Some Problems and Insights in the Lexicography of Two Non-Kindred Languages: Spanish and Swahili.

ERIC Educational Resources Information Center

Githiora, Chege

2001-01-01

Discusses problems and insights gained during the preparation of a bilingual dictionary of Spanish--a Romance and ultimately Indo-European language--and Swahili, a coastal Bantu language of the Niger-Congo stock of African languages. (Author/VWL)

Cortical Evolution: Judge the Brain by Its Cover

PubMed Central

Geschwind, Daniel H.; Rakic, Pasko

2014-01-01

To understand the emergence of human higher cognition, we must understand its biological substrate—the cerebral cortex, which considers itself the crowning achievement of evolution. Here, we describe how advances in developmental neurobiology, coupled with those in genetics, including adaptive protein evolution via gene duplications and the emergence of novel regulatory elements, can provide insights into the evolutionary mechanisms culminating in the human cerebrum. Given that the massive expansion of the cortical surface and elaboration of its connections in humans originates from developmental events, understanding the genetic regulation of cell number, neuronal migration to proper layers, columns, and regions, and ultimately their differentiation into specific phenotypes, is critical. The pre- and postnatal environment also interacts with the cellular substrate to yield a basic network that is refined via selection and elimination of synaptic connections, a process that is prolonged in humans. This knowledge provides essential insight into the pathogenesis of human-specific neuropsychiatric disorders. PMID:24183016

Discovering chemistry with an ab initio nanoreactor

DOE PAGES

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; ...

2014-11-02

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

Discovering chemistry with an ab initio nanoreactor

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

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

Retail video analytics: an overview and survey

NASA Astrophysics Data System (ADS)

Connell, Jonathan; Fan, Quanfu; Gabbur, Prasad; Haas, Norman; Pankanti, Sharath; Trinh, Hoang

2013-03-01

Today retail video analytics has gone beyond the traditional domain of security and loss prevention by providing retailers insightful business intelligence such as store traffic statistics and queue data. Such information allows for enhanced customer experience, optimized store performance, reduced operational costs, and ultimately higher profitability. This paper gives an overview of various camera-based applications in retail as well as the state-ofthe- art computer vision techniques behind them. It also presents some of the promising technical directions for exploration in retail video analytics.

Sleep Does Not Promote Solving Classical Insight Problems and Magic Tricks

PubMed Central

Schönauer, Monika; Brodt, Svenja; Pöhlchen, Dorothee; Breßmer, Anja; Danek, Amory H.; Gais, Steffen

2018-01-01

During creative problem solving, initial solution attempts often fail because of self-imposed constraints that prevent us from thinking out of the box. In order to solve a problem successfully, the problem representation has to be restructured by combining elements of available knowledge in novel and creative ways. It has been suggested that sleep supports the reorganization of memory representations, ultimately aiding problem solving. In this study, we systematically tested the effect of sleep and time on problem solving, using classical insight tasks and magic tricks. Solving these tasks explicitly requires a restructuring of the problem representation and may be accompanied by a subjective feeling of insight. In two sessions, 77 participants had to solve classical insight problems and magic tricks. The two sessions either occurred consecutively or were spaced 3 h apart, with the time in between spent either sleeping or awake. We found that sleep affected neither general solution rates nor the number of solutions accompanied by sudden subjective insight. Our study thus adds to accumulating evidence that sleep does not provide an environment that facilitates the qualitative restructuring of memory representations and enables problem solving. PMID:29535620

How evolutionary principles improve the understanding of human health and disease.

PubMed

Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S

2011-03-01

An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies.

How evolutionary principles improve the understanding of human health and disease

PubMed Central

Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S

2011-01-01

An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies. PMID:25567971

Using Health Provider Insights to Inform Pediatric HIV Disclosure: A Qualitative Study and Practice Framework from Kenya

PubMed Central

John-Stewart, Grace; Shah, Brandi; Wamalwa, Dalton; Maleche-Obimbo, Elizabeth; Kelley, Maureen

2014-01-01

Abstract Optimal pediatric HIV disclosure impacts illness and developmental experiences while improving access to timely treatment. However, disclosure rates in high HIV prevalence countries remain low and there are limited data on best practices. We conducted a qualitative study of disclosure practices and interviewed healthcare providers from five pediatric HIV clinics in Kenya. We identified themes central to disclosure practices, rationale for approaches, barriers to implementing disclosure, and creative strategies to overcome challenges. We used these insights to develop a practice-based framework for disclosure that is sensitive to practical challenges. Overall, providers had limited training but extensive experience in disclosure, endorsed individualized disclosure practices, invested substantial time on disclosure despite clinical burden, and noted adverse outcomes associated with unplanned or abrupt disclosure. Providers advocated for an approach to disclosure that is child-centered but respects caregiver fears and values. Caregiver support was provided to enable caregivers to be the person who ultimately disclosed HIV status to children. Unplanned or abrupt disclosure to children was reported to have severe and persistent adverse impact and was a stimulus to accelerate disclosure in scenarios when providers believed children may be suspecting their diagnosis. Based on these expert insights, the framework we developed incorporates concurrent evaluation of child and caregiver readiness, identifies cues to prompt disclosure discussions, includes caregiver education and support, and utilizes a gradual approach of unveiling HIV diagnosis to the child. PMID:25216105

Dental Wear: Attrition, Erosion, and Abrasion-A Palaeo-Odontological Approach.

PubMed

Sperber, Geoffrey H

2017-06-17

This paper reviews the surface ablation of early hominin teeth by attrition, abrasion, and erosive dental wear. The occurrence of these lesions is explored in a sample of South African fossil australopithecine dentitions revealing excessive wear. Interpretation of the nature of the dietary components causing such wear in the absence of carious erosion provides insight into the ecology of the Plio-pleistocene epoch (1-2 million years ago). Fossil teeth inform much of the living past by their retained evidence after death. Tooth wear is the ultimate forensic dental evidence of lives lived.

The Impact of New Payment Models on Quality of Diabetes Care and Outcomes.

PubMed

McGinley, Erin L; Gabbay, Robert A

2016-06-01

Historic changes in healthcare reimbursement and payment models due to the Affordable Care Act in the United States have the potential to transform how providers care for chronic diseases such as diabetes. Payment experimentation has provided insights into how changing incentives for primary care providers can yield improvements in the triple aim: improving patient experience, improving the health of populations, and reducing costs of healthcare. Much of this has involved leveraging widespread adoption of the patient-centered medical home (PCMH) with diabetes often the focus. While evidence is mounting that the PCMH can improve diabetes outcomes, some PCMH demonstrations have displayed mixed results. One of the first large-scale PCMH demonstrations developed around diabetes was conducted by the Commonwealth of Pennsylvania. Different payment models were employed across a series of staggered regional rollouts that provided a case study for the influence of innovative payment models. These learning laboratories provide insights into the role of reimbursement models and changes in how practice transformation is implemented. Ultimately, evolving payment systems focused on the total cost of care, such as Accountable Care Organizations, hold promise to transform diabetes care and produce significant cost savings through the prevention of complications.

Two-dimensional nanostructured Y{sub 2}O{sub 3} particles for viscosity modification

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

He, Xingliang; Xiao, Huaping; Liang, Hong, E-mail: hliang@tamu.edu

Nanoparticle additives have been shown to improve the mechanical and transport phenomena of various liquids; however, little has been done to try and explain the rheological modifications provided from such modifications from a theoretical standpoint. Here, we report a non-Einstein-like reduction of viscosity of mineral oil with the utilization of yttrium oxide nanosheet additives. Experimental results, coupled with generalized smoothed-particle hydrodynamics simulations, provide insight into the mechanism behind this reduction of fluid shear stress. The ordered inclination of these two-dimensional nanoparticle additives markedly improves the lubricating properties of the mineral oil, ultimately reducing the friction, and providing a way inmore » designing and understanding next generation of lubricants.« less

How can knowledge discovery methods uncover spatio-temporal patterns in environmental data?

NASA Astrophysics Data System (ADS)

Wachowicz, Monica

2000-04-01

This paper proposes the integration of KDD, GVis and STDB as a long-term strategy, which will allow users to apply knowledge discovery methods for uncovering spatio-temporal patterns in environmental data. The main goal is to combine innovative techniques and associated tools for exploring very large environmental data sets in order to arrive at valid, novel, potentially useful, and ultimately understandable spatio-temporal patterns. The GeoInsight approach is described using the principles and key developments in the research domains of KDD, GVis, and STDB. The GeoInsight approach aims at the integration of these research domains in order to provide tools for performing information retrieval, exploration, analysis, and visualization. The result is a knowledge-based design, which involves visual thinking (perceptual-cognitive process) and automated information processing (computer-analytical process).

Astrophysical observations: lensing and eclipsing Einstein's theories.

PubMed

Bennett, Charles L

2005-02-11

Albert Einstein postulated the equivalence of energy and mass, developed the theory of special relativity, explained the photoelectric effect, and described Brownian motion in five papers, all published in 1905, 100 years ago. With these papers, Einstein provided the framework for understanding modern astrophysical phenomena. Conversely, astrophysical observations provide one of the most effective means for testing Einstein's theories. Here, I review astrophysical advances precipitated by Einstein's insights, including gravitational redshifts, gravitational lensing, gravitational waves, the Lense-Thirring effect, and modern cosmology. A complete understanding of cosmology, from the earliest moments to the ultimate fate of the universe, will require developments in physics beyond Einstein, to a unified theory of gravity and quantum physics.

Leadership in Surgery

PubMed Central

Maykel, Justin A.

2013-01-01

Many opportunities exist for surgeons to be leaders in healthcare. Leadership training should begin in medical school and continue throughout residency training and in clinical practice. Most leadership skills can be developed and refined through a variety of training programs. Formal programs that result in degrees can provide surgeons with special insight, experience, and skill sets. Leadership skills are used in everyday practice and are particularly valuable when shifting roles or taking on new positions, whether at your home institution or within national organizations. Ultimately, physician leaders are responsible for leading healthcare and will directly impact the quality of care delivered to our patients. PMID:24436687

Dental Wear: Attrition, Erosion, and Abrasion—A Palaeo-Odontological Approach

PubMed Central

Sperber, Geoffrey H.

2017-01-01

This paper reviews the surface ablation of early hominin teeth by attrition, abrasion, and erosive dental wear. The occurrence of these lesions is explored in a sample of South African fossil australopithecine dentitions revealing excessive wear. Interpretation of the nature of the dietary components causing such wear in the absence of carious erosion provides insight into the ecology of the Plio-pleistocene epoch (1–2 million years ago). Fossil teeth inform much of the living past by their retained evidence after death. Tooth wear is the ultimate forensic dental evidence of lives lived. PMID:29563425

The cytogenetics of preimplantation human development: insights provided by traditional and novel techniques.

PubMed

Tempest, Helen G; Griffin, Darren K

2005-09-01

Our understanding of the incidence and origin of chromosome abnormalities in human preimplantation embryos is very limited due to the necessary ethical constraints involved in studying such material and the limited data ultimately produced. Several studies have addressed this issue, however, using techniques such as interphase fluorescence in situ hybridisation, modified G-banding preparation and the use of single-cell comparative genomic hybridisation (CGH). This review discusses the use of these techniques in assessing chromosome abnormalities in this, the earliest of human developmental stages. In addition, the prospects for the clinical use of CGH are discussed.

Experimental study of dissolution of minerals and CO2 sequestration in steel slag.

PubMed

Yadav, Shashikant; Mehra, Anurag

2017-06-01

This study strives to achieve a substantial amount of steel slag carbonation without using any harmful chemicals. For this purpose, experiments were performed in an aqueous medium, in a semi-batch reactor, to investigate the effect of varying reaction conditions during the steel slag CO 2 sequestration process. Further, studying the effect of dissolution on carbonation reactions and the mineralogical changes that subsequently occur within the slag helps provide insight into the parameters that ultimately have an impact on the carbonation rate as well the magnitude of the impact. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colloquium: Strong-field phenomena in periodic systems

NASA Astrophysics Data System (ADS)

Kruchinin, Stanislav Yu.; Krausz, Ferenc; Yakovlev, Vladislav S.

2018-04-01

The advent of visible-infrared laser pulses carrying a substantial fraction of their energy in a single field oscillation cycle has opened a new era in the experimental investigation of ultrafast processes in semiconductors and dielectrics (bulk as well as nanostructured), motivated by the quest for the ultimate frontiers of electron-based signal metrology and processing. Exploring ways to approach those frontiers requires insight into the physics underlying the interaction of strong high-frequency (optical) fields with electrons moving in periodic potentials. This Colloquium aims at providing this insight. Introduction to the foundations of strong-field phenomena defines and compares regimes of field-matter interaction in periodic systems, including (perfect) crystals as well as optical and semiconductor superlattices, followed by a review of recent experimental advances in the study of strong-field dynamics in crystals and nanostructures. Avenues toward measuring and controlling electronic processes up to petahertz frequencies are discussed.

Selected Insights from Application of Whole Genome Sequencing for Outbreak Investigations

PubMed Central

Le, Vien Thi Minh; Diep, Binh An

2014-01-01

Purpose of review The advent of high-throughput whole genome sequencing has the potential to revolutionize the conduct of outbreak investigation. Because of its ultimate pathogen strain resolution, whole genome sequencing could augment traditional epidemiologic investigations of infectious disease outbreaks. Recent findings The combination of whole genome sequencing and intensive epidemiologic analysis provided new insights on the sources and transmission dynamics of large-scale epidemics caused by Escherichia coli and Vibrio cholerae, nosocomial outbreaks caused by methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia, and Mycobacterium abscessus, community-centered outbreaks caused by Mycobacterium tuberculosis, and natural disaster-associated outbreak caused by environmentally acquired molds. Summary When combined with traditional epidemiologic investigation, whole genome sequencing has proven useful for elucidating sources and transmission dynamics of disease outbreaks. Development of a fully automated bioinformatics pipeline for analysis of whole genome sequence data is much needed to make this powerful tool more widely accessible. PMID:23856896

Studying neuroanatomy using MRI.

PubMed

Lerch, Jason P; van der Kouwe, André J W; Raznahan, Armin; Paus, Tomáš; Johansen-Berg, Heidi; Miller, Karla L; Smith, Stephen M; Fischl, Bruce; Sotiropoulos, Stamatios N

2017-02-23

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging and disease. Developments in MRI acquisition, image processing and data modeling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and for inferring microstructural properties; we also describe key artifacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, although methods need to improve and caution is required in interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

Birth asphyxia: pathophysiologic events and fetal adaptive changes.

PubMed

Woods, J R

1983-06-01

We have made significant advances toward understanding birth asphyxia and its effects upon neurologic development in the newborn and infant. The fetus is well adapted to compensate for moderate alterations in oxygen delivery. However, near lethal hypoxemia, prolonged exposure, and survival result in cell death and permanent neurologic sequelae. Neuroelectrical measurements such as the EEG and visual evoked potential provide insight into the acute alterations in nerve transmission during asphyxia, and in the recovery phase may ultimately provide information for long-term prognosis. These measurements are limited, however, by their inability once lost to distinguish cell inactivity from cell death. Permanent neurologic damage from asphyxia appears now to be a complex process in which severe hypoxemia precipitates a cascade of events leading to glycolysis, glycogenolysis, hypotension, and ultimately the accumulation of high concentrations of lactate at the cell level. As a consequence, cellular and extracellular fluid shifts produce cerebral edema, further impairment of cerebral circulation, and ultimately cell death. Clinical studies have helped to identify the newborn at high risk for neurologic impairment, but a cause-effect relationship remains unclear. That birth asphyxia can produce severe neurologic damage and death is generally accepted. Moreover, improper resuscitation of a severely depressed newborn increases the chance of permanent sequelae. The important clinical question is: Can one alter the natural course of asphyxia as has been alluded to through pharmacologic and ventilator manipulation? Answers to this question will depend upon continued study of the mechanisms of asphyctic damage in the central nervous system.

Diversifying Science: Intervention Programs Moderate the Effect of Stereotype Threat on Motivation and Career Choice

PubMed Central

Woodcock, Anna; Hernandez, Paul R.; Schultz, P. Wesley

2016-01-01

Stereotypes influence academic interests, performance, and ultimately career goals. The long-standing National Institutes of Health Research Initiative for Scientific Enhancement (RISE) training program has been shown to be effective at retaining underrepresented minorities in science. We argue that programs such as RISE may alter the experience and impact of stereotype threat on academic achievement goals and future engagement in a scientific career. We report analyses of a national sample comparing RISE students with a propensity score-matched control group over a 6-year period. Mediation analyses revealed that while RISE program membership did not buffer students from stereotype threat, it changed students' downstream responses and ultimately their academic outcomes. Nonprogram students were less likely than RISE students to persist in the sciences, partially because feelings of stereotype threat diminished their adoption of mastery goals. We discuss how these findings inform stereotype threat and goal orientation theories and provide insight into the success of intervention programs. PMID:27668075

Develop feedback system for intelligent dynamic resource allocation to improve application performance.

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

Gentile, Ann C.; Brandt, James M.; Tucker, Thomas

2011-09-01

This report provides documentation for the completion of the Sandia Level II milestone 'Develop feedback system for intelligent dynamic resource allocation to improve application performance'. This milestone demonstrates the use of a scalable data collection analysis and feedback system that enables insight into how an application is utilizing the hardware resources of a high performance computing (HPC) platform in a lightweight fashion. Further we demonstrate utilizing the same mechanisms used for transporting data for remote analysis and visualization to provide low latency run-time feedback to applications. The ultimate goal of this body of work is performance optimization in the facemore » of the ever increasing size and complexity of HPC systems.« less

Review: Metabolomics in the developmental origins of obesity and its cardiometabolic consequences

PubMed Central

Hivert, MF; Perng, W; Watkins, S; Newgard, CB; Kenny, LC; Kristal, BS; Patti, ME; Isganaitis, E; DeMeo, DL; Oken, E; Gillman, MW

2015-01-01

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course. Together, these data can ultimately help to elucidate mechanisms that underlie fetal metabolic programming. Finally, we review current gaps in knowledge and identify areas where the field of metabolomics is likely to provide insights into mechanisms linked to DOHaD in human populations. PMID:25631626

Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression

PubMed Central

DuPage, Michel; Cheung, Ann; Mazumdar, Claire; Winslow, Monte M.; Bronson, Roderick; Schmidt, Leah M.; Crowley, Denise; Chen, Jianzhu; Jacks, Tyler

2010-01-01

SUMMARY Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors. PMID:21251614

Computational models of the pulmonary circulation: Insights and the move towards clinically directed studies

PubMed Central

Tawhai, Merryn H.; Clark, Alys R.; Burrowes, Kelly S.

2011-01-01

Biophysically-based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study individual mechanisms that contribute to lung perfusion, to sophisticated multi-scale and -physics structure-based models that predict integrated structure-function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application; we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking; and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation. PMID:22034608

Taming Self-Organization Dynamics to Dramatically Control Porous Architectures.

PubMed

Daly, Ronan; Sader, John E; Boland, John J

2016-03-22

We demonstrate templating of functional materials with unexpected and intricate micro- and nanostructures by controlling the condensation, packing, and evaporation of water droplets on a polymer solution. Spontaneous evaporation of a polymer solution induces cooling of the liquid surface and water microdroplet condensation from the ambient vapor. These droplets pack together and act as a template to imprint an entangled polymer film. This breath figure (BF) phenomenon is an example of self-organization that involves the long-range ordering of droplets. Equilibrium-based analysis provides many insights into contact angles and drop stability of individual drops, but the BF phenomenon remains poorly understood thus far, preventing translation to real applications. Here we investigate the dynamics of this phenomenon to separate out the competing influences and then introduce a modulation scheme to ultimately manipulate the water vapor-liquid equilibrium independently from the solvent evaporation. This approach to BF control provides insights into the mechanism, a rationale for microstructure design, and evidence for the benefits of dynamical control of self-organization systems. We finally present dramatically different porous architectures from this approach reminiscent of microscale Petri dishes, conical flasks, and test tubes.

Pathogenesis of depression: insights from human and rodent studies

PubMed Central

MÉNARD, Caroline; HODES, Georgia E.; RUSSO, Scott J.

2015-01-01

Major depressive disorder (MDD) will affect one out of every five people in their lifetime and is the leading cause of disability worldwide. Nevertheless, mechanisms associated with the pathogenesis of MDD have yet to be completely understood and current treatments remain ineffective in a large subset of patients. In this review, we summarize the most recent discoveries and insights for which parallel findings have been obtained in human depressed subjects and rodent models of mood disorders in order to examine the potential etiology of depression. These mechanisms range from synaptic plasticity mechanisms to epigenetics and the immune system where there is strong evidence to support a functional role in the development of specific depression symptomology. Ultimately we conclude by discussing how novel therapeutic strategies targeting central and peripheral processes might ultimately aid in the development of effective new treatments for MDD and related stress disorders. PMID:26037806

Virulence as a model for interplanetary and interstellar colonization - parasitism or mutualism?

NASA Astrophysics Data System (ADS)

Starling, Jonathan; Forgan, Duncan H.

2014-01-01

In the light of current scientific assessments of human-induced climate change, we investigate an experimental model to inform how resource-use strategies may influence interplanetary and interstellar colonization by intelligent civilizations. In doing so, we seek to provide an additional aspect for refining the famed Fermi Paradox. The model described is necessarily simplistic, and the intent is to simply obtain some general insights to inform and inspire additional models. We model the relationship between an intelligent civilization and its host planet as symbiotic, where the relationship between the symbiont and the host species (the civilization and the planet's ecology, respectively) determines the fitness and ultimate survival of both organisms. We perform a series of Monte Carlo Realization simulations, where civilizations pursue a variety of different relationships/strategies with their host planet, from mutualism to parasitism, and can consequently `infect' other planets/hosts. We find that parasitic civilizations are generally less effective at survival than mutualist civilizations, provided that interstellar colonization is inefficient (the maximum velocity of colonization/infection is low). However, as the colonization velocity is increased, the strategy of parasitism becomes more successful, until they dominate the `population'. This is in accordance with predictions based on island biogeography and r/K selection theory. While heavily assumption dependent, we contend that this provides a fertile approach for further application of insights from theoretical ecology for extraterrestrial colonization - while also potentially offering insights for understanding the human-Earth relationship and the potential for extraterrestrial human colonization.

Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

PubMed Central

Skinner, Michael K.; Anway, Matthew D.

2018-01-01

Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

Primary school teachers' use of digital technology in mathematics: the complexities

NASA Astrophysics Data System (ADS)

Loong, Esther Yook-Kin; Herbert, Sandra

2018-02-01

This paper seeks to theorise primary teachers' degree of integration of digital technology in the mathematics classroom. In an age where digital technology use is ubiquitous, the issues surrounding teachers' choice, and ultimately their uptake of digital technologies in the classroom, is an area that need to be further unpacked. Cross-case analysis of the two teachers' uptake of digital technologies in their classroom, their pedagogical approaches and the reason for their choices provide insight into teachers' technological, pedagogical and content knowledge (TPACK). Differences in the way the teachers use digital technology in their classroom seem to be connected to their TPACK developmental stage.

The role of ecological theory in microbial ecology.

PubMed

Prosser, James I; Bohannan, Brendan J M; Curtis, Tom P; Ellis, Richard J; Firestone, Mary K; Freckleton, Rob P; Green, Jessica L; Green, Laura E; Killham, Ken; Lennon, Jack J; Osborn, A Mark; Solan, Martin; van der Gast, Christopher J; Young, J Peter W

2007-05-01

Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.

Laser Capture Microdissection in the Genomic and Proteomic Era: Targeting the Genetic Basis of Cancer

PubMed Central

Domazet, Barbara; MacLennan, Gregory T.; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-01-01

The advent of new technologies has enabled deeper insight into processes atsubcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy. PMID:18787684

Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer.

PubMed

Domazet, Barbara; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-03-15

The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy.

Network news: innovations in 21st century systems biology.

PubMed

Arkin, Adam P; Schaffer, David V

2011-03-18

A decade ago, seminal perspectives and papers set a strong vision for the field of systems biology, and a number of these themes have flourished. Here, we describe key technologies and insights that have elucidated the evolution, architecture, and function of cellular networks, ultimately leading to the first predictive genome-scale regulatory and metabolic models of organisms. Can systems approaches bridge the gap between correlative analysis and mechanistic insights? Copyright © 2011 Elsevier Inc. All rights reserved.

Fontan Surgical Planning: Previous Accomplishments, Current Challenges, and Future Directions.

PubMed

Trusty, Phillip M; Slesnick, Timothy C; Wei, Zhenglun Alan; Rossignac, Jarek; Kanter, Kirk R; Fogel, Mark A; Yoganathan, Ajit P

2018-04-01

The ultimate goal of Fontan surgical planning is to provide additional insights into the clinical decision-making process. In its current state, surgical planning offers an accurate hemodynamic assessment of the pre-operative condition, provides anatomical constraints for potential surgical options, and produces decent post-operative predictions if boundary conditions are similar enough between the pre-operative and post-operative states. Moving forward, validation with post-operative data is a necessary step in order to assess the accuracy of surgical planning and determine which methodological improvements are needed. Future efforts to automate the surgical planning process will reduce the individual expertise needed and encourage use in the clinic by clinicians. As post-operative physiologic predictions improve, Fontan surgical planning will become an more effective tool to accurately model patient-specific hemodynamics.

A Roundtable Discussion: Combination Products: Twice the Challenge?

PubMed

Baird, Nolan; Binion, Steven B; Cammack, Jon; Paine, Stephanie Del; Gonzales, Rosemary; Passut, Jena; Weiner, John Barlow Barr

2015-01-01

Combination products are therapeutic or diagnostic medical products that combine drugs, devices, and/or biological products with one another. FDA developed a regulation (final rule) on Current Good Manufacturing Practices (CGMP) for combination products that became effective July 22, 2013 (21 CFR Part 4). AAMI recently developed a technical information report (TIR) that provides information on how to effectively implement FDA's regulation. The overall goal of the TIR is to aid informed, risk-based decisions in establishing CGMP operating systems that support development, manufacture, premarket regulatory evaluation, and ultimately commercialization of combination products. This article, a result of an discussion with industry and FDA representatives, explores the landscape of combination products, highlights important considerations in developing and seeking marketing clearance for these innovative products, and provides insight on trends in the area.

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Autonomous Vehicles Require Socio-Political Acceptance—An Empirical and Philosophical Perspective on the Problem of Moral Decision Making

PubMed Central

Bergmann, Lasse T.; Schlicht, Larissa; Meixner, Carmen; König, Peter; Pipa, Gordon; Boshammer, Susanne; Stephan, Achim

2018-01-01

Autonomous vehicles, though having enormous potential, face a number of challenges. As a computer system interacting with society on a large scale and human beings in particular, they will encounter situations, which require moral assessment. What will count as right behavior in such situations depends on which factors are considered to be both morally justified and socially acceptable. In an empirical study we investigated what factors people recognize as relevant in driving situations. The study put subjects in several “dilemma” situations, which were designed to isolate different and potentially relevant factors. Subjects showed a surprisingly high willingness to sacrifice themselves to save others, took the age of potential victims in a crash into consideration and were willing to swerve onto a sidewalk if this saved more lives. The empirical insights are intended to provide a starting point for a discussion, ultimately yielding societal agreement whereby the empirical insights should be balanced with philosophical considerations. PMID:29541023

Autonomous Vehicles Require Socio-Political Acceptance-An Empirical and Philosophical Perspective on the Problem of Moral Decision Making.

PubMed

Bergmann, Lasse T; Schlicht, Larissa; Meixner, Carmen; König, Peter; Pipa, Gordon; Boshammer, Susanne; Stephan, Achim

2018-01-01

Autonomous vehicles, though having enormous potential, face a number of challenges. As a computer system interacting with society on a large scale and human beings in particular, they will encounter situations, which require moral assessment. What will count as right behavior in such situations depends on which factors are considered to be both morally justified and socially acceptable. In an empirical study we investigated what factors people recognize as relevant in driving situations. The study put subjects in several "dilemma" situations, which were designed to isolate different and potentially relevant factors. Subjects showed a surprisingly high willingness to sacrifice themselves to save others, took the age of potential victims in a crash into consideration and were willing to swerve onto a sidewalk if this saved more lives. The empirical insights are intended to provide a starting point for a discussion, ultimately yielding societal agreement whereby the empirical insights should be balanced with philosophical considerations.

A perspective on lyssavirus emergence and perpetuation.

PubMed

Rupprecht, Charles E; Turmelle, Amy; Kuzmin, Ivan V

2011-12-01

Rabies is propagated globally by viruses in the Family Rhabdoviridae, Genus Lyssavirus. These RNA viruses utilize the mammalian central nervous system as their ultimate niche, and exploit routine social mechanisms, as well as host behavioral alterations, to facilitate transmission by neural transport and innervations of the salivary glands, and ultimately excretion via the saliva, towards circulation thereafter in host populations. All mammals are susceptible to infection, but lyssavirus reservoirs are represented by several species of Carnivora, with viral global diversity and distribution in toto driven by a wide variety of the Chiroptera. Pathogen diversity is maintained by multiple faunas, and facilitated by pronounced host vagility, as exemplified by the ease of routine daily and seasonal movements by bats. Viral 'ensembles', or subpopulations associated with productive transmission events, emerge locally in vivo through a combination of naive host infections in some individuals versus acquired immunity by others, using complex metapopulation dynamics. Enhanced surveillance, improved diagnostics, increased pathogen detection, and an integrated One Health approach, targeting human, domestic animal and wildlife interfaces, provide modern insights to the ecology of bat lyssaviruses to augment future prevention and control. Published by Elsevier B.V.

Toward an Integrative Understanding of Social Behavior: New Models and New Opportunities

PubMed Central

Blumstein, Daniel T.; Ebensperger, Luis A.; Hayes, Loren D.; Vásquez, Rodrigo A.; Ahern, Todd H.; Burger, Joseph Robert; Dolezal, Adam G.; Dosmann, Andy; González-Mariscal, Gabriela; Harris, Breanna N.; Herrera, Emilio A.; Lacey, Eileen A.; Mateo, Jill; McGraw, Lisa A.; Olazábal, Daniel; Ramenofsky, Marilyn; Rubenstein, Dustin R.; Sakhai, Samuel A.; Saltzman, Wendy; Sainz-Borgo, Cristina; Soto-Gamboa, Mauricio; Stewart, Monica L.; Wey, Tina W.; Wingfield, John C.; Young, Larry J.

2010-01-01

Social interactions among conspecifics are a fundamental and adaptively significant component of the biology of numerous species. Such interactions give rise to group living as well as many of the complex forms of cooperation and conflict that occur within animal groups. Although previous conceptual models have focused on the ecological causes and fitness consequences of variation in social interactions, recent developments in endocrinology, neuroscience, and molecular genetics offer exciting opportunities to develop more integrated research programs that will facilitate new insights into the physiological causes and consequences of social variation. Here, we propose an integrative framework of social behavior that emphasizes relationships between ultimate-level function and proximate-level mechanism, thereby providing a foundation for exploring the full diversity of factors that underlie variation in social interactions, and ultimately sociality. In addition to identifying new model systems for the study of human psychopathologies, this framework provides a mechanistic basis for predicting how social behavior will change in response to environmental variation. We argue that the study of non-model organisms is essential for implementing this integrative model of social behavior because such species can be studied simultaneously in the lab and field, thereby allowing integration of rigorously controlled experimental manipulations with detailed observations of the ecological contexts in which interactions among conspecifics occur. PMID:20661457

Spatial patterns of phylogenetic diversity.

PubMed

Morlon, Hélène; Schwilk, Dylan W; Bryant, Jessica A; Marquet, Pablo A; Rebelo, Anthony G; Tauss, Catherine; Bohannan, Brendan J M; Green, Jessica L

2011-02-01

Ecologists and conservation biologists have historically used species-area and distance-decay relationships as tools to predict the spatial distribution of biodiversity and the impact of habitat loss on biodiversity. These tools treat each species as evolutionarily equivalent, yet the importance of species' evolutionary history in their ecology and conservation is becoming increasingly evident. Here, we provide theoretical predictions for phylogenetic analogues of the species-area and distance-decay relationships. We use a random model of community assembly and a spatially explicit flora dataset collected in four Mediterranean-type regions to provide theoretical predictions for the increase in phylogenetic diversity - the total phylogenetic branch-length separating a set of species - with increasing area and the decay in phylogenetic similarity with geographic separation. These developments may ultimately provide insights into the evolution and assembly of biological communities, and guide the selection of protected areas. © 2010 Blackwell Publishing Ltd/CNRS.

Sleep in vertebrate and invertebrate animals, and insights into the function and evolution of sleep.

PubMed

Miyazaki, Shinichi; Liu, Chih-Yao; Hayashi, Yu

2017-05-01

Many mammalian species, including humans, spend a substantial fraction of their life sleeping. Sleep deprivation in rats ultimately leads to death, indicating the essential role of sleep. Exactly why sleep is so essential, however, remains largely unknown. From an evolutionary point of view, almost all animal species that have been investigated exhibit sleep or sleep-like states, suggesting that sleep may benefit survival. In certain mammalian and avian species, sleep can be further divided into at least two stages, rapid eye movement (REM) sleep and non-REM sleep. In addition to a widely conserved role for sleep, these individual sleep stages may have roles unique to these animals. The recent use of state-of-the-art techniques, including optogenetics and chemogenetics, has greatly broadened our understanding of the neural mechanisms of sleep regulation, allowing us to address the function of sleep. Studies focusing on non-mammalian animals species have also provided novel insights into the evolution of sleep. This review provides a comprehensive overview regarding the current knowledge of the function and evolution of sleep. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Family perceptions of intellectual disability: Understanding and support in Dar es Salaam

PubMed Central

2012-01-01

When attempting to understand the construct of intellectual disability in different contexts, speaking to family members in addition to the individual with the disability may provide new insight about understandings of and responses to intellectual disability in society and may help to identify the forms of support that are available or needed to ensure the quality of life of people with disabilities. This article outlines and discusses interviews that were conducted in Dar es Salaam, Tanzania, with family members of children and adults with intellectual disabilities. These interviews explore how families came to understand that their child had an intellectual disability; the availability of family support; and family hopes and dreams for the future, and were a part of a wider exploratory study that gathered insight from individuals with disabilities, families, and other providers of support to explore understandings and perceptions of disability in Dar es Salaam. Understanding family experiences will help researchers, policy makers, non-governmental organisations, and others to identify family strengths and family support needs which can ultimately improve family quality of life and the quality of life of the member with a disability. PMID:28729979

Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections.

PubMed

Lorenz, Anne; Pawar, Vinay; Häussler, Susanne; Weiss, Siegfried

2016-11-01

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state-of-the-art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models. © 2016 Federation of European Biochemical Societies.

Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research

PubMed Central

Kim, Hyungsuk; Clark, David; Dionne, Raymond A.

2010-01-01

Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388

Integrating genomics into evolutionary medicine.

PubMed

Rodríguez, Juan Antonio; Marigorta, Urko M; Navarro, Arcadi

2014-12-01

The application of the principles of evolutionary biology into medicine was suggested long ago and is already providing insight into the ultimate causes of disease. However, a full systematic integration of medical genomics and evolutionary medicine is still missing. Here, we briefly review some cases where the combination of the two fields has proven profitable and highlight two of the main issues hindering the development of evolutionary genomic medicine as a mature field, namely the dissociation between fitness and health and the still considerable difficulties in predicting phenotypes from genotypes. We use publicly available data to illustrate both problems and conclude that new approaches are needed for evolutionary genomic medicine to overcome these obstacles. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monitoring volatilization products using Residual Gas Analyzers during MeV ion beam irradiations

NASA Astrophysics Data System (ADS)

Wetteland, C. J.; Kriewaldt, K.; Taylor, L. A.; McSween, H. Y.; Sickafus, K. E.

2018-03-01

The use of Residual Gas Analyzers (RGAs) during irradiation experiments can provide valuable information when incorporated into experimental end-stations. The instruments can track the volatilization products of beam-sensitive materials, which may ultimately aid researchers in selecting appropriate flux values for conducting experiments. Furthermore, the type of gaseous species released during an irradiation can be monitored directly, which may lead to new insights into the radiolysis and/or heating mechanisms responsible for gas evolution. A survey of several classes of materials exposed to extremes in particle flux is presented to show how RGA instrumentation can be incorporated to qualitatively assess ion-solid interactions in a variety of fields.

Solving difficult problems creatively: a role for energy optimised deterministic/stochastic hybrid computing

PubMed Central

Palmer, Tim N.; O’Shea, Michael

2015-01-01

How is the brain configured for creativity? What is the computational substrate for ‘eureka’ moments of insight? Here we argue that creative thinking arises ultimately from a synergy between low-energy stochastic and energy-intensive deterministic processing, and is a by-product of a nervous system whose signal-processing capability per unit of available energy has become highly energy optimised. We suggest that the stochastic component has its origin in thermal (ultimately quantum decoherent) noise affecting the activity of neurons. Without this component, deterministic computational models of the brain are incomplete. PMID:26528173

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part II--concepts for future development, 2003 and beyond.

PubMed

Liu, Charles Y; Spicer, Mark; Apuzzo, Michael L J

2003-01-01

The future development of the neurosurgical operative environment is driven principally by concurrent development in science and technology. In the new millennium, these developments are taking on a Jules Verne quality, with the ability to construct and manipulate the human organism and its surroundings at the level of atoms and molecules seemingly at hand. Thus, an examination of currents in technology advancement from the neurosurgical perspective can provide insight into the evolution of the neurosurgical operative environment. In the future, the optimal design solution for the operative environment requirements of specialized neurosurgery may take the form of composites of venues that are currently mutually distinct. Advances in microfabrication technology and laser optical manipulators are expanding the scope and role of robotics, with novel opportunities for bionic integration. Assimilation of biosensor technology into the operative environment promises to provide neurosurgeons of the future with a vastly expanded set of physiological data, which will require concurrent simplification and optimization of analysis and presentation schemes to facilitate practical usefulness. Nanotechnology derivatives are shattering the maximum limits of resolution and magnification allowed by conventional microscopes. Furthermore, quantum computing and molecular electronics promise to greatly enhance computational power, allowing the emerging reality of simulation and virtual neurosurgery for rehearsal and training purposes. Progressive minimalism is evident throughout, leading ultimately to a paradigm shift as the nanoscale is approached. At the interface between the old and new technological paradigms, issues related to integration may dictate the ultimate emergence of the products of the new paradigm. Once initiated, however, history suggests that the process of change will proceed rapidly and dramatically, with the ultimate neurosurgical operative environment of the future being far more complex in functional capacity but strikingly simple in apparent form.

Zodiacal Exoplanets in Time: Searching for Young Stars in K2

NASA Astrophysics Data System (ADS)

Morris, Nathan; Mann, Andrew W.

2017-06-01

Nearby young, open clusters such as the Hyades, Pleiades, and Praesepe provide an important reference point for the properties of stellar systems in general. In each cluster, all stars are of the same known age. As such, observations of planetary systems around these stars can be used to gain insight into the early stages of planetary system formation. K2, the revived Kepler mission, has provided a vast number of light curves for young stars in the and elsewhere in the K2 field. We aim to compute rotational periods from sunspot patterns for all K2 target stars and use gyrochronometric relationships derived from cluster stars to determine their ages. From there, we will search for planets around young stars outside the clusters with the ultimate goal of shedding light on how planets and planetary systems evolve with time.

A Survey of Architectural Techniques for Near-Threshold Computing

DOE PAGES

Mittal, Sparsh

2015-12-28

Energy efficiency has now become the primary obstacle in scaling the performance of all classes of computing systems. In low-voltage computing and specifically, near-threshold voltage computing (NTC), which involves operating the transistor very close to and yet above its threshold voltage, holds the promise of providing many-fold improvement in energy efficiency. However, use of NTC also presents several challenges such as increased parametric variation, failure rate and performance loss etc. Our paper surveys several re- cent techniques which aim to offset these challenges for fully leveraging the potential of NTC. By classifying these techniques along several dimensions, we also highlightmore » their similarities and differences. Ultimately, we hope that this paper will provide insights into state-of-art NTC techniques to researchers and system-designers and inspire further research in this field.« less

A Survey of Architectural Techniques for Near-Threshold Computing

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

Mittal, Sparsh

Energy efficiency has now become the primary obstacle in scaling the performance of all classes of computing systems. In low-voltage computing and specifically, near-threshold voltage computing (NTC), which involves operating the transistor very close to and yet above its threshold voltage, holds the promise of providing many-fold improvement in energy efficiency. However, use of NTC also presents several challenges such as increased parametric variation, failure rate and performance loss etc. Our paper surveys several re- cent techniques which aim to offset these challenges for fully leveraging the potential of NTC. By classifying these techniques along several dimensions, we also highlightmore » their similarities and differences. Ultimately, we hope that this paper will provide insights into state-of-art NTC techniques to researchers and system-designers and inspire further research in this field.« less

Perceived Physical Availability of Alcohol at Work and Workplace Alcohol Use and Impairment: Testing a Structural Model

PubMed Central

Frone, Michael R.; Trinidad, Jonathan R.

2014-01-01

This study develops and tests a new conceptual model of perceived physical availability of alcohol at work that provides unique insight into three dimensions of workplace physical availability of alcohol and their direct and indirect relations to workplace alcohol use and impairment. Data were obtained from a national probability sample of 2,727 U.S. workers. The results support the proposed conceptual model and provide empirical support for a positive relation of perceived physical availability of alcohol at work to workplace alcohol use and two dimensions of workplace impairment (workplace intoxication and workplace hangover). Ultimately, the findings suggest that perceived physical availability of alcohol at work is a risk factor for alcohol use and impairment during the workday, and that this relation is more complex than previously hypothesized. PMID:25243831

Deep Reflection on My Pedagogical Transformations

ERIC Educational Resources Information Center

Suzawa, Gilbert S.

2014-01-01

This retrospective essay contains my reflection on the deep concept of ambiguity (uncertainty) and a concomitant epistemological theory that all of our human knowledge is ultimately self-referential in nature. This new epistemological perspective is subsequently utilized as a platform for gaining insights into my experiences in conjunction with…

Evaluating the effects of the Dietary Guidelines for Americans on consumer behavior and health: methodological challenges.

PubMed

Guthrie, Joanne F; Smallwood, David M

2003-12-01

The Dietary Guidelines for Americans is the official nutrition policy statement for the United States. Government involvement in providing information on private behavior, such as food choice, is justified by the high cost of poor diets, as measured in medical expenses and lost productivity. The Guidelines are intended to provide an up-to-date, consistent information base for federal nutrition education and information efforts and food assistance program regulations. Through these policy mechanisms, the Guidelines are assumed to improve dietary behavior, and, ultimately, health. By law, the Dietary Guidelines for Americans must be updated every five years; however, there is no mandate for evaluation. Evaluation could provide useful information to assess the extent to which the Guidelines positively influence health and provide insights into reasons for their successes and limitations. However, evaluation would also present considerable challenges. This paper discusses the critical data and methodological needs for improving evaluation of the Dietary Guidelines for Americans.

Mineral Dissolution and Precipitation due to Carbon Dioxide-Water-Rock Interactions: The Significance of Accessory Minerals in Carbonate Reservoirs (Invited)

NASA Astrophysics Data System (ADS)

Kaszuba, J. P.; Marcon, V.; Chopping, C.

2013-12-01

Accessory minerals in carbonate reservoirs, and in the caprocks that seal these reservoirs, can provide insight into multiphase fluid (CO2 + H2O)-rock interactions and the behavior of CO2 that resides in these water-rock systems. Our program integrates field data, hydrothermal experiments, and geochemical modeling to evaluate CO2-water-rock reactions and processes in a variety of carbonate reservoirs in the Rocky Mountain region of the US. These studies provide insights into a wide range of geologic environments, including natural CO2 reservoirs, geologic carbon sequestration, engineered geothermal systems, enhanced oil and gas recovery, and unconventional hydrocarbon resources. One suite of experiments evaluates the Madison Limestone on the Moxa Arch, Southwest Wyoming, a sulfur-rich natural CO2 reservoir. Mineral textures and geochemical features developed in the experiments suggest that carbonate minerals which constitute the natural reservoir will initially dissolve in response to emplacement of CO2. Euhedral, bladed anhydrite concomitantly precipitates in response to injected CO2. Analogous anhydrite is observed in drill core, suggesting that secondary anhydrite in the natural reservoir may be related to emplacement of CO2 into the Madison Limestone. Carbonate minerals ultimately re-precipitate, and anhydrite dissolves, as the rock buffers the acidity and reasserts geochemical control. Another suite of experiments emulates injection of CO2 for enhanced oil recovery in the Desert Creek Limestone (Paradox Formation), Paradox Basin, Southeast Utah. Euhedral iron oxyhydroxides (hematite) precipitate at pH 4.5 to 5 and low Eh (approximately -0.1 V) as a consequence of water-rock reaction. Injection of CO2 decreases pH to approximately 3.5 and increases Eh by approximately 0.1 V, yielding secondary mineralization of euhedral pyrite instead of iron oxyhydroxides. Carbonate minerals also dissolve and ultimately re-precipitate, as determined by experiments in the Madison Limestone, but pyrite will persist and iron oxyhydroxides will not recrystallize.

Personal Development Plans: Insights from a Case Based Approach

ERIC Educational Resources Information Center

Greenan, Peter

2016-01-01

Purpose: In light of contemporary shifts away from annual appraisals, this study aims to explore the implications of using a personal development plan (PDP) as a means of focussing on continuous feedback and development to improve individual performance and ultimately organisational performance. Design/methodology/approach: Data were collected…

The Duke Lacrosse Scandal: New Insights, Many Perspectives

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2009

2009-01-01

An African-American stripper's false accusation of rape against three white Duke University lacrosse players in 2006--and the overzealous prosecution that followed--ultimately exposed prosecutorial misconduct, a rush to judgment, and simmering tensions of class, race, privilege, and gender. Michael L. Seigel, a professor of law at the University…

Dealing with Human Death: The Floating Perspective.

ERIC Educational Resources Information Center

Kenyon, Gary M.

1991-01-01

Explores approach to dealing with human death. Describes floating perspective, based on insights from Choron and Jaspers, as suggesting it is possible to deal with human death by refraining from taking ultimate position on the problem. Position encourages openness to death. Examines role of anxiety and describes possible meaningful outcomes of…

Essential Skills for Creative Writing: Integrating Multiple Domain-Specific Perspectives

ERIC Educational Resources Information Center

Barbot, Baptiste; Tan, Mei; Randi, Judi; Santa-Donato, Gabrielle; Grigorenko, Elena L.

2012-01-01

The aim of this work was to gather different perspectives on the "key ingredients" involved in creative writing by children--from experts of diverse disciplines, including teachers, linguists, psychologists, writers and art educators. Ultimately, we sought in the experts' convergence or divergence insights on the relative importance of the…

Ultrafast magnetodynamics with free-electron lasers

NASA Astrophysics Data System (ADS)

Malvestuto, Marco; Ciprian, Roberta; Caretta, Antonio; Casarin, Barbara; Parmigiani, Fulvio

2018-02-01

The study of ultrafast magnetodynamics has entered a new era thanks to the groundbreaking technological advances in free-electron laser (FEL) light sources. The advent of these light sources has made possible unprecedented experimental schemes for time-resolved x-ray magneto-optic spectroscopies, which are now paving the road for exploring the ultimate limits of out-of-equilibrium magnetic phenomena. In particular, these studies will provide insights into elementary mechanisms governing spin and orbital dynamics, therefore contributing to the development of ultrafast devices for relevant magnetic technologies. This topical review focuses on recent advancement in the study of non-equilibrium magnetic phenomena from the perspective of time-resolved extreme ultra violet (EUV) and soft x-ray spectroscopies at FELs with highlights of some important experimental results.

Patient Recruitment 2.0: Become a Partner in the Patient Journey Using Digital Media

PubMed Central

Lindemann, Michael; Freeman, Tobe; Kilchenmann, Timothy; Harrison, Shuree; Chan, Margaret; Wygonik, Mark; Haines, Lea

2016-01-01

We describe a digital platform, Pioneering Healthcare, designed to inform and empower people who are impacted by lung cancer. The platform enables Roche to support an online conversation with patients and caregivers about lung cancer, and about the role of lung cancer clinical studies in the development of future treatment options. This conversation is live and ongoing on the platform. It provides insights about the views and motivations of patients, and about how to better support patients pursuing treatment for life-threatening illness. We discuss the strategies used to deploy Pioneering Healthcare, and the advantages of using digital platforms for raising disease awareness, increasing patient engagement and, ultimately, for boosting patient enrollment into clinical trials. PMID:26818938

Perceived image quality for autostereoscopic holograms in healthcare training

NASA Astrophysics Data System (ADS)

Goldiez, Brian; Abich, Julian; Carter, Austin; Hackett, Matthew

2017-03-01

The current state of dynamic light field holography requires further empirical investigation to ultimately advance this developing technology. This paper describes a user-centered design approach for gaining insight into the features most important to clinical personnel using emerging dynamic holographic displays. The approach describes the generation of a high quality holographic model of a simulated traumatic amputation above the knee using 3D scanning. Using that model, a set of static holographic prints will be created varying in color or monochrome, contrast ratio, and polygon density. Leveraging methods from image quality research, the goal for this paper is to describe an experimental approach wherein participants are asked to provide feedback regarding the elements previously mentioned in order to guide the ongoing evolution of holographic displays.

Pathologic and Therapeutic Implications for the Cell Biology of Parkin

PubMed Central

Charan, Rakshita A.; LaVoie, Matthew J.

2015-01-01

Mutations in the E3 ligase parkin are the most common cause of autosomal recessive Parkinson's disease (PD), but it is believed that parkin dysfunction may also contribute to idiopathic PD. Since its discovery, parkin has been implicated in supporting multiple neuroprotective pathways, many revolving around the maintenance of mitochondrial health quality control and governance of cell survival. Recent advances across the structure, biochemistry, and cell biology of parkin have provided great insights into the etiology of parkin-linked and idiopathic PD and may ultimately generate novel therapeutic strategies to slow or halt disease progression. This review describes the various pathways in which parkin acts and the mechanisms by which parkin may be targeted for therapeutic intervention. PMID:25697646

Toward Usable Interactive Analytics: Coupling Cognition and Computation

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

Endert, Alexander; North, Chris; Chang, Remco

Interactive analytics provide users a myriad of computational means to aid in extracting meaningful information from large and complex datasets. Much prior work focuses either on advancing the capabilities of machine-centric approaches by the data mining and machine learning communities, or human-driven methods by the visualization and CHI communities. However, these methods do not yet support a true human-machine symbiotic relationship where users and machines work together collaboratively and adapt to each other to advance an interactive analytic process. In this paper we discuss some of the inherent issues, outlining what we believe are the steps toward usable interactive analyticsmore » that will ultimately increase the effectiveness for both humans and computers to produce insights.« less

A Journey in Science: Promise, Purpose, Privilege

PubMed Central

Nathan, Carl

2013-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the first Cerami Award Monograph, by Carl Nathan, MD, chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College, reflects towering genius and soaring inspiration. PMID:24089245

The link between a negative high resolution resist contrast/developer performance and the Flory-Huggins parameter estimated from the Hansen solubility sphere

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

StCaire, Lorri; Olynick, Deirdre L.; Chao, Weilun L.

We have implemented a technique to identify candidate polymer solvents for spinning, developing, and rinsing for a high resolution, negative electron beam resist hexa-methyl acetoxy calix(6)arene to elicit the optimum pattern development performance. Using the three dimensional Hansen solubility parameters for over 40 solvents, we have constructed a Hansen solubility sphere. From this sphere, we have estimated the Flory Huggins interaction parameter for solvents with hexa-methyl acetoxy calix(6)arene and found a correlation between resist development contrast and the Flory-Huggins parameter. This provides new insights into the development behavior of resist materials which are necessary for obtaining the ultimate lithographic resolution.

A journey in science: promise, purpose, privilege.

PubMed

Nathan, Carl

2013-10-03

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the first Cerami Award Monograph, by Carl Nathan, MD, chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College, reflects towering genius and soaring inspiration.

The Role of Positive Psychology in the Modern Medical Practice.

PubMed

Friedman, Scott E; Baum, Neil

2016-01-01

American healthcare has been shrouded in a cloak of negativity for too long. Many doctors are more pessimistic about the state of healthcare than they were even a few decades ago. In spite of extraordinary advances in the clinical aspects of healthcare, the business side of medicine has created a downward spiral in physician spirit, resulting in unnecessary stress, zapped energy, a rise in interpersonal conflict and, ultimately and as a byproduct of this negativity, reduced patient satisfaction. This downward spiral needs to be--and can be--stemmed. This article discuss how insights from the field of positive psychology and social neuroscience can help healthcare providers and their organizations flourish, in both their professional practices and personal lives.

Systems oncology: towards patient-specific treatment regimes informed by multiscale mathematical modelling.

PubMed

Powathil, Gibin G; Swat, Maciej; Chaplain, Mark A J

2015-02-01

The multiscale complexity of cancer as a disease necessitates a corresponding multiscale modelling approach to produce truly predictive mathematical models capable of improving existing treatment protocols. To capture all the dynamics of solid tumour growth and its progression, mathematical modellers need to couple biological processes occurring at various spatial and temporal scales (from genes to tissues). Because effectiveness of cancer therapy is considerably affected by intracellular and extracellular heterogeneities as well as by the dynamical changes in the tissue microenvironment, any model attempt to optimise existing protocols must consider these factors ultimately leading to improved multimodal treatment regimes. By improving existing and building new mathematical models of cancer, modellers can play important role in preventing the use of potentially sub-optimal treatment combinations. In this paper, we analyse a multiscale computational mathematical model for cancer growth and spread, incorporating the multiple effects of radiation therapy and chemotherapy in the patient survival probability and implement the model using two different cell based modelling techniques. We show that the insights provided by such multiscale modelling approaches can ultimately help in designing optimal patient-specific multi-modality treatment protocols that may increase patients quality of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pilot training: What can surgeons learn from it?

PubMed

Sommer, Kai-Jörg

2014-03-01

To provide healthcare professionals with an insight into training in aviation and its possible transfer into surgery. From research online and into company archives, relevant publications and information were identified. Current airline pilot training consists of two categories, basic training and type-rating. Training methods comprise classroom instruction, computer-based training and practical training, in either the aircraft or a flight-training device, which ranges from a fixed-base flight-training device to a full flight simulator. Pilot training not only includes technical and procedural instruction, but also training in non-technical skills like crisis management, decision-making, leadership and communication. Training syllabuses, training devices and instructors are internationally standardized and these standards are legally binding. Re-qualification and recurrent training are mandatory at all stages of a pilot's and instructor's career. Surgeons and pilots have much in common, i.e., they work in a 'real-time' three-dimensional environment under high physiological and psychological stress, operating expensive equipment, and the ultimate cost for error is measured in human lives. However, their training differs considerably. Transferring these well-tried aviation methods into healthcare will make surgical training more efficient, more effective and ultimately safer.

Brain activity and cognition: a connection from thermodynamics and information theory.

PubMed

Collell, Guillem; Fauquet, Jordi

2015-01-01

The connection between brain and mind is an important scientific and philosophical question that we are still far from completely understanding. A crucial point to our work is noticing that thermodynamics provides a convenient framework to model brain activity, whereas cognition can be modeled in information-theoretical terms. In fact, several models have been proposed so far from both approaches. A second critical remark is the existence of deep theoretical connections between thermodynamics and information theory. In fact, some well-known authors claim that the laws of thermodynamics are nothing but principles in information theory. Unlike in physics or chemistry, a formalization of the relationship between information and energy is currently lacking in neuroscience. In this paper we propose a framework to connect physical brain and cognitive models by means of the theoretical connections between information theory and thermodynamics. Ultimately, this article aims at providing further insight on the formal relationship between cognition and neural activity.

Closed-loop control of anesthesia: a primer for anesthesiologists.

PubMed

Dumont, Guy A; Ansermino, J Mark

2013-11-01

Feedback control is ubiquitous in nature and engineering and has revolutionized safety in fields from space travel to the automobile. In anesthesia, automated feedback control holds the promise of limiting the effects on performance of individual patient variability, optimizing the workload of the anesthesiologist, increasing the time spent in a more desirable clinical state, and ultimately improving the safety and quality of anesthesia care. The benefits of control systems will not be realized without widespread support from the health care team in close collaboration with industrial partners. In this review, we provide an introduction to the established field of control systems research for the everyday anesthesiologist. We introduce important concepts such as feedback and modeling specific to control problems and provide insight into design requirements for guaranteeing the safety and performance of feedback control systems. We focus our discussion on the optimization of anesthetic drug administration.

Communications systems technology assessment study. Volume 2: Results

NASA Technical Reports Server (NTRS)

Kelley, R. L.; Khatri, R. K.; Kiesling, J. D.; Weiss, J. A.

1977-01-01

The cost and technology characteristics are examined for providing special satellite services at UHF, 2.5 GHz, and 14/12 GHz. Considered are primarily health, educational, informational and emergency disaster type services. The total cost of each configuration including space segment, earth station, installation operation and maintenance was optimized to reduce the user's total annual cost and establish preferred equipment performance parameters. Technology expected to be available between now and 1985 is identified and comparisons made between selected alternatives. A key element of the study is a survey of earth station equipment updating past work in the field, providing new insight into technology, and evaluating production and test methods that can reduce costs in large production runs. Various satellite configurations were examined. The cost impact of rain attenuation at Ku-band was evaluated. The factors affecting the ultimate capacity achievable with the available orbital arc and available bandwidth were analyzed.

Plant microfossil record of the terminal Cretaceous event in the western United States and Canada

NASA Technical Reports Server (NTRS)

Nichols, D. J.; Fleming, R. F.

1988-01-01

Plant microfossils, principally pollen grains and spores produced by land plants, provide an excellent record of the terminal Cretaceous event in nonmarine environments. The record indicates regional devastation of the latest Cretaceous vegetation with the extinction of many groups, followed by a recolonization of the earliest Tertiary land surface, and development of a permanently changed land flora. The regional variations in depositional environments, plant communities, and paleoclimates provide insight into the nature and effects of the event, which were short-lived but profound. The plant microfossil data support the hypothesis that an abruptly initiated, major ecological crisis occurred at the end of the Cretaceous. Disruption of the Late Cretaceous flora ultimately contributred to the rise of modern vegetation. The plant microfossils together with geochemical and mineralogical data are consistent with an extraterrestrial impact having been the cause of the terminal Cretaceous event.

