the randomness and distinctiveness of these keys, it is concluded that the fast biometric based approach has great potential to be used to secure communication in BSNs for health applications.

Security Hardened Cyber Components for Nuclear Power Plants: Phase I SBIR Final Technical Report

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

Franusich, Michael D.

SpiralGen, Inc. built a proof-of-concept toolkit for enhancing the cyber security of nuclear power plants and other critical infrastructure with high-assurance instrumentation and control code. The toolkit is based on technology from the DARPA High-Assurance Cyber Military Systems (HACMS) program, which has focused on applying the science of formal methods to the formidable set of problems involved in securing cyber physical systems. The primary challenges beyond HACMS in developing this toolkit were to make the new technology usable by control system engineers and compatible with the regulatory and commercial constraints of the nuclear power industry. The toolkit, packaged as amore » Simulink add-on, allows a system designer to assemble a high-assurance component from formally specified and proven blocks and generate provably correct control and monitor code for that subsystem.« less

Principles of nanoparticle design for overcoming biological barriers to drug delivery

PubMed Central

Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

2016-01-01

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

Site-Directed Synthesis of Cobalt Oxide Clusters in a Metal–Organic Framework

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

Peters, Aaron W.; Otake, Kenichi; Platero-Prats, Ana E.

Here, direct control over structure and location of catalytic species deposited on amorphous supports represents a formidable challenge in heterogeneous catalysis. In contrast, a structurally well-defined, crystalline metal–organic framework (MOF) can be rationally designed using post-synthetic techniques to allow for desired structural or locational changes of deposited metal ions. Herein, naphthalene dicarboxylate linkers are incorporated in the MOF, NU-1000, to block the small cavities where few-atom clusters of cobalt oxide preferentially grow, inducing catalyst deposition towards hither-to ill-favored grafting sites orientated toward NU-1000’s mesoporous channels. Despite the different cobalt oxide location, the resulting material is still an active propane oxidativemore » dehydrogenation catalyst at low temperature, reaching a turnover frequency of 0.68 ± 0.05 h –1 at 230 °C and confirming the utility of MOFs as crystalline supports to guide rational design of catalysts.« less

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.

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants.

PubMed

Dasgupta, Nabarun; Beletsky, Leo; Ciccarone, Daniel

2018-02-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis' trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions.

Quasiparticle Approach to Molecules Interacting with Quantum Solvents.

PubMed

Lemeshko, Mikhail

2017-03-03

Understanding the behavior of molecules interacting with superfluid helium represents a formidable challenge and, in general, requires approaches relying on large-scale numerical simulations. Here, we demonstrate that experimental data collected over the last 20 years provide evidence that molecules immersed in superfluid helium form recently predicted angulon quasiparticles [Phys. Rev. Lett. 114, 203001 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.203001]. Most important, casting the many-body problem in terms of angulons amounts to a drastic simplification and yields effective molecular moments of inertia as straightforward analytic solutions of a simple microscopic Hamiltonian. The outcome of the angulon theory is in good agreement with experiment for a broad range of molecular impurities, from heavy to medium-mass to light species. These results pave the way to understanding molecular rotation in liquid and crystalline phases in terms of the angulon quasiparticle.

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.

Constraining the inferred paleohydrologic evolution of a deep unsaturated zone in the Amargosa Desert

USGS Publications Warehouse

Walvoord, Michelle Ann; Stonestrom, David A.; Andraski, Brian J.; Striegl, Robert G.

2004-01-01

Natural flow regimes in deep unsaturated zones of arid interfluvial environments are rarely in hydraulic equilibrium with near-surface boundary conditions imposed by present-day plant–soil–atmosphere dynamics. Nevertheless, assessments of water resources and contaminant transport require realistic estimates of gas, water, and solute fluxes under past, present, and projected conditions. Multimillennial transients that are captured in current hydraulic, chemical, and isotopic profiles can be interpreted to constrain alternative scenarios of paleohydrologic evolution following climatic and vegetational shifts from pluvial to arid conditions. However, interpreting profile data with numerical models presents formidable challenges in that boundary conditions must be prescribed throughout the entire Holocene, when we have at most a few decades of actual records. Models of profile development at the Amargosa Desert Research Site include substantial uncertainties from imperfectly known initial and boundary conditions when simulating flow and solute transport over millennial timescales. We show how multiple types of profile data, including matric potentials and porewater concentrations of Cl−, δD, δ18O, can be used in multiphase heat, flow, and transport models to expose and reduce uncertainty in paleohydrologic reconstructions. Results indicate that a dramatic shift in the near-surface water balance occurred approximately 16000 yr ago, but that transitions in precipitation, temperature, and vegetation were not necessarily synchronous. The timing of the hydraulic transition imparts the largest uncertainty to model-predicted contemporary fluxes. In contrast, the uncertainties associated with initial (late Pleistocene) conditions and boundary conditions during the Holocene impart only small uncertainties to model-predicted contemporaneous fluxes.

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.

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

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.

Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes

PubMed Central

Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B.

2016-01-01

Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5′→3′, 3′ →5′ or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically. Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm PMID:27515825

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.

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.

Quantification of soil structure based on Minkowski functions

NASA Astrophysics Data System (ADS)

Vogel, H.-J.; Weller, U.; Schlüter, S.

2010-10-01

The structure of soils and other geologic media is a complex three-dimensional object. Most of the physical material properties including mechanical and hydraulic characteristics are immediately linked to the structure given by the pore space and its spatial distribution. It is an old dream and still a formidable challenge to relate structural features of porous media to their functional properties. Using tomographic techniques, soil structure can be directly observed at a range of spatial scales. In this paper we present a scale-invariant concept to quantify complex structures based on a limited set of meaningful morphological functions. They are based on d+1 Minkowski functionals as defined for d-dimensional bodies. These basic quantities are determined as a function of pore size or aggregate size obtained by filter procedures using mathematical morphology. The resulting Minkowski functions provide valuable information on the size of pores and aggregates, the pore surface area and the pore topology having the potential to be linked to physical properties. The theoretical background and the related algorithms are presented and the approach is demonstrated for the pore structure of an arable soil and the pore structure of a sand both obtained by X-ray micro-tomography. We also analyze the fundamental problem of limited resolution which is critical for any attempt to quantify structural features at any scale using samples of different size recorded at different resolutions. The results demonstrate that objects smaller than 5 voxels are critical for quantitative analysis.

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.

Health workers and the weaponisation of health care in Syria: a preliminary inquiry for The Lancet-American University of Beirut Commission on Syria.

PubMed

Fouad, Fouad M; Sparrow, Annie; Tarakji, Ahmad; Alameddine, Mohamad; El-Jardali, Fadi; Coutts, Adam P; El Arnaout, Nour; Karroum, Lama Bou; Jawad, Mohammed; Roborgh, Sophie; Abbara, Aula; Alhalabi, Fadi; AlMasri, Ibrahim; Jabbour, Samer

2017-12-02

The conflict in Syria presents new and unprecedented challenges that undermine the principles and practice of medical neutrality in armed conflict. With direct and repeated targeting of health workers, health facilities, and ambulances, Syria has become the most dangerous place on earth for health-care providers. The weaponisation of health care-a strategy of using people's need for health care as a weapon against them by violently depriving them of it-has translated into hundreds of health workers killed, hundreds more incarcerated or tortured, and hundreds of health facilities deliberately and systematically attacked. Evidence shows use of this strategy on an unprecedented scale by the Syrian Government and allied forces, in what human rights organisations described as a war-crime strategy, although all parties seem to have committed violations. Attacks on health care have sparked a large-scale exodus of experienced health workers. Formidable challenges face health workers who have stayed behind, and with no health care a major factor in the flight of refugees, the effect extends well beyond Syria. The international community has left these violations of international humanitarian and human rights law largely unanswered, despite their enormous consequences. There have been repudiated denunciations, but little action on bringing the perpetrators to justice. This inadequate response challenges the foundation of medical neutrality needed to sustain the operations of global health and humanitarian agencies in situations of armed conflict. In this Health Policy, we analyse the situation of health workers facing such systematic and serious violations of international humanitarian law. We describe the tremendous pressures that health workers have been under and continue to endure, and the remarkable resilience and resourcefulness they have displayed in response to this crisis. We propose policy imperatives to protect and support health workers working in armed conflict zones. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Why Waveform Correlation Sometimes Fails

NASA Astrophysics Data System (ADS)

Carmichael, J.

