Sample records for roadblocks

  1. Challenges and Roadblocks

    ERIC Educational Resources Information Center

    Hargrove, Kathy

    2011-01-01

    Gifted education has many challenges, and gifted programs sometimes throw up significant roadblocks. But passionate teachers can still make a difference in developing the gifts of the children. In this article, the author summarizes the challenges teachers face in serving gifted students and the roadblocks preventing a strong, supportive gifted…

  2. Distributed biotin–streptavidin transcription roadblocks for mapping cotranscriptional RNA folding

    PubMed Central

    Strobel, Eric J.; Nedialkov, Yuri; Artsimovitch, Irina

    2017-01-01

    Abstract RNA folding during transcription directs an order of folding that can determine RNA structure and function. However, the experimental study of cotranscriptional RNA folding has been limited by the lack of easily approachable methods that can interrogate nascent RNA structure at nucleotide resolution. To address this, we previously developed cotranscriptional selective 2΄-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) to simultaneously probe all intermediate RNA transcripts during transcription by stalling elongation complexes at catalytically dead EcoRIE111Q roadblocks. While effective, the distribution of elongation complexes using EcoRIE111Q requires laborious PCR using many different oligonucleotides for each sequence analyzed. Here, we improve the broad applicability of cotranscriptional SHAPE-Seq by developing a sequence-independent biotin–streptavidin (SAv) roadblocking strategy that simplifies the preparation of roadblocking DNA templates. We first determine the properties of biotin–SAv roadblocks. We then show that randomly distributed biotin–SAv roadblocks can be used in cotranscriptional SHAPE-Seq experiments to identify the same RNA structural transitions related to a riboswitch decision-making process that we previously identified using EcoRIE111Q. Lastly, we find that EcoRIE111Q maps nascent RNA structure to specific transcript lengths more precisely than biotin–SAv and propose guidelines to leverage the complementary strengths of each transcription roadblock in cotranscriptional SHAPE-Seq. PMID:28398514

  3. Distributed biotin-streptavidin transcription roadblocks for mapping cotranscriptional RNA folding.

    PubMed

    Strobel, Eric J; Watters, Kyle E; Nedialkov, Yuri; Artsimovitch, Irina; Lucks, Julius B

    2017-07-07

    RNA folding during transcription directs an order of folding that can determine RNA structure and function. However, the experimental study of cotranscriptional RNA folding has been limited by the lack of easily approachable methods that can interrogate nascent RNA structure at nucleotide resolution. To address this, we previously developed cotranscriptional selective 2΄-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) to simultaneously probe all intermediate RNA transcripts during transcription by stalling elongation complexes at catalytically dead EcoRIE111Q roadblocks. While effective, the distribution of elongation complexes using EcoRIE111Q requires laborious PCR using many different oligonucleotides for each sequence analyzed. Here, we improve the broad applicability of cotranscriptional SHAPE-Seq by developing a sequence-independent biotin-streptavidin (SAv) roadblocking strategy that simplifies the preparation of roadblocking DNA templates. We first determine the properties of biotin-SAv roadblocks. We then show that randomly distributed biotin-SAv roadblocks can be used in cotranscriptional SHAPE-Seq experiments to identify the same RNA structural transitions related to a riboswitch decision-making process that we previously identified using EcoRIE111Q. Lastly, we find that EcoRIE111Q maps nascent RNA structure to specific transcript lengths more precisely than biotin-SAv and propose guidelines to leverage the complementary strengths of each transcription roadblock in cotranscriptional SHAPE-Seq. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Transcription through the roadblocks: the role of RNA polymerase cooperation

    PubMed Central

    Epshtein, Vitaly; Toulmé, Francine; Rahmouni, A.Rachid; Borukhov, Sergei; Nudler, Evgeny

    2003-01-01

    During transcription, cellular RNA polymerases (RNAP) have to deal with numerous potential roadblocks imposed by various DNA binding proteins. Many such proteins partially or completely interrupt a single round of RNA chain elongation in vitro. Here we demonstrate that Escherichia coli RNAP can effectively read through the site-specific DNA-binding proteins in vitro and in vivo if more than one RNAP molecule is allowed to initiate from the same promoter. The anti-roadblock activity of the trailing RNAP does not require transcript cleavage activity but relies on forward translocation of roadblocked complexes. These results support a cooperation model of transcription whereby RNAP molecules behave as ‘partners’ helping one another to traverse intrinsic and extrinsic obstacles. PMID:12970184

  5. Aspirations, Experience, and Roadblocks to the Hiring of Women in Educational Administration.

    ERIC Educational Resources Information Center

    Coffin, Gregory C.; Ekstrom, Ruth B.

    Sixty-four women who hold positions in educational administration completed questionnaires describing themselves, their professional aspirations, their experience in seeking employment as administrators, the roadblocks they believe limit their careers, and the factors that have contributed to their success. Almost all the respondents hold one or…

  6. Successful Writing: Five Roadblocks to Overcome

    ERIC Educational Resources Information Center

    King, Kathleen P.

    2013-01-01

    This article provides essential strategies to be more successful in one of the major roles in academia: writing. Most academics struggle with roadblocks in their writing process. We are forever battling to complete research articles, manuscripts, grant proposals or other documents. The strategies and perspective shared here help overcome several…

  7. The Body as Evidence: Helping Clients Identify Decision-Making Roadblocks

    ERIC Educational Resources Information Center

    Synard, Jacqueline T.

    2009-01-01

    Grad school or Europe for a year? A highly motivated, fourth-year liberal arts student makes her decision but still has doubts. What roles do emotion and a client's personal history play in career counselling? The case study utilizes experiential process to uncover decision-making roadblocks.

  8. Mechanism of Chromosomal Boundary Action: Roadblock, Sink, or Loop?

    PubMed Central

    Gohl, Daryl; Aoki, Tsutomu; Blanton, Jason; Shanower, Greg; Kappes, Gretchen; Schedl, Paul

    2011-01-01

    Boundary elements or insulators subdivide eukaryotic chromosomes into a series of structurally and functionally autonomous domains. They ensure that the action of enhancers and silencers is restricted to the domain in which these regulatory elements reside. Three models, the roadblock, sink/decoy, and topological loop, have been proposed to explain the insulating activity of boundary elements. Strong predictions about how boundaries will function in different experimental contexts can be drawn from these models. In the studies reported here, we have designed assays that test these predictions. The results of our assays are inconsistent with the expectations of the roadblock and sink models. Instead, they support the topological loop model. PMID:21196526

  9. Guidelines to the Development of Human Resources in Libraries: Rationale, Policies, Programs and Recommendations

    ERIC Educational Resources Information Center

    Library Trends, 1971

    1971-01-01

    It is apparent that there are many roadblocks preventing the release of the human potential in our libraries. These guidelines take the position that a great deal can be done toward diagnosing and removing these roadblocks by establishing and developing meaningful policies and programs. (49 references) (Author/NH)

  10. "Roadblocks" Revisited: Neural Change, Stuttering Treatment, and Recovery from Stuttering

    ERIC Educational Resources Information Center

    Ingham, Roger J.; Finn, Patrick; Bothe, Anne K.

    2005-01-01

    In light of emerging findings concerning untreated recovery and neural plasticity, this paper re-examines the viability of an NIH conference recommendation [Cooper, J. A. (1990). Research directions in stuttering: Consensus and conflict. In Cooper, J. A. (Ed.), "Research needs in stuttering: Roadblocks and future directions" (pp. 98-100).…

  11. Roadblocks on the Information Highway

    ERIC Educational Resources Information Center

    Celano, Donna; Neuman, Susan B.

    2010-01-01

    As blogs light up with lively conversations about iPads, netbooks, and smart phones, it's easy to forget one major roadblock to preparing all children for the future: the digital divide. Although middle-class students often take high-speed Internet access for granted, a full 65 percent of Americans who make less than $25,000 a year lack broadband…

  12. Children at Risk: Roadblocks to Achieving Potential. Eliminating the Barriers.

    ERIC Educational Resources Information Center

    Wyoming State Dept. of Education, Cheyenne.

    This booklet, prepared by the Wyoming Department of Education, lists roadblocks that impede the development of young people and suggests measures to be taken by the family, the community, and the schools to remove them. Data on youth involvement are given for Wyoming and for the United States on the following topics: (1) dropping out of school;…

  13. Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions.

    PubMed

    Brown, Maxwell W; Kim, Yoori; Williams, Gregory M; Huck, John D; Surtees, Jennifer A; Finkelstein, Ilya J

    2016-02-03

    DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2-Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2-Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2-Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2-Msh3 and Msh2-Msh6 navigate on a crowded genome and suggest how Msh2-Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin.

  14. Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions

    PubMed Central

    Brown, Maxwell W.; Kim, Yoori; Williams, Gregory M.; Huck, John D.; Surtees, Jennifer A.; Finkelstein, Ilya J.

    2016-01-01

    DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2–Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2–Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2–Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2–Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2–Msh3 and Msh2–Msh6 navigate on a crowded genome and suggest how Msh2–Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin. PMID:26837705

  15. Research to reduce the suicide rate among older adults: methodology roadblocks and promising paradigms

    PubMed Central

    Szanto, Katalin; Lenze, Eric J.; Waern, Margda; Duberstein, Paul; Bruce, Martha L.; Epstein-Lubow, Gary; Conwell, Yeates

    2013-01-01

    The National Institute of Mental Health and the National Action Alliance for Suicide Prevention have requested input into the development of a national suicide research agenda. In response, a working group of the American Association for Geriatric Psychiatry has prepared recommendations to ensure that the suicide prevention dialogue includes older adults, a large and fast-growing population at high risk of suicide. In this Open Forum, the working group describes three methodology roadblocks to research into suicide prevention among elderly persons and three paradigms that might provide directions for future research into suicide prevention strategies for older adults. PMID:23728601

  16. Research to reduce the suicide rate among older adults: methodology roadblocks and promising paradigms.

    PubMed

    Szanto, Katalin; Lenze, Eric J; Waern, Margda; Duberstein, Paul; Bruce, Martha L; Epstein-Lubow, Gary; Conwell, Yeates

    2013-06-01

    The National Institute of Mental Health and the National Action Alliance for Suicide Prevention have requested input into the development of a national suicide research agenda. In response, a working group of the American Association for Geriatric Psychiatry has prepared recommendations to ensure that the suicide prevention dialogue includes older adults, a large and fast-growing population at high risk of suicide. In this Open Forum, the working group describes three methodology roadblocks to research into suicide prevention among elderly persons and three paradigms that might provide directions for future research into suicide prevention strategies for older adults.

  17. Overcoming systemic roadblocks to sustainability: The evolutionary redesign of worldviews, institutions, and technologies

    PubMed Central

    Beddoe, Rachael; Costanza, Robert; Farley, Joshua; Garza, Eric; Kent, Jennifer; Kubiszewski, Ida; Martinez, Luz; McCowen, Tracy; Murphy, Kathleen; Myers, Norman; Ogden, Zach; Stapleton, Kevin; Woodward, John

    2009-01-01

    A high and sustainable quality of life is a central goal for humanity. Our current socio-ecological regime and its set of interconnected worldviews, institutions, and technologies all support the goal of unlimited growth of material production and consumption as a proxy for quality of life. However, abundant evidence shows that, beyond a certain threshold, further material growth no longer significantly contributes to improvement in quality of life. Not only does further material growth not meet humanity's central goal, there is mounting evidence that it creates significant roadblocks to sustainability through increasing resource constraints (i.e., peak oil, water limitations) and sink constraints (i.e., climate disruption). Overcoming these roadblocks and creating a sustainable and desirable future will require an integrated, systems level redesign of our socio-ecological regime focused explicitly and directly on the goal of sustainable quality of life rather than the proxy of unlimited material growth. This transition, like all cultural transitions, will occur through an evolutionary process, but one that we, to a certain extent, can control and direct. We suggest an integrated set of worldviews, institutions, and technologies to stimulate and seed this evolutionary redesign of the current socio-ecological regime to achieve global sustainability. PMID:19240221

  18. A small-molecule acts as a 'roadblock' on DNA, hampering its fundamental processes.

    PubMed

    Kumar, Amit

    2017-11-01

    DNA replication, RNA and protein synthesis are the most fundamental housekeeping processes involved in an organism's growth. Failure or dysregulation of these pathways are often deleterious to life. Therefore, selective inhibition of such processes can be crucial for the inhibition of the growth of any cell, including cancer cells, pathogenic bacteria or other deadly microbes. In the present study, a Zn 2+ complex is shown to act as a roadblock of DNA. The Zn 2+ complex inhibited DNA taq polymerase activity under the in vitro conditions of polymerase chain reaction (PCR). Under in vivo conditions, it readily crosses the cell wall of gram-negative bacteria (Escherichia coli), leading to the reduction of RNA levels as well as protein content. Growth of pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa) was also significantly retarded. The Zn 2+ complex binds to the grooves of the DNA without inducing conformational changes or exhibiting chemical nuclease activity. To the best current knowledge, this is first coordination complex exhibiting a 'roadblock' property under both in vitro and in vivo conditions (show at all three levels - DNA, RNA and protein). The label-free approach used in this study may offer an alternative route towards fighting pathogenic bacteria or cancer cells by hampering fundamental cellular processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Lightweight thermal energy recovery system based on shape memory alloys: a DOE ARPA-E initiative

    NASA Astrophysics Data System (ADS)

    Browne, Alan L.; Keefe, Andrew C.; Alexander, Paul W.; Mankame, Nilesh; Usoro, Patrick; Johnson, Nancy L.; Aase, Jan; Sarosi, Peter; McKnight, Geoffrey P.; Herrera, Guillermo; Churchill, Christopher; Shaw, John; Brown, Jeff

    2012-04-01

    Over 60% of energy that is generated is lost as waste heat with close to 90% of this waste heat being classified as low grade being at temperatures less than 200°C. Many technologies such as thermoelectrics have been proposed as means for harvesting this lost thermal energy. Among them, that of SMA (shape memory alloy) heat engines appears to be a strong candidate for converting this low grade thermal output to useful mechanical work. Unfortunately, though proposed initially in the late 60's and the subject of significant development work in the 70's, significant technical roadblocks have existed preventing this technology from moving from a scientific curiosity to a practical reality. This paper/presentation provides an overview of the work performed on SMA heat engines under the US DOE (Department of Energy) ARPA-E (Advanced Research Projects Agency - Energy) initiative. It begins with a review of the previous art, covers the identified technical roadblocks to past advancement, presents the solution path taken to remove these roadblocks, and describes significant breakthroughs during the project. The presentation concludes with details of the functioning prototypes developed, which, being able to operate in air as well as fluids, dramatically expand the operational envelop and make significant strides towards the ultimate goal of commercial viability.

  20. Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane

    PubMed Central

    Mu, Zongkai; Wang, Lei; Deng, Wei; Wang, Jiawei; Wu, Geng

    2017-01-01

    The mechanistic target of rapamycin (mTOR) signal-transduction pathway plays a key role in regulating many aspects of metabolic processes. The central player of the mTOR signaling pathway, mTOR complex 1 (mTORC1), is recruited by the pentameric Ragulator complex and the heterodimeric Rag GTPase complex to the lysosomal membrane and thereafter activated. Here, we determined the crystal structure of the human Ragulator complex, which shows that Lamtor1 possesses a belt-like shape and wraps the other four subunits around. Extensive hydrophobic interactions occur between Lamtor1 and the Lamtor2-Lamtor3, Lamtor4-Lamtor5 roadblock domain protein pairs, while there is no substantial contact between Lamtor2-Lamtor3 and Lamtor4-Lamtor5 subcomplexes. Interestingly, an α-helix from Lamtor1 occupies each of the positions on Lamtor4 and Lamtor5 equivalent to the α3-helices of Lamtor2 and Lamtor3, thus stabilizing Lamtor4 and Lamtor5. Structural comparison between Ragulator and the yeast Ego1-Ego2-Ego3 ternary complex (Ego-TC) reveals that Ego-TC only corresponds to half of the Ragulator complex. Coupling with the fact that in the Ego-TC structure, Ego2 and Ego3 are lone roadblock domain proteins without another roadblock domain protein pairing with them, we suggest that additional components of the yeast Ego complex might exist. PMID:29285400

  1. Mechanistic insights into how CMG helicase facilitates replication past DNA roadblocks.

    PubMed

    Trakselis, Michael A; Seidman, Michael M; Brosh, Robert M

    2017-07-01

    Before leaving the house, it is a good idea to check for road closures that may affect the morning commute. Otherwise, one may encounter significant delays arriving at the destination. While this is commonly true, motorists may be able to consult a live interactive traffic map and pick an alternate route or detour to avoid being late. However, this is not the case if one needs to catch the train which follows a single track to the terminus; if something blocks the track, there is a delay. Such is the case for the DNA replisome responsible for copying the genetic information that provides the recipe of life. When the replication machinery encounters a DNA roadblock, the outcome can be devastating if the obstacle is not overcome in an efficient manner. Fortunately, the cell's DNA synthesis apparatus can bypass certain DNA obstructions, but the mechanism(s) are still poorly understood. Very recently, two papers from the O'Donnell lab, one structural (Georgescu et al., 2017 [1]) and the other biochemical (Langston and O'Donnell, 2017 [2]), have challenged the conventional thinking of how the replicative CMG helicase is arranged on DNA, unwinds double-stranded DNA, and handles barricades in its path. These new findings raise important questions in the search for mechanistic insights into how DNA is copied, particularly when the replication machinery encounters a roadblock. Published by Elsevier B.V.

  2. Science in Quarantine: Academic Physics in Spain (1750-1900).

    ERIC Educational Resources Information Center

    Gonzalez, Antonio Moreno

    1998-01-01

    Provides historical information on the incorporation of physics as a subject into secondary schools in Spain. Cites religious and political tensions as early roadblocks to curriculum development. (DDR)

  3. Promotion-in-place: a logical approach.

    PubMed

    Futrell, D E

    1992-01-01

    The promotion-in-place system, says the author, can be a valuable tool for your healthcare institution. It can create a climate for individual achievement without the traditional roadblocks to success.

  4. Compounding the Challenge: Young Deaf Children and Learning Disabilities.

    ERIC Educational Resources Information Center

    Mauk, Gary W.; Mauk, Pamela P.

    1993-01-01

    This paper presents a definition of deaf and hard of hearing children with learning disabilities; notes the incidence of children with both disabilities; outlines roadblocks to learning; describes screening, diagnosis, and assessment practices; and offers suggestions for educational programming. (JDD)

  5. Gender Bias: Roadblock to Sustainable Development.

    ERIC Educational Resources Information Center

    Jacobson, Jodi L.

    1993-01-01

    Suggests that the problems of social justice, particularly related to the status of women, are closely associated with worldwide population issues, especially in the developing world. Ties gender bias to poverty, rapid population growth, and environmental degradation in government policy perpetuated cycles. (MCO)

  6. Be an Alumni Relations Revolutionary.

    ERIC Educational Resources Information Center

    Bickel, Kathy

    2000-01-01

    Presents marketing guru Guy Kawasaki's seven rules for revolutionaries, and examples of alumni relations innovators who are implementing change with cutting-edge programs, services, and business practices. Rules include: "jump curves" (look for new paths); "break down barriers" (challenge roadblocks of ignorance and inertia);…

  7. Removing the Tension from Extension

    ERIC Educational Resources Information Center

    Bradley, Lucy; Driscoll, Elizabeth; Bardon, Robert

    2012-01-01

    Job burnout and stress begin with day-to-day frustrations, roadblocks, and unmet expectations. These can transform job satisfaction and, ultimately, career choices, affecting the quality of programs, expense to universities, and relationships with the community. A series of innovative statewide workshops involving 97 agents and Extension directors…

  8. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  9. Organizational Knowledge Management Structure

    ERIC Educational Resources Information Center

    Walczak, Steven

    2005-01-01

    Purpose: To propose and evaluate a novel management structure that encourages knowledge sharing across an organization. Design/methodology/approach: The extant literature on the impact of organizational culture and its link to management structure is examined and used to develop a new knowledge sharing management structure. Roadblocks to…

  10. Inter-Institutional Collaboration and Team Teaching.

    ERIC Educational Resources Information Center

    Gatliff, Bee; Wendel, Frederick C.

    1998-01-01

    Inter-institutional collaboration and team teaching can enhance distance education. Of particular interest to those who are new to distance education or collaborative relationships, this article discusses several issues that should be considered in the planning process to avoid potential roadblocks and to maximize returns. (Author/AEF)

  11. Roadblocks to Change: Executive Behaviors Versus Executive Perceptions.

    ERIC Educational Resources Information Center

    Harris, Thomas E.

    A study analyzed the responses of chief executive officers (CEOs) and company presidents to a leadership test and an organizational environment test, to determine whether these individuals' managerial approaches coincided with their characterizations of their organizations' environments. Subjects, CEOs or presidents of 65 randomly selected…

  12. The crossroads of GIS and health information: a workshop on developing a research agenda to improve cancer control

    PubMed Central

    Pickle, Linda Williams; Szczur, Martha; Lewis, Denise Riedel; Stinchcomb, David G

    2006-01-01

    Cancer control researchers seek to reduce the burden of cancer by studying interventions, their impact in defined populations, and the means by which they can be better used. The first step in cancer control is identifying where the cancer burden is elevated, which suggests locations where interventions are needed. Geographic information systems (GIS) and other spatial analytic methods provide such a solution and thus can play a major role in cancer control. This report presents findings from a workshop held June 16–17, 2005, to bring together experts and stakeholders to address current issues in GIScience and cancer control. A broad range of areas of expertise and interest was represented, including epidemiology, geography, statistics, environmental health, social science, cancer control, cancer registry operations, and cancer advocacy. The goals of this workshop were to build consensus on important policy and research questions, identify roadblocks to future progress in this field, and provide recommendations to overcome these roadblocks. PMID:17118204

  13. Roadblocks to Scientific Thinking in Educational Decision Making

    ERIC Educational Resources Information Center

    Yates, Gregory C. R.