Making Patient Engagement a Reality.

PubMed

Pushparajah, Daphnee S

2018-02-01

Patients are increasingly recognised as the true customers of healthcare. By providing insights and perspectives, patients can help the wider healthcare community better understand their needs and ultimately enhance the value of healthcare solutions being developed. In the development of new medicines, for example, meaningful patient engagement can enable the pharmaceutical industry, healthcare providers and other stakeholders to achieve more meaningful health outcomes. While both the pharmaceutical industry and regulators have achieved some progress in incorporating patient perspectives into their activities, the lack of standardised best practices and metrics has made it challenging to achieve consistency and measure success in patient engagement. Practical guidance for patient engagement can facilitate better interactions between patients or patient groups and other collaborators, e.g. industry, regulators and other healthcare stakeholders. Accordingly, UCB has developed an internal model for Patient Group Engagement incorporating four key principles, based on shared ambition, transparency, accountability and respect, essential for effective collaborations.

Systems Genetics: A Novel Approach to Dissect the Genetic Basis of Osteoporosis

PubMed Central

Farber, Charles R.

2012-01-01

From the early 1990s to the middle of the last decade, the search for genes influencing osteoporosis proved difficult with few successes. However, over the last 5 years this has begun to change with the introduction of genome-wide association (GWA) studies. In this short period of time, GWA studies have significantly accelerated the pace of gene discovery, leading to the identification of nearly 100 independent associations for osteoporosis-related traits. However, GWA does not specifically pinpoint causal genes or provide functional context for associations. Thus, there is a need for approaches that provide systems-level insight on how associated variants influence cellular function, downstream gene networks, and ultimately disease. In this review we discuss the emerging field of “systems genetics” and how it is being used in combination with and independent of GWA to improve our understanding of the molecular mechanisms involved in bone fragility. PMID:22802146

Small Sample Reactivity Measurements in the RRR/SEG Facility: Reanalysis using TRIPOLI-4

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

Hummel, Andrew; Palmiotti, Guiseppe

2016-08-01

This work involved reanalyzing the RRR/SEG integral experiments performed at the Rossendorf facility in Germany throughout the 1970s and 80s. These small sample reactivity worth measurements were carried out using the pile oscillator technique for many different fission products, structural materials, and standards. The coupled fast-thermal system was designed such that the measurements would provide insight into elemental data, specifically the competing effects between neutron capture and scatter. Comparing the measured to calculated reactivity values can then provide adjustment criteria to ultimately improve nuclear data for fast reactor designs. Due to the extremely small reactivity effects measured (typically less thanmore » 1 pcm) and the specific heterogeneity of the core, the tool chosen for this analysis was TRIPOLI-4. This code allows for high fidelity 3-dimensional geometric modeling, and the most recent, unreleased version, is capable of exact perturbation theory.« less

Collagenolytic Matrix Metalloproteinase Structure-Function Relationships: Insights From Molecular Dynamics Studies.

PubMed

Karabencheva-Christova, Tatyana G; Christov, Christo Z; Fields, Gregg B

2017-01-01

Several members of the zinc-dependent matrix metalloproteinase (MMP) family catalyze collagen degradation. Experimental data reveal a collaboration between different MMP domains in order to achieve efficient collagenolysis. Molecular dynamics (MD) simulations have been utilized to provide atomistic details of the collagenolytic process. The triple-helical structure of collagen exhibits local regions of flexibility, with modulation of interchain salt bridges and water bridges contributing to accessibility of individual chains by the enzyme. In turn, the hemopexin-like (HPX) domain of the MMP initially binds the triple helix and facilitates the presentation of individual strands to active site in the catalytic (CAT) domain. Extensive positive and negative correlated motions are observed between the CAT and HPX domains when collagen is bound. Ultimately, the MD simulation studies have complemented structural (NMR spectroscopy, X-ray crystallography) and kinetic analyses to provide a more detailed mechanistic view of MMP-catalyzed collagenolysis. © 2017 Elsevier Inc. All rights reserved.

Global health and domestic policy - What motivated the development of the German Global Health Strategy?

PubMed

Aluttis, Christoph; Clemens, Timo; Krafft, Thomas

2017-09-01

In 2013, the German government published its national Global Health Strategy, outlining principles and focal topics for German engagement in global health. We asked the question of why Germany has decided to establish a national policy framework for global health at this point in time, and how the development process has taken place. The ultimate goal of this study was to achieve better insights into the respective health and foreign policy processes at the national level. This article reports on the results of semi-structured interviews with those actors that were responsible for initiating and drafting the German Global Health Strategy (GGHS). Our study shows that a series of external developments, stakeholders, and advocacy efforts created an environment conducive to the creation of the strategic document. In addition, a number of internal considerations, struggles, and capacities played a decisive role during the development phase of the GGHS. Understanding these factors better can not only provide substantial insights into global health related policy processes in Germany, but also contribute to the general discourse on the role of the nation state in global health governance.

Germanium Isotopes - the Global Budget and Paleoceanographic Potential

NASA Astrophysics Data System (ADS)

Baronas, J. J.; Hammond, D. E.; Rouxel, O. J.

2017-12-01

The distribution of element isotope ratios in rocks, sediments, rivers, and seawater can provide key insights about the operation and coupling of various biogeochemical cycles that are directly or indirectly responsible for the climate and habitability of the Earth surface environment. Germanium (Ge) is a trace element that shares many chemical similarities with silicon (Si), in addition to some siderophilic, chalcophilic, and organophilic properties. As a result, Ge stable isotope ratios (δ74Ge) and Ge/Si ratios can be used to trace various biogeochemical processes. These include silicate rock weathering, which modulates atmospheric pCO2 and supplies nutrients to ecosystems, biogenic silica formation, which is coupled to ocean productivity, and marine sediment diagenesis, which ultimately controls the removal of material from the Earth's surface. I will present an overview of my dissertation research concerning the global Ge isotope cycle, with insights into Ge isotope fractionation during secondary mineral precipitation during weathering on continents and during authigenesis in marine sediments. I will also discuss the potential for the δ74Ge sedimentary record to be used as a paleoceanographic proxy, given the constraints on the global Ge isotope budget.

Engineered in vitro disease models.

PubMed

Benam, Kambez H; Dauth, Stephanie; Hassell, Bryan; Herland, Anna; Jain, Abhishek; Jang, Kyung-Jin; Karalis, Katia; Kim, Hyun Jung; MacQueen, Luke; Mahmoodian, Roza; Musah, Samira; Torisawa, Yu-suke; van der Meer, Andries D; Villenave, Remi; Yadid, Moran; Parker, Kevin K; Ingber, Donald E

2015-01-01

The ultimate goal of most biomedical research is to gain greater insight into mechanisms of human disease or to develop new and improved therapies or diagnostics. Although great advances have been made in terms of developing disease models in animals, such as transgenic mice, many of these models fail to faithfully recapitulate the human condition. In addition, it is difficult to identify critical cellular and molecular contributors to disease or to vary them independently in whole-animal models. This challenge has attracted the interest of engineers, who have begun to collaborate with biologists to leverage recent advances in tissue engineering and microfabrication to develop novel in vitro models of disease. As these models are synthetic systems, specific molecular factors and individual cell types, including parenchymal cells, vascular cells, and immune cells, can be varied independently while simultaneously measuring system-level responses in real time. In this article, we provide some examples of these efforts, including engineered models of diseases of the heart, lung, intestine, liver, kidney, cartilage, skin and vascular, endocrine, musculoskeletal, and nervous systems, as well as models of infectious diseases and cancer. We also describe how engineered in vitro models can be combined with human inducible pluripotent stem cells to enable new insights into a broad variety of disease mechanisms, as well as provide a test bed for screening new therapies.

A Multi-Omic Systems-Based Approach Reveals Metabolic Markers of Bacterial Vaginosis and Insight into the Disease

PubMed Central

Yeoman, Carl J.; Thomas, Susan M.; Miller, Margret E. Berg; Ulanov, Alexander V.; Torralba, Manolito; Lucas, Sarah; Gillis, Marcus; Cregger, Melissa; Gomez, Andres; Ho, Mengfei; Leigh, Steven R.; Stumpf, Rebecca; Creedon, Douglas J.; Smith, Michael A.; Weisbaum, Jon S.; Nelson, Karen E.; Wilson, Brenda A.; White, Bryan A.

2013-01-01

Background Bacterial vaginosis (BV) is the most common vaginal disorder of reproductive-age women. Yet the cause of BV has not been established. To uncover key determinants of BV, we employed a multi-omic, systems-biology approach, including both deep 16S rRNA gene-based sequencing and metabolomics of lavage samples from 36 women. These women varied demographically, behaviorally, and in terms of health status and symptoms. Principal Findings 16S rRNA gene-based community composition profiles reflected Nugent scores, but not Amsel criteria. In contrast, metabolomic profiles were markedly more concordant with Amsel criteria. Metabolomic profiles revealed two distinct symptomatic BV types (SBVI and SBVII) with similar characteristics that indicated disruption of epithelial integrity, but each type was correlated to the presence of different microbial taxa and metabolites, as well as to different host behaviors. The characteristic odor associated with BV was linked to increases in putrescine and cadaverine, which were both linked to Dialister spp. Additional correlations were seen with the presence of discharge, 2-methyl-2-hydroxybutanoic acid, and Mobiluncus spp., and with pain, diethylene glycol and Gardnerella spp. Conclusions The results not only provide useful diagnostic biomarkers, but also may ultimately provide much needed insight into the determinants of BV. PMID:23405259

A multi-omic systems-based approach reveals metabolic markers of bacterial vaginosis and insight into the disease.

PubMed

Yeoman, Carl J; Thomas, Susan M; Miller, Margret E Berg; Ulanov, Alexander V; Torralba, Manolito; Lucas, Sarah; Gillis, Marcus; Cregger, Melissa; Gomez, Andres; Ho, Mengfei; Leigh, Steven R; Stumpf, Rebecca; Creedon, Douglas J; Smith, Michael A; Weisbaum, Jon S; Nelson, Karen E; Wilson, Brenda A; White, Bryan A

2013-01-01

Bacterial vaginosis (BV) is the most common vaginal disorder of reproductive-age women. Yet the cause of BV has not been established. To uncover key determinants of BV, we employed a multi-omic, systems-biology approach, including both deep 16S rRNA gene-based sequencing and metabolomics of lavage samples from 36 women. These women varied demographically, behaviorally, and in terms of health status and symptoms. 16S rRNA gene-based community composition profiles reflected Nugent scores, but not Amsel criteria. In contrast, metabolomic profiles were markedly more concordant with Amsel criteria. Metabolomic profiles revealed two distinct symptomatic BV types (SBVI and SBVII) with similar characteristics that indicated disruption of epithelial integrity, but each type was correlated to the presence of different microbial taxa and metabolites, as well as to different host behaviors. The characteristic odor associated with BV was linked to increases in putrescine and cadaverine, which were both linked to Dialister spp. Additional correlations were seen with the presence of discharge, 2-methyl-2-hydroxybutanoic acid, and Mobiluncus spp., and with pain, diethylene glycol and Gardnerella spp. The results not only provide useful diagnostic biomarkers, but also may ultimately provide much needed insight into the determinants of BV.

Contributions of treatment theory and enablement theory to rehabilitation research and practice.

PubMed

Whyte, John

2014-01-01

Scientific theory is crucial to the advancement of clinical research. The breadth of rehabilitation treatment requires that many different theoretical perspectives be incorporated into the design and testing of treatment interventions. In this article, the 2 broad classes of theory relevant to rehabilitation research and practice are defined, and their distinct but complementary contributions to research and clinical practice are explored. These theory classes are referred to as treatment theories (theories about how to effect change in clinical targets) and enablement theories (theories about how changes in a proximal clinical target will influence distal clinical aims). Treatment theories provide the tools for inducing clinical change but do not specify how far reaching the ultimate impact of the change will be. Enablement theories model the impact of changes on other areas of function but provide no insight as to how treatment can create functional change. Treatment theories are more critical in the early stages of treatment development, whereas enablement theories become increasingly relevant in specifying the clinical significance and practical effectiveness of more mature treatments. Understanding the differences in the questions these theory classes address and how to combine their insights is crucial for effective research development and clinical practice. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

DGIC Interconnection Insights | Distributed Generation Interconnection

Science.gov Websites

ripe for cost reductions. Utilities, public service commissions, legislators, and even developers can timelines, strand assets, stress debt service, and ultimately drive up the cost of solar energy. NREL ). The financier also indicated that solar's cost of capital, on the whole, is still 100-200 basis points

Toward Data-Driven Education Systems: Insights into Using Information to Measure Results and Manage Change

ERIC Educational Resources Information Center

Custer, Samantha; King, Elizabeth M.; Atinc, Tamar Manuelyan; Read, Lindsay; Sethi, Tanya

2018-01-01

Governments, organizations, and companies are generating copious amounts of data and analysis to support education decision-making around the world. While continued investments in data creation and management are necessary, the ultimate value of information is not in its "production," but its "use." Herein lies one of the…

Psychiatry and psychotherapy as political processes.

PubMed

Breggin, P R

1975-07-01

Therapy is applied politics. From hospitalizing a patient to offering psychoanalytic insight, a therapist's every action reflects his own attitudes toward political issues, including individual freedom vs. state control, or capitalism versus socialism. Ultimately every therapy implements some utopian political vision against which the client will measure his own success and failure in the therapy.

Chemical structure of the Chromophoric Dissolved Organic Matter (CDOM) fluorescent matter.

NASA Astrophysics Data System (ADS)

Blough, N. V.; Del Vecchio, R.; Cartisano, C. M.; Bianca, M.

2017-12-01

The structure(s), distribution and dynamics of CDOM have been investigated over the last several decades largely through optical spectroscopy (including both absorption and fluorescence) due to the fairly inexpensive instrumentation and the easy-to-gather data (over thousands published papers from 1990-2016). Yet, the chemical structure(s) of the light absorbing and emitting species or constituents within CDOM has only recently being proposed and tested through chemical manipulation of selected functional groups (such as carbonyl and carboxylic/phenolic containing molecules) naturally occurring within the organic matter pool. Similarly, fitting models (among which the PArallel FACtor analysis, PARAFAC) have been developed to better understand the nature of a subset of DOM, the CDOM fluorescent matter (FDOM). Fluorescence spectroscopy coupled with chemical tests and PARAFAC analyses could potentially provide valuable insights on CDOM sources and chemical nature of the FDOM pool. However, despite that applications (and publications) of PARAFAC model to FDOM have grown exponentially since its first application/publication (2003), a large fraction of such publications has misinterpreted the chemical meaning of the delivered PARAFAC `components' leading to more confusion than clarification on the nature, distribution and dynamics of the FDOM pool. In this context, we employed chemical manipulation of selected functional groups to gain further insights on the chemical structure of the FDOM and we tested to what extent the PARAFAC `components' represent true fluorophores through a controlled chemical approach with the ultimate goal to provide insights on the chemical nature of such `components' (as well as on the chemical nature of the FDOM) along with the advantages and limitations of the PARAFAC application.

The effects of aging on insight into illness in schizophrenia: a review†

PubMed Central

Gerretsen, Philip; Plitman, Eric; Rajji, Tarek K.; Graff-Guerrero, Ariel

2015-01-01

Objectives Impaired insight into illness is a prevalent feature of schizophrenia, which negatively influences treatment adherence and clinical outcomes. Little is known about the effects of aging on insight impairment. We aimed to review the available research literature on the effects of aging on insight into illness in schizophrenia, in relation to positive, negative, and cognitive symptoms. Ultimately, we propose a trajectory of insight in schizophrenia across the lifespan. Method A systematic Medline® literature search was conducted, searching for English language studies describing the relationship of insight into illness in schizophrenia with aging. Results We identified 62 studies. Insight impairment is associated with illness severity, premorbid intellectual function (i.e. IQ), executive function, and memory. Insight impairment improves modestly during midlife, worsening again in late life. It tends to fluctuate with each episode of psychosis, likely in relation to worsening positive symptoms that improve with antipsychotic treatment. The relationship between insight impairment and cognitive dysfunction appears to attenuate with age, while the relationship with lower premorbid intellectual function is preserved. The association between impaired insight and negative symptoms is unclear. Conclusions The available literature suggests that the course of insight impairment follows a U-shaped curve, where insight impairment is severe during the first episode of psychosis, modestly improves over midlife, and declines again in late life. Future studies are required to investigate the trajectory of insight into illness and its core domains across the lifespan from prodromal phase to late life. PMID:25055980

The Potential Impact of the Neurosciences on Religious and Spiritual Education: Ramifying from the Impact on Values Education

ERIC Educational Resources Information Center

Mudge, Peter; Fleming, Daniel; Lovat, Terence

2014-01-01

This article will argue that neuroscientific insights can inform religious and spiritual education's capacity for strengthening student understanding, promoting transformation and ultimately wisdom. Among other findings, it will show that current neuroscientific research supports a holistic approach to pedagogy which emphasises the cognitive,…

[The process of empowering community development: the experience of a community in Taipei city].

PubMed

Li, I-Chuan; Chen, Yu-Chi; Wang, Hui-Chun

2006-04-01

Community participation and development are the most difficult aspects of building healthy communities. They are also, however, the most essential parts of the process. It has been established that empowerment can ultimately enhance individual self-efficacy, influence organizational and social structures, and increase the sense of community and citizen's capabilities. This article demonstrates the experience of one community in Taipei City during a lengthy period of organization and development. It illustrates the different stages involved in community development and the functions of community health professionals. It seeks to provide insight into the importance of using empowerment in promoting communities' capabilities and the fact that only by developing organic communities that are rich in the energy of life can we develop sustainable communities.

Healthy aging: The ultimate preventative medicine.

PubMed

Kaeberlein, Matt; Rabinovitch, Peter S; Martin, George M

2015-12-04

Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity. Here we describe some of these advances, along with efforts to move geroscience from the bench to the clinic. We also propose that greater emphasis should be placed on research into basic aging processes, because interventions that slow aging will have a greater effect on quality of life compared with disease-specific approaches. Copyright © 2015, American Association for the Advancement of Science.

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

PubMed Central

Steinman, Lawrence

2016-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Lawrence Steinman, MD, of Stanford University in California. A visionary in the field of neurology, this is the story of Dr. Steinman’s scientific journey. PMID:27652378

Novel insights of microRNAs in the development of systemic lupus erythematosus.

PubMed

Le, Xiong; Yu, Xiang; Shen, Nan

2017-09-01

To provide a brief overview of recent progress in microRNA biogenesis and homeostasis, its function in immune system and systemic lupus erythematosus (SLE), as well as successful microRNA-based therapy in vivo. Stepwise microRNA biogenesis is elaborately regulated at multiple levels, ranging from transcription to ultimate function. Mature microRNAs have inhibitory effects on various biological molecules, which are crucial for stabilizing and normalizing differentiation and function of immune cells. Abnormality in microRNA expression contributes to dysfunction of lupus immune cells and resident cells in local tissues. Manipulation of dysregulated microRNAs in vivo through microRNA delivery or targeting microRNA might be promising for SLE treatment. Recent advances highlight that microRNAs are important in immunity, lupus autoimmunity and as potential therapy target for SLE.

Engineering of mCherry variants with long Stokes shift, red-shifted fluorescence, and low cytotoxicity

PubMed Central

Shen, Yi; Chen, Yingche; Wu, Jiahui; Shaner, Nathan C.; Campbell, Robert E.

2017-01-01

MCherry, the Discosoma sp. mushroom coral-derived monomeric red fluorescent protein (RFP), is a commonly used genetically encoded fluorophore for live cell fluorescence imaging. We have used a combination of protein design and directed evolution to develop mCherry variants with low cytotoxicity to Escherichia coli and altered excitation and emission profiles. These efforts ultimately led to a long Stokes shift (LSS)-mCherry variant (λex = 460 nm and λem = 610 nm) and a red-shifted (RDS)-mCherry variant (λex = 600 nm and λem = 630 nm). These new RFPs provide insight into the influence of the chromophore environment on mCherry’s fluorescence properties, and may serve as templates for the future development of fluorescent probes for live cell imaging. PMID:28241009

A Journey in Science: Medical Scientist in Translation

PubMed Central

Hansson, Göran K

2014-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed and treated. In this volume, the Cerami Award Monograph is by Göran K Hansson, MD, PhD, Karolinska Institute. A visionary in the field of cardiovascular research, this is the story of Dr. Hansson’s scientific journey. PMID:25356751

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

PubMed

Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

Ubiquilin-1 and protein quality control in Alzheimer disease.

PubMed

El Ayadi, Amina; Stieren, Emily S; Barral, José M; Boehning, Darren

2013-01-01

Single nucleotide polymorphisms in the ubiquilin-1 gene may confer risk for late-onset Alzheimer disease (AD). We have shown previously that ubiquilin-1 functions as a molecular chaperone for the amyloid precursor protein (APP) and that protein levels of ubiquilin-1 are decreased in the brains of AD patients. We have recently found that ubiquilin-1 regulates APP trafficking and subsequent secretase processing by stimulating non-degradative ubiquitination of a single lysine residue in the cytosolic domain of APP. Thus, ubiquilin-1 plays a central role in regulating APP biosynthesis, trafficking and ultimately toxicity. As ubiquilin-1 and other ubiquilin family members have now been implicated in the pathogenesis of numerous neurodegenerative diseases, these findings provide mechanistic insights into the central role of ubiquilin proteins in maintaining neuronal proteostasis.

A Case Study on the Persistence of Swidden Agriculture in the Context of Post-2015 Anti-Haze Regulation in West-Kalimantan.

PubMed

Thung, Paul Hasan

2018-01-01

This case study analyses a ban on the use of fire in a district of West-Kalimantan in response to the 2015 Southeast Asian Haze crisis. Based on stakeholder interviews and participant observation, I address the dilemmas encountered at the district and village level as a result of transnational environmental politics. A stark example of a wider tendency for policies to restrict swidden agriculture, the case study provides insight into the persistence of swidden . Contradictions between different stakeholders' experiences and understandings of local human ecology and haze politics ultimately rendered the ban ineffective. Future efforts at regulating fire in smallholder agriculture would therefore benefit from a clearer understanding of the relationships between fire, subsistence, and haze.

Zodiacal Exoplanets in Time: Searching for Young Stars in K2

NASA Astrophysics Data System (ADS)

Morris, Nathan Ryan; Mann, Andrew; Rizzuto, Aaron

2018-01-01

Observations of planetary systems around young stars provide insight into the early stages of planetary system formation. Nearby young open clusters such as the Hyades, Pleiades, and Praesepe provide important benchmarks for the properties of stellar systems in general. These clusters are all known to be less than 1 Gyr old, making them ideal targets for a survey of young planetary systems. Few transiting planets have been detected around clusters stars, however, so this alone is too small of a sample. K2, the revived Kepler mission, has provided a vast number of light curves for young stars in clusters and elsewhere in the K2 field. This provides us with the opportunity to extend the sample of young systems to field stars while calibrating with cluster stars. We compute rotational periods from starspot patterns for ~36,000 K2 targets and use gyrochronological relationships derived from cluster stars to determine their ages. From there, we have begun searching for planets around young stars outside the clusters with the ultimate goal of shedding light on how planets and planetary systems evolve in their early, most formative years.

A qualitative analysis of case managers' use of harm reduction in practice.

PubMed

Tiderington, Emmy; Stanhope, Victoria; Henwood, Benjamin F

2013-01-01

The harm reduction approach has become a viable framework within the field of addictions, yet there is limited understanding about how this approach is implemented in practice. For people who are homeless and have co-occurring psychiatric and substance use disorders, the Housing First model has shown promising results in employing such an approach. This qualitative study utilizes ethnographic methods to explore case managers' use of harm reduction within Housing First with a specific focus on the consumer-provider relationship. Analysis of observational data and in-depth interviews with providers and consumers revealed how communication between the two regarding the consumer's substance use interacted with the consumer-provider relationship. From these findings emerged a heuristic model of harm reduction practice that highlighted the profound influence of relationship quality on the paths of communication regarding substance use. This study provides valuable insight into how harm reduction is implemented in clinical practice that ultimately has public health implications in terms of more effectively addressing high rates of addiction that contribute to homelessness and health disparities. Copyright © 2013 Elsevier Inc. All rights reserved.

Non-active site mutations disturb the loop dynamics, dimerization, viral budding and egress of VP40 of the Ebola virus.

PubMed

Balmith, Marissa; Soliman, Mahmoud E S

2017-02-28

The first account of the dynamic features of the loop region of VP40 of the Ebola virus (EboV) using accelerated molecular dynamics (aMD) simulations is reported herein. Due to its major role in the Ebola life cycle, VP40 is considered a promising therapeutic target. The available experimental data on the N-terminal domain (NTD) loop indicates that mutations K127A, T129A and N130A demonstrate an unrecognized role for NTD-plasma membrane (PM) interaction for efficient VP40-PM localization, oligomerization, matrix assembly and egress. Despite experimental results, the molecular description of VP40 and the information it can provide still remain vague. Therefore, to gain further molecular insight into the effect of mutations on the loop region of VP40 and its effects on the overall protein conformation and VP40 dimerization, aMD simulations and post-dynamic analyses were employed for wildtype (WT) and mutant systems. The results showed significant variations in the presence of mutations as per RMSF, RMSD, R g , PCA and distance calculations in comparison to the WT. These results could provide researchers with insight with regards to the conformational aspects concerning VP40 and its close relation to the experimental data. We believe that the results presented in this study will ultimately provide a useful understanding of the structural landscape of the loop region of VP40, which would contribute towards the discovery of novel EboV inhibitors.

Effective communication tools to engage Torres Strait Islanders in scientific research

NASA Astrophysics Data System (ADS)

Jones, A.; Barnett, B.; Williams, A. J.; Grayson, J.; Busilacchi, S.; Duckworth, A.; Evans-Illidge, E.; Begg, G. A.; Murchie, C. D.

2008-09-01

Often, research activities in Torres Strait have not delivered full benefit to Torres Strait Islanders due to a lack of consultation, ineffectual communication of research information and lack of empathy for the needs of Islander communities. As for other stakeholder groups, integration of Islanders into the research process through practical involvement in research may overcome these problems. Three case studies from research projects conducted in Torres Strait are discussed to highlight a variety of communication and engagement activities carried out by non-Indigenous researchers. How these communication and extension activities facilitate collaboration between Torres Strait Islander and non-Indigenous researchers provides insight in the importance of these activities to the relative success of research projects. The benefits for Islanders in collaborating with researchers may be: improved understanding of the research and how it contributes to natural resource management; a sense of control in future management decisions; a greater likelihood of successful self-regulatory management systems; enhanced skills; and increased employment opportunities. The potential benefits for researchers are enhanced support for research projects resulting in increased access to data and logistic support that may ultimately impact the successful completion of projects. Such an approach will require researchers to take time to develop relationships with Torres Strait Islanders, effectively involve Islanders in research on an equitable basis and be flexible. This will ultimately require funding organisations to recognise the importance of such activities in research proposals and provide support through sufficient funding to enable these activities to be carried out.

Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

PubMed Central

Hooper, Cornelia M.; Hawes, Susan M.; Kees, Ursula R.; Gottardo, Nicholas G.; Dallas, Peter B.

2014-01-01

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10–15 and 20–30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies. PMID:25412507

Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

PubMed

Hooper, Cornelia M; Hawes, Susan M; Kees, Ursula R; Gottardo, Nicholas G; Dallas, Peter B

2014-01-01

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

Transcriptional Profiling of Metabolic Transitions during Development and Diapause Preparation in the Copepod Calanus finmarchicus.

PubMed

Tarrant, Ann M; Baumgartner, Mark F; Lysiak, Nadine S J; Altin, Dag; Størseth, Trond R; Hansen, Bjørn Henrik

2016-12-01

Calanus finmarchicus, like many other copepods in the family Calanidae, can enter into a facultative diapause during the last juvenile phase (fifth copepodid, C5) to enable survival during unfavorable periods. Diapause is essential to the persistence of Calanus populations and profoundly impacts energy flow within oceanic ecosystems, yet regulation of diapause is not understood in these animals. Transcriptional profiling has begun to provide insight into metabolic changes occurring as C. finmarchicus prepares for and enters into diapause or skips diapause to prepare for the terminal molt. In particular, components of the glycolysis, pentose phosphate and lipid synthesis pathways are upregulated early in the C5 stage when lipid stores are low. Currently, our ability to identify metabolic patterns is limited by the incomplete functional annotation of the C. finmarchicus transcriptome. Such limitations are widespread among studies of non-model organisms and addressing them should be a priority for future research. In addition, integrating the results across multiple emerging complementary transcriptomic studies will provide a more complete picture of copepod physiology than isolated studies. Ultimately, identifying molecular markers of copepod physiology could enable robust identification of animals preparing to enter into diapause and ultimately lead to a greatly improved understanding of diapause regulation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

The story of life: critical insights from evolutionary biology.

PubMed

Paulson, Steve; Chang, Melanie Lee; Tattersall, Ian; Morris, Simon Conway

2018-06-06

The notion that humans, in all their complexity, are merely an evolutionary accident, an insignificant speck in a boundless cosmos, is deeply unsatisfying for most nonscientists and fails to resonate with their life experience. What, then, can evolutionary biology ultimately tell us about the meaning of our lives? In conversation with Steve Paulson, executive producer and host of To the Best of Our Knowledge, paleoanthropologists Melanie Lee Chang and Ian Tattersall, and paleontologist Simon Conway Morris share their insights on these competing concepts and explain how meaning and purpose can be gleaned from the remarkable story of life itself. © 2018 New York Academy of Sciences.

Long-term data from silvicultural studies: interpreting and assessing old records for economic insights

Treesearch

Paul E. Sendak; Robert M. Frank; William B. Leak

2006-01-01

Long-term silvicultural studies on the Penobscot Experimental Forest in Maine and Bartlett Experimental Forest in New Hampshire offer opportunities for the patient financial analyst. The economist working with carefully collected growth and yield data can increase the value of these studies to other researchers and ultimately to forest managers. Issues related to data...

The Divine and Artistic Ideal: Ideas and Insights for Cross-Cultural Aesthetic Education

ERIC Educational Resources Information Center

Gu, Ming Dong

2008-01-01

Art has been related to the divine across cultures. In most traditions, the divine has been viewed as the ultimate aesthetic ideal, and aesthetics is full of notions, ideas, and concepts related to it without which artistic criticism and aesthetic education would be in a much impoverished state. The divine in art, however, is a slippery category.…

Culture, Pedagogy and Equity in a Meritocratic Education System: Teachers' Work and the Politics of Culture in Singapore

ERIC Educational Resources Information Center

Lim, Leonel; Tan, Michael

2018-01-01

Drawing upon insights gained from the extant work on culture and pedagogy, this paper explores the ways in which, in an ostensibly meritocratic education system, ideas about students' cultural backgrounds and its relevance for teaching are interpreted, negotiated, and ultimately drawn upon to engage students in the low-progress academic tracks.…

Direct in situ observation of ZnO nucleation and growth via transmission X-ray microscopy

NASA Astrophysics Data System (ADS)

Tay, S. E. R.; Goode, A. E.; Nelson Weker, J.; Cruickshank, A. A.; Heutz, S.; Porter, A. E.; Ryan, M. P.; Toney, M. F.

2016-01-01

The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation.The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation. Electronic supplementary information (ESI) available: Methods and videos of nanoparticle growth. See DOI: 10.1039/c5nr07019h

A systematic method for using 3D echocardiography to evaluate tricuspid valve insufficiency in hypoplastic left heart syndrome.

PubMed

Mart, Christopher Robin; Eckhauser, Aaron Wesley; Murri, Michael; Su, Jason Thomas

2014-09-01

With surgical palliation of hypoplastic left heart syndrome (HLHS), the tricuspid valve (TV) becomes the systemic atrioventricular valve and moderate/severe TV insufficiency (TVI), an adverse risk factor for survival to Fontan, has been reported in up to 35% of patients prior to stage I palliation. Precise echocardiographic identification of the mechanism of TVI cannot be determined by two-dimensional echocardiography. Three-dimensional echocardiography (3DE) can provide significant insight into the mechanisms of TVI. It is the intent of this report to propose a systematic method on how to evaluate and display 3DE images of the TV in HLHS which has not been done previously. TV anatomy, function, and the known mechanisms of insufficiency are reviewed. We defined three regions of the TV (anterior, posterior, septal) that can help define valve "leaflets" that incorporates the many variations of TV anatomy. To determine how the surgeon views the TV, a picture of a pathologic specimen of the TV was placed on a computer screen and rotated until it was oriented as it appears during surgery, the "surgeons view." We have proposed a systematic method for evaluating and displaying the TV using 3DE which can provide significant insight into the mechanisms causing TVI in HLHS. This has the potential to improve both the surgical approach to repairing the valve and, ultimately, patient outcomes.

A systematic method for using 3D echocardiography to evaluate tricuspid valve insufficiency in hypoplastic left heart syndrome

PubMed Central

Mart, Christopher Robin; Eckhauser, Aaron Wesley; Murri, Michael; Su, Jason Thomas

2014-01-01

With surgical palliation of hypoplastic left heart syndrome (HLHS), the tricuspid valve (TV) becomes the systemic atrioventricular valve and moderate/severe TV insufficiency (TVI), an adverse risk factor for survival to Fontan, has been reported in up to 35% of patients prior to stage I palliation. Precise echocardiographic identification of the mechanism of TVI cannot be determined by two-dimensional echocardiography. Three-dimensional echocardiography (3DE) can provide significant insight into the mechanisms of TVI. It is the intent of this report to propose a systematic method on how to evaluate and display 3DE images of the TV in HLHS which has not been done previously. TV anatomy, function, and the known mechanisms of insufficiency are reviewed. We defined three regions of the TV (anterior, posterior, septal) that can help define valve “leaflets” that incorporates the many variations of TV anatomy. To determine how the surgeon views the TV, a picture of a pathologic specimen of the TV was placed on a computer screen and rotated until it was oriented as it appears during surgery, the “surgeons view.” We have proposed a systematic method for evaluating and displaying the TV using 3DE which can provide significant insight into the mechanisms causing TVI in HLHS. This has the potential to improve both the surgical approach to repairing the valve and, ultimately, patient outcomes. PMID:25298694

Stress and reproductive hormones in grizzly bears reflect nutritional benefits and social consequences of a salmon foraging niche.

PubMed

Bryan, Heather M; Darimont, Chris T; Paquet, Paul C; Wynne-Edwards, Katherine E; Smits, Judit E G

2013-01-01

Physiological indicators of social and nutritional stress can provide insight into the responses of species to changes in food availability. In coastal British Columbia, Canada, grizzly bears evolved with spawning salmon as an abundant but spatially and temporally constrained food source. Recent and dramatic declines in salmon might have negative consequences on bear health and ultimately fitness. To examine broadly the chronic endocrine effects of a salmon niche, we compared cortisol, progesterone, and testosterone levels in hair from salmon-eating bears from coastal BC (n = 75) with the levels in a reference population from interior BC lacking access to salmon (n = 42). As predicted, testosterone was higher in coastal bears of both sexes relative to interior bears, possibly reflecting higher social density on the coast mediated by salmon availability. We also investigated associations between the amount of salmon individual bears consumed (as measured by stable isotope analysis) and cortisol and testosterone in hair. Also as predicted, cortisol decreased with increasing dietary salmon and was higher after a year of low dietary salmon than after a year of high dietary salmon. These findings at two spatial scales suggest that coastal bears might experience nutritional or social stress in response to on-going salmon declines, providing novel insights into the effects of resource availability on fitness-related physiology.

Understanding Lithium Solvation and Diffusion through Topological Analysis of First-Principles Molecular Dynamics

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

Bhatia, Harsh; Gyulassy, Attila; Ong, Mitchell

2016-09-27

The performance of lithium-ion batteries is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact, both, the solvation and diffusivity of Li ions. In this work, we present our application of the topological techniques to extract and predict such behavior in the data generated by the first-principles molecular dynamics simulation of Li ions in an important organic solvent -ethylene carbonate. More specifically, we use the scalar topology of the electron charge density field tomore » analyze the evolution of the solvation structures. This allows us to derive a parameter-free bond definition for lithium-oxygen bonds, to provide a quantitative measure for bond strength, and to understand the regions of influence of each atom in the simulation. This has provided new insights into how and under what conditions certain bonds may form and break. As a result, we can identify and, more importantly, predict, unstable configurations in solvation structures. This can be very useful in understanding when small changes to the atoms' movements can cause significantly different bond structures to evolve. Ultimately, this promises to allow scientists to explore lithium ion solvation and diffusion more systematically, with the aim of new insights and potentially accelerating the calculations themselves.« less

Stress and Reproductive Hormones in Grizzly Bears Reflect Nutritional Benefits and Social Consequences of a Salmon Foraging Niche

PubMed Central

Bryan, Heather M.; Darimont, Chris T.; Paquet, Paul C.; Wynne-Edwards, Katherine E.; Smits, Judit E. G.

2013-01-01

Physiological indicators of social and nutritional stress can provide insight into the responses of species to changes in food availability. In coastal British Columbia, Canada, grizzly bears evolved with spawning salmon as an abundant but spatially and temporally constrained food source. Recent and dramatic declines in salmon might have negative consequences on bear health and ultimately fitness. To examine broadly the chronic endocrine effects of a salmon niche, we compared cortisol, progesterone, and testosterone levels in hair from salmon-eating bears from coastal BC (n = 75) with the levels in a reference population from interior BC lacking access to salmon (n = 42). As predicted, testosterone was higher in coastal bears of both sexes relative to interior bears, possibly reflecting higher social density on the coast mediated by salmon availability. We also investigated associations between the amount of salmon individual bears consumed (as measured by stable isotope analysis) and cortisol and testosterone in hair. Also as predicted, cortisol decreased with increasing dietary salmon and was higher after a year of low dietary salmon than after a year of high dietary salmon. These findings at two spatial scales suggest that coastal bears might experience nutritional or social stress in response to on-going salmon declines, providing novel insights into the effects of resource availability on fitness-related physiology. PMID:24312230

Spare capacity and phenotypic flexibility in the digestive system of a migratory bird: defining the limits of animal design

PubMed Central

McWilliams, Scott R.; Karasov, William H.

2014-01-01

Flexible phenotypes enable animals to live in environments that change over space and time, and knowing the limits to and the required time scale for this flexibility provides insights into constraints on energy and nutrient intake, diet diversity and niche width. We quantified the level of immediate and ultimate spare capacity, and thus the extent of phenotypic flexibility, in the digestive system of a migratory bird in response to increased energy demand, and identified the digestive constraints responsible for the limits on sustained energy intake. Immediate spare capacity decreased from approximately 50% for birds acclimated to relatively benign temperatures to less than 20% as birds approached their maximum sustainable energy intake. Ultimate spare capacity enabled an increase in feeding rate of approximately 126% as measured in birds acclimated for weeks at −29°C compared with +21°C. Increased gut size and not tissue-specific differences in nutrient uptake or changes in digestive efficiency or retention time were primarily responsible for this increase in capacity with energy demand, and this change required more than 1–2 days. Thus, the pace of change in digestive organ size may often constrain energy intake and, for birds, retard the pace of their migration. PMID:24718764

Spare capacity and phenotypic flexibility in the digestive system of a migratory bird: defining the limits of animal design.

PubMed

McWilliams, Scott R; Karasov, William H

2014-05-22

Flexible phenotypes enable animals to live in environments that change over space and time, and knowing the limits to and the required time scale for this flexibility provides insights into constraints on energy and nutrient intake, diet diversity and niche width. We quantified the level of immediate and ultimate spare capacity, and thus the extent of phenotypic flexibility, in the digestive system of a migratory bird in response to increased energy demand, and identified the digestive constraints responsible for the limits on sustained energy intake. Immediate spare capacity decreased from approximately 50% for birds acclimated to relatively benign temperatures to less than 20% as birds approached their maximum sustainable energy intake. Ultimate spare capacity enabled an increase in feeding rate of approximately 126% as measured in birds acclimated for weeks at -29°C compared with +21°C. Increased gut size and not tissue-specific differences in nutrient uptake or changes in digestive efficiency or retention time were primarily responsible for this increase in capacity with energy demand, and this change required more than 1-2 days. Thus, the pace of change in digestive organ size may often constrain energy intake and, for birds, retard the pace of their migration.

Revisiting perceptions of quality of hospice care: managing for the ultimate referral.

PubMed

Churchman, Richard; York, Grady S; Woodard, Beth; Wainright, Charles; Rau-Foster, Mary

2014-08-01

Hospice services provided in the final months of life are delivered through complex interpersonal relationships between caregivers, patients, and families. Often, service value and quality are defined by these interpersonal interactions. This understanding provides hospice leaders with an enormous opportunity to create processes that provide the optimal level of care during the last months of life. The authors argue that the ultimate referral is attained when a family member observes the care of a loved one, and the family member conveys a desire to receive the same quality of services their loved one received at that facility. The point of this article is to provide evidence that supports the methods to ultimately enhance the patient's and family's experience and increase the potential for the ultimate referral. © The Author(s) 2013.

Towards a more molecular taxonomy of disease.

PubMed

Park, Jisoo; Hescott, Benjamin J; Slonim, Donna K

2017-07-27

Disease taxonomies have been designed for many applications, but they tend not to fully incorporate the growing amount of molecular-level knowledge of disease processes, inhibiting research efforts. Understanding the degree to which we can infer disease relationships from molecular data alone may yield insights into how to ultimately construct more modern taxonomies that integrate both physiological and molecular information. We introduce a new technique we call Parent Promotion to infer hierarchical relationships between disease terms using disease-gene data. We compare this technique with both an established ontology inference method (CliXO) and a minimum weight spanning tree approach. Because there is no gold standard molecular disease taxonomy available, we compare our inferred hierarchies to both the Medical Subject Headings (MeSH) category C forest of diseases and to subnetworks of the Disease Ontology (DO). This comparison provides insights about the inference algorithms, choices of evaluation metrics, and the existing molecular content of various subnetworks of MeSH and the DO. Our results suggest that the Parent Promotion method performs well in most cases. Performance across MeSH trees is also correlated between inference methods. Specifically, inferred relationships are more consistent with those in smaller MeSH disease trees than larger ones, but there are some notable exceptions that may correlate with higher molecular content in MeSH. Our experiments provide insights about learning relationships between diseases from disease genes alone. Future work should explore the prospect of disease term discovery from molecular data and how best to integrate molecular data with anatomical and clinical knowledge. This study nonetheless suggests that disease gene information has the potential to form an important part of the foundation for future representations of the disease landscape.

Dynamic systems approaches and levels of analysis in the nervous system

PubMed Central

Parker, David; Srivastava, Vipin

2013-01-01

Various analyses are applied to physiological signals. While epistemological diversity is necessary to address effects at different levels, there is often a sense of competition between analyses rather than integration. This is evidenced by the differences in the criteria needed to claim understanding in different approaches. In the nervous system, neuronal analyses that attempt to explain network outputs in cellular and synaptic terms are rightly criticized as being insufficient to explain global effects, emergent or otherwise, while higher-level statistical and mathematical analyses can provide quantitative descriptions of outputs but can only hypothesize on their underlying mechanisms. The major gap in neuroscience is arguably our inability to translate what should be seen as complementary effects between levels. We thus ultimately need approaches that allow us to bridge between different spatial and temporal levels. Analytical approaches derived from critical phenomena in the physical sciences are increasingly being applied to physiological systems, including the nervous system, and claim to provide novel insight into physiological mechanisms and opportunities for their control. Analyses of criticality have suggested several important insights that should be considered in cellular analyses. However, there is a mismatch between lower-level neurophysiological approaches and statistical phenomenological analyses that assume that lower-level effects can be abstracted away, which means that these effects are unknown or inaccessible to experimentalists. As a result experimental designs often generate data that is insufficient for analyses of criticality. This review considers the relevance of insights from analyses of criticality to neuronal network analyses, and highlights that to move the analyses forward and close the gap between the theoretical and neurobiological levels, it is necessary to consider that effects at each level are complementary rather than in competition. PMID:23386835

The impact of leadership coaching in an Australian healthcare setting.

PubMed

Grant, Anthony M; Studholme, Ingrid; Verma, Raj; Kirkwood, Lea; Paton, Bronwyn; O'Connor, Sean

2017-04-10

Purpose There is limited empirical literature on the effectiveness of leadership coaching in healthcare settings. The purpose of this paper is to explore the efficacy of leadership coaching for individuals implementing strategic change in the Australian public health system. Design/methodology/approach Using a within-subjects (pre-post) design, participants ( n=31) undertook six one-hour coaching sessions. Coaching was conducted by professional leadership coaches. Both quantitative and qualitative data were collected. Findings Participation was associated with significant improvements in goal attainment, solution-focused thinking, leadership self-efficacy, perspective-taking capacity, self-insight and resilience, and ambiguity tolerance. There were significant reductions in stress and anxiety. The benefits of coaching transferred from the workplace to the home. Many participants reported being able to use insights gained in coaching in their personal lives, and reported better work/life balance, less stress and better quality relationships at home. Originality/value Few studies have provided evaluation of leadership coaching in healthcare setting. Leadership coaching in the public health system may be an important methodology for facilitating goal attainment and fostering resilience in this vital social sector, benefiting workers in the health services, their families and ultimately their patients and the broader community.

New insights into epididymal biology and function.

PubMed

Cornwall, Gail A

2009-01-01

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

Crystal structure of chiral gammaPNA with complementary DNA strand: insights into the stability and specificity of recognition and conformational preorganization.

PubMed

Yeh, Joanne I; Shivachev, Boris; Rapireddy, Srinivas; Crawford, Matthew J; Gil, Roberto R; Du, Shoucheng; Madrid, Marcela; Ly, Danith H

2010-08-11

We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple-wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete gamma-backbone modification ("gammaPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular gammaPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred P-helical conformation upon hybridization with DNA. The unusual structural adaptability found in the gammaPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral gammaPNA is preorganized and stabilized, before and after hybridization with a cDNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology, and medicine.

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

26 CFR 48.6427-8 - Diesel fuel and kerosene; claims by ultimate purchasers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Diesel fuel and kerosene; claims by ultimate... kerosene; claims by ultimate purchasers. (a) Overview. This section provides rules under which ultimate purchasers of taxed diesel fuel and kerosene may claim the income tax credits or payments allowed by section...

Tandem Mass Spectrometry for Characterization of Covalent Adducts of DNA with Anti-cancer Therapeutics

PubMed Central

Silvestri, Catherine; Brodbelt, Jennifer S.

2012-01-01

The chemotherapeutic activities of many anticancer and antibacterial drugs arise from their interactions with nucleic acid substrates. Some of these ligands interact with DNA in a way that causes conformational changes or damage to the nucleic acid targets, ultimately altering recognition by key DNA-specific enzymes, interfering with DNA transcription or prohibiting replication, and terminating cell growth and proliferation. The design and synthesis of ligands that bind to nucleic acids remains a dynamic field in medicinal chemistry and pharmaceutical research. The quest for more selective and efficacious DNA-interactive anti-cancer chemotherapeutics has likewise catalyzed the need for sensitive analytical methods that can provide structural information about the nature of the resulting DNA adducts and provide insight into the mechanistic pathways of the DNA/drug interactions and the impact on the cellular processes in biological systems. This review focuses on the array of tandem mass spectrometric strategies developed and applied for characterization of covalent adducts formed between DNA and anti-cancer ligands. PMID:23150278

Brain activity and cognition: a connection from thermodynamics and information theory

PubMed Central

Collell, Guillem; Fauquet, Jordi

2015-01-01

The connection between brain and mind is an important scientific and philosophical question that we are still far from completely understanding. A crucial point to our work is noticing that thermodynamics provides a convenient framework to model brain activity, whereas cognition can be modeled in information-theoretical terms. In fact, several models have been proposed so far from both approaches. A second critical remark is the existence of deep theoretical connections between thermodynamics and information theory. In fact, some well-known authors claim that the laws of thermodynamics are nothing but principles in information theory. Unlike in physics or chemistry, a formalization of the relationship between information and energy is currently lacking in neuroscience. In this paper we propose a framework to connect physical brain and cognitive models by means of the theoretical connections between information theory and thermodynamics. Ultimately, this article aims at providing further insight on the formal relationship between cognition and neural activity. PMID:26136709

Body Mapping to Explore Reproductive Ethno-Physiological Beliefs and Knowledge of Contraception in Timor-Leste.

PubMed

Wallace, Heather Julie; McDonald, Susan; Belton, Suzanne; Miranda, Agueda Isolina; da Costa, Eurico; da Conceicao Matos, Livio; Henderson, Helen; Taft, Angela

2018-06-01

Maternal mortality remains a significant public health challenge for Timor-Leste. Although access to quality family planning measures may greatly reduce such deaths, consideration of indigenous perceptions, and how they influence reproductive health decision-making and behavior, is crucial if health services are to provide initiatives that are accepted and helpful in improving reproductive health outcomes. We aimed to demonstrate that body mapping is an effective method to traverse language and culture to gain emic insights and indigenous worldviews. The authors' two qualitative research projects (2013 and 2015) used a decolonizing methodology in four districts of Timor-Leste, body mapping with 67 men and 40 women to illuminate ethno-physiology and indigenous beliefs about conception, reproduction, and contraception. Body mapping provided a beneficial conduit for identifying established indigenous reproductive perceptions, understandings, and vocabulary, plus fears surrounding contraception. This may inform health service provision and engagement, ultimately improving the reproductive health of community members.

Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity.

PubMed

Jabir, Rafid Salim; Naidu, Rakesh; Annuar, Muhammad Azrif Bin Ahmad; Ho, Gwo Fuang; Munisamy, Murali; Stanslas, Johnson

2012-12-01

Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.

Projections for insulin treatment for diabetics.

PubMed

Cao, Ying; Lam, Laura

2002-06-01

The evolution of insulin treatment of diabetes has dramatically changed the natural course of this disease. Modern recombinant DNA technology has brought about many new insulin analogues with improved pharmacokinetics, resulting in better glycemic control. In addition, improved insulin delivery systems, such as insulin pumps and pens, have been introduced to provide convenience and to enhance patient compliance. Efforts are currently being devoted to developing noninvasive insulin formulations, such as oral and pulmonary insulin. A number of products are at different stages of clinical trials. Meanwhile, the quest for a permanent cure for diabetes continues. The frontier of diabetes research has gone through a period of substantial expansion, with the emergence of new areas that include gene therapy, islet cell transplantation and diabetic vaccine. Technological breakthroughs, such as recombinant DNA, nanotechnology, microarray-aided genomics and proteomics, will provide more profound insights into the pathogenesis, and the immunological and biological basis of diabetes. Our growing knowledge in these areas will ultimately contribute to the discovery of preventive methods against or a cure for this disease.

Operational properties of fluctuation X-ray scattering data

DOE PAGES

Malmerberg, Erik; Kerfeld, Cheryl A.; Zwart, Petrus H.

2015-03-20

X-ray scattering images collected on timescales shorter than rotation diffusion times using a (partially) coherent beam result in a significant increase in information content in the scattered data. These measurements, named fluctuation X-ray scattering (FXS), are typically performed on an X-ray free-electron laser (XFEL) and can provide fundamental insights into the structure of biological molecules, engineered nanoparticles or energy-related mesoscopic materials beyond what can be obtained with standard X-ray scattering techniques. In order to understand, use and validate experimental FXS data, the availability of basic data characteristics and operational properties is essential, but has been absent up to this point.more » In this communication, an intuitive view of the nature of FXS data and their properties is provided, the effect of FXS data on the derived structural models is highlighted, and generalizations of the Guinier and Porod laws that can ultimately be used to plan experiments and assess the quality of experimental data are presented.« less

Applying Evolutionary Anthropology

PubMed Central

Gibson, Mhairi A; Lawson, David W

2015-01-01

Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. PMID:25684561

Resource footprints and their ecosystem consequences

PubMed Central

Verones, Francesca; Moran, Daniel; Stadler, Konstantin; Kanemoto, Keiichiro; Wood, Richard

2017-01-01

A meaningful environmental impact analysis should go beyond the accounting of pressures from resource use and actually assess how resource demand affects ecosystems. The various currently available footprints of nations report the environmental pressures e.g. water use or pollutant emissions, driven by consumption. However, there have been limited attempts to assess the environmental consequences of these pressures. Ultimately, consequences, not pressures, should guide environmental policymaking. The newly released LC-Impact method demonstrates progress on the path to providing this missing link. Here we present “ecosystem impact footprints” in terms of the consequences for biodiversity and assess the differences in impact footprint results from MRIO-based pressure footprints. The new perspective reveals major changes in the relative contribution of nations to global footprints. Wealthy countries have high pressure footprints in lower-income countries but their impact footprints often have their origin in higher-income countries. This shift in perspective provides a different insight on where to focus policy responses to preserve biodiversity. PMID:28112168

Applying evolutionary anthropology.

PubMed

Gibson, Mhairi A; Lawson, David W

2015-01-01

Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. © 2015 Wiley Periodicals, Inc.

Effects of elasticity and geometry on the locomotion of a model bacterium

NASA Astrophysics Data System (ADS)

Nguyen, Frank; Graham, Michael

2017-11-01

The locomotion of flagellated bacteria in viscous fluid provides the blueprint for a number of micro-scale engineering applications. The elasticities of both the hook protein (connecting cell body and flagellum) and the flagella themselves play a key role in determining the stability of locomotion. We use a coarse-grained discretization of elastic flagella connected to a rigid cell body to examine trajectories and flow fields for free swimmers. We indeed find that hook and/or flagellar buckling occurs above a critical flexibility relative to the swimmer's torque input. This renders straight swimming ineffective, though not necessarily undesirable in practice. Simulations with multiple flagella show bundling may partially stabilize the buckling effect. For a single flagellum or single bundle, we define a parameter space of characteristic angles tracking the overall time-averaged shape of the swimmer while also delineating stability boundaries between different modes of buckling. Ultimately our results may provide insight on how swimmers move through complex environments and how to design microrobotic swimmers for specific applications. NHS, GERS.

Synthesis, characterization and on field evaluation of pesticide loaded sodium alginate nanoparticles.

PubMed

Kumar, Sandeep; Bhanjana, Gaurav; Sharma, Amit; Sidhu, M C; Dilbaghi, Neeraj

2014-01-30

The pesticide formulations in use these days have their own burdens on farming systems in terms of their accumulation in soil and ecosystems which can have serious effects on mankind and living organisms. With the help of nanotechnology, controlled release of agrochemicals, site targeted delivery of various macromolecules desired for improved plant disease resistance, enhanced plant growth and efficient nutrition utilization can be easily done. Nanoencapsulation has an advantage of safer handling and more efficient use of pesticides with less exposure to environment that guarantees ecoprotection. In plant entomology, nanotechnology targets specific agricultural problems in plant pests interaction and provide new ways for crop protection. The present investigation involves the delivery of imidacloprid (admire) pesticide in the form of nanoformulation to plants and investigation of their ultimate effects which can provide some insight for the safe use of this novel technology for the improvement of crop yield and safety. Copyright © 2013 Elsevier Ltd. All rights reserved.

Introducing GHOST: The Geospace/Heliosphere Observation & Simulation Tool-kit

NASA Astrophysics Data System (ADS)

Murphy, J. J.; Elkington, S. R.; Schmitt, P.; Wiltberger, M. J.; Baker, D. N.

2013-12-01

Simulation models of the heliospheric and geospace environments can provide key insights into the geoeffective potential of solar disturbances such as Coronal Mass Ejections and High Speed Solar Wind Streams. Advanced post processing of the results of these simulations greatly enhances the utility of these models for scientists and other researchers. Currently, no supported centralized tool exists for performing these processing tasks. With GHOST, we introduce a toolkit for the ParaView visualization environment that provides a centralized suite of tools suited for Space Physics post processing. Building on the work from the Center For Integrated Space Weather Modeling (CISM) Knowledge Transfer group, GHOST is an open-source tool suite for ParaView. The tool-kit plugin currently provides tools for reading LFM and Enlil data sets, and provides automated tools for data comparison with NASA's CDAweb database. As work progresses, many additional tools will be added and through open-source collaboration, we hope to add readers for additional model types, as well as any additional tools deemed necessary by the scientific public. The ultimate end goal of this work is to provide a complete Sun-to-Earth model analysis toolset.

Life cycle assessment part 2: current impact assessment practice.

PubMed

Pennington, D W; Potting, J; Finnveden, G; Lindeijer, E; Jolliet, O; Rydberg, T; Rebitzer, G

2004-07-01

Providing our society with goods and services contributes to a wide range of environmental impacts. Waste generation, emissions and the consumption of resources occur at many stages in a product's life cycle-from raw material extraction, energy acquisition, production and manufacturing, use, reuse, recycling, through to ultimate disposal. These all contribute to impacts such as climate change, stratospheric ozone depletion, photooxidant formation (smog), eutrophication, acidification, toxicological stress on human health and ecosystems, the depletion of resources and noise-among others. The need exists to address these product-related contributions more holistically and in an integrated manner, providing complimentary insights to those of regulatory/process-oriented methodologies. A previous article (Part 1, Rebitzer et al., 2004) outlined how to define and model a product's life cycle in current practice, as well as the methods and tools that are available for compiling the associated waste, emissions and resource consumption data into a life cycle inventory. This article highlights how practitioners and researchers from many domains have come together to provide indicators for the different impacts attributable to products in the life cycle impact assessment (LCIA) phase of life cycle assessment (LCA).