2015-12-01

Waveform correlation detectors used in explosion monitoring scan noisy geophysical data to test two competing hypotheses: either (1) an amplitude-scaled version of a template waveform is present, or, (2) no signal is present at all. In reality, geophysical wavefields that are monitored for explosion signatures include waveforms produced by non-target sources that are partially correlated with the waveform template. Such signals can falsely trigger correlation detectors, particularly at low thresholds required to monitor for smaller target explosions. This challenge is particularly formidable when monitoring known test sites for seismic disturbances, since uncatalogued natural seismicity is (generally) more prevalent at lower magnitudes, and could be mistaken for small explosions. To address these challenges, we identify real examples in which correlation detectors targeting explosions falsely trigger on both site-proximal earthquakes (Figure 1, below) and microseismic "noise". Motivated by these examples, we quantify performance loss when applying these detectors, and re-evaluate the correlation-detector's hypothesis test. We thereby derive new detectors from more general hypotheses that admit unknown background seismicity, and apply these to real data. From our treatment, we derive "rules of thumb'' for proper template and threshold selection in heavily cluttered signal environments. Last, we answer the question "what is the probability of falsely detecting an earthquake collocated at a test site?", using correlation detectors that include explosion-triggered templates. Figure Top: An eight-channel data stream (black) recorded from an earthquake near a mine. Red markers indicate a detection. Middle: The correlation statistic computed by scanning the template against the data stream at top. The red line indicates the threshold for event declaration, determined by a false-alarm on noise probability constraint, as computed from the signal-absent distribution using the Neyman Pearson criteria. Bottom: The histogram of the correlation statistic time series (gray) superimposed on the theoretical null distribution (black curve). The line shows the threshold, consistent with a right-tail probability, computed from the black curve.

From chemotherapy to signal therapy (1909-2009): A century pioneered by Paul Ehrlich.

PubMed

Maruta, H

2009-04-01

Paul Ehrlich (1854-1915), a German microbiologist who was awarded a 1908 Nobel Prize in Physiology/Medicine for his pioneer work on the antibody production, pioneered the modern chemotherapy by discovering his magic bullet for syphilis, called "606" or "Salvarsan" in 1909 with a Japanese young scientist, Sahachiro Hata (1873-1938) from "Denken" (Institute for Infectious Diseases, now called IMS for Institute for Medical Sciences) in Tokyo. His magic bullet was used to eradicate syphilis for more than a half century until a more safe and effective antibiotic called "Penicillin" was introduced to this world towards the end of WWII by Howard Florey (1898-1968). Celebrating this year the 100th anniversary of his discovery, this brief review will discuss how Ehrlich, now known as the Father of Chemotherapy, managed to design the first effective therapeutic for this then formidable sexually transmitted disease, which is equivalent to AIDS, HIV-infection, in the present century, and how so many new chemotherapeutics have been successfully developed during the past 100 years for other formidable diseases such as cancers and AIDS by his followers (microbe hunters and oncogene hunters) such as Alexander Fleming (1881-1955), Hamao Umezawa (1914-1986) and Brian Druker, culminating in the first signal therapeutics of cancers such as "Gleevec" that block the oncogenic signaling, around the turn of this century.

Complex and biofluids: From Maxwell to nowadays

NASA Astrophysics Data System (ADS)

Misbah, Chaouqi

2009-11-01

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

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.

Identification, purification and characterization of furfural transforming enzymes from Clostridium beijerinckii NCIMB 8052.

PubMed

Zhang, Yan; Ujor, Victor; Wick, Macdonald; Ezeji, Thaddeus Chukwuemeka

2015-06-01

Generation of microbial inhibitory compounds such as furfural and 5-hydroxymethylfurfural (HMF) is a formidable roadblock to fermentation of lignocellulose-derived sugars to butanol. Bioabatement offers a cost effective strategy to circumvent this challenge. Although Clostridium beijerinckii NCIMB 8052 can transform 2-3 g/L of furfural and HMF to their less toxic alcohols, higher concentrations present in biomass hydrolysates are intractable to microbial transformation. To delineate the mechanism by which C. beijerinckii detoxifies furfural and HMF, an aldo/keto reductase (AKR) and a short-chain dehydrogenase/reductase (SDR) found to be over-expressed in furfural-challenged cultures of C. beijerinckii were cloned and over-expressed in Escherichia coli Rosetta-gami™ B(DE3)pLysS, and purified by histidine tag-assisted immobilized metal affinity chromatography. Protein gel analysis showed that the molecular weights of purified AKR and SDR are close to the predicted values of 37 kDa and 27 kDa, respectively. While AKR has apparent Km and Vmax values of 32.4 mM and 254.2 mM s(-1) respectively, using furfural as substrate, SDR showed lower Km (26.4 mM) and Vmax (22.6 mM s(-1)) values on the same substrate. However, AKR showed 7.1-fold higher specific activity on furfural than SDR. Further, both AKR and SDR were found to be active on HMF, benzaldehyde, and butyraldehyde. Both enzymes require NADPH as a cofactor for aldehydes reduction. Based on these results, it is proposed that AKR and SDR are involved in the biotransformation of furfural and HMF by C. beijerinckii. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

An Efficient Workflow Environment to Support the Collaborative Development of Actionable Climate Information Using the NCAR Climate Risk Management Engine (CRMe)

NASA Astrophysics Data System (ADS)

Ammann, C. M.; Vigh, J. L.; Lee, J. A.

2016-12-01

Society's growing needs for robust and relevant climate information have fostered an explosion in tools and frameworks for processing climate projections. Many top-down workflows might be employed to generate sets of pre-computed data and plots, frequently served in a "loading-dock style" through a metadata-enabled search and discovery engine. Despite these increasing resources, the diverse needs of applications-driven projects often result in data processing workflow requirements that cannot be fully satisfied using past approaches. In parallel to the data processing challenges, the provision of climate information to users in a form that is also usable represents a formidable challenge of its own. Finally, many users do not have the time nor the desire to synthesize and distill massive volumes of climate information to find the relevant information for their particular application. All of these considerations call for new approaches to developing actionable climate information. CRMe seeks to bridge the gap between the diversity and richness of bottom-up needs of practitioners, with discrete, structured top-down workflows typically implemented for rapid delivery. Additionally, CRMe has implemented web-based data services capable of providing focused climate information in usable form for a given location, or as spatially aggregated information for entire regions or countries following the needs of users and sectors. Making climate data actionable also involves summarizing and presenting it in concise and approachable ways. CRMe is developing the concept of dashboards, co-developed with the users, to condense the key information into a quick summary of the most relevant, curated climate data for a given discipline, application, or location, while still enabling users to efficiently conduct deeper discovery into rich datasets on an as-needed basis.

Arctic sea-ice variations from time-lapse passive microwave imagery

USGS Publications Warehouse

Campbell, W.J.; Ramseier, R.O.; Zwally, H.J.; Gloersen, P.

1980-01-01

This paper presents: (1) a short historical review of the passive microwave research on sea ice which established the observational and theoretical base permitting the interpretation of the first passive microwave images of Earth obtained by the Nimbus-5 ESMR; (2) the construction of a time-lapse motion picture film of a 16-month set of serial ESMR images to aid in the formidable data analysis task; and (3) a few of the most significant findings resulting from an early analysis of these data, using selected ESMR images to illustrate these findings. ?? 1980 D. Reidel Publishing Co.

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.

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

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

Endodontic applications of 3D printing.

PubMed

Anderson, J; Wealleans, J; Ray, J

2018-02-27

Computer-aided design (CAD) and computer-aided manufacturing (CAM) technologies can leverage cone beam computed tomography data for production of objects used in surgical and nonsurgical endodontics and in educational settings. The aim of this article was to review all current applications of 3D printing in endodontics and to speculate upon future directions for research and clinical use within the specialty. A literature search of PubMed, Ovid and Scopus was conducted using the following terms: stereolithography, 3D printing, computer aided rapid prototyping, surgical guide, guided endodontic surgery, guided endodontic access, additive manufacturing, rapid prototyping, autotransplantation rapid prototyping, CAD, CAM. Inclusion criteria were articles in the English language documenting endodontic applications of 3D printing. Fifty-one articles met inclusion criteria and were utilized. The endodontic literature on 3D printing is generally limited to case reports and pre-clinical studies. Documented solutions to endodontic challenges include: guided access with pulp canal obliteration, applications in autotransplantation, pre-surgical planning and educational modelling and accurate location of osteotomy perforation sites. Acquisition of technical expertise and equipment within endodontic practices present formidable obstacles to widespread deployment within the endodontic specialty. As knowledge advances, endodontic postgraduate programmes should consider implementing 3D printing into their curriculums. Future research directions should include clinical outcomes assessments of treatments employing 3D printed objects. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Best-Matched Internal Standard Normalization in Liquid Chromatography-Mass Spectrometry Metabolomics Applied to Environmental Samples.