    2008-01-01

    Principles of scientific data accumulation and evidence-based practices are vehicles of professional enhancement. In this article, the author argues that a scientific knowledge base exists descriptive of the relationship between teachers' activities and student learning. This database appears barely recognised however, for reasons including (a)…

  14. Leveraging Guided Pathways to Improve Financial Aid Design and Delivery

    ERIC Educational Resources Information Center

    Luna-Torres, Maria; Leafgreen, Melet; McKinney, Lyle

    2017-01-01

    To address low completion rates, postsecondary leaders are championing a "guided pathways" approach that puts students on a prescribed route towards graduation. Designing solutions to address low completion rates is complex; in addition to academic roadblocks, insufficient financial resources coupled with a complicated financial aid…

  15. Teachers Know Best: Teachers' Views on Professional Development

    ERIC Educational Resources Information Center

    Bill & Melinda Gates Foundation, 2014

    2014-01-01

    To gain insights into the roadblocks to implementing effective professional development, the Bill & Melinda Gates Foundation contracted with the Boston Consulting Group in 2014 to reach more than 1,300 teachers, professional development leaders in district and state education agencies, principals, professional development providers, and…

  16. Technological Innovation in the 80's.

    ERIC Educational Resources Information Center

    Coles, James S., Ed.

    This six-chapter book presents background papers used by participants at a meeting designed to examine the prospects for and roadblocks to scientific and technological innovations as the 21st century is approached. They include: (1) "Research Universities and Industrial Innovation in America" (Steven Muller); (2) "The Role of…

  17. Teacher Perceptions Impeding Child Behavior Assessment in an Early Childhood Setting

    ERIC Educational Resources Information Center

    Edwards, Nicole Megan

    2017-01-01

    Researchers acknowledge the utility of external consultants in helping teachers address problem behavior. To build teachers' capacity, the author explored emerging roadblocks during a consultation process. This investigation involved consultation and training on multitiered positive behavior supports for early childhood co-teaching dyads who…

  18. Bypassing Evolutionary Roadblocks: Phenotypic Diversity in Isogenic Population Bridges Tradeoff in Evolution of a New Function

    NASA Astrophysics Data System (ADS)

    Petrie, K. L.; Meyer, J. R.

    2017-07-01

    A novel mechanism of innovation bridges fitness valleys by violating the one gene-one phenotype dogma. Protein products of a single gene partition into populations, some of which carry out a new function and some the old, avoiding tradeoffs.

  19. School Board Ethics and Effectiveness

    ERIC Educational Resources Information Center

    Feuerstein, Abe

    2009-01-01

    Since the early 1980s, educational policy has increasingly been focused on improving student performance (Conley, 2003, Murphy, 1990). School governance in general, and school boards in particular, have often been viewed as either the means of implementing needed reforms or as roadblocks in their way (Boyd, 2003; Delagardelle, M.; 2008; Howell,…

  20. Acoustics in Physical Education Settings: The Learning Roadblock

    ERIC Educational Resources Information Center

    Ryan, Stu; Mendel, Lisa Lucks

    2010-01-01

    Background: The audibility of teachers and peers is an essential factor in determining the academic performance of school children. However, acoustic conditions in most classrooms are less than optimal and have been viewed as "hostile listening environments" that undermine the learning of children in school. While research has shown that…

  1. Mathematics from High School to Community College: Preparation, Articulation, and College Un-Readiness

    ERIC Educational Resources Information Center

    Jaffe, Louise

    2012-01-01

    This research studied the role of mathematics as a roadblock to college completion for community college-bound students in California. Using longitudinal quantitative analysis, I observed the educational pipeline between high school and community college and analyzed how different high school mathematics histories predicted readiness, or…

  2. Dealing with Resistance to Change

    ERIC Educational Resources Information Center

    Williamson, Ronald; Blackburn, Barbara R.

    2010-01-01

    One of the biggest roadblocks to addressing instructional rigor in schools is the resistance to change that is displayed by teachers, students, parents, and other building and district leaders. Every person deals differently with change. Some are more accepting, others more resistant. No change is successful if the people being asked to change…

  3. The Great Firewall of China

    ERIC Educational Resources Information Center

    Healy, Shawn

    2007-01-01

    Although China has made notable progress in liberalizing its economy over the past three decades, the Communist Party maintains a stranglehold on political freedom, and in no place is this more apparent than the roadblocks it places on the Information Superhighway. Indeed, according to Reporters Without Borders, China stands as "... the…

  4. Is the Public Ready to Pay?

    ERIC Educational Resources Information Center

    Penning, Nick

    1988-01-01

    With the federal education budget for fiscal 1989 barely exceeding inflation costs, pressure is mounting for greater federal participation in educational finance--even from business and industry. Numerous schemes, such as a payroll tax and a college scholarship fund for women and minorities, are suggested and major roadblocks discussed. (MLH)

  5. Counselor Educators and Students with Problems of Professional Competence: A Survey and Discussion

    ERIC Educational Resources Information Center

    Brown-Rice, Kathleen; Furr, Susan

    2016-01-01

    A total of 370 counselor educators in CACREP-accredited [Council for Accreditation of Counseling and Related Educational Programs] programs were surveyed to determine their knowledge of master's students' problems of professional competence (PPC) and their perception of roadblocks that affect gatekeeping practices. Findings suggest that educators…

  6. Bacteria engineered for fuel ethanol production: current status

    Treesearch

    B.S. Dien; M.A. Cotta; T.W. Jeffries

    2003-01-01

    The lack of industrially suitable microorganisms for converting biomass into fuel ethanol has traditionally been cited as a major technical roadblock to developing a bioethanol industry. In the last two decades, numerous microorganisms have been engineered to selectively produce ethanol. Lignocellulosic biomass contains complex carbohydrates that necessitate utilizing...

  7. Roadblocks to Reform? A Review of Union Contracts in Michigan Schools

    ERIC Educational Resources Information Center

    Spalding, Audrey

    2014-01-01

    This study focuses on Public Act 103 of 2011, which made teacher evaluation, layoff policies and teacher placement prohibited subjects of bargaining, among other things. After surveying 200 Michigan school district collective bargaining agreements, this study finds that as many as 60 percent of districts could have collective bargaining agreements…

  8. Finding Susceptibility Genes for Developmental Disorders of Speech: The Long and Winding Road.

    ERIC Educational Resources Information Center

    Felsenfeld, Susan

    2002-01-01

    This article explores the gene-finding process for developmental speech disorders (DSDs), specifically disorders of articulation/phonology and stuttering. It reviews existing behavioral genetic studies of these phenotypes, discusses roadblocks that may impede the molecular study of DSDs, and reviews the findings of the small number of molecular…

  9. Reformers or Roadblocks: Educational Interest Groups and State Policy Formation

    ERIC Educational Resources Information Center

    Emerson, Joseph; Lemasters, Linda; Howerton, Everett

    2008-01-01

    Given the overt political nature of this topic, an additional theoretical postulate, the Triadic Theory of Power was also presented as another framework to conceptualize the external and internal forces which shape the formation of contemporary education policy. Predicated upon the scholarship of Nobel laureate James Q. Wilson, Andrew McFarland…

  10. Oral Language Needs: Making Math Meaningful

    ERIC Educational Resources Information Center

    Pace, Michelle H.; Ortiz, Enrique

    2015-01-01

    As a Title I kindergarten teacher, Michelle Pace, second grade teacher at Lake Mary Elementary School in Florida, has seen firsthand how oral language can create roadblocks for students in all areas of the curriculum, both academically and socially. At the time this article was written, the state of Florida had recently adopted the Common Core…

  11. Top Ten Musings about Publishing Qualitative Manuscripts: Managing the Devil in the Details

    ERIC Educational Resources Information Center

    Palladino, John M.

    2011-01-01

    The purpose of this presentation was to engage in dialogue with editors of other qualitative journals and conference participants about the common roadblocks that hinder the publication possibilities for qualitative research studies. All audience participants were conference presenters and/or qualitative researchers, novice level and above. The…

  12. ENHANCED SUSTAINABILITY THROUGH STRAW-BALE CONSTRUCTION: EDUCATION-RESEARCH BUILDING DEMONSTRATING HOW TO LIVE SUSTAINABLY IN THE MIDWEST

    EPA Science Inventory

    The greatest roadblock to a shift to sustainability is the false assumption that humankind is disconnected from the laws of nature and local limits. The greatest challenge is the inability to understand the true relationship among people, prosperity, and planet. This project...

  13. Roadblocks to Integrating Technology into Classroom Instruction

    ERIC Educational Resources Information Center

    Knight, Courteney Lester

    2012-01-01

    Although research has concluded that technology can enhance the teaching and learning processes, teachers have not yet fully adopted technology to support their teaching methodologies. In the last decade or so, as the accessible gap narrowed, the focus switched to other factors. This study attempts to answer the question: Why teachers do not fully…

  14. Why Not Charter School Boards?

    ERIC Educational Resources Information Center

    Schlechty, Phillip C.; Cole, Robert W.

    1994-01-01

    Argues that for a community to maintain control over its public schools it must make the school board accountable for the performance of the school and all of its employees. The authors suggest a new approach to school-board elections, addresses key elements needed in state legislation, and explains the existing roadblocks to change. (GLR)

  15. Roadblocks on the Way to School Reform in West Virginia.

    ERIC Educational Resources Information Center

    Meckley, Richard; Hazi, Helen M.

    1998-01-01

    West Virginia has yet to satisfy its circuit and supreme courts, despite massive efforts to reform the K-12 system and its financial support plan. Reasons for failure include lack of statewide financial commitment to public education, a resistant cultural climate, downsizing of staff, decreasing enrollments, lack of consensus about educational…

  16. Effective Stack Design in Air Pollution Control.

    ERIC Educational Resources Information Center

    Clarke, John H.

    1968-01-01

    Stack design problems fall into two general caterories--(1) those of building re-entry, and (2) those of general area pollution. Extensive research has developed adequate information, available in the literature, to permit effective stack design. A major roadblock to effective design has been the strong belief by architects and engineers that high…

  17. Retrieval Cues on Tests: A Strategy for Helping Students Overcome Retrieval Failure

    ERIC Educational Resources Information Center

    Gallagher, Kristel M.

    2017-01-01

    Students often struggle to recall information on tests, frequently claiming to experience a "retrieval failure" of learned information. Thus, the retrieval of information from memory may be a roadblock to student success. I propose a relatively simple adjustment to the wording of test items to help eliminate this potential barrier.…

  18. Teacher Control over Interagency Collaboration: A Roadblock for Effective Transitioning of Youth with Disabilities

    ERIC Educational Resources Information Center

    Meadows, Denis; Davies, Michael; Beamish, Wendi

    2014-01-01

    Poor post-school outcomes for youth with disabilities have consistently been reported internationally. Interagency collaboration between school systems and post-school services is critical and key to improving post-school life for these youth. An initial Queensland study that benchmarked the teacher practice of 104 transition teachers and…

  19. Guideposts and Roadblocks to the Career-Long Scholarly Engagement of Physical Education Teacher Education Faculty

    ERIC Educational Resources Information Center

    Berei, Catherine P.; Pratt, Erica; Parker, Melissa; Shephard, Kevin; Liang, Tanjian; Nampai, Udon; Neamphoka, Guntima

    2017-01-01

    Purpose: Scholarship is essential for the growth and development of the physical education field. Over time, scholarship expectations have changed, forcing faculty members to alter time spent for research, teaching, and service. Social-cognitive career theory (SCCT) presents a model for understanding performance and persistence in an occupational…

  20. Challenges in Engaging Communities in Bottom-Up Literacies for Democratic Citizenship

    ERIC Educational Resources Information Center

    Torres, Myriam N.

    2010-01-01

    The purpose of this article is to examine the authors' experiences while trying to enter and engage local communities in bottom-up literacies through participatory action research (PAR) toward the community's own collective self-development. In trying to enter five different communities, I have found several challenges and roadblocks such as…

  1. School Evaluation: A Lever for Meaningful Change.

    ERIC Educational Resources Information Center

    Evans, Max W.

    The principal who genuinely wants to change things in his school has a potentially powerful tool in the North Central Association plan for school evaluation. A major roadblock to reform has been conservatism both in the profession and among the public. The emerging role of the principal saddles him with the responsibility for bringing about change…

  2. Improving Occupational Orientation Programs for Junior High School Students in Metropolitan Areas. Final Report.

    ERIC Educational Resources Information Center

    Needham, Raymond; Binnie, Arthur

    Participants representing 18 western states and 37 cities attended an inservice institute designed to (1) identify trends, (2) examine current innovative programs, (3) look at roadblock programs, and (4) develop impact plans to cause improvement in occupational programs in the participants' home cities and states. Participants, including…

  3. Adult Student Learning Behaviors in a Roadblock Mathematics Course

    ERIC Educational Resources Information Center

    Tennant, Aimee

    2012-01-01

    Adult students are a growing population on college campuses. Adult students have lower graduation rates and longer times to graduation than traditional-age students. The ability to pass a college level mathematics course is a key factor in the graduation rates of all students. Past research has identified developmental mathematics, college…

  4. Mainstreaming Human Rights Education--A New NCSS Community Looks Forward

    ERIC Educational Resources Information Center

    Blanchard, Rosemary Ann

    2014-01-01

    Efforts to bring human rights (HR) and international humanitarian law (IHL) into the mainstream of social studies education in the United States often encounter roadblocks and digressions that are difficult to understand from outside the arena of US public education. Educational standards, curricula and core practices in U.S. public schools…

  5. International Aid Offers Promise, but Roadblocks Remain

    ERIC Educational Resources Information Center

    Lloyd, Marion

    2012-01-01

    In the aftermath of the devastating January 2010 earthquake in Haiti, international humanitarian groups and volunteers poured into the country, bolstering what was already one of the world's hot spots for nongovernmental organizations. But the magnitude of the disaster--an estimated 300,000 were killed and one million left homeless out of a…

  6. Security Considerations of Doing Business via the Internet: Cautions To Be Considered.

    ERIC Educational Resources Information Center

    Aldridge, Alicia; White, Michele; Forcht, Karen

    1997-01-01

    Lack of security is perceived as a major roadblock to doing business online. This article examines system, user, and commercial transaction privacy on the World Wide Web and discusses methods of protection: operating systems security, file and data protection, user education, access restrictions, data authentication, perimeter and transaction…

  7. Development of a Work-Based Learning Model for Youth with Disabilities from the Perspective of Employers

    ERIC Educational Resources Information Center

    Sametz, Rebecca R.

    2017-01-01

    For youth with disabilities, transitioning from school to work and adult life often means overcoming multiple social, academic, and environmental constraints that may present as roadblocks to meeting society's expectations of 'successful transition' (Lehman, Clark, Bullis, Rinkin, & Castellanos, 2002). According to the United States Department…

  8. Tom Bonner Prize Lecture: The Beta Spectrum of Tritium and the Problem of Neutrino Mass

    NASA Astrophysics Data System (ADS)

    Robertson, R. G. Hamish

    1997-04-01

    Enrico Fermi showed more than 60 years ago that the shape of beta spectra was sensitive to the mass of the unobserved particle, the neutrino, proposed by Wolfgang Pauli. With the discovery of tritium and its small decay energy, increasingly stringent limits were placed on the electron antineutrino mass. A roadblock at about 50 eV, namely the atomic and molecular structure of tritium-containing substances, was surmounted in the 1980s with the development at Los Alamos of methods for high-resolution beta spectroscopy with gases, together with worldwide theoretical work on the structure of diatomic T2 and T^3He^+. It was then possible to reach the very interesting region of cosmological relevance below 20 eV. An unexpected and strange new roadblock has now been encountered in all experiments on T_2. The spectrum near the endpoint is not consistent with theory either with or without neutrino mass. The questions now are, do the experiments all report the same phenomenon, and (if so) is it atomic theory, particle theory, or perhaps cosmology that needs repair?

  9. U.S. hospitals mired in bureaucracy: 10 roadblocks to change.

    PubMed

    Thompson, R E

    2000-01-01

    Given the dot.com revolution in health care, advancing medical technology, and dissatisfaction with managed care, fundamental change is the order of the day in U.S. hospitals. Some hospital leaders are responding effectively to these new century challenges. But too many only tinker with existing systems, hoping to get by with choices that are comfortable, conventional, and convenient. Meanwhile, the sharks of dwindling public confidence and lost political support circle ever closer. The vice president of medical affairs (VPMA) is positioned at the vertex of disparate organizational, interpersonal, and external forces and can lead the way in recognizing and removing common roadblocks delaying needed change. External obstacles include: (1) Too much regulation; (2) too many attorneys; and (3) theatrical local TV newscasts. Internal factors include: (4) A natural fear of change; (5) arguing when we do not really disagree; (6) Cake Committee management mentality; (7) over-aggressive downsizing; (8) natural conflict in choosing a health care ethic; (9) the past; and (10) lack of trust. Hospital leaders need to effectively act, not just think, "outside the box."

  10. Quantum Dots in a Polymer Composite: A Convenient Particle-in-a-Box Laboratory Experiment

    ERIC Educational Resources Information Center

    Rice, Charles V.; Giffin, Guinevere A.

    2008-01-01

    Semiconductor quantum dots are at the forefront of materials science chemistry with applications in biological imaging and photovoltaic technologies. We have developed a simple laboratory experiment to measure the quantum-dot size from fluorescence spectra. A major roadblock of quantum-dot based exercises is the particle synthesis and handling;…

  11. Practices of and Roadblocks to Teacher Leadership in the United Arab Emirates' Schools

    ERIC Educational Resources Information Center

    Al-Taneiji, Shaikah; Ibrahim, Ali

    2017-01-01

    This study investigates teachers' perceptions of their leadership practices in United Arab Emirates schools and the contextual and personal factors which support or deter them from becoming teacher leaders. The study used a mixed research design. First, a self-administered questionnaire was completed by 937 teachers in one big city in the UAE.…

  12. Meeting Women's and Girls' Special Needs: "Gender-Sensitive" Environments and the Roadblocks Women Science Educators Face.

    ERIC Educational Resources Information Center

    Davis, Kathleen S.

    Groups and educators have sought to construct gender-sensitive learning environments for women and girls in science, thus providing them with opportunities to legitimately participate in the science and science education communities. Results of the study reported in this paper show that women science educators who work to provide such contexts…

  13. Using Job Analytic Perceptions to Predict Stressor Levels among Factory Supervisors.

    ERIC Educational Resources Information Center

    Love, Kevin G.; And Others

    Job stress is recognized as a primary roadblock to achieving job satisfaction. In order to investigate the linkage between important job characteristics and stressor levels, 378 factory supervisors (aged 45-54; 89 percent male; 93 percent white with an average of 21 years with the company) completed a two-part job analysis questionnaire. In the…

  14. Is a Simple Measurement Task a Roadblock to Student Understanding of Wave Phenomena?

    ERIC Educational Resources Information Center

    Kryjevskaia, Mila; Stetzer, MacKenzie R.; Heron, Paula R. L

    2012-01-01

    We present results from our ongoing investigation of student understanding of periodic waves and interference phenomena at the introductory physics level. We have found that many students experience significant difficulties when they attempt to express a distance of interest in terms of the wavelength of a periodic wave. We argue that for these…

  15. Redefining the School District in Tennessee. Part One of a Three-Part Series

    ERIC Educational Resources Information Center

    Smith, Nelson

    2013-01-01

    As the challenges of education governance loom ever larger and the dysfunction and incapacity of the traditional K-12 system reveal themselves as major roadblocks to urgently needed reforms across that system, many have asked, "What's the alternative?" Part of the answer is the Recovery School District, a new state-created entity that…

  16. Copyright Renewal for Libraries: Seven Steps toward a User-Friendly Law

    ERIC Educational Resources Information Center

    Smith, Kevin L.

    2010-01-01

    Copyright law is a source of a great deal of bewilderment and frustration to academic librarians. Beyond the basics of copyright protection and fair use, most librarians struggle to grasp the complexity of the law and the roadblocks it presents to access and use. This article attempts to elucidate some of those complexities by suggesting seven…

  17. Advocating for Equitable Science-Learning Opportunities for Girls in an Urban City Youth Club and the Roadblocks Faced by Women Science Educators.

    ERIC Educational Resources Information Center

    Davis, Kathleen S.

    2002-01-01

    Reports on a study that examined the obstacles women science educators faced as they facilitated Explorers, an after-school science program for girls aged 6-12. The program provides girls with opportunities to legitimately participate in science activities. (Contains 39 references.) (Author/YDS)

  18. Financial Roadblocks to Renewing and Enhancing Washington's Public Schools.

    ERIC Educational Resources Information Center

    Theobald, Neil D.

    Many states are trying to balance interests in school between taxpayers' concerns and providing students with a good education. Washington is trying to overcome these problems and renew and enhance its public schools. Three court decisions in the late 1970s and early 1980s set strict constraints within which Washington's school funding system must…

  19. Heart-Healthy Families. Helping Your Kids Stay Fit Could Prevent Heart Disease in Their Futures.

    ERIC Educational Resources Information Center

    Vagnini, Frederic J.; Malone, Mary Jo

    1994-01-01

    The conditions and habits that lead to heart disease begin early in life. Obesity is the predecessor of a host of cardiovascular-related diseases; childhood obesity poses serious physical and psychological roadblocks for youngsters as they mature. The article suggests how families can adopt fitter lifestyles and instill good eating and exercise…

  20. Overcoming Roadblocks on the Way to Work. Bridges to Work Field Report. Field Report Series.

    ERIC Educational Resources Information Center

    Elliott, Mark; Palubinsky, Beth; Tierney, Joseph

    Five programs in the Bridges to Work demonstration have functioned as a labor market exchange--with the main services being job matching and transportation coordination--for job-ready inner-city workers and suburban employment. The logistics of transportation have been simple; the basics of employment have been an ongoing challenge. Sites have…

  1. An Ex-Soldier Finds a New Mission

    ERIC Educational Resources Information Center

    Sander, Libby

    2012-01-01

    Matthew Reilly's roundabout journey to college took a painful, decisive turn after a nighttime crash in Iraq. In 2008, six months into his first combat tour with the Army, Mr. Reilly and nine soldiers from his platoon were pursuing an insurgent when their armored fighting vehicle slammed into a roadblock. It was 2 o'clock in the morning, and fresh…

  2. Tangential scanning of hardwood logs: developing an industrial computer tomography scanner

    Treesearch

    Nand K. Gupta; Daniel L. Schmoldt; Bruce Isaacson

    1999-01-01

    It is generally believed that noninvasive scanning of hardwood logs such as computer tomography (CT) scanning prior to initial breakdown will greatly improve the processing of logs into lumber. This belief, however, has not translated into rapid development and widespread installation of industrial CT scanners for log processing. The roadblock has been more operational...