Basic Energy Sciences Program Update

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

None, None

2016-01-04

The U.S. Department of Energy’s (DOE) Office of Basic Energy Sciences (BES) supports fundamental research to understand, predict, and ultimately control matter and energy at the electronic, atomic, and molecular levels to provide the foundations for new energy technologies and to support DOE missions in energy, environment, and national security. The research disciplines covered by BES—condensed matter and materials physics, chemistry, geosciences, and aspects of physical biosciences— are those that discover new materials and design new chemical processes. These disciplines touch virtually every aspect of energy resources, production, conversion, transmission, storage, efficiency, and waste mitigation. BES also plans, constructs, andmore » operates world-class scientific user facilities that provide outstanding capabilities for imaging and spectroscopy, characterizing materials of all kinds ranging from hard metals to fragile biological samples, and studying the chemical transformation of matter. These facilities are used to correlate the microscopic structure of materials with their macroscopic properties and to study chemical processes. Such experiments provide critical insights to electronic, atomic, and molecular configurations, often at ultrasmall length and ultrafast time scales.« less

Recent advances in metastasis research.

PubMed

Molloy, Tim; van 't Veer, Laura J

2008-02-01

Advances in the early prediction, detection, and treatment of metastatic disease has improved the outlook in cancer patients in recent decades, however, metastasis remains the major cause of death in affected individuals. Metastasis occurs in a series of discreet biological steps in which a single, frequently clinically occult micrometastatic cell travels from the primary tumor to a distant location, where it lodges, grows, and ultimately results in the patient's death. Recent work has provided many new insights in the mechanisms and biology behind metastatic spread. This short review surveys some of the most important recent developments that have helped increase our understanding of the three broad phases of metastasis - the genesis of the metastatic cell through the loss of local constraints in the primary tumor microenvironment, dissemination of the cell to a distant organ while avoiding immune surveillance, and finally lodging and growth of the overt metastasis. These studies are providing mounting evidence that the interactions between tumor and normal cells and tissues are critical for disease progression - a paradigm that will provide a fertile area for future research.

Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis

PubMed Central

Gaylo, Alison; Overstreet, Michael G.; Fowell, Deborah J.

2016-01-01

The ability of CD4 T cells to carry out effector functions is dependent upon the rapid and efficient migration of these cells in inflamed peripheral tissues through an as-yet undefined mechanism. The application of multiphoton microscopy to the study of the immune system provides a tool to measure the dynamics of immune responses within intact tissues. Here we present a protocol for non-invasive intravital multiphoton imaging of CD4 T cells in the inflamed mouse ear dermis. Use of a custom imaging platform and a venous catheter allows for the visualization of CD4 T cell dynamics in the dermal interstitium, with the ability to interrogate these cells in real-time via the addition of blocking antibodies to key molecular components involved in motility. This system provides advantages over both in vitro models and surgically invasive imaging procedures. Understanding the pathways used by CD4 T cells for motility may ultimately provide insight into the basic function of CD4 T cells as well as the pathogenesis of both autoimmune diseases and pathology from chronic infections. PMID:27078264

Data mashups deliver value to physician practices. New data visualization technology not just for consumers any longer.

PubMed

McBride, Jack

2013-01-01

Data mashup technology is one way medical practices can achieve greater insight into the operations of their business. Ultimately, this can lead to higher reimbursements. But what is a mashup, and how does it work? This article discusses how mashups--combining data from two or more disparate sources into a new useful service--are cropping up everywhere.

Paulo Freire: The Man from Recife. Counterpoints: Studies in the Postmodern Theory of Education. Volume 385

ERIC Educational Resources Information Center

Kirylo, James D.

2011-01-01

The unfolding of Paulo Freire's philosophy, uniqueness, and the lens through which he viewed the world, which ultimately brought this gentle spirit of a man onto the world stage, began at a young age in his hometown of Recife, Brazil. Remarkably grounded in the wisdom of humility, yet gifted with a determined strength, deep insight, and perceptive…

Differential network entropy reveals cancer system hallmarks

PubMed Central

West, James; Bianconi, Ginestra; Severini, Simone; Teschendorff, Andrew E.

2012-01-01

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network we here demonstrate that cancer cells are characterised by an increase in network entropy. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local network entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local correlation patterns. In particular, we find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in network entropy. These findings may have potential implications for identifying novel drug targets. PMID:23150773

Focusing and the healing sequence: reclaiming authentic emotions as an aid to communication and well-being in medicine.

PubMed

Bub, Barry

2007-01-01

The reality and prevalence of suicide presents us with myriad questions and levels of concern. What does the dying person do in the face of seemingly endless adversity, loss, fear of abandonment, disfigurement, dependence, and/or unmitigated pain? Everyone working in end-of-life palliative care keeps these very concerns foremost in heart and mind. Yet how can providers process the unfinished spiritual and emotional business that remains when one of our former patients indeed nosedives into Jobian loss and makes the ultimate decision? This dilemma has been a constant companion in the end-of-life terrain, and our guest author Dr Barry Bub brings a wealth of insight into the healing power of authentic emotion in his narrative about the death of the gourmet chef named Ben.

Epigenetics: relevance and implications for public health.

PubMed

Rozek, Laura S; Dolinoy, Dana C; Sartor, Maureen A; Omenn, Gilbert S

2014-01-01

Improved understanding of the multilayer regulation of the human genome has led to a greater appreciation of environmental, nutritional, and epigenetic risk factors for human disease. Chromatin remodeling, histone tail modifications, and DNA methylation are dynamic epigenetic changes responsive to external stimuli. Careful interpretation can provide insights for actionable public health through collaboration between population and basic scientists and through integration of multiple data sources. We review key findings in environmental epigenetics both in human population studies and in animal models, and discuss the implications of these results for risk assessment and public health protection. To ultimately succeed in identifying epigenetic mechanisms leading to complex phenotypes and disease, researchers must integrate the various animal models, human clinical approaches, and human population approaches while paying attention to life-stage sensitivity, to generate effective prescriptions for human health evaluation and disease prevention.

Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents

PubMed Central

Dawed, Adem Yesuf; Zhou, Kaixin; Pearson, Ewan Robert

2016-01-01

Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome. Despite the presence of conflicting results, significant progress has been made in an effort to identify the genetic markers associated with pharmacokinetics, pharmacodynamics, and ultimately therapeutic response and/or adverse outcomes to OHAs. As such, this article presents a comprehensive review of current knowledge on pharmacogenetics of OHAs and provides insights into knowledge gaps and future directions. PMID:27103840

The short-lived African turquoise killifish: an emerging experimental model for ageing

PubMed Central

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-01-01

ABSTRACT Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID:26839399

Covariant C and O Isotope Trends in Some Terrestrial Carbonates and ALH 84001: Possible Linkage Through Similar Formation Processes

NASA Technical Reports Server (NTRS)

Volk, Kathryn E.; Niles, Paul B.; Socki, Richard A.

2011-01-01

Carbonate minerals found on the surface of Mars and in martian meteorites indicate that liquid water has played a significant role in the planet's history. These findings have raised questions regarding the history of the martian hydrosphere and atmosphere as well as the possibility of life. Sunset Crater, Arizona is a dry environment with relatively high evaporation and brief periods of precipitation. This environment resembles Mars and may make Sunset Crater a good analog to martian carbonates. In this study we sought to identify discrete micro-scale isotopic variation within the carbonate crusts in Sunset Crater to see if they resembled the micro-scale isotope variation found in ALH 84001 carbonates. Sunset Crater carbonate formation may be used as a martian analog and ultimately provide insight into carbonate formation in ALH 84001.

The whispering gallery mode biosensor: label-free detection from virus to single protein

NASA Astrophysics Data System (ADS)

Holler, S.; Dantham, V. R.; Keng, D.; Kolchenko, V.; Arnold, S.; Mulroe, Brigid; Paspaley-Grbavac, M.

2014-08-01

The whispering gallery mode (WGM) biosensor is a micro-optical platform capable of sensitive label-free detection of biological particles. Described by the reactive sensing principle (RSP), this analytic formulation quantifies the response of the system to the adsorption of bioparticles. Guided by the RSP, the WGM biosensor enabling from detection of virus (e.g., Human Papillomavirus, HPV) to the ultimate goal of single protein detection. The latter was derived from insights into the RSP, which resulted in the development of a hybrid plasmonic WGM biosensor, which has recently demonstrated detection of individual protein cancer markers. Enhancements from bound gold nanoparticles provide the sensitivity to detect single protein molecules (66 kDa) with good signal-to-noise (S/N > 10), and project that detection of proteins as small as 5 kDa.

A Journey in Science: “Not Lost in Translation”

PubMed Central

Mak, Tak

2016-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Tak Mak, PhD, Professor, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret Cancer Centre in Toronto. A visionary in the field of cancer, this is the story of Dr. Mak’s scientific journey. PMID:27819109

Strain Rate and Anisotropic Microstructure Dependent Mechanical Behaviors of Silkworm Cocoon Shells

PubMed Central

Xu, Jun; Zhang, Wen; Gao, Xiang; Meng, Wanlin; Guan, Juan

2016-01-01

Silkworm cocoons are multi-layered composite structures comprised of high strength silk fiber and sericin, and their mechanical properties have been naturally selected to protect pupas during metamorphosis from various types of external attacks. The present study attempts to gain a comprehensive understanding of the mechanical properties of cocoon shell materials from wild silkworm species Antheraea pernyi under dynamic loading rates. Five dynamic strain rates from 0.00625 s-1 to 12.5 s-1 are tested to show the strain rate sensitivity of the cocoon shell material. In the meantime, the anisotropy of the cocoon shell is considered and the cocoon shell specimens are cut along 0°, 45° and 90° orientation to the short axis of cocoons. Typical mechanical properties including Young’s modulus, yield strength, ultimate strength and ultimate strain are extracted and analyzed from the stress-strain curves. Furthermore, the fracture morphologies of the cocoon shell specimens are observed under scanning electron microscopy to help understand the relationship between the mechanical properties and the microstructures of the cocoon material. A discussion on the dynamic strain rate effect on the mechanical properties of cocoon shell material is followed by fitting our experimental results to two previous models, and the effect could be well explained. We also compare natural and dried cocoon materials for the dynamic strain rate effect and interestingly the dried cocoon shells show better overall mechanical properties. This study provides a different perspective on the mechanical properties of cocoon material as a composite material, and provides some insight for bio-inspired engineering materials. PMID:26939063

Ionic liquid processing of cellulose.

PubMed

Wang, Hui; Gurau, Gabriela; Rogers, Robin D

2012-02-21

Utilization of natural polymers has attracted increasing attention because of the consumption and over-exploitation of non-renewable resources, such as coal and oil. The development of green processing of cellulose, the most abundant biorenewable material on Earth, is urgent from the viewpoints of both sustainability and environmental protection. The discovery of the dissolution of cellulose in ionic liquids (ILs, salts which melt below 100 °C) provides new opportunities for the processing of this biopolymer, however, many fundamental and practical questions need to be answered in order to determine if this will ultimately be a green or sustainable strategy. In this critical review, the open fundamental questions regarding the interactions of cellulose with both the IL cations and anions in the dissolution process are discussed. Investigations have shown that the interactions between the anion and cellulose play an important role in the solvation of cellulose, however, opinions on the role of the cation are conflicting. Some researchers have concluded that the cations are hydrogen bonding to this biopolymer, while others suggest they are not. Our review of the available data has led us to urge the use of more chemical units of solubility, such as 'g cellulose per mole of IL' or 'mol IL per mol hydroxyl in cellulose' to provide more consistency in data reporting and more insight into the dissolution mechanism. This review will also assess the greenness and sustainability of IL processing of biomass, where it would seem that the choices of cation and anion are critical not only to the science of the dissolution, but to the ultimate 'greenness' of any process (142 references).

Simultaneous refraction measurement and OCT axial biometry of the eye during accommodation (Conference Presentation)

NASA Astrophysics Data System (ADS)

De Freitas, Carolina; Hernandez, Victor M.; Ruggeri, Marco; Durkee, Heather A.; Williams, Siobhan; Gregori, Giovanni; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

2016-03-01

The purpose of this project is to design and evaluate a system that will enable objective assessment of the optical accommodative response in real-time while acquiring axial biometric information. The system combines three sub-systems which were integrated and mounted on a joystick x-y-z adjustable modified slit-lamp base to facilitate alignment and data acquisition: (1) a Shack-Hartmann wavefront sensor for dynamic refraction measurement, provided software calculates sphere, cylinder and axis values, (2) an extended-depth Optical Coherence Tomography (OCT) system using an optical switch records high-resolution cross-sectional images across the length of the eye, from which, dynamic axial biometry (corneal thickness, anterior chamber depth, crystalline lens thickness and vitreous depth) can be extracted, and (3) a modified dual-channel accommodation stimulus unit based on the Badal optometer for providing a step change in accommodative stimulus. The prototypal system is capable of taking simultaneous measurements of both the optical and the mechanical response of lens accommodation. These measurements can provide insight into correlating changes in lens shape with changes in lens power and ocular refraction and ultimately provide a more comprehensive understanding of accommodation, presbyopia and an objective assessment of presbyopia correction techniques.

Physics of cancer propagation: A game theory perspective

NASA Astrophysics Data System (ADS)

Cleveland, Chris; Liao, David; Austin, Robert

2012-03-01

This is a theoretical paper which examines at a game theoretical perspective the dynamics of cooperators and cheater cells under metabolic stress conditions and high spatial heterogeneity. Although the ultimate aim of this work is to understand the dynamics of cancer tumor evolution under stress, we use a simple bacterial model to gain fundamental insights into the progression of resistance to drugs under high competition and stress conditions.

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line

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

Barhoumi, Rola, E-mail: rmouneimne@cvm.tamu.edu; Mouneimne, Youssef; Ramos, Ernesto

2011-05-15

Dynamic analysis of the uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) and their metabolites within live cells in real time has the potential to provide novel insights into genotoxic and non-genotoxic mechanisms of cellular injury caused by PAHs. The present work, combining the use of metabolite spectra generated from metabolite standards using multiphoton spectral analysis and an 'advanced unmixing process', identifies and quantifies the uptake, partitioning, and metabolite formation of one of the most important PAHs (benzo[a]pyrene, BaP) in viable cultured rat liver cells over a period of 24 h. The application of the advanced unmixing process resulted inmore » the simultaneous identification of 8 metabolites in live cells at any single time. The accuracy of this unmixing process was verified using specific microsomal epoxide hydrolase inhibitors, glucuronidation and sulfation inhibitors as well as several mixtures of metabolite standards. Our findings prove that the two-photon microscopy imaging surpasses the conventional fluorescence imaging techniques and the unmixing process is a mathematical technique that seems applicable to the analysis of BaP metabolites in living cells especially for analysis of changes of the ultimate carcinogen benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide. Therefore, the combination of the two-photon acquisition with the unmixing process should provide important insights into the cellular and molecular mechanisms by which BaP and other PAHs alter cellular homeostasis.« less

Morphology, development, and evolution of fetal membranes and placentation in squamate reptiles.

PubMed

Blackburn, Daniel G; Flemming, Alexander F

2009-09-15

Current studies on fetal membranes of reptiles are providing insight into three major historical transformations: evolution of the amniote egg, evolution of viviparity, and evolution of placentotrophy. Squamates (lizards and snakes) are ideal for such studies because their fetal membranes sustain embryos in oviparous species and contribute to placentas in viviparous species. Ultrastructure of the fetal membranes in oviparous corn snakes (Pituophis guttatus) shows that the chorioallantois is specialized for gas exchange and the omphalopleure, for water absorption. Transmission and scanning electron microscopic studies of viviparous thamnophine snakes (Thamnophis, Storeria) have revealed morphological specializations for gas exchange and absorption in the intra-uterine environment that represent modifications of features found in oviparous species. Thus, fetal membranes in oviparous species show morphological differentiation for distinct functions that have been recruited and enhanced under viviparous conditions. The ultimate in specialization of fetal membranes is found in viviparous skinks of South America (Mabuya) and Africa (Trachylepis, Eumecia), in which placentotrophy accounts for nearly all of the nutrients for development. Ongoing research on these lizards has revealed morphological specializations of the chorioallantoic placenta through which nutrient transfer is accomplished. In addition, African Trachylepis show an invasive form of implantation, in which uterine epithelium is replaced by invading chorionic cells. Ongoing analysis of these lizards shows how integration of multiple lines of evidence can provide insight into the evolution of developmental and reproductive specializations once thought to be confined to eutherian mammals.

High-resolution cross-borehole thermal tracer testing in granite: preliminary field results

NASA Astrophysics Data System (ADS)

Brixel, Bernard; Klepikova, Maria; Jalali, Mohammadreza; Amann, Florian; Loew, Simon

2017-04-01

Understanding how heat is transported, stored and exchanged across fractured media is becoming increasingly relevant in our society, as manifested from the growing popularity of modern technologies relying on the subsurface to either source or store heat. One good example is the utilization of heat from deep hydrothermal or petrothermal systems to generate electricity for base load power generation, a technology also known as deep geothermal energy (DGE). While very attractive in principle, the number of geothermal fields producing economical levels of electricity to this day is still very limited - largely due to the difficulty of either locating deep reservoirs that are both sufficiently hot and permeable or, in the absence of the latter, creating them. In this context, the Swiss Competence Center for Energy Research - Supply of Electricity (SCCER - SoE) is carrying out an in situ stimulation and circulation (ISC) experiment at the Grimsel Test Site (GTS), an underground rock lab located in the Aar massif, in the Swiss Alps. The circulation experiment planned for the post-stimulation phase represents one of the key components of this experimental research program, and the outcome of this test is expected to ultimately provide key insights in the factors controlling the performance of enhanced geothermal reservoirs. Therefore, to support the design of this experiment, short-term thermal tracer tests (TTT) were conducted with the objective to (i) assess the feasibility of conducting TTTs in a relatively intact granite (where fluid flow is controlled by a limited number of discrete fractures); (ii) determine optimal experimental setups; and to ultimately (iii) monitor thermal breakthroughs at high spatial and temporal resolution, providing insights on heat transport and complementing the characterization of hydrogeological conditions carried out through conventional means (e.g. hydraulic and/or solute tracer tests). Presented herein are the results of a 10-day thermal tracer test conducted by continuously injecting water at 40°C (ambient groundwater temperatures average around 12-13 °C) across a discrete fractured zone, isolated with packers. Monitoring was achieved using a combination of discrete temperature sensors (PT1000) and FO DTS (Silixa XT system) deployed along a network of both packed-off and open boreholes situated approx. 6-20 m apart from the injection zone. Thermal breakthrough was observed in multiple boreholes, as early as 6-7 hours following the injection of hot water. The rate of increase in temperatures was observed to significantly diminish over time, allowing water in the fracture carrying the majority of heat to reach a temperature of 17°C at the closest observation location. Furthermore, temperature declined along the fracture length. These data allowed us identifying the precise location of conductive fractures, thereby improving our understanding of the connectivity structure of our experimental rock volume. In addition, these results provide significant insights on heat transport and the efficiency of heat-exchange between fractures and the surrounding rock mass at Grimsel.

EGFR G796D mutation mediates resistance to osimertinib.

PubMed

Zheng, Di; Hu, Min; Bai, Yu; Zhu, Xuehua; Lu, Xuesong; Wu, Chunyan; Wang, Jiying; Liu, Li; Wang, Zheng; Ni, Jian; Yang, Zhenfan; Xu, Jianfang

2017-07-25

Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification. However, a comprehensive view is still missing. In this study, we presented the first case of Chinese NSCLC patient who developed resistance to osimertinib, and discovered de novo EGFR G796D mutation as a potential mechanism. Our findings provided insights into mechanisms of resistance to osimertinib and highlighted tumor heterogeneity and clonal evolution during the development of drug resistance.

EGFR G796D mutation mediates resistance to osimertinib

PubMed Central

Bai, Yu; Zhu, Xuehua; Lu, Xuesong; Wu, Chunyan; Wang, Jiying; Liu, Li; Wang, Zheng; Ni, Jian; Yang, Zhenfan; Xu, Jianfang

2017-01-01

Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification. However, a comprehensive view is still missing. In this study, we presented the first case of Chinese NSCLC patient who developed resistance to osimertinib, and discovered de novo EGFR G796D mutation as a potential mechanism. Our findings provided insights into mechanisms of resistance to osimertinib and highlighted tumor heterogeneity and clonal evolution during the development of drug resistance. PMID:28572531

Identification and Spectroscopic Characterization of Nonheme Iron(III) Hypochlorite Intermediates.

PubMed

Draksharapu, Apparao; Angelone, Davide; Quesne, Matthew G; Padamati, Sandeep K; Gómez, Laura; Hage, Ronald; Costas, Miquel; Browne, Wesley R; de Visser, Sam P

2015-03-27

Fe III -hypohalite complexes have been implicated in a wide range of important enzyme-catalyzed halogenation reactions including the biosynthesis of natural products and antibiotics and post-translational modification of proteins. The absence of spectroscopic data on such species precludes their identification. Herein, we report the generation and spectroscopic characterization of nonheme Fe III -hypohalite intermediates of possible relevance to iron halogenases. We show that Fe III -OCl polypyridylamine complexes can be sufficiently stable at room temperature to be characterized by UV/Vis absorption, resonance Raman and EPR spectroscopies, and cryo-ESIMS. DFT methods rationalize the pathways to the formation of the Fe III -OCl, and ultimately Fe IV =O, species and provide indirect evidence for a short-lived Fe II -OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases.

Identification and Spectroscopic Characterization of Nonheme Iron(III) Hypochlorite Intermediates**

PubMed Central

Draksharapu, Apparao; Angelone, Davide; Quesne, Matthew G; Padamati, Sandeep K; Gómez, Laura; Hage, Ronald; Costas, Miquel; Browne, Wesley R; de Visser, Sam P

2015-01-01

FeIII–hypohalite complexes have been implicated in a wide range of important enzyme-catalyzed halogenation reactions including the biosynthesis of natural products and antibiotics and post-translational modification of proteins. The absence of spectroscopic data on such species precludes their identification. Herein, we report the generation and spectroscopic characterization of nonheme FeIII–hypohalite intermediates of possible relevance to iron halogenases. We show that FeIII-OCl polypyridylamine complexes can be sufficiently stable at room temperature to be characterized by UV/Vis absorption, resonance Raman and EPR spectroscopies, and cryo-ESIMS. DFT methods rationalize the pathways to the formation of the FeIII-OCl, and ultimately FeIV=O, species and provide indirect evidence for a short-lived FeII-OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases. PMID:25663379

Retrograde Signals: Integrators of Interorganellar Communication and Orchestrators of Plant Development.

PubMed

de Souza, Amancio; Wang, Jin-Zheng; Dehesh, Katayoon

2017-04-28

Interorganellar cooperation maintained via exquisitely controlled retrograde-signaling pathways is an evolutionary necessity for maintenance of cellular homeostasis. This signaling feature has therefore attracted much research attention aimed at improving understanding of the nature of these communication signals, how the signals are sensed, and ultimately the mechanism by which they integrate targeted processes that collectively culminate in organellar cooperativity. The answers to these questions will provide insight into how retrograde-signal-mediated regulatory mechanisms are recruited and which biological processes are targeted, and will advance our understanding of how organisms balance metabolic investments in growth against adaptation to environmental stress. This review summarizes the present understanding of the nature and the functional complexity of retrograde signals as integrators of interorganellar communication and orchestrators of plant development, and offers a perspective on the future of this critical and dynamic area of research.

The entropic cost of quantum generalized measurements

NASA Astrophysics Data System (ADS)

Mancino, Luca; Sbroscia, Marco; Roccia, Emanuele; Gianani, Ilaria; Somma, Fabrizia; Mataloni, Paolo; Paternostro, Mauro; Barbieri, Marco

2018-03-01

Landauer's principle introduces a symmetry between computational and physical processes: erasure of information, a logically irreversible operation, must be underlain by an irreversible transformation dissipating energy. Monitoring micro- and nano-systems needs to enter into the energetic balance of their control; hence, finding the ultimate limits is instrumental to the development of future thermal machines operating at the quantum level. We report on the experimental investigation of a lower bound to the irreversible entropy associated to generalized quantum measurements on a quantum bit. We adopted a quantum photonics gate to implement a device interpolating from the weakly disturbing to the fully invasive and maximally informative regime. Our experiment prompted us to introduce a bound taking into account both the classical result of the measurement and the outcoming quantum state; unlike previous investigation, our entropic bound is based uniquely on measurable quantities. Our results highlight what insights the information-theoretic approach provides on building blocks of quantum information processors.

Sexual harassment induces a temporary fitness cost but does not constrain the acquisition of environmental information in fruit flies.

PubMed

Teseo, Serafino; Veerus, Liisa; Moreno, Céline; Mery, Frédéric

2016-01-01

Across animals, sexual harassment induces fitness costs for females and males. However, little is known about the cognitive costs involved, i.e. whether it constrains learning processes, which could ultimately affect an individual's fitness. Here we evaluate the acquisition of environmental information in groups of fruit flies challenged with various levels of male sexual harassment. We show that, although high sexual harassment induces a temporary fitness cost for females, all fly groups of both sexes exhibit similar levels of learning. This suggests that, in fruit flies, the fitness benefits of acquiring environmental information are not affected by the fitness costs of sexual harassment, and that selection may favour cognition even in unfavourable social contexts. Our study provides novel insights into the relationship between sexual conflicts and cognition and the evolution of female counterstrategies against male sexual harassment. © 2016 The Author(s).

Mercury in gray wolves (Canis lupus) in Alaska: Increased exposure through consumption of marine prey

USGS Publications Warehouse

McGrew, Ashley K.; Ballweber, Lora R.; Moses, Sara K.; Stricker, Craig A.; Beckmen, Kimberlee B.; Salman, Mo D.; O’Hara, Todd M.

2013-01-01

Mercury (Hg) bioaccumulates in the tissues of organismsand biomagnifies within food-webs. Graywolves (Canis lupus) in Alaska primarily acquire Hg through diet; therefore, comparing the extent of Hg exposure inwolves, in conjunction with stable isotopes, from interior and coastal regions of Alaska offers important insight into their feeding ecology. Liver, kidney, and skeletal muscle samples from 162 graywolves were analyzed for total mercury (THg) concentrations and stable isotopic signatures (δ13C, δ15N, and δ34S).Median hepatic THg concentrations were significantly higher in wolves with coastal access compared to wolves from interior Alaska. Stable isotope ratios, in conjunction with THg concentrations, provide strong evidence that coastal wolves are utilizing marine prey representing several trophic levels. The utilization of cross-ecosystem food resources by coastal wolves is clearly contributing to increased THg exposure, and may ultimately have negative health implications for these animals.

Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and management

PubMed Central

Fu, Mei R

2014-01-01

The global burden of breast cancer continues to increase largely because of the aging and growth of the world population. More than 1.38 million women worldwide were estimated to be diagnosed with breast cancer in 2008, accounting for 23% of all diagnosed cancers in women. Given that the 5-year survival rate for breast cancer is now 90%, experiencing breast cancer is ultimately about quality of life. Women treated for breast cancer are facing a life-time risk of developing lymphedema, a chronic condition that occurs in up to 40% of this population and negatively affects breast cancer survivors’ quality of life. This review offers an insightful understanding of the condition by providing clinically relevant and evidence based knowledge regarding lymphedema symptoms, diagnosis, risk reduction, and management with the intent to inform health care professionals so that they might be better equipped to care for patients. PMID:25114841

A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

NASA Astrophysics Data System (ADS)

Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

2016-07-01

Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.

The short-lived African turquoise killifish: an emerging experimental model for ageing.

PubMed

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-02-01

Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. © 2016. Published by The Company of Biologists Ltd.

Characterization of newly synthesized pyrimidine derivatives for corrosion inhibition as inferred from computational chemical analysis

NASA Astrophysics Data System (ADS)

El-Taib Heakal, F.; Rizk, S. A.; Elkholy, A. E.

2018-01-01

Corrosion of metallic constructions is a serious problem in most industries worldwide that can be controlled via addition of special chemicals having adsorption capability on metal surfaces and hence isolating it from the aggressive environment. These chemicals are characterized by being rich in functional groups containing free lone pairs of electrons and/or π-electrons. In the present study four newly imidazole-pyrimidine based ionic derivatives have been synthesized and their structures were characterized by means of elemental analysis and different spectroscopic techniques. Quantum chemical calculations were carried out to give insights into the structural and electronic characteristics of these fabricated compounds. Monte Carlo simulation was also applied to shed the light on our prepared corrosion inhibitor molecules by examining their aptitude to adsorb on iron surface. Our ultimate goal is to help industries in fighting corrosion by providing them with a cheap and efficient anti-corrosion molecules.

Multiple convergent supergene evolution events in mating-type chromosomes.

PubMed

Branco, Sara; Carpentier, Fantin; Rodríguez de la Vega, Ricardo C; Badouin, Hélène; Snirc, Alodie; Le Prieur, Stéphanie; Coelho, Marco A; de Vienne, Damien M; Hartmann, Fanny E; Begerow, Dominik; Hood, Michael E; Giraud, Tatiana

2018-05-21

Convergent adaptation provides unique insights into the predictability of evolution and ultimately into processes of biological diversification. Supergenes (beneficial gene linkage) are striking examples of adaptation, but little is known about their prevalence or evolution. A recent study on anther-smut fungi documented supergene formation by rearrangements linking two key mating-type loci, controlling pre- and post-mating compatibility. Here further high-quality genome assemblies reveal four additional independent cases of chromosomal rearrangements leading to regions of suppressed recombination linking these mating-type loci in closely related species. Such convergent transitions in genomic architecture of mating-type determination indicate strong selection favoring linkage of mating-type loci into cosegregating supergenes. We find independent evolutionary strata (stepwise recombination suppression) in several species, with extensive rearrangements, gene losses, and transposable element accumulation. We thus show remarkable convergence in mating-type chromosome evolution, recurrent supergene formation, and repeated evolution of similar phenotypes through different genomic changes.

Evidence from data storage tags for the presence of lunar and semilunar behavioral cycles in spawning Atlantic cod

USGS Publications Warehouse

Grabowski, Timothy B.; McAdam, Bruce J.; Thorsteinsson, Vilhjalmur; Marteinsdóttir, Gudrún

2015-01-01

Understanding the environmental processes determining the timing and success of reproduction is of critical importance to developing effective management strategies of marine fishes. Unfortunately it has proven difficult to comprehensively study the reproductive behavior of broadcast-spawning fishes. The use of electronic data storage tags (DSTs) has the potential to provide insights into the behavior of fishes. These tags allow for data collection over relatively large spatial and temporal scales that can be correlated to predicted environmental conditions and ultimately be used to refine predictions of year class strength. In this paper we present data retrieved from DSTs demonstrating that events putatively identified as Atlantic cod spawning behavior is tied to a lunar cycle with a pronounced semi-lunar cycle within it. Peak activity occurs around the full and new moon with no evidence of relationship with day/night cycles.

Opening (and Swallowing) A Can of Worms to Treat My Crohn's Disease.

PubMed

Ahrens, Sean

2016-07-01

Editor's Note: This article discusses the experience, ingenuity, and determination of Sean Ahrens, a young patient with Crohn's disease who took it upon himself to treat his longstanding, symptomatic Crohn's disease with pig whipworm eggs. Reading this story will make some of you uncomfortable. You might question whether this work belongs in a medical journal or sends the wrong message to readers. However, we recognize that this topic is controversial and that N=1 reports cannot and should not change practice. The purpose of this story is not to encourage the use of pig whipworm or to demonstrate its efficacy (or lack thereof). We firmly believe that patients are uniquely qualified to provide insights into how they view their illnesses, weigh risks and benefits, and ultimately achieve self-efficacy. Stories like this are important for us to acknowledge and understand, even if they do not change our practice.

Computational studies of physical properties of Nb-Si based alloys

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

Ouyang, Lizhi

2015-04-16

The overall goal is to provide physical properties data supplementing experiments for thermodynamic modeling and other simulations such as phase filed simulation for microstructure and continuum simulations for mechanical properties. These predictive computational modeling and simulations may yield insights that can be used to guide materials design, processing, and manufacture. Ultimately, they may lead to usable Nb-Si based alloy which could play an important role in current plight towards greener energy. The main objectives of the proposed projects are: (1) developing a first principles method based supercell approach for calculating thermodynamic and mechanic properties of ordered crystals and disordered latticesmore » including solid solution; (2) application of the supercell approach to Nb-Si base alloy to compute physical properties data that can be used for thermodynamic modeling and other simulations to guide the optimal design of Nb-Si based alloy.« less

Objective support for subjective reports of successful inner speech in two people with aphasia.

PubMed

Hayward, William; Snider, Sarah F; Luta, George; Friedman, Rhonda B; Turkeltaub, Peter E

2016-01-01

People with aphasia frequently report being able to say a word correctly in their heads, even if they are unable to say that word aloud. It is difficult to know what is meant by these reports of "successful inner speech". We probe the experience of successful inner speech in two people with aphasia. We show that these reports are associated with correct overt speech and phonologically related nonword errors, that they relate to word characteristics associated with ease of lexical access but not ease of production, and that they predict whether or not individual words are relearned during anomia treatment. These findings suggest that reports of successful inner speech are meaningful and may be useful to study self-monitoring in aphasia, to better understand anomia, and to predict treatment outcomes. Ultimately, the study of inner speech in people with aphasia could provide critical insights that inform our understanding of normal language.

Colloidal characterization of silicon nitride and silicon carbide

NASA Technical Reports Server (NTRS)

Feke, Donald L.

1986-01-01

The colloidal behavior of aqueous ceramic slips strongly affects the forming and sintering behavior and the ultimate mechanical strength of the final ceramic product. The colloidal behavior of these materials, which is dominated by electrical interactions between the particles, is complex due to the strong interaction of the solids with the processing fluids. A surface titration methodology, modified to account for this interaction, was developed and used to provide fundamental insights into the interfacial chemistry of these systems. Various powder pretreatment strategies were explored to differentiate between true surface chemistry and artifacts due to exposure history. The colloidal behavior of both silicon nitride and carbide is dominated by silanol groups on the powder surfaces. However, the colloid chemistry of silicon nitride is apparently influenced by an additional amine group. With the proper powder treatments, silicon nitride and carbide powder can be made to appear colloidally equivalent. The impact of these results on processing control will be discussed.

Why marine phytoplankton calcify.

PubMed

Monteiro, Fanny M; Bach, Lennart T; Brownlee, Colin; Bown, Paul; Rickaby, Rosalind E M; Poulton, Alex J; Tyrrell, Toby; Beaufort, Luc; Dutkiewicz, Stephanie; Gibbs, Samantha; Gutowska, Magdalena A; Lee, Renee; Riebesell, Ulf; Young, Jeremy; Ridgwell, Andy

2016-07-01

Calcifying marine phytoplankton-coccolithophores- are some of the most successful yet enigmatic organisms in the ocean and are at risk from global change. To better understand how they will be affected, we need to know "why" coccolithophores calcify. We review coccolithophorid evolutionary history and cell biology as well as insights from recent experiments to provide a critical assessment of the costs and benefits of calcification. We conclude that calcification has high energy demands and that coccolithophores might have calcified initially to reduce grazing pressure but that additional benefits such as protection from photodamage and viral/bacterial attack further explain their high diversity and broad spectrum ecology. The cost-benefit aspect of these traits is illustrated by novel ecosystem modeling, although conclusive observations remain limited. In the future ocean, the trade-off between changing ecological and physiological costs of calcification and their benefits will ultimately decide how this important group is affected by ocean acidification and global warming.

Why marine phytoplankton calcify

PubMed Central

Monteiro, Fanny M.; Bach, Lennart T.; Brownlee, Colin; Bown, Paul; Rickaby, Rosalind E. M.; Poulton, Alex J.; Tyrrell, Toby; Beaufort, Luc; Dutkiewicz, Stephanie; Gibbs, Samantha; Gutowska, Magdalena A.; Lee, Renee; Riebesell, Ulf; Young, Jeremy; Ridgwell, Andy

2016-01-01

Calcifying marine phytoplankton—coccolithophores— are some of the most successful yet enigmatic organisms in the ocean and are at risk from global change. To better understand how they will be affected, we need to know “why” coccolithophores calcify. We review coccolithophorid evolutionary history and cell biology as well as insights from recent experiments to provide a critical assessment of the costs and benefits of calcification. We conclude that calcification has high energy demands and that coccolithophores might have calcified initially to reduce grazing pressure but that additional benefits such as protection from photodamage and viral/bacterial attack further explain their high diversity and broad spectrum ecology. The cost-benefit aspect of these traits is illustrated by novel ecosystem modeling, although conclusive observations remain limited. In the future ocean, the trade-off between changing ecological and physiological costs of calcification and their benefits will ultimately decide how this important group is affected by ocean acidification and global warming. PMID:27453937

On the relation between orbital-localization and self-interaction errors in the density functional theory treatment of organic semiconductors.

PubMed

Körzdörfer, T

2011-03-07

It is commonly argued that the self-interaction error (SIE) inherent in semilocal density functionals is related to the degree of the electronic localization. Yet at the same time there exists a latent ambiguity in the definitions of the terms "localization" and "self-interaction," which ultimately prevents a clear and readily accessible quantification of this relationship. This problem is particularly pressing for organic semiconductor molecules, in which delocalized molecular orbitals typically alternate with localized ones, thus leading to major distortions in the eigenvalue spectra. This paper discusses the relation between localization and SIEs in organic semiconductors in detail. Its findings provide further insights into the SIE in the orbital energies and yield a new perspective on the failure of self-interaction corrections that identify delocalized orbital densities with electrons. © 2011 American Institute of Physics.

Theophylline prevents NAD{sup +} depletion via PARP-1 inhibition in human pulmonary epithelial cells

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

Moonen, Harald J.J.; Geraets, Liesbeth; Vaarhorst, Anika

2005-12-30

Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD{sup +}, resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD{sup +} pool, and of NAD{sup +}-dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD{sup +} levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzymemore » inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies.« less

Relating stress models of magma emplacement to volcano-tectonic earthquakes

NASA Astrophysics Data System (ADS)

Vargas-Bracamontes, D.; Neuberg, J.

2007-12-01

Among the various types of seismic signals linked to volcanic processes, volcano-tectonic earthquakes are probably the earliest precursors of volcanic eruptions. Understanding their relationship with magma emplacement can provide insight into the mechanisms of magma transport at depth and assist in the ultimate goal of forecasting eruptions. Volcano-tectonic events have been observed to occur on faults that experience increases in Coulomb stress changes as the result of magma intrusions. To simulate stress changes associated with magmatic injections, we test different models of volcanic sources in an elastic half-space. For each source model, we look at several aspects that influence the stress conditions of the magmatic system such as the regional tectonic setting, the effect of varying the elastic parameters of the media, the evolution of the magma with time, as well as the volume and rheology of the ascending magma.

High performance aluminum–cerium alloys for high-temperature applications

DOE PAGES

Sims, Zachary C.; Rios, Orlando R.; Weiss, David; ...

2017-08-01

Light-weight high-temperature alloys are important to the transportation industry where weight, cost, and operating temperature are major factors in the design of energy efficient vehicles. Aluminum alloys fill this gap economically but lack high-temperature mechanical performance. Alloying aluminum with cerium creates a highly castable alloy, compatible with traditional aluminum alloy additions, that exhibits dramatically improved high-temperature performance. These compositions display a room temperature ultimate tensile strength of 400 MPa and yield strength of 320 MPa, with 80% mechanical property retention at 240 °C. A mechanism is identified that addresses the mechanical property stability of the Al-alloys to at least 300more » °C and their microstructural stability to above 500 °C which may enable applications without the need for heat treatment. Lastly, neutron diffraction under load provides insight into the unusual mechanisms driving the mechanical strength.« less

NDMA formation kinetics from three pharmaceuticals in four water matrices.

PubMed

Shen, Ruqiao; Andrews, Susan A

2011-11-01

N, N-nitrosodimethylamine (NDMA) is an emerging disinfection by-product (DBP) that has been widely detected in many drinking water systems and commonly associated with the chloramine disinfection process. Some amine-based pharmaceuticals have been demonstrated to form NDMA during chloramination, but studies regarding the reaction kinetics are largely lacking. This study investigates the NDMA formation kinetics from ranitidine, chlorphenamine, and doxylamine under practical chloramine disinfection conditions. The formation profile was monitored in both lab-grade water and real water matrices, and a statistical model is proposed to describe and predict the NDMA formation from selected pharmaceuticals in various water matrices. The results indicate the significant impact of water matrix components and reaction time on the NDMA formation from selected pharmaceuticals, and provide fresh insights on the estimation of ultimate NDMA formation potential from pharmaceutical precursors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Automated motion artifact removal for intravital microscopy, without a priori information.

PubMed

Lee, Sungon; Vinegoni, Claudio; Sebas, Matthew; Weissleder, Ralph

2014-03-28

Intravital fluorescence microscopy, through extended penetration depth and imaging resolution, provides the ability to image at cellular and subcellular resolution in live animals, presenting an opportunity for new insights into in vivo biology. Unfortunately, physiological induced motion components due to respiration and cardiac activity are major sources of image artifacts and impose severe limitations on the effective imaging resolution that can be ultimately achieved in vivo. Here we present a novel imaging methodology capable of automatically removing motion artifacts during intravital microscopy imaging of organs and orthotopic tumors. The method is universally applicable to different laser scanning modalities including confocal and multiphoton microscopy, and offers artifact free reconstructions independent of the physiological motion source and imaged organ. The methodology, which is based on raw data acquisition followed by image processing, is here demonstrated for both cardiac and respiratory motion compensation in mice heart, kidney, liver, pancreas and dorsal window chamber.

Automated motion artifact removal for intravital microscopy, without a priori information

PubMed Central

Lee, Sungon; Vinegoni, Claudio; Sebas, Matthew; Weissleder, Ralph

2014-01-01

Intravital fluorescence microscopy, through extended penetration depth and imaging resolution, provides the ability to image at cellular and subcellular resolution in live animals, presenting an opportunity for new insights into in vivo biology. Unfortunately, physiological induced motion components due to respiration and cardiac activity are major sources of image artifacts and impose severe limitations on the effective imaging resolution that can be ultimately achieved in vivo. Here we present a novel imaging methodology capable of automatically removing motion artifacts during intravital microscopy imaging of organs and orthotopic tumors. The method is universally applicable to different laser scanning modalities including confocal and multiphoton microscopy, and offers artifact free reconstructions independent of the physiological motion source and imaged organ. The methodology, which is based on raw data acquisition followed by image processing, is here demonstrated for both cardiac and respiratory motion compensation in mice heart, kidney, liver, pancreas and dorsal window chamber. PMID:24676021

A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model.

PubMed

Foldi, C J; Milton, L K; Oldfield, B J

2017-10-01

Patients suffering anorexia nervosa (AN) become anhedonic, unable or unwilling to derive normal pleasures and tend to avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia model recapitulates many of the pathophysiological and behavioural hallmarks of the human condition, including a reduction in food intake, excessive exercise, dramatic weight loss, loss of reproductive cycles, hypothermia and anhedonia, and therefore it allows investigation into the underlying neurobiology of anorexia nervosa. The use of this model has directed attention to disruptions in central reward neurocircuitry, which may contribute to disease susceptibility. The purpose of this review is to demonstrate the utility of this unique model to provide insight into the mechanisms of reward relevant to feeding and weight loss, which may ultimately help to unravel the neurobiology of anorexia nervosa and, in a broader sense, the foundation of reward-based feeding. © 2017 British Society for Neuroendocrinology.

Mitochondrial Function in Sepsis

PubMed Central

Arulkumaran, Nishkantha; Deutschman, Clifford S.; Pinsky, Michael R.; Zuckerbraun, Brian; Schumacker, Paul T.; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

2015-01-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

MITOCHONDRIAL FUNCTION IN SEPSIS.

PubMed

Arulkumaran, Nishkantha; Deutschman, Clifford S; Pinsky, Michael R; Zuckerbraun, Brian; Schumacker, Paul T; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

2016-03-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide.

Enhanced micro-vibration sensitive high-damping capacity and mechanical strength achieved in Al matrix composites reinforced with garnet-like lithium electrolyte

NASA Astrophysics Data System (ADS)

Wang, Xian-Ping; Zhang, Yi; Xia, Yu; Jiang, Wei-Bing; Liu, Hui; Liu, Wang; Gao, Yun-Xia; Zhang, Tao; Fang, Qian-Feng

2017-03-01

A novel micro-vibration sensitive-type high-damping Al matrix composites reinforced with Li7- x La3Zr2- x Nb x O12 (LLZNO, x = 0.25) was designed and prepared using an advanced spark plasma sintering (SPS) technique. The damping capacity and mechanical properties of LLZNO/Al composites (LLZNO content: 0-40 wt.%) were found to be greatly improved by the LLZNO addition. The maximum damping capacity and the ultimate tensile strength (UTS) of LLZNO/Al composite can be respectively up to 0.033 and 101.2 MPa in the case of 20 wt.% LLZNO addition. The enhancement of damping and mechanical properties of the composites was ascribed to the intrinsic high-damping capacity and strengthening effects of hard LLZNO particulate. This investigation provides a new insight to sensitively suppress micro-vibration of payloads in the aerospace environment.

Targeting the androgen receptor in prostate and breast cancer – several new agents in development

PubMed Central

Proverbs-Singh, Tracy; Feldman, Jarett L.; Morris, Michael J.; Autio, Karen A.; Traina, Tiffany A.

2016-01-01

Prostate cancer and breast cancer share similarities as hormone-sensitive cancers with a wide heterogeneity of both phenotype and biology. The androgen receptor (AR) is a hormone receptor involved in both benign and malignant processes. Targeting androgen synthesis and the AR pathway has been and remains central to prostate cancer therapy. Recently, there is increased interest in the role of the AR in breast cancer development and growth, with data suggesting AR co-expression with estrogen, progesterone and human epidermal growth factor receptors, across all intrinsic subtypes of breast cancer. Targeting the AR axis is an evolving field with novel therapies in development which may ultimately be applicable for both tumor types. In this review, we offer an overview of available agents which target the AR axis in both prostate and breast cancer and provide insight into the novel drugs in development for targeting this signaling pathway. PMID:25722318

EJE Prize 2012: Obesity: from genes to behaviour.

PubMed

Farooqi, I Sadaf

2014-11-01

An increase in the consumption of highly palatable foods coupled with a reduction in the amount of voluntary exercise undertaken has contributed to the rising prevalence of obesity. However, despite the obvious environmental influences, there is considerable evidence to support a genetic component to weight gain. In some people, particularly those who are severely obese, genetic factors play a major role in the development of their obesity and associated complications. Studies into the genetic basis of obesity have yielded insights into the mechanisms involved in the regulation of weight. We now understand that weight is regulated by neural mechanisms that regulate appetite and energy expenditure and that disruption of these pathways can result in severe obesity in some patients. These studies provide a starting point for investigating patients with severe obesity and may ultimately guide the development of more rational targeted therapies. © 2014 European Society of Endocrinology.

15 CFR 748.11 - Statement by Ultimate Consignee and Purchaser.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ultimate consignee, provided the required statements are contained in Block 24 on the license application... copy submitted by the applicant must be of sufficient quality to ensure all assertions made on the...) Form or letter. The ultimate consignee and purchaser must complete either a statement on company...

15 CFR 748.11 - Statement by Ultimate Consignee and Purchaser.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ultimate consignee, provided the required statements are contained in Block 24 on the license application... copy submitted by the applicant must be of sufficient quality to ensure all assertions made on the...) Form or letter. The ultimate consignee and purchaser must complete either a statement on company...

From Streaming Data to Streaming Insights: The Impact of Data Velocities on Mental Models

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

Endert, Alexander; Pike, William A.; Cook, Kristin A.

The rise of Big Data has influenced the design and technical implementation of visual analytic tools required to handle the increased volumes, velocities, and varieties of data. This has required a set of data management and computational advancements to allow us to store and compute on such datasets. However, as the ultimate goal of visual analytic technology is to enable the discovery and creation of insights from the users, an under-explored area is understanding how these datasets impact their mental models. That is, how have the analytic processes and strategies of users changed? How have users changed their perception ofmore » how to leverage, and ask questions of, these datasets?« less

Replication Stress: A Lifetime of Epigenetic Change

PubMed Central

Khurana, Simran; Oberdoerffer, Philipp

2015-01-01

DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to both genome instability and irreversible cell cycle arrest (senescence). Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function. PMID:26378584

Big Data, Global Development, and Complex Social Systems

NASA Astrophysics Data System (ADS)

Eagle, Nathan

2010-03-01

Petabytes of data about human movements, transactions, and communication patterns are continuously being generated by everyday technologies such as mobile phones and credit cards. This unprecedented volume of information facilitates a novel set of research questions applicable to a wide range of development issues. In collaboration with the mobile phone, internet, and credit card industries, my colleagues and I are aggregating and analyzing behavioral data from over 250 million people from North and South America, Europe, Asia and Africa. I will discuss a selection of projects arising from these collaborations that involve inferring behavioral dynamics on a broad spectrum of scales; from risky behavior in a group of MIT freshman to population-level behavioral signatures, including cholera outbreaks in Rwanda and wealth in the UK. Access to the movement patterns of the majority of mobile phones in East Africa also facilitates realistic models of disease transmission as well as slum formations. This vast volume of data requires new analytical tools - we are developing a range of large-scale network analysis and machine learning algorithms that we hope will provide deeper insight into human behavior. However, ultimately our goal is to determine how we can use these insights to actively improve the lives of the billions of people who generate this data and the societies in which they live.

Predicting the effects of unmodeled dynamics on an aircraft flight control system design using eigenspace assignment

NASA Technical Reports Server (NTRS)

Johnson, Eric N.; Davidson, John B.; Murphy, Patrick C.

1994-01-01

When using eigenspace assignment to design an aircraft flight control system, one must first develop a model of the plant. Certain questions arise when creating this model as to which dynamics of the plant need to be included in the model and which dynamics can be left out or approximated. The answers to these questions are important because a poor choice can lead to closed-loop dynamics that are unpredicted by the design model. To alleviate this problem, a method has been developed for predicting the effect of not including certain dynamics in the design model on the final closed-loop eigenspace. This development provides insight as to which characteristics of unmodeled dynamics will ultimately affect the closed-loop rigid-body dynamics. What results from this insight is a guide for eigenstructure control law designers to aid them in determining which dynamics need or do not need to be included and a new way to include these dynamics in the flight control system design model to achieve a required accuracy in the closed-loop rigid-body dynamics. The method is illustrated for a lateral-directional flight control system design using eigenspace assignment for the NASA High Alpha Research Vehicle (HARV).

Insight into Coenzyme A cofactor binding and the mechanism of acyl-transfer in an acylating aldehyde dehydrogenase from Clostridium phytofermentans

PubMed Central

Tuck, Laura R.; Altenbach, Kirsten; Ang, Thiau Fu; Crawshaw, Adam D.; Campopiano, Dominic J.; Clarke, David J.; Marles-Wright, Jon

2016-01-01

The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, the pathway for the breakdown of fucose and rhamnose is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester the toxic aldehyde intermediates and allow the efficient action of acylating aldehyde dehydrogenase enzymes to produce an acyl-CoA that is ultimately used in substrate-level phosphorylation to produce ATP. Here we analyse the kinetics of the aldehyde dehydrogenase enzyme from the fucose/rhamnose utilisation BMC with different short-chain fatty aldehydes and show that it has activity against substrates with up to six carbon atoms, with optimal activity against propionaldehyde. We have also determined the X-ray crystal structure of this enzyme in complex with CoA and show that the adenine nucleotide of this cofactor is bound in a distinct pocket to the same group in NAD+. This work is the first report of the structure of CoA bound to an aldehyde dehydrogenase enzyme and our crystallographic model provides important insight into the differences within the active site that distinguish the acylating from non-acylating aldehyde dehydrogenase enzymes. PMID:26899032

Insight into Coenzyme A cofactor binding and the mechanism of acyl-transfer in an acylating aldehyde dehydrogenase from Clostridium phytofermentans.

PubMed

Tuck, Laura R; Altenbach, Kirsten; Ang, Thiau Fu; Crawshaw, Adam D; Campopiano, Dominic J; Clarke, David J; Marles-Wright, Jon

2016-02-22

The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, the pathway for the breakdown of fucose and rhamnose is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester the toxic aldehyde intermediates and allow the efficient action of acylating aldehyde dehydrogenase enzymes to produce an acyl-CoA that is ultimately used in substrate-level phosphorylation to produce ATP. Here we analyse the kinetics of the aldehyde dehydrogenase enzyme from the fucose/rhamnose utilisation BMC with different short-chain fatty aldehydes and show that it has activity against substrates with up to six carbon atoms, with optimal activity against propionaldehyde. We have also determined the X-ray crystal structure of this enzyme in complex with CoA and show that the adenine nucleotide of this cofactor is bound in a distinct pocket to the same group in NAD(+). This work is the first report of the structure of CoA bound to an aldehyde dehydrogenase enzyme and our crystallographic model provides important insight into the differences within the active site that distinguish the acylating from non-acylating aldehyde dehydrogenase enzymes.

Fracture and Stress Evolution on Europa: New Insights Into Fracture Interpretation and Ice Thickness Estimates Using Fracture Mechanics Analyses

NASA Technical Reports Server (NTRS)

Kattenhorn, Simon

2004-01-01

The work completed during the funding period has provided many important insights into fracturing behavior in Europa's ice shell. It has been determined that fracturing through time is likely to have been controlled by the effects of nonsynchronous rotation stresses and that as much as 720 deg of said rotation may have occurred during the visible geologic history. It has been determined that there are at least two distinct styles of strike-slip faulting and that their mutual evolutionary styles are likely to have been different, with one involving a significant dilational component during shear motion. It has been determined that secondary fracturing in perturbed stress fields adjacent to older structures such as faults is a prevalent process on Europa. It has been determined that cycloidal ridges are likely to experience shear stresses along the existing segment portions as they propagate, which affects propagation direction and ultimately induces tailcracking at the segment tip than then initiates a new cycle of cycloid segment growth. Finally, it has been established that mechanical methods (e.g., flexure analysis) can be used to determine the elastic thickness of the ice shell, which, although probably only several km thick, is likely to be spatially variable, being thinner under bands but thicker under ridged plains terrain.

Utilizing plasma physics to create biomolecular movies

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

Hau-Riege, S

In spring of 2000, the LCLS Scientific Advisory Committee selected the top scientific experiments for LCLS. One of the proposed flagship experiments is atomic-resolution three-dimensional structure determination of isolated biolgical macromolecules and particles, with the ultimate goal of obtaining molecular (snapshot) movies. The key enabling insight was that radiation damage may be overcome by using x-ray pulses that are shorter than the time it takes for damage to manifest itself.

Common causes of dyspnoea in athletes: a practical approach for diagnosis and management

PubMed Central

Mohseni, Zahra S.; Berwager, Jeffrey D.; Hegedus, Eric J.

2016-01-01

Key points “Dyspnoea” during exercise is a common complaint in seemingly otherwise healthy athletes, which may be associated with fatigue and underperformance. Because dyspnoea is an general term and may be caused by numerous factors, ranging from poor aerobic fitness to serious, potentially fatal respiratory and nonrespiratory pathologies, it is important for clinicians to obtain an appropriate case history and ask relevant exercise-specific questions to fully characterise the nature of the complaint so that a targeted diagnostic plan can be developed. Exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction are two common causes of dyspnoea in athletes, and both are regularly misdiagnosed and mismanaged due to poor adherence to available practice parameters. Aside from airway dysfunction, iron deficiency and anaemia, infectious disease, and musculoskeletal conditions are common problems in athletes which ultimately may lead to complaints of dyspnoea. Educational aims To inform readers of the common causes of dyspnoea encountered in athletes. To highlight that airway diseases, such as asthma and exercise-induced bronchoconstriction, are commonly misdiagnosed and mismanaged. To introduce readers to common nonairway causes of dyspnoea in athletes, including clinical features and general principles of diagnosis, and management. To emphasise the importance of a detailed case history and proper adherence to established protocols in evaluating and managing the dyspnoeic athlete. To provide readers with a general framework of appropriate questions that are useful for developing a targeted diagnostic plan for evaluating dyspnoeic athletes. Dyspnoea during exercise is a common chief complaint in athletes and active individuals. It is not uncommon for dyspnoeic athletes to be diagnosed with asthma, “exercise-induced asthma” or exercise-induced bronchoconstriction based on their symptoms, but this strategy regularly leads to misdiagnosis and improper patient management. Dyspnoea during exercise can ultimately be caused by numerous respiratory and nonrespiratory conditions, ranging from nonpathological to potentially fatal in severity. As, such it is important for healthcare providers to be familiar with the many factors that can cause dyspnoea during exercise in seemingly otherwise-healthy individuals and have a general understanding of the clinical approach to this patient population. This article reviews common conditions that ultimately cause athletes to report dyspnoea and associated symptoms, and provides insight for developing an efficient diagnostic plan. PMID:27408644

Subduction Zone Dewatering at the Southern End of New Zealand's Hikurangi Margin - Insights from 2D Seismic Tomography

NASA Astrophysics Data System (ADS)

Crutchley, G. J.; Klaeschen, D.

2016-12-01

The southern end of New Zealand's Hikurangi subduction margin is characterised by highly-oblique convergence as it makes a southward transition into a right-lateral transform plate boundary. Long-offset seismic data that cross part of the offshore portion of this transition zone give new insight into the nature of the margin. We have carried out two-dimensional pre-stack depth migrations with an iterative reflection tomography to update the velocity field on two seismic lines in this area. The depth-migrated sections show much-improved imaging of faulting within the wedge, and the seismic velocities themselves give clues about the distribution of gas and/or overpressured regions at the plate boundary and within the overlying wedge. A fascinating observation is a major splay fault that has been (or continues to be) a preferred dewatering pathway through the wedge, evidenced by a thermal anomaly that has left its mark on the overlying gas hydrate layer. Another interesting observation is a thick and laterally extensive low velocity zone beneath the subduction interface, which might have important implications for the long-term mechanical stability of the interface. Our on-going work on these data is focused on amplitude versus offset analysis in an attempt to better understand the nature of the subduction interface and also the shallower gas hydrate system. This study is an example of how distinct disturbances of the gas hydrate system can provide insight into subduction zone fluid flow processes that are important for understanding wedge stability and ultimately earthquake hazard.