PubMed

Boysen, Angela K; Heal, Katherine R; Carlson, Laura T; Ingalls, Anitra E

2018-01-16

The goal of metabolomics is to measure the entire range of small organic molecules in biological samples. In liquid chromatography-mass spectrometry-based metabolomics, formidable analytical challenges remain in removing the nonbiological factors that affect chromatographic peak areas. These factors include sample matrix-induced ion suppression, chromatographic quality, and analytical drift. The combination of these factors is referred to as obscuring variation. Some metabolomics samples can exhibit intense obscuring variation due to matrix-induced ion suppression, rendering large amounts of data unreliable and difficult to interpret. Existing normalization techniques have limited applicability to these sample types. Here we present a data normalization method to minimize the effects of obscuring variation. We normalize peak areas using a batch-specific normalization process, which matches measured metabolites with isotope-labeled internal standards that behave similarly during the analysis. This method, called best-matched internal standard (B-MIS) normalization, can be applied to targeted or untargeted metabolomics data sets and yields relative concentrations. We evaluate and demonstrate the utility of B-MIS normalization using marine environmental samples and laboratory grown cultures of phytoplankton. In untargeted analyses, B-MIS normalization allowed for inclusion of mass features in downstream analyses that would have been considered unreliable without normalization due to obscuring variation. B-MIS normalization for targeted or untargeted metabolomics is freely available at https://github.com/IngallsLabUW/B-MIS-normalization .

Cobalt encapsulated N-doped defect-rich carbon nanotube as pH universal hydrogen evolution electrocatalyst

NASA Astrophysics Data System (ADS)

Zhang, Suyun; Xiao, Xinxin; Lv, Taotao; Lv, Xiaomeng; Liu, Botao; Wei, Wei; Liu, Jun

2018-07-01

Exploring efficient and economical Pt-free electrocatalysts is of great significance for the electrocatalytic hydrogen evolution reaction (HER). However, the rational design on an industrial scale is a formidable challenge. Herein, we reported a facile calcination at controlled temperatures to fabricate rationally assembled cobalt nanoparticles embedded in defect-rich N-doped carbon nanotubes (Co-NCNTs), which was derived from low-cost dicyanadiamide thermally polymerized with cobalt precursor forming metal-organic frameworks, then further calculation leading to final products. The as-obtained samples were endowed with high content of N as electrocatalytic active site, defect-rich structure and excellent synergistic effect between cobalt nanoparticles and carbon nanotubes toward electrocatalytic HER. As expected, Co-NCNTs were highly active and long-term stable with onset potentials of c.a. 15 mV in acidic electrolytes (0.5 M H2SO4), 70 mV in alkaline (1 M KOH) and 300 mV in neutral media (pH 7). Specially, to achieve the current density of 10 mA cm-2, the overpotential of 103 mV in acid, 204 mV in alkaline and 337 mV in neutral media was obtained. The enhanced HER performance was discussed in detail by adjusting the molar ratio of precursor and metal species. Moreover, the present synthetic route is easy to scale up and expand to other non-noble metal and alloy.

A Shell-Shaped Carbon Architecture with High-Loading Capability for Lithium Sulfide Cathodes

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

Chung, Sheng-Heng; Han, Pauline; Chang, Chi-Hao

We present that lithium sulfide (Li 2S) is considered a highly attractive cathode for establishing high-energy-density rechargeable batteries, especially due to its high charge-storage capacity and compatibility with lithium-metal-free anodes. Although various approaches have recently been pursued with Li 2S to obtain high performance, formidable challenges still remain with cell design (e.g., low Li 2S loading, insufficient Li 2S content, and an excess electrolyte) to realize high areal, gravimetric, and volumetric capacities. This study demonstrates a shell-shaped carbon architecture for holding pure Li 2S, offering innovation in cell-design parameters and gains in electrochemical characteristics. The Li 2S core–carbon shell electrodemore » encapsulates the redox products within the conductive shell so as to facilitate facile accessibility to electrons and ions. The fast redox-reaction kinetics enables the cells to attain the highest Li 2S loading of 8 mg cm -2 and the lowest electrolyte/Li 2S ratio of 9/1, which is the best cell-design specifications ever reported with Li 2S cathodes so far. Lastly, benefiting from the excellent cell-design criterion, the core–shell cathodes exhibit stable cyclability from slow to fast cycle rates and, for the first time, simultaneously achieve superior performance metrics with areal, gravimetric, and volumetric capacities.« less

The Utility of Inquiry-Based Exercises in Mexican Science Classrooms: Reports from a Professional Development Workshop for Science Teachers in Quintana Roo, Mexico

NASA Astrophysics Data System (ADS)

Racelis, A. E.; Brovold, A. A.

2010-12-01

The quality of science teaching is of growing importance in Mexico. Mexican students score well below the world mean in math and science. Although the government has recognized these deficiencies and has implemented new policies aimed to improve student achievement in the sciences, teachers are still encountering in-class barriers to effective teaching, especially in public colleges. This paper reports on the utility of inquiry based exercises in Mexican classrooms. In particular, it describes a two-day professional development workshop with science teachers at the Instituto Tecnologico Superior in Felipe Carrillo Puerto in the Mexican state of Quintana Roo. Felipe Carrillo Puerto is an indigenous municipality where a significant majority of the population speak Maya as their first language. This alone presents a unique barrier to teaching science in the municipality, but accompanied with other factors such as student apathy, insufficient prior training of both students and teachers, and pressure to deliver specific science curriculum, science teachers have formidable challenges for effective science teaching. The goals of the workshop were to (1) have a directed discussion regarding science as both content and process, (2) introduce inquiry based learning as one tool of teaching science, and (3) get teachers to think about how they can apply these techniques in their classes.

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

Interventions for hyperthyroidism pre-pregnancy and during pregnancy.

PubMed

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2013-11-19

Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. To identify interventions used in the management of hyperthyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). We planned to include randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antithyroid interventions for hyperthyroidism pre-pregnancy or during pregnancy with another intervention or no intervention (placebo or no treatment). Two review authors assessed trial eligibility and planned to assess trial quality and extract the data independently. No trials were included in the review. As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid interventions for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.

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.

A Shell-Shaped Carbon Architecture with High-Loading Capability for Lithium Sulfide Cathodes

DOE PAGES

Chung, Sheng-Heng; Han, Pauline; Chang, Chi-Hao; ...

2017-05-11

We present that lithium sulfide (Li 2S) is considered a highly attractive cathode for establishing high-energy-density rechargeable batteries, especially due to its high charge-storage capacity and compatibility with lithium-metal-free anodes. Although various approaches have recently been pursued with Li 2S to obtain high performance, formidable challenges still remain with cell design (e.g., low Li 2S loading, insufficient Li 2S content, and an excess electrolyte) to realize high areal, gravimetric, and volumetric capacities. This study demonstrates a shell-shaped carbon architecture for holding pure Li 2S, offering innovation in cell-design parameters and gains in electrochemical characteristics. The Li 2S core–carbon shell electrodemore » encapsulates the redox products within the conductive shell so as to facilitate facile accessibility to electrons and ions. The fast redox-reaction kinetics enables the cells to attain the highest Li 2S loading of 8 mg cm -2 and the lowest electrolyte/Li 2S ratio of 9/1, which is the best cell-design specifications ever reported with Li 2S cathodes so far. Lastly, benefiting from the excellent cell-design criterion, the core–shell cathodes exhibit stable cyclability from slow to fast cycle rates and, for the first time, simultaneously achieve superior performance metrics with areal, gravimetric, and volumetric capacities.« less

Computational Prediction of Neutralization Epitopes Targeted by Human Anti-V3 HIV Monoclonal Antibodies

PubMed Central

Shmelkov, Evgeny; Krachmarov, Chavdar; Grigoryan, Arsen V.; Pinter, Abraham; Statnikov, Alexander; Cardozo, Timothy

2014-01-01

The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design. PMID:24587168

Elemental-sensitive Detection of the Chemistry in Batteries through Soft X-ray Absorption Spectroscopy and Resonant Inelastic X-ray Scattering.