  3. Perception Gaps and the Adoption of Information Technology in the Clinical Healthcare Environment

    ERIC Educational Resources Information Center

    Hare, Karen

    2008-01-01

    Implementation of information systems has lagged in many areas of clinical healthcare for a variety of reasons. Economics, data complexity and resistance are among the often quoted roadblocks. Research suggests that physicians play a major part in the adoption, use and diffusion of information technology (IT) in clinical settings. There are also…

  4. Toyota's tips drive dramatic ED improvements.

    PubMed

    2002-11-01

    The Toyota Motor Corp.'s key concepts of allowing workers to make changes, putting the customer first, and reducing waste can have a dramatic impact when implemented in emergency departments. Staff should be empowered to make changes to improve quality. A chain of events should be set in motion for each customer request. Identify and eliminate roadblocks that cause delays.

  5. Low Wages = Low Quality: Solving the Real Preschool Teacher Crisis. NIEER Preschool Policy Matters, Issue 3.

    ERIC Educational Resources Information Center

    Barnett, W. Steven

    Recruiting and retaining good teachers ranks as one of the most significant roadblocks to solving the preschool quality crises facing the country. Evidence points to the low wages and benefits offered to preschool teachers as the single most important factor in hiring and keeping good teachers. This policy brief examines what is known about the…

  6. Patterns of Global Terrorism: 1997.

    DTIC Science & Technology

    1998-04-01

    four Colombian Coca - Cola employees at a roadblock in Norte de Santander. The rebels seek individual ransoms and a payoff from Coca - Cola to prevent...further kidnappings and have approached other Coca - Cola officials demanding a protection payoff. 23 December Pakistan Unidentified assailants...economic sanctions on Sudan for its sponsorship of international terrorism, its efforts to destabilize neighboring countries, and its abysmal human

  7. An Action Research Intervention for Improving Soldiers' Success in Their Off-Duty Education Pursuits

    ERIC Educational Resources Information Center

    Ferby, Clifford Jerome

    2013-01-01

    Many soldiers are interested in pursuing their college education but discover there are barriers and roadblocks that hamper their ability to take college courses. The notion of taking the classroom to the soldiers within their military unit should be studied further. The reason for this research was to improve soldiers' success in pursuing their…

  8. Speed Bumps, Roadblocks and Tollbooths: How Culturally and Linguistically Diverse Parents Navigate the Highways and Byways of Giftedness in Ontario

    ERIC Educational Resources Information Center

    Cobb, Cam

    2012-01-01

    In reviewing literature on culturally and linguistically diverse (CLD) parental inclusion and disproportionality, Cam Cobb, assistant professor at the University of Windsor, Ontario, illustrates how CLD giftedness--and especially CLD giftedness in Canadian settings--represents an area in need of further research. In part, this article begins to…

  9. The Community College: Bridge or Roadblock to Higher Education for US Adult Immigrant English-Language Learners?

    ERIC Educational Resources Information Center

    Janis, Thomas

    2013-01-01

    While community colleges have been accessible for adult learners with an immigrant and an English Language Learning (ELL) background, there is a gap between preparation and academic success on the college level among these students. Within community colleges, older adult English as a Second Language (ESL) students have the lowest first-semester…

  10. Transformational Assessment: A Simplified Model of Strategic Planning

    ERIC Educational Resources Information Center

    Bardwell, Rebecca

    2008-01-01

    Strategic planning is a way to evaluate a present situation and set a course for the future. While there is no dearth of literature on Strategic Planning, there appears to be reluctance on the part of K-12 educators to engage in strategic planning. Besides the cynicism about change, another roadblock to strategic planning is the time it takes.…

  11. The Visions Program of Orangeburg-Calhoun Technical College Presents a Communication Skills Enhancement Workshop for the Patient Management Department at TRMC.

    ERIC Educational Resources Information Center

    Ray, Elizabeth

    This document contains the instructional materials developed and presented in workshops on communications skills improvement at a regional hospital. The workshop was designed to help participants gain skills that enable them to do the following: (1) identify and overcome roadblocks to effective communication; (2) decode "hidden messages"; (3)…

  12. Independent Synthesis Projects in the Organic Chemistry Teaching Laboratories: Bridging the Gap between Student and Researcher

    ERIC Educational Resources Information Center

    Keller, Valerie A.; Kendall, Beatrice Lin

    2017-01-01

    Science educators strive to teach students how to be well-rounded scientists with the ability to problem solve, anticipate errors, and adapt to unexpected roadblocks. Traditional organic chemistry experiments seldom teach these skills, no matter how novel or contemporary the subject material. This paper reports on the success of a quarter-long…

  13. Examining the Use of Internal Defect Information for Information-Augmented Hardwood Log Breakdown

    Treesearch

    Luis G. Occeña; Daniel L. Schmoldt; Suraphan Thawornwong

    1997-01-01

    In present-day hardwood sawmills, log breakdown is hampered by incomplete information about log geometry and internal features. When internal log scanning becomes operational, it will remove this roadblock and provide a complete view of each logâs interior. It is not currently obvious, however, how dramatically this increased level of information will improve log...

  14. Evolution of a Vietnamese Village - Part 3: Duc Lap Since November 1964 and Some Comments on Village Pacification

    DTIC Science & Technology

    1967-02-01

    meters high. Whoever built this roadblock had a sense of the comic, for in its center stood a full-grown, live banana tree plus several other small...clumps of freshly planted flowers . One house in the hamlet was located just inside the perimeter fence, approximately 15 meters from the first

  15. One-Stop Shopping: The Road to Healthy Mothers and Children. A Report of the National Commission To Prevent Infant Mortality.

    ERIC Educational Resources Information Center

    National Commission To Prevent Infant Mortality, Washington, DC.

    This report promotes one-stop shopping for health and social services as an effective strategy for accommodating the needs of pregnant women and their children. Roadblocks to receipt of care by pregnant women include ignorance of prenatal or preventive pediatric services, poverty, weak referral networks, and the fragmentation of programs and…

  16. Influence of Academic Self-Regulation, Critical Thinking, and Age on Online Graduate Students' Academic Help-Seeking

    ERIC Educational Resources Information Center

    Dunn, Karee E.; Rakes, Glenda C.; Rakes, Thomas A.

    2014-01-01

    Academic help-seeking is an invaluable learning strategy that has not yet received much attention in the distance education research literature. The asynchronous nature of distance education and many online courses presents an inherent roadblock to help-seeking. The purpose of this study was to explore the effect of academic self-regulation,…

  17. Schools as Sites of Socio-Economic Inclusion: Improving the Fabric of Indian Society

    ERIC Educational Resources Information Center

    Rani, Bhavana

    2016-01-01

    This article examines the Right of Children to Free and Compulsory Education Act (RTE, 2009) in India, including its origin, the system of schools to which it gave rise, and its importance against the backdrop of the larger Indian society. This article further assesses the progress made in the implementation of the RTE, the roadblocks, and the…

  18. The Hidden Turmoil: Females Achieving Longevity in the Outdoor Learning Profession

    ERIC Educational Resources Information Center

    Wright, Michelle; Gray, Tonia

    2013-01-01

    Being a woman in the outdoor learning profession can bring distinctive challenges and roadblocks. Even more difficult is sustaining a life-long career, flourishing into a woman's 50s or 60s. Based on this premise, career longevity seems elusive for some women who aspire to work in the outdoors. This paper analyses the autobiographies of three…

  19. The role of repressor kinetics in relief of transcriptional interference between convergent promoters

    PubMed Central

    Hao, Nan; Palmer, Adam C.; Ahlgren-Berg, Alexandra; Shearwin, Keith E.; Dodd, Ian B.

    2016-01-01

    Transcriptional interference (TI), where transcription from a promoter is inhibited by the activity of other promoters in its vicinity on the same DNA, enables transcription factors to regulate a target promoter indirectly, inducing or relieving TI by controlling the interfering promoter. For convergent promoters, stochastic simulations indicate that relief of TI can be inhibited if the repressor at the interfering promoter has slow binding kinetics, making it either sensitive to frequent dislodgement by elongating RNA polymerases (RNAPs) from the target promoter, or able to be a strong roadblock to these RNAPs. In vivo measurements of relief of TI by CI or Cro repressors in the bacteriophage λ PR–PRE system show strong relief of TI and a lack of dislodgement and roadblocking effects, indicative of rapid CI and Cro binding kinetics. However, repression of the same λ promoter by a catalytically dead CRISPR Cas9 protein gave either compromised or no relief of TI depending on the orientation at which it binds DNA, consistent with dCas9 being a slow kinetics repressor. This analysis shows how the intrinsic properties of a repressor can be evolutionarily tuned to set the magnitude of relief of TI. PMID:27378773

  20. Roadblocks en route to the clinical application of induced pluripotent stem cells.

    PubMed

    Lowry, William E; Quan, William L

    2010-03-01

    Since the first studies of human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs), the stem-cell field has been abuzz with the promise that these pluripotent populations will one day be a powerful therapeutic tool. Although it has been proposed that hiPSCs will supersede hESCs with respect to their research and/or clinical potential because of the ease of their derivation and the ability to create immunologically matched iPSCs for each individual patient, recent evidence suggests that iPSCs in fact have several underappreciated characteristics that might mean they are less suitable for clinical application. Continuing research is revealing the similarities, differences and deficiencies of various pluripotent stem-cell populations, and suggests that many years will pass before the clinical utility of hESCs and hiPSCs is realized. There are a plethora of ethical, logistical and technical roadblocks on the route to the clinical application of pluripotent stem cells, particularly of iPSCs. In this Essay, we discuss what we believe are important issues that should be considered when attempting to bring hiPSC-based technology to the clinic.

  1. Innovation in cardiovascular disease in Europe with focus on arrhythmias: current status, opportunities, roadblocks, and the role of multiple stakeholders.

    PubMed

    Prinzen, Frits W; Dagres, Nikolaos; Bollmann, Andreas; Arnar, David O; Bove, Sylvie; Camm, John; Casadei, Barbara; Kirchhof, Paulus; Kuck, Karl-Heinz; Lumens, Joost; Michel, Martin C; Schwartz, Peter J; Van Vleymen, Betty; Vardas, Panos; Hindricks, Gerhard

    2018-05-01

    The European Heart Rhythm Association (EHRA) held an Innovation Forum in February 2016, to consider issues around innovation. The objective of the forum was to extend the innovation debate outside of the narrow world of arrhythmia specialists and cardiology in general, and seek input from all stakeholders including regulators, strategists, technologists, industry, academia, health providers, medical societies, payers, and patients. Innovation is indispensable for a continuing improvement in health care, preferably at higher efficacy and lower costs. It requires people who have been trained in a good scientific environment, high-quality research for achieving ground breaking inventions and the certainty of return on innovation investments. In the context of cardiovascular disease, innovation can imply better risk assessment and stratification, device technology, drug development, and process design. Several areas of promising developments were identified as well as several roadblocks to innovation. To drive innovation forward all stakeholders need to play a significant role. In a globalized and extremely competitive world, the leading role of Europe in medical innovation can only be achieved through a combined and well-coordinated effort from all involved parties.

  2. The use of genetically-engineered animals in science: perspectives of Canadian Animal Care Committee members.

    PubMed

    Ormandy, Elisabeth H; Dale, Julie; Griffin, Gilly

    2013-05-01

    The genetic engineering of animals for their use in science challenges the implementation of refinement and reduction in several areas, including the invasiveness of the procedures involved, unanticipated welfare concerns, and the numbers of animals required. Additionally, the creation of genetically-engineered animals raises problems with the Canadian system of reporting animal numbers per Category of Invasiveness, as well as raising issues of whether ethical limits can, or should, be placed on genetic engineering. A workshop was held with the aim of bringing together Canadian animal care committee members to discuss these issues, to reflect on progress that has been made in addressing them, and to propose ways of overcoming any challenges. Although previous literature has made recommendations with regard to refinement and reduction when creating new genetically-engineered animals, the perception of the workshop participants was that some key opportunities are being missed. The participants identified the main roadblocks to the implementation of refinement and reduction alternatives as confidentiality, cost and competition. If the scientific community is to make progress concerning the implementation of refinement and reduction, particularly in the creation and use of genetically-engineered animals, addressing these roadblocks needs to be a priority. 2013 FRAME.

  3. Public-private relationships in biobanking: a still underestimated key component of open innovation.

    PubMed

    Hofman, Paul; Bréchot, Christian; Zatloukal, Kurt; Dagher, Georges; Clément, Bruno

    2014-01-01

    Access to human bioresources is essential to the understanding of human diseases and to the discovery of new biomarkers aimed at improving the diagnosis, prognosis, and the predictive response of patients to treatments. The use of biospecimens is strictly controlled by ethical assessment, which complies with the laws of the country. These laws regulate the partnerships between the biobanks and industrial actors. However, private-public partnerships (PPP) can be limiting for several reasons, which can hamper the discovery of new biological tests and new active molecules targeted to human diseases. The bottlenecks and roadblocks in establishing these partnerships include: poor organization of the biobank in setting up PPP, evaluation of the cost of human samples, the absence of experience on the public side in setting up contracts with industry, and the fact that public and private partners may not share the same objectives. However, it is critical, in particular for academic biobanks, to establish strong PPP to accelerate translational research for the benefits of patients, and to allow the sustainability of the biobank. The purpose of this review is to discuss the main bottlenecks and roadblocks that can hamper the establishment of PPP based on solid and trusting relationships.

  4. Drugs for solid cancer: the productivity crisis prompts a rethink

    PubMed Central

    Rösel, Daniel; Brábek, Jan; Veselý, Pavel; Fernandes, Michael

    2013-01-01

    Despite remarkable progress in cancer-drug discovery, the delivery of novel, safe, and sustainably effective products to the clinic has stalled. Using Src as a model, we examine key steps in drug development. The preclinical evidence on the relationship between Src and solid cancer is in sharp contrast with the modest anticancer effect noted in conventional clinical trials. Here, we consider Src inhibitors as an example of a promising drug class directed to invasion and metastasis and identify roadblocks in translation. We question the assumption that a drug-induced tumor shrinkage in preclinical and clinical studies predicts a successful outcome. Our analysis indicates that the key areas requiring attention are related, and include preclinical models (in vitro and mouse models), meaningful clinical trial end points, and an appreciation of the role of metastasis in morbidity and mortality. Current regulations do not reflect the natural history of the disease, and may be unrelated to the key complications: local invasion, metastasis, and the development of resistance. Alignment of preclinical and clinical studies and regulations based on mechanistic trial end points and platforms may help in overcoming these roadblocks. Viewed kaleidoscopically, most elements necessary and sufficient for a novel translational paradigm are in place. PMID:23836990

  5. Collision Broadening Using Alkali-Filled, Hollow Core Fibers

    DTIC Science & Technology

    2007-09-01

    Glenn P. Perram (Member) Date ____________________________________ ________________ David E. Weeks (Member) Date AFIT/GAP/ENP/07-S01...what we wanted despite our vague descriptions. Theoretical roadblocks were deftly cleared by the incomparable Dr Glen Perram and Dr David Weeks...John Callahan, Capt Ryan Givens, Mark Spencer , and Capt Justin Spring all helped me to look at problems in different ways, which didn’t always help but

  6. "What Do We Do about Student Grammar--All Those Missing -'ed's' and -'s's'?" Using Comparison and Contrast to Teach Standard English in Dialectally Diverse Classrooms

    ERIC Educational Resources Information Center

    Wheeler, Rebecca S.

    2006-01-01

    This paper explores the long and winding road to integrating linguistic approaches to vernacular dialects in the classroom. After exploring past roadblocks, the author shares vignettes and classroom practices of her collaborator, Rachel Swords, who has succeeded in bringing Contrastive Analysis and Code-switching to her second and third-grade…

  7. A new approach to large area microchannel plate manufacture

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Methods of manufacture of twisted single elements as the base for producing microchannel plates (MCP) are discussed. Initial evaluations validated the off-axis channel concept and no technological roadblocks were identified which would prevent fabrication of high gain, high spatial resolution, large format MCP's using this technique. The first MP's have operated at stable gains of 3 million with pulse height resolution superior to results obtained by standard chevron MCP's.

  8. Novel Genetic Tools to Accelerate Our Understanding of Photosynthesis and Lipid Accumulation

    DTIC Science & Technology

    2014-08-20

    understanding of photosynthesis and lipid accumulation Martin C. Jonikas, Ph.D. Carnegie Institution for Science, Department of Plant Biology 260...knowledge of algal lipid metabolism and photosynthesis . Advances in our basic understanding of these processes will facilitate genetic engineering of...algae to improve lipid yields. Currently, one of the greatest roadblocks in the study of algal photosynthesis and lipid metabolism is the slow pace of

  9. Roadblocks to a 4-Year University: Understanding College Undermatch and College Choice Process of First-Generation, Low-Income High School Latina/o Students

    ERIC Educational Resources Information Center

    Naranjo, Melissa M.

    2016-01-01

    Research on college access and enrollment indicates that a college education is one of the most effective avenues to increase social mobility. Each year, low-income students of color face a number of barriers to college access and success at every stage of their educational trajectory (Gandara, 2000; Gandara, 2002; Gandara & Contreras, 2009;…

  10. VCSEL Scaling, Laser Integration on Silicon, and Bit Energy

    DTIC Science & Technology

    2017-03-01

    need of high efficiency with high temperature operation eliminates essentially all laser diode technologies except VCSELs. Therefore scaling of the...CW laser diode and separate modulator. Lower diagram circuitry shows the case for a DML VCSEL. The small gain volume and high speed modulation...speed of the modulator. However the CW laser that is needed for the modulator appears to create a technological roadblock for laser diode platforms

  11. POWERING AIRPOWER: IS THE AIR FORCES ENERGY SECURE

    DTIC Science & Technology

    2016-02-01

    needs. More on-site renewable energy generation increases AF readiness in crisis times by minimizing the AF’s dependency on fossil fuels. Financing...reducing the need for traditional fossil fuels, and the high investment cost of onsite renewable energy sources is still a serious roadblock in this...help installations better plan holistically. This research will take the form of problem/solution framework. With any complex problem, rarely does a

  12. Weapons Effects in Cities. Volume 2. Appendices

    DTIC Science & Technology

    1974-12-01

    reenforced 1st Division’s defense of the compound, its manpower decimated by the roadblock fight which had also cost it 12 AFCs destroyed. On coming...CONFIDENTIAL). 159. Calfee, Dewey , E. Limited Range Test of the M-16 Rifle with Eight Types of Rifle and Hand Grenades. (AD458570), Eglin Air...30 September 1954. 165. Defense Documentation Center. Propellant Flashes. A DDC Biblio- graphy (U). (AD516700), Alexandria, Virginia: Defense

  13. Political Advertising: A Roadblock in Teaching Social Studies Students the Importance of Truthful Political Communication to a Democratic Society

    ERIC Educational Resources Information Center

    Martinson, David L.

    2009-01-01

    The author contends that too much political advertising is a form of public relations "spin" in which the truth is sacrificed and the political process damaged as a result. The goal of much of this advertising too frequently focuses on transmitting "disinformation" that, while perhaps not technically a lie, is intended not to inform the public but…

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

    ERIC Educational Resources Information Center

    Reavis, Tangela Blakely

    2017-01-01

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

  15. Changing course. Columbia the buyer becomes Columbia the builder as the company seeks to overcome market impediments.

    PubMed

    Japsen, B; Snow, C

    1997-04-14

    In an attempt to overcome market roadblocks, Columbia/HCA Healthcare Corp is revising its strategy from buying existing hospitals to constructing new ones. In this issue we take a look at the investor-owned giant's changing tactics as well as its sometimes rocky relations with the media. We also examine Columbia's performance in its former headquarters city, Louisville, Ky.

  16. Knowledge about the Brain for Parents, Students, and Teachers: The Keys to Removing the Invisible Roadblocks to Learning and High Self-Esteem for All Students.

    ERIC Educational Resources Information Center

    Beamish, Claude R.

    This paper presents basic information about the brain and how learning takes place, considers causes of differing human temperaments as explained by principles of Jungian psychology, reports on research on the causes of low achievement, and suggests a method to correct many educational problems. Principles of developmental neurology and right/left…

  17. SHI(EL)DS: A Novel Hardware-Based Security Backplane to Enhance Security with Minimal Impact to System Operation

    DTIC Science & Technology

    2008-03-01

    executables. The current roadblock to detecting Type I Malware consistantly is the practice of legitimate software , such as antivirus programs, using this... Software Security Systems . . 31 3.2.2 Advantages of Hardware . . . . . . . . . . . . . 32 3.2.3 Trustworthiness of Information . . . . . . . . . 33...Towards a Hardware Security Backplane . . . . . . . . . 42 IV. Review of State of the Art Computer Security Solutions . . . . . 46 4.1 Software

  18. Synthetic Molecular Evolution of Membrane-Active Peptides

    NASA Astrophysics Data System (ADS)

    Wimley, William

    The physical chemistry of membrane partitioning largely determines the function of membrane active peptides. Membrane-active peptides have potential utility in many areas, including in the cellular delivery of polar compounds, cancer therapy, biosensor design, and in antibacterial, antiviral and antifungal therapies. Yet, despite decades of research on thousands of known examples, useful sequence-structure-function relationships are essentially unknown. Because peptide-membrane interactions within the highly fluid bilayer are dynamic and heterogeneous, accounts of mechanism are necessarily vague and descriptive, and have little predictive power. This creates a significant roadblock to advances in the field. We are bypassing that roadblock with synthetic molecular evolution: iterative peptide library design and orthogonal high-throughput screening. We start with template sequences that have at least some useful activity, and create small, focused libraries using structural and biophysical principles to design the sequence space around the template. Orthogonal high-throughput screening is used to identify gain-of-function peptides by simultaneously selecting for several different properties (e.g. solubility, activity and toxicity). Multiple generations of iterative library design and screening have enabled the identification of membrane-active sequences with heretofore unknown properties, including clinically relevant, broad-spectrum activity against drug-resistant bacteria and enveloped viruses as well as pH-triggered macromolecular poration.

  19. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release.