Critical aspects in the production of periodically ordered mesoporous titania thin films

NASA Astrophysics Data System (ADS)

Soler-Illia, Galo J. A. A.; Angelomé, Paula C.; Fuertes, M. Cecilia; Grosso, David; Boissiere, Cedric

2012-03-01

Periodically ordered mesoporous titania thin films (MTTF) present a high surface area, controlled porosity in the 2-20 nm pore diameter range and an amorphous or crystalline inorganic framework. These materials are nowadays routinely prepared by combining soft chemistry and supramolecular templating. Photocatalytic transparent coatings and titania-based solar cells are the immediate promising applications. However, a wealth of new prospective uses have emerged on the horizon, such as advanced catalysts, perm-selective membranes, optical materials based on plasmonics and photonics, metamaterials, biomaterials or new magnetic nanocomposites. Current and novel applications rely on the ultimate control of the materials features such as pore size and geometry, surface functionality and wall structure. Even if a certain control of these characteristics has been provided by the methods reported so far, the needs for the next generation of MTTF require a deeper insight in the physical and chemical processes taking place in their preparation and processing. This article presents a critical discussion of these aspects. This discussion is essential to evolve from know-how to sound knowledge, aiming at a rational materials design of these fascinating systems.Periodically ordered mesoporous titania thin films (MTTF) present a high surface area, controlled porosity in the 2-20 nm pore diameter range and an amorphous or crystalline inorganic framework. These materials are nowadays routinely prepared by combining soft chemistry and supramolecular templating. Photocatalytic transparent coatings and titania-based solar cells are the immediate promising applications. However, a wealth of new prospective uses have emerged on the horizon, such as advanced catalysts, perm-selective membranes, optical materials based on plasmonics and photonics, metamaterials, biomaterials or new magnetic nanocomposites. Current and novel applications rely on the ultimate control of the materials features such as pore size and geometry, surface functionality and wall structure. Even if a certain control of these characteristics has been provided by the methods reported so far, the needs for the next generation of MTTF require a deeper insight in the physical and chemical processes taking place in their preparation and processing. This article presents a critical discussion of these aspects. This discussion is essential to evolve from know-how to sound knowledge, aiming at a rational materials design of these fascinating systems. Dedicated to Clément Sanchez, on the first anniversary of his appointment to the Hybrid Materials Chair of the Collège de France.

Chromophoric Dissolved Organic Matter across a Marine Distributed Biological Observatory in the Pacific Arctic Region

NASA Astrophysics Data System (ADS)

Berman, S. L.; Frey, K. E.; Shake, K. L.; Cooper, L. W.; Grebmeier, J. M.

2014-12-01

Dissolved organic matter (DOM) plays an important role in marine ecosystems as both a carbon source for the microbial food web (and thus a source of CO2 to the atmosphere) and as a light inhibitor in marine environments. The presence of chromophoric dissolved organic matter (CDOM; the optically active portion of total DOM) can have significant controlling effects on transmittance of sunlight through the water column and therefore on primary production as well as the heat balance of the upper ocean. However, CDOM is also susceptible to photochemical degradation, which decreases the flux of solar radiation that is absorbed. Knowledge of the current spatial and temporal distribution of CDOM in marine environments is thus critical for understanding how ongoing and future changes in climate may impact these biological, biogeochemical, and physical processes. We describe the quantity and quality of CDOM along five key productive transects across a developing Distributed Biological Observatory (DBO) in the Pacific Arctic region. The samples were collected onboard the CCGS Sir Wilfred Laurier in July 2013 and 2014. Monitoring of the variability of CDOM along transects of high productivity can provide important insights into biological and biogeochemical cycling across the region. Our analyses include overall concentrations of CDOM, as well as proxy information such as molecular weight, lability, and source (i.e., autochthonous vs. allochthonous) of organic matter. We utilize these field observations to compare with satellite-derived CDOM concentrations determined from the Aqua MODIS satellite platform, which ultimately provides a spatially and temporally continuous synoptic view of CDOM concentrations throughout the region. Examining the current relationships among CDOM, sea ice variability, biological productivity, and biogeochemical cycling in the Pacific Arctic region will likely provide key insights for how ecosystems throughout the region will respond in future scenarios of climate change.

Power System Simulation for Policymaking and Making Policymakers

NASA Astrophysics Data System (ADS)

Cohen, Michael Ari

Power system simulation is a vital tool for anticipating, planning for and ultimately addressing future conditions on the power grid, especially in light of contemporary shifts in power generation, transmission and use that are being driven by a desire to utilize more environmentally responsible energy sources. This dissertation leverages power system simulation and engineering-economic analysis to provide initial answers to one open question about future power systems: how will high penetrations of distributed (rooftop) solar power affect the physical and economic operation of distribution feeders? We find that the overall impacts of distributed solar power (both positive and negative) on the feeders we modeled are minor compared to the overall cost of energy, but that there is on average a small net benefit provided by distributed generation. We then describe an effort to make similar analyses more accessible to a non-engineering (high school) audience by developing an educational video game called "Griddle" that is based on the same power system simulation techniques used in the first study. We describe the design and evaluation of Griddle and find that it demonstrates potential to provide students with insights about key power system learning objectives.

Framing the nano-biointeractions by proteomics

NASA Astrophysics Data System (ADS)

Sabella, S.; Maiorano, G.; Rizzello, L.; Kote, S.; Cingolani, R.; Pompa, P. P.

2012-03-01

Knowledge of the molecular mechanisms underlying the interactions between nanomaterials and living systems is fundamental for providing more effective products for nanomedicine and drug delivery. Controlling the response of cells/bacteria (such as activation of inflammatory processes or apoptosis/necrosis in tumor cells or pathogenic bacteria) by tuning specific properties of the nanomaterials is ultimately the challenging goal. Notably, this may also provide crucial information in the assessment of any toxic risks induced by nanoparticles on humans. However, in studying the nano-biointeractions, it is imperative to take into account the dynamic evolutions of nanoparticles in the biological environments (in terms of protein corona formation, size and charge changes) in synergy with the dynamic events occurring in cells, including signal transduction, metabolic processes, homeostasis and membrane trafficking. In this context, we discuss the impact of analytical technologies, especially in the field of proteomics, which can provide major insights into the processes affecting the NPs surface as well as the cells and bacteria functionalities. In particular, we show that a precise control of the chemical-physical characteristics of the interacting nanoparticles or nanostructures may impact the cells by inducing changes in the proteomic profiles with direct consequences on their viability.

Metabolic microscopy of head and neck cancer organoids

NASA Astrophysics Data System (ADS)

Shah, Amy T.; Skala, Melissa C.

2016-03-01

Studies for head and neck cancer have primarily relied on cell lines or in vivo animal studies. However, a technique that combines the benefits of high-throughput in vitro studies with a complex, physiologically relevant microenvironment would be advantageous for understanding drug effects. Organoids provide a unique platform that fulfills these goals. Organoids are generated from excised and digested tumor tissue and are grown in culture. Fluorescence microscopy provides high-resolution images on a similar spatial scale as organoids. In particular, autofluorescence imaging of the metabolic cofactors NAD(P)H and FAD can provide insight into response to anti-cancer treatment. The optical redox ratio reflects relative amounts of NAD(P)H and FAD, and the fluorescence lifetime reflects enzyme activity of NAD(P)H and FAD. This study optimizes and characterizes the generation and culture of organoids grown from head and neck cancer tissue. Additionally, organoids were treated for 24 hours with a standard chemotherapy, and metabolic response in the organoids was measured using optical metabolic imaging. Ultimately, combining head and neck cancer organoids with optical metabolic imaging could be applied to test drug sensitivity for drug development studies as well as treatment planning for cancer patients.

Amine Landscaping to Maximize Protein-Dye Fluorescence and Ultrastable Protein-Ligand Interaction.

PubMed

Jacobsen, Michael T; Fairhead, Michael; Fogelstrand, Per; Howarth, Mark

2017-08-17

Chemical modification of proteins provides great opportunities to control and visualize living systems. The most common way to modify proteins is reaction of their abundant amines with N-hydroxysuccinimide (NHS) esters. Here we explore the impact of amine number and positioning on protein-conjugate behavior using streptavidin-biotin, a central research tool. Dye-NHS modification of streptavidin severely damaged ligand binding, necessitating development of a new streptavidin-retaining ultrastable binding after labeling. Exploring the ideal level of dye modification, we engineered a panel bearing 1-6 amines per subunit: "amine landscaping." Surprisingly, brightness increased as amine number decreased, revealing extensive quenching following conventional labeling. We ultimately selected Flavidin (fluorophore-friendly streptavidin), combining ultrastable ligand binding with increased brightness after conjugation. Flavidin enhanced fluorescent imaging, allowing more sensitive and specific cell labeling in tissues. Flavidin should have wide application in molecular detection, providing a general insight into how to optimize simultaneously the behavior of the biomolecule and the chemical probe. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

Soul searching: a brief history of the mind/body debate in the neurosciences.

PubMed

Dolan, Brian

2007-01-01

Anatomical and physiological understandings of the structure and function of the brain have worked to establish it as the "seat of the soul." As an organ of reflection, meditation, and memory, the brain becomes synonymous with what defines the "self" through the existence of consciousness--of mind. Thus, the brain has been associated with a range of transcendent concepts--the soul, spirit, mind, and consciousness--that all relate in fundamental ways to each other both in terms of their perceived location within the brain and because of the way each works ultimately to define the person to whom the brain belongs. In this article, the author provides a brief exploration of how interrelated these categories have been when seen in the context of ancient, Renaissance, early modern, and modern philosophical and medical concerns; how the brain has variously been perceived as home to these intimate states of being; and how practitioners from the neurosciences have reflected on these questions. The author provides novel insights into the interrelationships of philosophy, theology, and medicine by examining these issues through the lens of the history of neuroscience.

Measuring the shapes of macromolecules – and why it matters

PubMed Central

Li, Jie; Mach, Paul; Koehl, Patrice

2013-01-01

The molecular basis of life rests on the activity of biological macromolecules, mostly nucleic acids and proteins. A perhaps surprising finding that crystallized over the last handful of decades is that geometric reasoning plays a major role in our attempt to understand these activities. In this paper, we address this connection between geometry and biology, focusing on methods for measuring and characterizing the shapes of macromolecules. We briefly review existing numerical and analytical approaches that solve these problems. We cover in more details our own work in this field, focusing on the alpha shape theory as it provides a unifying mathematical framework that enable the analytical calculations of the surface area and volume of a macromolecule represented as a union of balls, the detection of pockets and cavities in the molecule, and the quantification of contacts between the atomic balls. We have shown that each of these quantities can be related to physical properties of the molecule under study and ultimately provides insight on its activity. We conclude with a brief description of new challenges for the alpha shape theory in modern structural biology. PMID:24688748

Game theory and strategy in medical training.

PubMed

Blake, Amy; Carroll, Bryan T

2016-11-01

This paper analyses how game theory can provide a framework for understanding the strategic decision-making that occurs in everyday scenarios in medical training and practice, and ultimately serves as a tool for improving the work environment and patient care. Game theory has been applied to a variety of fields outside of its native economics, but has not been thoroughly studied in the context of health care provision. The paper discusses four of the most common 'games' and applies each to a scenario in medicine to provide new insight on the incentives and drivers for certain types of behaviour and a deeper understanding of why certain results are valued more strongly than others. Using game theory as an integrative tool, in conjunction with good judgement and a sound knowledge base, trainees and physicians can work to better recognise where competing priorities exist, understand the motivations and interactions of the various players, and learn to adjust their approaches in order to 'change the game' when their preferred outcome is not the most likely one. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Microspectrometric insights on the uptake of antibiotics at the single bacterial cell level

PubMed Central

Cinquin, Bertrand; Maigre, Laure; Pinet, Elizabeth; Chevalier, Jacqueline; Stavenger, Robert A.; Mills, Scott; Réfrégiers, Matthieu; Pagès, Jean-Marie

2015-01-01

Bacterial multidrug resistance is a significant health issue. A key challenge, particularly in Gram-negative antibacterial research, is to better understand membrane permeation of antibiotics in clinically relevant bacterial pathogens. Passing through the membrane barrier to reach the required concentration inside the bacterium is a pivotal step for most antibacterials. Spectrometric methodology has been developed to detect drugs inside bacteria and recent studies have focused on bacterial cell imaging. Ultimately, we seek to use this method to identify pharmacophoric groups which improve penetration, and therefore accumulation, of small-molecule antibiotics inside bacteria. We developed a method to quantify the time scale of antibiotic accumulation in living bacterial cells. Tunable ultraviolet excitation provided by DISCO beamline (synchrotron Soleil) combined with microscopy allows spectroscopic analysis of the antibiotic signal in individual bacterial cells. Robust controls and measurement of the crosstalk between fluorescence channels can provide real time quantification of drug. This technique represents a new method to assay drug translocation inside the cell and therefore incorporate rational drug design to impact antibiotic uptake. PMID:26656111

Challenges With Research Contract Negotiations in Community-Based Cancer Research.

PubMed

Thompson, Michael A; Hurley, Patricia A; Faller, Bryan; Longinette, Jean; Richter, Katie; Stewart, Teresa L; Robert, Nicholas

2016-06-01

Community-based research programs face many barriers to participation in clinical trials. Although the majority of people with cancer are diagnosed and treated in the community setting, only roughly 3% are enrolled onto clinical trials. Research contract and budget negotiations have been consistently identified as time consuming and a barrier to participation in clinical trials. ASCO's Community Research Forum conducted a survey about specific challenges of research contract and budget negotiation processes in community-based research settings. The goal was to ultimately identify potential solutions to these barriers. A survey was distributed to 780 community-based physician investigators and research staff. The survey included questions to provide insight into contract and budget negotiation processes and perceptions about related barriers. A total of 77% of the 150 respondents acknowledged barriers in the process. Respondents most frequently identified budget-related issues (n = 133), inefficiencies in the process (n = 80), or legal review and negotiation issues (n = 70). Of the respondents, 44.1% indicated that contract research organizations made the contract negotiations process harder for their research program, and only 5% believed contract research organizations made the process easier. The contract negotiations process is perceived to be impeded by sponsors through underestimation of costs, lack of flexibility with the contract language, and excessive delays. Improving clinical trial activation processes and reducing inefficiencies would be beneficial to all interested stakeholders, including patients who may ultimately stand to benefit from participation in clinical trials. The following key recommendations were made: standardization of contracts and negotiation processes to promulgate transparency and efficiencies, improve sponsor processes to minimize burden on sites, create and promote use of contract templates and best practices, and provide education and consultation. Copyright © 2016 by American Society of Clinical Oncology.

Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis

DTIC Science & Technology

2008-12-01

Isaacs WB, De Marzo AM, Luo J. GOLPH2 and MYO6: putative prostate cancer markers localized to the Golgi apparatus . Prostate. 2008 Sep 15;68(13):1387...may be caused by ingestion of cooked meats. This result will open up new areas of investigation into this question. For example, it would be highly...by this award has added significant new insights and discoveries that will help us to ultimately reach our overarching goal. This report will

How Asking a Very Basic Research Question Led Us to a Model for at Least Three Diseases | Poster

Cancer.gov

By Howard Young Editor’s note: This article is adapted from Dr. Young’s January 12, 2015, post to the I am Intramural Blog of the Intramural Research Program. When I started this project, it was not my objective to develop a model for any specific disease, nor did I even suspect that the ultimate result would be some insight into autoimmune disease. The basic research question

Adaptive polymeric nanomaterials utilizing reversible covalent and hydrogen bonding

NASA Astrophysics Data System (ADS)

Neikirk, Colin

Adaptive materials based on stimuli responsive and reversible bonding moieties are a rapidly developing area of materials research. Advances in supramolecular chemistry are now being adapted to novel molecular architectures including supramolecular polymers to allow small, reversible changes in molecular and nanoscale structure to affect large changes in macroscale properties. Meanwhile, dynamic covalent chemistry provides a complementary approach that will also play a role in the development of smart adaptive materials. In this thesis, we present several advances to the field of adaptive materials and also provide relevant insight to the areas of polymer nanocomposites and polymer nanoparticles. First, we have utilized the innate molecular recognition and binding capabilities of the quadruple hydrogen bonding group ureidopyrimidinone (UPy) to prepare supramolecular polymer nanocomposites based on supramolecular poly(caprolactone) which show improved mechanical properties, but also an increase in particle aggregation with nanoparticle UPy functionalization. We also present further insight into the relative effects of filler-filler, filler-matrix, and matrix-matrix interactions using a UPy side-chain functional poly(butyl acrylate). These nanocomposites have markedly different behavior depending on the amount of UPy sidechain functionality. Meanwhile, our investigations of reversible photo-response showed that coumarin functionality in polymer nanoparticles not only facilitates light mediated aggregation/dissociation behavior, but also provides a substantial overall reduction in particle size and improvement in nanoparticle stability for particles prepared by Flash NanoPrecipitation. Finally, we have combined these stimuli responsive motifs as a starting point for the development of multiresponsive adaptive materials. The synthesis of a library of multifunctional materials has provided a strong base for future research in this area, although our initial investigations were ultimately unsuccessful due to photodegradation of the UPy moiety in chloroform solution. This thesis has provided the Priestley lab with a solid base for the further investigation of the diverse applications and unsolved science of stimuli responsive adaptive materials.

Optogenetics in preclinical neuroscience and psychiatry research: recent insights and potential applications.

PubMed

McDevitt, Ross A; Reed, Sean J; Britt, Jonathan P

2014-01-01

There have been significant advances in the treatment of psychiatric disease in the last half century, but it is still unclear which neural circuits are ultimately responsible for specific disease states. Fortunately, technical limitations that have constrained this research have recently been mitigated by advances in research tools that facilitate circuit-based analyses. The most prominent of these tools is optogenetics, which refers to the use of genetically encoded, light-sensitive proteins that can be used to manipulate discrete neural circuits with temporal precision. Optogenetics has recently been used to examine the neural underpinnings of both psychiatric disease and symptom relief, and this research has rapidly identified novel therapeutic targets for what could be a new generation of rational drug development. As these and related methodologies for controlling neurons ultimately make their way into the clinic, circuit-based strategies for alleviating psychiatric symptoms could become a remarkably refined approach to disease treatment.

Hallmarks of response to immune checkpoint blockade

PubMed Central

Cogdill, Alexandria P; Andrews, Miles C; Wargo, Jennifer A

2017-01-01

Unprecedented advances have been made in the treatment of cancer through the use of immune checkpoint blockade, with approval of several checkpoint blockade regimens spanning multiple cancer types. However, responses to this form of therapy are not universal, and insights are clearly needed to identify optimal biomarkers of response and to combat mechanisms of therapeutic resistance. A working knowledge of the hallmarks of cancer yields insight into responses to immune checkpoint blockade, although the focus of this is rather tumour-centric and additional factors are pertinent, including host immunity and environmental influences. Herein, we describe the foundation for pillars and hallmarks of response to immune checkpoint blockade, with a discussion of their relevance to immune monitoring and mechanisms of resistance. Evolution of this understanding will ultimately help guide treatment strategies to enhance therapeutic responses. PMID:28524159

Application of isotopic labeling, and gas chromatography mass spectrometry, to understanding degradation products and pathways in the thermal-oxidative aging of Nylon 6.6

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

White, Gregory Von; Clough, Roger L.; Hochrein, James M.

2013-12-01

Nylon 6.6 containing 13C isotopic labels at specific positions along the macromolecular backbone has been subjected to extensive thermal-oxidative aging at 138 °C for time periods up to 243 days. In complementary experiments, unlabeled Nylon 6.6 was subjected to the same aging conditions under an atmosphere of 18O 2. Volatile organic degradation products were analyzed by cryofocusing gas chromatography mass spectrometry (cryo-GC/MS) to identify the isotopic labeling. The labeling results, combined with basic considerations of free radical reaction chemistry, provided insights to the origin of degradation species, with respect to the macromolecular structure. A number of inferences on chemical mechanismsmore » were drawn, based on 1) the presence (or absence) of the isotopic labels in the various products, 2) the location of the isotope within the product molecule, and 3) the relative abundance of products as indicated by large differences in peak intensities in the gas chromatogram. The overall degradation results can be understood in terms of free radical pathways originating from initial attacks on three different positions along the nylon chain which include hydrogen abstraction from: the (CH 2) group adjacent to the nitrogen atom, at the (CH 2) adjacent the carbonyl group, and direct radical attack on the carbonyl. Understanding the pathways which lead to Nylon 6.6 degradation ultimately provides new insight into changes that can be leveraged to detect and reduce early aging and minimize problems associated with material degradation.« less

Space Shuttle Ascent Flight Design Process: Evolution and Lessons Learned

NASA Technical Reports Server (NTRS)

Picka, Bret A.; Glenn, Christopher B.

2011-01-01

The Space Shuttle Ascent Flight Design team is responsible for defining a launch to orbit trajectory profile that satisfies all programmatic mission objectives and defines the ground and onboard reconfiguration requirements for this high-speed and demanding flight phase. This design, verification and reconfiguration process ensures that all applicable mission scenarios are enveloped within integrated vehicle and spacecraft certification constraints and criteria, and includes the design of the nominal ascent profile and trajectory profiles for both uphill and ground-to-ground aborts. The team also develops a wide array of associated training, avionics flight software verification, onboard crew and operations facility products. These key ground and onboard products provide the ultimate users and operators the necessary insight and situational awareness for trajectory dynamics, performance and event sequences, abort mode boundaries and moding, flight performance and impact predictions for launch vehicle stages for use in range safety, and flight software performance. These products also provide the necessary insight to or reconfiguration of communications and tracking systems, launch collision avoidance requirements, and day of launch crew targeting and onboard guidance, navigation and flight control updates that incorporate the final vehicle configuration and environment conditions for the mission. Over the course of the Space Shuttle Program, ascent trajectory design and mission planning has evolved in order to improve program flexibility and reduce cost, while maintaining outstanding data quality. Along the way, the team has implemented innovative solutions and technologies in order to overcome significant challenges. A number of these solutions may have applicability to future human spaceflight programs.

Trace elements at the intersection of marine biological and geochemical evolution

USGS Publications Warehouse

Robbins, Leslie J.; Lalonde, Stefan V.; Planavsky, Noah J.; Partin, Camille A.; Reinhard, Christopher T.; Kendall, Brian; Scott, Clinton T.; Hardisty, Dalton S.; Gill, Benjamin C.; Alessi, Daniel S.; Dupont, Christopher L.; Saito, Mak A.; Crowe, Sean A.; Poulton, Simon W.; Bekker, Andrey; Lyons, Timothy W.; Konhauser, Kurt O.

2016-01-01

Life requires a wide variety of bioessential trace elements to act as structural components and reactive centers in metalloenzymes. These requirements differ between organisms and have evolved over geological time, likely guided in some part by environmental conditions. Until recently, most of what was understood regarding trace element concentrations in the Precambrian oceans was inferred by extrapolation, geochemical modeling, and/or genomic studies. However, in the past decade, the increasing availability of trace element and isotopic data for sedimentary rocks of all ages has yielded new, and potentially more direct, insights into secular changes in seawater composition – and ultimately the evolution of the marine biosphere. Compiled records of many bioessential trace elements (including Ni, Mo, P, Zn, Co, Cr, Se, and I) provide new insight into how trace element abundance in Earth's ancient oceans may have been linked to biological evolution. Several of these trace elements display redox-sensitive behavior, while others are redox-sensitive but not bioessential (e.g., Cr, U). Their temporal trends in sedimentary archives provide useful constraints on changes in atmosphere-ocean redox conditions that are linked to biological evolution, for example, the activity of oxygen-producing, photosynthetic cyanobacteria. In this review, we summarize available Precambrian trace element proxy data, and discuss how temporal trends in the seawater concentrations of specific trace elements may be linked to the evolution of both simple and complex life. We also examine several biologically relevant and/or redox-sensitive trace elements that have yet to be fully examined in the sedimentary rock record (e.g., Cu, Cd, W) and suggest several directions for future studies.

Leaf evolution in early-diverging ferns: insights from a new fern-like plant from the Late Devonian of China

PubMed Central

Wang, De-Ming; Xu, Hong-He; Xue, Jin-Zhuang; Wang, Qi; Liu, Le

2015-01-01

Background and Aims With the exception of angiosperms, the main euphyllophyte lineages (i.e. ferns sensu lato, progymnosperms and gymnosperms) had evolved laminate leaves by the Late Devonian. The evolution of laminate leaves, however, remains unclear for early-diverging ferns, largely represented by fern-like plants. This study presents a novel fern-like taxon with pinnules, which provides new insights into the early evolution of laminate leaves in early-diverging ferns. Methods Macrofossil specimens were collected from the Upper Devonian (Famennian) Wutong Formation of Anhui and Jiangsu Provinces, South China. A standard degagement technique was employed to uncover compressed plant portions within the rock matrix. Key Results A new fern-like taxon, Shougangia bella gen. et sp. nov., is described and represents an early-diverging fern with highly derived features. It has a partially creeping stem with adventitious roots only on one side, upright primary and secondary branches arranged in helices, tertiary branches borne alternately or (sub)oppositely, laminate and usually lobed leaves with divergent veins, and complex fertile organs terminating tertiary branches and possessing multiple divisions and numerous terminal sporangia. Conclusions Shougangia bella provides unequivocal fossil evidence for laminate leaves in early-diverging ferns. It suggests that fern-like plants, along with other euphyllophyte lineages, had independently evolved megaphylls by the Late Devonian, possibly in response to a significant decline in atmospheric CO2 concentration. Among fern-like plants, planate ultimate appendages are homologous with laminate pinnules, and in the evolution of megaphylls, fertile organs tend to become complex. PMID:25979918

Fine Scale Phytoplankton Diversity of Galveston Bay: Imaging FlowCytobot Provides Insight into Microbial Community Dynamics

NASA Astrophysics Data System (ADS)

Preischel, H.; Sosik, H. M.; Lawrence, S.; Lucchese, A.; Genzer, J.; Steichen, J. L.; Quigg, A.

2016-02-01

Galveston Bay, the largest watershed in Texas, is impacted by anthropogenic nutrient inputs from two growing major cities: Houston and Dallas-Fort Worth. Expansion of the Panama Canal in 2016 will lead to an increase in shipping into Galveston Bay, which in turn will lead to an increase in discharge of ballast water into the bay. These two inputs combined are likely to lead to an increase in invasive phytoplankton species and nutrient inputs and ultimately an increase in the frequency of algal blooms, some of which may be harmful. Because of this, it is important to understand the current phytoplankton diversity in order to know which harmful algal species are present, when they are abundant, and when they are most likely to produce blooms. Ultimately this information will provide early detection, avoid human illness from shellfish poisoning and possibly lead to regulation of nutrient inputs. Historically, diatoms have been found to be the most abundant phytoplankton in the winter and spring, when nutrient inputs into Galveston Bay are higher. Small flagellates and cyanobacteria have been found to be the most abundant phytoplankton during times of warmer weather and low nutrient inputs. Daily samples are being taken from Galveston Bay near the entrance to the Gulf of Mexico. These samples are being examined with an Imaging FlowCytobot to document community composition shifts down to lowest practical identification level. Relative diversity is being assessed with traditional indices including the Shannon-Weiner and Simpson's diversity indices. Compared to previous studies, this approach will allow us to characterize much finer scale community composition changes concurrently with those in temperature and salinity. This information will also provide a library of phytoplankton types in Galveston Bay and, with concurrent water quality data, will be used to develop predictive tools or determine under which scenarios if any, harmful algal blooms are more likely to occur.

Reform Doesn't Work: Grassroots Efforts Can Provide Answers to School Improvement

ERIC Educational Resources Information Center

Babbage, Keen

2012-01-01

Where does education happen? In classrooms. Teachers can provide the ultimate reform of education and teachers can be the ultimate reformers of education. Still, teachers cannot create all of the needed improvements in education alone. Input from, involvement from, ideas from, and participation from many other people can combine with what only…

Volatile reservoirs below the surface of the Elysium region of Mars: Geomorphic evidence

NASA Technical Reports Server (NTRS)

Christiansen, Eric H.; Hopler, Jennifer A.

1987-01-01

The Elysium volcanic province contains a variety of geomorphic evidence for the existence of large volatile reservoirs of subsurface volatiles. Study of these landforms yields insight into the distribution and size of these reservoirs and how they interact with the surface environment and will ultimately place constraints on the geometry, constitution, origin, time of formation, and temporal evolution of these important components of the Martian crust. Three principal types of landforms appear to be related to subsurface volatile reservoirs in the Elysium region of Mars: small outflow channels; large lahars; and vast expanses of knobby terranes around the margins of the Elysium dome. The evidence provided by these landforms is internally consistent with the presence of a large relatively shallow volatile reservoir in the Elysium region. If the geologic features described are reliable indicators of subsurface volatiles, they imply that: volatile reservoirs lie relatively close to the surface and underlie millions of sq km in this region; there is no apparent latitudinal variation in the depth or thickness of the volatile reservoirs; the precursors of the knobby terranes are or were important volatile reservoirs; volatiles may be lost in a variety of ways from these reservoirs; and volatiles were incorporated in an easily eroded surficial deposit in the middle history of Mars. The ultimate origin of water in this reservoir is uncertain. A model to explain the preferential entrapment of volatiles into the region's surface materials may be required.

Adjudicating pathological criminal incapacity within a climate of ultimate issue barriers: a comparative perspective.

PubMed

Stevens, Geert Philip

2015-01-01

Mental health experts are increasingly being utilised by the criminal justice system to provide assistance to courts during the assessment of issues falling beyond the knowledge and/or experience of the courts. A particular domain where the assistance of qualified psychiatrists and psychologists is becoming essential is where the defence of pathological criminal incapacity falls to be assessed. Mental health professionals testifying during trials where the defence of pathological criminal incapacity is raised will present opinion evidence which is one of the exceptions to the rule of inadmissibility of opinion evidence. Mental health professionals providing their opinion evidence are, however, prohibited from expressing opinions on so-called "ultimate issues" upon which only the court may ultimately rule upon. The latter rule is also commonly known in practice as the "ultimate issue" rule which presents multifaceted challenges in respect of the application of the defence of pathological criminal incapacity. In this article, the author assesses the application of the ultimate issue rule with reference to the defence of pathological criminal incapacity as it operates within the South African criminal law context. A comparative analysis is also provided with reference to the rule as it operates in the United States of America and more specifically Federal Rule 704. It is concluded that the ultimate issue rule unnecessarily restricts testimony provided by mental health professionals as such placing a barrier on such evidence. As such, it is argued that the rule is superfluous as it remains within the discretion of the trier of fact to decide as to what weight to attach to such evidence. Copyright © 2015. Published by Elsevier Ltd.

Arranged Marriages: Relationships Between Regular and Irregular Forces, During the Early American Revolutionary War in Monmouth County, New Jersey

DTIC Science & Technology

2013-12-10

like an arranged marriage, regular and irregular forces can make the best of the situation and make it work , or hold onto preconceived notions and let...ultimately failed. In contrast, the rebels found a way to make the arrangement work . This monograph begins with a discussion of irregular units as a...it concludes with a few insights to consider when approaching future relationships. The difficulty and necessity of building positive working

Electron Transport Modeling of Molecular Nanoscale Bridges Used in Energy Conversion Schemes

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

Dunietz, Barry D

2016-08-09

The goal of the research program is to reliably describe electron transport and transfer processes at the molecular level. Such insight is essential for improving molecular applications of solar and thermal energy conversion. We develop electronic structure models to study (1) photoinduced electron transfer and transport processes in organic semiconducting materials, and (2) charge and heat transport through molecular bridges. We seek fundamental understanding of key processes, which lead to design new experiments and ultimately to achieve systems with improved properties.

Biogenesis: number mysticism in protein thinking.

PubMed

Klotz, I M

1993-10-01

Historically, great minds have been tantalized by the idea that integers contain hidden, subtle meanings that could give us deep insights into natural (and supernatural) phenomena. Numerological analysis has been used in religion, mythology, and the sciences. In the field of proteins, integers played a stimulating role during early struggles to unravel structure, but they ultimately proved constrictive and misleading. In contrast, the introduction of imaginary (or complex) numbers into the algebra and numerical analysis of ligand-protein affinities can open new perspectives into such interactions.

Sharing the Sky: The Role of Family and Consumer Sciences in Sustainability.

ERIC Educational Resources Information Center

Makela, Carole J.

2003-01-01

Explains why sustainability is integral to family and consumer sciences. Presents a framework depicting the relationship of ultimate means, intermediate means, intermediate ends, and ultimate ends. Provides classroom activities. (SK)

Management of carbon across sectors and scales: Insights from land use decision making

NASA Astrophysics Data System (ADS)

Dilling, L.; Failey, E. L.

2008-12-01

Carbon management is increasingly becoming a topic of interest among policy circles and business entrepreneurs alike. In the United States, while no binding regulatory framework exists, carbon management is nonetheless being pursued both by voluntary actions at a variety of levels, from the individual to the national level, and through mandatory policies at state and local levels. Controlling the amount of carbon dioxide in the atmosphere for climate purposes will ultimately require a form of governance that will ensure that the actions taken and being rewarded financially are indeed effective with respect to the global atmosphere on long time scales. Moreover, this new system of governance will need to interface with existing governance structures and decision criteria that have been established to arbitrate among various societal values and priorities. These existing institutions and expressed values will need to be examined against those proposed for effective carbon governance, such as the permanence of carbon storage, the additionality of credited activities, and the prevention of leakage, or displacement of prohibited activities to another region outside the governance boundary. The latter issue suggests that interactions among scales of decision making and governance will be extremely important in determining the ultimate success of any future system of carbon governance. The goal of our study is to understand the current context of land use decision making in different sectors and examine the potential for future carbon policy to be effective given this context. This study examined land use decision making in the U.S. state of Colorado from a variety of ownership perspectives, including US Federal land managers, individual private owners, and policy makers involved in land use at a number of different scales. This paper will report on the results of interviews with land managers and provide insight into the policy context for carbon management through land use. The study also examined the role of information in making decisions, and we will report some interesting contrasts between Federal and private land owner practices. Implications for science policy and the provision of useful information for decision making will be discussed.

Spatiotemporal Segmentation and Modeling of the Mitral Valve in Real-Time 3D Echocardiographic Images.

PubMed

Pouch, Alison M; Aly, Ahmed H; Lai, Eric K; Yushkevich, Natalie; Stoffers, Rutger H; Gorman, Joseph H; Cheung, Albert T; Gorman, Joseph H; Gorman, Robert C; Yushkevich, Paul A

2017-09-01

Transesophageal echocardiography is the primary imaging modality for preoperative assessment of mitral valves with ischemic mitral regurgitation (IMR). While there are well known echocardiographic insights into the 3D morphology of mitral valves with IMR, such as annular dilation and leaflet tethering, less is understood about how quantification of valve dynamics can inform surgical treatment of IMR or predict short-term recurrence of the disease. As a step towards filling this knowledge gap, we present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE). The framework integrates multi-atlas label fusion and template-based medial modeling to generate quantitatively descriptive models of valve dynamics. The novelty of this work is that temporal consistency in the rt-3DE segmentations is enforced during both the segmentation and modeling stages with the use of groupwise label fusion and Kalman filtering. The algorithm is evaluated on rt-3DE data series from 10 patients: five with normal mitral valve morphology and five with severe IMR. In these 10 data series that total 207 individual 3DE images, each 3DE segmentation is validated against manual tracing and temporal consistency between segmentations is demonstrated. The ultimate goal is to generate accurate and consistent representations of valve dynamics that can both visually and quantitatively provide insight into normal and pathological valve function.

Insights on energy selective contacts for thermal energy harvesting using double resonant tunneling contacts and numerical modeling

NASA Astrophysics Data System (ADS)

Julian, A.; Jehl, Z.; Miyashita, N.; Okada, Y.; Guillemoles, J.-F.

2016-12-01

Energy selective electrical contacts have been proposed as a way to approach ultimate efficiencies both for thermoelectric and photovoltaic devices as they allow a reduction of the entropy production during the energy conversion process. A self-consistent numerical model based on the transfer matrix approach in the effective mass and envelope function approximation has been developed to calculate the electronic properties of double resonant tunneling barriers used as energy selective contacts in hot carrier solar cells. It is found that the application of an external electric bias significantly degrades the electronic transmission of the structure, and thus the tunneling current in the current-voltage characteristic. This is due to a symmetry breaking which can be offset using finely tuned asymmetric double resonant tunneling barriers, leading to a full recovery of the tunneling current in our model. Moreover, we model the heterostructure using electrons temperature in the emitter higher than that of the lattice, providing insights on the interpretation of experimental devices functioning in hot carrier conditions, especially regarding the previously reported shift of the resonance peak (negative differential resistance), which we interpret as related to a shift in the hot electron distribution while the maximum remains at the conduction band edge of the emitter. Finally, experimental results are presented using asymmetric structure showing significantly improved resonant properties at room temperature with very sharp negative differential resistance.

Template-Free Synthesis of Highly Porous Boron Nitride: Insights into Pore Network Design and Impact on Gas Sorption.

PubMed

Marchesini, Sofia; McGilvery, Catriona M; Bailey, Josh; Petit, Camille

2017-10-24

Production of biocompatible and stable porous materials, e.g., boron nitride, exhibiting tunable and enhanced porosity is a prerequisite if they are to be employed to address challenges such as drug delivery, molecular separations, or catalysis. However, there is currently very limited understanding of the formation mechanisms of porous boron nitride and the parameters controlling its porosity, which ultimately prevents exploiting the material's full potential. Herein, we produce boron nitride with high and tunable surface area and micro/mesoporosity via a facile template-free method using multiple readily available N-containing precursors with different thermal decomposition patterns. The gases are gradually released, creating hierarchical pores, high surface areas (>1900 m 2 /g), and micropore volumes. We use 3D tomography techniques to reconstruct the pore structure, allowing direct visualization of the mesopore network. Additional imaging and analytical tools are employed to characterize the materials from the micro- down to the nanoscale. The CO 2 uptake of the materials rivals or surpasses those of commercial benchmarks or other boron nitride materials reported to date (up to 4 times higher), even after pelletizing. Overall, the approach provides a scalable route to porous boron nitride production as well as fundamental insights into the material's formation, which can be used to design a variety of boron nitride structures.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

PubMed

Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Sugar Transporters in Plants: New Insights and Discoveries.

PubMed

Julius, Benjamin T; Leach, Kristen A; Tran, Thu M; Mertz, Rachel A; Braun, David M

2017-09-01

Carbohydrate partitioning is the process of carbon assimilation and distribution from source tissues, such as leaves, to sink tissues, such as stems, roots and seeds. Sucrose, the primary carbohydrate transported long distance in many plant species, is loaded into the phloem and unloaded into distal sink tissues. However, many factors, both genetic and environmental, influence sucrose metabolism and transport. Therefore, understanding the function and regulation of sugar transporters and sucrose metabolic enzymes is key to improving agriculture. In this review, we highlight recent findings that (i) address the path of phloem loading of sucrose in rice and maize leaves; (ii) discuss the phloem unloading pathways in stems and roots and the sugar transporters putatively involved; (iii) describe how heat and drought stress impact carbohydrate partitioning and phloem transport; (iv) shed light on how plant pathogens hijack sugar transporters to obtain carbohydrates for pathogen survival, and how the plant employs sugar transporters to defend against pathogens; and (v) discuss novel roles for sugar transporters in plant biology. These exciting discoveries and insights provide valuable knowledge that will ultimately help mitigate the impending societal challenges due to global climate change and a growing population by improving crop yield and enhancing renewable energy production. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The James Blundell Award Lecture 2006: transfusion and the treatment of haemorrhage: past, present and future.

PubMed

Dzik, W H

2007-10-01

In the early years of the 19th century, James Blundell reported in the Lancet the first clinical application of blood transfusion for the treatment of haemorrhage. Although these initial experiments may appear to us to have burst upon the medical world, Blundell had in fact done a decade of pre clinical research using animal models to establish principles to be brought to the clinic. His pivotal pre clinical experiments and the insights he gained are described in detail. Today, blood transfusion remains the cornerstone of treatment for serious bleeding - not only to restore oxygen carrying capacity but also to improve haemostasis, arrest and prevent bleeding. However, the indications for the use of blood components to treat bleeding remain ill-defined. In particular, despite the enormous volumes of fresh frozen plasma (FFP) transfused worldwide, the evidence that commonly used coagulation tests are reliable guides to transfusion with FFP is scant. Recent laboratory and clinical studies provide insight into the weaknesses of current coagulation tests as a guide to blood management. In the future, the application of genomics to haemostasis will uncover genetic polymorphisms leading to improved diagnostics and more tailored medical therapeutics. Examples of the emerging use of clinical genomics are presented. Ultimately, the application of widescale genomics testing will refresh our understanding of human physiology and will reassert the importance of the individual in patient care.

Alternative Splicing and Cross-Talk with Light Signaling.

PubMed

Cheng, You-Liang; Tu, Shih-Long

2018-06-01

Alternative splicing (AS) is the main source of proteome diversity that in large part contributes to the complexity of eukaryotes. Recent global analysis of AS with RNA sequencing has revealed that AS is prevalent in plants, particularly when responding to environmental changes. Light is one of the most important environmental factors for plant growth and development. To optimize light absorption, plants evolve complex photoreceptors and signaling systems to regulate gene expression and biological processes in the cell. Genome-wide analyses have shown that light induces intensive AS in plants. However, the biochemical mechanisms of light regulating AS remain poorly understood. In this review, we aim to discuss recent progress in investigating the functions of AS, discovery of cross-talk between AS and light signaling, and the potential mechanism of light-regulated AS. Understanding how light signaling regulates the efficiency of AS and the biological significance of light-regulated AS in plant systems will provide new insights into the adaptation of plants to their environment and, ultimately, crop improvement.

Investigation of Coating and Corrosion Mitigation Strategies in Magnesium/Mixed Metal Assemblies

NASA Astrophysics Data System (ADS)

Forsmark, Joy H.; McCune, Robert C.; Giles, Terry; Audette, Michelle; Snowden, Jasmine; Stalker, Jeff; Morey, Matthew; O'Keefe, Matt; Castano, Carlos

The US Automotive Materials Partnership through the Magnesium-Intensive Front End Development Project (MFERD) is currently investigating a number of joining, coating and corrosion mitigation strategies to incorporate magnesium components into the automotive body-in-white with the ultimate goal of decreasing vehicle curb weight, thus improving fuel economy. Because Mg is anodic to all other structural metals, this is a key hurdle to Mg component implementation in vehicles. This paper will discuss the results of a study to examine the effectiveness of different corrosion mitigation strategies in joined plate assemblies and provide some insight into the systems challenges of incorporation of Mg parts into a vehicle. Details of a statistically-designed experiment developed to explore the interaction of several materials of construction (magnesium, steel and aluminum), pretreatment and topcoatings, joining methods and standardized test protocols including SAE J-2334 and ASTM B-117 are discussed. A number of avenues have emerged from this study as potential strategies for corrosion mitigation.

Understanding positive immigrant youth adaptation in the context of multiculturalism.

PubMed

Sam, David L

2018-01-01

This commentary highlights some of the strengths of the papers in this special issue focusing on how they advance acculturation research; how they link immigrant youth research with positive youth development and how they provide some insights into understanding how immigrant youth thrive in their adoptive societies. The commentary takes as its point of departure the prototypical research question for immigrant youth research within the perspective of positive youth development and the ultimate goals of acculturation research, i.e., to (i) promote positive psychological acculturation and the well-being of individuals and (ii) the attainment of harmonious intercultural relations among all groups in contact, and argues that the four papers fall short in addressing the second goal. The second goal is subsequently linked to multiculturalism and suggest that to do full justice to the prototypical research question, more attention should be directed to incorporating indicators of multiculturalism in acculturation research. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Think first job! Preferences and expectations of engineering students in a French `Grande Ecole'

NASA Astrophysics Data System (ADS)

Gerwel Proches, Cecile N.; Chelin, Nathalie; Rouvrais, Siegfried

2018-03-01

A career in engineering may be appealing owing to the prospect of a good salary and a dynamic work environment. There may, however, be challenges for students wishing to enter their first job. In engineering education, career preparation courses may be included so as to prepare students adequately for their first job, future careers, and to reinforce career decision-making skills. This study explored the first-job preferences and expectations of engineering students at a generalist French 'Grande Ecole' before their compulsory internship. The study ultimately provided insight into ways in which future engineers may best be equipped for their first jobs. A qualitative research study was employed, using four focus groups to collect data, which was analysed thematically. Key findings indicate the resolute importance that engineering students place on having a challenging job, teamwork, independence, opportunities for development, and a participative style of being managed. The research findings may be of value in order to renew an engineering curriculum with better alignment between students' expectations and industry needs.

Analysis of Dependencies and Impacts of Metroplex Operations

NASA Technical Reports Server (NTRS)

DeLaurentis, Daniel A.; Ayyalasomayajula, Sricharan

2010-01-01

This report documents research performed by Purdue University under subcontract to the George Mason University (GMU) for the Metroplex Operations effort sponsored by NASA's Airportal Project. Purdue University conducted two tasks in support of the larger efforts led by GMU: a) a literature review on metroplex operations followed by identification and analysis of metroplex dependencies, and b) the analysis of impacts of metroplex operations on the larger U.S. domestic airline service network. The tasks are linked in that the ultimate goal is an understanding of the role of dependencies among airports in a metroplex in causing delays both locally and network-wide. The Purdue team has formulated a system-of-systems framework to analyze metroplex dependencies (including simple metrics to quantify them) and develop compact models to predict delays based on network structure. These metrics and models were developed to provide insights for planners to formulate tailored policies and operational strategies that streamline metroplex operations and mitigate delays and congestion.

Assimilable organic carbon (AOC) variation in reclaimed water: Insight on biological stability evaluation and control for sustainable water reuse.

PubMed

Chen, Zhuo; Yu, Tong; Ngo, Huu Hao; Lu, Yun; Li, Guoqiang; Wu, Qianyuan; Li, Kuixiao; Bai, Yu; Liu, Shuming; Hu, Hong-Ying

2018-04-01

This review highlights the importance of conducting biological stability evaluation due to water reuse progression. Specifically, assimilable organic carbon (AOC) has been identified as a practical indicator for microbial occurrence and regrowth which ultimately influence biological stability. Newly modified AOC bioassays aimed for reclaimed water are introduced. Since elevated AOC levels are often detected after tertiary treatment, the review emphasizes that actions can be taken to either limit AOC levels prior to disinfection or conduct post-treatment (e.g. biological filtration) as a supplement to chemical oxidation based approaches (e.g. ozonation and chlorine disinfection). During subsequent distribution and storage, microbial community and possible microbial regrowth caused by complex interactions are discussed. It is suggested that microbial surveillance, AOC threshold values, real-time field applications and surrogate parameters could provide additional information. This review can be used to formulate regulatory plans and strategies, and to aid in deriving relevant control, management and operational guidance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nation-Based Occurrence and Endogenous Biological Reduction of Mycotoxins in Medicinal Herbs and Spices.

PubMed

Do, Kee Hun; An, Tae Jin; Oh, Sang-Keun; Moon, Yuseok

2015-10-14

Medicinal herbs have been increasingly used for therapeutic purposes against a diverse range of human diseases worldwide. Moreover, the health benefits of spices have been extensively recognized in recent studies. However, inevitable contaminants, including mycotoxins, in medicinal herbs and spices can cause serious problems for humans in spite of their health benefits. Along with the different nation-based occurrences of mycotoxins, the ultimate exposure and toxicities can be diversely influenced by the endogenous food components in different commodities of the medicinal herbs and spices. The phytochemicals in these food stuffs can influence mold growth, mycotoxin production and biological action of the mycotoxins in exposed crops, as well as in animal and human bodies. The present review focuses on the occurrence of mycotoxins in medicinal herbs and spices and the biological interaction between mold, mycotoxin and herbal components. These networks will provide insights into the methods of mycotoxin reduction and toxicological risk assessment of mycotoxin-contaminated medicinal food components in the environment and biological organisms.

Nation-Based Occurrence and Endogenous Biological Reduction of Mycotoxins in Medicinal Herbs and Spices

PubMed Central

Do, Kee Hun; An, Tae Jin; Oh, Sang-Keun; Moon, Yuseok

2015-01-01

Medicinal herbs have been increasingly used for therapeutic purposes against a diverse range of human diseases worldwide. Moreover, the health benefits of spices have been extensively recognized in recent studies. However, inevitable contaminants, including mycotoxins, in medicinal herbs and spices can cause serious problems for humans in spite of their health benefits. Along with the different nation-based occurrences of mycotoxins, the ultimate exposure and toxicities can be diversely influenced by the endogenous food components in different commodities of the medicinal herbs and spices. The phytochemicals in these food stuffs can influence mold growth, mycotoxin production and biological action of the mycotoxins in exposed crops, as well as in animal and human bodies. The present review focuses on the occurrence of mycotoxins in medicinal herbs and spices and the biological interaction between mold, mycotoxin and herbal components. These networks will provide insights into the methods of mycotoxin reduction and toxicological risk assessment of mycotoxin-contaminated medicinal food components in the environment and biological organisms. PMID:26473926

The lysosomal storage disease continuum with ageing-related neurodegenerative disease.

PubMed

Lloyd-Evans, Emyr; Haslett, Luke J

2016-12-01

Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing. The lysosome should no longer be considered as just the stomach of the cell or as a suicide bag, it has an emerging role in cellular signalling, nutrient sensing and recycling. The lysosome is of fundamental importance in the pathophysiology of diseases of ageing and by comparing against the LSDs we not only identify common pathways but also therapeutic targets so that ultimately more effective treatments can be developed for all neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

Change detection and change blindness in pigeons (Columba livia).

PubMed

Herbranson, Walter T; Trinh, Yvan T; Xi, Patricia M; Arand, Mark P; Barker, Michael S K; Pratt, Theodore H

2014-05-01

Change blindness is a phenomenon in which even obvious details in a visual scene change without being noticed. Although change blindness has been studied extensively in humans, we do not yet know if it is a phenomenon that also occurs in other animals. Thus, investigation of change blindness in a nonhuman species may prove to be valuable by beginning to provide some insight into its ultimate causes. Pigeons learned a change detection task in which pecks to the location of a change in a sequence of stimulus displays were reinforced. They were worse at detecting changes if the stimulus displays were separated by a brief interstimulus interval, during which the display was blank, and this primary result matches the general pattern seen in previous studies of change blindness in humans. A second experiment attempted to identify specific stimulus characteristics that most reliably produced a failure to detect changes. Change detection was more difficult when interstimulus intervals were longer and when the change was iterated fewer times. ©2014 APA, all rights reserved.

Use of Interrupted Helium Flow in the Analysis of Vapor Samples with Flowing Atmospheric-Pressure Afterglow-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Storey, Andrew P.; Zeiri, Offer M.; Ray, Steven J.; Hieftje, Gary M.

2017-02-01

The flowing atmospheric-pressure afterglow (FAPA) source was used for the mass-spectrometric analysis of vapor samples introduced between the source and mass spectrometer inlet. Through interrupted operation of the plasma-supporting helium flow, helium consumption is greatly reduced and dynamic gas behavior occurs that was characterized by schlieren imaging. Moreover, mass spectra acquired immediately after the onset of helium flow exhibit a signal spike before declining and ultimately reaching a steady level. This initial signal appears to be due to greater interaction of sample vapor with the afterglow of the source when helium flow resumes. In part, the initial spike in signal can be attributed to a pooling of analyte vapor in the absence of helium flow from the source. Time-resolved schlieren imaging of the helium flow during on and off cycles provided insight into gas-flow patterns between the FAPA source and the MS inlet that were correlated with mass-spectral data.

Distinct myocardial lineages break atrial symmetry during cardiogenesis in zebrafish

PubMed Central

Stone, Oliver; Arnaout, Rima; Guenther, Stefan; Ahuja, Suchit; Uribe, Verónica; Vanhollebeke, Benoit; Stainier, Didier YR

2018-01-01

The ultimate formation of a four-chambered heart allowing the separation of the pulmonary and systemic circuits was key for the evolutionary success of tetrapods. Complex processes of cell diversification and tissue morphogenesis allow the left and right cardiac compartments to become distinct but remain poorly understood. Here, we describe an unexpected laterality in the single zebrafish atrium analogous to that of the two atria in amniotes, including mammals. This laterality appears to derive from an embryonic antero-posterior asymmetry revealed by the expression of the transcription factor gene meis2b. In adult zebrafish hearts, meis2b expression is restricted to the left side of the atrium where it controls the expression of pitx2c, a regulator of left atrial identity in mammals. Altogether, our studies suggest that the multi-chambered atrium in amniotes arose from a molecular blueprint present before the evolutionary emergence of cardiac septation and provide insights into the establishment of atrial asymmetry. PMID:29762122

GLIMPSE: a rapid decision framework for energy and environmental policy.

PubMed

Akhtar, Farhan H; Pinder, Robert W; Loughlin, Daniel H; Henze, Daven K

2013-01-01

Over the coming decades, new energy production technologies and the policies that oversee them will affect human health, the vitality of our ecosystems, and the stability of the global climate. The GLIMPSE decision model framework provides insights about the implications of technology and policy decisions on these outcomes. Using GLIMPSE, decision makers can identify alternative techno-policy futures, examining their air quality, health, and short- and long-term climate impacts. Ultimately, GLIMPSE will support the identification of cost-effective strategies for simultaneously achieving performance goals for these metrics. Here, we demonstrate the utility of GLIMPSE by analyzing several future energy scenarios under existing air quality regulations and potential CO2 emission reduction policies. We find opportunities for substantial cobenefits in setting both climate change mitigation and health-benefit based air quality improvement targets. Though current policies which prioritize public health protection increase near-term warming, establishing policies that also reduce greenhouse gas emissions may offset warming in the near-term and lead to significant reductions in long-term warming.

Memory Transmission in Small Groups and Large Networks: An Agent-Based Model.

PubMed

Luhmann, Christian C; Rajaram, Suparna

2015-12-01

The spread of social influence in large social networks has long been an interest of social scientists. In the domain of memory, collaborative memory experiments have illuminated cognitive mechanisms that allow information to be transmitted between interacting individuals, but these experiments have focused on small-scale social contexts. In the current study, we took a computational approach, circumventing the practical constraints of laboratory paradigms and providing novel results at scales unreachable by laboratory methodologies. Our model embodied theoretical knowledge derived from small-group experiments and replicated foundational results regarding collaborative inhibition and memory convergence in small groups. Ultimately, we investigated large-scale, realistic social networks and found that agents are influenced by the agents with which they interact, but we also found that agents are influenced by nonneighbors (i.e., the neighbors of their neighbors). The similarity between these results and the reports of behavioral transmission in large networks offers a major theoretical insight by linking behavioral transmission to the spread of information. © The Author(s) 2015.

Objective support for subjective reports of successful inner speech in two people with aphasia

PubMed Central

Hayward, William; Snider, Sarah F.; Luta, George; Friedman, Rhonda B.; Turkeltaub, Peter E.

2016-01-01

People with aphasia frequently report being able to say a word correctly in their heads, even if they are unable to say that word aloud. It is difficult to know what is meant by these reports of “successful inner speech”. We probe the experience of successful inner speech in two people with aphasia. We show that these reports are associated with correct overt speech and phonologically related nonwords errors, that they relate to word characteristics associated with ease of lexical access but not ease of production, and that they predict whether or not individual words are relearned during anomia treatment. These findings suggest that reports of successful inner speech are meaningful and may be useful to study self-monitoring in aphasia, to better understand anomia, and to predict treatment outcomes. Ultimately, the study of inner speech in people with aphasia could provide critical insights that inform our understanding of normal language. PMID:27469037

Whole-genome sequencing of giant pandas provides insights into demographic history and local adaptation.

PubMed

Zhao, Shancen; Zheng, Pingping; Dong, Shanshan; Zhan, Xiangjiang; Wu, Qi; Guo, Xiaosen; Hu, Yibo; He, Weiming; Zhang, Shanning; Fan, Wei; Zhu, Lifeng; Li, Dong; Zhang, Xuemei; Chen, Quan; Zhang, Hemin; Zhang, Zhihe; Jin, Xuelin; Zhang, Jinguo; Yang, Huanming; Wang, Jian; Wang, Jun; Wei, Fuwen

2013-01-01

The panda lineage dates back to the late Miocene and ultimately leads to only one extant species, the giant panda (Ailuropoda melanoleuca). Although global climate change and anthropogenic disturbances are recognized to shape animal population demography their contribution to panda population dynamics remains largely unknown. We sequenced the whole genomes of 34 pandas at an average 4.7-fold coverage and used this data set together with the previously deep-sequenced panda genome to reconstruct a continuous demographic history of pandas from their origin to the present. We identify two population expansions, two bottlenecks and two divergences. Evidence indicated that, whereas global changes in climate were the primary drivers of population fluctuation for millions of years, human activities likely underlie recent population divergence and serious decline. We identified three distinct panda populations that show genetic adaptation to their environments. However, in all three populations, anthropogenic activities have negatively affected pandas for 3,000 years.

The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary Vasculature

PubMed Central

Malczyk, Monika; Erb, Alexandra; Veith, Christine; Ghofrani, Hossein Ardeschir; Schermuly, Ralph T.; Gudermann, Thomas; Dietrich, Alexander; Weissmann, Norbert; Sydykov, Akylbek

2017-01-01

Canonical or classical transient receptor potential channel 6 (TRPC6) is a Ca2+-permeable non-selective cation channel that is widely expressed in the heart, lung, and vascular tissues. The use of TRPC6-deficient (“knockout”) mice has provided important insights into the role of TRPC6 in normal physiology and disease states of the pulmonary vasculature. Evidence indicates that TRPC6 is a key regulator of acute hypoxic pulmonary vasoconstriction. Moreover, several studies implicated TRPC6 in the pathogenesis of pulmonary hypertension. Furthermore, a unique genetic variation in the TRPC6 gene promoter has been identified, which might link the inflammatory response to the upregulation of TRPC6 expression and ultimate development of pulmonary vascular abnormalities in idiopathic pulmonary arterial hypertension. Additionally, TRPC6 is critically involved in the regulation of pulmonary vascular permeability and lung edema formation during endotoxin or ischemia/reperfusion-induced acute lung injury. In this review, we will summarize latest findings on the role of TRPC6 in the pulmonary vasculature. PMID:28670316

Warning signal brightness variation: sexual selection may work under the radar of natural selection in populations of a polytypic poison frog.