PubMed

Wu, Jinpeng; Sallis, Shawn; Qiao, Ruimin; Li, Qinghao; Zhuo, Zengqing; Dai, Kehua; Guo, Zixuan; Yang, Wanli

2018-04-17

Energy storage has become more and more a limiting factor of today's sustainable energy applications, including electric vehicles and green electric grid based on volatile solar and wind sources. The pressing demand of developing high-performance electrochemical energy storage solutions, i.e., batteries, relies on both fundamental understanding and practical developments from both the academy and industry. The formidable challenge of developing successful battery technology stems from the different requirements for different energy-storage applications. Energy density, power, stability, safety, and cost parameters all have to be balanced in batteries to meet the requirements of different applications. Therefore, multiple battery technologies based on different materials and mechanisms need to be developed and optimized. Incisive tools that could directly probe the chemical reactions in various battery materials are becoming critical to advance the field beyond its conventional trial-and-error approach. Here, we present detailed protocols for soft X-ray absorption spectroscopy (sXAS), soft X-ray emission spectroscopy (sXES), and resonant inelastic X-ray scattering (RIXS) experiments, which are inherently elemental-sensitive probes of the transition-metal 3d and anion 2p states in battery compounds. We provide the details on the experimental techniques and demonstrations revealing the key chemical states in battery materials through these soft X-ray spectroscopy techniques.

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.

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.

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.

Hydraulic tomography offers improved imaging of heterogeneity in fractured rocks

NASA Astrophysics Data System (ADS)

Illman, W. A.

2013-12-01

Fractured rocks have presented formidable challenges for accurately predicting groundwater flow and contaminant transport. This is mainly due to our difficulty in mapping the fracture-rock matrix system, their hydraulic properties and connectivity at resolutions that are meaningful for groundwater flow and especially transport modeling. Over the last several decades, considerable effort has gone into creating maps of subsurface heterogeneity in hydraulic conductivity (K) and specific storage (Ss) of fractured rocks. Developed methods include kriging, stochastic simulation, stochastic inverse modeling, and hydraulic tomography. In this presentation, I review the evolution of various heterogeneity mapping approaches and contend that hydraulic tomography, a recently developed aquifer characterization technique for unconsolidated deposits, is also a promising approach in yielding robust maps (or tomograms) of K and Ss heterogeneity for fractured rocks. While hydraulic tomography has recently been shown to be a robust technique, the resolution of the K and Ss tomograms mainly depends on the density of pumping and monitoring locations and the quality of data. The resolution will be improved through the development of new devices for higher density monitoring of pressure responses at discrete intervals in boreholes and potentially through the integration of other data from single-hole tests, borehole flowmeter profiling and tracer tests. Other data from temperature and geophysical surveys as well as geological investigations may improve the accuracy of the maps, but more research is needed. Technological advances will undoubtedly lead to more accurate maps. However, more effort should go into evaluating these maps so that one can gain more confidence in their reliability.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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

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 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

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.

Tuning structural motifs and alloying of bulk immiscible Mo-Cu bimetallic nanoparticles by gas-phase synthesis

NASA Astrophysics Data System (ADS)

Krishnan, Gopi; Verheijen, Marcel A.; Ten Brink, Gert H.; Palasantzas, George; Kooi, Bart J.

2013-05-01

Nowadays bimetallic nanoparticles (NPs) have emerged as key materials for important modern applications in nanoplasmonics, catalysis, biodiagnostics, and nanomagnetics. Consequently the control of bimetallic structural motifs with specific shapes provides increasing functionality and selectivity for related applications. However, producing bimetallic NPs with well controlled structural motifs still remains a formidable challenge. Hence, we present here a general methodology for gas phase synthesis of bimetallic NPs with distinctively different structural motifs ranging at a single particle level from a fully mixed alloy to core-shell, to onion (multi-shell), and finally to a Janus/dumbbell, with the same overall particle composition. These concepts are illustrated for Mo-Cu NPs, where the precise control of the bimetallic NPs with various degrees of chemical ordering, including different shapes from spherical to cube, is achieved by tailoring the energy and thermal environment that the NPs experience during their production. The initial state of NP growth, either in the liquid or in the solid state phase, has important implications for the different structural motifs and shapes of synthesized NPs. Finally we demonstrate that we are able to tune the alloying regime, for the otherwise bulk immiscible Mo-Cu, by achieving an increase of the critical size, below which alloying occurs, closely up to an order of magnitude. It is discovered that the critical size of the NP alloy is not only affected by controlled tuning of the alloying temperature but also by the particle shape.Nowadays bimetallic nanoparticles (NPs) have emerged as key materials for important modern applications in nanoplasmonics, catalysis, biodiagnostics, and nanomagnetics. Consequently the control of bimetallic structural motifs with specific shapes provides increasing functionality and selectivity for related applications. However, producing bimetallic NPs with well controlled structural motifs still remains a formidable challenge. Hence, we present here a general methodology for gas phase synthesis of bimetallic NPs with distinctively different structural motifs ranging at a single particle level from a fully mixed alloy to core-shell, to onion (multi-shell), and finally to a Janus/dumbbell, with the same overall particle composition. These concepts are illustrated for Mo-Cu NPs, where the precise control of the bimetallic NPs with various degrees of chemical ordering, including different shapes from spherical to cube, is achieved by tailoring the energy and thermal environment that the NPs experience during their production. The initial state of NP growth, either in the liquid or in the solid state phase, has important implications for the different structural motifs and shapes of synthesized NPs. Finally we demonstrate that we are able to tune the alloying regime, for the otherwise bulk immiscible Mo-Cu, by achieving an increase of the critical size, below which alloying occurs, closely up to an order of magnitude. It is discovered that the critical size of the NP alloy is not only affected by controlled tuning of the alloying temperature but also by the particle shape. Electronic supplementary information (ESI) available: Experimental details including schematics of the gas phase synthesis set up, target arrangement, synthesis condition for various structures, and TEM images of alloy, core-shell and Mo-Cu-Mo onion nanoparticles. See DOI: 10.1039/c3nr00565h

Einstein’s Legacy to Astronomy: From Black Holes to the Expanding Universe

NASA Astrophysics Data System (ADS)

Bartusiak, Marcia

2006-12-01

Albert Einstein placed a formidable imprint on astronomy. Not since the time of Isaac Newton, three centuries ago, has a single individual so influenced the field. Many of the great astronomical findings of the 20th century--the expanding universe, compact stars, origin of the Sun’s power, black holes, gravitational lensing, dark energy, gravity waves--are rooted in the physics that Einstein so brilliantly deduced. This illustrated presentation, the Gemant Award Lecture sponsored by the American Institute of Physics, will provide a guided tour through the cosmos and explain how our understanding of the universe was transformed by Einstein’s theories of special and general relativity.

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.

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.

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

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

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.

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

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.

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...

Informing Decisions with a Climate Synthesis Product: Implications for Regional Climate Services

NASA Astrophysics Data System (ADS)

Guido, Z.; Hill, D.; Crimmins, M.; Ferguson, D. B.

2012-12-01

The demand for regional climate information is increasing and spurring efforts to provide a broad slate of climate services that inform policy and resource management and elevate general knowledge. Routine syntheses of existing climate-related information may be an effective strategy for connecting climate information to decision making, but few studies have formally assessed their contribution to informing decisions. During the 2010-2011 winter, drought conditions expanded and intensified in Arizona and New Mexico, creating an opportunity to develop and evaluate a pithy, monthly regional climate communication product—La Niña Drought Tracker—that synthesized and interpreted drought and climate information. Six issues were published and subsequently evaluated through an online survey. On average, 417 people consulted the publication each month. Many of the survey respondents indicated that they made at least one drought-related decision, and the product at least moderately influenced the majority of those decisions, some of which helped mitigate economic losses and reduce climate vulnerability. The product also improved understanding of climate and drought for more than 90 percent of the respondents and helped the majority of them better prepare for drought. These, and other results demonstrate that routine interpretation and synthesis of existing climate information can help enhance access to and understanding and use of climate information in decision-making. Moreover, developing regional, contextual knowledge within climate service programs can facilitate the implementation of activities like the Tracker that enhance the use of climate information without engaging in time-consuming collaborative processes that can prevent the timely production of the services. We present results from the case study of the Tracker and place it within the context of the challenges and opportunities associated with providing climate services, particularly those services that require several-to-many months of work but often do not generate substantial financial sponsorship. These medium-term climate services, like the Tracker, present formidable challenges. However, we argue, they are vital to satisfying stakeholder demand, creating new and strengthening existing partnerships, aiding decisions, advancing climate literacy, and fostering future projects—main goals of climate services.