    PubMed

    Jiskoot, Wim; Randolph, Theodore W; Volkin, David B; Middaugh, C Russell; Schöneich, Christian; Winter, Gerhard; Friess, Wolfgang; Crommelin, Daan J A; Carpenter, John F

    2012-03-01

    Protein instability and immunogenicity are two main roadblocks to the clinical success of novel protein drug delivery systems. In this commentary, we discuss the need for more extensive analytical characterization in relation to concerns about protein instability in injectable drug delivery systems for sustained release. We then will briefly address immunogenicity concerns and outline current best practices for using state-of-the-art analytical assays to monitor protein stability for both conventional and novel therapeutic protein dosage forms. Next, we provide a summary of the stresses on proteins arising during preparation of drug delivery systems and subsequent in vivo release. We note the challenges and difficulties in achieving the absolute requirement of quantitatively assessing the degradation of protein molecules in a drug delivery system. We describe the potential roles for academic research in further improving protein stability and developing new analytical technologies to detect protein degradation byproducts in novel drug delivery systems. Finally, we provide recommendations for the appropriate approaches to formulation design and assay development to ensure that stable, minimally immunogenic formulations of therapeutic proteins are created. These approaches should help to increase the probability that novel drug delivery systems for sustained protein release will become more readily available as effective therapeutic agents to treat and benefit patients. Copyright © 2011 Wiley Periodicals, Inc.

  20. Workshop IV: Professional Development and Leadership

    NASA Astrophysics Data System (ADS)

    Sui, Man-Ling; Yoon, Jin-Hee

    2015-12-01

    The Professional Development and Leadership workshop of the 5th IUPAP International Conference on Women in Physics was aimed at identifying and overcoming the personal and professional roadblocks that female physicists experience while pursuing their careers and obtaining leadership positions. Participants shared their thoughts and experiences related to the workshop's three sessions—Leadership, Education, and Inspiration—and concluded by formulating resolutions and recommendations to present to the International Union of Pure and Applied Physics (IUPAP).

  1. Genome Science and Personalized Cancer Treatment

    ScienceCinema

    Gray, Joe

    2017-12-09

    August 4, 2009 Berkeley Lab lecture: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks — particularly with regard to breast cancer.

  2. Sandia using RapTOR technology for understanding algal pond collapse.

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

    Lane, Todd W.; Janes, Michael

    2010-09-01

    As industry continues to find a profitable way to meet the nation's alternative energy objectives, more and more start-up companies, it seems, are growing production ponds of algae. Algae are widely viewed as a potential source of renewable fuel, but the technology to mass-produce fuel-grade algae is still in the early stages. A major roadblock is the inability to produce large amounts of the greenish, chlorophyll-containing organisms.

  3. Bacteriophage Transduction in Staphylococcus aureus.

    PubMed

    Olson, Michael E

    2016-01-01

    The genetic manipulation of Staphylococcus aureus for molecular experimentation is a valuable tool for assessing gene function and virulence. Genetic variability between strains coupled with difficult laboratory techniques for strain construction is a frequent roadblock in S. aureus research. Bacteriophage transduction greatly increases the speed and ease of S. aureus studies by allowing movement of chromosomal markers and plasmids between strains. This technique enables the S. aureus research community to focus investigations on clinically relevant isolates.

  4. Time-and-Spatially Adapting Simulations for Efficient Dynamic Stall Predictions

    DTIC Science & Technology

    2015-09-01

    Experi- mental Investigation and Fundamental Understand- ing of a Full-Scale Slowed Rotor at High Advance Ratios,” Journal of the American Helicopter ...remains a major roadblock in the design and analysis of conventional rotors as well as new concepts for future vertical lift. Several approaches to...of conventional rotors as well as new concepts for future vertical lift. Several approaches to reduce the cost of these dynamic stall simulations for

  5. A Report on the Navy SBIR Program: Best Practices, Roadblocks and Recommendations for Technology Transition

    DTIC Science & Technology

    2008-04-01

    a recommendation to the Phase I Sponsor, the NAVSEA SBIR Program Manager, and the PCO between 90 and 180 days after Phase I contract execution...determine eligibility for Phase II and send recommendations to sponsor Between 90 and 180 days after contract execution PCO Invites Phase II Proposals...manning study to evaluate the claim of inadequate numbers of contracting personnel. Although there were symptoms that contract delays were in part

  6. Genome Science and Personalized Cancer Treatment (LBNL Summer Lecture Series)

    ScienceCinema

    Gray, Joe [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division and Associate Lab. Director for Life and Environmental Sciences

    2018-05-04

    Summer Lecture Series 2009: Results from the Human Genome Project are enabling scientists to understand how individual cancers form and progress. This information, when combined with newly developed drugs, can optimize the treatment of individual cancers. Joe Gray, director of Berkeley Labs Life Sciences Division and Associate Laboratory Director for Life and Environmental Sciences, will focus on this approach, its promise, and its current roadblocks — particularly with regard to breast cancer.

  7. Education Regulations: Roadblocks to Student Choice in Higher Education. Hearing before the Committee on Education and the Workforce, U.S. House of Representatives, One Hundred Twelfth Congress, First Session (March 17, 2011). Serial Number 112-13

    ERIC Educational Resources Information Center

    US House of Representatives, 2011

    2011-01-01

    This paper presents the fourth Committee on Education and the Workforce hearing on the federal rules and regulations that undermine the strength of this nation's education system. Congress has purposely never defined the term "gainful employment," despite its presence in the statute for the past 50 years. It was decided that any attempt to define…

  8. Roads to advanced vaccines: influenza case study.

    PubMed

    Riese, Peggy; Guzmán, Carlos A

    2017-09-01

    Vaccines represent a cornerstone to ensure healthy lives and promote well-being for all at all ages. However, there are many diseases for which vaccines are not available, are relatively ineffective or need to be adapted periodically. Advances in microbial biotechnology will contribute to overcoming these roadblocks by laying the groundwork for improving and creating new approaches for developing better vaccines, as illustrated here in the case of influenza. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  9. Device Connectivity

    PubMed Central

    Walsh, John; Roberts, Ruth; Morris, Richard

    2015-01-01

    Patients with diabetes have to take numerous factors/data into their therapeutic decisions in daily life. Connecting the devices they are using by feeding the data generated into a database/app is supposed to help patients to optimize their glycemic control. As this is not established in practice, the different roadblocks have to be discussed to open the road. That large telecommunication companies are now entering this market might be a big help in pushing this forward. Smartphones offer an ideal platform for connectivity solutions. PMID:25614015

  10. Studies in Intelligence. Volume 55, Number 1, March 2011

    DTIC Science & Technology

    2011-03-01

    They were stopped several times at roadblocks manned by security personnel, but Liska, wearing his uniform, “always knew what to say .” The Pros...must we have something to say that people there cannot get somewhere else—which has to be more than hav- ing secrets—but we have to be mindful of...congressional hearing or eviscerated on an edito- rial page. And when I say forever, I mean forever. Rela- tively few people have read the now infamous NIE

  11. Mastery inspired activities to help at risk students

    NASA Astrophysics Data System (ADS)

    Stelzer, Tim; Gladding, Gary; Gutmann, Brianne; Lundsgaard, Morten; Schroeder, Noah

    2016-03-01

    Introductory physics is a roadblock for many aspiring engineers at the University of Illinois. The overall attrition rate in our introductory mechanics and E&M courses is approximately 15%, however that rate doubles for some under-represented populations. We introduced a set of online activities designed to provide students both an accurate assessment of their current understanding, and the resources to improve their performance. This talk will describe the design of these activities, and their impact on student attitude and understanding.

  12. Guideposts and Roadblocks to the Career-Long Scholarly Engagement of Physical Education Teacher Education Faculty.

    PubMed

    Berei, Catherine P; Pratt, Erica; Parker, Melissa; Shephard, Kevin; Liang, Tanjian; Nampai, Udon; Neamphoka, Guntima

    2017-12-01

    Scholarship is essential for the growth and development of the physical education field. Over time, scholarship expectations have changed, forcing faculty members to alter time spent for research, teaching, and service. Social-cognitive career theory (SCCT) presents a model for understanding performance and persistence in an occupational environment. The interconnected aspects of SCCT have different emphasis related to self-efficacy, outcome expectations, or personal goals pursuit. This study explored physical education teacher education (PETE) faculty members' continuing engagement in scholarly activity through SCCT. Data collection included interviews with 9 senior PETE faculty members who met the criteria for "productive scholars over time." Curriculum vitae were collected to verify productivity. Data analysis revealed guidepost themes that included collaborating, finding balance, defining a research process, and maintaining a strong work ethic. Roadblocks encountered included other obligations and lack of support for research. Participants demonstrated strong self-efficacy; held high, positive expectations for success; and set very specific, clear, and deliberate goals. Participant behavior was moderated by their personal attributes (capacity to build relationships, set goals, and maintain interest and passion) and was tempered by the environments in which they worked. Fostering similar behaviors has the potential to guide future and current PETE faculty members in creating supportive and encouraging atmospheres for sustained productivity. The lack of literature relating to this topic warrants the need for more research exploring the influential factors and benefits gained from sustained scholarly productivity over time for PETE faculty members.

  13. Benthic-Pelagic Coupling in Biogeochemical and Climate Models: Existing Approaches, Recent developments and Roadblocks

    NASA Astrophysics Data System (ADS)

    Arndt, Sandra

    2016-04-01

    Marine sediments are key components in the Earth System. They host the largest carbon reservoir on Earth, provide the only long term sink for atmospheric CO2, recycle nutrients and represent the most important climate archive. Biogeochemical processes in marine sediments are thus essential for our understanding of the global biogeochemical cycles and climate. They are first and foremost, donor controlled and, thus, driven by the rain of particulate material from the euphotic zone and influenced by the overlying bottom water. Geochemical species may undergo several recycling loops (e.g. authigenic mineral precipitation/dissolution) before they are either buried or diffuse back to the water column. The tightly coupled and complex pelagic and benthic process interplay thus delays recycling flux, significantly modifies the depositional signal and controls the long-term removal of carbon from the ocean-atmosphere system. Despite the importance of this mutual interaction, coupled regional/global biogeochemical models and (paleo)climate models, which are designed to assess and quantify the transformations and fluxes of carbon and nutrients and evaluate their response to past and future perturbations of the climate system either completely neglect marine sediments or incorporate a highly simplified representation of benthic processes. On the other end of the spectrum, coupled, multi-component state-of-the-art early diagenetic models have been successfully developed and applied over the past decades to reproduce observations and quantify sediment-water exchange fluxes, but cannot easily be coupled to pelagic models. The primary constraint here is the high computation cost of simulating all of the essential redox and equilibrium reactions within marine sediments that control carbon burial and benthic recycling fluxes: a barrier that is easily exacerbated if a variety of benthic environments are to be spatially resolved. This presentation provides an integrative overview of the benthic-pelagic coupling that accounts for the complex process interplay from the euphotic ocean to the deep sediment. It explores the intensity of the benthic-pelagic coupling across different environments and from the seasonal to the geological timescale. Different modelling approaches of coupling sediment and water column dynamics in regional/global biogeochemical models and (paleo)climate models are critically evaluated and their most important limitations, as well as the implications for our ability to predict the response of the global carbon cycle to past or future perturbations is discussed. Finally, the presentation identifies major roadblocks to the development of new model approaches and highlights how new techniques, new observational and laboratory data, as well as a close interdisciplinary collaboration can overcome these roadblocks.

  14. Tailoring dye-sensitized upconversion nanoparticle excitation bands towards excitation wavelength selective imaging

    DOE PAGES

    Wu, Xiang; Lee, Hyungseok; Bilsel, Osman; ...

    2015-01-01

    One of the key roadblocks in UCNP development is its extremely limited choices of excitation wavelengths. We report a generic design to program UCNPs to possess highly tunable dye characteristic excitation bands. Using such distinctive properties, we were able to develop a new excitation wavelength selective security imaging. Finally, this work unleashed the greater freedom of the excitation wavelengths of the upconversion nanoparticles and we believe it is a game-changer in the field and this method will enable numerous applications that are currently limited by existing UCNPs.

  15. Molecular mechanism-based model to enhance outcomes of dietary intervention studies for disease prevention

    PubMed Central

    Dey, Moul

    2014-01-01

    Advances in “omics”-based fields have produced an explosion of new information, fueling high expectations for improved public and individualized health. Unfortunately, there exists a widening gap between basic biochemistry and “omics”-based population research, with both disciplines failing to translate their full potential impact to human health applications. A paucity of comprehensive study systems is one of the many roadblocks faced by translational research today. This commentary will highlight the current status of such research, particularly emphasizing the role of nutrigenomics. PMID:25364700

  16. Utility of hyperspectral imagers in the mining industry: Italy's gypsum reserves

    NASA Astrophysics Data System (ADS)

    Wilson, Janette H.; Greenberger, Rebecca N.

    2014-05-01

    The mining industry is plagued with socioeconomic and safety roadblocks with not many solutions in the midst of a demanding market. As more and more geologic research using hyperspectral technology has been performed, along with an affordable price point for commercial use of hyperspectral technology, the benefits of hyperspectral imaging to the mining industry has become apparent. This study identifies the key areas of use for hyperspectral imaging in the mining industry through a case study of gypsum mine samples obtained from a mine in central Tuscany.

  17. Utilization of a Marketing Strategy at Naval Regional Medical Center Great Lakes, Great Lakes, Illinois

    DTIC Science & Technology

    1983-06-01

    meet the needs of each target market. Ś __-- - ,’ -m (-"b---"m m m 47 FOOTNOTES Philip Kotler , Marketing for Non-profit Organizations, 2nd Edition...for Branch Clinic, and Isley, Wynett A., ENS, MSC, USN, Officer-in-Charge, Branch Clinic 237. Interview, 15 April 1983. Books Kotler , Philip . Marketing...8217Healers’ Replace M.D.’s?" Medical Economics 59 (August 9, 1982): 89. 6Larry M. Robinson and Philip D. Cooper, "Roadblocks to Hospital Marketing

  18. Process Developed for Fabricating Engineered Pore Structures for High- Fuel-Utilization Solid Oxide Fuel Cells

    NASA Technical Reports Server (NTRS)

    Sofie, Stephen W.; Cable, Thomas L.; Salamone, Sam M.

    2005-01-01

    Solid oxide fuel cells (SOFCs) have tremendous commercial potential because of their high efficiency, high energy density, and flexible fuel capability (ability to use fossil fuels). The drive for high-power-utilizing, ultrathin electrolytes (less than 10 microns), has placed an increased demand on the anode to provide structural support, yet allow sufficient fuel entry for sustained power generation. Concentration polarization, a condition where the fuel demand exceeds the supply, is evident in all commercial-based anode-supported cells, and it presents a significant roadblock to SOFC commercialization.

  19. Protein diffusion along DNA: on the effect of roadblocks and crowders

    NASA Astrophysics Data System (ADS)

    Krepel, Dana; Levy, Yaakov

    2016-12-01

    Rapid recognition by a protein of its DNA target site is achieved through a combination of one- and three-dimensional (1D and 3D) diffusion, which allows efficient scanning of the many alternative sites. This facilitated diffusion mechanism is expected to be affected by cellular conditions, particularly crowding, given that up to 40% of the total cellular volume may by occupied by macromolecules. Both experimental and theoretical studies showed that crowding particles can enhance facilitated diffusion and accelerate search kinetics. This effect may originate from crowding forcing a trade-off between 3D and 1D diffusion. In this study, using coarse-grained molecular dynamic simulations, we investigate how the molecular properties of the crowders may modulate the effect exerted by crowding on a searcher protein. We show that crowders with an affinity to the DNA are less effective search facilitators than particles whose contribution is solely entropic. Crowders that have affinity to DNA may occupy DNA sites and thereby function as obstacles or roadblocks that slow down the searcher protein, and they may also produce a smaller excluded volume effect and so reduce usage of the hopping searching mode in favor of less-effective 3D diffusion in the bulk. We discuss how strong repulsive interactions between the crowding particles themselves may affect the overall dynamics of the crowders and their excluded volume effect. Our study shows that search kinetics and its mechanism are modulated not only by salt concentration and crowding occupancy, but also by the properties of the crowding particles.

  20. Managing by commitments.

    PubMed

    Sull, Donald N

    2003-06-01

    What makes a great manager great? Despite differences in their personal attributes, successful managers all excel in the making, honoring, and remaking of commitments. Managerial commitments take many forms, from capital investments to personnel decisions to public statements, but each exerts both immediate and enduring influence on a company. A leader's commitments shape a business's identity, define its strengths and weaknesses, establish its opportunities and limitations, and set its direction. Executives can all too easily forget that commitments are extraordinarily powerful. Caught up in the present, managers often take actions that, while beneficial in the near term, impose lasting constraints on their operations and organizations. When market or competitive conditions change, they can find themselves unable to respond effectively. Managers who understand the nature and power of their commitments can wield them more effectively throughout a company's life cycle. Entrepreneurs can avoid taking actions that imprint a new venture with a dysfunctional character. Managers in established enterprises can buttress past commitments that retain their currency and learn to recognize when commitments have become roadblocks to needed changes. The manager can then replace those roadblocks with new, rejuvenating commitments. That doesn't mean you should try to anticipate all the long-run consequences of every commitment--and it certainly doesn't mean you should shy away from making commitments. But it does mean that before making important decisions about, say, operating processes or partnerships, you should always ask yourself: Is this a process or relationship that we can live with in the future? Am I locking us into a course that we'll come to regret?

  1. Lost in Translation? Ethical Challenges of Implementing a New Diagnostic Procedure.

    PubMed

    Schmitz, Dagmar

    2016-01-01

    Since cell-free DNA (cfDNA) fragments of placental origin can be isolated and analyzed from the blood of pregnant women. Applications of this finding have been developed and implemented in clinical care pathways worldwide at an unprecedented pace and manner. Implementation patterns, however, exhibit considerable insufficiencies. Different "motors" of implementation processes, like the market or various regulatory institutions, can be identified at a national level. Each "motor" entails characteristic ethical challenges which are exemplified impressively by a rising number of case reports.Empirical data demonstrate that there are significant "losses" in the respective translational processes, especially when the results from clinical research are to be translated into the clinical reality of NIPT (the so called "second roadblock" (T2)). These "losses" are perceived in the fields of knowledge transfer, professional standardization and ethical debate. Recommendations of professional organizations often fail to reach general practitioners. Blindsided by the new diagnostic procedure in their clinical practice, professionals in prenatal care express their insecurities with regard to its handling. Ethical debate appears to adhere to pre-existing (and partly already proven to be insufficient) normative frameworks for prenatal testing. While all of these deficits are typical for the implementation processes of many new molecular diagnostic procedures, especially in NIPT, they show a high variability between different nations.A critical assessment of the preferred strategy of implementation against the background of already existing national ethical frameworks is indispensable, if potential adverse effects are to be diminished. The described translational losses seem to be significantly reducible by granting the translational process in roadblock T2 more time.

  2. Airship Industry Study

    NASA Technical Reports Server (NTRS)

    Hochstetler, Ron; Chachad, Girish; Melton, John

    2016-01-01

    There is an ongoing Government interest in the potential of airships for cargo transport; Conducting vertical or near-vertical airlift of heavy, outsized freight with little or no ground infrastructure is an attractive cargo transport option. USTRANSCOM wanted to understand the principal issues that are holding back commercial development of airship transports. NASA Ames Research Center was commissioned by USTRANSCOM to study the airship industry’s ability to design, develop, and operate cargo airships. Principal study objectives were to identify: (1) Current and near term state of the cargo airship industry; (2) Roadblocks hindering cargo airship development; (3) Steps needed to remove impediments to cargo airship deployment.

  3. Student Performance in Measuring Distance with Wavelengths in Various Settings

    NASA Astrophysics Data System (ADS)

    White, Gary

    2015-04-01

    When physics students are asked to measure the distance between two fixed locations using a pre-defined wavelength as a ruler, there is a surprising failure rate, at least partially due to the fact that the ``ruler'' to be used is not fixed in length (see ``Is a Simple Measurement Task a Roadblock to Student Understanding of Wave Phenomena?,'' by and references therein). I will show some data from introductory classes (algebra- and calculus-based) that replicate this result, and also show some interesting features when comparing a setting involving slinkies with a setting involving surface waves on water.

  4. Proteins mediating DNA loops effectively block transcription.

    PubMed

    Vörös, Zsuzsanna; Yan, Yan; Kovari, Daniel T; Finzi, Laura; Dunlap, David

    2017-07-01

    Loops are ubiquitous topological elements formed when proteins simultaneously bind to two noncontiguous DNA sites. While a loop-mediating protein may regulate initiation at a promoter, the presence of the protein at the other site may be an obstacle for RNA polymerases (RNAP) transcribing a different gene. To test whether a DNA loop alters the extent to which a protein blocks transcription, the lac repressor (LacI) was used. The outcome of in vitro transcription along templates containing two LacI operators separated by 400 bp in the presence of LacI concentrations that produced both looped and unlooped molecules was visualized with scanning force microscopy (SFM). An analysis of transcription elongation complexes, moving for 60 s at an average of 10 nt/s on unlooped DNA templates, revealed that they more often surpassed LacI bound to the lower affinity O2 operator than to the highest affinity Os operator. However, this difference was abrogated in looped DNA molecules where LacI became a strong roadblock independently of the affinity of the operator. Recordings of transcription elongation complexes, using magnetic tweezers, confirmed that they halted for several minutes upon encountering a LacI bound to a single operator. The average pause lifetime is compatible with RNAP waiting for LacI dissociation, however, the LacI open conformation visualized in the SFM images also suggests that LacI could straddle RNAP to let it pass. Independently of the mechanism by which RNAP bypasses the LacI roadblock, the data indicate that an obstacle with looped topology more effectively interferes with transcription. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  5. Roadmap to achieve 25% hypertension control in Africa by 2025

    PubMed Central

    Dzudie, Anastase; Kingue, Samuel; Dzudie, Anastase; Sliwa, Karen; Mayosi, Bongani; Dzudie, Anastase; Sliwa, Karen; Rayner, Brian; Ojji, Dike; Schutte, Aletta E; Twagirumukiza, Marc; Damasceno, Albertino; Ba, Seringe Abdou; Kane, Abdoul; Kramoh, Euloge; Kacou, Jean Baptiste Anzouan; Onwubere, Basden; Cornick, Ruth; Anisiuba, Benedict; Mocumbi, Ana Olga; Ogola, Elijah; Awad, Mohamed; Nel, George; Otieno, Harun; Toure, Ali Ibrahim; Kengne, Andre Pascal; Perel, Pablo; Adler, Alm; Poulter, Neil

    2017-01-01

    Summary Background and aim: The Pan-African Society of Cardiology (PASCAR) has identified hypertension as the highest area of priority for action to reduce heart disease and stroke on the continent. The aim of this PASCAR roadmap on hypertension was to develop practical guidance on how to implement strategies that translate existing knowledge into effective action and improve detection, treatment and control of hypertension and cardiovascular health in sub-Saharan Africa (SSA) by the year 2025. Methods: Development of this roadmap started with the creation of a consortium of experts with leadership skills in hypertension. In 2014, experts in different fields, including physicians and non-physicians, were invited to join. Via faceto- face meetings and teleconferences, the consortium made a situation analysis, set a goal, identified roadblocks and solutions to the management of hypertension and customised the World Heart Federation roadmap to Africa. Results: Hypertension is a major crisis on the continent but very few randomised, controlled trials have been conducted on its management. Also, only 25.8% of the countries have developed or adopted guidelines for the management of hypertension. Other major roadblocks are either government and health-system related or healthcare professional or patient related. The PASCAR hypertension task force identified a 10-point action plan to be implemented by African ministries of health to achieve 25% control of hypertension in Africa by 2025. Conclusions: Hypertension affects millions of people in SSA and if left untreated, is a major cause of heart disease and stroke. Very few SSA countries have a clear hypertension policy. This PASCAR roadmap identifies practical and effective solutions that would improve detection, treatment and control of hypertension on the continent and could be implemented as is or adapted to specific national settings. PMID:28906541

  6. Financial impact of divorce on children and their families.

    PubMed

    Teachman, J D; Paasch, K M

    1994-01-01

    This article reviews the evidence pertaining to the financial impact of divorce on children and their families. While there is some variance as to the degree of change, the preponderance of evidence suggests that women and children experience substantial financial declines upon divorce while divorced men's relative income remains stable or even increases. Given this decline in women and children's economic status, the impact of public assistance programs is next considered followed by a discussion of child support and property settlements. The authors then present a discussion of roadblocks to economic recovery and recommend policies to improve the financial status of divorced mothers with children.