PubMed

Crothers, Laura R; Cummings, Molly E

2013-05-01

Though theory predicts consistency of warning signals in aposematic species to facilitate predator learning, variation in these signals often occurs in nature. The strawberry poison frog Dendrobates pumilio is an exceptionally polytypic (populations are phenotypically distinct) aposematic frog exhibiting variation in warning color and brightness. In the Solarte population, males and females both respond differentially to male brightness variation. Here, we demonstrate through spectrophotometry and visual modeling that aposematic brightness variation within this population is likely visible to two putative predators (crabs, snakes) and conspecifics but not to the presumed major predator (birds). This study thus suggests that signal brightness within D. pumilio populations can be shaped by sexual selection, with limited opportunity for natural selection to influence this trait due to predator sensory constraints. Because signal brightness changes can ultimately lead to changes in hue, our findings at the within-population level can provide insights into understanding this polytypism at across-population scales.

Plant iTRAQ-based proteomics

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

Handakumbura, Pubudu; Hixson, Kim K.; Purvine, Samuel O.

We present a simple one-­pot extraction protocol, which rapidly isolates hydrophyllic metabolites, lipids, and proteins from the same pulverized plant sample. Also detailed is a global plant proteomics sample preparation method utilizing iTRAQ multiplexing reagents that enables deep proteome coverage due to the use of HPLC fractionation of the peptides prior to mass spectrometric analysis. We have successfully used this protocol on several different plant tissues (e.g., roots, stems, leaves) from different plants (e.g., sorghum, poplar, Arabidopsis, soybean), and have been able to successfully detect and quantify thousands of proteins. Multiplexing strategies such as iTRAQ and the bioinformatics strategy outlinedmore » here, ultimately provide insight into which proteins are significantly changed in abundance between two or more groups (e.g., control, perturbation). Our bioinformatics strategy yields z-­score values, which normalize the expression data into a format that can easily be cross-­compared with other expression data (i.e., metabolomics, transcriptomics) obtained from different analytical methods and instrumentation.« less

Advertisement recognition using mode voting acoustic fingerprint

NASA Astrophysics Data System (ADS)

Fahmi, Reza; Abedi Firouzjaee, Hosein; Janalizadeh Choobbasti, Ali; Mortazavi Najafabadi, S. H. E.; Safavi, Saeid

2017-12-01

Emergence of media outlets and public relations tools such as TV, radio and the Internet since the 20th century provided the companies with a good platform for advertising their goods and services. Advertisement recognition is an important task that can help companies measure the efficiency of their advertising campaigns in the market and make it possible to compare their performance with competitors in order to get better business insights. Advertisement recognition is usually performed manually with help of human labor or is done through automated methods that are mainly based on heuristics features, these methods usually lack abilities such as scalability, being able to be generalized and be used in different situations. In this paper, we present an automated method for advertisement recognition based on audio processing method that could make this process fairly simple and eliminate the human factor out of the equation. This method has ultimately been used in Miras information technology in order to monitor 56 TV channels to detect all ad video clips broadcast over some networks.

Advance of Mechanically Controllable Break Junction for Molecular Electronics.

PubMed

Wang, Lu; Wang, Ling; Zhang, Lei; Xiang, Dong

2017-06-01

Molecular electronics stands for the ultimate size of functional elements, keeping up with an unstoppable trend over the past few decades. As a vital component of molecular electronics, single molecular junctions have attracted significant attention from research groups all over the world. Due to its pronounced superiority, the mechanically controllable break junctions (MCBJ) technique has been widely applied to characterize the dynamic performance of single molecular junctions. This review presents a system analysis for single-molecule junctions and offers an overview of four test-beds for single-molecule junctions, thus offering more insight into the mechanisms of electron transport. We mainly focus on the development of state-of-the-art mechanically controlled break junctions. The three-terminal gated MCBJ approaches are introduced to manipulate the electron transport of molecules, and MCBJs are combined with characterization techniques. Additionally, applications of MCBJs and remarkable properties of single molecules are addressed. Finally, the challenges and perspective for the mechanically controllable break junctions technique are provided.

Insight into the Physical and Dynamical Processes that Control Rapid Increases in Total Flash Rate

NASA Technical Reports Server (NTRS)

Schultz, Christopher J.; Carey, Lawrence D.; Schultz, Elise V.; Blakeslee, Richard J.; Goodman, Steven J.

2015-01-01

Rapid increases in total lightning (also termed "lightning jumps") have been observed for many decades. Lightning jumps have been well correlated to severe and hazardous weather occurrence. The main focus of lightning jump work has been on the development of lightning algorithms to be used in real-time assessment of storm intensity. However, in these studies it is typically assumed that the updraft "increases" without direct measurements of the vertical motion, or specification of which updraft characteristic actually increases (e.g., average speed, maximum speed, or convective updraft volume). Therefore, an end-to-end physical and dynamical basis for coupling rapid increases in total flash rate to increases in updraft speed and volume must be understood in order to ultimately relate lightning occurrence to severe storm metrics. Herein, we use polarimetric, multi-Doppler, and lightning mapping array measurements to provide physical context as to why rapid increases in total lightning are closely tied to severe and hazardous weather.

Understanding the emergence of state goal orientation in organizational work groups: the role of leadership and multilevel climate perceptions.

PubMed

Dragoni, Lisa

2005-11-01

This article attends to a broad range of practically significant employee motivations and provides insight into how to enhance individual-level performance by examining individual-level state goal orientation emergence in organizational work groups. Leadership and multilevel climate processes are theorized to parallel each dimension of state goal orientation to cue and ultimately induce the corresponding achievement focus among individual work group members. It is argued that the patterns of leader behavior, which elucidate the leader's achievement priority, shape group members' psychological and work group climate to embody this priority. Resulting multilevel climate perceptions signal and compel group members to adopt the ascribed form of state goal orientation. The quality of the leader-member exchange relationship is viewed as a means to clarify leader messages in the formation of group members' psychological climate and internalize these cues in the emergence of state goal orientation. Considerations for future research and practice are discussed. ((c) 2005 APA, all rights reserved).

On the impact of water activity on reversal tolerant fuel cell anode performance and durability

NASA Astrophysics Data System (ADS)

Hong, Bo Ki; Mandal, Pratiti; Oh, Jong-Gil; Litster, Shawn

2016-10-01

Durability of polymer electrolyte fuel cells in automotive applications can be severely affected by hydrogen starvation arising due to transients during the drive-cycle. It causes individual cell voltage reversal, yielding water electrolysis and carbon corrosion reactions at the anode, ultimately leading to catastrophic cell failure. A popular material-based mitigation strategy is to employ a reversal tolerant anode (RTA) that includes oxygen evolution reaction (OER) catalyst (e.g., IrO2) to promote water electrolysis over carbon corrosion. Here we report that RTA performance surprisingly drops under not only water-deficient but also water-excess conditions. This presents a significant technical challenge since the most common triggers for cell reversal involve excess liquid water. Our findings from detailed electrochemical diagnostics and nano-scale X-ray computed tomography provide insight into how automotive fuel cells can overcome critical vulnerabilities using material-based solutions. Our work also highlights the need for improved materials, electrode designs, and operation strategies for robust RTAs.

Molybdenum L-Edge XAS Spectra of MoFe Nitrogenase

PubMed Central

Bjornsson, Ragnar; Delgado-Jaime, Mario U; Lima, Frederico A; Sippel, Daniel; Schlesier, Julia; Weyhermüller, Thomas; Einsle, Oliver; Neese, Frank; DeBeer, Serena

2015-01-01

A molybdenum L-edge X-ray absorption spectroscopy (XAS) study is presented for native and oxidized MoFe protein of nitrogenase as well as Mo-Fe model compounds. Recently collected data on MoFe protein (in oxidized and reduced forms) is compared to previously published Mo XAS data on the isolated FeMo cofactor in NMF solution and put in context of the recent Mo K-edge XAS study, which showed a MoIII assignment for the molybdenum atom in FeMoco. The L3-edge data are interpreted within a simple ligand-field model, from which a time-dependent density functional theory (TDDFT) approach is proposed as a way to provide further insights into the analysis of the molybdenum L3-edges. The calculated results reproduce well the relative spectral trends that are observed experimentally. Ultimately, these results give further support for the MoIII assignment in protein-bound FeMoco, as well as isolated FeMoco. PMID:26213424

Effect of Terminal Modification on the Molecular Assembly and Mechanical Properties of Protein-Based Block Copolymers.

PubMed

Jacobsen, Matthew M; Tokareva, Olena S; Ebrahimi, Davoud; Huang, Wenwen; Ling, Shengjie; Dinjaski, Nina; Li, David; Simon, Marc; Staii, Cristian; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

2017-09-01

Accurate prediction and validation of the assembly of bioinspired peptide sequences into fibers with defined mechanical characteristics would aid significantly in designing and creating materials with desired properties. This process may also be utilized to provide insight into how the molecular architecture of many natural protein fibers is assembled. In this work, computational modeling and experimentation are used in tandem to determine how peptide terminal modification affects a fiber-forming core domain. Modeling shows that increased terminal molecular weight and hydrophilicity improve peptide chain alignment under shearing conditions and promote consolidation of semicrystalline domains. Mechanical analysis shows acute improvements to strength and elasticity, but significantly reduced extensibility and overall toughness. These results highlight an important entropic function that terminal domains of fiber-forming peptides exhibit as chain alignment promoters, which ultimately has notable consequences on the mechanical behavior of the final fiber products. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Matz, Dallas L.; Schalnat, Matthew C.; Pemberton, Jeanne E.

The reaction between small organic molecules and low work function metals is of interest in organometallic, astronomical, and optoelectronic device chemistry. Here, thin, solid-state, amorphous benzene and pyridine films are reacted with Ca at 30 K under ultrahigh vacuum with the reaction progress monitored by Raman spectroscopy. Although both films react with Ca to produce product species identifiable by their vibrational spectroscopic signatures, benzene is less reactive with Ca than pyridine. Benzene reacts by electron transfer from Ca to benzene producing multiple species including the phenyl radical anion, the phenyl radical, and the benzyne diradical. Pyridine initially reacts along amore » similar electron transfer pathway as indicated by the presence of the corresponding pyridyl radical and pyridyne diradical species, but these pyridyl radicals are less stable and subject to further ring-opening reactions that lead to a complex array of smaller molecule reaction products and ultimately amorphous carbon. The elucidation of this reaction pathway provides insight into the reactions of aromatics with Ca that are relevant in the areas of catalysis, astrochemistry, and organic optoelectronics.« less

Mercury in gray wolves (Canis lupus) in Alaska: increased exposure through consumption of marine prey.

PubMed

McGrew, Ashley K; Ballweber, Lora R; Moses, Sara K; Stricker, Craig A; Beckmen, Kimberlee B; Salman, Mo D; O'Hara, Todd M

2014-01-15

Mercury (Hg) bioaccumulates in the tissues of organisms and biomagnifies within food-webs. Gray wolves (Canis lupus) in Alaska primarily acquire Hg through diet; therefore, comparing the extent of Hg exposure in wolves, in conjunction with stable isotopes, from interior and coastal regions of Alaska offers important insight into their feeding ecology. Liver, kidney, and skeletal muscle samples from 162 gray wolves were analyzed for total mercury (THg) concentrations and stable isotopic signatures (δ(13)C, δ(15)N, and δ(34)S). Median hepatic THg concentrations were significantly higher in wolves with coastal access compared to wolves from interior Alaska. Stable isotope ratios, in conjunction with THg concentrations, provide strong evidence that coastal wolves are utilizing marine prey representing several trophic levels. The utilization of cross-ecosystem food resources by coastal wolves is clearly contributing to increased THg exposure, and may ultimately have negative health implications for these animals. © 2013 Elsevier B.V. All rights reserved.

The value of remote sensing techniques in supporting effective extrapolation across multiple marine spatial scales.

PubMed

Strong, James Asa; Elliott, Michael

2017-03-15

The reporting of ecological phenomena and environmental status routinely required point observations, collected with traditional sampling approaches to be extrapolated to larger reporting scales. This process encompasses difficulties that can quickly entrain significant errors. Remote sensing techniques offer insights and exceptional spatial coverage for observing the marine environment. This review provides guidance on (i) the structures and discontinuities inherent within the extrapolative process, (ii) how to extrapolate effectively across multiple spatial scales, and (iii) remote sensing techniques and data sets that can facilitate this process. This evaluation illustrates that remote sensing techniques are a critical component in extrapolation and likely to underpin the production of high-quality assessments of ecological phenomena and the regional reporting of environmental status. Ultimately, is it hoped that this guidance will aid the production of robust and consistent extrapolations that also make full use of the techniques and data sets that expedite this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Secretome analysis of the thermophilic xylanase hyper-producer Thermomyces lanuginosus SSBP cultivated on corn cobs.

PubMed

Winger, A M; Heazlewood, J L; Chan, L J G; Petzold, C J; Permaul, K; Singh, S

2014-11-01

Thermomyces lanuginosus is a thermophilic fungus known for its ability to produce industrially important enzymes including large amounts of xylanase, the key enzyme in hemicellulose hydrolysis. The secretome of T. lanuginosus SSBP was profiled by shotgun proteomics to elucidate important enzymes involved in hemicellulose saccharification and to characterise the presence of other industrially interesting enzymes. This study reproducibly identified a total of 74 proteins in the supernatant following growth on corn cobs. An analysis of proteins revealed nine glycoside hydrolase (GH) enzymes including xylanase GH11, β-xylosidase GH43, β-glucosidase GH3, α-galactosidase GH36 and trehalose hydrolase GH65. Two commercially produced Thermomyces enzymes, lipase and amylase, were also identified. In addition, other industrially relevant enzymes not currently explored in Thermomyces were identified including glutaminase, fructose-bisphosphate aldolase and cyanate hydratase. Overall, these data provide insight into the novel ability of a cellulase-free fungus to utilise lignocellulosic material, ultimately producing a number of enzymes important to various industrial processes.

A foot in both worlds: education and the transformation of Chinese medicine in the United States.

PubMed

Flesch, Hannah

2013-01-01

Although insufficiently studied, schools of complementary and alternative medicine (CAM) provide substantial insight into the transformation of medicine in the United States. Scholars have suggested that the increasing acceptance of CAM is due to its alignment with biomedical models of professionalization, education, research, and practice. At West Coast University, students of acupuncture and Oriental medicine learn to straddle both Western and Eastern medical worlds through an increasingly science-oriented curriculum and the inculcation of professional values associated with West Coast University's emphasis upon integration with Western medicine as a means of achieving professional status and legitimacy vis-à-vis the dominant biomedical paradigm. The implications of integration with biomedicine for the identity of Chinese medicine are discussed: from the perspective of critical medical anthropology, integration reproduces biomedical hegemony; paving the way toward co-optation of Chinese medicine, the subordination of its practitioners, and, ultimately, the constraint of medical pluralism in the United States.

A melding of the minds: when primatology meets personality and social psychology.

PubMed

Brosnan, Sarah F; Newton-Fisher, Nicholas E; van Vugt, Mark

2009-05-01

Social and personality psychology and behavioral primatology both enjoy long histories of research aimed at uncovering the proximate and ultimate determinants of primate-human and nonhuman-social behavior. Although they share research themes, methodologies, and theories, and although their studied species are closely related, there is currently very little interaction between the fields. This separation means that researchers in these disciplines miss out on opportunities to advance understanding by combining insights from both fields. Social and personality psychologists also miss the opportunity for a phylogenetic analysis. The time has come to integrate perspectives on primate social psychology. Here, the authors provide a historical background and document the main similarities and differences in approaches. Next, they present some examples of research programs that may benefit from an integrated primate perspective. Finally, the authors propose a framework for developing a social psychology inclusive of all primates. Such a melding of minds promises to greatly benefit those who undertake the challenge.

High-pressure synthesis of a pentazolate salt [High-pressure synthesis of condensed-phase pentazolate

DOE PAGES

Steele, Brad A.; Stavrou, Elissaios; Crowhurst, Jonathan C.; ...

2016-12-06

The pentazolates, the last all-nitrogen members of the azole series, have been notoriously elusive for the last hundred years despite enormous efforts to make these compounds in either gas or condensed phases. Here, we report a successful synthesis of a solid state compound consisting of isolated pentazolate anions N 5 –, which is achieved by compressing and laser heating cesium azide (CsN 3) mixed with N 2 cryogenic liquid in a diamond anvil cell. The experiment was guided by theory, which predicted the transformation of the mixture at high pressures to a new compound, cesium pentazolate salt (CsN 5). Electronmore » transfer from Cs atoms to N 5 rings enables both aromaticity in the pentazolates as well as ionic bonding in the CsN 5 crystal. As a result, this work provides critical insight into the role of extreme conditions in exploring unusual bonding routes that ultimately lead to the formation of novel high nitrogen content species.« less

Use of Interrupted Helium Flow in the Analysis of Vapor Samples with Flowing Atmospheric-Pressure Afterglow-Mass Spectrometry.

PubMed

Storey, Andrew P; Zeiri, Offer M; Ray, Steven J; Hieftje, Gary M

2017-02-01

The flowing atmospheric-pressure afterglow (FAPA) source was used for the mass-spectrometric analysis of vapor samples introduced between the source and mass spectrometer inlet. Through interrupted operation of the plasma-supporting helium flow, helium consumption is greatly reduced and dynamic gas behavior occurs that was characterized by schlieren imaging. Moreover, mass spectra acquired immediately after the onset of helium flow exhibit a signal spike before declining and ultimately reaching a steady level. This initial signal appears to be due to greater interaction of sample vapor with the afterglow of the source when helium flow resumes. In part, the initial spike in signal can be attributed to a pooling of analyte vapor in the absence of helium flow from the source. Time-resolved schlieren imaging of the helium flow during on and off cycles provided insight into gas-flow patterns between the FAPA source and the MS inlet that were correlated with mass-spectral data. Graphical Abstract ᅟ.

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

PubMed Central

Durak, Omer; Gao, Fan; Kaeser-Woo, Yea Jin; Rueda, Richard; Martorell, Anthony J.; Nott, Alexi; Liu, Carol Y.; Watson, L. Ashley; Tsai, Li-Huei

2016-01-01

De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the basic biology of CHD8 remains poor understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8. PMID:27694995

Patient Blood Management: An International Perspective.

PubMed

Eichbaum, Quentin; Murphy, Michael; Liu, Yu; Kajja, Isaac; Hajjar, Ludhmila Abrahao; Smit Sibinga, Cees Th; Shan, Hua

2016-12-01

This article describes practices in patient blood management (PBM) in 4 countries on different continents that may provide insights for anesthesiologists and other physicians working in global settings. The article has its foundation in the proceedings of a session at the 2014 AABB annual meeting during which international experts from England, Uganda, China, and Brazil presented the programs and implementation strategies in PBM developed in their respective countries. To systematize the review and enhance the comparability between these countries on different continents, authors were requested to respond to the same set of 6 key questions with respect to their country's PBM program(s). Considerable variation exists between these country regions that is driven both by differences in health contexts and by disparities in resources. Comparing PBM strategies from low-, middle-, and high-income countries, as described in this article, allows them to learn bidirectionally from one another and to work toward implementing innovative and preferably evidence-based strategies for improvement. Sharing and distributing knowledge from such programs will ultimately also improve transfusion outcomes and patient safety.

Palliative Care Matters: Lessons From the Loss of a Facility Dog.

PubMed

Holman, Elizabeth; Levy, Cari; Kennedy, Brenda

2018-01-01

Animal-assisted intervention is gaining attention as a stress reduction modality. Quantitative data demonstrate its effectiveness, as a recent study published in AJHPM supported that a Veterans Affairs (VA) hospital facility dog paired with a palliative care psychologist had a measurable impact on salivary cortisol levels and heart rate in hospitalized veterans. There remains an important role for qualitative insights. The Denver VA palliative care team learned a range of lessons from the sudden loss of their facility dog, many of which relate directly to palliative care. The importance of communication, adjusting to changing teams, and the need for consultation and support based in shared goals and values all became evident in the course of the facility dog's illness. After her death, lessons shifted to grief and loss and how providers, patients, and a community care for each other. People's connection to the facility dog ultimately proved to be a critical factor in helping them connect with one another.

Molecular biology of Fanconi anaemia--an old problem, a new insight.

PubMed

Ahmad, Shamim I; Hanaoka, Fumio; Kirk, Sandra H

2002-05-01

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a complex mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double-strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation. Copyright 2002 Wiley Periodicals, Inc.

The use of mixed methods in studying a chronic illness.

PubMed

Jason, Leonard A; Reed, Jordan

This article explores mixed methods approaches with an illness called Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Qualitative and Quantitative data were used to investigate the epidemiology of this illness, as well as explore attributions based on the name of the illness, and finally treatment approaches. In each of the domains within the ME and CFS research reviewed, our analyses were richer and our findings ultimately more impactful when we integrated qualitative and quantitative research methods. The use of a multiphase mixed methods research program provided our team unique vantage points for better understanding social and community issues involving this controversial chronic illness. Further, this approach allowed us to implement the insights gained through an advocacy lens to change policy, recommend and evaluate treatments, and amplify voices within the patient population. In this way, we believe that the practice of methodological pluralism is especially applicable and effective to the study of chronic illness, and believe other investigators will benefit from the use of these approaches with similar disenfranchised and unfairly treated populations.

A stochastic reaction-diffusion model for protein aggregation on DNA

NASA Astrophysics Data System (ADS)

Voulgarakis, Nikolaos K.

Vital functions of DNA, such as transcription and packaging, depend on the proper clustering of proteins on the double strand. The present study investigates how the interplay between DNA allostery and electrostatic interactions affects protein clustering. The statistical analysis of a simple but transparent computational model reveals two major consequences of this interplay. First, depending on the protein and salt concentration, protein filaments exhibit a bimodal DNA stiffening and softening behavior. Second, within a certain domain of the control parameters, electrostatic interactions can cause energetic frustration that forces proteins to assemble in rigid spiral configurations. Such spiral filaments might trigger both positive and negative supercoiling, which can ultimately promote gene compaction and regulate the promoter. It has been experimentally shown that bacterial histone-like proteins assemble in similar spiral patterns and/or exhibit the same bimodal behavior. The proposed model can, thus, provide computational insights into the physical mechanisms used by proteins to control the mechanical properties of the DNA.

Camouflage, communication and thermoregulation: lessons from colour changing organisms.

PubMed

Stuart-Fox, Devi; Moussalli, Adnan

2009-02-27

Organisms capable of rapid physiological colour change have become model taxa in the study of camouflage because they are able to respond dynamically to the changes in their visual environment. Here, we briefly review the ways in which studies of colour changing organisms have contributed to our understanding of camouflage and highlight some unique opportunities they present. First, from a proximate perspective, comparison of visual cues triggering camouflage responses and the visual perception mechanisms involved can provide insight into general visual processing rules. Second, colour changing animals can potentially tailor their camouflage response not only to different backgrounds but also to multiple predators with different visual capabilities. We present new data showing that such facultative crypsis may be widespread in at least one group, the dwarf chameleons. From an ultimate perspective, we argue that colour changing organisms are ideally suited to experimental and comparative studies of evolutionary interactions between the three primary functions of animal colour patterns: camouflage; communication; and thermoregulation.

Camouflage, communication and thermoregulation: lessons from colour changing organisms

PubMed Central

Stuart-Fox, Devi; Moussalli, Adnan

2008-01-01

Organisms capable of rapid physiological colour change have become model taxa in the study of camouflage because they are able to respond dynamically to the changes in their visual environment. Here, we briefly review the ways in which studies of colour changing organisms have contributed to our understanding of camouflage and highlight some unique opportunities they present. First, from a proximate perspective, comparison of visual cues triggering camouflage responses and the visual perception mechanisms involved can provide insight into general visual processing rules. Second, colour changing animals can potentially tailor their camouflage response not only to different backgrounds but also to multiple predators with different visual capabilities. We present new data showing that such facultative crypsis may be widespread in at least one group, the dwarf chameleons. From an ultimate perspective, we argue that colour changing organisms are ideally suited to experimental and comparative studies of evolutionary interactions between the three primary functions of animal colour patterns: camouflage; communication; and thermoregulation. PMID:19000973

Propellant injection systems and processes

NASA Technical Reports Server (NTRS)

Ito, Jackson I.

1995-01-01

The previous 'Art of Injector Design' is maturing and merging with the more systematic 'Science of Combustion Device Analysis.' This technology can be based upon observation, correlation, experimentation and ultimately analytical modeling based upon basic engineering principles. This methodology is more systematic and far superior to the historical injector design process of 'Trial and Error' or blindly 'Copying Past Successes.' The benefit of such an approach is to be able to rank candidate design concepts for relative probability of success or technical risk in all the important combustion device design requirements and combustion process development risk categories before committing to an engine development program. Even if a single analytical design concept cannot be developed to predict satisfying all requirements simultaneously, a series of risk mitigation key enabling technologies can be identified for early resolution. Lower cost subscale or laboratory experimentation to demonstrate proof of principle, critical instrumentation requirements, and design discriminating test plans can be developed based on the physical insight provided by these analyses.

The promise of translational and personalised approaches for paediatric obstructive sleep apnoea: an 'Omics' perspective.

PubMed

Tan, Hui-Leng; Kheirandish-Gozal, Leila; Gozal, David

2014-05-01

Obstructive sleep apnoea (OSA) can result in significant morbidities including the cardiovascular, metabolic and neurocognitive systems. These effects are purportedly mediated via activation of inflammatory cascades and the induction of oxidative stress, ultimately resulting in cellular injury and dysfunction. While great advances have been made in sleep medicine research in the past decades, there are still wide gaps in our knowledge concerning the exact underlying pathophysiological mechanisms of OSA and consequences. Without resolving these issues, the reasons why patients with a similar severity of OSA can have markedly different clinical presentation and end-organ morbidity, that is, phenotype, will continue to remain elusive. This review aims to highlight the recent exciting discoveries in genotype-phenotype interactions, epigenetics, genomics and proteomics related to OSA. Just as PCR revolutionised the field of genetics, the potential power of 'Omics' promises to transform the field of sleep medicine, and provide critical insights into the downstream pathological cascades inherent to OSA, thereby enabling personalised diagnosis and management for this highly prevalent sleep disorder.

Advancing diversity and inclusion through AGU's mentoring programs

NASA Astrophysics Data System (ADS)

Asher, P. M.; Marasco, L.; Hurtado, C.; Hanlon, S. M.; Ambrogio, O.

2017-12-01

AGU offers three separate mentoring programs at the Fall Meeting. These are the Undergraduate Mentoring Program, Career and Research Advice Mentorship (CRAM) sessions, and the Sharing Science mentoring program. While each of these have had an impact on students and mentors, these programs are limited in that the mentor and mentee interactions only occur during the Fall Meeting. To increase the impact of mentoring beyond the Fall Meeting, AGU is piloting a new program that is entirely virtual. This virtual program, called Mentoring365, is designed to have a diverse set of mentees and mentors interacting over a three-month period. Mentoring365 offers participants with a mentor that they can "meet and interact with" outside of Fall Meeting and potentially continue a relationship beyond the duration of the program. It is intended to build or add to a student's professional network and provide a student with additional support outside their research, academic, and/or graduate advisor. This presentation will highlight some of the features of the program as well as provide insight into the progress of the Mentoring365 pilot. The ultimate intent is to expand the program efficacy by collaborating across organizations in the Earth and space sciences to provide a robust and diverse pool of mentors and mentees.

A comprehensive survey of government auditors' self-efficacy and professional development for improving audit quality.

PubMed

Lee, Shue-Ching; Su, Jau-Ming; Tsai, Sang-Bing; Lu, Tzu-Li; Dong, Weiwei

2016-01-01

Government audit authorities supervise the implementation of government budgets and evaluate the use of administrative resources to ensure that funding is used wisely, economically, and effectively. A quality audit involves reviewing policies according to international standards and perspectives, and provides insight, predictions, and warnings to related organizations. Such practice can reflect the effectiveness of a government. Professional development and self-efficacy have strong influence upon the performance of auditors. To further understand the factors that may enhance their performance and to ultimately provide practical recommendations for the audit authorities, we have surveyed about 50 % of all the governmental auditors in Taiwan using the stratified random sampling method. The result showed that any auditing experience and professionalization can positively influence the professional awareness. Also, acquired knowledge and skillset of an auditor can effectively improve ones professional judgment. We also found that professional development (including organizational culture and training opportunities) and self-efficacy (including profession and experience as well as trends and performance) may significantly impact audit quality. We concluded that to retain auditors, audit authorities must develop an attractive future outlook emphasizing feedback and learning within an organization. Our study provides a workable management guidelines for strengthening the professional development and self-efficacy of audit authorities in Taiwan.

Enhanced recovery after surgery: Current research insights and future direction

PubMed Central

Abeles, Aliza; Kwasnicki, Richard Mark; Darzi, Ara

2017-01-01

Since the concept of enhanced recovery after surgery (ERAS) was introduced in the late 1990s the idea of implementing specific interventions throughout the peri-operative period to improve patient recovery has been proven to be beneficial. Minimally invasive surgery is an integral component to ERAS and has dramatically improved post-operative outcomes. ERAS can be applicable to all surgical specialties with the core generic principles used together with added specialty specific interventions to allow for a comprehensive protocol, leading to improved clinical outcomes. Diffusion of ERAS into mainstream practice has been hindered due to minimal evidence to support individual facets and lack of method for monitoring and encouraging compliance. No single outcome measure fully captures recovery after surgery, rather multiple measures are necessary at each stage. More recently the pre-operative period has been the target of a number of strategies to improve clinical outcomes, described as prehabilitation. Innovation of technology in the surgical setting is also providing opportunities to overcome the challenges within ERAS, e.g., the use of wearable activity monitors to record information and provide feedback and motivation to patients peri-operatively. Both modernising ERAS and providing evidence for key strategies across specialties will ultimately lead to better, more reliable patient outcomes. PMID:28289508

Instream sand and gravel mining: Environmental issues and regulatory process in the United States

USGS Publications Warehouse

Meador, M.R.; Layher, A.O.

1998-01-01

Sand and gravel are widely used throughout the U.S. construction industry, but their extraction can significantly affect the physical, chemical, and biological characteristics of mined streams. Fisheries biologists often find themselves involved in the complex environmental and regulatory issues related to instream sand and gravel mining. This paper provides an overview of information presented in a symposium held at the 1997 midyear meeting of the Southern Division of the American Fisheries Society in San Antonio, Texas, to discuss environmental issues and regulatory procedures related to instream mining. Conclusions from the symposium suggest that complex physicochemical and biotic responses to disturbance such as channel incision and alteration of riparian vegetation ultimately determine the effects of instream mining. An understanding of geomorphic processes can provide insight into the effects of mining operations on stream function, and multidisciplinary empirical studies are needed to determine the relative effects of mining versus other natural and human-induced stream alterations. Mining regulations often result in a confusing regulatory process complicated, for example, by the role of the U.S. Army Corps of Engineers, which has undergone numerous changes and remains unclear. Dialogue among scientists, miners, and regulators can provide an important first step toward developing a plan that integrates biology and politics to protect aquatic resources.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol

NASA Astrophysics Data System (ADS)

Liriano, Melissa L.; Carrasco, Javier; Lewis, Emily A.; Murphy, Colin J.; Lawton, Timothy J.; Marcinkowski, Matthew D.; Therrien, Andrew J.; Michaelides, Angelos; Sykes, E. Charles H.

2016-03-01

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopic understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule's intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network's enantioselective interaction with other molecules.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol

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

Liriano, Melissa L.; Lewis, Emily A.; Murphy, Colin J.

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopicmore » understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule’s intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network’s enantioselective interaction with other molecules.« less

Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes

NASA Technical Reports Server (NTRS)

Romanov, S. R.; Kozakiewicz, B. K.; Holst, C. R.; Stampfer, M. R.; Haupt, L. M.; Tlsty, T. D.

2001-01-01

Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

Computational tools for comparative phenomics; the role and promise of ontologies

PubMed Central

Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

2012-01-01

A major aim of the biological sciences is to gain an understanding of human physiology and disease. One important step towards such a goal is the discovery of the function of genes that will lead to better understanding of the physiology and pathophysiology of organisms ultimately providing better understanding, diagnosis, and therapy. Our increasing ability to phenotypically characterise genetic variants of model organisms coupled with systematic and hypothesis-driven mutagenesis is resulting in a wealth of information that could potentially provide insight to the functions of all genes in an organism. The challenge we are now facing is to develop computational methods that can integrate and analyse such data. The introduction of formal ontologies that make their semantics explicit and accessible to automated reasoning promises the tantalizing possibility of standardizing biomedical knowledge allowing for novel, powerful queries that bridge multiple domains, disciplines, species and levels of granularity. We review recent computational approaches that facilitate the integration of experimental data from model organisms with clinical observations in humans. These methods foster novel cross species analysis approaches, thereby enabling comparative phenomics and leading to the potential of translating basic discoveries from the model systems into diagnostic and therapeutic advances at the clinical level. PMID:22814867

Evaluating remedial alternatives for an acid mine drainage stream: A model post audit

USGS Publications Warehouse

Runkel, Robert L.; Kimball, Briant A.; Walton-Day, Katherine; Verplanck, Philip L.; Broshears, Robert E.

2012-01-01

A post audit for a reactive transport model used to evaluate acid mine drainage treatment systems is presented herein. The post audit is based on a paired synoptic approach in which hydrogeochemical data are collected at low (existing conditions) and elevated (following treatment) pH. Data obtained under existing, low-pH conditions are used for calibration, and the resultant model is used to predict metal concentrations observed following treatment. Predictions for Al, As, Fe, H+, and Pb accurately reproduce the observed reduction in dissolved concentrations afforded by the treatment system, and the information provided in regard to standard attainment is also accurate (predictions correctly indicate attainment or nonattainment of water quality standards for 19 of 25 cases). Errors associated with Cd, Cu, and Zn are attributed to misspecification of sorbent mass (precipitated Fe). In addition to these specific results, the post audit provides insight in regard to calibration and sensitivity analysis that is contrary to conventional wisdom. Steps taken during the calibration process to improve simulations of As sorption were ultimately detrimental to the predictive results, for example, and the sensitivity analysis failed to bracket observed metal concentrations.

Palaeoproteomics for human evolution studies

NASA Astrophysics Data System (ADS)

Welker, Frido

2018-06-01

The commonplace sequencing of Neanderthal, Denisovan and ancient modern human DNA continues to revolutionize our understanding of hominin phylogeny and interaction(s). The challenge with older fossils is that the progressive fragmentation of DNA even under optimal conditions, a function of time and temperature, results in ever shorter fragments of DNA. This process continues until no DNA can be sequenced or reliably aligned. Ancient proteins ultimately suffer a similar fate, but are a potential alternative source of biomolecular sequence data to investigate hominin phylogeny given their slower rate of fragmentation. In addition, ancient proteins have been proposed to potentially provide insights into in vivo biological processes and can be used to provide additional ecological information through large scale ZooMS (Zooarchaeology by Mass Spectrometry) screening of unidentifiable bone fragments. However, as initially with ancient DNA, most ancient protein research has focused on Late Pleistocene or Holocene samples from Europe. In addition, only a limited number of studies on hominin remains have been published. Here, an updated review on ancient protein analysis in human evolutionary contexts is given, including the identification of specific knowledge gaps and existing analytical limits, as well as potential avenues to overcome these.

Using geographic information science to evaluate legal restrictions on freight transportation routing in disruptive scenarios

DOE PAGES

Fialkoff, Marc R.; Omitaomu, Olufemi A.; Peterson, Steven K.; ...

2016-12-23

Disasters have consequences and freight transportation is not immune from the effects of such disruptions. In the aftermath of disasters, planners and policymakers have to utilize scarce resources and work within legal frameworks to provide recovery for affected citizens and business. As seen with Hurricane Sandy, various observers noted the challenge with freight rerouting due to inoperable infrastructure and legal barriers involved with intermodal freight transportation. This paper focuses on how Geographic Information Systems (GIS); specifically WebTRAGIS (Transportation Routing Analysis GIS), a transportation routing platform developed at Oak Ridge National Laboratory, can be used to evaluate different routing options formore » freight transportation. In the case of freight transportation, the Merchant Marine Act of 1920 (also known as the Jones Act) restricts Short Sea Shipping (SSS) between coastwise points within U.S. territorial waters. This restriction leads to reliance on land-side modes for handling increased freight resulting from cargo diversion. Using Hurricane Sandy and the closure of the Port of New York/New Jersey as a case study, different modal studies were conducted; ultimately highlighting the various routes and provides insight into potential review of modal restrictions such as the Jones Act.« less

Seed birth to death: dual functions of reactive oxygen species in seed physiology.

PubMed

Jeevan Kumar, S P; Rajendra Prasad, S; Banerjee, Rintu; Thammineni, Chakradhar

2015-09-01

Reactive oxygen species (ROS) are considered to be detrimental to seed viability. However, recent studies have demonstrated that ROS have key roles in seed germination particularly in the release of seed dormancy and embryogenesis, as well as in protection from pathogens. This review considers the functions of ROS in seed physiology. ROS are present in all cells and at all phases of the seed life cycle. ROS accumulation is important in breaking seed dormancy, and stimulating seed germination and protection from pathogens. However, excessive ROS accumulation can be detrimental. Therefore, knowledge of the mechanisms by which ROS influence seed physiology will provide insights that may not only allow the development of seed quality markers but also help us understand how dormancy can be broken in several recalcitrant species. Reactive oxygen species have a dual role in seed physiology. Understanding the relative importance of beneficial and detrimental effects of ROS provides great scope for the improvement and maintenance of seed vigour and quality, factors that may ultimately increase crop yields. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Examining the Cultural Competence of Third- and Fourth-Year Nutrition Students: A Pilot Study.

PubMed

Hack, Rebekah; Hekmat, Sharareh; Ahmadi, Latifeh

2015-12-01

The purpose of this study was to provide preliminary Canadian research assessing nutrition students' cultural competence and to identify areas for future education initiatives in dietetic education that could ultimately improve dietitians' cultural competence. A mixed-methods study was conducted using a 24-item questionnaire that was administered to students enrolled in third- and fourth-year undergraduate nutrition classes (n = 133). In total, 115 questionnaires were analyzed for quantitative data, and 109 were analyzed for qualitative data. The students scored an overall medium-high level of cultural competence. Out of the 5 areas examined (skills, attitudes, awareness, desires, knowledge), students' multicultural knowledge scores were the lowest. It was found that a lower number of barriers to learning about other cultures were significantly associated with a higher overall cultural competence score, and taking a course in cultural foods significantly increased the students' knowledge and overall cultural competence (P ≤ 0.05). The qualitative data found that students felt the cultural competence curriculum had gaps and identified several ideas for improvement. In conclusion, this research data provides novel insights into the cultural competence of Canadian dietetic students and additionally supports future research and curriculum development to enhance cultural competence.

Microsensors to monitor missile storage and maintenance needs

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

Mee, D.K.; Thundat, T.G.; Oden, P.I.

1997-10-30

Accurate assessments of reliability and condition based maintenance can only be implemented where a good understanding of ammunition stockpile condition exists. Use of miniaturized intelligent sensors provides an inexpensive means of nondestructively gaining insight into stockpile condition while keeping costs low. In the past, evaluation of ammunition lifetimes has utilized humidity, temperature, pressure, shock, and corrosion. New technologies provide the possibility of obtaining these environmental parameters, as well as a number of other indicators of propellant degradation, including NOx by utilizing a microsensor with capability for remote wireless monitoring. Micro-electro-mechanical systems (MEMS) like microcantilevers promise to revolutionize the field ofmore » sensor design. In the automobile industry, micromachined acceleration sensors are now used for triggering airbags and pressure sensors adjust the air-fuel intake ratio in the engine. By applying coatings to the sensor`s surface the behavior of the microdevice can be measurably altered to respond to chemical species as demonstrated by ORNL using microcantilevers to detect mercury vapor and humidity. Ultimately, single-chip detectors with electronics and telemetry could be developed with conceivably hundreds of individual microsensors on each chip to simultaneously monitor identify, and quantify many important chemical species for ammunition as well as measure environmental parameters.« less

A critical period for second language acquisition: Evidence from 2/3 million English speakers.

PubMed

Hartshorne, Joshua K; Tenenbaum, Joshua B; Pinker, Steven

2018-08-01

Children learn language more easily than adults, though when and why this ability declines have been obscure for both empirical reasons (underpowered studies) and conceptual reasons (measuring the ultimate attainment of learners who started at different ages cannot by itself reveal changes in underlying learning ability). We address both limitations with a dataset of unprecedented size (669,498 native and non-native English speakers) and a computational model that estimates the trajectory of underlying learning ability by disentangling current age, age at first exposure, and years of experience. This allows us to provide the first direct estimate of how grammar-learning ability changes with age, finding that it is preserved almost to the crux of adulthood (17.4 years old) and then declines steadily. This finding held not only for "difficult" syntactic phenomena but also for "easy" syntactic phenomena that are normally mastered early in acquisition. The results support the existence of a sharply-defined critical period for language acquisition, but the age of offset is much later than previously speculated. The size of the dataset also provides novel insight into several other outstanding questions in language acquisition. Copyright © 2018 Elsevier B.V. All rights reserved.

Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing

NASA Astrophysics Data System (ADS)

Crane, Nicole J.; Elster, Eric A.

2012-01-01

Wound care and management accounted for over 1.8 million hospital discharges in 2009. The complex nature of wound physiology involves hundreds of overlapping processes that we have only begun to understand over the past three decades. The management of wounds remains a significant challenge for inexperienced clinicians. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjective. Some wounds fail to close, or dehisce, despite the use and application of novel wound-specific treatment modalities. An understanding of the molecular environment of acute and chronic wounds throughout the wound-healing process can provide valuable insight into the mechanisms associated with the patient's outcome. Pathologic alterations of wounds are accompanied by fundamental changes in the molecular environment that can be analyzed by vibrational spectroscopy. Vibrational spectroscopy, specifically Raman and Fourier transform infrared spectroscopy, offers the capability to accurately detect and identify the various molecules that compose the extracellular matrix during wound healing in their native state. The identified changes might provide the objective markers of wound healing, which can then be integrated with clinical characteristics to guide the management of wounds.

Visualizing the dynamic structure of the plant photosynthetic membrane.

PubMed

Ruban, Alexander V; Johnson, Matthew P

2015-11-03

The chloroplast thylakoid membrane is the site for the initial steps of photosynthesis that convert solar energy into chemical energy, ultimately powering almost all life on earth. The heterogeneous distribution of protein complexes within the membrane gives rise to an intricate three-dimensional structure that is nonetheless extremely dynamic on a timescale of seconds to minutes. These dynamics form the basis for the regulation of photosynthesis, and therefore the adaptability of plants to different environments. High-resolution microscopy has in recent years begun to provide new insights into the structural dynamics underlying a number of regulatory processes such as membrane stacking, photosystem II repair, photoprotective energy dissipation, state transitions and alternative electron transfer. Here we provide an overview of the essentials of thylakoid membrane structure in plants, and consider how recent advances, using a range of microscopies, have substantially increased our knowledge of the thylakoid dynamic structure. We discuss both the successes and limitations of the currently available techniques and highlight newly emerging microscopic methods that promise to move the field beyond the current 'static' view of membrane organization based on frozen snapshots to a 'live' view of functional membranes imaged under native aqueous conditions at ambient temperature and responding dynamically to external stimuli.

Using geographic information science to evaluate legal restrictions on freight transportation routing in disruptive scenarios

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

Fialkoff, Marc R.; Omitaomu, Olufemi A.; Peterson, Steven K.

Disasters have consequences and freight transportation is not immune from the effects of such disruptions. In the aftermath of disasters, planners and policymakers have to utilize scarce resources and work within legal frameworks to provide recovery for affected citizens and business. As seen with Hurricane Sandy, various observers noted the challenge with freight rerouting due to inoperable infrastructure and legal barriers involved with intermodal freight transportation. This paper focuses on how Geographic Information Systems (GIS); specifically WebTRAGIS (Transportation Routing Analysis GIS), a transportation routing platform developed at Oak Ridge National Laboratory, can be used to evaluate different routing options formore » freight transportation. In the case of freight transportation, the Merchant Marine Act of 1920 (also known as the Jones Act) restricts Short Sea Shipping (SSS) between coastwise points within U.S. territorial waters. This restriction leads to reliance on land-side modes for handling increased freight resulting from cargo diversion. Using Hurricane Sandy and the closure of the Port of New York/New Jersey as a case study, different modal studies were conducted; ultimately highlighting the various routes and provides insight into potential review of modal restrictions such as the Jones Act.« less

Establishment of an Italian chronic migraine database: a multicenter pilot study.

PubMed

Barbanti, Piero; Fofi, L; Cevoli, S; Torelli, P; Aurilia, C; Egeo, G; Grazzi, L; D'Amico, D; Manzoni, G C; Cortelli, P; Infarinato, F; Vanacore, N

2018-05-01

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

Complex networks with scale-free nature and hierarchical modularity

NASA Astrophysics Data System (ADS)

Shekatkar, Snehal M.; Ambika, G.

2015-09-01

Generative mechanisms which lead to empirically observed structure of networked systems from diverse fields like biology, technology and social sciences form a very important part of study of complex networks. The structure of many networked systems like biological cell, human society and World Wide Web markedly deviate from that of completely random networks indicating the presence of underlying processes. Often the main process involved in their evolution is the addition of links between existing nodes having a common neighbor. In this context we introduce an important property of the nodes, which we call mediating capacity, that is generic to many networks. This capacity decreases rapidly with increase in degree, making hubs weak mediators of the process. We show that this property of nodes provides an explanation for the simultaneous occurrence of the observed scale-free structure and hierarchical modularity in many networked systems. This also explains the high clustering and small-path length seen in real networks as well as non-zero degree-correlations. Our study also provides insight into the local process which ultimately leads to emergence of preferential attachment and hence is also important in understanding robustness and control of real networks as well as processes happening on real networks.

Evaluating remedial alternatives for an acid mine drainage stream: a model post audit.

PubMed

Runkel, Robert L; Kimball, Briant A; Walton-Day, Katherine; Verplanck, Philip L; Broshears, Robert E

2012-01-03

A post audit for a reactive transport model used to evaluate acid mine drainage treatment systems is presented herein. The post audit is based on a paired synoptic approach in which hydrogeochemical data are collected at low (existing conditions) and elevated (following treatment) pH. Data obtained under existing, low-pH conditions are used for calibration, and the resultant model is used to predict metal concentrations observed following treatment. Predictions for Al, As, Fe, H(+), and Pb accurately reproduce the observed reduction in dissolved concentrations afforded by the treatment system, and the information provided in regard to standard attainment is also accurate (predictions correctly indicate attainment or nonattainment of water quality standards for 19 of 25 cases). Errors associated with Cd, Cu, and Zn are attributed to misspecification of sorbent mass (precipitated Fe). In addition to these specific results, the post audit provides insight in regard to calibration and sensitivity analysis that is contrary to conventional wisdom. Steps taken during the calibration process to improve simulations of As sorption were ultimately detrimental to the predictive results, for example, and the sensitivity analysis failed to bracket observed metal concentrations.

A strategic vision for telemedicine and medical informatics in space flight

NASA Technical Reports Server (NTRS)

Williams, D. R.; Bashshur, R. L.; Pool, S. L.; Doarn, C. R.; Merrell, R. C.; Logan, J. S.

2000-01-01

This Workshop was designed to assist in the ongoing development and application of telemedicine and medical informatics to support extended space flight. Participants included specialists in telemedicine and medical/health informatics (terrestrial and space) medicine from NASA, federal agencies, academic centers, and research and development institutions located in the United States and several other countries. The participants in the working groups developed vision statements, requirements, approaches, and recommendations pertaining to developing and implementing a strategy pertaining to telemedicine and medical informatics. Although some of the conclusions and recommendations reflect ongoing work at NASA, others provided new insight and direction that may require a reprioritization of current NASA efforts in telemedicine and medical informatics. This, however, was the goal of the Workshop. NASA is seeking other perspectives and views from leading practitioners in the fields of telemedicine and medical informatics to invigorate an essential and high-priority component of the International Space Station and future extended exploration missions. Subsequent workshops will further define and refine the general findings and recommendations achieved here. NASA's ultimate aim is to build a sound telemedicine and medical informatics operational system to provide the best medical care available for astronauts going to Mars and beyond.

Attention to 'details': etiquette and the pharmaceutical salesman in postwar American.

PubMed

Greene, Jeremy A

2004-04-01

This paper provides a sketch of the emerging role of the pharmaceutical salesman, or 'detail man', in the growth years of the American post-World War II pharmaceutical industry. Using training manuals, trade literature, in-house company newsletters, memoirs, and a variety of other published sources, the paper follows the delicate tactics employed by salesmen and their managers in their attempts to recast drug salesmanship as a 'professional service' fulfilling vital functions within medical education. As they worked to legitimate their presence in the nation's hospitals and clinics, particular emphasis was given to precise management of the etiquette of doctor-salesman interaction. Ultimately, the techniques employed by mid-century salesmen and their managers were to prove successful in generating a widespread acceptance of the industry representative within the clinical spaces of hospital and clinic. Indeed, many of the practices of market research and market strategy employed across the pharmaceutical industry today have their origins in the practices of the individual detail man. Exploration of the postwar pharmaceutical salesman as an overlooked historical 'type' provides significant insights into the intersection of medicine and the consumer marketplace during the later 20th century.

Risk Mitigation Approach to Commercial Resupply to the International Space Station

NASA Technical Reports Server (NTRS)

Koons, Diane S.; Schreiber, Craig

2010-01-01

In August 2006, NASA awarded Space Act Agreements (SAAs) for Commercial Orbital Transportation Services (COTS) under the Commercial Crew and Cargo Project Office at Johnson Space Center. One of the goals of the SAAs is to facilitate U.S. private industry demonstration of cargo transportation capabilities, ultimately achieving reliable, cost effective access to low-Earth orbit (LEO). Each COTS provider is required to complete International Space Stations (ISS) Integration activities, which includes meeting the physical and functional interfaces and interface requirements between the ISS and COTS vehicles. These requirements focus on the areas of risk to the ISS during rendezvous and proximity operations, as well as the integration operations while the COTS vehicle is berthed to the ISS. On December 23, 2008, NASA awarded Commercial Resupply Service (CRS) contracts to provide resupply services to the ISS, following the Shuttle retirement. In addition to performing any ISS Integration activities, NASA will be performing independent assessments of the launch vehicle and orbital vehicle to evaluate the readiness of the contractor to deliver NASA cargo safely to the ISS. This paper will address the activities NASA Centers, both JSC and KSC, in the oversight and insight function over commercial visiting vehicles to the ISS.

Practical insights into gluten-free diets.

PubMed

See, Jacalyn A; Kaukinen, Katri; Makharia, Govind K; Gibson, Peter R; Murray, Joseph A

2015-10-01

Coeliac disease is a global disease, and the only currently available treatment is a gluten-free diet (GFD). Although conceptually simple, the diet changes are substantial and have a profound effect on a patient's life. Untreated coeliac disease is associated with complications, including excess mortality, most of which can be avoided with a strict GFD. However, there are many barriers, including availability, cost and safety of gluten-free foods, and gluten cross-contamination. The GFD can be restrictive in social situations, leading to poor quality of life and, ultimately, nonadherence. As the number of patients with coeliac disease increases worldwide, clinicians need to be aware of the challenges patients face. Heightened awareness by physicians, dietitians and other providers can help maximize successful treatment, improve outcomes, and reduce health-care costs and disease burden. Routine follow-up is necessary to reinforce the need for a GFD, provide social and emotional support, and achieve mucosal healing, leading to reduced risk of complications. Unfortunately, there is wide variation in follow-up practices. The objective of this Review is to increase awareness of the challenges, management and follow-up of patients with coeliac disease to help them achieve GFD adherence and prevent complications whilst preserving their quality of life.

Ab initio phonon thermal transport in monolayer InSe, GaSe, GaS, and alloys

NASA Astrophysics Data System (ADS)

Pandey, Tribhuwan; Parker, David S.; Lindsay, Lucas

2017-11-01

We compare vibrational properties and phonon thermal conductivities (κ) of monolayer InSe, GaSe, and GaS systems using density functional theory and Peierls-Boltzmann transport methods. In going from InSe to GaSe to GaS, system mass decreases giving both increasing acoustic phonon velocities and decreasing scattering of these heat-carrying modes with optic phonons, ultimately giving {κ }{InSe}< {κ }{GaSe}< {κ }{GaS}. This behavior is demonstrated by correlating the scattering phase space limited by fundamental conservation conditions with mode scattering rates and phonon dispersions for each material. We also show that, unlike flat monolayer systems such as graphene, in InSe, GaSe and GaS thermal transport is governed by in-plane vibrations. Alloying of InSe, GaSe, and GaS systems provides an effective method for modulating their κ through intrinsic vibrational modifications and phonon scattering from mass disorder giving reductions ˜2-3.5 times. This disorder also suppresses phonon mean free paths in the alloy systems compared to those in their crystalline counterparts. This work provides fundamental insights of lattice thermal transport from basic vibrational properties for an interesting set of two-dimensional materials.

A strategic vision for telemedicine and medical informatics in space flight.

PubMed

Williams, D R; Bashshur, R L; Pool, S L; Doarn, C R; Merrell, R C; Logan, J S

2000-01-01

This Workshop was designed to assist in the ongoing development and application of telemedicine and medical informatics to support extended space flight. Participants included specialists in telemedicine and medical/health informatics (terrestrial and space) medicine from NASA, federal agencies, academic centers, and research and development institutions located in the United States and several other countries. The participants in the working groups developed vision statements, requirements, approaches, and recommendations pertaining to developing and implementing a strategy pertaining to telemedicine and medical informatics. Although some of the conclusions and recommendations reflect ongoing work at NASA, others provided new insight and direction that may require a reprioritization of current NASA efforts in telemedicine and medical informatics. This, however, was the goal of the Workshop. NASA is seeking other perspectives and views from leading practitioners in the fields of telemedicine and medical informatics to invigorate an essential and high-priority component of the International Space Station and future extended exploration missions. Subsequent workshops will further define and refine the general findings and recommendations achieved here. NASA's ultimate aim is to build a sound telemedicine and medical informatics operational system to provide the best medical care available for astronauts going to Mars and beyond.

Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models.

PubMed

Bakker, Sietske T; de Winter, Johan P; te Riele, Hein

2013-01-01

Fanconi anaemia (FA) is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF), haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL)-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.

Network inference from multimodal data: A review of approaches from infectious disease transmission.

PubMed

Ray, Bisakha; Ghedin, Elodie; Chunara, Rumi

2016-12-01

Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, and microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Leaf evolution in early-diverging ferns: insights from a new fern-like plant from the Late Devonian of China.

PubMed

Wang, De-Ming; Xu, Hong-He; Xue, Jin-Zhuang; Wang, Qi; Liu, Le

2015-06-01

With the exception of angiosperms, the main euphyllophyte lineages (i.e. ferns sensu lato, progymnosperms and gymnosperms) had evolved laminate leaves by the Late Devonian. The evolution of laminate leaves, however, remains unclear for early-diverging ferns, largely represented by fern-like plants. This study presents a novel fern-like taxon with pinnules, which provides new insights into the early evolution of laminate leaves in early-diverging ferns. Macrofossil specimens were collected from the Upper Devonian (Famennian) Wutong Formation of Anhui and Jiangsu Provinces, South China. A standard degagement technique was employed to uncover compressed plant portions within the rock matrix. A new fern-like taxon, SHOUGANGIA BELLA GEN ET SP NOV: , is described and represents an early-diverging fern with highly derived features. It has a partially creeping stem with adventitious roots only on one side, upright primary and secondary branches arranged in helices, tertiary branches borne alternately or (sub)oppositely, laminate and usually lobed leaves with divergent veins, and complex fertile organs terminating tertiary branches and possessing multiple divisions and numerous terminal sporangia. Shougangia bella provides unequivocal fossil evidence for laminate leaves in early-diverging ferns. It suggests that fern-like plants, along with other euphyllophyte lineages, had independently evolved megaphylls by the Late Devonian, possibly in response to a significant decline in atmospheric CO2 concentration. Among fern-like plants, planate ultimate appendages are homologous with laminate pinnules, and in the evolution of megaphylls, fertile organs tend to become complex. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The ultimate limits of the relativistic rocket equation. The Planck photon rocket

NASA Astrophysics Data System (ADS)

Haug, Espen Gaarder

2017-07-01

In this paper we look at the ultimate limits of a photon propulsion rocket. The maximum velocity for a photon propulsion rocket is just below the speed of light and is a function of the reduced Compton wavelength of the heaviest subatomic particles in the rocket. We are basically combining the relativistic rocket equation with Haug's new insight on the maximum velocity for anything with rest mass. An interesting new finding is that in order to accelerate any subatomic "fundamental" particle to its maximum velocity, the particle rocket basically needs two Planck masses of initial load. This might sound illogical until one understands that subatomic particles with different masses have different maximum velocities. This can be generalized to large rockets and gives us the maximum theoretical velocity of a fully-efficient and ideal rocket. Further, no additional fuel is needed to accelerate a Planck mass particle to its maximum velocity; this also might sound absurd, but it has a very simple and logical solution that is explained in this paper.

Reduced Design Load Basis for Ultimate Blade Loads Estimation in Multidisciplinary Design Optimization Frameworks

NASA Astrophysics Data System (ADS)

Pavese, Christian; Tibaldi, Carlo; Larsen, Torben J.; Kim, Taeseong; Thomsen, Kenneth

2016-09-01

The aim is to provide a fast and reliable approach to estimate ultimate blade loads for a multidisciplinary design optimization (MDO) framework. For blade design purposes, the standards require a large amount of computationally expensive simulations, which cannot be efficiently run each cost function evaluation of an MDO process. This work describes a method that allows integrating the calculation of the blade load envelopes inside an MDO loop. Ultimate blade load envelopes are calculated for a baseline design and a design obtained after an iteration of an MDO. These envelopes are computed for a full standard design load basis (DLB) and a deterministic reduced DLB. Ultimate loads extracted from the two DLBs with the two blade designs each are compared and analyzed. Although the reduced DLB supplies ultimate loads of different magnitude, the shape of the estimated envelopes are similar to the one computed using the full DLB. This observation is used to propose a scheme that is computationally cheap, and that can be integrated inside an MDO framework, providing a sufficiently reliable estimation of the blade ultimate loading. The latter aspect is of key importance when design variables implementing passive control methodologies are included in the formulation of the optimization problem. An MDO of a 10 MW wind turbine blade is presented as an applied case study to show the efficacy of the reduced DLB concept.