Efficacy of endoscopic management of leak after foregut surgery with endoscopic covered self-expanding metal stents (SEMS).

PubMed

Aryaie, Amir H; Singer, Jordan L; Fayezizadeh, Mojtaba; Lash, Jon; Marks, Jeffrey M

2017-02-01

Anastomotic or staple-line leak after foregut surgery presents a formidable management challenge. In recent years, with advancement of endoscopy, self-expanding covered stents have been gaining popularity. In this study, we aimed to determine the safety and effectiveness of self-expanding covered stents in management of leak after foregut surgery. Consecutive patients who received a fully covered self-expandable metal stent (SEMS) due to an anastomotic leak after upper gastrointestinal surgery between 2009 and 2014 were retrospectively reviewed. Demographic data, stent placement and removal, clinical success, time to resolution, and complications were collected. Predictive factors for clinical success rate were assessed. A total of 20 consecutive patients underwent placement of fully covered SEMS for anastomotic leak, following esophagectomy (n = 5), esophageal diverticulectomy (n = 1), gastric sleeve (n = 4), gastric bypass (n = 3), partial gastrectomy (n = 4), and total gastrectomy (n = 3). All the stents were removed successfully, and clinical resolution was achieved in 18 patients (90 %) after a median of two (range 1-3) procedures and a mean of 6.2 weeks (range 0.4-14). Complications presented in 12 patients (60 %), including stent migration (n = 8), mucosal friability (n = 4), tissue integration (n = 2), and bleeding (n = 2). Two (10 %) patients' treatment was complicated by aorto-esophageal fistula formation resulting in one death. Demographic factors, comorbidities, and type of surgery were not predictive of clinical success rate or time to resolution. SEMS are effective tools for the management of leaks after foregut surgery. The biggest challenge with this approach is stent migration. Caution is warranted due to the risk of fatal complications such as aorto-esophageal fistula formation. No type of surgery or particular patient factor, including age, sex, BMI, albumin, history of radiation, malignancy, and comorbid diabetes or coronary artery disease, appeared to be correlated with success rate. Larger studies are needed to determine factors predictive of clinical success.

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

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

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.

Sorting through the chaff, nDNA gene trees for phylogenetic inference and hybrid identification of annual sunflowers (Helianthus sect. Helianthus).

PubMed

Moody, Michael L; Rieseberg, Loren H

2012-07-01

The annual sunflowers (Helianthus sect. Helianthus) present a formidable challenge for phylogenetic inference because of ancient hybrid speciation, recent introgression, and suspected issues with deep coalescence. Here we analyze sequence data from 11 nuclear DNA (nDNA) genes for multiple genotypes of species within the section to (1) reconstruct the phylogeny of this group, (2) explore the utility of nDNA gene trees for detecting hybrid speciation and introgression; and (3) test an empirical method of hybrid identification based on the phylogenetic congruence of nDNA gene trees from tightly linked genes. We uncovered considerable topological heterogeneity among gene trees with or without three previously identified hybrid species included in the analyses, as well as a general lack of reciprocal monophyly of species. Nonetheless, partitioned Bayesian analyses provided strong support for the reciprocal monophyly of all species except H. annuus (0.89 PP), the most widespread and abundant annual sunflower. Previous hypotheses of relationships among taxa were generally strongly supported (1.0 PP), except among taxa typically associated with H. annuus, apparently due to the paraphyly of the latter in all gene trees. While the individual nDNA gene trees provided a useful means for detecting recent hybridization, identification of ancient hybridization was problematic for all ancient hybrid species, even when linkage was considered. We discuss biological factors that affect the efficacy of phylogenetic methods for hybrid identification.

Herbivorous ecomorphology and specialization patterns in theropod dinosaur evolution.

PubMed

Zanno, Lindsay E; Makovicky, Peter J

2011-01-04

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

Herbivorous ecomorphology and specialization patterns in theropod dinosaur evolution

PubMed Central

Zanno, Lindsay E.; Makovicky, Peter J.

2011-01-01

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

Towards development of an operational snow on sea ice product

NASA Astrophysics Data System (ADS)

Stroeve, J.; Liston, G. E.; Barrett, A. P.; Tschudi, M. A.; Stewart, S.

2017-12-01

Sea ice has been visibly changing over the past couple of decades; most notably the annual minimum extent which has shown a distinct downward, and recently accelerating, trend. September mean sea ice extent was over 7×106 km2 in the 1980's, but has averaged less than 5×106 km2 in the last decade. Should this loss continue, there will be wide-ranging impacts on marine ecosystems, coastal communities, prospects for resource extraction and marine activity, and weather conditions in the Arctic and beyond. While changes in the spatial extent of sea ice have been routinely monitored since the 1970s, less is known about how the thickness of the ice cover has changed. While estimates of ice thickness across the Arctic Ocean have become available over the past 20 years based on data from ERS-1/2, Envisat, ICESat, CryoSat-2 satellites and Operation IceBridge aircraft campaigns, the variety of these different measurement approaches, sensor technologies and spatial coverage present formidable challenges. Key among these is that measurement techniques do not measure ice thickness directly - retrievals also require snow depth and density. Towards that end, a sophisticated snow accumulation model is tested in a Lagrangian framework to map daily snow depths across the Arctic sea ice cover using atmospheric reanalysis data as input. Accuracy of the snow accumulation is assessed through comparison with Operation IceBridge data and ice mass balance buoys (IMBs). Impacts on ice thickness retrievals are further discussed.

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

PubMed

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

2015-04-21

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

Climate change, renewable energy and population impact on future energy demand for Burkina Faso build environment

NASA Astrophysics Data System (ADS)

Ouedraogo, B. I.

This research addresses the dual challenge faced by Burkina Faso engineers to design sustainable low-energy cost public buildings and domestic dwellings while still providing the required thermal comfort under warmer temperature conditions caused by climate change. It was found base don climate change SRES scenario A2 that predicted mean temperature in Burkina Faso will increase by 2oC between 2010 and 2050. Therefore, in order to maintain a thermally comfortable 25oC inside public buildings, the projected annual energy consumption for cooling load will increase by 15%, 36% and 100% respectively for the period between 2020 to 2039, 2040 to 2059 and 2070 to 2089 when compared to the control case. It has also been found that a 1% increase in population growth will result in a 1.38% and 2.03% increase in carbon emission from primary energy consumption and future electricity consumption respectively. Furthermore, this research has investigated possible solutions for adaptation to the severe climate change and population growth impact on energy demand in Burkina Faso. Shading devices could potentially reduce the cooling load by up to 40%. Computer simulation programming of building energy consumption and a field study has shown that adobe houses have the potential of significantly reducing energy demand for cooling and offer a formidable method for climate change adaptation. Based on the Net Present Cost, hybrid photovoltaic (PV) and Diesel generator energy production configuration is the most cost effective local electricity supply system, for areas without electricity at present, with a payback time of 8 years when compared to diesel generator stand-alone configuration. It is therefore a viable solution to increase electricity access to the majority of the population.

Dental prosthetic status and prosthetic needs of institutionalised elderly population in oldage homes of jabalpur city, madhya pradesh, India.