  7. Innovations in deep brain stimulation methodology.

    PubMed

    Kühn, Andrea A; Volkmann, Jens

    2017-01-01

    Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  8. Innovative strategies for nursing education program evaluation.

    PubMed

    Story, Lachel; Butts, Janie B; Bishop, Sandra B; Green, Lisa; Johnson, Kathy; Mattison, Haley

    2010-06-01

    Nursing programs are mandated by accreditation bodies to report data significant to program quality and outcomes. The history at one school of nursing in the southern United States revealed the program evaluation committee experienced roadblocks in retrieving such information. Creative approaches were adopted to overcome some of the barriers to program evaluation, including the use of more technological-based approaches to engage alumni who embrace this technology as a way of life. Among the many advantages of these approaches were convenience, ease of administration and analysis, cost effectiveness, and more meaningful data. The advantages far outweighed the few disadvantages incurred, with the most prominent being potential sampling bias. Copyright 2010, SLACK Incorporated.

  9. MPD work at MIT

    NASA Technical Reports Server (NTRS)

    Martinez-Sanchez, Manuel

    1991-01-01

    MPD work at MIT is presented in the form of the view-graphs. The following subject areas are covered: the MIT program, its goals, achievements, and roadblocks; quasi one-dimensional modeling; two-dimensional modeling - transport effects and Hall effect; microscopic instabilities in MPD flows and modified two stream instability; electrothermal stability theory; separation of onset and anode depletion; exit plane spectroscopic measurements; phenomena of onset as performance limiter; explanations of onset; geometry effects on onset; onset at full ionization and its consequences; relationship to anode depletion; summary on self-field MPD; applied field MPD - the logical growth path; the case for AF; the challenges of AF MPD; and recommendations.

  10. Impact of materials engineering on edge placement error (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Freed, Regina; Mitra, Uday; Zhang, Ying

    2017-04-01

    Transistor scaling has transitioned from wavelength scaling to multi-patterning techniques, due to the resolution limits of immersion of immersion lithography. Deposition and etch have enabled scaling in the by means of SADP and SAQP. Spacer based patterning enables extremely small linewidths, sufficient for several future generations of transistors. However, aligning layers in Z-direction, as well as aligning cut and via patterning layers, is becoming a road-block due to global and local feature variation and fidelity. This presentation will highlight the impact of deposition and etch on this feature alignment (EPE) and illustrate potential paths toward lowering EPE using material engineering.

  11. Rejuvenating Strategies for Stem Cell-based Therapies in Aging

    PubMed Central

    Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

    2017-01-01

    SUMMARY Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for development of new strategies to improve stem cell function and optimize tissue repair processes. PMID:28157498

  12. Productivity improvement through industrial engineering in the semiconductor industry

    NASA Astrophysics Data System (ADS)

    Meyersdorf, Doron

    1996-09-01

    Industrial Engineering is fairly new to the semiconductor industry, though the awareness to its importance has increased in recent years. The US semiconductor industry in particular has come to the realization that in order to remain competitive in the global market it must take the lead not only in product development but also in manufacturing. Industrial engineering techniques offer one ofthe most effective strategies for achieving manufacturing excellence. Industrial engineers play an important role in the success of the manufacturing facility. This paper defines the Industrial engineers role in the IC facility, set the visions of excellence in semiconductor manufacturing and highlights 10 roadblocks on the journey towards manufacturing excellence.

  13. Roadblocks in the gut: barriers to enteric infection.

    PubMed

    Gill, Navkiran; Wlodarska, Marta; Finlay, B Brett

    2011-05-01

    This review discusses the barriers an enteric pathogen encounters when establishing an infection in the intestinal tract. There are potential barriers in the lumen that increase competition for nutrients and space. The role of mucus layer, and the antimicrobial peptides and secretory IgA sequestered within it, are also significant barriers. After overcoming these defences, the pathogen encounters the epithelial layer. This layer can be broken down into various protective components including enterocytes, Paneth cells, goblet cells, M cells and pathogen recognition receptors. Collectively, these intestinal defences constitute significant barriers that pathogens must overcome to successfully colonize this important mucosal surface. © 2011 Blackwell Publishing Ltd.

  14. Is editing the roadblock to the internationalization of Chinese academic journals?

    PubMed

    Lu, Jian-ping

    2011-06-01

    "China's internationalization" is in part realized through the dissemination of Chinese publications, such as academic journals. Therefore, editorial proficiency in the English language is of vital importance to the quality of the journals. This article analyzes the results of the two projects sponsored by the General Administration of Press and Publication of the People's Republic of China in 2007 and 2010 respectively, namely the "Analytical Evaluation of Language and Editing Quality of Chinese Academic Journals in English Language Issued in 2006", and the "Evaluation of Publication Quality of the China-Grown English Periodicals Issued in 2009, Sanctioned from 2005 to 2009", and proposes solutions to the problems presented therein.

  15. One size fits one: pharmacogenetics in gastroenterology.

    PubMed

    Porayette, Prashanth; Flockhart, David; Gupta, Sandeep K

    2014-04-01

    Individual variability in response and development of adverse effects to drugs is a major challenge in clinical practice. Pharmacogenomics refers to the aspect of personalized medicine where the patient's genetic information instructs the selection and dosage of therapy while also predicting its adverse effects profile. Sequencing of the entire human genome has given us the opportunity to study commonly used drugs as well as newer therapeutic agents in a new light, opening up opportunities for better drug efficacy and decreased adverse effects. This article highlights developments in pharmacogenomics, relates these to practice of gastroenterology, and outlines roadblocks in translation of this knowledge into clinical practice. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Challenging Roadblocks to Cancer Cure.

    PubMed

    Loda, Massimo

    2016-09-01

    The Pezcoller Symposium in Trento, Italy, June 2015, focused entirely on the question of why advanced cancer cure is so uncommon despite the extraordinarily rapid growth of invaluable therapeutic information. Participants were asked to define and to critically evaluate real and potential obstacles to permanent disease eradication. High-level concepts on potential road blocks to cures as well as opportunities for intervention in diverse areas of investigation ranging from genomic alterations to metabolism, microenvironment, immunity, and mechanotransduction were discussed. Provocative concepts and novel therapeutic avenues were proposed. What follows is a critical analysis of the highlights of this meeting. Cancer Res; 76(17); 4924-30. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. The promise and the pitfalls of autism research: an introductory note for new autism researchers.

    PubMed

    Amaral, David G

    2011-03-22

    The last decade has seen an enormous growth in the quantity of research directed at understanding the biological underpinnings of autism spectrum disorders. This increase has been spurred on, in part, by research funding provided through private, parent advocacy groups. While increased funding and entry into autism research by scientists from many disciplines has facilitated the speed of discoveries germane to establishing the etiologies of autism, there remain a number of roadblocks to understanding autism sufficiently well to foster new treatments. This short article provides a brief overview of some of the achievements and some of the difficulties in conducting autism research. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Productivity improvement through industrial engineering in the semiconductor industry

    NASA Astrophysics Data System (ADS)

    Meyersdorf, Doron

    1996-09-01

    Industrial engineering is fairly new to the semiconductor industry, though the awareness to its importance has increased in recent years. The U.S. semiconductor industry in particular has come to the realization that in order to remain competitive in the global market it must take the lead not only in product development but also in manufacturing. Industrial engineering techniques offer one of the most effective strategies for achieving manufacturing excellence. Industrial engineers play an important role in the success of the manufacturing facility. This paper defines the industrial engineers role in the IC facility, sets the visions of excellence in semiconductor manufacturing and highlights 10 roadblocks on the journey towards manufacturing excellence.

  19. Achieving EMC Emissions Compliance for an Aeronautics Power Line Communications System

    NASA Astrophysics Data System (ADS)

    Dominiak, S.; Vos, G.; ter Meer, T.; Widmer, H.

    2012-05-01

    Transmitting data over the power distribution network - Power Line Communications (PLC) -provides an interesting solution to reducing the weight and complexity of wiring networks in commercial aircraft. One of the potential roadblocks for the introduction of this technology is achieving EMC emissions compliance. In this article an overview of the EMC conducted and radiated emissions testing for PLC- enabled aeronautics equipment is presented. Anomalies resulting from chamber resonances leading to discrepancies between the conducted emissions tests and the measured radiated emissions are identified and described. Measurements made according to the current version of the civil aeronautical EMC standard, EUROCAE ED-14F (RTCA DO-160F), show that PLC equipment can achieve full EMC emissions compliance.

  20. Computational insights into charge transfer across functionalized semiconductor surfaces

    NASA Astrophysics Data System (ADS)

    Kearney, Kara; Rockett, Angus; Ertekin, Elif

    2017-12-01

    Photoelectrochemical water-splitting is a promising carbon-free fuel production method for producing H2 and O2 gas from liquid water. These cells are typically composed of at least one semiconductor photoelectrode which is prone to degradation and/or oxidation. Various surface modifications are known for stabilizing semiconductor photoelectrodes, yet stabilization techniques are often accompanied by a decrease in photoelectrode performance. However, the impact of surface modification on charge transport and its consequence on performance is still lacking, creating a roadblock for further improvements. In this review, we discuss how density functional theory and finite-element device simulations are reliable tools for providing insight into charge transport across modified photoelectrodes.

  1. Generalized theory on the mechanism of site-specific DNA-protein interactions

    NASA Astrophysics Data System (ADS)

    Niranjani, G.; Murugan, R.

    2016-05-01

    We develop a generalized theoretical framework on the binding of transcription factor proteins (TFs) with specific sites on DNA that takes into account the interplay of various factors regarding overall electrostatic potential at the DNA-protein interface, occurrence of kinetic traps along the DNA sequence, presence of other roadblock protein molecules along DNA and crowded environment, conformational fluctuations in the DNA binding domains (DBDs) of TFs, and the conformational state of the DNA. Starting from a Smolochowski type theoretical framework on site-specific binding of TFs we logically build our model by adding the effects of these factors one by one. Our generalized two-step model suggests that the electrostatic attractive forces present inbetween the positively charged DBDs of TFs and the negatively charged phosphate backbone of DNA, along with the counteracting shielding effects of solvent ions, is the core factor that creates a fluidic type environment at the DNA-protein interface. This in turn facilitates various one-dimensional diffusion (1Dd) processes such as sliding, hopping and intersegmental transfers. These facilitating processes as well as flipping dynamics of conformational states of DBDs of TFs between stationary and mobile states can enhance the 1Dd coefficient on a par with three-dimensional diffusion (3Dd). The random coil conformation of DNA also plays critical roles in enhancing the site-specific association rate. The extent of enhancement over the 3Dd controlled rate seems to be directly proportional to the maximum possible 1Dd length. We show that the overall site-specific binding rate scales with the length of DNA in an asymptotic way. For relaxed DNA, the specific binding rate will be independent of the length of DNA as length increases towards infinity. For condensed DNA as in in vivo conditions, the specific binding rate depends on the length of DNA in a turnover way with a maximum. This maximum rate seems to scale with the maximum possible 1Dd length of TFs in a square root manner. Results suggest that 1Dd processes contribute much less to the enhancement of specific binding rate under in vivo conditions for condensed DNA. There exists a critical length of binding stretch of TFs beyond which the probability associated with the random occurrence of similar specific binding sites will be close to zero. TFs in natural systems from prokaryotes to eukaryotes seem to handle sequence-mediated kinetic traps via increasing the length of their recognition stretch or combinatorial binding. TFs overcome the hurdles of roadblocks via switching efficiently between sliding, hopping and intersegmental transfer modes. The site-specific binding rate as well as the maximum possible 1Dd length seem to be directly proportional to the square root of the probability (p R) of finding a nonspecific binding site to be free from dynamic roadblocks. Here p R seems to be a function of the number of nsbs available per DNA binding protein (ϕ) inside the living cell. It seems that p R  >  0.8 when ϕ  >  10 which is true for the Escherichia coli cell system.

  2. Electrode Nanostructures in Lithium‐Based Batteries

    PubMed Central

    Mahmood, Nasir

    2014-01-01

    Lithium‐based batteries possessing energy densities much higher than those of the conventional batteries belong to the most promising class of future energy devices. However, there are some fundamental issues related to their electrodes which are big roadblocks in their applications to electric vehicles (EVs). Nanochemistry has advantageous roles to overcome these problems by defining new nanostructures of electrode materials. This review article will highlight the challenges associated with these chemistries both to bring high performance and longevity upon considering the working principles of the various types of lithium‐based (Li‐ion, Li‐air and Li‐S) batteries. Further, the review discusses the advantages and challenges of nanomaterials in nanostructured electrodes of lithium‐based batteries, concerns with lithium metal anode and the recent advancement in electrode nanostructures. PMID:27980896

  3. Multidisciplinary Environments: A History of Engineering Framework Development

    NASA Technical Reports Server (NTRS)

    Padula, Sharon L.; Gillian, Ronnie E.

    2006-01-01

    This paper traces the history of engineering frameworks and their use by Multidisciplinary Design Optimization (MDO) practitioners. The approach is to reference papers that have been presented at one of the ten previous Multidisciplinary Analysis and Optimization (MA&O) conferences. By limiting the search to MA&O papers, the authors can (1) identify the key ideas that led to general purpose MDO frameworks and (2) uncover roadblocks that delayed the development of these ideas. The authors make no attempt to assign credit for revolutionary ideas or to assign blame for missed opportunities. Rather, the goal is to trace the various threads of computer architecture and software framework research and to observe how these threads contributed to the commercial framework products available today.

  4. The Grape Antioxidant Resveratrol for Skin Disorders: Promise, Prospects, and Challenges

    PubMed Central

    Ndiaye, Mary; Philippe, Carol; Mukhtar, Hasan; Ahmad, Nihal

    2011-01-01

    Resveratrol, a phytoalexin antioxidant found in red grapes, has been shown to have both chemopreventive and therapeutic effects against many diseases and disorders, including those of the skin. Studies have shown protective effects of resveratrol against ultraviolet radiation mediated oxidative stress and cutaneous damages including skin cancer. Because many of the skin conditions stem from ultraviolet radiation and oxidative stress, this antioxidant appears to have promise and prospects against a wide range of cutaneous disorders including skin aging and skin cancers. However, there are a few roadblocks in the way of this promising agent regarding its translation from the bench to the bedside. This review discusses the promise and prospects of resveratrol in the management of skin disorders and the associated challenges. PMID:21215251

  5. Electronic health information system at an opioid treatment programme: roadblocks to implementation

    PubMed Central

    Louie, Ben; Kritz, Steven; Brown, Lawrence S.; Chu, Melissa; Madray, Charles; Zavala, Roberto

    2012-01-01

    Rationale Electronic health systems are commonly included in health care reform discussions. However, their embrace by the health care community has been slow. Methods At Addiction Research and Treatment Corporation, a methadone maintenance programme that also provides primary medical care, HIV medical care and case management, substance abuse counselling and vocational services, we describe our experience in implementing an electronic health information system that encompasses all of these areas. Results We describe the challenges and opportunities of this process in terms of change management, hierarchy of corporate objectives, process mastering, training issues, information technology governance, electronic security, and communication and collaboration. Conclusion This description may provide practical insights to other institutions seeking to pursue this technology. PMID:21414111

  6. Synthesizing and databasing fossil calibrations: divergence dating and beyond

    PubMed Central

    Ksepka, Daniel T.; Benton, Michael J.; Carrano, Matthew T.; Gandolfo, Maria A.; Head, Jason J.; Hermsen, Elizabeth J.; Joyce, Walter G.; Lamm, Kristin S.; Patané, José S. L.; Phillips, Matthew J.; Polly, P. David; Van Tuinen, Marcel; Ware, Jessica L.; Warnock, Rachel C. M.; Parham, James F.

    2011-01-01

    Divergence dating studies, which combine temporal data from the fossil record with branch length data from molecular phylogenetic trees, represent a rapidly expanding approach to understanding the history of life. National Evolutionary Synthesis Center hosted the first Fossil Calibrations Working Group (3–6 March, 2011, Durham, NC, USA), bringing together palaeontologists, molecular evolutionists and bioinformatics experts to present perspectives from disciplines that generate, model and use fossil calibration data. Presentations and discussions focused on channels for interdisciplinary collaboration, best practices for justifying, reporting and using fossil calibrations and roadblocks to synthesis of palaeontological and molecular data. Bioinformatics solutions were proposed, with the primary objective being a new database for vetted fossil calibrations with linkages to existing resources, targeted for a 2012 launch. PMID:21525049

  7. Electronic health information system at an opioid treatment programme: roadblocks to implementation.

    PubMed

    Louie, Ben; Kritz, Steven; Brown, Lawrence S; Chu, Melissa; Madray, Charles; Zavala, Roberto

    2012-08-01

    Electronic health systems are commonly included in health care reform discussions. However, their embrace by the health care community has been slow. At Addiction Research and Treatment Corporation, a methadone maintenance programme that also provides primary medical care, HIV medical care and case management, substance abuse counselling and vocational services, we describe our experience in implementing an electronic health information system that encompasses all of these areas. We describe the challenges and opportunities of this process in terms of change management, hierarchy of corporate objectives, process mastering, training issues, information technology governance, electronic security, and communication and collaboration. This description may provide practical insights to other institutions seeking to pursue this technology. © 2011 Blackwell Publishing Ltd.

  8. Is editing the roadblock to the internationalization of Chinese academic journals?*

    PubMed Central

    Lu, Jian-ping

    2011-01-01

    “China’s internationalization” is in part realized through the dissemination of Chinese publications, such as academic journals. Therefore, editorial proficiency in the English language is of vital importance to the quality of the journals. This article analyzes the results of the two projects sponsored by the General Administration of Press and Publication of the People’s Republic of China in 2007 and 2010 respectively, namely the “Analytical Evaluation of Language and Editing Quality of Chinese Academic Journals in English Language Issued in 2006”, and the “Evaluation of Publication Quality of the China-Grown English Periodicals Issued in 2009, Sanctioned from 2005 to 2009”, and proposes solutions to the problems presented therein. PMID:21634045

  9. Electrode Nanostructures in Lithium-Based Batteries.

    PubMed

    Mahmood, Nasir; Hou, Yanglong

    2014-12-01

    Lithium-based batteries possessing energy densities much higher than those of the conventional batteries belong to the most promising class of future energy devices. However, there are some fundamental issues related to their electrodes which are big roadblocks in their applications to electric vehicles (EVs). Nanochemistry has advantageous roles to overcome these problems by defining new nanostructures of electrode materials. This review article will highlight the challenges associated with these chemistries both to bring high performance and longevity upon considering the working principles of the various types of lithium-based (Li-ion, Li-air and Li-S) batteries. Further, the review discusses the advantages and challenges of nanomaterials in nanostructured electrodes of lithium-based batteries, concerns with lithium metal anode and the recent advancement in electrode nanostructures.

  10. Pragmatic open space box utilization: asteroid survey model using distributed objects management based articulation (DOMBA)

    NASA Astrophysics Data System (ADS)

    Mohammad, Atif Farid; Straub, Jeremy

    2015-05-01

    A multi-craft asteroid survey has significant data synchronization needs. Limited communication speeds drive exacting performance requirements. Tables have been used in Relational Databases, which are structure; however, DOMBA (Distributed Objects Management Based Articulation) deals with data in terms of collections. With this, no read/write roadblocks to the data exist. A master/slave architecture is created by utilizing the Gossip protocol. This facilitates expanding a mission that makes an important discovery via the launch of another spacecraft. The Open Space Box Framework facilitates the foregoing while also providing a virtual caching layer to make sure that continuously accessed data is available in memory and that, upon closing the data file, recharging is applied to the data.

  11. Open innovation in early drug discovery: roadmaps and roadblocks.

    PubMed

    Reichman, Melvin; Simpson, Peter B

    2016-05-01

    Open innovation in pharmaceutical R&D evolved from a triple helix of convergent paradigm shifts in academic, industrial and government research sectors. The birth of the biotechnology sector catalyzed shifts in location dynamics that led to the first wave of open innovation in pharmaceutical R&D between big pharma and startup companies. The National Institutes of Health (NIH) Roadmap was a crucial inflection point that set the stage for a new wave of open innovation models between pharmaceutical companies and universities that have the potential to transform the pharmaceutical R&D landscape. We highlight the attributes of leading protected open innovation models that foster the sharing of proprietary small molecule collections by lowering the risk of premature escape of intellectual property, particularly structure-activity data. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Key anticipated regulatory issues for clinical use of human induced pluripotent stem cells.