The `Miracle' of Applicability? The Curious Case of the Simple Harmonic Oscillator

NASA Astrophysics Data System (ADS)

Bangu, Sorin; Moir, Robert H. C.

2018-05-01

The paper discusses to what extent the conceptual issues involved in solving the simple harmonic oscillator model fit Wigner's famous point that the applicability of mathematics borders on the miraculous. We argue that although there is ultimately nothing mysterious here, as is to be expected, a careful demonstration that this is so involves unexpected difficulties. Consequently, through the lens of this simple case we derive some insight into what is responsible for the appearance of mystery in more sophisticated examples of the Wigner problem.

The `Miracle' of Applicability? The Curious Case of the Simple Harmonic Oscillator

NASA Astrophysics Data System (ADS)

Bangu, Sorin; Moir, Robert H. C.

2018-03-01

The paper discusses to what extent the conceptual issues involved in solving the simple harmonic oscillator model fit Wigner's famous point that the applicability of mathematics borders on the miraculous. We argue that although there is ultimately nothing mysterious here, as is to be expected, a careful demonstration that this is so involves unexpected difficulties. Consequently, through the lens of this simple case we derive some insight into what is responsible for the appearance of mystery in more sophisticated examples of the Wigner problem.

Molecular electronics with single molecules in solid-state devices.

PubMed

Moth-Poulsen, Kasper; Bjørnholm, Thomas

2009-09-01

The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule, and on how the electron transport properties of the molecule depend on the strength of the electronic coupling between it and the electrodes. A variety of phenomena are observed depending on whether this coupling is weak, intermediate or strong.

Computational Foundations of Natural Intelligence

PubMed Central

van Gerven, Marcel

2017-01-01

New developments in AI and neuroscience are revitalizing the quest to understanding natural intelligence, offering insight about how to equip machines with human-like capabilities. This paper reviews some of the computational principles relevant for understanding natural intelligence and, ultimately, achieving strong AI. After reviewing basic principles, a variety of computational modeling approaches is discussed. Subsequently, I concentrate on the use of artificial neural networks as a framework for modeling cognitive processes. This paper ends by outlining some of the challenges that remain to fulfill the promise of machines that show human-like intelligence. PMID:29375355

Fostering new relational experience: clinical process in couple psychotherapy.

PubMed

Marmarosh, Cheri L

2014-03-01

One of the most critical goals for couple psychotherapy is to foster a new relational experience in the session where the couple feels safe enough to reveal more vulnerable emotions and to explore their defensive withdrawal, aggressive attacking, or blaming. The lived intimate experience in the session offers the couple an opportunity to gain integrative insight into their feelings, expectations, and behaviors that ultimately hinder intimacy. The clinical processes that are necessary include empathizing with the couple and facilitating safety within the session, looking for opportunities to explore emotions, ruptures, and unconscious motivations that maintain distance in the relationship, and creating a new relational experience in the session that has the potential to engender integrative insight. These clinical processes will be presented with empirical support. Experts from a session will be used to highlight how these processes influence the couple and promote increased intimacy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Insights from in-situ X-ray computed tomography during axial impregnation of unidirectional fiber beds

DOE PAGES

Larson, Natalie M.; Zok, Frank W.

2017-12-27

In-situ X-ray computed tomography during axial impregnation of unidirectional fiber beds is used to study coupled effects of fluid velocity, fiber movement and preferred flow channeling on permeability. Here, in order to interpret the experimental measurements, a new computational tool for predicting axial permeability of very large 2D arrays of non-uniformly packed fibers is developed. The results show that, when the impregnation velocity is high, full saturation is attained behind the flow front and the fibers rearrange into a less uniform configuration with higher permeability. In contrast, when the velocity is low, fluid flows preferentially in the narrowest channels betweenmore » fibers, yielding unsaturated permeabilities that are lower than those in the saturated state. Lastly, these insights combined with a new computational tool will enable improved prediction of permeability, ultimately for use in optimization of composite manufacturing via liquid impregnation.« less

Insights from in-situ X-ray computed tomography during axial impregnation of unidirectional fiber beds

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

Larson, Natalie M.; Zok, Frank W.

In-situ X-ray computed tomography during axial impregnation of unidirectional fiber beds is used to study coupled effects of fluid velocity, fiber movement and preferred flow channeling on permeability. Here, in order to interpret the experimental measurements, a new computational tool for predicting axial permeability of very large 2D arrays of non-uniformly packed fibers is developed. The results show that, when the impregnation velocity is high, full saturation is attained behind the flow front and the fibers rearrange into a less uniform configuration with higher permeability. In contrast, when the velocity is low, fluid flows preferentially in the narrowest channels betweenmore » fibers, yielding unsaturated permeabilities that are lower than those in the saturated state. Lastly, these insights combined with a new computational tool will enable improved prediction of permeability, ultimately for use in optimization of composite manufacturing via liquid impregnation.« less

Learning Collaboratives: Insights And A New Taxonomy From AHRQ's Two Decades Of Experience.

PubMed

Nix, Mary; McNamara, Peggy; Genevro, Janice; Vargas, Natalia; Mistry, Kamila; Fournier, Alaina; Shofer, Margie; Lomotan, Edwin; Miller, Therese; Ricciardi, Richard; Bierman, Arlene S

2018-02-01

Learning collaboratives are increasingly used as mechanisms to support and hasten the diffusion and implementation of innovation, clinical evidence, and effective models of care. Factors contributing to the collaboratives' success or failure are poorly understood. The Agency for Healthcare Research and Quality (AHRQ) has sponsored collaboratives for nearly two decades to support improvements in health care quality and value by accelerating the diffusion and implementation of innovation. We examined AHRQ's experience with these collaboratives to characterize their attributes, identify factors that might contribute to their success or failure, and assess the challenges they encountered. Building on the literature and insights from AHRQ's experience, we propose a taxonomy that can offer guidance to decision makers and funders about the factors they should consider in developing collaboratives and planning their evaluation, as well as to researchers who seek to conduct research that will ultimately help decision makers make better investments in diffusing innovation and evidence.

Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

PubMed

Bossong, Matthijs G; Niesink, Raymond J M

2010-11-01

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central. Copyright © 2010 Elsevier Ltd. All rights reserved.

Assessment of Gait Characteristics in Total Knee Arthroplasty Patients Using a Hierarchical Partial Least Squares Method.

PubMed

Wang, Wei; Ackland, David C; McClelland, Jodie A; Webster, Kate E; Halgamuge, Saman

2018-01-01

Quantitative gait analysis is an important tool in objective assessment and management of total knee arthroplasty (TKA) patients. Studies evaluating gait patterns in TKA patients have tended to focus on discrete data such as spatiotemporal information, joint range of motion and peak values of kinematics and kinetics, or consider selected principal components of gait waveforms for analysis. These strategies may not have the capacity to capture small variations in gait patterns associated with each joint across an entire gait cycle, and may ultimately limit the accuracy of gait classification. The aim of this study was to develop an automatic feature extraction method to analyse patterns from high-dimensional autocorrelated gait waveforms. A general linear feature extraction framework was proposed and a hierarchical partial least squares method derived for discriminant analysis of multiple gait waveforms. The effectiveness of this strategy was verified using a dataset of joint angle and ground reaction force waveforms from 43 patients after TKA surgery and 31 healthy control subjects. Compared with principal component analysis and partial least squares methods, the hierarchical partial least squares method achieved generally better classification performance on all possible combinations of waveforms, with the highest classification accuracy . The novel hierarchical partial least squares method proposed is capable of capturing virtually all significant differences between TKA patients and the controls, and provides new insights into data visualization. The proposed framework presents a foundation for more rigorous classification of gait, and may ultimately be used to evaluate the effects of interventions such as surgery and rehabilitation.

The relationship between consumer insight and provider-consumer agreement regarding consumer's quality of life.

PubMed

Hasson-Ohayon, Ilanit; Roe, David; Kravetz, Shlomo; Levy-Frank, Itamar; Meir, Taly

2011-10-01

This study examined the relationship between insight and mental health consumers and providers agreement regarding consumers rated quality of life (QoL). Seventy mental health consumers and their 23 care providers filled-out parallel questionnaires designed to measure consumer QoL. Consumers' insight was also assessed. For most QoL domains, agreement between consumers and providers was higher for persons with high insight. For the Psychological well being dimension a negative correlation was uncovered for persons with low insight indicating disagreement between consumer and provider. These findings are discussed within the context of the literature on insight and agreement between consumer and provider as related to the therapeutic alliance.

Silicon wafer-based tandem cells: The ultimate photovoltaic solution?

NASA Astrophysics Data System (ADS)

Green, Martin A.

2014-03-01

Recent large price reductions with wafer-based cells have increased the difficulty of dislodging silicon solar cell technology from its dominant market position. With market leaders expected to be manufacturing modules above 16% efficiency at 0.36/Watt by 2017, even the cost per unit area (60-70/m2) will be difficult for any thin-film photovoltaic technology to significantly undercut. This may make dislodgement likely only by appreciably higher energy conversion efficiency approaches. A silicon wafer-based cell able to capitalize on on-going cost reductions within the mainstream industry, but with an appreciably higher than present efficiency, might therefore provide the ultimate PV solution. With average selling prices of 156 mm quasi-square monocrystalline Si photovoltaic wafers recently approaching 1 (per wafer), wafers now provide clean, low cost templates for overgrowth of thin, wider bandgap high performance cells, nearly doubling silicon's ultimate efficiency potential. The range of possible Si-based tandem approaches is reviewed together with recent results and ultimate prospects.

Dynamics of a New 5D Hyperchaotic System of Lorenz Type

NASA Astrophysics Data System (ADS)

Zhang, Fuchen; Chen, Rui; Wang, Xingyuan; Chen, Xiusu; Mu, Chunlai; Liao, Xiaofeng

Ultimate boundedness of chaotic dynamical systems is one of the fundamental concepts in dynamical systems, which plays an important role in investigating the stability of the equilibrium, estimating the Lyapunov dimension of attractors and the Hausdorff dimension of attractors, the existence of periodic solutions, chaos control, chaos synchronization. However, it is often difficult to obtain the bounds of the hyperchaotic systems due to the complex algebraic structure of the hyperchaotic systems. This paper has investigated the boundedness of solutions of a nonlinear hyperchaotic system. We have obtained the global exponential attractive set and the ultimate bound set for this system. To obtain the ellipsoidal ultimate bound, the ultimate bound of the proposed system is theoretically estimated using Lagrange multiplier method, Lyapunov stability theory and optimization theory. To show the ultimate bound region, numerical simulations are provided.

40 CFR 86.128-79 - Transmissions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., shall be run according to the manufacturer's recommendations to the ultimate purchaser, Provided, That... recommendations to the ultimate purchaser. (c) Idle modes less than one minute in length shall be run with automatic transmissions in “Drive” and the wheels braked; manual transmissions shall be in gear with the...

What Are the Principles That Guide Behaviors in the Operating Room?: Creating a Framework to Define and Measure Performance.

PubMed

Madani, Amin; Vassiliou, Melina C; Watanabe, Yusuke; Al-Halabi, Becher; Al-Rowais, Mohammed S; Deckelbaum, Dan L; Fried, Gerald M; Feldman, Liane S

2017-02-01

To identify the core principles that guide expert intraoperative behaviors and to use these principles to develop a universal framework that defines intraoperative performance. Surgical outcomes are associated with intraoperative cognitive skills. Yet, our understanding of factors that control intraoperative judgment and decision-making are limited. As a result, current methods for training and measuring performance are somewhat subjective-more task rather than procedure-oriented-and usually not standardized. They thus provide minimal insight into complex cognitive processes that are fundamental to patient safety. Cognitive task analyses for 6 diverse surgical procedures were performed using semistructured interviews and field observations to describe the thoughts, behaviors, and actions that characterize and guide expert performance. Verbal data were transcribed, supplemented with content from published literature, coded, thematically analyzed using grounded-theory by 4 independent reviewers, and synthesized into a list of items. A conceptual framework was developed based on 42 semistructured interviews lasting 45 to 120 minutes, 5 expert panels and 51 field observations involving 35 experts, and 135 sources from the literature. Five domains of intraoperative performance were identified: psychomotor skills, declarative knowledge, advanced cognitive skills, interpersonal skills, and personal resourcefulness. Within the advanced cognitive skills domain, 21 themes were perceived to guide the behaviors of surgeons: 18 for surgical planning and error prevention, and 3 for error/injury recognition, rescue, and recovery. The application of these thought patterns was highly case-specific and variable amongst subspecialties, environments, and individuals. This study provides a comprehensive definition of intraoperative expertise, with greater insight into the complex cognitive processes that seem to underlie optimal performance. This framework provides trainees and other nonexperts with the necessary information to use in deliberate practice and the creation of effective thought habits that characterize expert performance. It may help to identify gaps in performance, and to isolate root causes of surgical errors with the ultimate goal of improving patient safety.

Investigating Hydrocarbon Seep Environments with High-Resolution, Three-Dimensional Geographic Visualizations.

NASA Astrophysics Data System (ADS)

Doolittle, D. F.; Gharib, J. J.; Mitchell, G. A.

2015-12-01

Detailed photographic imagery and bathymetric maps of the seafloor acquired by deep submergence vehicles such as Autonomous Underwater Vehicles (AUV) and Remotely Operated Vehicles (ROV) are expanding how scientists and the public view and ultimately understand the seafloor and the processes that modify it. Several recently acquired optical and acoustic datasets, collected during ECOGIG (Ecosystem Impacts of Oil and Gas Inputs to the Gulf) and other Gulf of Mexico expeditions using the National Institute for Undersea Science Technology (NIUST) Eagle Ray, and Mola Mola AUVs, have been fused with lower resolution data to create unique three-dimensional geovisualizations. Included in these data are multi-scale and multi-resolution visualizations over hydrocarbon seeps and seep related features. Resolution of the data range from 10s of mm to 10s of m. When multi-resolution data is integrated into a single three-dimensional visual environment, new insights into seafloor and seep processes can be obtained from the intuitive nature of three-dimensional data exploration. We provide examples and demonstrate how integration of multibeam bathymetry, seafloor backscatter data, sub-bottom profiler data, textured photomosaics, and hull-mounted multibeam acoustic midwater imagery are made into a series a three-dimensional geovisualizations of actively seeping sites and associated chemosynthetic communities. From these combined and merged datasets, insights on seep community structure, morphology, ecology, fluid migration dynamics, and process geomorphology can be investigated from new spatial perspectives. Such datasets also promote valuable inter-comparisons of sensor resolution and performance.

Linking microbial and ecosystem ecology using ecological stoichiometry: a synthesis of conceptual and empirical approaches

USGS Publications Warehouse

Hall, E.K.; Maixner, F.; Franklin, O.; Daims, H.; Richter, A.; Battin, T.

2011-01-01

Currently, one of the biggest challenges in microbial and ecosystem ecology is to develop conceptual models that organize the growing body of information on environmental microbiology into a clear mechanistic framework with a direct link to ecosystem processes. Doing so will enable development of testable hypotheses to better direct future research and increase understanding of key constraints on biogeochemical networks. Although the understanding of phenotypic and genotypic diversity of microorganisms in the environment is rapidly accumulating, how controls on microbial physiology ultimately affect biogeochemical fluxes remains poorly understood. We propose that insight into constraints on biogeochemical cycles can be achieved by a more rigorous evaluation of microbial community biomass composition within the context of ecological stoichiometry. Multiple recent studies have pointed to microbial biomass stoichiometry as an important determinant of when microorganisms retain or recycle mineral nutrients. We identify the relevant cellular components that most likely drive changes in microbial biomass stoichiometry by defining a conceptual model rooted in ecological stoichiometry. More importantly, we show how X-ray microanalysis (XRMA), nanoscale secondary ion mass spectroscopy (NanoSIMS), Raman microspectroscopy, and in situ hybridization techniques (for example, FISH) can be applied in concert to allow for direct empirical evaluation of the proposed conceptual framework. This approach links an important piece of the ecological literature, ecological stoichiometry, with the molecular front of the microbial revolution, in an attempt to provide new insight into how microbial physiology could constrain ecosystem processes.

A systems biology approach toward understanding seed composition in soybean.

PubMed

Li, Ling; Hur, Manhoi; Lee, Joon-Yong; Zhou, Wenxu; Song, Zhihong; Ransom, Nick; Demirkale, Cumhur Yusuf; Nettleton, Dan; Westgate, Mark; Arendsee, Zebulun; Iyer, Vidya; Shanks, Jackie; Nikolau, Basil; Wurtele, Eve Syrkin

2015-01-01

The molecular, biochemical, and genetic mechanisms that regulate the complex metabolic network of soybean seed development determine the ultimate balance of protein, lipid, and carbohydrate stored in the mature seed. Many of the genes and metabolites that participate in seed metabolism are unknown or poorly defined; even more remains to be understood about the regulation of their metabolic networks. A global omics analysis can provide insights into the regulation of seed metabolism, even without a priori assumptions about the structure of these networks. With the future goal of predictive biology in mind, we have combined metabolomics, transcriptomics, and metabolic flux technologies to reveal the global developmental and metabolic networks that determine the structure and composition of the mature soybean seed. We have coupled this global approach with interactive bioinformatics and statistical analyses to gain insights into the biochemical programs that determine soybean seed composition. For this purpose, we used Plant/Eukaryotic and Microbial Metabolomics Systems Resource (PMR, http://www.metnetdb.org/pmr, a platform that incorporates metabolomics data to develop hypotheses concerning the organization and regulation of metabolic networks, and MetNet systems biology tools http://www.metnetdb.org for plant omics data, a framework to enable interactive visualization of metabolic and regulatory networks. This combination of high-throughput experimental data and bioinformatics analyses has revealed sets of specific genes, genetic perturbations and mechanisms, and metabolic changes that are associated with the developmental variation in soybean seed composition. Researchers can explore these metabolomics and transcriptomics data interactively at PMR.

Effect of bioaugmentation and biostimulation on sulfate-reducing column startup captured by functional gene profiling.

PubMed

Pereyra, Luciana P; Hiibel, Sage R; Perrault, Elizabeth M; Reardon, Kenneth F; Pruden, Amy

2012-10-01

Sulfate-reducing permeable reactive zones (SR-PRZs) depend upon a complex microbial community to utilize a lignocellulosic substrate and produce sulfides, which remediate mine drainage by binding heavy metals. To gain insight into the impact of the microbial community composition on the startup time and pseudo-steady-state performance, functional genes corresponding to cellulose-degrading (CD), fermentative, sulfate-reducing, and methanogenic microorganisms were characterized in columns simulating SR-PRZs using quantitative polymerase chain reaction (qPCR) and denaturing gradient gel electrophoresis (DGGE). Duplicate columns were bioaugmented with sulfate-reducing or CD bacteria or biostimulated with ethanol or carboxymethyl cellulose and compared with baseline dairy manure inoculum and uninoculated controls. Sulfate removal began after ~ 15 days for all columns and pseudo-steady state was achieved by Day 30. Despite similar performance, DGGE profiles of 16S rRNA gene and functional genes at pseudo-steady state were distinct among the column treatments, suggesting the potential to control ultimate microbial community composition via bioaugmentation and biostimulation. qPCR revealed enrichment of functional genes in all columns between the initial and pseudo-steady-state time points. This is the first functional gene-based study of CD, fermentative and sulfate-reducing bacteria and methanogenic archaea in a lignocellulose-based environment and provides new qualitative and quantitative insight into startup of a complex microbial system. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

PubMed Central

Roussotte, Florence; Soderberg, Lindsay

2010-01-01

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

Impact of visual impairment on the lives of young adults in the Netherlands: a concept-mapping approach.

PubMed

Elsman, Ellen Bernadette Maria; van Rens, Gerardus Hermanus Maria Bartholomeus; van Nispen, Ruth Marie Antoinette

2017-12-01

While the impact of visual impairments on specific aspects of young adults' lives is well recognised, a systematic understanding of its impact on all life aspects is lacking. This study aims to provide an overview of life aspects affected by visual impairment in young adults (aged 18-25 years) using a concept-mapping approach. Visually impaired young adults (n = 22) and rehabilitation professionals (n = 16) participated in online concept-mapping workshops (brainstorm procedure), to explore how having a visual impairment influences the lives of young adults. Statements were categorised based on similarity and importance. Using multidimensional scaling, concept maps were produced and interpreted. A total of 59 and 260 statements were generated by young adults and professionals, respectively, resulting in 99 individual statements after checking and deduplication. The combined concept map revealed 11 clusters: work, study, information and regulations, social skills, living independently, computer, social relationships, sport and activities, mobility, leisure time, and hobby. The concept maps provided useful insight into activities influenced by visual impairments in young adults, which can be used by rehabilitation centres to improve their services. This might help in goal setting, rehabilitation referral and successful transition to adult life, ultimately increasing participation and quality of life. Implications for rehabilitation Having a visual impairment affects various life-aspects related to participation, including activities related to work, study, social skills and relationships, activities of daily living, leisure time and mobility. Concept-mapping helped to identify the life aspects affected by low vision, and quantify these aspects in terms of importance according to young adults and low vision rehabilitation professionals. Low vision rehabilitation centres should focus on all life aspects found in this study when identifying the needs of young adults, as this might aid goal setting and rehabilitation referral, ultimately leading to more successful transitions, better participation and quality of life.

Wilderness education: The ultimate commitment to quality wilderness stewardship

Treesearch

Gregory F. Hansen; Tom Carlson

2007-01-01

The effective planning, implementation, and monitoring of a wilderness education program will ultimately produce measurable results that can be instrumental in achieving wilderness management goals and objectives. This paper will provide a simple step-by-step overview of how to develop and maintain a successful wilderness education program through planning,...

Using Mixed Methods and Collaboration to Evaluate an Education and Public Outreach Program (Invited)

NASA Astrophysics Data System (ADS)

Shebby, S.; Shipp, S. S.

2013-12-01

Traditional indicators (such as the number of participants or Likert-type ratings of participant perceptions) are often used to provide stakeholders with basic information about program outputs and to justify funding decisions. However, use of qualitative methods can strengthen the reliability of these data and provide stakeholders with more meaningful information about program challenges, successes, and ultimate impacts (Stern, Stame, Mayne, Forss, David & Befani, 2012). In this session, presenters will discuss how they used a mixed methods evaluation to determine the impact of an education and public outreach (EPO) program. EPO efforts were intended to foster more effective, sustainable, and efficient utilization of science discoveries and learning experiences through three main goals 1) increase engagement and support by leveraging of resources, expertise, and best practices; 2) organize a portfolio of resources for accessibility, connectivity, and strategic growth; and 3) develop an infrastructure to support coordination. The evaluation team used a mixed methods design to conduct the evaluation. Presenters will first discuss five potential benefits of mixed methods designs: triangulation of findings, development, complementarity, initiation, and value diversity (Greene, Caracelli & Graham, 2005). They will next demonstrate how a 'mix' of methods, including artifact collection, surveys, interviews, focus groups, and vignettes, was included in the EPO project's evaluation design, providing specific examples of how alignment between the program theory and the evaluation plan was best achieved with a mixed methods approach. The presentation will also include an overview of different mixed methods approaches and information about important considerations when using a mixed methods design, such as selection of data collection methods and sources, and the timing and weighting of quantitative and qualitative methods (Creswell, 2003). Ultimately, this presentation will provide insight into how a mixed methods approach was used to provide stakeholders with important information about progress toward program goals. Creswell, J.W. (2003). Research design: Qualitative, quantitative, and mixed approaches. Thousand Oaks, CA: Sage. Greene, J. C., Caracelli, V. J., & Graham, W. D. (1989). Toward a conceptual framework for mixed-method evaluation designs. Educational Evaluation and Policy Analysis, 11(3), 255-274. Stern, E; Stame, N; Mayne, J; Forss, K; Davis, R & Befani, B (2012) Broadening the range of designs and methods for impact evaluation. Department for International Development.

Visualising Three Dimensional Damage and Failure Envelopes: Implications for True Triaxial Deformation

NASA Astrophysics Data System (ADS)

Harland, S. R.; Browning, J.; Healy, D.; Meredith, P. G.; Mitchell, T. M.

2017-12-01

Ultimate failure in brittle rocks is commonly accepted to occur as a coalescence of micro-crack damage into a single failure plane. The geometry and evolution with stress of the cracks (damage) within the medium will play a role in dictating the geometry of the ultimate failure plane. Currently, the majority of experimental studies investigating damage evolution and rock failure use conventional triaxial stress states (σ1 > σ2 = σ3). Results from these tests can easily be represented on a Mohr-Coulomb plot (σn - τ), conveniently allowing the user to determine the geometry of the resultant failure plane. In reality however, stress in the subsurface is generally truly triaxial (σ1 > σ2 > σ3) and in this case, the Mohr-Coulomb failure criterion is inadequate as it incorporates no dependence on the intermediate stress (σ2), which has been shown to play an important role in controlling failure. It has recently been shown that differential stress is the key driver in initiating crack growth, regardless of the mean stress. Polyaxial failure criteria that incorporate the effect of the intermediate stress do exist and include the Modified Lade, Modified Wiebols and Cook, and the Drucker-Prager criteria. However, unlike the Mohr-Coulomb failure criterion, these polyaxial criteria do not offer any prediction of, or insight into, the geometry of the resultant failure plane. An additional downfall of all of the common conventional and polyaxial failure criteria is that they fail to describe the geometry of the damage (i.e. pre-failure microcracking) envelope with progressive stress; it is commonly assumed that the damage envelope is parallel to the ultimate brittle failure envelope. Here we use previously published polyaxial failure data for the Shirahama sandstone and Westerley granite to illustrate that the commonly used Mohr-Coulomb and polyaxial failure criteria do not sufficiently describe or capture failure or damage envelopes under true triaxial stress states. We investigate if and how Mohr-Coulomb type constructions can provide geometrical solutions to truly-triaxial problems. We look to incorporate both the intermediate stress and the differential stress as the controlling parameters in failure and examine the geometry of damage envelopes using damage onset data.

A Thermo-Poromechanics Finite Element Model for Predicting Arterial Tissue Fusion

NASA Astrophysics Data System (ADS)

Fankell, Douglas P.

This work provides modeling efforts and supplemental experimental work performed towards the ultimate goal of modeling heat transfer, mass transfer, and deformation occurring in biological tissue, in particular during arterial fusion and cutting. Developing accurate models of these processes accomplishes two goals. First, accurate models would enable engineers to design devices to be safer and less expensive. Second, the mechanisms behind tissue fusion and cutting are widely unknown; models with the ability to accurately predict physical phenomena occurring in the tissue will allow for insight into the underlying mechanisms of the processes. This work presents three aims and the efforts in achieving them, leading to an accurate model of tissue fusion and more broadly the thermo-poromechanics (TPM) occurring within biological tissue. Chapters 1 and 2 provide the motivation for developing accurate TPM models of biological tissue and an overview of previous modeling efforts. In Chapter 3, a coupled thermo-structural finite element (FE) model with the ability to predict arterial cutting is offered. From the work presented in Chapter 3, it became obvious a more detailed model was needed. Chapter 4 meets this need by presenting small strain TPM theory and its implementation in an FE code. The model is then used to simulate thermal tissue fusion. These simulations show the model's promise in predicting the water content and temperature of arterial wall tissue during the fusion process, but it is limited by its small deformation assumptions. Chapters 5-7 attempt to address this limitation by developing and implementing a large deformation TPM FE model. Chapters 5, 6, and 7 present a thermodynamically consistent, large deformation TPM FE model and its ability to simulate tissue fusion. Ultimately, this work provides several methods of simulating arterial tissue fusion and the thermo-poromechanics of biological tissue. It is the first work, to the author's knowledge, to simulate the fully coupled TPM of biological tissue and the first to present a fully coupled large deformation TPM FE model. In doing so, a stepping stone for more advanced modeling of biological tissue has been laid.

The Ultimate Sampling Dilemma in Experience-Based Decision Making

ERIC Educational Resources Information Center

Fiedler, Klaus

2008-01-01

Computer simulations and 2 experiments demonstrate the ultimate sampling dilemma, which constitutes a serious obstacle to inductive inferences in a probabilistic world. Participants were asked to take the role of a manager who is to make purchasing decisions based on positive versus negative feedback about 3 providers in 2 different product…

Gaming science innovations to integrate health systems science into medical education and practice.

PubMed

White, Earla J; Lewis, Joy H; McCoy, Lise

2018-01-01

Health systems science (HSS) is an emerging discipline addressing multiple, complex, interdependent variables that affect providers' abilities to deliver patient care and influence population health. New perspectives and innovations are required as physician leaders and medical educators strive to accelerate changes in medical education and practice to meet the needs of evolving populations and systems. The purpose of this paper is to introduce gaming science as a lens to magnify HSS integration opportunities in the scope of medical education and practice. Evidence supports gaming science innovations as effective teaching and learning tools to promote learner engagement in scientific and systems thinking for decision making in complex scenarios. Valuable insights and lessons gained through the history of war games have resulted in strategic thinking to minimize risk and save lives. In health care, where decisions can affect patient and population outcomes, gaming science innovations have the potential to provide safe learning environments to practice crucial decision-making skills. Research of gaming science limitations, gaps, and strategies to maximize innovations to further advance HSS in medical education and practice is required. Gaming science holds promise to equip health care teams with HSS knowledge and skills required for transformative practice. The ultimate goals are to empower providers to work in complex systems to improve patient and population health outcomes and experiences, and to reduce costs and improve care team well-being.

Strength Enhancement of Car Front Bumper for Slow Speed Impact by FEA Method as per IIHS Regulation

NASA Astrophysics Data System (ADS)

Sonawane, Chandrakant Rameshchandra; Shelar, Ajit Lavaji

2017-05-01

Low speed collisions happen significantly due to on road slow moving heavy traffic as well as during parking of vehicles. The bumpers are provided in front and back side of a vehicle has two main purposes: first is to absorb the energy generated during these kinds of slow speed impacts and secondly to protect the expensive parts like main engine parts, radiators and connected engine cooling mechanism, headlights, taillights, etc, by slowing down the vehicles. The problem often in various cars bumper is that they doesn't line-up vertically during low speed impact and leads to damage of various parts which are costly to repair. Many a times bumper design does not have sufficient capacity to absorb the energy generated during these impact. Guideline by International Institute Highway Safety (IIHS) regulation provides useful insight for such low speed impact study. In this paper, slow speed impact test were conducted as per IIHS regulation in three positions namely central impact, left hand corner impact and right hand corner impact. Parameters including bumper material, shape, thickness and impact condition are analyzed using fine element analysis (FEA) to enhance crashworthiness design in low speed impact. Then the vehicle front structure has been modified suitably. It has been observed that lining up the front metal bumper with suitable stiffness provides the best result which ultimately reduces the damage to the vehicle parts.

Implementing Genome-Driven Oncology

PubMed Central

Hyman, David M.; Taylor, Barry S.; Baselga, José

2017-01-01

Early successes in identifying and targeting individual oncogenic drivers, together with the increasing feasibility of sequencing tumor genomes, have brought forth the promise of genome-driven oncology care. As we expand the breadth and depth of genomic analyses, the biological and clinical complexity of its implementation will be unparalleled. Challenges include target credentialing and validation, implementing drug combinations, clinical trial designs, targeting tumor heterogeneity, and deploying technologies beyond DNA sequencing, among others. We review how contemporary approaches are tackling these challenges and will ultimately serve as an engine for biological discovery and increase our insight into cancer and its treatment. PMID:28187282

Cancer biology and implications for practice.

PubMed

Rieger, Paula Trahan

2006-08-01

The media seem to announce a new scientific discovery related to cancer daily. Oncology nurses are challenged to keep up with the explosion of new knowledge and to understand how it ultimately relates to the care of patients with cancer. A framework for classifying new knowledge can be useful as nurses seek to understand the biology of cancer and its related implications for practice. To understand the molecular roots of cancer, healthcare practitioners specializing in cancer care require insight into genes, their messages, and the proteins produced from those messages, as well as the new tools of molecular biology.

Guidelines for Computing Longitudinal Dynamic Stability Characteristics of a Subsonic Transport

NASA Technical Reports Server (NTRS)

Thompson, Joseph R.; Frank, Neal T.; Murphy, Patrick C.

2010-01-01

A systematic study is presented to guide the selection of a numerical solution strategy for URANS computation of a subsonic transport configuration undergoing simulated forced oscillation about its pitch axis. Forced oscillation is central to the prevalent wind tunnel methodology for quantifying aircraft dynamic stability derivatives from force and moment coefficients, which is the ultimate goal for the computational simulations. Extensive computations are performed that lead in key insights of the critical numerical parameters affecting solution convergence. A preliminary linear harmonic analysis is included to demonstrate the potential of extracting dynamic stability derivatives from computational solutions.

[Friedrich Nietzsche's last lucid year].

PubMed

Figueroa, Gustavo

2007-05-01

As an outstanding philosopher Nietzsche poses the question whether his creativeness persisted in spite of his deteriorating disease or appeared, among other features, as a consequence of his illness. A thorough psychopathological understanding of his last lucid year is attempted. He had an exaggerated self-esteem and grandiose sense of confidence and achievements. But his lack of insight did not lead him to engage in activities that could harm himself or his loved ones. Between January 1888 and until his ultimate deterioration in January 1889, Nietzsche was exceedingly productive. During this period, polar changes along with moderately overlapping periods appeared.

Gold(I)-Catalysed Direct Thioetherifications Using Allylic Alcohols: an Experimental and Computational Study

PubMed Central

Herkert, Lorena; Green, Samantha L J; Barker, Graeme; Johnson, David G; Young, Paul C; Macgregor, Stuart A; Lee, Ai-Lan

2014-01-01

A gold(I)-catalysed direct thioetherification reaction between allylic alcohols and thiols is presented. The reaction is generally highly regioselective (SN2′). This dehydrative allylation procedure is very mild and atom economical, producing only water as the by-product and avoiding any unnecessary waste/steps associated with installing a leaving or activating group on the substrate. Computational studies are presented to gain insight into the mechanism of the reaction. Calculations indicate that the regioselectivity is under equilibrium control and is ultimately dictated by the thermodynamic stability of the products. PMID:25080400

Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?

PubMed

Yeh, Albert C; Ramaswamy, Sridhar

2015-12-01

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.

Mechanisms of Cancer Cell Dormancy – Another Hallmark of Cancer?

PubMed Central

Yeh, Albert C.; Ramaswamy, Sridhar

2015-01-01

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biological level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biological insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately down-regulate the Ras/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. PMID:26354021

Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

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

DeLoache, William; Russ, Zachary; Samson, Jennifer

The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurementsmore » of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis

PubMed Central

2013-01-01

Background In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation. Model Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer. Conclusions A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention. PMID:23758735

Proteomics of the Human Placenta: Promises and Realities

PubMed Central

Robinson, J.M.; Ackerman, W.E.; Kniss, D.A.; Takizawa, T.; Vandré, D.D.

2015-01-01

Proteomics is an area of study that sets as its ultimate goal the global analysis of all of the proteins expressed in a biological system of interest. However, technical limitations currently hamper proteome-wide analyses of complex systems. In a more practical sense, a desired outcome of proteomics research is the translation of large protein data sets into formats that provide meaningful information regarding clinical conditions (e.g., biomarkers to serve as diagnostic and/or prognostic indicators of disease). Herein, we discuss placental proteomics by describing existing studies, pointing out their strengths and weaknesses. In so doing, we strive to inform investigators interested in this area of research about the current gap between hyperbolic promises and realities. Additionally, we discuss the utility of proteomics in discovery-based research, particularly as regards the capacity to unearth novel insights into placental biology. Importantly, when considering under studied systems such as the human placenta and diseases associated with abnormalities in placental function, proteomics can serve as a robust ‘shortcut’ to obtaining information unlikely to be garnered using traditional approaches. PMID:18222537

New tools for classification and monitoring of autoimmune diseases

PubMed Central

Maecker, Holden T.; Lindstrom, Tamsin M.; Robinson, William H.; Utz, Paul J.; Hale, Matthew; Boyd, Scott D.; Shen-Orr, Shai S.; Fathman, C. Garrison

2012-01-01

Rheumatologists see patients with a range of autoimmune diseases. Phenotyping these diseases for diagnosis, prognosis and selection of therapies is an ever increasing problem. Advances in multiplexed assay technology at the gene, protein, and cellular level have enabled the identification of `actionable biomarkers'; that is, biological metrics that can inform clinical practice. Not only will such biomarkers yield insight into the development, remission, and exacerbation of a disease, they will undoubtedly improve diagnostic sensitivity and accuracy of classification, and ultimately guide treatment. This Review provides an introduction to these powerful technologies that could promote the identification of actionable biomarkers, including mass cytometry, protein arrays, and immunoglobulin and T-cell receptor high-throughput sequencing. In our opinion, these technologies should become part of routine clinical practice for the management of autoimmune diseases. The use of analytical tools to deconvolve the data obtained from use of these technologies is also presented here. These analyses are revealing a more comprehensive and interconnected view of the immune system than ever before and should have an important role in directing future treatment approaches for autoimmune diseases. PMID:22647780

Evidence of local and regional freshening of Northeast Greenland coastal waters.

PubMed

Sejr, Mikael K; Stedmon, Colin A; Bendtsen, Jørgen; Abermann, Jakob; Juul-Pedersen, Thomas; Mortensen, John; Rysgaard, Søren

2017-10-13

The supply of freshwater to fjord systems in Greenland is increasing as a result of climate change-induced acceleration in ice sheet melt. However, insight into the marine implications of the melt water is impaired by lack of observations demonstrating the fate of freshwater along the Greenland coast and providing evaluation basis for ocean models. Here we present 13 years of summer measurements along a 120 km transect in Young Sound, Northeast Greenland and show that sub-surface coastal waters are decreasing in salinity with an average rate of 0.12 ± 0.05 per year. This is the first observational evidence of a significant freshening on decadal scale of the waters surrounding the ice sheet and comes from a region where ice sheet melt has been less significant. It implies that ice sheet dynamics in Northeast Greenland could be of key importance as freshwater is retained in southward flowing coastal currents thus reducing density of water masses influencing major deep water formation areas in the Subarctic Atlantic Ocean. Ultimately, the observed freshening could have implications for the Atlantic meridional overturning circulation.

Inactivation of JNK1 enhances innate IL-10 production and dampens autoimmune inflammation in the brain.

PubMed

Tran, Elise H; Azuma, Yasu-Taka; Chen, Manchuan; Weston, Claire; Davis, Roger J; Flavell, Richard A

2006-09-05

Environmental insults such as microbial pathogens can contribute to the activation of autoreactive T cells, leading to inflammation of target organs and, ultimately, autoimmune disease. Various infections have been linked to multiple sclerosis and its animal counterpart, autoimmune encephalomyelitis. The molecular process by which innate immunity triggers autoreactivity is not currently understood. By using a mouse model of multiple sclerosis, we found that the genetic loss of the MAPK, c-Jun N-terminal kinase 1 (JNK1), enhances IL-10 production, rendering innate myeloid cells unresponsive to certain microbes and less capable of generating IL-17-producing, encephalitogenic T cells. Moreover, JNK1-deficient central nervous system myeloid cells are unable to respond to effector T cell inflammatory cytokines, preventing further progression to neuroinflammation. Thus, we have identified the JNK1 signal transduction pathway in myeloid cells to be a critical component of a regulatory circuit mediating inflammatory responses in autoimmune disease. Our findings provide further insights into the pivotal MAPK-regulated network of innate and adaptive cytokines in the progression to autoimmunity.

Mechanistic Insights from Discrete Molecular Dynamics Simulations of Pesticide-Nanoparticle Interactions.

PubMed

Geitner, Nicholas K; Zhao, Weilu; Ding, Feng; Chen, Wei; Wiesner, Mark R

2017-08-01

Nanoscale particles have the potential to modulate the transport, lifetimes, and ultimate uptake of pesticides that may otherwise be bound to agricultural soils. Engineered nanoparticles provide a unique platform for studying these interactions. In this study, we utilized discrete molecular dynamics (DMD) as a screening tool for examining nanoparticle-pesticide adsorptive interactions. As a proof-of-concept, we selected a library of 15 pesticides common in the United States and 4 nanomaterials with likely natural or incidental sources, and simulated all possible nanoparticle-pesticide pairs. The resulting adsorption coefficients derived from DMD simulations ranged over several orders of magnitude, and in many cases were significantly stronger than pesticide adsorption on clay surfaces, highlighting the significance of specific nanoscale phases as a preferential media with which pesticides may associate. Binding was found to be significantly enhanced by the capacity to form hydrogen bonds with slightly hydroxylated fullerols, highlighting the importance of considering the precise nature of weathered nanomaterials as opposed to pristine precursors. Results were compared to experimental adsorption studies using selected pesticides, with a Pearson correlation coefficient of 0.97.

A Multimodal Deep Log-Based User Experience (UX) Platform for UX Evaluation

PubMed Central

Ali Khan, Wajahat; Hur, Taeho; Muhammad Bilal, Hafiz Syed; Ul Hassan, Anees; Lee, Sungyoung

2018-01-01

The user experience (UX) is an emerging field in user research and design, and the development of UX evaluation methods presents a challenge for both researchers and practitioners. Different UX evaluation methods have been developed to extract accurate UX data. Among UX evaluation methods, the mixed-method approach of triangulation has gained importance. It provides more accurate and precise information about the user while interacting with the product. However, this approach requires skilled UX researchers and developers to integrate multiple devices, synchronize them, analyze the data, and ultimately produce an informed decision. In this paper, a method and system for measuring the overall UX over time using a triangulation method are proposed. The proposed platform incorporates observational and physiological measurements in addition to traditional ones. The platform reduces the subjective bias and validates the user’s perceptions, which are measured by different sensors through objectification of the subjective nature of the user in the UX assessment. The platform additionally offers plug-and-play support for different devices and powerful analytics for obtaining insight on the UX in terms of multiple participants. PMID:29783712

Pranked by Audubon: Constantine S. Rafinesque's description of John James Audubon's imaginary Kentucky mammals

USGS Publications Warehouse

Woodman, Neal

2016-01-01

The North American naturalist Constantine S. Rafinesque spent much of the year 1818 engaged in a solo journey down the Ohio River Valley to explore parts of what was then the western United States. Along the way, he visited a number of fellow naturalists, and he spent more than a week at the Henderson, Kentucky, home of artist and ornithologist John James Audubon. During the succeeding two years, Rafinesque published descriptions of new species that resulted from his expedition, including eleven species of fishes that eventually proved to have been invented by Audubon as a prank on the credulous naturalist. Less well known are a number of “wild rats” described by Rafinesque that include one recognized species (Musculus leucopus) and ten other, imaginary “species” fabricated by Audubon (Gerbillus leonurus, G. megalops, Spalax trivittata, Cricetus fasciatus, Sorex cerulescens, S. melanotis, Musculus nigricans, Lemmus albovittatus, L. talpoides, Sciurus ruber). Rafinesque's unpublished sketches of these animals provide important insight regarding the supposed nature of the animals invented by Audubon and ultimately published by Rafinesque.

A Multimodal Deep Log-Based User Experience (UX) Platform for UX Evaluation.

PubMed

Hussain, Jamil; Khan, Wajahat Ali; Hur, Taeho; Bilal, Hafiz Syed Muhammad; Bang, Jaehun; Hassan, Anees Ul; Afzal, Muhammad; Lee, Sungyoung

2018-05-18

The user experience (UX) is an emerging field in user research and design, and the development of UX evaluation methods presents a challenge for both researchers and practitioners. Different UX evaluation methods have been developed to extract accurate UX data. Among UX evaluation methods, the mixed-method approach of triangulation has gained importance. It provides more accurate and precise information about the user while interacting with the product. However, this approach requires skilled UX researchers and developers to integrate multiple devices, synchronize them, analyze the data, and ultimately produce an informed decision. In this paper, a method and system for measuring the overall UX over time using a triangulation method are proposed. The proposed platform incorporates observational and physiological measurements in addition to traditional ones. The platform reduces the subjective bias and validates the user's perceptions, which are measured by different sensors through objectification of the subjective nature of the user in the UX assessment. The platform additionally offers plug-and-play support for different devices and powerful analytics for obtaining insight on the UX in terms of multiple participants.

Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications.

PubMed

Patel, Siddharth; Athirasala, Avathamsa; Menezes, Paula P; Ashwanikumar, N; Zou, Ting; Sahay, Gaurav; Bertassoni, Luiz E

2018-06-07

The ability to control cellular processes and precisely direct cellular reprogramming has revolutionized regenerative medicine. Recent advances in in vitro transcribed (IVT) mRNA technology with chemical modifications have led to development of methods that control spatiotemporal gene expression. Additionally, there is a current thrust toward the development of safe, integration-free approaches to gene therapy for translational purposes. In this review, we describe strategies of synthetic IVT mRNA modifications and nonviral technologies for intracellular delivery. We provide insights into the current tissue engineering approaches that use a hydrogel scaffold with genetic material. Furthermore, we discuss the transformative potential of novel mRNA formulations that when embedded in hydrogels can trigger controlled genetic manipulation to regenerate tissues and organs in vitro and in vivo. The role of mRNA delivery in vascularization, cytoprotection, and Cas9-mediated xenotransplantation is additionally highlighted. Harmonizing mRNA delivery vehicle interactions with polymeric scaffolds can be used to present genetic cues that lead to precise command over cellular reprogramming, differentiation, and secretome activity of stem cells-an ultimate goal for tissue engineering.

A Compact Airborne System for SO2 and DMS Measurements for Use on Future GTE Missions Aboard the P-3 or DC-8

NASA Technical Reports Server (NTRS)

Saltzman, Eric S.; DeBruyn, Warren J.

2000-01-01

This project involved the design and construction of a new instrument for airborne measurement of DMS and SO2. The instrument is intended for use on field missions to study the global atmospheric sulfur cycle. The ultimate scientific goal is to provide insight into the mechanisms of atmospheric transport and transformations impacting both natural and anthropogenic sulfur emissions. This report summarizes the progress made to date and the goals for future work on the project. The PI's for this project have recently relocated from the University of Miami to the University of California, Irvine, and a request has been made to transfer remaining funds to UCI. All equipment associated with this project has been transferred to UCI. The instrument design goal was to develop an instrument roughly one quarter the size and weight of currently available airborne instrumentation used for DMS and S02 measurements. Another goal was full automation, to allow unattended operation for the duration of a P-3 or DC-8 flight. The original performance design specifications for the instrument are given.

Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels

PubMed Central

Nivedita, Nivedita; Ligrani, Phillip; Papautsky, Ian

2017-01-01

A wide range of microfluidic cell-sorting devices has emerged in recent years, based on both passive and active methods of separation. Curvilinear channel geometries are often used in these systems due to presence of secondary flows, which can provide high throughput and sorting efficiency. Most of these devices are designed on the assumption of two counter rotating Dean vortices present in the curved rectangular channels and existing in the state of steady rotation and amplitude. In this work, we investigate these secondary flows in low aspect ratio spiral rectangular microchannels and define their development with respect to the channel aspect ratio and Dean number. This work is the first to experimentally and numerically investigate Dean flows in microchannels for Re > 100, and show presence of secondary Dean vortices beyond a critical Dean number. We further demonstrate the impact of these multiple vortices on particle and cell focusing. Ultimately, this work offers new insights into secondary flow instabilities for low-aspect ratio, spiral microchannels, with improved flow models for design of more precise and efficient microfluidic devices for applications such as cell sorting and micromixing. PMID:28281579

Dynamic crystallography reveals early signalling events in ultraviolet photoreceptor UVR8

DOE PAGES

Zeng, Xiaoli; Ren, Zhong; Wu, Qi; ...

2015-01-08

Arabidopsis thaliana UVR8 (AtUVR8) is a long-sought-after photoreceptor that undergoes dimer dissociation in response to UV-B light. Crystallographic and mutational studies have identified two crucial tryptophan residues for UV-B responses in AtUVR8. However, the mechanism of UV-B perception and structural events leading up to dimer dissociation remain elusive at the molecular level. We applied dynamic crystallography to capture light-induced structural events in photoactive AtUVR8 crystals. Here we report two intermediate structures at 1.67Å resolution. At the epicenter of UV-B signaling, concerted motions associated with Trp285/Trp233 lead to ejection of a water molecule, which weakens an intricate network of hydrogen bondsmore » and salt bridges at the dimer interface. Partial opening of the β-propeller structure due to thermal relaxation of conformational strains originating in the epicenter further disrupts the dimer interface and leads to dimer dissociation. Ultimately, these dynamic crystallographic observations provide structural insights into the photo-perception and signaling mechanism of UVR8.« less

Genomic Diversity in the Endosymbiotic Bacterium Rhizobium leguminosarum.

PubMed

Sánchez-Cañizares, Carmen; Jorrín, Beatriz; Durán, David; Nadendla, Suvarna; Albareda, Marta; Rubio-Sanz, Laura; Lanza, Mónica; González-Guerrero, Manuel; Prieto, Rosa Isabel; Brito, Belén; Giglio, Michelle G; Rey, Luis; Ruiz-Argüeso, Tomás; Palacios, José M; Imperial, Juan

2018-01-24

Rhizobium leguminosarum bv. viciae is a soil α-proteobacterium that establishes a diazotrophic symbiosis with different legumes of the Fabeae tribe. The number of genome sequences from rhizobial strains available in public databases is constantly increasing, although complete, fully annotated genome structures from rhizobial genomes are scarce. In this work, we report and analyse the complete genome of R. leguminosarum bv. viciae UPM791. Whole genome sequencing can provide new insights into the genetic features contributing to symbiotically relevant processes such as bacterial adaptation to the rhizosphere, mechanisms for efficient competition with other bacteria, and the ability to establish a complex signalling dialogue with legumes, to enter the root without triggering plant defenses, and, ultimately, to fix nitrogen within the host. Comparison of the complete genome sequences of two strains of R. leguminosarum bv. viciae , 3841 and UPM791, highlights the existence of different symbiotic plasmids and a common core chromosome. Specific genomic traits, such as plasmid content or a distinctive regulation, define differential physiological capabilities of these endosymbionts. Among them, strain UPM791 presents unique adaptations for recycling the hydrogen generated in the nitrogen fixation process.

Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models

PubMed Central

Todd, Robert G.; van der Zee, Lucas

2016-01-01

Abstract The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network. PMID:27993914

Competing opinion diffusion on social networks.

PubMed

Hu, Haibo

2017-11-01

Opinion competition is a common phenomenon in real life, such as with opinions on controversial issues or political candidates; however, modelling this competition remains largely unexplored. To bridge this gap, we propose a model of competing opinion diffusion on social networks taking into account degree-dependent fitness or persuasiveness. We study the combined influence of social networks, individual fitnesses and attributes, as well as mass media on people's opinions, and find that both social networks and mass media act as amplifiers in opinion diffusion, the amplifying effect of which can be quantitatively characterized. We analytically obtain the probability that each opinion will ultimately pervade the whole society when there are no committed people in networks, and the final proportion of each opinion at the steady state when there are committed people in networks. The results of numerical simulations show good agreement with those obtained through an analytical approach. This study provides insight into the collective influence of individual attributes, local social networks and global media on opinion diffusion, and contributes to a comprehensive understanding of competing diffusion behaviours in the real world.

Conducting pharmaceutical R&D in India - Critical components of entry strategies.

PubMed

Gulati, Rajiv

2008-11-01

In the face of challenges associated with expiring patents, the rising cost of R&D and pressure on pricing, most major pharmaceutical companies are seeking ways to enhance productivity, reduce costs and augment the late-stage new-product pipeline. Exploiting the R&D capabilities in India is one option that can be helpful in achieving these goals. However, considering the challenges involved, important considerations must be incorporated to ensure that an appropriate R&D strategy is meticulously implemented. In creating suitable strategies, it is important to understand the historical perspective that provides insight into the relative strengths of companies in India across the R&D value chain. In addition, the ability of a company to take risks and commit to a long-term investment will largely determine the model that is selected. To implement a given model, an understanding of cultural differences and infrastructural challenges that must be overcome is extremely important. The ultimate factor that determines success or failure, however, lies within the organization. Preparing an organization by establishing appropriate structures and processes is imperative.

The use of mixed methods in studying a chronic illness

PubMed Central

Jason, Leonard A.; Reed, Jordan

2016-01-01

This article explores mixed methods approaches with an illness called Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Qualitative and Quantitative data were used to investigate the epidemiology of this illness, as well as explore attributions based on the name of the illness, and finally treatment approaches. In each of the domains within the ME and CFS research reviewed, our analyses were richer and our findings ultimately more impactful when we integrated qualitative and quantitative research methods. The use of a multiphase mixed methods research program provided our team unique vantage points for better understanding social and community issues involving this controversial chronic illness. Further, this approach allowed us to implement the insights gained through an advocacy lens to change policy, recommend and evaluate treatments, and amplify voices within the patient population. In this way, we believe that the practice of methodological pluralism is especially applicable and effective to the study of chronic illness, and believe other investigators will benefit from the use of these approaches with similar disenfranchised and unfairly treated populations. PMID:27088060

Dendrite-free Li metal anode enabled by a 3D free-standing lithiophilic nitrogen-enriched carbon sponge

NASA Astrophysics Data System (ADS)

Hou, Guangmei; Ren, Xiaohua; Ma, Xiaoxin; Zhang, Le; Zhai, Wei; Ai, Qing; Xu, Xiaoyan; Zhang, Lin; Si, Pengchao; Feng, Jinkui; Ding, Fei; Ci, Lijie

2018-05-01

Lithium metal is considered as the ultimate anode material for high-energy Li battery systems. However, the commercial application of lithium anode is impeded by issues with safety and low coulombic efficiency induced by Li dendrite growth. Herein, a free-standing three-dimensional nitrogen-enriched graphitic carbon sponge with a high nitrogen content is proposed as a multifunctional current collect for Lithium accommodation. The abundant lithiophilic N-containing functional groups are served as preferred nucleation sites to guide a uniform Li deposition. In addition, the nitrogen-enriched graphitic carbon sponge with a high specific surface area can effectively reduce the local current density. As a result of the synergistic effect, the nitrogen-enriched graphitic carbon sponge electrode realizes a long-term stable cycling without dendrites formation. Notably, the as-obtained composite electrode can deliver an ultra-high specific capacity of ∼3175 mA h g-1. The nitrogen-enriched graphitic carbon sponge might provide innovative insights to design a superior matrix for dendrite-free Li anode.

Competing opinion diffusion on social networks

PubMed Central

2017-01-01

Opinion competition is a common phenomenon in real life, such as with opinions on controversial issues or political candidates; however, modelling this competition remains largely unexplored. To bridge this gap, we propose a model of competing opinion diffusion on social networks taking into account degree-dependent fitness or persuasiveness. We study the combined influence of social networks, individual fitnesses and attributes, as well as mass media on people’s opinions, and find that both social networks and mass media act as amplifiers in opinion diffusion, the amplifying effect of which can be quantitatively characterized. We analytically obtain the probability that each opinion will ultimately pervade the whole society when there are no committed people in networks, and the final proportion of each opinion at the steady state when there are committed people in networks. The results of numerical simulations show good agreement with those obtained through an analytical approach. This study provides insight into the collective influence of individual attributes, local social networks and global media on opinion diffusion, and contributes to a comprehensive understanding of competing diffusion behaviours in the real world. PMID:29291101

Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome.

PubMed

Ewing, Grace; Tatarchuk, Yekaterina; Appleby, Dina; Schwartz, Nadav; Kim, Deborah

2015-04-01

Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy. Because antidepressants freely cross into the intrauterine environment, we aim to summarize the current findings on placental transfer of antidepressants. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome (PNAS). Specifically, we explore whether the antidepressants most closely associated with PNAS (paroxetine, fluoxetine, venlafaxine) cross the placenta to a greater extent than other antidepressants. We review research on antidepressants in the context of placental anatomy, placental transport mechanisms, placental metabolism, pharmacokinetics, as well as non-placental maternal and fetal factors. This provides insight into the complexity involved in understanding how placental transfer of antidepressants may relate to adverse perinatal outcomes. Ultimately, from this data there is no pattern in which PNAS is related to placental transfer of antidepressant medications. In general, there is large interindividual variability for each type of antidepressant. To make the most clinically informed decisions about the use of antidepressants in pregnancy, studies that link maternal, placental and fetal genetic polymorphisms, placental transfer rates and infant outcomes are needed.

Solvent viscosity and friction in protein folding dynamics.

PubMed

Hagen, Stephen J

2010-08-01

The famous Kramers rate theory for diffusion-controlled reactions has been extended in numerous ways and successfully applied to many types of reactions. Its application to protein folding reactions has been of particular interest in recent years, as many researchers have performed experiments and simulations to test whether folding reactions are diffusion-controlled, whether the solvent is the source of the reaction friction, and whether the friction-dependence of folding rates generally can provide insight into folding dynamics. These experiments involve many practical difficulties, however. They have also produced some unexpected results. Here we briefly review the Kramers theory for reactions in the presence of strong friction and summarize some of the subtle problems that arise in the application of the theory to protein folding. We discuss how the results of these experiments ultimately point to a significant role for internal friction in protein folding dynamics. Studies of friction in protein folding, far from revealing any weakness in Kramers theory, may actually lead to new approaches for probing diffusional dynamics and energy landscapes in protein folding.

NSAID-activated gene 1 and its implications for mucosal integrity and intervention beyond NSAIDs.