PubMed

Deogade, Suryakant C; Vinay, S; Naidu, Sonal

2013-12-01

Oral disorders are cumulative throughout life and hence unfavourable outcomes are likely to be greatest among the elderly. A descriptive cross-sectional study was conducted among institutionalized geriatric population in old-age homes of Jabalpur city, Madhya Pradesh, to assess their prosthetic status and prosthetic needs. A cross-sectional survey was conducted in all the four old-age homes of Jabalpur city, Madhya Pradesh state, India. All residents aged 60 years and above formed the study population. The recording of prosthetic status and prosthetic needs was carried out according to the World Health Organisation (WHO) Oral Health Assessment Form (1997). A total of 224 individuals were included in the study of which 123 were females and 101 were males. Seventy five percent of the females and 55 % of the males had no prostheses in their upper arch and 61 % of the females and 76 % of the males had no prostheses in their lower arch. More number of males presented with 'Bridges' in their upper arch when compared to females (P value = 0.006). Highest prosthetic need in males was multi-unit prosthesis (42 % in upper arch and 41 % in lower arch) whereas, females' required full prosthesis (39 % in both the upper arch and lower arches). Ageing presents some formidable challenges, particularly with the institutionalised. This study clearly demonstrates a high insufficiency of prosthetic care among the institutionalized elderly population. Any preparation towards the provision of oral health care should not be limited to treatment alone but, more importantly focus on empowering this elderly community with information and education programmes.

Properties of crosslinked ultra-high-molecular-weight polyethylene.

PubMed

Lewis, G

2001-02-01

Substantially reducing the rate of generation of wear particles at the surfaces of ultra-high-molecular-weight polyethylene (UHMWPE) orthopedic implant bearing components, in vivo, is widely regarded as one of the most formidable challenges in modern arthroplasty. In the light of this, much research attention has been paid to the myriad of endogenous and exogenous factors that have been postulated to affect this wear rate, one such factor being the polymer itself. In recent years, there has been a resurgence of interest in crosslinking the polymer as a way of improving its properties that are considered relevant to its use for fabricating bearing components. Such properties include wear resistance, fatigue life, and fatigue crack propagation rate. Although a large volume of literature exists on the topic on the impact of crosslinking on the properties of UHMWPE, no critical appraisal of this literature has been published. This is one of the goals of the present article, which emphasizes three aspects. The first is the trade-off between improvement in wear resistance and depreciation in other mechanical and physical properties. The second aspect is the presentation of a method of estimating the optimal value of a crosslinking process variable (such as dose in radiation-induced crosslinking) that takes into account this trade-off. The third aspect is the description of a collection of under- and unexplored research areas in the field of crosslinked UHMWPE, such as the role of starting resin on the properties of the crosslinked polymer, and the in vitro evaluation of the wear rate of crosslinked tibial inserts and other bearing components that, in vivo, are subjected to nearly unidirectional motion.

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.

Character and Moral Education: A Reader

ERIC Educational Resources Information Center

DeVitis, Joseph L., Ed.; Yu, Tianlong, Ed.

2011-01-01

Against a formidable national discourse that emphasizes academic standardization, accountability, and high-stakes testing in educational policy, "Character and Moral Education: A Reader" seeks to re-introduce and revive the moral mission of education in public conversation and practices in America's schools. With contributions from a…

How Do We Match Instructional Effectiveness with Learning Curves?

ERIC Educational Resources Information Center

Branum-Martin, Lee; Mehta, Paras D.; Taylor, W. Patrick; Carlson, Coleen D.; Lei, Xiaoxuan; Hunter, C. Vincent; Francis, David J.

2015-01-01

In order to examine the effectiveness of instruction, the authors confront formidable statistical problems, including multivariate structure of classroom observations, longitudinal dependence of both classroom observations and student outcomes. As the authors begin to examine instruction, classroom observations involve multiple variables for which…

The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration

PubMed Central

2013-01-01

Most neurons are born with the potential to live for the entire lifespan of the organism. In addition, neurons are highly polarized cells with often long axons, extensively branched dendritic trees and many synaptic contacts. Longevity together with morphological complexity results in a formidable challenge to maintain synapses healthy and functional. This challenge is often evoked to explain adult-onset degeneration in numerous neurodegenerative disorders that result from otherwise divergent causes. However, comparably little is known about the basic cell biological mechanisms that keep normal synapses alive and functional in the first place. How the basic maintenance mechanisms are related to slow adult-onset degeneration in different diseasesis largely unclear. In this review we focus on two basic and interconnected cell biological mechanisms that are required for synaptic maintenance: endomembrane recycling and calcium (Ca2+) homeostasis. We propose that subtle defects in these homeostatic processes can lead to late onset synaptic degeneration. Moreover, the same basic mechanisms are hijacked, impaired or overstimulated in numerous neurodegenerative disorders. Understanding the pathogenesis of these disorders requires an understanding of both the initial cause of the disease and the on-going changes in basic maintenance mechanisms. Here we discuss the mechanisms that keep synapses functional over long periods of time with the emphasis on their role in slow adult-onset neurodegeneration. PMID:23829673

Future Directions in the Design, Development, and Investigation of Technology as a Service Delivery Vehicle

PubMed Central

Jones, Deborah J.

2013-01-01

Treatment outcome research with children and adolescents has progressed to such an extent that numerous handbooks have been devoted to reviewing and summarizing the evidence base. Ensuring that consumers of these advancements in state-of-the-field interventions have the opportunity to access, engage in, and benefit from this evidence-base, however, has been wrought with challenge. As such, much discussion exists about innovative strategies for overcoming the gap between research and practice; yet, no other potential solution that has received more attention in both the popular and academic press than technology. The promise of technology is not surprising given the fast-paced evolution in development and, in turn, a seemingly endless range of possibilities for novel service delivery platforms. Yet, this is precisely the most formidable challenge threatening to upset the very promise of this potential solution: The rate of emerging technologies is far outpacing the field’s capacity to demonstrate the conceptual or empirical benefits of such an approach. Accordingly, this paper aims to provide a series of recommendations that better situate empirical enquiry at the core of a collaborative development, testing, and deployment process that must define this line of work if the promise of mental health technologies is going to be a reality for front-line clinicians and the clients they serve. PMID:24400723

Formulation of medicines for children

PubMed Central

Nunn, Tony; Williams, Julie

2005-01-01

The development of age-adapted dosage forms and taste-masking of bitter-tasting drugs administered orally for children, are formidable challenges for formulation scientists. Childhood is a period of maturation requiring knowledge of developmental pharmacology to establish dose but the ability of the child to manage different dosage forms and devices also changes. Paediatric formulations must allow accurate administration of the dose to children of widely varying age and weight. Whilst the oral route will be preferred for long term use and the intravenous route for the acutely ill, many of the dosage forms designed for adults, such as oro-dispersible tablets, buccal gels and transdermal patches, would also benefit children if they contained an appropriate paediatric dose. The age at which children can swallow conventional tablets is of great importance for their safety. Liquid medicines are usually recommended for infants and younger dhildren so the ability to mask unpleasant taste with sweeteners and flavours is crucial. More sophisticated formulations such as granules and oro-dispersible tablets may be required but there will be limitations on choice and concentration of excipients. There are many gaps in our knowledge about paediatric formulations and many challenges for the industry if suitable preparations are to be available for all ranges. A CHMP points to consider document is soon to be released. More research and clinical feedback are important because a formulation with poor acceptability may affect compliance, prescribing practice and ultimately commercial viability. PMID:15948931

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.

Primordial prevention of cardiovascular disease among African-Americans: a social epidemiological perspective.

PubMed

James, S A

1999-12-01

The primordial prevention of cardiovascular disease (CVD) among African-Americans represents a formidable challenge for public health. This paper discusses the nature of this challenge, highlighting the role that economic and cultural factors play in shaping the distributions of major CVD risk factors among African-Americans. The paper concludes with specific suggestions for research. Data from recent national health surveys on black/white differences in major CVD risk factors like hypertension, obesity, cholesterol, cigarette smoking, and physical inactivity were reviewed for the purpose of identifying promising avenues for primordial prevention research among African-Americans. Cigarette smoking has a delayed onset among African-Americans compared to whites. Black/white differences in "vigorous" leisure-time physical activity (e.g., social dancing and team sports) are not apparent until around age 40. These findings have relevance for primordial prevention work in black communities since they suggest the existence of broad-based, health-relevant cultural norms which could support primordial prevention programs, such as regular physical activity, across the life cycle. CVD primordial prevention programs among African-Americans must be grounded in an understanding of how cultural values as well as economic conditions shape CVD risk factor distributions in this population. Ultimate success will depend on the strength of the partnerships that public health researchers, primary care providers, and community residents are able to build.

Extensively Drug-resistant Tuberculosis (XDR-TB): A daunting challenge to the current End TB Strategy and policy recommendations.

PubMed

Rahman, Md Arifur; Sarkar, Atanu

2017-07-01

Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Salvus: A scalable software suite for full-waveform modelling & inversion

NASA Astrophysics Data System (ADS)

Afanasiev, M.; Boehm, C.; van Driel, M.; Krischer, L.; Fichtner, A.