    PubMed

    Knoepfler, Paul S

    2012-09-01

    The production of human induced pluripotent stem cells (hiPSCs) has greatly expanded the realm of possible stem cell-based regenerative medicine therapies and has particularly exciting potential for autologous therapies. However, future therapies based on hiPSCs will first have to address not only similar regulatory issues as those facing human embryonic stem cells with the US FDA and international regulatory agencies, but also hiPSCs have raised unique concerns as well. While the first possible clinical use of hiPSCs remains down the road, as a field it would be wise for us to anticipate potential roadblocks and begin formulating solutions. In this article, I discuss the potential regulatory issues facing hiPSCs and propose some potential changes in the direction of the field in response.

  13. The future of automotive lithium-ion battery recycling: Charting a sustainable course

    DOE PAGES

    Gaines, Linda

    2014-12-01

    This paper looks ahead, beyond the projected large-scale market penetration of vehicles containing advanced batteries, to the time when the spent batteries will be ready for final disposition. It describes a working system for recycling, using lead–acid battery recycling as a model. Recycling of automotive lithium-ion (Li-ion) batteries is more complicated and not yet established because few end-of-life batteries will need recycling for another decade. There is thus the opportunity now to obviate some of the technical, economic, and institutional roadblocks that might arise. The paper considers what actions can be started now to avoid the impediments to recycling andmore » ensure that economical and sustainable options are available at the end of the batteries' useful life.« less

  14. Mentor Advice Giving in an Alternative Certification Program for Secondary Science Teaching: Opportunities and Roadblocks in Developing a Knowledge Base for Teaching

    NASA Astrophysics Data System (ADS)

    Upson Bradbury, Leslie; Koballa, Thomas R., Jr.

    2007-12-01

    Mentoring is often an important component of alternative certification programs, yet little is known about what novices learn about science teaching through mentoring relationships. This study investigated the advice given by two mentor science teachers to their protégés. Findings indicate that mentors gave more advice related to general pedagogical knowledge than science-specific pedagogical content knowledge. Specifically, there was little to no advice related to the topics of inquiry, the nature of science, or the development of scientific literacy. Implications call for an increase in communication between university teacher education programs and school-based mentors, the development of benchmarks to help guide mentor-protégé interactions, and the importance of a multiyear induction process.

  15. Distinct functions of human RecQ helicases during DNA replication.

    PubMed

    Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

    2017-06-01

    DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Mi Casa es Su Casa: how an intracellular symbiont manipulates host biology.

    PubMed

    Bhattacharya, Tamanash; Newton, Irene L G

    2017-10-27

    Wolbachia pipientis, the most common intracellular infection on the planet, infects 40% of insects as well as nematodes, isopods and arachnids. Wolbachia are obligately intracellular and challenging to study; there are no genetic tools for manipulating Wolbachia nor can they be cultured outside of host cells. Despite these roadblocks, the research community has defined a set of Wolbachia loci involved in host interaction: Wolbachia effectors. Through the use of Drosophila genetics, surrogate systems and biochemistry, the field has begun to define the toolkit Wolbachia use for host manipulation. Below we review recent findings identifying these Wolbachia effectors and point to potential, as yet uncharacterized, links between known phenotypes induced by Wolbachia infection and predicted effectors. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Plasmodium knowlesi: from severe zoonosis to animal model.

    PubMed

    Cox-Singh, Janet; Culleton, Richard

    2015-06-01

    Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The future of automotive lithium-ion battery recycling: Charting a sustainable course

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

    Gaines, Linda

    This paper looks ahead, beyond the projected large-scale market penetration of vehicles containing advanced batteries, to the time when the spent batteries will be ready for final disposition. It describes a working system for recycling, using lead–acid battery recycling as a model. Recycling of automotive lithium-ion (Li-ion) batteries is more complicated and not yet established because few end-of-life batteries will need recycling for another decade. There is thus the opportunity now to obviate some of the technical, economic, and institutional roadblocks that might arise. The paper considers what actions can be started now to avoid the impediments to recycling andmore » ensure that economical and sustainable options are available at the end of the batteries' useful life.« less

  19. Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

    PubMed Central

    Mokalled, Mayssa H.; Patra, Chinmoy; Dickson, Amy L.; Endo, Toyokazu; Stainier, Didier Y. R.; Poss, Kenneth D.

    2016-01-01

    Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a relatively unexplored process. Here, we performed a genome-wide profiling screen for secreted factors that are upregulated during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupt spinal cord repair, while transgenic ctgfa overexpression and local human CTGF recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration. PMID:27811277

  20. National Kidney Registry: 213 transplants in three years.

    PubMed

    Veale, Jeffrey; Hil, Garet

    2010-01-01

    Since its establishment in 2008, the National Kidney Registry has facilitated 213 kidney transplants between unrelated living donors and recipients at 28 transplant centers. Rapid innovations in matching strategies, advanced computer technologies, good communication and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 91% as a result of changes to the HLA typing requirements for potential donors and improved mechanisms to list unacceptable HLA antigens for sensitized patients. A uniform financial agreement among participating centers eliminated a major roadblock to facilitate unbalanced donor kidney exchanges among centers. The NKR transplanted 64% of the patients registered since 2008 and the average waiting time for those transplanted in 2010 was 11 months.

  1. Arsenic: a roadblock to potential animal waste management solutions.

    PubMed

    Nachman, Keeve E; Graham, Jay P; Price, Lance B; Silbergeld, Ellen K

    2005-09-01

    The localization and intensification of the poultry industry over the past 50 years have incidentally created a largely ignored environmental management crisis. As a result of these changes in poultry production, concentrated animal feeding operations (CAFOs) produce far more waste than can be managed by land disposal within the regions where it is produced. As a result, alternative waste management practices are currently being implemented, including incineration and pelletization of waste. However, organic arsenicals used in poultry feed are converted to inorganic arsenicals in poultry waste, limiting the feasibility of waste management alternatives. The presence of inorganic arsenic in incinerator ash and pelletized waste sold as fertilizer creates opportunities for population exposures that did not previously exist. The removal of arsenic from animal feed is a critical step toward safe poultry waste management.

  2. Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?

    PubMed Central

    Grimm, Dirk; Kay, Mark A.

    2007-01-01

    With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for a wide array of diseases. Numerous studies document RNAi efficacy in laboratory animals, and the first clinical trials are underway and thus far suggest that RNAi is safe to use in humans. Yet substantial hurdles have also surfaced and must be surmounted before therapeutic RNAi applications can become a standard therapy. Here we review the most critical roadblocks and concerns for clinical RNAi transition, delivery, and safety. We highlight emerging solutions and concurrently discuss novel therapeutic RNAi-based concepts. The current rapid advances create realistic optimism that the establishment of RNAi as a new and potent clinical modality in humans is near. PMID:18060021

  3. Electrical Guidance of Human Stem Cells in the Rat Brain.

    PubMed

    Feng, Jun-Feng; Liu, Jing; Zhang, Lei; Jiang, Ji-Yao; Russell, Michael; Lyeth, Bruce G; Nolta, Jan A; Zhao, Min

    2017-07-11

    Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Sheaffer, P.; Lemar, P.; Honton, E. J.

    The Universal Interconnection Technology (UIT) Workshop - sponsored by the U.S. Department of Energy, Distributed Energy and Electric Reliability (DEER) Program, and Distribution and Interconnection R&D - was held July 25-26, 2002, in Chicago, Ill., to: (1) Examine the need for a modular universal interconnection technology; (2) Identify UIT functional and technical requirements; (3) Assess the feasibility of and potential roadblocks to UIT; (4) Create an action plan for UIT development. These proceedings begin with an overview of the workshop. The body of the proceedings provides a series of industry representative-prepared papers on UIT functions and features, present interconnection technology,more » approaches to modularization and expandability, and technical issues in UIT development as well as detailed summaries of group discussions. Presentations, a list of participants, a copy of the agenda, and contact information are provided in the appendices of this document.« less

  5. Reconfigurable water-substrate based antennas with temperature control

    NASA Astrophysics Data System (ADS)

    Mobashsher, Ahmed Toaha; Abbosh, Amin

    2017-06-01

    We report an unexplored reconfigurable antenna development technique utilizing the concept of temperature variable electromagnetic properties of water. By applying this physical phenomena, we present highly efficient water-substrate based antennas whose operating frequencies can be continuously tuned. While taking the advantage of cost-effectiveness of liquid water, this dynamic tuning technique also alleviates the roadblocks to widespread use of reconfigurable liquid-based antennas for VHF and UHF bands. The dynamic reconfigurability is controlled merely via external thermal stimulus and does not require any physical change of the resonating structure. We demonstrate dynamic control of omnidirectional and directional antennas covering more than 14 and 12% fractional bandwidths accordingly, with more than 85% radiation efficiency. Our temperature control approach paves the intriguing way of exploring dynamic reconfigurability of water-based compact electromagnetic devices for non-static, in-motion and low-cost real-world applications.

  6. Data and monitoring needs for a more ecological agriculture

    NASA Astrophysics Data System (ADS)

    Zaks, David P. M.; Kucharik, Christopher J.

    2011-01-01

    Information on the life-cycle environmental impacts of agricultural production is often limited. As demands grow for increasing agricultural output while reducing its negative environmental impacts, both existing and novel data sources can be leveraged to provide more information to producers, consumers, scientists and policy makers. We review the components and organization of an agroecological sensor web that integrates remote sensing technologies and in situ sensors with models in order to provide decision makers with effective management options at useful spatial and temporal scales for making more informed decisions about agricultural productivity while reducing environmental burdens. Several components of the system are already in place, but by increasing the extent and accessibility of information, decision makers will have the opportunity to enhance food security and environmental quality. Potential roadblocks to implementation include farmer acceptance, data transparency and technology deployment.

  7. Beyond Reason: Eight Great Problems That Reveal the Limits of Science

    NASA Astrophysics Data System (ADS)

    Dewdney, A. K.

    2004-04-01

    A mind-bending excursion to the limits of science and mathematics Are some scientific problems insoluble? In Beyond Reason, internationally acclaimed math and science author A. K. Dewdney answers this question by examining eight insurmountable mathematical and scientific roadblocks that have stumped thinkers across the centuries, from ancient mathematical conundrums such as "squaring the circle," first attempted by the Pythagoreans, to G?del's vexing theorem, from perpetual motion to the upredictable behavior of chaotic systems such as the weather. A. K. Dewdney, PhD (Ontario, Canada), was the author of Scientific American's "Computer Recreations" column for eight years. He has written several critically acclaimed popular math and science books, including A Mathematical Mystery Tour (0-471-40734-8); Yes, We Have No Neutrons (0-471-29586-8); and 200% of Nothing (0-471-14574-2).

  8. Keys to Taking Your Nanotech Inventions to the Market

    NASA Astrophysics Data System (ADS)

    Rickert, Scott

    Although many scientists and engineers may wish to be an owner of something they invented, and then take that something to the market, there are many obstacles to do so. Many of these roadblocks are self-imposed, and many more are there because most of us are not aware of the very strict rules that exist in the world of marketing, selling, and manufacturing in the United States. This lecture will identify a small subset of these obstacles and discuss some ways to overcome them. Belief in your goals is most important, and this belief must be shared by others, or you cannot succeed. Believe it or not, no one wants to steal your ideas or inventions. They would much rather have you take it to market yourself. This really is a lecture about winning.

  9. Tailoring ZSM-5 Zeolites for the Fast Pyrolysis of Biomass to Aromatic Hydrocarbons.

    PubMed

    Hoff, Thomas C; Gardner, David W; Thilakaratne, Rajeeva; Wang, Kaige; Hansen, Thomas W; Brown, Robert C; Tessonnier, Jean-Philippe

    2016-06-22

    The production of aromatic hydrocarbons from cellulose by zeolite-catalyzed fast pyrolysis involves a complex reaction network sensitive to the zeolite structure, crystallinity, elemental composition, porosity, and acidity. The interplay of these parameters under the reaction conditions represents a major roadblock that has hampered significant improvement in catalyst design for over a decade. Here, we studied commercial and laboratory-synthesized ZSM-5 zeolites and combined data from 10 complementary characterization techniques in an attempt to identify parameters common to high-performance catalysts. Crystallinity and framework aluminum site accessibility were found to be critical to achieve high aromatic yields. These findings enabled us to synthesize a ZSM-5 catalyst with enhanced activity, which offers the highest aromatic hydrocarbon yield reported to date. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Forecasting techno-social systems: how physics and computing help to fight off global pandemics

    NASA Astrophysics Data System (ADS)

    Vespignani, Alessandro

    2010-03-01

    The crucial issue when planning for adequate public health interventions to mitigate the spread and impact of epidemics is risk evaluation and forecast. This amount to the anticipation of where, when and how strong the epidemic will strike. In the last decade advances in performance in computer technology, data acquisition, statistical physics and complex networks theory allow the generation of sophisticated simulations on supercomputer infrastructures to anticipate the spreading pattern of a pandemic. For the first time we are in the position of generating real time forecast of epidemic spreading. I will review the history of the current H1N1 pandemic, the major road-blocks the community has faced in its containment and mitigation and how physics and computing provide predictive tools that help us to battle epidemics.

  11. Overview of gene therapy clinical progress including cancer treatment with gene-modified T cells

    PubMed Central

    Brenner, Malcolm K.; Okur, Fatma V.

    2010-01-01

    It is now twenty years since the first legal gene transfer studies were approved, and there has been considerable disappointment in the slow rate of progress that followed the initial studies. Gradually, however, as the limitations of available vectors are acknowledged and overcome, and with advances in our understanding of the molecular and cell biology of genetic diseases and of cancer, unequivocal successes are now being reported. In this paper we describe the remaining major roadblocks to successful gene therapy and outline approaches to overcome them. We also illustrate how genetically modified immune system cells are already being used for the effective treatment of hematological and other malignancies, and how these approaches are being modified so that they can be effective in treating a broader range of malignancies. PMID:20008253

  12. When Medicine Meets Engineering—Paradigm Shifts in Diagnostics and Therapeutics

    PubMed Central

    Wang, Hann; Silva, Aleidy; Ho, Chih-Ming

    2013-01-01

    During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics. PMID:26835672

  13. Strategies and Innovative Approaches for the Future of Space Weather Forecasting

    NASA Astrophysics Data System (ADS)

    Hoeksema, J. T.

    2012-12-01

    The real and potential impacts of space weather have been well documented, yet neither the required research and operations programs, nor the data, modeling and analysis infrastructure necessary to develop and sustain a reliable space weather forecasting capability for a society are in place. The recently published decadal survey "Solar and Space Physics: A Science for a Technological Society" presents a vision for the coming decade and calls for a renewed national commitment to a comprehensive program in space weather and climatology. New resources are imperative. Particularly in the current fiscal environment, implementing a responsible strategy to address these needs will require broad participation across agencies and innovative approaches to make the most of existing resources, capitalize on current knowledge, span gaps in capabilities and observations, and focus resources on overcoming immediate roadblocks.

  14. 4D Bioprinting for Biomedical Applications.

    PubMed

    Gao, Bin; Yang, Qingzhen; Zhao, Xin; Jin, Guorui; Ma, Yufei; Xu, Feng

    2016-09-01

    3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Photo-activation of Single Molecule Magnet Behavior in a Manganese-based Complex

    NASA Astrophysics Data System (ADS)

    Fetoh, Ahmed; Cosquer, Goulven; Morimoto, Masakazu; Irie, Masahiro; El-Gammal, Ola; El-Reash, Gaber Abu; Breedlove, Brian K.; Yamashita, Masahiro

    2016-03-01

    A major roadblock to fully realizing molecular electronic devices is the ability to control the properties of each molecule in the device. Herein we report the control of the magnetic properties of single-molecule magnets (SMMs), which can be used in memory devices, by using a photo-isomerizable diarthylenthene ligand. Photo-isomerization of the diarylethene ligand bridging two manganese salen complexes with visible light caused a significant change in the SMM behavior due to opening of the six-membered ring of diarylethene ligand, accompanied by reorganization of the entire molecule. The ring-opening activated the frequency-dependent magnetization of the complex. Our results are a major step towards the realization of molecular memory devices composed of SMMs because the SMM behaviour can be turned on and off simply by irradiating the molecule.

  16. Will studies in individuals with systemic lupus erythematosus be the key to future HIV vaccine design?

    PubMed

    Bonsignori, Mattia

    2014-11-01

    The induction of HIV-1 broadly neutralizing antibodies (bnAbs) remains the primary goal of a preventive HIV-1 vaccine but no HIV-1 vaccine candidate has succeeded in inducing bnAbs. All the bnAbs isolated from chronically HIV-1 infected subjects display one or more traits associated with control by host tolerance and immunoregulatory mechanisms, including reactivity against self antigens. Recent studies on a HIV-1 patient with concurrent systemic lupus erythematosus have informed on how similar bnAbs are to typical autoantibodies controlled by immune tolerance mechanisms. Future studies aimed at elucidating the intersection between autoantibodies generated in the context of systemic lupus erythematosus and the development of HIV-1 bnAbs will further our knowledge of specific roadblocks that hamper the production of bnAbs and, ultimately, inform us on how to implement vaccine strategies to circumvent them.

  17. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.

    PubMed

    Bunker, Richard D; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J; Pentelute, Bradley L; Lott, J Shaun; Kent, Stephen B H; Baker, Edward N

    2015-04-07

    Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.

  18. Elucidating the power in empowerment and the participation in participatory action research: a story about research team and elementary school change.

    PubMed

    Dworski-Riggs, Deanne; Langhout, Regina Day

    2010-06-01

    Community psychologists are increasingly using Participatory Action Research (PAR) as a way to promote social justice by creating conditions that foster empowerment. Yet, little attention has been paid to the differences between the power structure that PAR advocates and the local community power structures. This paper seeks to evaluate the level of participation in a PAR project for multiple stakeholder groups, determine how PAR was adjusted to better fit community norms, and whether our research team was able to facilitate the emergence of PAR by adopting an approach that was relevant to the existing power relations. We conclude that power differences should not be seen as roadblocks to participation, but rather as moments of opportunity for the researchers to refine their methods and for the community and the community psychologist to challenge existing power structures.

  19. Congressional liaison task force - a briefing of the October 1994 meeting

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

    NONE

    1994-12-31

    As the US Senate overturned roadblocks attempting-unsuccessfully-to halt passage of the elementary and secondary education reauthorization legislation representatives from several federal agencies and laboratories addressed Congressional Liaison Task Force (CLTF) participants October 12th. They spoke about their commitment, programs, and accomplishments toward the nation`s science knowledge, particularly at the precollege level. Marjorie S. Steinberg legislative assistant to bill cosponsor Sen. Jeff Bingaman (DNM), and Gary Allen, Triangle Coalition director of Governmental affairs, spoke about education legislation and specifically about the Technology for Education Act that was on the Senate floor for a vote in October and now is law. Brucemore » A. Fuchs talked about the National Institute of Health`s (NIH) work in science literacy and education. The National Aeronautics and Space Administration`s (NASA) Frank C. Owens and Eddie Anderson contributed to this report.« less

  20. Roadblocks on the kill curve: Testing the Raup hypothesis

    USGS Publications Warehouse

    Poag, C.W.

    1997-01-01

    The documented presence of two large (~100-km diameter), possibly coeval impact craters of late Eocene age, requires modification of the impact-kill curve proposed by David M. Raup. Though the estimated meteorite size for each crater alone is large enough to have produced considerable global environmental stress, no horizons of mass mortality or pulsed extinction are known to be associated with either crater or their ejecta deposits. Thus, either there is no fixed relationship between extinction magnitude and crater diameter, or a meteorite that would produce a crater of >100-km diameter is required to raise extinction rates significantly above a ~5% background level. Both impacts took place ~1-2 m.y. before the "Terminal Eocene Event" ( =early Oligocene pulsed extinction). Their collective long-term environmental effects, however, may have either delayed that extinction pulse or produced threshold conditions necessary for it to take place.

  1. Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities.

    PubMed

    Dasari, Vijayendra; Bhatt, Kunal H; Smith, Corey; Khanna, Rajiv

    2017-04-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations. In this review, we discuss developmental strategies for prophylactic and therapeutic EBV vaccines which have been assessed in preclinical and clinical settings. Expert commentary: Major roadblocks in EBV vaccine development include no precise understanding of the clinical correlates of protection, uncertainty about adjuvant selection and the unavailability of appropriate animal models. Recent development of new EBV vaccine formulations provides exciting opportunities for the formal clinical assessment of novel formulations.

  2. Gene and Cell Therapy for β-Thalassemia and Sickle Cell Disease with Induced Pluripotent Stem Cells (iPSCs): The Next Frontier.

    PubMed

    Papapetrou, Eirini P

    2017-01-01

    In recent years, breakthroughs in human pluripotent stem cell (hPSC) research, namely cellular reprogramming and the emergence of sophisticated genetic engineering technologies, have opened new frontiers for cell and gene therapy. The prospect of using hPSCs, either autologous or histocompatible, as targets of genetic modification and their differentiated progeny as cell products for transplantation, presents a new paradigm of regenerative medicine of potential tremendous value for the treatment of blood disorders, including beta-thalassemia (BT) and sickle cell disease (SCD). Despite advances at a remarkable pace and great promise, many roadblocks remain before clinical translation can be realistically considered. Here we discuss the theoretical advantages of cell therapies utilizing hPSC derivatives, recent proof-of-principle studies and the main challenges towards realizing the potential of hPSC therapies in the clinic.

  3. Elucidating the Power in Empowerment and the Participation in Participatory Action Research: A Story About Research Team and Elementary School Change

    PubMed Central

    Dworski-Riggs, Deanne

    2010-01-01

    Community psychologists are increasingly using Participatory Action Research (PAR) as a way to promote social justice by creating conditions that foster empowerment. Yet, little attention has been paid to the differences between the power structure that PAR advocates and the local community power structures. This paper seeks to evaluate the level of participation in a PAR project for multiple stakeholder groups, determine how PAR was adjusted to better fit community norms, and whether our research team was able to facilitate the emergence of PAR by adopting an approach that was relevant to the existing power relations. We conclude that power differences should not be seen as roadblocks to participation, but rather as moments of opportunity for the researchers to refine their methods and for the community and the community psychologist to challenge existing power structures. PMID:20232244

  4. Overcoming the Roadblocks to Cardiac Cell Therapy Using Tissue Engineering.

    PubMed

    Yanamandala, Mounica; Zhu, Wuqiang; Garry, Daniel J; Kamp, Timothy J; Hare, Joshua M; Jun, Ho-Wook; Yoon, Young-Sup; Bursac, Nenad; Prabhu, Sumanth D; Dorn, Gerald W; Bolli, Roberto; Kitsis, Richard N; Zhang, Jianyi

    2017-08-08

    Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Life begins at 40

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

    Neal, L.