PubMed

Moon, Yuseok

2017-07-01

In spite of the beneficial actions of non-steroid anti-inflammatory drugs (NSAIDs) in epithelial inflammation and cancers, their use is limited because of their cyclooxygenase-dependent or independent gastrointestinal toxicity. As an eicosanoid-independent mediator, NSAID-activated gene 1 (NAG-1) has been assessed for its involvement in cellular integrity and pathogenesis in mucosal inflammation and carcinogenesis. At the cellular levels, NAG-1 is involved in the cell growth regulation (cell death, cell cycle arrest, or proliferation) in epithelial and mesenchymal tissues. Moreover, NAG-1 can modulate inflammatory responses in either direct or indirect manner, which ultimately affects fibrogenic and tumorigenic processes in various disease states. Finally, NAG-1 has been assessed for its contribution to cellular behavior, such as the mobility of epithelial and malignant cells in response to the external insults or oncogenic stimulation in the mucosa. This review on the "Yin-Yang" nature of NAG-1-mediated responses provides comprehensive insights into therapeutic and diagnostic interventions for mucosal health and integrity in the human body. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Neuron-specific Chromatin Regulatory Subunit BAF53b is Necessary for Synaptic Plasticity and Memory

PubMed Central

Vogel-Ciernia, Annie; Matheos, Dina P.; Barrett, Ruth M.; Kramár, Enikö; Azzawi, Soraya; Chen, Yuncai; Magnan, Christophe N.; Zeller, Michael; Sylvain, Angelina; Haettig, Jakob; Jia, Yousheng; Tran, Anthony; Dang, Richard; Post, Rebecca J.; Chabrier, Meredith; Babayan, Alex; Wu, Jiang I.; Crabtree, Gerald R.; Baldi, Pierre; Baram, Tallie Z.; Lynch, Gary; Wood, Marcelo A.

2013-01-01

Recent exome sequencing studies have implicated polymorphic BAF complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Post mitotic neurons express a neuron specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in longterm memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, indicating a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appear to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our studies provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders. PMID:23525042

The PEREGRINETM program: using physics and computer simulation to improve radiation therapy for cancer

NASA Astrophysics Data System (ADS)

Hartmann Siantar, Christine L.; Moses, Edward I.

1998-11-01

When using radiation to treat cancer, doctors rely on physics and computer technology to predict where the radiation dose will be deposited in the patient. The accuracy of computerized treatment planning plays a critical role in the ultimate success or failure of the radiation treatment. Inaccurate dose calculations can result in either insufficient radiation for cure, or excessive radiation to nearby healthy tissue, which can reduce the patient's quality of life. This paper describes how advanced physics, computer, and engineering techniques originally developed for nuclear weapons and high-energy physics research are being used to predict radiation dose in cancer patients. Results for radiation therapy planning, achieved in the Lawrence Livermore National Laboratory (LLNL) 0143-0807/19/6/005/img2 program show that these tools can give doctors new insights into their patients' treatments by providing substantially more accurate dose distributions than have been available in the past. It is believed that greater accuracy in radiation therapy treatment planning will save lives by improving doctors' ability to target radiation to the tumour and reduce suffering by reducing the incidence of radiation-induced complications.

Critical aspects in the production of periodically ordered mesoporous titania thin films.

PubMed

Soler-Illia, Galo J A A; Angelomé, Paula C; Fuertes, M Cecilia; Grosso, David; Boissiere, Cedric

2012-04-21

Periodically ordered mesoporous titania thin films (MTTF) present a high surface area, controlled porosity in the 2-20 nm pore diameter range and an amorphous or crystalline inorganic framework. These materials are nowadays routinely prepared by combining soft chemistry and supramolecular templating. Photocatalytic transparent coatings and titania-based solar cells are the immediate promising applications. However, a wealth of new prospective uses have emerged on the horizon, such as advanced catalysts, perm-selective membranes, optical materials based on plasmonics and photonics, metamaterials, biomaterials or new magnetic nanocomposites. Current and novel applications rely on the ultimate control of the materials features such as pore size and geometry, surface functionality and wall structure. Even if a certain control of these characteristics has been provided by the methods reported so far, the needs for the next generation of MTTF require a deeper insight in the physical and chemical processes taking place in their preparation and processing. This article presents a critical discussion of these aspects. This discussion is essential to evolve from know-how to sound knowledge, aiming at a rational materials design of these fascinating systems.

A methyltransferase gene from arbuscular mycorrhizal fungi involved in arsenic methylation and volatilization.

PubMed

Li, Jinglong; Sun, Yuqing; Zhang, Xin; Hu, Yajun; Li, Tao; Zhang, Xuemeng; Wang, Zhi; Wu, Songlin; Wu, Zhaoxiang; Chen, Baodong

2018-06-20

Arbuscular mycorrhizal fungi (AMF), ubiquitous symbiotic fungi associated with the majority of terrestrial plants, were demonstrated to play important roles in arsenic (As) translocation and transformation in the plant-soil continuum, and substantially influence plant As tolerance. However, the direct involvement of AMF in As methylation and volatilization and their molecular mechanisms remain unsolved. Here, an arsenite methyltransferase gene RiMT-11 was identified and characterized from AM fungus Rhizophagus irregularis. Heterologous expression of RiMT-11 enhanced arsenite resistance of E. coli (Δars) through methylating As into monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and ultimately volatile trimethyl arsine (TMAs). In a two-compartment in vitro monoxenic cultivation system, methylated and volatile As were also detected from AM symbioses with arsenate addition, accompanied by strong up-regulation of RiMT-11 expression in extraradical hyphae. The present study provided direct evidence and illustrated an underlying mechanism of As methylation and volatilization by AMF, leading to a deeper insight into the role of AMF in As biogeochemical cycling. Copyright © 2018 Elsevier Ltd. All rights reserved.

A dictionary without definitions: romanticist science in the production and presentation of the Grimm brothers' German dictionary, 1838-1863.

PubMed

Kistner, Kelly

2014-12-01

Between 1838 and 1863 the Grimm brothers led a collaborative research project to create a new kind of dictionary documenting the history of the German language. They imagined the work would present a scientific account of linguistic cohesiveness and strengthen German unity. However, their dictionary volumes (most of which were arranged and written by Jacob Grimm) would be variously criticized for their idiosyncratic character and ultimately seen as a poor, and even prejudicial, piece of scholarship. This paper argues that such criticisms may reflect a misunderstanding of the dictionary. I claim it can be best understood as an artifact of romanticist science and its epistemological privileging of subjective perception coupled with a deeply-held faith in inter-subjective congruence. Thus situated, it is a rare and detailed case of Romantic ideas and ideals applied to the scientific study of social artifacts. Moreover, the dictionary's organization, reception, and legacy provide insights into the changing landscape of scientific practice in Germany, showcasing the difficulties of implementing a romanticist vision of science amidst widening gaps between the public and professionals, generalists and specialists.

Energy levels distribution in supersaturated silicon with titanium for photovoltaic applications

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

Pérez, E., E-mail: eduper@ele.uva.es; Castán, H.; García, H.

2015-01-12

In the attempt to form an intermediate band in the bandgap of silicon substrates to give it the capability to absorb infrared radiation, we studied the deep levels in supersaturated silicon with titanium. The technique used to characterize the energy levels was the thermal admittance spectroscopy. Our experimental results showed that in samples with titanium concentration just under Mott limit there was a relationship among the activation energy value and the capture cross section value. This relationship obeys to the well known Meyer-Neldel rule, which typically appears in processes involving multiple excitations, like carrier capture/emission in deep levels, and itmore » is generally observed in disordered systems. The obtained characteristic Meyer-Neldel parameters were Tmn = 176 K and kTmn = 15 meV. The energy value could be associated to the typical energy of the phonons in the substrate. The almost perfect adjust of all experimental data to the same straight line provides further evidence of the validity of the Meyer Neldel rule, and may contribute to obtain a deeper insight on the ultimate meaning of this phenomenon.« less

An Empirical Study of Chronic Diseases in the United States: A Visual Analytics Approach to Public Health

PubMed Central

Raghupathi, Wullianallur; Raghupathi, Viju

2018-01-01

In this research we explore the current state of chronic diseases in the United States, using data from the Centers for Disease Control and Prevention and applying visualization and descriptive analytics techniques. Five main categories of variables are studied, namely chronic disease conditions, behavioral health, mental health, demographics, and overarching conditions. These are analyzed in the context of regions and states within the U.S. to discover possible correlations between variables in several categories. There are widespread variations in the prevalence of diverse chronic diseases, the number of hospitalizations for specific diseases, and the diagnosis and mortality rates for different states. Identifying such correlations is fundamental to developing insights that will help in the creation of targeted management, mitigation, and preventive policies, ultimately minimizing the risks and costs of chronic diseases. As the population ages and individuals suffer from multiple conditions, or comorbidity, it is imperative that the various stakeholders, including the government, non-governmental organizations (NGOs), policy makers, health providers, and society as a whole, address these adverse effects in a timely and efficient manner. PMID:29494555

General fuel cell hybrid synergies and hybrid system testing status

NASA Astrophysics Data System (ADS)

Winkler, Wolfgang; Nehter, Pedro; Williams, Mark C.; Tucker, David; Gemmen, Randy

FCT hybrid power systems offer the highest efficiency and the cleanest emissions of all fossil fuelled power. The engineering for the highest possible efficiency at lowest cost and weight depends on general system architecture issues and the performance of the components. Presented in this paper are system studies which provide direction for the most efficient path toward achieving the most beneficial result for this technology. Ultimately, fuel cell-turbine (FCT) hybrid systems applicable to integrated gasification combined cycle power systems will form the basis for reaching the goals for advanced coal-based power generation. The FCT hybrid power island will also be important for the FutureGen plant and will provide new options for carbon dioxide capture and sequestration as well as power and hydrogen generation. The system studies presented in this paper provide insight to current technology 'benchmarks' versus expected benefits from hybrid applications. Discussion is also presented on the effects of different balance of plant arrangements and approaches. Finally, we discuss the status of US DOE is sponsored projects that are looking to help understand the unique requirements for these systems. One of these projects, Hyper, will provide information on FCT dynamics and will help identify technical needs and opportunities for cycle advancement. The methods studied show promise for effective control of a hybrid system without the direct intervention of isolation valves or check valves in the main pressure loop of the system, which introduce substantial pressure losses, allowing for realization of the full potential efficiency of the hybrid system.

‘Like sugar and honey’: The embedded ethics of a larval control project in The Gambia

PubMed Central

Kelly, Ann H.; Ameh, David; Majambere, Silas; Lindsay, Steve; Pinder, Margaret

2010-01-01

This paper describes a malaria research project in The Gambia to provoke thinking on the social value of transnational research. The Larval Control Project (LCP) investigated the efficacy of a microbial insecticide to reduce vector density and, ultimately, clinical malaria in Gambian children. The LCP’s protocol delineated a clinical surveillance scheme that involved Village Health Workers (VHWs) supported by project nurses. Combining insights from ethnographic fieldwork conducted at the Medical Research Council (MRC) Laboratories in Farafenni from 2005 to 2009, open-ended interviews with project nurses, and eight focus group discussions held with participant mothers in October 2007, we consider the social impact of the LCP’s investigative method against the backdrop of several years of research activity. We found that while participants associated the LCP with the clinical care it provided, they also regarded the collaboration between the nurses and VHWs added additional benefits. Organised around the operational functions of the trial, small-scale collaborations provided the platform from which to build local capacity. While ethical guidelines emphasise the considerations that must be added to experimental endeavour in southern countries (e.g. elaborating processes of informed consent, developing strategies of community engagement or providing therapeutic access to participants after the trial concludes), these findings suggest that shifting attention from supplementing ethical protocols to the everyday work of research – embedding ethics through scientific activity – may provide a sounder basis to reinforce the relationship between scientific rigour and social value. PMID:20362381

Minireview: The Molecular and Genomic Basis for Prostate Cancer Health Disparities

PubMed Central

Bollig-Fischer, Aliccia

2013-01-01

Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, race disparities persist. For African American men (AAM), PCa is more often an aggressive disease showing increased metastases and greater PCa-related mortality compared with European American men. The earliest research points to how distinctions are likely the result of a combination of factors, including ancestry genetics and lifestyle variables. More recent research considers that cancer, although influenced by external forces, is ultimately a disease primarily driven by aberrations observed in the molecular genetics of the tumor. Research studying PCa predominantly from European American men shows that indolent and advanced or metastatic prostate tumors have distinguishing molecular genomic make-ups. Early yet increasing evidence suggests that clinically distinct PCa from AAM also display molecular distinctions. It is reasonable to predict that further study will reveal molecular subtypes and various frequencies for PCa subtypes among diverse patient groups, thereby providing insight as to the genomic lesions and gene signatures that are functionally implicated in carcinogenesis or aggressive PCa in AAM. That knowledge will prove useful in developing strategies to predict who will develop advanced PCa among AAM and will provide the rationale to develop effective individualized treatment strategies to overcome disparities. PMID:23608645

Using Smart Pumps to Understand and Evaluate Clinician Practice Patterns to Ensure Patient Safety

PubMed Central

Mansfield, Jennifer; Jarrett, Steven

2013-01-01

Background: Safety software installed on intravenous (IV) infusion pumps has been shown to positively impact the quality of patient care through avoidance of medication errors. The data derived from the use of smart pumps are often overlooked, although these data provide helpful insight into the delivery of quality patient care. Objective: The objectives of this report are to describe the value of implementing IV infusion safety software and analyzing the data and reports generated by this system. Case study: Based on experience at the Carolinas HealthCare System (CHS), executive score cards provide an aggregate view of compliance rate, number of alerts, overrides, and edits. The report of serious errors averted (ie, critical catches) supplies the location, date, and time of the critical catch, thereby enabling management to pinpoint the end-user for educational purposes. By examining the number of critical catches, a return on investment may be calculated. Assuming 3,328 of these events each year, an estimated cost avoidance would be $29,120,000 per year for CHS. Other reports allow benchmarking between institutions. Conclusion: A review of the data about medication safety across CHS has helped garner support for a medication safety officer position with the goal of ultimately creating a safer environment for the patient. PMID:24474836

Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

PubMed

Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A; Birkholtz, Lyn-Marie

2015-05-01

Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.

Laurentide Ice Sheet Meltwater Geochemistry During the MIS 3 Warm Phase from Single-Shell Trace Element and Isotope Measurements

NASA Astrophysics Data System (ADS)

Branson, O.; Vetter, L.; Fehrenbacher, J. S.; Spero, H. J.

2016-12-01

The geochemical variability between individual foraminifera within single core intervals records both palaeo-oecanographic conditions and ecology. Within the biological context of foraminiferal species, this population variability may be interpreted to provide unparalleled paleoenvironmental information. For example, coupled trace element and stable isotope analyses of single O. universa offer a powerful tool for reconstructing the δ18O of Laurentide Ice Sheet (LIS) meltwater, by calculating the intercept between temperature-corrected δ18O water and Ba/Ca salinity estimates (Vetter et al., in review). This offers valuable insights into the dynamics of ice sheet melting at the end of the last glacial maximum. Here we apply similar coupled single-shell laser ablation (LA-ICP-MS) and isotope ratio mass spectrometry (IRMS) techniques to explore the δ18O of Laurentide meltwater during H4 and bracketing intervals. The application of these methods to down-core samples requires the development of robust LA-ICP-MS data processing techniques to identify primary signals within Ba contaminated samples, and careful consideration of palaeo Ba/Ca-salinity relationships. Our analyses offer a significant advance in systematic LA-ICP-MS data processing methods, offer constraints on the variability of riverine Ba fluxes, and ultimately provide δ18O estimates of LIS meltwater during H4.

The effect of nanoparticle packing on capacitive electrode performance.

PubMed

Lee, Younghee; Noh, Seonmyeong; Kim, Min-Sik; Kong, Hye Jeong; Im, Kyungun; Kwon, Oh Seok; Kim, Sungmin; Yoon, Hyeonseok

2016-06-09

Nanoparticles pack together to form macro-scale electrodes in various types of devices, and thus, optimization of the nanoparticle packing is a prerequisite for the realization of a desirable device performance. In this work, we provide in-depth insight into the effect of nanoparticle packing on the performance of nanoparticle-based electrodes by combining experimental and computational findings. As a model system, polypyrrole nanospheres of three different diameters were used to construct pseudocapacitive electrodes, and the performance of the electrodes was examined at various nanosphere diameter ratios and mixed weight fractions. Two numerical algorithms are proposed to simulate the random packing of the nanospheres on the electrode. The binary nanospheres exhibited diverse, complicated packing behaviors compared with the monophasic packing of each nanosphere species. The packing of the two nanosphere species with lower diameter ratios at an optimized composition could lead to more dense packing of the nanospheres, which in turn could contribute to better device performance. The dense packing of the nanospheres would provide more efficient transport pathways for ions because of the reduced inter-nanosphere pore size and enlarged surface area for charge storage. Ultimately, it is anticipated that our approach can be widely used to define the concept of "the best nanoparticle packing" for desirable device performance.

Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

PubMed Central

Lewis, David J. M.; Lythgoe, Mark P.

2015-01-01

Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing. PMID:26380327

In situ TEM study of lithiation behavior of silicon nanoparticles attached to and embedded in a carbon matrix.

PubMed

Gu, Meng; Li, Ying; Li, Xiaolin; Hu, Shenyang; Zhang, Xiangwu; Xu, Wu; Thevuthasan, Suntharampillai; Baer, Donald R; Zhang, Ji-Guang; Liu, Jun; Wang, Chongmin

2012-09-25

Rational design of silicon and carbon nanocomposite with a special topological feature has been demonstrated to be a feasible way for mitigating the capacity fading associated with the large volume change of silicon anode in lithium ion batteries. Although the lithiation behavior of silicon and carbon as individual components has been well understood, lithium ion transport behavior across a network of silicon and carbon is still lacking. In this paper, we probe the lithiation behavior of silicon nanoparticles attached to and embedded in a carbon nanofiber using in situ TEM and continuum mechanical calculation. We found that aggregated silicon nanoparticles show contact flattening upon initial lithiation, which is characteristically analogous to the classic sintering of powder particles by a neck-growth mechanism. As compared with the surface-attached silicon particles, particles embedded in the carbon matrix show delayed lithiation. Depending on the strength of the carbon matrix, lithiation of the embedded silicon nanoparticles can lead to the fracture of the carbon fiber. These observations provide insights on lithium ion transport in the network-structured composite of silicon and carbon and ultimately provide fundamental guidance for mitigating the failure of batteries due to the large volume change of silicon anodes.

Designing robots for care: care centered value-sensitive design.

PubMed

van Wynsberghe, Aimee

2013-06-01

The prospective robots in healthcare intended to be included within the conclave of the nurse-patient relationship--what I refer to as care robots--require rigorous ethical reflection to ensure their design and introduction do not impede the promotion of values and the dignity of patients at such a vulnerable and sensitive time in their lives. The ethical evaluation of care robots requires insight into the values at stake in the healthcare tradition. What's more, given the stage of their development and lack of standards provided by the International Organization for Standardization to guide their development, ethics ought to be included into the design process of such robots. The manner in which this may be accomplished, as presented here, uses the blueprint of the Value-sensitive design approach as a means for creating a framework tailored to care contexts. Using care values as the foundational values to be integrated into a technology and using the elements in care, from the care ethics perspective, as the normative criteria, the resulting approach may be referred to as care centered value-sensitive design. The framework proposed here allows for the ethical evaluation of care robots both retrospectively and prospectively. By evaluating care robots in this way, we may ultimately ask what kind of care we, as a society, want to provide in the future.

A conceptualisation framework for building consensus on environmental sensitivity.

PubMed

González Del Campo, Ainhoa

2017-09-15

Examination of the intrinsic attributes of a system that render it more or less sensitive to potential stressors provides further insight into the baseline environment. In impact assessment, sensitivity of environmental receptors can be conceptualised on the basis of their: a) quality status according to statutory indicators and associated thresholds or targets; b) statutory protection; or c) inherent risk. Where none of these considerations are pertinent, subjective value judgments can be applied to determine sensitivity. This pragmatic conceptual framework formed the basis of a stakeholder consultation process for harmonising degrees of sensitivity of a number of environmental criteria. Harmonisation was sought to facilitate their comparative and combined analysis. Overall, full or wide agreement was reached on relative sensitivity values for the large majority of the reviewed criteria. Consensus was easier to reach on some themes (e.g. biodiversity, water and cultural heritage) than others (e.g. population and soils). As anticipated, existing statutory measures shaped the outcomes but, ultimately, knowledge-based values prevailed. The agreed relative sensitivities warrant extensive consultation but the conceptual framework provides a basis for increasing stakeholder consensus and objectivity of baseline assessments. This, in turn, can contribute to improving the evidence-base for characterising the significance of potential impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ab initio phonon thermal transport in monolayer InSe, GaSe, GaS, and alloys

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

Pandey, Tribhuwan; Parker, David S.; Lindsay, Lucas

We compare vibrational properties and phonon thermal conductivities (κ) of monolayer InSe, GaSe and GaS systems using density functional theory and Peierls-Boltzmann transport methods. In going from InSe to GaSe to GaS, system mass decreases giving both increasing acoustic phonon velocities and decreasing scattering of these heat-carrying modes with optic phonons, ultimately giving κInSe< κGaSe< κGaS. This behavior is demonstrated by correlating the scattering phase space limited by fundamental conservation conditions with mode scattering rates and phonon dispersions for each material. We also show that, unlike flat monolayer systems such as graphene, thermal transport is governed by in-plane vibrations inmore » InSe, GaSe and GaS, similar to buckled monolayer materials such as silicene. Alloying of InSe, GaSe and GaS systems provides an effective method for modulating their κ through intrinsic vibrational modifications and phonon scattering from mass disorder giving reductions ~2-3.5 times. This disorder also suppresses phonon mean free paths in the alloy systems compared to those in their crystalline counterparts. This work provides fundamental insights of lattice thermal transport from basic vibrational properties for an interesting set of two-dimensional materials.« less

Sequence-based analysis of the microbial composition of water kefir from multiple sources.

PubMed

Marsh, Alan J; O'Sullivan, Orla; Hill, Colin; Ross, R Paul; Cotter, Paul D

2013-11-01

Water kefir is a water-sucrose-based beverage, fermented by a symbiosis of bacteria and yeast to produce a final product that is lightly carbonated, acidic and that has a low alcohol percentage. The microorganisms present in water kefir are introduced via water kefir grains, which consist of a polysaccharide matrix in which the microorganisms are embedded. We aimed to provide a comprehensive sequencing-based analysis of the bacterial population of water kefir beverages and grains, while providing an initial insight into the corresponding fungal population. To facilitate this objective, four water kefirs were sourced from the UK, Canada and the United States. Culture-independent, high-throughput, sequencing-based analyses revealed that the bacterial fraction of each water kefir and grain was dominated by Zymomonas, an ethanol-producing bacterium, which has not previously been detected at such a scale. The other genera detected were representatives of the lactic acid bacteria and acetic acid bacteria. Our analysis of the fungal component established that it was comprised of the genera Dekkera, Hanseniaspora, Saccharomyces, Zygosaccharomyces, Torulaspora and Lachancea. This information will assist in the ultimate identification of the microorganisms responsible for the potentially health-promoting attributes of these beverages. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Post-translational Regulation of Neuronal Nitric Oxide Synthase: Implications for sympatho-excitatory states

PubMed Central

Sharma, Neeru M; Patel, Kaushik P

2017-01-01

Introduction Nitric oxide (NO) synthesized via neuronal nitric oxide synthase (nNOS) plays a significant role in regulation/modulation of autonomic control of circulation. Various pathological states are associated with diminished nNOS expression and blunted autonomic effects of NO in the central nervous system (CNS) including heart failure, hypertension, diabetes mellitus, chronic renal failure etc. Therefore, elucidation of the molecular mechanism/s involved in dysregulation of nNOS is essential to understand the pathogenesis of increased sympathoexcitation in these diseased states. Areas Covered nNOS is a highly regulated enzyme, being regulated at transcriptional and posttranslational levels via protein-protein interactions and modifications viz. phosphorylation, ubiquitination, and sumoylation. The enzyme activity of nNOS also depends on the optimal concentration of substrate, cofactors and association with regulatory proteins. This review focuses on the posttranslational regulation of nNOS in the context of normal and diseased states within the CNS. Expert Opinion Gaining insight into the mechanism/s involved in the regulation of nNOS would provide novel strategies for manipulating nNOS directed therapeutic modalities in the future, including catalytically active dimer stabilization and protein-protein interactions with intracellular protein effectors. Ultimately, this is expected to provide tools to improve autonomic dysregulation in various diseases such as heart failure, hypertension, and diabetes. PMID:27885874

Molecular nutrition research: the modern way of performing nutritional science.

PubMed

Norheim, Frode; Gjelstad, Ingrid Merethe Fange; Hjorth, Marit; Vinknes, Kathrine J; Langleite, Torgrim M; Holen, Torgeir; Jensen, Jørgen; Dalen, Knut Tomas; Karlsen, Anette S; Kielland, Anders; Rustan, Arild C; Drevon, Christian A

2012-12-03

In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.

Molecular Nutrition Research—The Modern Way Of Performing Nutritional Science

PubMed Central

Norheim, Frode; Gjelstad, Ingrid M. F.; Hjorth, Marit; Vinknes, Kathrine J.; Langleite, Torgrim M.; Holen, Torgeir; Jensen, Jørgen; Dalen, Knut Tomas; Karlsen, Anette S.; Kielland, Anders; Rustan, Arild C.; Drevon, Christian A.

2012-01-01

In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases. PMID:23208524

Mutual Photoluminescence Quenching and Photovoltaic Effect in Large-Area Single-Layer MoS2-Polymer Heterojunctions.

PubMed

Shastry, Tejas A; Balla, Itamar; Bergeron, Hadallia; Amsterdam, Samuel H; Marks, Tobin J; Hersam, Mark C

2016-11-22

Two-dimensional transition metal dichalcogenides (TMDCs) have recently attracted attention due to their superlative optical and electronic properties. In particular, their extraordinary optical absorption and semiconducting band gap have enabled demonstrations of photovoltaic response from heterostructures composed of TMDCs and other organic or inorganic materials. However, these early studies were limited to devices at the micrometer scale and/or failed to exploit the unique optical absorption properties of single-layer TMDCs. Here we present an experimental realization of a large-area type-II photovoltaic heterojunction using single-layer molybdenum disulfide (MoS 2 ) as the primary absorber, by coupling it to the organic π-donor polymer PTB7. This TMDC-polymer heterojunction exhibits photoluminescence intensity that is tunable as a function of the thickness of the polymer layer, ultimately enabling complete quenching of the TMDC photoluminescence. The strong optical absorption in the TMDC-polymer heterojunction produces an internal quantum efficiency exceeding 40% for an overall cell thickness of less than 20 nm, resulting in exceptional current density per absorbing thickness in comparison to other organic and inorganic solar cells. Furthermore, this work provides insight into the recombination processes in type-II TMDC-polymer heterojunctions and thus provides quantitative guidance to ongoing efforts to realize efficient TMDC-based solar cells.

Abraham Lincoln, psychotherapist to the nation: the use of metaphors.

PubMed

Leetz, K L

1997-01-01

Metaphors are widely utilized in psychotherapy to effect change in patients. Psychotherapeutic metaphors, in their various versions, may offer new choices and ways of viewing oneself to the patient which are more palatable than straight discussions or sterile insights. By addressing resistances indirectly, metaphors can be an effective tool for the therapist to use, regardless of theoretical orientation. Abraham Lincoln, a master of metaphor, utilized this tool effectively in dealing with crises and the ultimate fragmentation, disunion of the national identity. The author argues that Lincoln was able to address complex issues (such as slavery, liberty, nationhood, union, and conduct of the war) with metaphors, much as a skilled psychotherapist addresses complex issues within his or her purview. Abraham Lincoln effectively disarmed his critics, established a means of communication with the people, and sought to make his points in an understandable nonconfrontational fashion. These are skills highly valued by psychotherapists. One might say that Abraham Lincoln conducted psychotherapy on a national scale. Without formal training, he was ultimately able to create a new and more stable sense of national self using a metaphorical approach.

A hypothesis linking chrysophyte microfossils to lake carbon dynamics on ecological and evolutionary time scales

NASA Astrophysics Data System (ADS)

Wolfe, Alexander P.; Siver, Peter A.

2013-12-01

Chrysophyte algae are common in the plankton of oligotrophic lakes and produce a rich microfossil record of siliceous cysts and scales. Paleolimnological investigations and phytoplankton records suggest that chrysophyte populations are increasing in a wide range of boreal and arctic lakes, ultimately representing one component of the limnological response to contemporary global changes. However, the exact mechanisms responsible for widespread increases of chrysophyte populations remain elusive. We hypothesize that recent increases in chrysophytes are related to rising pCO2 in lakes, in part because these algae lack carbon concentrating mechanisms and therefore rely on diffusive entry of CO2 to Rubisco during photosynthesis. We assessed the abundance of modern sediment chrysophyte microfossils in relation to summer CO2 relative saturation in 46 New England (USA) lakes, revealing significant positive relationships for both cysts and scales. These observations imply that correlations between chrysophytes and limnological conditions including low pH, oligotrophy, and elevated dissolved organic matter are ultimately underscored by the high pCO2 associated with these conditions. In lakes where chrysophyte populations have expanded over recent decades, we infer that increasingly heterotrophic conditions with respect to CO2 have stimulated production by these organisms. This linkage is supported by the remarkable abundance and diversity of chrysophytes from middle Eocene lake sediments, deposited under atmospheric CO2 concentrations significantly higher than present. The Eocene assemblages suggest that any chrysophyte-CO2 connection borne out of results from modern and sub-recent sediments also operated on evolutionary time scales, and thus the absence of carbon concentrating mechanisms appears to be an ancient feature within the group. Chrysophyte microfossils may potentially provide important insights concerning the temporal dynamics of carbon cycling in aquatic ecosystems.

Non-invasive detection and quantification of brain microvascular deficits by near-infrared spectroscopy in a rat model of Vascular Cognitive Impairment

NASA Astrophysics Data System (ADS)

Hallacoglu, Bertan; Sassaroli, Angelo M.; Rosenberg, Irwin H.; Troen, Aron; Fantini, Sergio

2011-02-01

Structural abnormalities in brain microvasculature are commonly associated with Alzheimer's Disease and other dementias. However, the extent to which structural microvascular abnormalities cause functional impairments in brain circulation and thereby to cognitive impairment is unclear. Non-invasive, near-infrared spectroscopy (NIRS) methods can be used to determine the absolute hemoglobin concentration and saturation in brain tissue, from which additional parameters such as cerebral blood volume (a theoretical correlate of brain microvascular density) can be derived. Validating such NIRS parameters in animal models, and understanding their relationship to cognitive function is an important step in the ultimate application of these methods to humans. To this end we applied a non-invasive multidistance NIRS method to determine the absolute concentration and saturation of cerebral hemoglobin in rat, by separately measuring absorption and reduced scattering coefficients without relying on pre- or post-correction factors. We applied this method to study brain circulation in folate deficient rats, which express brain microvascular pathology1 and which we have shown to develop cognitive impairment.2 We found absolute brain hemoglobin concentration ([HbT]) and oxygen saturation (StO2) to be significantly lower in folate deficient rats (n=6) with respect to control rats (n=5) (for [HbT]: 73+/-10 μM vs. 95+/-14 μM for StO2: 55%+/-7% vs. 66% +/-4%), implicating microvascular pathology and diminished oxygen delivery as a mechanism of cognitive impairment. More generally, our study highlights how noninvasive, absolute NIRS measurements can provide unique insight into the pathophysiology of Vascular Cognitive Impairment. Applying this method to this and other rat models of cognitive impairment will help to validate physiologically meaningful NIRS parameters for the ultimate goal of studying cerebral microvascular disease and cognitive decline in humans.

Mining Protein Evolution for Insights into Mechanisms of Voltage-Dependent Sodium Channel Auxiliary Subunits.

PubMed

Molinarolo, Steven; Granata, Daniele; Carnevale, Vincenzo; Ahern, Christopher A

2018-02-21

Voltage-gated sodium channel (VGSC) beta (β) subunits have been called the "overachieving" auxiliary ion channel subunit. Indeed, these subunits regulate the trafficking of the sodium channel complex at the plasma membrane and simultaneously tune the voltage-dependent properties of the pore-forming alpha-subunit. It is now known that VGSC β-subunits are capable of similar modulation of multiple isoforms of related voltage-gated potassium channels, suggesting that their abilities extend into the broader voltage-gated channels. The gene family for these single transmembrane immunoglobulin beta-fold proteins extends well beyond the traditional VGSC β1-β4 subunit designation, with deep roots into the cell adhesion protein family and myelin-related proteins - where inherited mutations result in a myriad of electrical signaling disorders. Yet, very little is known about how VGSC β-subunits support protein trafficking pathways, the basis for their modulation of voltage-dependent gating, and, ultimately, their role in shaping neuronal excitability. An evolutionary approach can be useful in yielding new clues to such functions as it provides an unbiased assessment of protein residues, folds, and functions. An approach is described here which indicates the greater emergence of the modern β-subunits roughly 400 million years ago in the early neurons of Bilateria and bony fish, and the unexpected presence of distant homologues in bacteriophages. Recent structural breakthroughs containing α and β eukaryotic sodium channels containing subunits suggest a novel role for a highly conserved polar contact that occurs within the transmembrane segments. Overall, a mixture of approaches will ultimately advance our understanding of the mechanism for β-subunit interactions with voltage-sensor containing ion channels and membrane proteins.

CN-Wheat, a functional–structural model of carbon and nitrogen metabolism in wheat culms after anthesis. II. Model evaluation

PubMed Central

Barillot, Romain; Chambon, Camille; Andrieu, Bruno

2016-01-01

Background and Aims Simulating resource allocation in crops requires an integrated view of plant functioning and the formalization of interactions between carbon (C) and nitrogen (N) metabolisms. This study evaluates the functional–structural model CN-Wheat developed for winter wheat after anthesis. Methods In CN-Wheat the acquisition and allocation of resources between photosynthetic organs, roots and grains are emergent properties of sink and source activities and transfers of mobile metabolites. CN-Wheat was calibrated for field plants under three N fertilizations at anthesis. Model parameters were taken from the literature or calibrated on the experimental data. Key Results The model was able to predict the temporal variations and the distribution of resources in the culm. Thus, CN-Wheat accurately predicted the post-anthesis kinetics of dry masses and N content of photosynthetic organs and grains in response to N fertilization. In our simulations, when soil nitrates were non-limiting, N in grains was ultimately determined by availability of C for root activity. Dry matter accumulation in grains was mostly affected by photosynthetic organ lifespan, which was regulated by protein turnover and C-regulated root activity. Conclusions The present study illustrates that the hypotheses implemented in the model were able to predict realistic dynamics and spatial patterns of C and N. CN-Wheat provided insights into the interplay of C and N metabolism and how the depletion of mobile metabolites due to grain filling ultimately results in the cessation of resource capture. This enabled us to identify processes that limit grain mass and protein content and are potential targets for plant breeding. PMID:27497243

Destruction of amyloid fibrils by graphene through penetration and extraction of peptides

NASA Astrophysics Data System (ADS)

Yang, Zaixing; Ge, Cuicui; Liu, Jiajia; Chong, Yu; Gu, Zonglin; Jimenez-Cruz, Camilo A.; Chai, Zhifang; Zhou, Ruhong

2015-11-01

Current therapies for Alzheimer's disease (AD) can provide a moderate symptomatic reduction or delay progression at various stages of the disease, but such treatments ultimately do not arrest the advancement of AD. As such, novel approaches for AD treatment and prevention are urgently needed. We here provide both experimental and computational evidence that pristine graphene and graphene-oxide nanosheets can inhibit Aβ peptide monomer fibrillation and clear mature amyloid fibrils, thus impacting the central molecular superstructures correlated with AD pathogenesis. Our molecular dynamics simulations for the first time reveal that graphene nanosheets can penetrate and extract a large number of peptides from pre-formed amyloid fibrils; these effects seem to be related to exceptionally strong dispersion interactions between peptides and graphene that are further enhanced by strong π-π stacking between the aromatic residues of extracted Aβ peptides and the graphene surface. Atomic force microscopy images confirm these predictions by demonstrating that mature amyloid fibrils can be cut into pieces and cleared by graphene oxides. Thioflavin fluorescence assays further illustrate the detailed dynamic processes by which graphene induces inhibition of monomer aggregation and clearance of mature amyloid fibrils, respectively. Cell viability and ROS assays indicate that graphene oxide can indeed mitigate cytotoxicity of Aβ peptide amyloids. Our findings provide new insights into the underlying molecular mechanisms that define graphene-amyloid interaction and suggest that further research on nanotherapies for Alzheimer's and other protein aggregation-related diseases is warranted.Current therapies for Alzheimer's disease (AD) can provide a moderate symptomatic reduction or delay progression at various stages of the disease, but such treatments ultimately do not arrest the advancement of AD. As such, novel approaches for AD treatment and prevention are urgently needed. We here provide both experimental and computational evidence that pristine graphene and graphene-oxide nanosheets can inhibit Aβ peptide monomer fibrillation and clear mature amyloid fibrils, thus impacting the central molecular superstructures correlated with AD pathogenesis. Our molecular dynamics simulations for the first time reveal that graphene nanosheets can penetrate and extract a large number of peptides from pre-formed amyloid fibrils; these effects seem to be related to exceptionally strong dispersion interactions between peptides and graphene that are further enhanced by strong π-π stacking between the aromatic residues of extracted Aβ peptides and the graphene surface. Atomic force microscopy images confirm these predictions by demonstrating that mature amyloid fibrils can be cut into pieces and cleared by graphene oxides. Thioflavin fluorescence assays further illustrate the detailed dynamic processes by which graphene induces inhibition of monomer aggregation and clearance of mature amyloid fibrils, respectively. Cell viability and ROS assays indicate that graphene oxide can indeed mitigate cytotoxicity of Aβ peptide amyloids. Our findings provide new insights into the underlying molecular mechanisms that define graphene-amyloid interaction and suggest that further research on nanotherapies for Alzheimer's and other protein aggregation-related diseases is warranted. Electronic supplementary information (ESI) available: Other representative trajectories for all the four types of simulated models with double or single graphene nanosheets; instruction to the video; two representative trajectories to show graphene sheet(s) spontaneously penetrating into the fibril; role of interfacial water in assisting graphene's insertion into fibril; AFM images of s-GO and GO; potential of mean force; sketches of restraints in all four types of simulated systems. Correspondence and requests for materials should be addressed to R.H.Z. See DOI: 10.1039/c5nr01172h

An introduction to UGRS: the ultimate grading and remanufacturing system

Treesearch

John Moody; Charles J. Gatchell; Elizabeth S. Walker; Powsiri Klinkhachorn

1998-01-01

The Ultimate Grading and Remanufactming System (UGRS) is an advanced computer program for grading and remanufacturing lumber. It is an interactive program that will both grade lumber according to NHLA rules and remanufacture it for maximum value. UGRS is written to run under Microsoft Windows 3.0 or later updates and provides a sophisticated graphical user interface....

Ultimate Limit State Assessment of Timber Bolt Connection Subjected to Double Unequal Shears

NASA Astrophysics Data System (ADS)

Musilek, Josef; Plachy, Jan

2017-10-01

Nowadays the problems occur when a structure engineer need to assess the ultimate limit state of timber bolt connection which is subjected to double unequal shears. This assessment of ultimate limit state shows the reliability of these connections. In assessing the reliability of this connection in ultimate limit state is a problem, because the formulas and equations that are currently available in design standards and available literature, describing only connections loaded symmetrically - this mean that they describe the timber bolt connection subjected to double equal shears. This fact causes problems because structural engineers have no available support, according to which they could assess reliability of the connection in terms of the ultimate limit state. They must therefore often report following an asymmetrically loaded connections carry about using formulas, which are primarily designed for checking connections loaded symmetrically. This leads logically to the fact that it is not respected by the actual behaviour of the connection in the ultimate limit state. Formulas derived in this paper provide the possibility to assess the ultimate limit state for such connection. The formulas derived in this article allow to carry out a reliability assessment of the ultimate limit state of timber bolt connection subjected to double shear. The using of the formulas derived in this paper leads to better description of the behaviour of this type of connection and also to the more economic design. An example of using these derived formulas is shown. There is shown in this example, how to assess the reliability of timber bolt connection subjected to double unequal shears in terms of ultimate limit states.

Ultimate pier and contraction scour prediction in cohesive soils at selected bridges in Illinois

USGS Publications Warehouse

Straub, Timothy D.; Over, Thomas M.; Domanski, Marian M.

2013-01-01

The Scour Rate In COhesive Soils-Erosion Function Apparatus (SRICOS-EFA) method includes an ultimate scour prediction that is the equilibrium maximum pier and contraction scour of cohesive soils over time. The purpose of this report is to present the results of testing the ultimate pier and contraction scour methods for cohesive soils on 30 bridge sites in Illinois. Comparison of the ultimate cohesive and noncohesive methods, along with the Illinois Department of Transportation (IDOT) cohesive soil reduction-factor method and measured scour are presented. Also, results of the comparison of historic IDOT laboratory and field values of unconfined compressive strength of soils (Qu) are presented. The unconfined compressive strength is used in both ultimate cohesive and reduction-factor methods, and knowing how the values from field methods compare to the laboratory methods is critical to the informed application of the methods. On average, the non-cohesive method results predict the highest amount of scour, followed by the reduction-factor method results; and the ultimate cohesive method results predict the lowest amount of scour. The 100-year scour predicted for the ultimate cohesive, noncohesive, and reduction-factor methods for each bridge site and soil are always larger than observed scour in this study, except 12% of predicted values that are all within 0.4 ft of the observed scour. The ultimate cohesive scour prediction is smaller than the non-cohesive scour prediction method for 78% of bridge sites and soils. Seventy-six percent of the ultimate cohesive predictions show a 45% or greater reduction from the non-cohesive predictions that are over 10 ft. Comparing the ultimate cohesive and reduction-factor 100-year scour predictions methods for each bridge site and soil, the scour predicted by the ultimate cohesive scour prediction method is less than the reduction-factor 100-year scour prediction method for 51% of bridge sites and soils. Critical shear stress remains a needed parameter in the ultimate scour prediction for cohesive soils. The unconfined soil compressive strength measured by IDOT in the laboratory was found to provide a good prediction of critical shear stress, as measured by using the erosion function apparatus in a previous study. Because laboratory Qu analyses are time-consuming and expensive, the ability of field-measured Rimac data to estimate unconfined soil strength in the critical shear–soil strength relation was tested. A regression analysis was completed using a historic IDOT dataset containing 366 data pairs of laboratory Qu and field Rimac measurements from common sites with cohesive soils. The resulting equations provide a point prediction of Qu, given any Rimac value with the 90% confidence interval. The prediction equations are not significantly different from the identity Qu = Rimac. The alternative predictions of ultimate cohesive scour presented in this study assume Qu will be estimated using Rimac measurements that include computed uncertainty. In particular, the ultimate cohesive predicted scour is greater than observed scour for the entire 90% confidence interval range for predicting Qu at the bridges and soils used in this study, with the exception of the six predicted values that are all within 0.6 ft of the observed scour.

The GC-rich mitochondrial and plastid genomes of the green alga Coccomyxa give insight into the evolution of organelle DNA nucleotide landscape

DOE PAGES

Smith, David Roy; Burki, Fabien; Yamada, Takashi; ...

2011-08-26

Here, most of the available mitochondrial and plastid genome sequences are biased towards adenine and thymine (AT) over guanine and cytosine (GC). Examples of GC-rich organelle DNAs are limited to a small but eclectic list of species, including certain green algae. Here, to gain insight in the evolution of organelle nucleotide landscape, we present the GC-rich mitochondrial and plastid DNAs from the trebouxiophyte green alga Coccomyxa sp. C-169. We compare these sequences with other GC-rich organelle DNAs and argue that the forces biasing them towards G and C are nonadaptive and linked to the metabolic and/or life history features ofmore » this species. The Coccomyxa organelle genomes are also used for phylogenetic analyses, which highlight the complexities in trying to resolve the interrelationships among the core chlorophyte green algae, but ultimately favour a sister relationship between the Ulvophyceae and Chlorophyceae, with the Trebouxiophyceae branching at the base of the chlorophyte crown.« less

Secretins revealed: structural insights into the giant gated outer membrane portals of bacteria.

PubMed

Majewski, Dorothy D; Worrall, Liam J; Strynadka, Natalie Cj

2018-03-23

The acquisition and evolution of customized and often highly complex secretion systems allows Gram-negative bacteria to efficiently passage large macromolecules across both inner and outer membranes and, in some cases, that of the infected host. Essential to the virulence and ultimate survival of the many pathogenic species that encode them, secretion systems export a wide variety of effector proteins and DNA as well as the downstream extracellular filaments of the secretion apparatus themselves. Although these customized secretion systems differ in their cytosolic and inner membrane components, several commonly rely on the secretin family of giant pores to allow these large substrates to traverse the outer membrane. Recently, several near-atomic resolution cryo-EM secretin structures have unveiled the first insights into the unique structural motifs required for outer membrane localization, assembly, hallmark ultrastable nature, spontaneous membrane insertion, and mechanism of action-including the requisite central gating needed to prevent deleterious passage of periplasmic contents to the extracellular space. Copyright © 2018. Published by Elsevier Ltd.

NEW INSIGHTS INTO THE PRESENCE OF BILIRUBIN IN A PLANT SPECIES STRELITZIA NICOLAI (STRELITZIACEAE).

PubMed

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Baijnath, Himansu

2017-01-01

The fortuitous discovery of an animal pigment bilirubin found in the plant Strelitzia nicolai has opened an enormous number of questions regarding bilirubin's formation and its ultimate function in the human body. A methodical review of bilirubin in humans and animals was carried out, information was gathered using published scientific journals, books and conference proceedings. Articles based on case studies of elevated levels of bilirubin were analysed thoroughly. Even though for numerous years bilirubin was assumed to be merely a desecrate product of the heme catabolic pathway by greatest, and a likely lethal compound at worst; statistics from the last few decades clearly shows that placidly high serum bilirubin levels are robustly related to have abundant beneficial effects on the human body. This study reveals new insights into the presence of the only animal pigment found in Strelitzia nicolai arils, the potential advantages of bilirubin found in a plant and its therapeutic value indications. This review hopes to resuscitate researchers' credence regarding bilirubin as a toxic compound.

Probing the Surface of Platinum during the Hydrogen Evolution Reaction in Alkaline Electrolyte

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

Stoerzinger, Kelsey A.; Favaro, Marco; Ross, Philip N.

Understanding the surface chemistry of electrocatalysts in operando can bring insight into the reaction mechanism, and ultimately the design of more efficient materials for sustainable energy storage and conversion. Recent progress in synchrotron based X-ray spectroscopies for in operando characterization allows us to probe the solid/liquid interface directly while applying an external potential, applied here to the model system of Pt in alkaline electrolyte for the hydrogen evolution reaction (HER). We employ ambient pressure X-ray photoelectron spectroscopy (AP-XPS) to identify the oxidation and reduction of Pt-oxides and hydroxides on the surface as a function of applied potential, and further assessmore » the potential for hydrogen adsorption and absorption (hydride formation) during and after the HER. This new window into the surface chemistry of Pt in alkaline brings insight into the nature of the rate limiting step, the extent of H ad/absorption and it’s persistence at more anodic potentials.« less

The GC-Rich Mitochondrial and Plastid Genomes of the Green Alga Coccomyxa Give Insight into the Evolution of Organelle DNA Nucleotide Landscape

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

Smith, David Roy; Burki, Fabien; Yamada, Takashi

2011-05-13

Most of the available mitochondrial and plastid genome sequences are biased towards adenine and thymine (AT) over guanine and cytosine (GC). Examples of GC-rich organelle DNAs are limited to a small but eclectic list of species, including certain green algae. Here, to gain insight in the evolution of organelle nucleotide landscape, we present the GC-rich mitochondrial and plastid DNAs from the trebouxiophyte green alga Coccomyxa sp. C-169. We compare these sequences with other GC-rich organelle DNAs and argue that the forces biasing them towards G and C are nonadaptive and linked to the metabolic and/or life history features of thismore » species. The Coccomyxa organelle genomes are also used for phylogenetic analyses, which highlight the complexities in trying to resolve the interrelationships among the core chlorophyte green algae, but ultimately favour a sister relationship between the Ulvophyceae and Chlorophyceae, with the Trebouxiophyceae branching at the base of the chlorophyte crown.« less

The life in sight application study (LISA): design of a randomized controlled trial to assess the role of an assisted structured reflection on life events and ultimate life goals to improve quality of life of cancer patients

PubMed Central

2013-01-01

Background It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients. Methods/Design Based on the findings of our previous research, we have developed a brief interview model that allows spiritual counsellors to explore, explicate and discuss life events and ultimate life goals with cancer patients. To support the interview, we created an e-application for a PC or tablet. To examine whether this assisted reflection improves quality of life we will conduct a randomized trial. Patients with advanced cancer not amenable to curative treatment options will be randomized to either the intervention or the control group. The intervention group will have two consultations with a spiritual counsellor using the interview scheme supported by the e-application. The control group will receive care as usual. At baseline and one and three months after randomization all patients fill out questionnaires regarding quality of life, spiritual wellbeing, empowerment, satisfaction with life, anxiety and depression and health care consumption. Discussion Having insight into one’s ultimate life goals may help integrating a life event such as cancer into one’s life story. This is the first randomized controlled trial to evaluate the role of an assisted structured reflection on ultimate life goals to improve patients’ quality of life and spiritual well being. The intervention is brief and based on concepts and skills that spiritual counsellors are familiar with, it can be easily implemented in routine patient care and incorporated in guidelines on spiritual care. Trial registration The study is registered at ClinicalTrials.gov: NCT01830075 PMID:23889978

Magnetic quantum tunneling: insights from simple molecule-based magnets.

PubMed

Hill, Stephen; Datta, Saiti; Liu, Junjie; Inglis, Ross; Milios, Constantinos J; Feng, Patrick L; Henderson, John J; del Barco, Enrique; Brechin, Euan K; Hendrickson, David N

2010-05-28

This perspectives article takes a broad view of the current understanding of magnetic bistability and magnetic quantum tunneling in single-molecule magnets (SMMs), focusing on three families of relatively simple, low-nuclearity transition metal clusters: spin S = 4 Ni(II)(4), Mn(III)(3) (S = 2 and 6) and Mn(III)(6) (S = 4 and 12). The Mn(III) complexes are related by the fact that they contain triangular Mn(III)(3) units in which the exchange may be switched from antiferromagnetic to ferromagnetic without significantly altering the coordination around the Mn(III) centers, thereby leaving the single-ion physics more-or-less unaltered. This allows for a detailed and systematic study of the way in which the individual-ion anisotropies project onto the molecular spin ground state in otherwise identical low- and high-spin molecules, thus providing unique insights into the key factors that control the quantum dynamics of SMMs, namely: (i) the height of the kinetic barrier to magnetization relaxation; and (ii) the transverse interactions that cause tunneling through this barrier. Numerical calculations are supported by an unprecedented experimental data set (17 different compounds), including very detailed spectroscopic information obtained from high-frequency electron paramagnetic resonance and low-temperature hysteresis measurements. Comparisons are made between the giant spin and multi-spin phenomenologies. The giant spin approach assumes the ground state spin, S, to be exact, enabling implementation of simple anisotropy projection techniques. This methodology provides a basic understanding of the concept of anisotropy dilution whereby the cluster anisotropy decreases as the total spin increases, resulting in a barrier that depends weakly on S. This partly explains why the record barrier for a SMM (86 K for Mn(6)) has barely increased in the 15 years since the first studies of Mn(12)-acetate, and why the tiny Mn(3) molecule can have a barrier approaching 60% of this record. Ultimately, the giant spin approach fails to capture all of the key physics, although it works remarkably well for the purely ferromagnetic cases. Nevertheless, diagonalization of the multi-spin Hamiltonian matrix is necessary in order to fully capture the interplay between exchange and local anisotropy, and the resultant spin-state mixing which ultimately gives rise to the tunneling matrix elements in the high symmetry SMMs (ferromagnetic Mn(3) and Ni(4)). The simplicity (low-nuclearity, high-symmetry, weak disorder, etc.) of the molecules highlighted in this study proves to be of crucial importance. Not only that, these simple molecules may be considered among the best SMMs: Mn(6) possesses the record anisotropy barrier, and Mn(3) is the first SMM to exhibit quantum tunneling selection rules that reflect the intrinsic symmetry of the molecule.

'I love nursing, but..'- qualitative findings from Australian aged-care nurses about their intrinsic, extrinsic and social work values.

PubMed

Tuckett, Anthony; Parker, Deborah; Eley, Robert M; Hegney, Desley

2009-12-01

Aim.  The aim of this qualitative analysis - a component of a larger survey study, was to provide insights and understandings about intrinsic and extrinsic work values for nurses in aged-care. Background.  Intrinsic and extrinsic work values impact on nurses' job satisfaction and ultimately nursing retention. This study contributes further to knowledge development in this area by building on a previous work values study in aged-care nursing. Methods.  This paper presents the qualitative research findings from the final open-ended question from a survey of nurses employed in the aged-care sector in the State of Queensland, Australia in 2007. Data from a cohort of 105 aged care sector nurses was analysed relying on deductive content analysis. Findings.  Two intrinsic work values emerged - low morale and images of nursing and two extrinsic work values emerged - remuneration and working conditions. The work value 'working conditions' comprised four aspects of aged-care work, specifically staff turnover, workplace violence, care team membership specifically the Assistants-in-Nursing and paperwork. A single social workplace value 'support by management' is discussed as identified as important to these nurses. Conclusion.  Qualitative insights into aged-care nurses' intrinsic and extrinsic work values suggest that work satisfaction is low. Workforce policy makers and employers of nurses in aged-care need to comprehend the relationship between job satisfaction, retention and work values. Relevance to clinical practice.  These findings have implications for recruitment, retention and workforce planning within the aged-care environment. © 2009 Blackwell Publishing Ltd.

X-rays in the Cryo-EM Era: Structural Biology’s Dynamic Future

PubMed Central

Shoemaker, Susannah C.; Ando, Nozomi

2018-01-01

Over the past several years, single-particle cryo-electron microscopy (cryo-EM) has emerged as a leading method for elucidating macromolecular structures at near-atomic resolution, rivaling even the established technique of X-ray crystallography. Cryo-EM is now able to probe proteins as small as hemoglobin (64 kDa), while avoiding the crystallization bottleneck entirely. The remarkable success of cryo-EM has called into question the continuing relevance of X-ray methods, particularly crystallography. To say that the future of structural biology is either cryo-EM or crystallography, however, would be misguided. Crystallography remains better suited to yield precise atomic coordinates of macromolecules under a few hundred kDa in size, while the ability to probe larger, potentially more disordered assemblies is a distinct advantage of cryo-EM. Likewise, crystallography is better equipped to provide high-resolution dynamic information as a function of time, temperature, pressure, and other perturbations, whereas cryo-EM offers increasing insight into conformational and energy landscapes, particularly as algorithms to deconvolute conformational heterogeneity become more advanced. Ultimately, the future of both techniques depends on how their individual strengths are utilized to tackle questions on the frontiers of structural biology. Structure determination is just one piece of a much larger puzzle: a central challenge of modern structural biology is to relate structural information to biological function. In this perspective, we share insight from several leaders in the field and examine the unique and complementary ways in which X-ray methods and cryo-EM can shape the future of structural biology. PMID:29227642

Clinical medical sciences for undergraduate dental students in the United Kingdom and Ireland - a curriculum.

PubMed

Mighell, A J; Atkin, P A; Webster, K; Thomas, S J; McCreary, C E; Healy, C M; Gibson, J; Crighton, A J; Dawson, L J; Smalley, J O; Allan, R B; Oliver, R J; Pattrick, M G; Pemberton, M N; Theaker, E D; Poate, T W; Buchanan, J A G; Greenwood, M; Bee, D; Yates, J M; Crean, St J; Napier, S S

2011-08-01

The technical aspects of dentistry need to be practised with insight into the spectrum of human diseases and illnesses and how these impact upon individuals and society. Application of this insight is critical to decision-making related to the planning and delivery of safe and appropriate patient-centred healthcare tailored to the needs of the individual. Provision for the necessary training is included in undergraduate programmes, but in the United Kingdom and Ireland there is considerable variation between centres without common outcomes. In 2009 representatives from 17 undergraduate dental schools in the United Kingdom and Ireland agreed to move towards a common, shared approach to meet their own immediate needs and that might also be of value to others in keeping with the Bologna Process. To provide a clear identity the term 'Clinical Medical Sciences in Dentistry' was agreed in preference to other names such as 'Human Disease' or 'Medicine and Surgery'. The group was challenged to define consensus outcomes. Contemporary dental education documents informed, but did not drive the process. The consensus curriculum for undergraduate Clinical Medical Sciences in Dentistry teaching agreed by the participating centres is reported. Many of the issues are generic and it includes elements that are likely to be applicable to others. This document will act as a focus for a more unified approach to the outcomes required by graduates of the participating centres and act as a catalyst for future developments that ultimately aim to enhance the quality of patient care. © 2011 John Wiley & Sons A/S.

Queerspawn Speak out: A Review of "Let's Get This Straight: The Ultimate Handbook for Youth with LGBTQ Parents"

ERIC Educational Resources Information Center

Ryan, Caitlin L.

2012-01-01

"Let's Get This Straight: The Ultimate Handbook for Youth With LGBTQ Parents" provides an engaging and accessible set of tools for youth from LGBTQ-headed families. The stories and resources shared encourage these youth to take pride in their families, value their diverse experiences, and work against homophobia, transphobia, and other forms of…

Human Choice and CCS Deployment: What have we learned from the social sciences about CCS?

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

Dooley, James J.

2013-08-20

It is my pleasure to present this Virtual Special Issue of key social science papers that have been published in the International Journal of Greenhouse Gas Control (IJGCC). These papers show that the social science research community has significantly advanced the state-of-the-art from vague discussions about the “acceptance of CCS” to a body of deeply insightful and actionable knowledge about how CCS is likely to be framed and how framing will impact the ultimate deployment of CCS as a means of mitigating anthropogenic climate change. The papers assembled here shed light on core issues such as how do humans makemore » decisions about a new technology like CCS that they have no direct personal experience with and what is it is about “new” technologies that we find unsettling. These papers also speak to what are the best, and for that matter the worst, ways of presenting inherently highly technical information to lay audiences, including insights about the substance of the information, the form in which the information is delivered, and who delivers it. An extended editorial about this virtual special issue is freely available on ScienceDirect. I hope you find the papers contained in this Virtual Issue to be as informative and insightful as I do.« less

Cell motility in cancer invasion and metastasis: insights from simple model organisms.