2017-12-01

Full-waveform inversion (FWI), whether at the lab, exploration, or planetary scale, requires the cooperation of five principal components. (1) The geometry of the domain needs to be properly discretized and an initial guess of the model parameters must be projected onto it; (2) Large volumes of recorded waveform data must be collected, organized, and processed; (3) Synthetic waveform data must be efficiently and accurately computed through complex domains; (4) Suitable misfit functions and optimization techniques must be used to relate discrepancies in data space to perturbations in the model; and (5) Some form of workflow management must be employed to schedule and run (1) - (4) in the correct order. Each one of these components can represent a formidable technical challenge which redirects energy from the true task at hand: using FWI to extract new information about some underlying continuum.In this presentation we give an overview of the current status of the Salvus software suite, which was introduced to address the challenges listed above. Specifically, we touch on (1) salvus_mesher, which eases the discretization of complex Earth models into hexahedral meshes; (2) salvus_seismo, which integrates with LASIF and ObsPy to streamline the processing and preparation of seismic data; (3) salvus_wave, a high-performance and scalable spectral-element solver capable of simulating waveforms through general unstructured 2- and 3-D domains, and (4) salvus_opt, an optimization toolbox specifically designed for full-waveform inverse problems. Tying everything together, we also discuss (5) salvus_flow: a workflow package designed to orchestrate and manage the rest of the suite. It is our hope that these developments represent a step towards the automation of large-scale seismic waveform inversion, while also lowering the barrier of entry for new applications. We include several examples of Salvus' use in (extra-) planetary seismology, non-destructive testing, and medical imaging.

Interactive Effects of Cognitive Representations of Formidability and Technology on Aggression

DTIC Science & Technology

2014-09-08

defensive technologies; their fighting skill ; the number and proximity of their allies; the quality of their leadership; their degree of unit...since the last review) 1. Gneezy, A. and Fessler, D.M.T. (2011) Conflict, sticks, and carrots: War increases prosocial punishments and rewards

Deposition of aerosol particles in human lungs: in vivo measurements and modeling

EPA Science Inventory

The deposition dose and site of inhaled particles within the lung are the key determinants in health risk assessment of particulate pollutants. Accurate dose estimation, however, is a formidable task because aerosol transport and deposition in the lung are governed by many factor...

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

PubMed

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

2016-10-01

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

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

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

DOE PAGES

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

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 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

Tessera: Open source software for accelerated data science

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

Sego, Landon H.; Hafen, Ryan P.; Director, Hannah M.

2014-06-30

Extracting useful, actionable information from data can be a formidable challenge for the safeguards, nonproliferation, and arms control verification communities. Data scientists are often on the “front-lines” of making sense of complex and large datasets. They require flexible tools that make it easy to rapidly reformat large datasets, interactively explore and visualize data, develop statistical algorithms, and validate their approaches—and they need to perform these activities with minimal lines of code. Existing commercial software solutions often lack extensibility and the flexibility required to address the nuances of the demanding and dynamic environments where data scientists work. To address this need,more » Pacific Northwest National Laboratory developed Tessera, an open source software suite designed to enable data scientists to interactively perform their craft at the terabyte scale. Tessera automatically manages the complicated tasks of distributed storage and computation, empowering data scientists to do what they do best: tackling critical research and mission objectives by deriving insight from data. We illustrate the use of Tessera with an example analysis of computer network data.« less

Withaferin-A—A Natural Anticancer Agent with Pleitropic Mechanisms of Action

PubMed Central

Lee, In-Chul; Choi, Bu Young

2016-01-01

Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A. PMID:26959007

Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action.

PubMed

Lee, In-Chul; Choi, Bu Young

2016-03-04

Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A.

Beyond Peaceful Coexistence: The Emergence of Space, Time and Quantum

NASA Astrophysics Data System (ADS)

Licata, Ignazio

A physical theory consists of a formal structure and one or more interpretations. The latter can come out from cultural and cognitive tension going far beyond any sound operational pact between theoretical constructs and empirical data. We have no reason to doubt about the consistency and efficacy of syntaxes if properly used in the right range. The formal side of Physics has grown in a strongly connected and stratified way through an almost autopoietic, self-dual procedure (let's think of the extraordinary success of the gauge theories), whereas the foundational debate is still blustering about the two pillars of such monumental construction. The general relativity (GR) and the quantum mechanics (QM), which still appear to be greatly incompatible and stopped in a limited peaceful coexistence between local causality in space-time and quantum non-locality [1]. The formidable challenges waiting for us beyond the Standard Model seem to require a new semantic consistency [2] within the two theories, so as to build a new way to look at them, to work and to relate them...

A Mixed-Method Study on Correlates of HIV-Related Stigma Among Gay and Bisexual Men in the Southern United States.

PubMed

Berg, Rigmor C; Carter, Dakota; Ross, Michael W

Societal prejudice against people living with HIV infection is a formidable public health challenge that can negatively impact health and well-being. We recruited a multiethnic sample of 129 gay and bisexual men living with HIV who completed a brief survey; a subset of participants completed semi-structured qualitative interviews to contextualize the data. In bivariate analyses, stigma was positively and significantly correlated with depression (r = .402, p < .001) and negatively correlated with social support (r = -.482, p < .001). Qualitative interview results captured the mental suffering caused by stigma and coping strategies the men had developed. Although some of the coping strategies reduced the likelihood of experiencing acts of stigmatization, they also exacerbated the psychological stress of living with a stigmatized disease and limited the potential for social support. Our results highlight the need to scale up stigma-reduction programs, particularly those that can bolster social support networks. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

PubMed Central

Feng, Pengju; Ngai, Ming-Yu

2016-01-01

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 °C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials. PMID:26862864

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.

Cost effective malaria risk control using remote sensing and environmental data

NASA Astrophysics Data System (ADS)

Rahman, Md. Z.; Roytman, Leonid; Kadik, Abdel Hamid

2012-06-01

Malaria transmission in many part of the world specifically in Bangladesh and southern African countries is unstable and epidemic. An estimate of over a million cases is reported annually. Malaria is heterogeneous, potentially due to variations in ecological settings, socio-economic status, land cover, and agricultural practices. Malaria control only relies on treatment and supply of bed networks. Drug resistance to these diseases is widespread. Vector control is minimal. Malaria control in those countries faces many formidable challenges such as inadequate accessibility to effective treatment, lack of trained manpower, inaccessibility of endemic areas, poverty, lack of education, poor health infrastructure and low health budgets. Health facilities for malaria management are limited, surveillance is inadequate, and vector control is insufficient. Control can only be successful if the right methods are used at the right time in the right place. This paper aims to improve malaria control by developing malaria risk maps and risk models using satellite remote sensing data by identifying, assessing, and mapping determinants of malaria associated with environmental, socio-economic, malaria control, and agricultural factors.

Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

PubMed Central

Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

2013-01-01

Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

Resilient parenting of children at developmental risk across middle childhood.

PubMed

Ellingsen, Ruth; Baker, Bruce L; Blacher, Jan; Crnic, Keith

2014-06-01

This paper focuses on factors that might influence positive parenting during middle childhood when a parent faces formidable challenges defined herein as "resilient parenting." Data were obtained from 162 families at child age 5 and 8 years. Using an adapted ABCX model, we examined three risk domains (child developmental delay, child ADHD/ODD diagnosis, and low family income) and three protective factors (mother's education, health, and optimism). The outcome of interest was positive parenting as coded from mother-child interactions. We hypothesized that each of the risk factors would predict poorer parenting and that higher levels of each protective factor would buffer the risk-parenting relationship. Positive parenting scores decreased across levels of increasing risk. Maternal optimism appeared to be a protective factor for resilient parenting concurrently at age 5 and predictively to age 8, as well as a predictor of positive change in parenting from age 5 to age 8, above and beyond level of risk. Maternal education and health were not significantly protective for positive parenting. Limitations, future directions, and implications for intervention are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resilient Parenting of Children at Developmental Risk Across Middle Childhood