    1995-12-31

    A new rule makes nuclear power plant license renewal a viable option. A small group of corporate executives will soon face one of the toughest decisions of their careers-a decision that will affect 17 million American homes. Forty-five commercial nuclear power plants will reach the end of their operating licenses early in the next century. They represent billions of dollars in capital investment, and the companies that own them must decide whether to keep them on the grid or scrap them. But before a company decides whether to pull the plug on a big generating plant, it will have tomore » do some homework. Company executives will have to roll up their sleeves and dig deep into projections of electricity demand, assessments of generating options and cold, hard economics. At the same time, they must keep wary eyes on the political landscape, scanning ahead for roadblocks and quicksand.« less

  6. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

    PubMed

    Roybal, Kole T; Lim, Wendell A

    2017-04-26

    The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

  7. Creation of first malaria vaccine raises troubling questions about "intellectual racism". Interview by Kirsteen MacLeod.

    PubMed Central

    Patarroyo, M

    1995-01-01

    Some of the problems caused by malaria, which places a huge roadblock in front of economic progress in the Third World, may be solved by a new vaccine created by Dr. Manuel Patarroyo, a Columbian physician and researcher. "Imagine how things would be if Canadians had malaria," he says. "Episodes last 10 days, then there are 10 days of recovering. This leaves only 10 days each month in which to do some productive work. Then imagine killing the population of Toronto each year, and you can see the huge toll in terms of the number of yearly deaths globally from malaria." His discovery also raises the issue of "intellectual racism" because of criticism of Patarroyo's methods by Western scientists. Patarroyo, meanwhile, turned down a $60-million offer for his vaccine, and instead donated the patent to the World Health Organization. Images p1320-a PMID:7497394

  8. Towards a just, courageous, and honest resolution of the futility debate.

    PubMed

    Tong, R

    1995-04-01

    This essay discusses the history of the "futility debate" and the motives that sometimes prompt health care professionals, health care providers, patients, and surrogates to take different sides in it. Changes in the health care system, financial responsibility shifts, technical medical advances, and medical care rationing are analyzed as contributors to the futility debate. So too are variations in the definition of futility examined as part of the current controversy. The respective attitudes of professionals, providers, patients, and surrogates in accepting the goals, capabilities, and limits of medicine are also explored. In particular, the lack of honest communication between health care professionals/health care providers on the one hand and patients/surrogates on the other is acknowledged as a major roadblock in the building of care-focused futility policies. Finally, various initial attempts of hospitals to create futility guidelines are evaluated in order to detect problem areas and to suggest lines of improvement.

  9. Outcome Measures in Myasthenia Gravis: Incorporation Into Clinical Practice.

    PubMed

    Muppidi, Srikanth

    2017-03-01

    The development of validated assessment tools for evaluating disease status and response to interventions in patients with myasthenia gravis (MG) has been driven by clinical studies of emerging MG therapies. However, only a small proportion of MG-focused neurology practices have adopted these assessment tools for routine clinical use. This article reviews the suitability of 5 assessment instruments for incorporation into clinical practice, which should be driven by their ability to contribute to improved patient outcomes, and to be implemented within practice personnel and resource constraints. It is recommended that assessments based on both physician-evaluated and patient-reported outcomes be selected, to adequately evaluate both point-in-time symptom load and functional impact of MG symptoms over time. Provider resource allocation and reimbursement issues may be the most significant roadblocks to successful ongoing use of these tools; to that end, the addition of regular assessments to MG standards of care is recommended.

  10. A Neural Network Approach to Infer Optical Depth of Thick Ice Clouds at Night

    NASA Technical Reports Server (NTRS)

    Minnis, P.; Hong, G.; Sun-Mack, S.; Chen, Yan; Smith, W. L., Jr.

    2016-01-01

    One of the roadblocks to continuously monitoring cloud properties is the tendency of clouds to become optically black at cloud optical depths (COD) of 6 or less. This constraint dramatically reduces the quantitative information content at night. A recent study found that because of their diffuse nature, ice clouds remain optically gray, to some extent, up to COD of 100 at certain wavelengths. Taking advantage of this weak dependency and the availability of COD retrievals from CloudSat, an artificial neural network algorithm was developed to estimate COD values up to 70 from common satellite imager infrared channels. The method was trained using matched 2007 CloudSat and Aqua MODIS data and is tested using similar data from 2008. The results show a significant improvement over the use of default values at night with high correlation. This paper summarizes the results and suggests paths for future improvement.

  11. Real-Time Measurement of Nanotube Resonator Fluctuations in an Electron Microscope

    PubMed Central

    2017-01-01

    Mechanical resonators based on low-dimensional materials provide a unique platform for exploring a broad range of physical phenomena. The mechanical vibrational states are indeed extremely sensitive to charges, spins, photons, and adsorbed masses. However, the roadblock is often the readout of the resonator, because the detection of the vibrational states becomes increasingly difficult for smaller resonators. Here, we report an unprecedentedly sensitive method to detect nanotube resonators with effective masses in the 10–20 kg range. We use the beam of an electron microscope to resolve the mechanical fluctuations of a nanotube in real-time for the first time. We obtain full access to the thermally driven Brownian motion of the resonator, both in space and time domains. Our results establish the viability of carbon nanotube resonator technology at room temperature and pave the way toward the observation of novel thermodynamics regimes and quantum effects in nanomechanics. PMID:28186773

  12. Constellation Stretch Goals: Review of Industry Inputs

    NASA Technical Reports Server (NTRS)

    Lang, John

    2006-01-01

    Many good ideas received based on industry experience: a) Shuttle operations; b) Commercial aircraft production; c) NASA's historical way of doing business; d) Military and commercial programs. Aerospace performed preliminary analysis: a) Potential savings; b) Cost of implementation; c) Performance or other impact/penalties; d) Roadblocks; e) Unintended consequences; f) Bottom line. Significant work ahead for a "Stretch Goal"to become a good, documented requirement: 1) As a group, the relative "value" of goals are uneven; 2) Focused analysis on each goal is required: a) Need to ensure that a new requirement produces the desired consequence; b) It is not certain that some goals will not create problems elsewhere. 3) Individual implementation path needs to be studied: a) Best place to insert requirement (what level, which document); b) Appropriate wording for the requirement. Many goals reflect "best practices" based on lessons learned and may have value beyond near-term CxP requirements process.

  13. Negotiating roadblocks to IDS-physician equity joint ventures.

    PubMed

    Dubow, S F; Benoff, M

    1998-09-01

    Integrated delivery systems (IDSs) may find that forming an equity joint venture relationship with a physician group practice is the best way to integrate physicians into their networks. IDSs have a choice between two basic equity structures: affiliated group practice, in which a management services organization (MSO) handles all practice management infrastructure and the physician group is a physician-only organization; and integrated group practice, in which the physician group encompasses both the physician practice and the administrative infrastructure. The choice of equity structure and how it should be implemented hinge on several legal issues, including the existence of a corporate-practice-of-medicine statute in the IDS's state, compliance with the Federal antikickback statute and Stark laws, and various issues regarding the IDS's tax-exempt status. IDSs also should consider pragmatic issues, particularly those associated with aligning the economic incentives of the two partners.

  14. Bidirectional helical motility of cytoplasmic dynein around microtubules

    PubMed Central

    Can, Sinan; Dewitt, Mark A; Yildiz, Ahmet

    2014-01-01

    Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo transport along microtubules (MTs). Dynein motility has previously been studied on surface-immobilized MTs in vitro, which constrains the motors to move in two dimensions. In this study, we explored dynein motility in three dimensions using an MT bridge assay. We found that dynein moves in a helical trajectory around the MT, demonstrating that it generates torque during cargo transport. Unlike other cytoskeletal motors that produce torque in a specific direction, dynein generates torque in either direction, resulting in bidirectional helical motility. Dynein has a net preference to move along a right-handed helical path, suggesting that the heads tend to bind to the closest tubulin binding site in the forward direction when taking sideways steps. This bidirectional helical motility may allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo transport. DOI: http://dx.doi.org/10.7554/eLife.03205.001 PMID:25069614

  15. Working Group Reports and Presentations: Virtual Worlds and Virtual Exploration

    NASA Technical Reports Server (NTRS)

    LAmoreaux, Claudia

    2006-01-01

    Scientists and engineers are continually developing innovative methods to capitalize on recent developments in computational power. Virtual worlds and virtual exploration present a new toolset for project design, implementation, and resolution. Replication of the physical world in the virtual domain provides stimulating displays to augment current data analysis techniques and to encourage public participation. In addition, the virtual domain provides stakeholders with a low cost, low risk design and test environment. The following document defines a virtual world and virtual exploration, categorizes the chief motivations for virtual exploration, elaborates upon specific objectives, identifies roadblocks and enablers for realizing the benefits, and highlights the more immediate areas of implementation (i.e. the action items). While the document attempts a comprehensive evaluation of virtual worlds and virtual exploration, the innovative nature of the opportunities presented precludes completeness. The authors strongly encourage readers to derive additional means of utilizing the virtual exploration toolset.

  16. Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

    PubMed Central

    Molina, Douglas M.; Finney, Olivia C.; Arevalo-Herrera, Myriam; Herrera, Socrates; Felgner, Philip L.; Gardner, Malcolm J.; Liang, Xiaowu; Wang, Ruobing

    2012-01-01

    The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria. PMID:22826492

  17. Experimental quantum compressed sensing for a seven-qubit system

    PubMed Central

    Riofrío, C. A.; Gross, D.; Flammia, S. T.; Monz, T.; Nigg, D.; Blatt, R.; Eisert, J.

    2017-01-01

    Well-controlled quantum devices with their increasing system size face a new roadblock hindering further development of quantum technologies. The effort of quantum tomography—the reconstruction of states and processes of a quantum device—scales unfavourably: state-of-the-art systems can no longer be characterized. Quantum compressed sensing mitigates this problem by reconstructing states from incomplete data. Here we present an experimental implementation of compressed tomography of a seven-qubit system—a topological colour code prepared in a trapped ion architecture. We are in the highly incomplete—127 Pauli basis measurement settings—and highly noisy—100 repetitions each—regime. Originally, compressed sensing was advocated for states with few non-zero eigenvalues. We argue that low-rank estimates are appropriate in general since statistical noise enables reliable reconstruction of only the leading eigenvectors. The remaining eigenvectors behave consistently with a random-matrix model that carries no information about the true state. PMID:28513587

  18. Barriers and paths to market for genetically engineered crops.

    PubMed

    Rommens, Caius M

    2010-02-01

    Each year, billions of dollars are invested in efforts to improve crops through genetic engineering (GE). These activities have resulted in a surge of publications and patents on technologies and genes: a momentum in basic research that, unfortunately, is not sustained throughout the subsequent phases of product development. After more than two decades of intensive research, the market for transgenic crops is still dominated by applications of just a handful of methods and genes. This discrepancy between research and development reflects difficulties in understanding and overcoming seven main barriers-to-entry: (1) trait efficacy in the field, (2) critical product concepts, (3) freedom-to-operate, (4) industry support, (5) identity preservation and stewardship, (6) regulatory approval and (7) retail and consumer acceptance. In this review, I describe the various roadblocks to market for transgenic crops and also discuss methods and approaches on how to overcome these, especially in the United States.

  19. Interrogation of bimetallic particle oxidation in three dimensions at the nanoscale

    PubMed Central

    Han, Lili; Meng, Qingping; Wang, Deli; Zhu, Yimei; Wang, Jie; Du, Xiwen; Stach, Eric A.; Xin, Huolin L.

    2016-01-01

    An understanding of bimetallic alloy oxidation is key to the design of hollow-structured binary oxides and the optimization of their catalytic performance. However, one roadblock encountered in studying these binary oxide systems is the difficulty in describing the heterogeneities that occur in both structure and chemistry as a function of reaction coordinate. This is due to the complexity of the three-dimensional mosaic patterns that occur in these heterogeneous binary systems. By combining real-time imaging and chemical-sensitive electron tomography, we show that it is possible to characterize these systems with simultaneous nanoscale and chemical detail. We find that there is oxidation-induced chemical segregation occurring on both external and internal surfaces. Additionally, there is another layer of complexity that occurs during the oxidation, namely that the morphology of the initial oxide surface can change the oxidation modality. This work characterizes the pathways that can control the morphology in binary oxide materials. PMID:27928998

  20. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

    PubMed Central

    Roybal, Kole T.; Lim, Wendell A.

    2017-01-01

    The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases. PMID:28446063

  1. Prediction of High-Lift Flows using Turbulent Closure Models

    NASA Technical Reports Server (NTRS)

    Rumsey, Christopher L.; Gatski, Thomas B.; Ying, Susan X.; Bertelrud, Arild

    1997-01-01

    The flow over two different multi-element airfoil configurations is computed using linear eddy viscosity turbulence models and a nonlinear explicit algebraic stress model. A subset of recently-measured transition locations using hot film on a McDonnell Douglas configuration is presented, and the effect of transition location on the computed solutions is explored. Deficiencies in wake profile computations are found to be attributable in large part to poor boundary layer prediction on the generating element, and not necessarily inadequate turbulence modeling in the wake. Using measured transition locations for the main element improves the prediction of its boundary layer thickness, skin friction, and wake profile shape. However, using measured transition locations on the slat still yields poor slat wake predictions. The computation of the slat flow field represents a key roadblock to successful predictions of multi-element flows. In general, the nonlinear explicit algebraic stress turbulence model gives very similar results to the linear eddy viscosity models.

  2. Characterization of the Hispanic or Latino Population in Health Research: A Systematic Review

    PubMed Central

    Hayes, Susan L.; Chen, Mei Hsuan; González, Javier; Gany, Francesca M.

    2015-01-01

    The size and diversity of the Hispanic population in the United States has dramatically increased, with vast implications for health research. We conducted a systematic review of the characterization of the Hispanic population in health research and described its implications. Relevant studies were identified by searches of PubMed, Embase Scopus, and Science/Social Sciences Citation Index from 2000 to 2011. 131 articles met criteria. 56 % of the articles reported only “Hispanic” or “Latino” as the characteristic of the Hispanic research population while no other characteristics were reported. 29 % of the articles reported language, 27 % detailed country of origin and 2 % provided the breakdown of race. There is great inconsistency in reported characteristics of Hispanics in health research. The lack of detailed characterization of this population ultimately creates roadblocks in translating evidence into practice when providing care to the large and increasingly diverse Hispanic population in the US. PMID:23315046

  3. Ideological roadblocks to humanizing dentistry, an evaluative case study of a continuing education course on social determinants of health.

    PubMed

    Lévesque, Martine C; Levine, Alissa; Bedos, Christophe

    2015-04-30

    Front line providers of care are frequently lacking in knowledge on and sensitivity to social and structural determinants of underprivileged patients' health. Developing and evaluating approaches to raising health professional awareness and capacity to respond to social determinants is a crucial step in addressing this issue. McGill University, in partnership with Université de Montréal, Québec dental regulatory authorities, and the Québec anti-poverty coalition, co-developed a continuing education (CE) intervention that aims to transfer knowledge and improve the practices of oral health professionals with people living on welfare. Through the use of original educational tools integrating patient narratives and a short film, the onsite course aims to elicit affective learning and critical reflection on practices, as well as provide staff coaching. A qualitative case study was conducted, in Montreal Canada, among members of a dental team who participated in this innovative CE course over a period of four months. Data collection consisted in a series of semi-structured individual interviews conducted with 15 members of the dental team throughout the training, digitally recorded group discussions linked to the CE activities, clinic administrative documents and researcher-trainer field notes and journal. In line with adult transformative learning theory, interpretive analysis aimed to reveal learning processes, perceived outcomes and collective perspectives that constrain individual and organizational change. The findings presented in this article consist in four interactive themes, reflective of clinic culture and context, that act as barriers to humanizing patient care: 1) belief in the "ineluctable" commoditization of dentistry; 2) "equal treatment", a belief constraining concern for equity and the recognition of discriminatory practices; 3) a predominantly biomedical orientation to care; and 4) stereotypical categorization of publically insured patients into "deserving" vs. "non-deserving" poor. We discuss implications for oral health policy, orientations for dental education, as well as the role dental regulatory authorities should play in addressing discrimination and prejudice. Humanizing care and developing oral health practitioners' capacity to respond to social determinants of health, are challenged by significant ideological roadblocks. These require multi-level and multi-sectorial action if gains in social equity in oral health are to be made.

  4. Abscisic acid perception and signaling: structural mechanisms and applications

    PubMed Central

    Ng, Ley Moy; Melcher, Karsten; Teh, Bin Tean; Xu, H Eric

    2014-01-01

    Adverse environmental conditions are a threat to agricultural yield and therefore exert a global effect on livelihood, health and the economy. Abscisic acid (ABA) is a vital plant hormone that regulates abiotic stress tolerance, thereby allowing plants to cope with environmental stresses. Previously, attempts to develop a complete understanding of the mechanisms underlying ABA signaling have been hindered by difficulties in the identification of bona fide ABA receptors. The discovery of the PYR/PYL/RCAR family of ABA receptors therefore represented a major milestone in the effort to overcome these roadblocks; since then, many structural and functional studies have provided detailed insights into processes ranging from ABA perception to the activation of ABA-responsive gene transcription. This understanding of the mechanisms of ABA perception and signaling has served as the basis for recent, preliminary developments in the genetic engineering of stress-resistant crops as well as in the design of new synthetic ABA agonists, which hold great promise for the agricultural enhancement of stress tolerance. PMID:24786231

  5. High-resolution Myogenic Lineage Mapping by Single-Cell Mass Cytometry

    PubMed Central

    Porpiglia, Ermelinda; Samusik, Nikolay; Ho, Andrew Tri Van; Cosgrove, Benjamin D.; Mai, Thach; Davis, Kara L.; Jager, Astraea; Nolan, Garry P.; Bendall, Sean C.; Fantl, Wendy J.; Blau, Helen M.

    2017-01-01

    Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progenitor populations that precede differentiation. We discovered two cell surface markers, CD9 and CD104, whose combined expression enabled in vivo identification and prospective isolation of stem and progenitor cells. Data analysis using the X-shift algorithm paired with single-cell force directed layout visualization, defined a molecular signature of the activated stem cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during recovery from acute muscle injury. Our studies uncover the dynamics of skeletal muscle regeneration in vivo and pave the way for the elucidation of the regulatory networks that underlie cell-state transitions in muscle diseases and aging. PMID:28414312

  6. Scaling, Similarity, and the Fourth Paradigm for Hydrology

    NASA Technical Reports Server (NTRS)

    Peters-Lidard, Christa D.; Clark, Martyn; Samaniego, Luis; Verhoest, Niko E. C.; van Emmerik, Tim; Uijlenhoet, Remko; Achieng, Kevin; Franz, Trenton E.; Woods, Ross

    2017-01-01

    In this synthesis paper addressing hydrologic scaling and similarity, we posit that roadblocks in the search for universal laws of hydrology are hindered by our focus on computational simulation (the third paradigm), and assert that it is time for hydrology to embrace a fourth paradigm of data-intensive science. Advances in information-based hydrologic science, coupled with an explosion of hydrologic data and advances in parameter estimation and modelling, have laid the foundation for a data-driven framework for scrutinizing hydrological scaling and similarity hypotheses. We summarize important scaling and similarity concepts (hypotheses) that require testing, describe a mutual information framework for testing these hypotheses, describe boundary condition, state flux, and parameter data requirements across scales to support testing these hypotheses, and discuss some challenges to overcome while pursuing the fourth hydrological paradigm. We call upon the hydrologic sciences community to develop a focused effort towards adopting the fourth paradigm and apply this to outstanding challenges in scaling and similarity.

  7. Chemistry and students with blindness: The hurdles are not what you think

    NASA Astrophysics Data System (ADS)

    Lewis, Amy L. Micklos

    Statistics have shown that individuals with disabilities are underrepresented in the science, technology, engineering, and mathematics (STEM) fields. This work focused on exploring how three students with blindness enrolled in a full-inclusion high-school chemistry class experienced and conceptualized content in order to inform educators, curriculum designers, textbook manufacturers, researchers, and individuals with vision impairments about roadblocks that can inhibit student learning. A critical theory lens was used to explore how the student participants discussed experiences, models, and visualizations (Talanquer, 2010) during six semi-structured interviews. The findings of the study suggest that students with blindness focus on direct experiences when formulating macroscopic descriptions of matter; they form alternative models of the atom and develop incomplete understandings of symbolic representations. Students with blindness also had inhibited learning experiences based on what tactile materials, tools, and vocabulary are available to them. Finally, access to scientific information requires proper organization otherwise meaning cannot be made from the common tables, graphs, or representations.

  8. Dissemination of psychosocial treatments for anxiety: the importance of taking a broad perspective.

    PubMed

    Taylor, Steven; Abramowitz, Jonathan S

    2013-12-01

    Dissemination methods are used to increase the likelihood that a given treatment or form of clinical practice is implemented by clinicians in the community. Therapist training in treatment methods is an important component of dissemination. Successful dissemination also requires that roadblocks to treatment implementation are identified and circumvented, such as misconceptions that clinicians might hold about a given treatment. The present article offers a commentary on the papers included in the special issue on treatment dissemination for anxiety disorders. Most papers focus on issues concerning the training and education of clinicians with regard to exposure therapy. Training and education is an important step but should be part of a broad, multifaceted approach. There are several other important methods of treatment dissemination, including methods developed and implemented with success by the pharmaceutical industry, might also be used to disseminate psychosocial therapies. Optimal dissemination likely requires a broad perspective in which multiple dissemination methods are considered for implementation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Probiotics and prebiotics: prospects for public health and nutritional recommendations.