PubMed

Stuelten, Christina H; Parent, Carole A; Montell, Denise J

2018-05-01

Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening. We highlight insights derived from each of these organisms, including the detailed signalling network that governs chemotaxis towards chemokines; a novel mechanism of basement membrane invasion; the positive role of E-cadherin in collective direction-sensing; the identification and optimization of kinase inhibitors for metastatic thyroid cancer on the basis of work in flies; and the value of zebrafish for live imaging, especially of vascular remodelling and interactions between tumour cells and host tissues. While the motility of tumour cells and certain host cells promotes metastatic spread, the motility of tumour-reactive T cells likely increases their antitumour effects. Therefore, it is important to elucidate the mechanisms underlying all types of cell motility, with the ultimate goal of identifying combination therapies that will increase the motility of beneficial cells and block the spread of harmful cells.

The ultimate picture-the combination of live cell superresolution microscopy and single molecule tracking yields highest spatio-temporal resolution.

PubMed

Dersch, Simon; Graumann, Peter L

2018-06-01

We are witnessing a breathtaking development in light (fluorescence) microscopy, where structures can be resolved down to the size of a ribosome within cells. This has already yielded surprising insight into the subcellular structure of cells, including the smallest cells, bacteria. Moreover, it has become possible to visualize and track single fluorescent protein fusions in real time, and quantify molecule numbers within individual cells. Combined, super resolution and single molecule tracking are pushing the limits of our understanding of the spatio-temporal organization even of the smallest cells to an unprecedented depth. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-awareness: a review and analysis of a basic nursing concept.

PubMed

Eckroth-Bucher, Margie

2010-01-01

Self-awareness has long been addressed as fundamental for the professional nurse with the accepted view that self-awareness will lead to greater competence. Therefore, it is important to understand the historical evolution of the concept, attributes, antecedents, and consequences. Rodgers' evolutionary method was used for critical analysis of nursing, social sciences, and education literature. Analysis indicates that self-awareness is a dynamic, transformative process of self. Ultimately, self-awareness is the use of self-insights and presence knowingly to guide behavior that is genuine and authentic to create a healing interpersonal environment. Future research areas within practice and education are identified.

The Syllogism of Neuro-Economics.

PubMed

Padoa-Schioppa, Camillo

2008-01-01

If Neuroscience is to contribute to Economics, it will do so by the way of Psychology. Neural data can and do lead to better psychological theories, and psychological insights can and do lead to better economic models. Hence, Neuroscience can in principle contribute to Economics. Whether it actually will do so is an empirical question and the jury is still out. Economics currently faces theoretical and empirical challenges analogous to those faced by Physics at the turn of the 20(th) century and ultimately addressed by quantum theory. If "quantum Economics" will emerge in the coming decades, it may well be founded on such concepts as cognitive processes and brain activity.

A lesbian-feminist journey through queer nation.

PubMed

Zimmerman, Bonnie

2007-01-01

This article is an auto-ethnographical review of the political experiences and literary career of one of the early lesbian feminist critics and theorists. It poses the question: what does it mean to be shaped by one theoretical and political discourse (Lesbian Feminism) and then thrust by historical change into another (Queer Theory)? With the author's life and work as a frame and exemplar, it illustrates the development of lesbian feminist thought. Ultimately, it argues that the insights and values of Lesbian Feminism should not be suppressed by those of Queer Theory, and calls upon lesbian feminists to re-insert themselves into current scholarly and theoretical debates.

Leadership styles in nursing.

PubMed

Cope, Vicki; Murray, Melanie

2017-06-21

Nurses are often asked to think about leadership, particularly in times of rapid change in healthcare, and where questions have been raised about whether leaders and managers have adequate insight into the requirements of care. This article discusses several leadership styles relevant to contemporary healthcare and nursing practice. Nurses who are aware of leadership styles may find this knowledge useful in maintaining a cohesive working environment. Leadership knowledge and skills can be improved through training, where, rather than having to undertake formal leadership roles without adequate preparation, nurses are able to learn, nurture, model and develop effective leadership behaviours, ultimately improving nursing staff retention and enhancing the delivery of safe and effective care.

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

Zhao, T; Ruan, D

Purpose: The growing size and heterogeneity in training atlas necessitates sophisticated schemes to identify only the most relevant atlases for the specific multi-atlas-based image segmentation problem. This study aims to develop a model to infer the inaccessible oracle geometric relevance metric from surrogate image similarity metrics, and based on such model, provide guidance to atlas selection in multi-atlas-based image segmentation. Methods: We relate the oracle geometric relevance metric in label space to the surrogate metric in image space, by a monotonically non-decreasing function with additive random perturbations. Subsequently, a surrogate’s ability to prognosticate the oracle order for atlas subset selectionmore » is quantified probabilistically. Finally, important insights and guidance are provided for the design of fusion set size, balancing the competing demands to include the most relevant atlases and to exclude the most irrelevant ones. A systematic solution is derived based on an optimization framework. Model verification and performance assessment is performed based on clinical prostate MR images. Results: The proposed surrogate model was exemplified by a linear map with normally distributed perturbation, and verified with several commonly-used surrogates, including MSD, NCC and (N)MI. The derived behaviors of different surrogates in atlas selection and their corresponding performance in ultimate label estimate were validated. The performance of NCC and (N)MI was similarly superior to MSD, with a 10% higher atlas selection probability and a segmentation performance increase in DSC by 0.10 with the first and third quartiles of (0.83, 0.89), compared to (0.81, 0.89). The derived optimal fusion set size, valued at 7/8/8/7 for MSD/NCC/MI/NMI, agreed well with the appropriate range [4, 9] from empirical observation. Conclusion: This work has developed an efficacious probabilistic model to characterize the image-based surrogate metric on atlas selection. Analytical insights lead to valid guiding principles on fusion set size design.« less

Analysis of rainfall-induced slope instability using a field of local factor of safety

USGS Publications Warehouse

Lu, Ning; Şener-Kaya, Başak; Wayllace, Alexandra; Godt, Jonathan W.

2012-01-01

Slope-stability analyses are mostly conducted by identifying or assuming a potential failure surface and assessing the factor of safety (FS) of that surface. This approach of assigning a single FS to a potentially unstable slope provides little insight on where the failure initiates or the ultimate geometry and location of a landslide rupture surface. We describe a method to quantify a scalar field of FS based on the concept of the Coulomb stress and the shift in the state of stress toward failure that results from rainfall infiltration. The FS at each point within a hillslope is called the local factor of safety (LFS) and is defined as the ratio of the Coulomb stress at the current state of stress to the Coulomb stress of the potential failure state under the Mohr-Coulomb criterion. Comparative assessment with limit-equilibrium and hybrid finite element limit-equilibrium methods show that the proposed LFS is consistent with these approaches and yields additional insight into the geometry and location of the potential failure surface and how instability may initiate and evolve with changes in pore water conditions. Quantitative assessments applying the new LFS field method to slopes under infiltration conditions demonstrate that the LFS has the potential to overcome several major limitations in the classical FS methodologies such as the shape of the failure surface and the inherent underestimation of slope instability. Comparison with infinite-slope methods, including a recent extension to variably saturated conditions, shows further enhancement in assessing shallow landslide occurrence using the LFS methodology. Although we use only a linear elastic solution for the state of stress with no post-failure analysis that require more sophisticated elastoplastic or other theories, the LFS provides a new means to quantify the potential instability zones in hillslopes under variably saturated conditions using stress-field based methods.

Ultimate Attainment in Late Second Language Acquisition: Phonetic and Grammatical Challenges in Advanced Dutch-English Bilingualism

ERIC Educational Resources Information Center

Schmid, Monika S.; Gilbers, Steven; Nota, Amber

2014-01-01

The present article provides an exploration of ultimate attainment in second language (L2) and its limitations. It is argued that the question of maturational constraints can best be investigated when the reference population is bilingual and exposed on a regular basis to varieties of their first language (L1) that show cross-linguistic influence.…

ALS-linked mutant SOD1 proteins promote Aβ aggregates in ALS through direct interaction with Aβ.

PubMed

Jang, Ja-Young; Cho, Hyungmin; Park, Hye-Yoon; Rhim, Hyangshuk; Kang, Seongman

2017-11-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons. Aggregation of ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) is a hallmark of a subset of familial ALS (fALS). Recently, intracellular amyloid-β (Aβ) is detected in motor neurons of both sporadic and familial ALS. We have previously shown that intracellular Aβ specifically interacts with G93A, an ALS-linked SOD1 mutant. However, little is known about the pathological and biological effect of this interaction in neurons. In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

How does vineyard management intensity affect ecosystem services and disservices - insights from a meta-analysis

NASA Astrophysics Data System (ADS)

Winter, Silvia; Zaller, Johann G.; Kratschmer, Sophie; Pachinger, Bärbel; Strauss, Peter; Bauer, Thomas; Paredes, Daniel; Gómez, José A.; Guzmán, Gema; Landa, Blanca; Nicolai, Annegret; Burel, Francoise; Cluzeau, Daniel; Popescu, Daniela; Bunea, Claudiu-Ioan; Potthoff, Martin; Guernion, Muriel; Batáry, Péter

2016-04-01

Viticultural agro-ecosystems provide a range of different ecosystem services which are affected by management decisions of winegrowers. At the global scale, vineyards are often high intensity agricultural systems with bare soil or inter-row vegetation consisting of only a few plant species. These systems primarily aim at optimizing wine production by reducing competition for water and nutrients between grapevines and weeds and by preventing the outbreak of pests and diseases. At the same time, this kind of management is often associated with ecosystem disservices such as high rates of soil erosion, degradation of soil structure and fertility, contamination of groundwater and decline of biodiversity. Recently, several initiatives across the world tried to overcome detrimental effects of that management style by creating biodiversity friendly vineyards. The consequences of establishing divers cover crop mixes or tolerating spontaneous vegetation in vineyards for ecosystem services (including yield) overstretching local case studies has not been investigated yet. This meta-analysis will provide an overview of all published studies comparing the effects of different vineyard management practices on a range of different ecosystem services like biodiversity, pest control, pollination, soil conservation and carbon sequestration. The aggregated effect size will point out which management measures can provide the best overall net sum of ecosystem services. This meta-analysis is part of the transdisciplinary BiodivERsA project VineDivers and will ultimately lead into management and policy recommendations for various stakeholder groups engaged in viticulture.

Geoheritage Values at Greenmantle Farm

NASA Astrophysics Data System (ADS)

Etches, J. D.

2009-05-01

The Greenmantle Farm occurrence near Wilberforce, Ontario is a marble feature within the Grenville Province of the Precambrian Shield that hosts a diverse suite of amphibole minerals. The marble is of undetermined petrogenesis, and is possibly either a primary carbonatite intrusion or a derived melt of metasedimentary origin. The site is the type locality for the rare mineral fluorrichterite. Other minerals of note are orthoclase and apatite. Crystal size is relatively large, and all minerals, with the exception of calcite, exhibit generally good to excellent euhedral form. Of note is that the mineral occurrences at this site have not been subjected to any human disturbance including mechanical or hand tool disruption. The site also provides excellent examples of a number of geological features and ecosystem dynamics. In particular, faulting, moisture regime landscape interrelationships, order of crystallization in zoned dykes, and calciphile plant associations are demonstrated. This site represents an exceptional viewing opportunity of an unspoiled mineral occurrence while providing illustrative examples of the interrelationship of abiotic and biotic features. In terms of research, the site will prove to be a valuable subject in regard to amphibole composition, amphibole differentiation in calcareous melts, and will ultimately provide insight into the formation of the occurrence. Determination of what circumstances these marble bodies formed under would add a significant piece of information to the complex history of the Grenville province. This research will be assisted by the completely uncompromised nature of the site. The potential educational value of the site for researchers and grade school students alike is exceptional.

Exploring the state of health and safety management system performance measurement in mining organizations.

PubMed

Haas, Emily Joy; Yorio, Patrick

2016-03-01

Complex arguments continue to be articulated regarding the theoretical foundation of health and safety management system (HSMS) performance measurement. The culmination of these efforts has begun to enhance a collective understanding. Despite this enhanced theoretical understanding, however, there are still continuing debates and little consensus. The goal of the current research effort was to empirically explore common methods to HSMS performance measurement in mining organizations. The purpose was to determine if value and insight could be added into the ongoing approaches of the best ways to engage in health and safety performance measurement. Nine site-level health and safety management professionals were provided with 133 practices corresponding to 20 HSMS elements, each fitting into the plan, do, check, act phases common to most HSMS. Participants were asked to supply detailed information as to how they (1) assess the performance of each practice in their organization, or (2) would assess each practice if it were an identified strategic imperative. Qualitative content analysis indicated that the approximately 1200 responses provided could be described and categorized into interventions , organizational performance , and worker performance . A discussion of how these categories relate to existing indicator frameworks is provided. The analysis also revealed divergence in two important measurement issues; (1) quantitative vs qualitative measurement and reporting; and (2) the primary use of objective or subjective metrics. In lieu of these findings we ultimately recommend a balanced measurement and reporting approach within the three metric categories and conclude with suggestions for future research.

Exploring the state of health and safety management system performance measurement in mining organizations

PubMed Central

Haas, Emily Joy; Yorio, Patrick

2016-01-01

Complex arguments continue to be articulated regarding the theoretical foundation of health and safety management system (HSMS) performance measurement. The culmination of these efforts has begun to enhance a collective understanding. Despite this enhanced theoretical understanding, however, there are still continuing debates and little consensus. The goal of the current research effort was to empirically explore common methods to HSMS performance measurement in mining organizations. The purpose was to determine if value and insight could be added into the ongoing approaches of the best ways to engage in health and safety performance measurement. Nine site-level health and safety management professionals were provided with 133 practices corresponding to 20 HSMS elements, each fitting into the plan, do, check, act phases common to most HSMS. Participants were asked to supply detailed information as to how they (1) assess the performance of each practice in their organization, or (2) would assess each practice if it were an identified strategic imperative. Qualitative content analysis indicated that the approximately 1200 responses provided could be described and categorized into interventions, organizational performance, and worker performance. A discussion of how these categories relate to existing indicator frameworks is provided. The analysis also revealed divergence in two important measurement issues; (1) quantitative vs qualitative measurement and reporting; and (2) the primary use of objective or subjective metrics. In lieu of these findings we ultimately recommend a balanced measurement and reporting approach within the three metric categories and conclude with suggestions for future research. PMID:26823642

Block copolymer based composition and morphology control in nanostructured hybrid materials for energy conversion and storage: solar cells, batteries, and fuel cells.

PubMed

Orilall, M Christopher; Wiesner, Ulrich

2011-02-01

The development of energy conversion and storage devices is at the forefront of research geared towards a sustainable future. However, there are numerous issues that prevent the widespread use of these technologies including cost, performance and durability. These limitations can be directly related to the materials used. In particular, the design and fabrication of nanostructured hybrid materials is expected to provide breakthroughs for the advancement of these technologies. This tutorial review will highlight block copolymers as an emerging and powerful yet affordable tool to structure-direct such nanomaterials with precise control over structural dimensions, composition and spatial arrangement of materials in composites. After providing an introduction to materials design and current limitations, the review will highlight some of the most recent examples of block copolymer structure-directed nanomaterials for photovoltaics, batteries and fuel cells. In each case insights are provided into the various underlying fundamental chemical, thermodynamic and kinetic formation principles enabling general and relatively inexpensive wet-polymer chemistry methodologies for the efficient creation of multiscale functional materials. Examples include nanostructured ceramics, ceramic-carbon composites, ceramic-carbon-metal composites and metals with morphologies ranging from hexagonally arranged cylinders to three-dimensional bi-continuous cubic networks. The review ends with an outlook towards the synthesis of multicomponent and hierarchical multifunctional hybrid materials with different nano-architectures from self-assembly of higher order blocked macromolecules which may ultimately pave the way for the further development of energy conversion and storage devices.

Improvements in SMR Modular Construction through Supply Chain Optimization and Lessons Learned

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

White III, Chelsea C.; Petrovic, Bojan

Affordable energy is a critical societal need. Capital construction cost is a significant portion of nuclear energy cost. By controlling and reducing cost, companies can build more competitive nuclear power plants and hence provide access to more affordable energy. Modular construction provides an opportunity to reduce the cost of construction, and as projects scale up in number, the cost of each unit can be further reduced. The objective of this project was to advance design and construction methods for manufacturing Small Modular Reactors (SMRs), and in particular to improve modular construction techniques and develop best practices for designing and operatingmore » supply chains that take advantage of these techniques. The overarching objectives were to accelerate the construction schedule and reduce its variability, reduce the cost of construction, reduce interest costs accrued during construction (IDC), and thus enhance the economic attractiveness of SMRs. Our fundamental measure of merit was total capital investment cost (TCIC). To achieve these objectives, this project developed a decision support system, EVAL, to support identifying, addressing, and resolving or ameliorating challenges and deficiencies in the current modular construction approach. The results of this effort were consistent with the facts that the cost of a construction activity is often smallest when accomplished in the factory, greatest when accomplished at the construction site, and at an intermediate level when accomplished at an assembly area close to the construction site. Further, EVAL can aid in providing insight into ways to reduce waste, improve quality, efficiency, and throughput and reflects the fact that the more done early in the construction process, i.e., in the factory, the more upfront funding is required and hence the more IDC will be accrued. The analysis has lead to a better understanding of circumstances under which modular construction performed mainly in the factory will result in lower expected total cost, relative to more traditional, on-site construction procedures. Further, we anticipate that EVAL can be used to gain insight regarding what role standardization can play in order for modularization to be most effectively defined. Such results would ultimately benefit all (small and large) new nuclear construction.« less

Quantifying the Temporal Inequality of Nutrient Loads with a Novel Metric

NASA Astrophysics Data System (ADS)

Gall, H. E.; Schultz, D.; Rao, P. S.; Jawitz, J. W.; Royer, M.

2015-12-01

Inequality is an emergent property of many complex systems. For a given series of stochastic events, some events generate a disproportionately large contribution to system responses compared to other events. In catchments, such responses cause streamflow and solute loads to exhibit strong temporal inequality, with the vast majority of discharge and solute loads exported during short periods of time during which high-flow events occur. These periods of time are commonly referred to as "hot moments". Although this temporal inequality is widely recognized, there is currently no uniform metric for assessing it. We used a novel application of Lorenz Inequality, a method commonly used in economics to quantify income inequality, to quantify the spatial and temporal inequality of streamflow and nutrient (nitrogen and phosphorus) loads exported to the Chesapeake Bay. Lorenz Inequality and the corresponding Gini Coefficient provide an analytical tool for quantifying inequality that can be applied at any temporal or spatial scale. The Gini coefficient (G) is a formal measure of inequality that varies from 0 to 1, with a value of 0 indicating perfect equality (i.e., fluxes and loads are constant in time) and 1 indicating perfect inequality (i.e., all of the discharge and solute loads are exported during one instant in time). Therefore, G is a simple yet powerful tool for providing insight into the temporal inequality of nutrient transport. We will present the results of our detailed analysis of streamflow and nutrient time series data collected since the early 1980's at 30 USGS gauging stations in the Chesapeake Bay watershed. The analysis is conducted at an annual time scale, enabling trends and patterns to be assessed both temporally (over time at each station) and spatially (for the same period of time across stations). The results of this analysis have the potential to create a transformative new framework for identifying "hot moments", improving our ability to temporally and spatially target implementation of best management practices to ultimately improve water quality in the Chesapeake Bay. This method also provides insight into the temporal scales at which hydrologic and biogeochemical variability dominate nutrient export dynamics.

"Sniffing" Jupiter's moon Europa through ground-based IR observations

NASA Astrophysics Data System (ADS)

Paganini, Lucas; Mumma, Michael J.; Hurford, Terry; Roth, Lorenz; Villanueva, Geronimo Luis

2016-10-01

The ability to sample possible plumes from the subsurface ocean in Europa represents a major step in our search for extraterrestrial life. If plumes exist, sampling the effluent material would provide insights into their chemistry and relevant information about the prospect that life could exist, or now exists, within the ocean. Most of the difficulties in detecting plumes come from the less frequent observational coverage of Europa, which contrasts strongly with the frequent Cassini flybys of Enceladus (Spencer & Nimmo 2013). Recent observations have been taken with HST/STIS in 2014/2015, but results have shown no evident confirmation of the 2012 plume detection (Roth et al. 2014, 2015). Future in situ observations (Europa Mission) will provide definitive insights, but not before the spacecraft's arrival in ~2025, thus an interim approach is needed to inform such space mission planning and to complement existing observations at other wavelengths.In 2015, we initiated a strong campaign to build a comprehensive survey of possible plumes on Europa through high-resolution IR spectroscopy with Keck/NIRSPEC. We were awarded 10 nights out of 15 total nights available for Key Strategic Mission Support projects for the 2016A, 2016B, 2017A, and 2017B semesters under NASA time with the Keck Observatory. In 2016A, we observed Europa during 10 half-nights and will continue to do so for another 10 half-nights in 2017A. We target a serendipitous search of gaseous activity from Europa to confirm and constrain the chemical composition of possible Europan plumes that can aid the investigation of physical processes underlying (or on) its surface. Ultimately, we seek to: (1) provide information that can inform planning for NASA's Europa mission, (2) further our current understanding of Europa's gas environment, and (3) complement studies that are currently underway with other facilities (like the Hubble Space Telescope). In this presentation, we will discuss preliminary results, challenges, and future plans of our observing campaign.* This work was supported by a NASA Keck PI Data Award (PI LP), administered by the NASA Exoplanet Science Institute, and by the NASA Astrobiology Institute under proposal 13-13NAI7-0032 (PI MJM).

Research Technology

NASA Image and Video Library

2004-04-15

Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

Discussion of the Method to Determine the Ultimate Bearing Capacity of Soil Foundation

NASA Astrophysics Data System (ADS)

Du, Peng; Liu, Xiaoling; Zhang, Yangfu

2017-12-01

Combining literature examples, this paper has carried out Contrastive analysis of the theoretical formula method and finite element method about the ultimate bearing capacity of foundation, To verify rationality and superiority of the incremental load method in finite element ABAQUS in solving the bearing capacity of foundation soil. The study can provide certain reference for practical engineering calculation and analysis of foundation bearing capacity.

Book Review: The end of time: the next revolution in our understanding of the universe. Julian Barbour, Weidenfeld and Nicholson, London, 384 pp., 16.95, ISBN 0195145925

NASA Astrophysics Data System (ADS)

Ellis, G. F. R.

In the early part of this century, physicists, led notably by Albert Einstein and the pioneers of quantum theory-in particular Neils Bohr, Werner Heisenberg, and Paul Dirac-discovered that the underlying nature of physical reality is stranger than anyone had ever imagined. A series of brilliant insights led to the realisation, on the one hand, of the relative nature of space and time measurements, and hence of our basic concepts of space and time (ultimately leading to the discovery of nuclear energy), and on the other hand, of the quantum nature of matter, with its associated quantum statistics and uncertainty of prediction (leading to transistors and lasers). Combining these views ultimately led to a realisation of the necessity of the existence of anti-matter, and of the dynamic nature of the vacuum. Further developments led to an understanding of the existence of symmetries characterising the various families of elementary particles, and of the unified nature of the fundamental interactions when described as gauge theories with forces mediated by exchange of gauge bosons. These properties have all been confirmed by carefully controlled experiments.

Leveraging health information exchange to improve population health reporting processes: lessons in using a collaborative-participatory design process.

PubMed

Revere, Debra; Dixon, Brian E; Hills, Rebecca; Williams, Jennifer L; Grannis, Shaun J

2014-01-01

Surveillance, or the systematic monitoring of disease within a population, is a cornerstone function of public health. Despite significant investment in information technologies (IT) to improve the public's health, health care providers continue to rely on manual, spontaneous reporting processes that can result in incomplete and delayed surveillance activities. Participatory design principles advocate including real users and stakeholders when designing an information system to ensure high ecological validity of the product, incorporate relevance and context into the design, reduce misconceptions designers can make due to insufficient domain expertise, and ultimately reduce barriers to adoption of the system. This paper focuses on the collaborative and informal participatory design process used to develop enhanced, IT-enabled reporting processes that leverage available electronic health records in a health information exchange to prepopulate notifiable-conditions report forms used by public health authorities. Over nine months, public health stakeholders, technical staff, and informatics researchers were engaged in a multiphase participatory design process that included public health stakeholder focus groups, investigator-engineering team meetings, public health survey and census regarding high-priority data elements, and codesign of exploratory prototypes and final form mock-ups. A number of state-mandated report fields that are not highly used or desirable for disease investigation were eliminated, which allowed engineers to repurpose form space for desired and high-priority data elements and improve the usability of the forms. Our participatory design process ensured that IT development was driven by end user expertise and needs, resulting in significant improvements to the layout and functionality of the reporting forms. In addition to informing report form development, engaging with public health end users and stakeholders through the participatory design process provided new insights into public health workflow and allowed the team to quickly triage user requests while managing user expectations within the realm of engineering possibilities. Engaging public health, engineering staff, and investigators in a shared codesigning process ensured that the new forms will not only meet real-life needs but will also support development of a product that will be adopted and, ultimately, improve communicable and infectious disease reporting by clinicians to public health.

Gaming science innovations to integrate health systems science into medical education and practice

PubMed Central

White, Earla J; Lewis, Joy H; McCoy, Lise

2018-01-01

Health systems science (HSS) is an emerging discipline addressing multiple, complex, interdependent variables that affect providers’ abilities to deliver patient care and influence population health. New perspectives and innovations are required as physician leaders and medical educators strive to accelerate changes in medical education and practice to meet the needs of evolving populations and systems. The purpose of this paper is to introduce gaming science as a lens to magnify HSS integration opportunities in the scope of medical education and practice. Evidence supports gaming science innovations as effective teaching and learning tools to promote learner engagement in scientific and systems thinking for decision making in complex scenarios. Valuable insights and lessons gained through the history of war games have resulted in strategic thinking to minimize risk and save lives. In health care, where decisions can affect patient and population outcomes, gaming science innovations have the potential to provide safe learning environments to practice crucial decision-making skills. Research of gaming science limitations, gaps, and strategies to maximize innovations to further advance HSS in medical education and practice is required. Gaming science holds promise to equip health care teams with HSS knowledge and skills required for transformative practice. The ultimate goals are to empower providers to work in complex systems to improve patient and population health outcomes and experiences, and to reduce costs and improve care team well-being.

The spectrum of genomic signatures: from dinucleotides to chaos game representation.

PubMed

Wang, Yingwei; Hill, Kathleen; Singh, Shiva; Kari, Lila

2005-02-14

In the post genomic era, access to complete genome sequence data for numerous diverse species has opened multiple avenues for examining and comparing primary DNA sequence organization of entire genomes. Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes. Herein, we demonstrate that DRAP is one particular genomic signature contained within a broader spectrum of signatures. Within this spectrum, an alternative genomic signature, Chaos Game Representation (CGR), provides a unique visualization of patterns in sequence organization. A genomic signature is associated with a particular integer order or subsequence length that represents a measure of the resolution or granularity in the analysis of primary DNA sequence organization. We quantitatively explore the organizational information provided by genomic signatures of different orders through different distance measures, including a novel Image Distance. The Image Distance and other existing distance measures are evaluated by comparing the phylogenetic trees they generate for 26 complete mitochondrial genomes from a diversity of species. The phylogenetic tree generated by the Image Distance is compatible with the known relatedness of species. Quantitative evaluation of the spectrum of genomic signatures may be used to ultimately gain insight into the determinants and biological relevance of the genome signatures.

Pathology Dynamics Predict Spinal Cord Injury Therapeutic Success

PubMed Central

Mitchell, Cassie S.

2008-01-01

Abstract Secondary injury, the complex cascade of cellular events following spinal cord injury (SCI), is a major source of post-insult neuron death. Experimental work has focused on the details of individual factors or mechanisms that contribute to secondary injury, but little is known about the interactions among factors leading to the overall pathology dynamics that underlie its propagation. Prior hypotheses suggest that the pathology is dominated by interactions, with therapeutic success lying in combinations of neuroprotective treatments. In this study, we provide the first comprehensive, system-level characterization of the entire secondary injury process using a novel relational model methodology that aggregates the findings of ~250 experimental studies. Our quantitative examination of the overall pathology dynamics suggests that, while the pathology is initially dominated by “fire-like,” rate-dependent interactions, it quickly switches to a “flood-like,” accumulation-dependent process with contributing factors being largely independent. Our evaluation of ~20,000 potential single and combinatorial treatments indicates this flood-like pathology results in few highly influential factors at clinically realistic treatment time frames, with multi-factor treatments being merely additive rather than synergistic in reducing neuron death. Our findings give new fundamental insight into the understanding of the secondary injury pathology as a whole, provide direction for alternative therapeutic strategies, and suggest that ultimate success in treating SCI lies in the pursuit of pathology dynamics in addition to individually involved factors. PMID:19125684

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core-Shell, Multilayer, and Gradient Concentration Profiles.

PubMed

Haring, Alexander P; Tong, Yuxin; Halper, Justin; Johnson, Blake N

2018-06-10

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The nematode Pristionchus pacificus as a model system for integrative studies in evolutionary biology.

PubMed

Sommer, Ralf J; McGaughran, Angela

2013-05-01

Comprehensive studies of evolution have historically been hampered by the division among disciplines. Now, as biology moves towards an '-omics' era, it is more important than ever to tackle the evolution of function and form by considering all those research areas involved in the regulation of phenotypes. Here, we review recent attempts to establish the nematode Pristionchus pacificus as a model organism that allows integrative studies of development and evo-devo, with ecology and population genetics. Originally developed for comparative study with the nematode Caenorhabditis elegans, P. pacificus provided insight into developmental pathways including dauer formation, vulva and gonad development, chemosensation, innate immunity and neurobiology. Its subsequent discovery across a wide geographic distribution in association with scarab beetles enabled its evaluation in a biogeographic context. Development of an evolutionary field station on La Réunion Island, where P. pacificus is present in high abundance across a number of widespread habitat types, allows examination of the microfacets of evolution - processes of natural selection, adaptation and drift among populations can now be examined in this island setting. The combination of laboratory-based functional studies with fieldwork in P. pacificus has the long-term prospective to provide both proximate (mechanistic) and ultimate (evolutionary and ecological) causation and might therefore help to overcome the long-term divide between major areas in biology. © 2013 Blackwell Publishing Ltd.

Functional Neuroimaging of Spike-Wave Seizures

PubMed Central

Motelow, Joshua E.; Blumenfeld, Hal

2013-01-01

Generalized spike-wave seizures are typically brief events associated with dynamic changes in brain physiology, metabolism, and behavior. Functional magnetic resonance imaging (fMRI) provides a relatively high spatio-temporal resolution method for imaging cortical-subcortical network activity during spike-wave seizures. Patients with spike-wave seizures often have episodes of staring and unresponsiveness which interfere with normal behavior. Results from human fMRI studies suggest that spike-wave seizures disrupt specific networks in the thalamus and fronto-parietal association cortex which are critical for normal attentive consciousness. However, the neuronal activity underlying imaging changes seen during fMRI is not well understood, particularly in abnormal conditions such as seizures. Animal models have begun to provide important fundamental insights into the neuronal basis for fMRI changes during spike-wave activity. Work from these models including both fMRI and direct neuronal recordings suggest that, like in humans, specific cortical-subcortical networks are involved in spike-wave, while other regions are spared. Regions showing fMRI increases demonstrate correlated increases in neuronal activity in animal models. The mechanisms of fMRI decreases in spike-wave will require further investigation. A better understanding of the specific brain regions involved in generating spike-wave seizures may help guide efforts to develop targeted therapies aimed at preventing or reversing abnormal excitability in these brain regions, ultimately leading to a cure for this disorder. PMID:18839093

Developing a toolbox for analysis of warrior wound biopsies: vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Crane, Nicole J.; O'Brien, Frederick P.; Forsberg, Jonathan A.; Potter, Benjamin K.; Elster, Eric A.

2011-03-01

The management of modern traumatic war wounds remains a significant challenge for clinicians. This is a reflection of the extensive osseous and soft-tissue damage caused by blasts and high-energy projectiles. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjectively based. Some wounds require an extended period of time to close or fail to remain closed, despite the use and application of novel wound-specific treatment modalities. Aside from impaired wound healing, additional wound complications include wound infection, biofilm formation, and heterotopic ossification (the pathological mineralization of soft tissues). An understanding of the molecular environment of acute wounds throughout the debridement process can provide valuable insight into the mechanisms associated with the eventual wound outcome. The analysis of Raman spectra of ex vivo wound biopsy tissue obtained from serial traumatic wound debridements reveals a decreased 1665 cm-1/1445 cm-1 band area ratio in impaired healing wounds, indicative of an impaired remodeling process, in addition to a decreased 1240 cm-1/1270cm-1. The examination of debrided tissue exhibits mineralization during the early development of heterotopic ossification. Finally, preliminary results suggest that Fourier transform infrared (FT-IR) images of wound effluent may be able to provide early microbiological information about the wound.

Phylogenetic and ecological factors impact the gut microbiota of two Neotropical primate species.

PubMed

Amato, Katherine R; Martinez-Mota, Rodolfo; Righini, Nicoletta; Raguet-Schofield, Melissa; Corcione, Fabiana Paola; Marini, Elisabetta; Humphrey, Greg; Gogul, Grant; Gaffney, James; Lovelace, Elijah; Williams, LaShanda; Luong, Albert; Dominguez-Bello, Maria Gloria; Stumpf, Rebecca M; White, Bryan; Nelson, Karen E; Knight, Rob; Leigh, Steven R

2016-03-01

Recent studies suggest that variation in diet across time and space results in changes in the mammalian gut microbiota. This variation may ultimately impact host ecology by altering nutritional status and health. Wild animal populations provide an excellent opportunity for understanding these interactions. However, compared to clinical studies, microbial research targeting wild animals is currently limited, and many published studies focus only on a single population of a single host species. In this study we utilize fecal samples from two species of howler monkey (Alouatta pigra and A. palliata) collected at four sites to investigate factors influencing the gut microbiota at three scales: taxonomic (host species), ecosystemic (forest type), and local (habitat disturbance/season). The results demonstrate that the effect of host species on the gut microbiota is stronger than the effect of host forest type, which is stronger than the effect of habitat disturbance or seasonality. Nevertheless, within host species, gut microbiota composition differs in response to forest type, habitat disturbance, and season. Variations in the effect size of these factors are associated both with host species and environment. This information may be beneficial for understanding ecological and evolutionary questions associated with Mesoamerican howler monkeys, as well as determining conservation challenges facing each species. These mechanisms may also provide insight into the ecology of other species of howler monkeys, non-human primates, and mammals.

"The developmental and functional logic of neuronal circuits": commentary on the Kavli Prize in Neuroscience.

PubMed

Glover, J C

2009-11-10

The first Kavli Prize in Neuroscience recognizes a confluence of career achievements that together provide a fundamental understanding of how brain and spinal cord circuits are assembled during development and function in the adult. The members of the Kavli Neuroscience Prize Committee have decided to reward three scientists (Sten Grillner, Thomas Jessell, and Pasko Rakic) jointly "for discoveries on the developmental and functional logic of neuronal circuits". Pasko Rakic performed groundbreaking studies of the developing cerebral cortex, including the discovery of how radial glia guide the neuronal migration that establishes cortical layers and for the radial unit hypothesis and its implications for cortical connectivity and evolution. Thomas Jessell discovered molecular principles governing the specification and patterning of different neuron types and the development of their synaptic interconnection into sensorimotor circuits. Sten Grillner elucidated principles of network organization in the vertebrate locomotor central pattern generator, along with its command systems and sensory and higher order control. The discoveries of Rakic, Jessell and Grillner provide a framework for how neurons obtain their identities and ultimate locations, establish appropriate connections with each other, and how the resultant neuronal networks operate. Their work has significantly advanced our understanding of brain development and function and created new opportunities for the treatment of neurological disorders. Each has pioneered an important area of neuroscience research and left a legacy of exceptional scientific achievement, insight, communication, mentoring and leadership.

A Saliency Guided Semi-Supervised Building Change Detection Method for High Resolution Remote Sensing Images

PubMed Central

Hou, Bin; Wang, Yunhong; Liu, Qingjie

2016-01-01

Characterizations of up to date information of the Earth’s surface are an important application providing insights to urban planning, resources monitoring and environmental studies. A large number of change detection (CD) methods have been developed to solve them by utilizing remote sensing (RS) images. The advent of high resolution (HR) remote sensing images further provides challenges to traditional CD methods and opportunities to object-based CD methods. While several kinds of geospatial objects are recognized, this manuscript mainly focuses on buildings. Specifically, we propose a novel automatic approach combining pixel-based strategies with object-based ones for detecting building changes with HR remote sensing images. A multiresolution contextual morphological transformation called extended morphological attribute profiles (EMAPs) allows the extraction of geometrical features related to the structures within the scene at different scales. Pixel-based post-classification is executed on EMAPs using hierarchical fuzzy clustering. Subsequently, the hierarchical fuzzy frequency vector histograms are formed based on the image-objects acquired by simple linear iterative clustering (SLIC) segmentation. Then, saliency and morphological building index (MBI) extracted on difference images are used to generate a pseudo training set. Ultimately, object-based semi-supervised classification is implemented on this training set by applying random forest (RF). Most of the important changes are detected by the proposed method in our experiments. This study was checked for effectiveness using visual evaluation and numerical evaluation. PMID:27618903

Connecting thermodynamics and economics: well-lit roads and burned bridges.

PubMed

Glucina, Mark David; Mayumi, Kozo

2010-01-01

Almost 40 years have passed since Georgescu-Roegen's seminal work, The Entropy Law and the Economic Process. During this time there has been much debate on the relevance of thermodynamics to economics, and many attempts to build bridges between the two. There has also been much confusion as to what the laws of thermodynamics actually say. This article clearly explains heat, work, and the thermodynamic laws, the meaning of entropy, and the importance of kinetics as a barrier to thermodynamically favorable processes. The two most important misunderstandings in the literature, namely entropy as disorder, and entropy as a measure of information, are highlighted. Reviewing the literature shows that thermodynamics is most relevant for building a descriptive model, or preanalytic vision of economics, because it implies physical constraints on production and consumption. Similarly, it suggests that there may be serious flaws with neoclassical economic models, and in particular the primacy of sustained growth. However, thermodynamics does not seem to aid mathematical modeling in economics, nor does it provide normative insights. As an aid to energy policy, thermodynamics is useful for assessing the feasibility of technology options--those that have the potential to meet our goals, and should be counted as options, and those that should not. But it does not provide a prescription outside of this technical realm. Factors, such as environmental impact, cost, and social acceptability, will ultimately determine which technically feasible options are most desirable.

An intersectionality-based policy analysis framework: critical reflections on a methodology for advancing equity.

PubMed

Hankivsky, Olena; Grace, Daniel; Hunting, Gemma; Giesbrecht, Melissa; Fridkin, Alycia; Rudrum, Sarah; Ferlatte, Olivier; Clark, Natalie

2014-12-10

In the field of health, numerous frameworks have emerged that advance understandings of the differential impacts of health policies to produce inclusive and socially just health outcomes. In this paper, we present the development of an important contribution to these efforts - an Intersectionality-Based Policy Analysis (IBPA) Framework. Developed over the course of two years in consultation with key stakeholders and drawing on best and promising practices of other equity-informed approaches, this participatory and iterative IBPA Framework provides guidance and direction for researchers, civil society, public health professionals and policy actors seeking to address the challenges of health inequities across diverse populations. Importantly, we present the application of the IBPA Framework in seven priority health-related policy case studies. The analysis of each case study is focused on explaining how IBPA: 1) provides an innovative structure for critical policy analysis; 2) captures the different dimensions of policy contexts including history, politics, everyday lived experiences, diverse knowledges and intersecting social locations; and 3) generates transformative insights, knowledge, policy solutions and actions that cannot be gleaned from other equity-focused policy frameworks. The aim of this paper is to inspire a range of policy actors to recognize the potential of IBPA to foreground the complex contexts of health and social problems, and ultimately to transform how policy analysis is undertaken.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

PubMed Central

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

2016-01-01

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. PMID:26724381

Nationwide citizen access to their health data: analysing and comparing experiences in Denmark, Estonia and Australia.

PubMed

Nøhr, Christian; Parv, Liisa; Kink, Pille; Cummings, Elizabeth; Almond, Helen; Nørgaard, Jens Rahbek; Turner, Paul

2017-08-07

Most countries face an ageing population, increasing chronic diseased, and constrictions on budget for providing health services. Involving patients in their own care by allowing them access to their patient data is a trend seen in many places. Data on the type and level of access citizens have to their own health data in three countries was gathered from public sources. Data from each individual country is presented and the experiences of Denmark, Estonia and Australia are examined whilst similarities and differences explored. The discussion adopts a citizen-centred perspective to consider how the different e-portal systems support, protect and structure citizen interactions with their own health data in three key areas: Security, privacy and data protection; User support; and Citizen adoption and use. The paper highlights the impact of opt-in/opt-out approaches on citizen access and the lack of a structured approach to addressing differences in citizen health and e-health literacy. This research also confirms while current data provides detail on the availability and use of personal health data by citizens, questions still remain over the ultimate impact on patient outcomes of these initiatives. It is anticipated the insights generated from the three countries experiences, supporting citizen access to their health data will be useful to improve these initiatives and guide other countries aspiring to support similar initiatives.

Effects of patch quality and network structure on patch occupancy dynamics of a yellow-bellied marmot metapopulation.

PubMed

Ozgul, Arpat; Armitage, Kenneth B; Blumstein, Daniel T; Vanvuren, Dirk H; Oli, Madan K

2006-01-01

1. The presence/absence of a species at a particular site is the simplest form of data that can be collected during ecological field studies. We used 13 years (1990-2002) of survey data to parameterize a stochastic patch occupancy model for a metapopulation of the yellow-bellied marmot in Colorado, and investigated the significance of particular patches and the influence of site quality, network characteristics and regional stochasticity on the metapopulation persistence. 2. Persistence of the yellow-bellied marmot metapopulation was strongly dependent on the high quality colony sites, and persistence probability was highly sensitive to small changes in the quality of these sites. 3. A relatively small number of colony sites was ultimately responsible for the regional persistence. However, lower quality satellite sites also made a significant contribution to long-term metapopulation persistence, especially when regional stochasticity was high. 4. The northern network of the marmot metapopulation was more stable compared to the southern network, and the persistence of the southern network depended heavily on the northern network. 5. Although complex models of metapopulation dynamics may provide a more accurate description of metapopulation dynamics, such models are data-intensive. Our study, one of the very few applications of stochastic patch occupancy models to a mammalian species, suggests that stochastic patch occupancy models can provide important insights into metapopulation dynamics using data that are easy to collect.

Identifying Novel Phenotypes of Vulnerability and Resistance to Activity-Based Anorexia in Adolescent Female Rats

PubMed Central

Barbarich-Marsteller, Nicole C.; Underwood, Mark D.; Foltin, Richard W.; Myers, Michael M.; Walsh, B. Timothy; Barrett, Jeffrey S.; Marsteller, Douglas A.

2018-01-01

Objective Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. Method Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30–35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. Results Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. Discussion The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa. PMID:23853140

A Saliency Guided Semi-Supervised Building Change Detection Method for High Resolution Remote Sensing Images.

PubMed

Hou, Bin; Wang, Yunhong; Liu, Qingjie

2016-08-27

Characterizations of up to date information of the Earth's surface are an important application providing insights to urban planning, resources monitoring and environmental studies. A large number of change detection (CD) methods have been developed to solve them by utilizing remote sensing (RS) images. The advent of high resolution (HR) remote sensing images further provides challenges to traditional CD methods and opportunities to object-based CD methods. While several kinds of geospatial objects are recognized, this manuscript mainly focuses on buildings. Specifically, we propose a novel automatic approach combining pixel-based strategies with object-based ones for detecting building changes with HR remote sensing images. A multiresolution contextual morphological transformation called extended morphological attribute profiles (EMAPs) allows the extraction of geometrical features related to the structures within the scene at different scales. Pixel-based post-classification is executed on EMAPs using hierarchical fuzzy clustering. Subsequently, the hierarchical fuzzy frequency vector histograms are formed based on the image-objects acquired by simple linear iterative clustering (SLIC) segmentation. Then, saliency and morphological building index (MBI) extracted on difference images are used to generate a pseudo training set. Ultimately, object-based semi-supervised classification is implemented on this training set by applying random forest (RF). Most of the important changes are detected by the proposed method in our experiments. This study was checked for effectiveness using visual evaluation and numerical evaluation.

Identifying novel phenotypes of vulnerability and resistance to activity-based anorexia in adolescent female rats.

PubMed

Barbarich-Marsteller, Nicole C; Underwood, Mark D; Foltin, Richard W; Myers, Michael M; Walsh, B Timothy; Barrett, Jeffrey S; Marsteller, Douglas A

2013-11-01

Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30-35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa. Copyright © 2013 Wiley Periodicals, Inc.

Insights into the use of polyethylene oxide in energy storage/conversion devices: a critical review

NASA Astrophysics Data System (ADS)

Arya, Anil; Sharma, A. L.

2017-11-01

In this review, the latest updates in poly (ethylene oxide) based electrolytes are summarized. The ultimate goal of researchers globally is towards the development of free-standing solid polymeric separators for energy storage devices. This single free-standing solid polymeric separator may replace the liquid and separator (organic/inorganic) used in existing efficient/smart energy technology. As an example, polyethylene oxide (PEO) consists of an electron donor-rich group which provides coordinating sites to the cation for migration. Owing to this exclusive structure, PEO exhibits some remarkable properties, such as a low glass transition temperature, excellent flexibility, and the ability to make complexation with various metal salts which are unattainable by another polymer host. Hence, the PEO is an emerging candidate that has been most examined or is currently under consideration for application in energy storage devices. This review article first provides a detailed study of the PEO properties, characteristics of the constituents of the polymer electrolyte, and suitable approaches for the modification of polymer electrolytes. Then, the synthesization and characterizations techniques are outlined. The structures, characteristics, and performance during charge-discharge of four types of electrolyte/separators (liquid, plasticized, and dispersed and intercalated electrolyte) are highlighted. The suitable ion transport mechanism proposed by researchers in different renowned groups have been discussed for the better understanding of the ion dynamics in such systems.

Infiltration of late Palaeozoic evaporative brines in the reelfoot rift: A possible salt source for Illinois Basin formation waters and MVT mineralizing fluids

USGS Publications Warehouse

Rowan, E.L.; De Marsily, G.

2001-01-01

Salinities and homogenization temperatures of fluid inclusions in Mississippi Valley-type (MVT) deposits provide important insights into the regional hydrology of the Illinois basin/Reelfoot rift system in late Palaeozoic time. Although the thermal regime of this basin system has been plausibly explained, the origin of high salinities in the basin fluids remains enigmatic. Topographically driven flow appears to have been essential in forming these MVT districts, as well as many other districts worldwide. However, this type of flow is recharged by fresh water making it difficult to account for the high salinities of the mineralizing fluids over extended time periods. Results of numerical experiments carried out in this study provide a possible solution to the salinity problem presented by the MVT zinc-lead and fluorite districts at the margins of the basin system. Evaporative concentration of surface water and subsequent infiltration into the subsurface are proposed to account for large volumes of brine that are ultimately responsible for mineralization of these districts. This study demonstrates that under a range of geologically reasonable conditions, brine infiltration into an aquifer in the deep subsurface can coexist with topographically driven flow. Infiltration combined with regional flow and local magmatic heat sources in the Reelfoot rift explain the brine concentrations as well as the temperatures observed in the Southern Illinois and Upper Mississippi Valley districts.

Fasting - the ultimate diet?

PubMed

Johnstone, A M

2007-05-01

Adult humans often undertake acute fasts for cosmetic, religious or medical reasons. For example, an estimated 14% of US adults have reported using fasting as a means to control body weight and this approach has long been advocated as an intermittent treatment for gross refractory obesity. There are unique historical data sets on extreme forms of food restriction that give insight into the consequences of starvation or semi-starvation in previously healthy, but usually non-obese subjects. These include documented medical reports on victims of hunger strike, famine and prisoners of war. Such data provide a detailed account on how the body adapts to prolonged starvation. It has previously been shown that fasting for the biblical period of 40 days and 40 nights is well within the overall physiological capabilities of a healthy adult. However, the specific effects on the human body and mind are less clearly documented, either in the short term (hours) or in the longer term (days). This review asks the following three questions, pertinent to any weight-loss therapy, (i) how effective is the regime in achieving weight loss, (ii) what impact does it have on psychology? and finally, (iii) does it work long-term?

Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull.

PubMed

Chambless, Lola B; Angel, Federica B; Abel, Ty W; Xia, Fen; Weaver, Kyle D

2010-10-25

Cerebral radiation necrosis is a relatively common complication of radiation therapy for intracranial malignancies which can also rarely be encountered after radiation of extracranial lesions of the head and neck. We present the first reported case of cerebral radiation necrosis in a patient who underwent radiation therapy for a plasmacytoma of the skull. A 68-year-old male with multiple myeloma presented with an enhancing right frontal mass, 8 years after receiving radiation therapy for a plasmacytoma of the left frontal skull. The patient underwent a diagnostic and therapeutic craniotomy for a presumed neoplastic lesion. The pathologic diagnosis made in this case was delayed radiation necrosis. The patient was followed for over a year during which this process continued to evolve before the ultimate resolution of his clinical symptoms and radiographic abnormality. This case highlights the importance of considering radiation necrosis in the differential diagnosis of any patient with an intracranial mass and a history of radiation for an extracranial head and neck malignancy, regardless of timing and laterality. This case also provides unique insights into the ongoing debate regarding the role of the aberrant immune response in the pathogenesis of delayed cerebral radiation necrosis.

Big data in psychology: A framework for research advancement.

PubMed

Adjerid, Idris; Kelley, Ken

2018-02-22

The potential for big data to provide value for psychology is significant. However, the pursuit of big data remains an uncertain and risky undertaking for the average psychological researcher. In this article, we address some of this uncertainty by discussing the potential impact of big data on the type of data available for psychological research, addressing the benefits and most significant challenges that emerge from these data, and organizing a variety of research opportunities for psychology. Our article yields two central insights. First, we highlight that big data research efforts are more readily accessible than many researchers realize, particularly with the emergence of open-source research tools, digital platforms, and instrumentation. Second, we argue that opportunities for big data research are diverse and differ both in their fit for varying research goals, as well as in the challenges they bring about. Ultimately, our outlook for researchers in psychology using and benefiting from big data is cautiously optimistic. Although not all big data efforts are suited for all researchers or all areas within psychology, big data research prospects are diverse, expanding, and promising for psychology and related disciplines. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Structural Stigma and Health Inequalities: Research Evidence and Implications for Psychological Science

PubMed Central

Hatzenbuehler, Mark L.

2016-01-01

Psychological research has provided essential insights into how stigma operates to disadvantage those who are targeted by it. At the same time, stigma research has been criticized for being too focused on the perceptions of stigmatized individuals and on micro-level interactions, rather than attending to structural forms of stigma. This article describes the relatively new field of research on structural stigma, which is defined as societal-level conditions, cultural norms, and institutional policies that constrain the opportunities, resources, and wellbeing of the stigmatized. I review emerging evidence that structural stigma related to mental illness and sexual orientation (1) exerts direct and synergistic effects on stigma processes that have long been the focus of psychological inquiry (e.g., concealment, rejection sensitivity); (2) serves as a contextual moderator of the efficacy of psychological interventions; and (3) contributes to numerous adverse health outcomes for members of stigmatized groups—ranging from dysregulated physiological stress responses to premature mortality—indicating that structural stigma represents an under-recognized mechanism producing health inequalities. Each of these pieces of evidence suggests that structural stigma is relevant to psychology and therefore deserves the attention of psychological scientists interested in understanding and ultimately reducing the negative effects of stigma. PMID:27977256

Adaptive Optics for the Human Eye

NASA Astrophysics Data System (ADS)

Williams, D. R.

2000-05-01

Adaptive optics can extend not only the resolution of ground-based telescopes, but also the human eye. Both static and dynamic aberrations in the cornea and lens of the normal eye limit its optical quality. Though it is possible to correct defocus and astigmatism with spectacle lenses, higher order aberrations remain. These aberrations blur vision and prevent us from seeing at the fundamental limits set by the retina and brain. They also limit the resolution of cameras to image the living retina, cameras that are a critical for the diagnosis and treatment of retinal disease. I will describe an adaptive optics system that measures the wave aberration of the eye in real time and compensates for it with a deformable mirror, endowing the human eye with unprecedented optical quality. This instrument provides fresh insight into the ultimate limits on human visual acuity, reveals for the first time images of the retinal cone mosaic responsible for color vision, and points the way to contact lenses and laser surgical methods that could enhance vision beyond what is currently possible today. Supported by the NSF Science and Technology Center for Adaptive Optics, the National Eye Institute, and Bausch and Lomb, Inc.

Early-Life Stressors, Personality Development, and Fast Life Strategies: An Evolutionary Perspective on Malevolent Personality Features.

PubMed

Csathó, Árpád; Birkás, Béla

2018-01-01

Life history theory posits that behavioral adaptation to various environmental (ecological and/or social) conditions encountered during childhood is regulated by a wide variety of different traits resulting in various behavioral strategies. Unpredictable and harsh conditions tend to produce fast life history strategies, characterized by early maturation, a higher number of sexual partners to whom one is less attached, and less parenting of offspring. Unpredictability and harshness not only affects dispositional social and emotional functioning, but may also promote the development of personality traits linked to higher rates of instability in social relationships or more self-interested behavior. Similarly, detrimental childhood experiences, such as poor parental care or high parent-child conflict, affect personality development and may create a more distrustful, malicious interpersonal style. The aim of this brief review is to survey and summarize findings on the impact of negative early-life experiences on the development of personality and fast life history strategies. By demonstrating that there are parallels in adaptations to adversity in these two domains, we hope to lend weight to current and future attempts to provide a comprehensive insight of personality traits and functions at the ultimate and proximate levels.

Dramatic Enhancement of Graphene Oxide/Silk Nanocomposite Membranes: Increasing Toughness, Strength, and Young's modulus via Annealing of Interfacial Structures.

PubMed

Wang, Yaxian; Ma, Ruilong; Hu, Kesong; Kim, Sunghan; Fang, Guangqiang; Shao, Zhengzhong; Tsukruk, Vladimir V

2016-09-21

We demonstrate that stronger and more robust nacre-like laminated GO (graphene oxide)/SF (silk fibroin) nanocomposite membranes can be obtained by selectively tailoring the interfacial interactions between "bricks"-GO sheets and "mortar"-silk interlayers via controlled water vapor annealing. This facial annealing process relaxes the secondary structure of silk backbones confined between flexible GO sheets. The increased mobility leads to a significant increase in ultimate strength (by up to 41%), Young's modulus (up to 75%) and toughness (up to 45%). We suggest that local silk recrystallization is initiated in the proximity to GO surface by the hydrophobic surface regions serving as nucleation sites for β-sheet domains formation and followed by SF assembly into nanofibrils. Strong hydrophobic-hydrophobic interactions between GO layers with SF nanofibrils result in enhanced shear strength of layered packing. This work presented here not only gives a better understanding of SF and GO interfacial interactions, but also provides insight on how to enhance the mechanical properties for the nacre-mimic nanocomposites by focusing on adjusting the delicate interactions between heterogeneous "brick" and adaptive "mortar" components with water/temperature annealing routines.

Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti

PubMed Central

2013-01-01

Background Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week. Results In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin. Conclusions These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties. PMID:23394545

The Efficient Utilization of Open Source Information

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

Baty, Samuel R.

These are a set of slides on the efficient utilization of open source information. Open source information consists of a vast set of information from a variety of sources. Not only does the quantity of open source information pose a problem, the quality of such information can hinder efforts. To show this, two case studies are mentioned: Iran and North Korea, in order to see how open source information can be utilized. The huge breadth and depth of open source information can complicate an analysis, especially because open information has no guarantee of accuracy. Open source information can provide keymore » insights either directly or indirectly: looking at supporting factors (flow of scientists, products and waste from mines, government budgets, etc.); direct factors (statements, tests, deployments). Fundamentally, it is the independent verification of information that allows for a more complete picture to be formed. Overlapping sources allow for more precise bounds on times, weights, temperatures, yields or other issues of interest in order to determine capability. Ultimately, a "good" answer almost never comes from an individual, but rather requires the utilization of a wide range of skill sets held by a team of people.« less

Strong texturing of lithium metal in batteries

DOE PAGES

Shi, Feifei; Pei, Allen; Vailionis, Arturas; ...

2017-10-30

Lithium, with its high theoretical specific capacity and lowest electrochemical potential, has been recognized as the ultimate negative electrode material for next-generation lithium-based high-energy-density batteries. However, a key challenge that has yet to be overcome is the inferior reversibility of Li plating and stripping, typically thought to be related to the uncontrollable morphology evolution of the Li anode during cycling. Here we show that Li-metal texturing (preferential crystallographic orientation) occurs during electrochemical deposition, which governs the morphological change of the Li anode. X-ray diffraction pole-figure analysis demonstrates that the texture of Li deposits is primarily dependent on the type ofmore » additive or cross-over molecule from the cathode side. With adsorbed additives, like LiNO 3 and polysulfide, the lithium deposits are strongly textured, with Li (110) planes parallel to the substrate, and thus exhibit uniform, rounded morphology. A growth diagram of lithium deposits is given to connect various texture and morphology scenarios for different battery electrolytes. In conclusion, this understanding of lithium electrocrystallization from the crystallographic point of view provides significant insight for future lithium anode materials design in high-energy-density batteries.« less

Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

PubMed Central

Sistrunk, Jeticia R.; Nickerson, Kourtney P.; Chanin, Rachael B.; Rasko, David A.

2016-01-01

SUMMARY Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens. PMID:27464994