PubMed Central

Baker, Bruce L.; Blacher, Jan; Crnic, Keith

2015-01-01

This paper focuses on factors that might influence positive parenting during middle childhood when a parent faces formidable challenges defined herein as “resilient parenting.” Data were obtained from 162 families at child age 5 and 8 years. Using an adapted ABCX model, we examined three risk domains (child developmental delay, child ADHD/ODD diagnosis, and low family income) and three protective factors (mother’s education, health, and optimism). The outcome of interest was positive parenting as coded from mother-child interactions. We hypothesized that each of the risk factors would predict poorer parenting and that higher levels of each protective factor would buffer the risk-parenting relationship. Positive parenting scores decreased across levels of increasing risk. Maternal optimism appeared to be a protective factor for resilient parenting concurrently at age 5 and predictively to age 8, as well as a predictor of positive change in parenting from age 5 to age 8, above and beyond level of risk. Maternal education and health were not significantly protective for positive parenting. Limitations, future directions, and implications for intervention are discussed. PMID:24713516

Probabilistic models of eukaryotic evolution: time for integration

PubMed Central

Lartillot, Nicolas

2015-01-01

In spite of substantial work and recent progress, a global and fully resolved picture of the macroevolutionary history of eukaryotes is still under construction. This concerns not only the phylogenetic relations among major groups, but also the general characteristics of the underlying macroevolutionary processes, including the patterns of gene family evolution associated with endosymbioses, as well as their impact on the sequence evolutionary process. All these questions raise formidable methodological challenges, calling for a more powerful statistical paradigm. In this direction, model-based probabilistic approaches have played an increasingly important role. In particular, improved models of sequence evolution accounting for heterogeneities across sites and across lineages have led to significant, although insufficient, improvement in phylogenetic accuracy. More recently, one main trend has been to move away from simple parametric models and stepwise approaches, towards integrative models explicitly considering the intricate interplay between multiple levels of macroevolutionary processes. Such integrative models are in their infancy, and their application to the phylogeny of eukaryotes still requires substantial improvement of the underlying models, as well as additional computational developments. PMID:26323768

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.

Knowledge About HIV/AIDS Among Secondary School Students.

PubMed

Gupta, Pratibha; Anjum, Fatima; Bhardwaj, Pankaj; Srivastav, Jp; Zaidi, Zeashan Haider

2013-02-01

HIV/AIDS has emerged as the single most formidable challenge to public health. School children of today are exposed to the risk of HIV/AIDS. The study was conducted to determine the knowledge among secondary school students regarding HIV/AIDS and provide suggestions for HIV/AIDS education in schools. A cross-sectional study was conducted among students of tenth to twelfth standard in the intermediate schools of Lucknow, India, from July to October 2011. A total of 215 students, both boys and girls, were enrolled in the study. In this study, for majority of the students (85%), the source of information about HIV/AIDS was the television. Regarding knowledge about modes of transmission of HIV/AIDS among girl students, 95.1% of them told that it is through unprotected sex. A total of 75.8% students said that it was transmitted from mother to child. It was observed that the knowledge of the school students was quite satisfactory for most of the variables like modes of transmission, including mother-to-child transmission of the disease. However, schools should come forward to design awareness campaigns for the benefit of the students.

Conceptual Development of a National Volcanic Hazard Model for New Zealand

NASA Astrophysics Data System (ADS)

Stirling, Mark; Bebbington, Mark; Brenna, Marco; Cronin, Shane; Christophersen, Annemarie; Deligne, Natalia; Hurst, Tony; Jolly, Art; Jolly, Gill; Kennedy, Ben; Kereszturi, Gabor; Lindsay, Jan; Neall, Vince; Procter, Jonathan; Rhoades, David; Scott, Brad; Shane, Phil; Smith, Ian; Smith, Richard; Wang, Ting; White, James D. L.; Wilson, Colin J. N.; Wilson, Tom

2017-06-01

We provide a synthesis of a workshop held in February 2016 to define the goals, challenges and next steps for developing a national probabilistic volcanic hazard model for New Zealand. The workshop involved volcanologists, statisticians, and hazards scientists from GNS Science, Massey University, University of Otago, Victoria University of Wellington, University of Auckland, and University of Canterbury. We also outline key activities that will develop the model components, define procedures for periodic update of the model, and effectively articulate the model to end-users and stakeholders. The development of a National Volcanic Hazard Model is a formidable task that will require long-term stability in terms of team effort, collaboration and resources. Development of the model in stages or editions that are modular will make the process a manageable one that progressively incorporates additional volcanic hazards over time, and additional functionalities (e.g. short-term forecasting). The first edition is likely to be limited to updating and incorporating existing ashfall hazard models, with the other hazards associated with lahar, pyroclastic density currents, lava flow, ballistics, debris avalanche, and gases/aerosols being considered in subsequent updates.

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

PubMed Central

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

2015-01-01

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. DOI: http://dx.doi.org/10.7554/eLife.09960.001 PMID:26402459

Controlling Tensegrity Robots Through Evolution

NASA Technical Reports Server (NTRS)

Iscen, Atil; Agogino, Adrian; SunSpiral, Vytas; Tumer, Kagan

2013-01-01

Tensegrity structures (built from interconnected rods and cables) have the potential to offer a revolutionary new robotic design that is light-weight, energy-efficient, robust to failures, capable of unique modes of locomotion, impact tolerant, and compliant (reducing damage between the robot and its environment). Unfortunately robots built from tensegrity structures are difficult to control with traditional methods due to their oscillatory nature, nonlinear coupling between components and overall complexity. Fortunately this formidable control challenge can be overcome through the use of evolutionary algorithms. In this paper we show that evolutionary algorithms can be used to efficiently control a ball-shaped tensegrity robot. Experimental results performed with a variety of evolutionary algorithms in a detailed soft-body physics simulator show that a centralized evolutionary algorithm performs 400 percent better than a hand-coded solution, while the multi-agent evolution performs 800 percent better. In addition, evolution is able to discover diverse control solutions (both crawling and rolling) that are robust against structural failures and can be adapted to a wide range of energy and actuation constraints. These successful controls will form the basis for building high-performance tensegrity robots in the near future.

Stigma, American military personnel and mental health care: challenges from Iraq and Afghanistan.

PubMed

Schreiber, Michael; McEnany, Geoffry Phillips

2015-02-01

Since 2001, more than 2.5 million United States military personnel have been deployed for combat. Over one million have served multiple deployments. Combat generally involved repeated exposure to highly traumatic events. Personnel were also victims of military sexual trauma (MST), a major risk factor for psychiatric illness. Most survivors do not seek or receive mental health care. Stigma is one of the main barriers to that care. To explore the impact of stigma on personnel with psychiatric illness, and suggest some innovative ways to potentially reduce stigma and improve care. Cinahl and PubMed databases were searched from 2001 to 2014. Anonymity, the use of non-stigmatizing language, peer-to-peer, and stigma-reduction programs help military personnel receive mental health care. Technology offers the opportunity for effective and appropriate education and treatment. Although stigma is formidable, several innovative services are available or being developed for military victims of trauma. Commitment of resources for program development and further research to explore which interventions offer the best clinical outcomes are needed to increase efforts to combat stigma and ensure quality care.

Group cohesion and nurse satisfaction: examination of a team-building approach.

PubMed

DiMeglio, Karen; Padula, Cynthia; Piatek, Carolyn; Korber, Susan; Barrett, Ann; Ducharme, Maria; Lucas, Sandra; Piermont, Nicole; Joyal, Elaine; DeNicola, Virginia; Corry, Karen

2005-03-01

The purpose of this study was to determine the impact of a team-building intervention on group cohesion, nurse satisfaction, and turnover rates. Creating an environment that supports and retains nurses represents a formidable challenge for nursing leaders. Research related to strategies that positively impact the culture in which nurses practice, thus potentially improving nurse satisfaction and reducing turnover, is critically needed. Registered nurses (RNs) employed on inpatient units in a 247-bed, private acute care Magnet teaching hospital participated in this quasi experimental preintervention and postintervention design. The RN-RN interaction subscale from the National Database of Nursing Quality Indicators Adapted Index of Work Satisfaction, the National Database of Nursing Quality Indicators Adapted Index of Job Enjoyment, the Group Cohesion Scale, and a facilitator-developed measure were completed preimplementation and postimplementation of unit-tailored intervention strategies, which took place over a 12-month period. Turnover rates were collected 6 month preintervention and postintervention. Improvement in group cohesion, RN-RN interaction, job enjoyment, and turnover was demonstrated. Targeted, unit-based strategies can be an effective means of reducing turnover rates and improving group cohesion and nurse satisfaction.