    PubMed

    Sanders, Mary Ellen; Lenoir-Wijnkoop, Irene; Salminen, Seppo; Merenstein, Daniel J; Gibson, Glenn R; Petschow, Bryon W; Nieuwdorp, Max; Tancredi, Daniel J; Cifelli, Christopher J; Jacques, Paul; Pot, Bruno

    2014-02-01

    Probiotics and prebiotics are useful interventions for improving human health through direct or indirect effects on the colonizing microbiota. However, translation of these research findings into nutritional recommendations and public health policy endorsements has not been achieved in a manner consistent with the strength of the evidence. More progress has been made with clinical recommendations. Conclusions include that beneficial cultures, including probiotics and live cultures in fermented foods, can contribute towards the health of the general population; prebiotics, in part due to their function as a special type of soluble fiber, can contribute to the health of the general population; and a number of challenges must be addressed in order to fully realize probiotic and prebiotic benefits, including the need for greater awareness of the accumulated evidence on probiotics and prebiotics among policy makers, strategies to cope with regulatory roadblocks to research, and high-quality human trials that address outstanding research questions in the field. © 2014 New York Academy of Sciences.

  10. The Advanced Labs Website: resources for upper-level laboratories

    NASA Astrophysics Data System (ADS)

    Torres-Isea, Ramon

    2012-03-01

    The Advanced Labs web resource collection is an effort to create a central, comprehensive information base for college/university faculty who teach upper-level undergraduate laboratories. The website is produced by the American Association of Physics Teachers (AAPT). It is a part of ComPADRE, the online collection of resources in physics and astronomy education, which itself is a part of the National Science Foundation-funded National Science Digital Library (NSDL). After a brief review of its history, we will discuss the current status of the website while describing the various types of resources available at the site and presenting examples of each. We will detail a step-by-step procedure for submitting resources to the website. The resource collection is designed to be a community effort and thus welcomes input and contributions from its users. We will also present plans, and will seek audience feedback, for additional website services and features. The constraints, roadblocks, and rewards of this project will also be addressed.

  11. Stabilization of weak ferromagnetism by strong magnetic response to epitaxial strain in multiferroic BiFeO 3

    DOE PAGES

    Cooper, Valentino R.; Lee, Jun Hee; Krogel, Jaron T.; ...

    2015-08-06

    Multiferroic BiFeO 3 exhibits excellent magnetoelectric coupling critical for magnetic information processing with minimal power consumption. Thus, the degenerate nature of the easy spin axis in the (111) plane presents roadblocks for real world applications. Here, we explore the stabilization and switchability of the weak ferromagnetic moments under applied epitaxial strain using a combination of first-principles calculations and group-theoretic analyses. We demonstrate that the antiferromagnetic moment vector can be stabilized along unique crystallographic directions ([110] and [-110]) under compressive and tensile strains. A direct coupling between the anisotropic antiferrodistortive rotations and Dzyaloshinskii-Moria interactions drives the stabilization of weak ferromagnetism. Furthermore,more » energetically competing C- and G-type magnetic orderings are observed at high compressive strains, suggesting that it may be possible to switch the weak ferromagnetism on and off under application of strain. These findings emphasize the importance of strain and antiferrodistortive rotations as routes to enhancing induced weak ferromagnetism in multiferroic oxides.« less

  12. Education and personalized genomics: deciphering the public's genetic health report

    PubMed Central

    Lamb, Neil E; Myers, Richard M; Gunter, Chris

    2010-01-01

    Where do members of the public turn to understand what genetic tests mean in terms of their own health? Now that genome-wide association studies and complete genome sequencing are widely available, the importance of education in personalized genomics cannot be overstated. Although some media have introduced the concept of genetic testing to better understand health and disease, the public's understanding of the scope and impact of genetic variation has not kept up with the pace of the science or technology. Unfortunately, the likely sources to which the public turn to for guidance – their physician and the media – are often no better prepared. We examine several venues for information, including print and online guides for both lay and health-oriented audiences, and summarize selected resources in multiple formats. We also note on the roadblocks to progress and discuss ways to remove them, as urgent action is needed to connect people with their genomes in a meaningful way. PMID:20161675

  13. Examining hydrogen transitions.

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

    Plotkin, S. E.; Energy Systems

    2007-03-01

    This report describes the results of an effort to identify key analytic issues associated with modeling a transition to hydrogen as a fuel for light duty vehicles, and using insights gained from this effort to suggest ways to improve ongoing modeling efforts. The study reported on here examined multiple hydrogen scenarios reported in the literature, identified modeling issues associated with those scenario analyses, and examined three DOE-sponsored hydrogen transition models in the context of those modeling issues. The three hydrogen transition models are HyTrans (contractor: Oak Ridge National Laboratory), MARKAL/DOE* (Brookhaven National Laboratory), and NEMS-H2 (OnLocation, Inc). The goals ofmore » these models are (1) to help DOE improve its R&D effort by identifying key technology and other roadblocks to a transition and testing its technical program goals to determine whether they are likely to lead to the market success of hydrogen technologies, (2) to evaluate alternative policies to promote a transition, and (3) to estimate the costs and benefits of alternative pathways to hydrogen development.« less

  14. The need for separate operational and engineering user interfaces for command and control of airborne synthetic aperture radar systems

    NASA Astrophysics Data System (ADS)

    Klein, Laura M.; McNamara, Laura A.

    2017-05-01

    In this paper, we address the needed components to create usable engineering and operational user interfaces (UIs) for airborne Synthetic Aperture Radar (SAR) systems. As airborne SAR technology gains wider acceptance in the remote sensing and Intelligence, Surveillance, and Reconnaissance (ISR) communities, the need for effective and appropriate UIs to command and control these sensors has also increased. However, despite the growing demand for SAR in operational environments, the technology still faces an adoption roadblock, in large part due to the lack of effective UIs. It is common to find operational interfaces that have barely grown beyond the disparate tools engineers and technologists developed to demonstrate an initial concept or system. While sensor usability and utility are common requirements to engineers and operators, their objectives for interacting with the sensor are different. As such, the amount and type of information presented ought to be tailored to the specific application.

  15. A Tale of Two Small Business Grants: The Best of Times, the Worst of Times from the NASA Ames Small Business Innovative Research (SBIR) Program

    NASA Technical Reports Server (NTRS)

    Kojiro, Daniel R.; Lee, Geoffrey S.

    2006-01-01

    The purposes of the SBIR Program are to: stimulate technological innovation in the private sector; strengthen the role of Small Business Concerns (SBCs) in meeting Federal research and development needs; increase the commercial application of these research results; and encourage participation of socially and economically disadvantaged persons and women-owned small businesses. The process can be highly rewarding, providing the small business with resources to pursue research and development with a focus on providing NASA with new and advanced capabilities. We present two examples of how the NASA Ames SBIR Program has addressed these purposes, nurturing innovative ideas from small, businesses into commercially viable products that also address analytical needs in space research. These examples, from the Science Instruments for Conducting Solar System Exploration Subtopic, describe the journey from innovative concept to analytical instrument, one successful and one hampered by numerous roadblocks (including some international intrigue}.

  16. A Key concept in Magnesium Secondary Battery Electrolytes.

    PubMed

    Bertasi, Federico; Hettige, Chaminda; Sepehr, Fatemeh; Bogle, Xavier; Pagot, Gioele; Vezzù, Keti; Negro, Enrico; Paddison, Stephen J; Greenbaum, Steve G; Vittadello, Michele; Di Noto, Vito

    2015-09-21

    A critical roadblock toward practical Mg-based energy storage technologies is the lack of reversible electrolytes that are safe and electrochemically stable. Here, we report on high-performance electrolytes based on 1-ethyl-3-methylimidazolium chloride (EMImCl) doped with AlCl3 and highly amorphous δ-MgCl2 . The phase diagram of the electrolytes reveals the presence of four thermal transitions that strongly depend on salt content. High-level density functional theory (DFT)-based electronic structure calculations substantiate the structural and vibrational assignment of the coordination complexes. A 3D chloride-concatenated dynamic network model accounts for the outstanding redox behaviour and the electric and magnetic properties, providing insight into the conduction mechanism of the electrolytes. Mg anode cells assembled using the electrolytes were cyclically discharged at a high rate (35 mA g(-1) ), exhibiting an initial capacity of 80 mA h g(-1) and a steady-state voltage of 2.3 V. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Virus-Like Particle, Liposome, and Polymeric Particle-Based Vaccines against HIV-1

    PubMed Central

    Gao, Yong; Wijewardhana, Chanuka; Mann, Jamie F. S.

    2018-01-01

    It is acknowledged that vaccines remain the best hope for eliminating the HIV-1 epidemic. However, the failure to produce effective vaccine immunogens and the inability of conventional delivery strategies to elicit the desired immune responses remains a central theme and has ultimately led to a significant roadblock in HIV vaccine development. Consequently, significant efforts have been applied to generate novel vaccine antigens and delivery agents, which mimic viral structures for optimal immune induction. Here, we review the latest developments that have occurred in the nanoparticle vaccine field, with special emphasis on strategies that are being utilized to attain highly immunogenic, systemic, and mucosal anti-HIV humoral and cellular immune responses. This includes the design of novel immunogens, the central role of antigen-presenting cells, delivery routes, and biodistribution of nanoparticles to lymph nodes. In particular, we will focus on virus-like-particle formulations and their preclinical uses within the HIV prophylactic vaccine setting. PMID:29541072

  18. CRISPR-UMI: single-cell lineage tracing of pooled CRISPR-Cas9 screens.

    PubMed

    Michlits, Georg; Hubmann, Maria; Wu, Szu-Hsien; Vainorius, Gintautas; Budusan, Elena; Zhuk, Sergei; Burkard, Thomas R; Novatchkova, Maria; Aichinger, Martin; Lu, Yiqing; Reece-Hoyes, John; Nitsch, Roberto; Schramek, Daniel; Hoepfner, Dominic; Elling, Ulrich

    2017-12-01

    Pooled CRISPR screens are a powerful tool for assessments of gene function. However, conventional analysis is based exclusively on the relative abundance of integrated single guide RNAs (sgRNAs) between populations, which does not discern distinct phenotypes and editing outcomes generated by identical sgRNAs. Here we present CRISPR-UMI, a single-cell lineage-tracing methodology for pooled screening to account for cell heterogeneity. We generated complex sgRNA libraries with unique molecular identifiers (UMIs) that allowed for screening of clonally expanded, individually tagged cells. A proof-of-principle CRISPR-UMI negative-selection screen provided increased sensitivity and robustness compared with conventional analysis by accounting for underlying cellular and editing-outcome heterogeneity and detection of outlier clones. Furthermore, a CRISPR-UMI positive-selection screen uncovered new roadblocks in reprogramming mouse embryonic fibroblasts as pluripotent stem cells, distinguishing reprogramming frequency and speed (i.e., effect size and probability). CRISPR-UMI boosts the predictive power, sensitivity, and information content of pooled CRISPR screens.

  19. Jet and flash imprint defectivity: assessment and reduction for semiconductor applications

    NASA Astrophysics Data System (ADS)

    Malloy, Matt; Litt, Lloyd C.; Johnson, Steve; Resnick, Douglas J.; Lovell, David

    2011-04-01

    Defectivity has been historically identified as a leading technical roadblock to the implementation of nanoimprint lithography for semiconductor high volume manufacturing. The lack of confidence in nanoimprint's ability to meet defect requirements originates in part from the industry's past experiences with 1X lithography and the shortage in end-user generated defect data. SEMATECH has therefore initiated a defect assessment aimed at addressing these concerns. The goal is to determine whether nanoimprint, specifically Jet and Flash Imprint Lithography from Molecular Imprints, is capable of meeting semiconductor industry defect requirements. At this time, several cycles of learning have been completed in SEMATECH's defect assessment, with promising results. J-FIL process random defectivity of < 0.1 def/cm2 has been demonstrated using a 120nm half-pitch template, providing proof of concept that a low defect nanoimprint process is possible. Template defectivity has also improved significantly as shown by a pre-production grade template at 80nm pitch. Cycles of learning continue on feature sizes down to 22nm.

  20. "It's like pay or don't have it and now I'm doing without": the voice of transitional uninsured former foster youth.

    PubMed

    Kruszka, Bonnie J; Lindell, Deborah; Killion, Cheryl; Criss, Sam

    2012-02-01

    Twenty-four thousand American youth lose Medicaid entitlements after discharge from foster care annually. The circumstance of being uninsured is a formidable barrier to health care that leaves the youth vulnerable to unmet health care needs. Given that foster youth often develop physical and/or mental health problems as a result of abuse or neglect, continuous access to health care is especially important. This descriptive phenomenology study explores the lived experience of transitional uninsured former foster youth. Nine uninsured former foster youth were recruited from a nonprofit community organization in an urban county and interviewed using semistructured interviews. Four themes identified from the analysis were (a) "Surviving the real world": emancipation without essential documentation; (b) "It's not always going to be fine": managing mental and physical health without health care insurance; (c) "Roadblocks": barriers to securing health care insurance; and (d) "Just not knowing": Medicaid eligible albeit without health care insurance.

  1. Proceedings of the 2004 NASA/ONR Circulation Control Workshop, Part 1

    NASA Technical Reports Server (NTRS)

    Jones, Gregory S. (Editor); Joslin, Ronald D. (Editor)

    2005-01-01

    As technological advances influence the efficiency and effectiveness of aerodynamic and hydrodynamic applications, designs and operations, this workshop was intended to address the technologies, systems, challenges and successes specific to Coanda driven circulation control in aerodynamics and hydrodynamics. A major goal of this workshop was to determine the 2004 state-of-the-art in circulation control and understand the roadblocks to its application. The workshop addressed applications, CFD, and experiments related to circulation control, emphasizing fundamental physics, systems analysis, and applied research. The workshop consisted of 34 single session oral presentations and written papers that focused on Naval hydrodynamic vehicles (e.g. submarines), Fixed Wing Aviation, V/STOL platforms, propulsion systems (including wind turbine systems), ground vehicles (automotive and trucks) and miscellaneous applications (e.g., poultry exhaust systems and vacuum systems). Several advanced CFD codes were benchmarked using a two-dimensional NCCR circulation control airfoil. The CFD efforts highlighted inconsistencies in turbulence modeling, separation and performance predictions.

  2. Crystal Facets Make a Profound Difference in Polyoxometalate-Containing Metal-Organic Frameworks as Catalysts for Biodiesel Production.

    PubMed

    Liu, Yiwei; Liu, Shumei; He, Danfeng; Li, Ning; Ji, Yujuan; Zheng, Zhiping; Luo, Fang; Liu, Shuxia; Shi, Zhan; Hu, Changwen

    2015-10-07

    An inherent challenge in using metal-organic frameworks (MOFs) for catalysis is how to access the catalytic sites generally confined inside the porous structure, in particular for substrates larger than the pores. We present here a promising solution to bypass this roadblock by modulating the facets of a crystalline MOF NENU-3a to enhance the facet exposure of the catalytic sites and the adsorption of substrates. Specifically, by transforming it with encapsulated catalysis-responsible polyoxometalate from octahedron characterized entirely by {111} facets to cube with only {100} facets, much enhanced catalytic activities were observed, especially for sterically demanding substrates that are otherwise hard to diffuse into the pores. Crystallographic analysis and adsorption/desorption experiments collectively established the critical effects of morphological control on the enhanced catalysis. The cubic crystals were then applied for biodiesel production, reaching more than 90% conversion of fatty acids (C12-C22) in comparison to <22% using octahedral crystals.

  3. Compatibility of a Conventional Non-aqueous Magnesium Electrolyte with a High Voltage V 2O 5 Cathode and Mg Anode

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

    Sa, Niya; Proffit, Danielle L.; Lipson, Albert L.

    2015-08-01

    A major roadblock for magnesium ion battery development is the availability of an electrolyte that can deposit Mg reversibly and at the same time is compatible with a high voltage cathode. We report a prospective full magnesium cell utilizing a simple, non-aqueous electrolyte composed of high concentration magnesium bis(trifluoromethane sulfonyl)imide in diglyme, which is compatible with a high voltage vanadium pentoxide (V 2O 5) cathode and a Mg metal anode. For this system, plating and stripping of Mg metal can be achieved with magnesium bis(trifluoromethane sulfonyl)imide in diglyme electrolyte over a wide concentration range, however, reversible insertion of Mg intomore » V 2O 5 cathode can only be attained at high electrolyte concentrations. Reversible intercalation of Mg into V 2O 5 is characterized and confirmed by X-ray diffraction, X-ray absorption near edge spectroscopy and energy dispersive spectroscopy.« less

  4. From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

    PubMed Central

    Wang, Wei

    2010-01-01

    This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities. PMID:21161384

  5. Active learning as a path to critical thinking: are competencies a roadblock?

    PubMed

    Tedesco-Schneck, Mary

    2013-01-01

    Nursing educators are called to graduate students who are critical thinkers able to face the challenge of negotiating increasingly complex health care systems (Candela, 2011; Cerullo and da Cruz, 2010). Active learning has been incited as a mechanism to foster critical thinking skills (Michel et al., 2009; Pascarella, 2005; Walker, 2003). Yet despite evidence and academic applause in favor of active pedagogies, passive pedagogies continue to dominant the nursing education landscape (Brown et al., 2009; Burbach et al., 2004; Schnell, 2005). Although, scholarly literature in nursing and education substantiate existence of various obstacles that inhibit faculty incorporation of active pedagogies, perhaps the insidious culture of competencies in nursing education is what truly engenders a milieu for the continued use of passive pedagogies. In this article, I aim to stimulate debate about the culture of competencies in nursing education as the overriding force which perpetuates use of passive pedagogies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density.

    PubMed

    Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y; Meinhardt, Kerry D; Chang, Hee Jung; Canfield, Nathan L; Sprenkle, Vincent L

    2016-02-11

    Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg(-1), higher than that of conventional tubular sodium-nickel chloride batteries (280 °C), is obtained for planar sodium-nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.

  7. Grand challenges in the management and conservation of North American inland fishes and fisheries

    USGS Publications Warehouse

    Lynch, Abigail; Cooke, Steven J.; Beard, Douglas; Kao, Yu-Chun; Lorenzen, Kai; Song, Andrew M.; Allen, Micheal S.; Basher, Zeenatul; Bunnell, David B.; Camp, Edward V.; Cowx, Ian G.; Freedman, Jonathan A.; Nguyen, Vivian M.; Nohner, Joel K.; Rogers, Mark W.; Siders, Zachary A.; Taylor, William W.; Youn, So-Jung

    2017-01-01

    Even with long-standing management and extensive science support, North American inland fish and fisheries still face many conservation and management challenges. We used a grand challenges approach to identify critical roadblocks that if removed would help solve important problems in the management and long-term conservation of North American inland fish and fisheries. We identified seven grand challenges within three themes (valuation, governance, and externalities) and 34 research needs and management actions. The major themes identified are to (1) raise awareness of diverse values associated with inland fish and fisheries, (2) govern inland fish and fisheries to satisfy multiple use and conservation objectives, and (3) ensure productive inland fisheries given nonfishing sector externalities. Addressing these grand challenges will help the broader community understand the diverse values of inland fish and fisheries, promote open forums for engagement of diverse stakeholders in fisheries management, and better integrate the inland fish sector into the greater water and land use policy process.

  8. Advanced intermediate temperature sodium-nickel chloride batteries with ultra-high energy density

    NASA Astrophysics Data System (ADS)

    Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y.; Meinhardt, Kerry D.; Chang, Hee Jung; Canfield, Nathan L.; Sprenkle, Vincent L.

    2016-02-01

    Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg-1, higher than that of conventional tubular sodium-nickel chloride batteries (280 °C), is obtained for planar sodium-nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs.

  9. Interrogation of bimetallic particle oxidation in three dimensions at the nanoscale

    DOE PAGES

    Han, Lili; Meng, Qingping; Wang, Deli; ...

    2016-12-08

    An understanding of bimetallic alloy oxidation is key to the design of hollow-structured binary oxides and the optimization of their catalytic performance. However, one roadblock encountered in studying these binary oxide systems is the difficulty in describing the heterogeneities that occur in both structure and chemistry as a function of reaction coordinate. This is due to the complexity of the three-dimensional mosaic patterns that occur in these heterogeneous binary systems. By combining real-time imaging and chemical-sensitive electron tomography, we show that it is possible to characterize these systems with simultaneous nanoscale and chemical detail. We find that there is oxidation-inducedmore » chemical segregation occurring on both external and internal surfaces. Additionally, there is another layer of complexity that occurs during the oxidation, namely that the morphology of the initial oxide surface can change the oxidation modality. As a result, this work characterizes the pathways that can control the morphology in binary oxide materials.« less

  10. Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

    PubMed

    Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

    2013-06-01

    The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

  11. Approaches to the induction of HIV broadly neutralizing antibodies.

    PubMed

    Moore, Penny L; Williamson, Carolyn

    2016-11-01

    A vaccine that elicits antibody responses that can neutralize the diversity of HIV clades has not yet been achieved, and is a major focus of HIV vaccine research. Here, we provide an update on the barriers to eliciting such antibodies, and how advances in immunogen design may circumvent these roadblocks, focusing on data published in the last year. Studies of how broadly neutralizing antibodies (bNAbs) develop in HIV-infected donors continue to produce key insights, suggesting that for some viral targets there are common pathways to developing breadth. Germline-targeting strategies, that aim to recruit rare precursors of bNAbs, have shown promise in immunogenicity studies, and structural biology has led to advances in immunogen design. Mapping of strain-specific tier 2 vaccine responses has highlighted the challenges that remain in driving antibodies toward breadth. Elucidation of the HIV envelope structure, together with an understanding of how bNAbs emerge in vivo has guided the design of new immunogens and vaccine strategies that show promise for eliciting protective antibodies.

  12. Wireless Microstimulators for Neural Prosthetics

    PubMed Central

    Sahin, Mesut; Pikov, Victor

    2016-01-01

    One of the roadblocks in the field of neural prosthetics is the lack of microelectronic devices for neural stimulation that can last a lifetime in the central nervous system. Wireless multi-electrode arrays are being developed to improve the longevity of implants by eliminating the wire interconnects as well as the chronic tissue reactions due to the tethering forces generated by these wires. An area of research that has not been sufficiently investigated is a simple single-channel passive microstimulator that can collect the stimulus energy that is transmitted wirelessly through the tissue and immediately convert it into the stimulus pulse. For example, many neural prosthetic approaches to intraspinal microstimulation require only a few channels of stimulation. Wired spinal cord implants are not practical for human subjects because of the extensive flexions and rotations that the spinal cord experiences. Thus, intraspinal microstimulation may be a pioneering application that can benefit from submillimetersize floating stimulators. Possible means of energizing such a floating microstimulator, such as optical, acoustic, and electromagnetic waves, are discussed. PMID:21488815

  13. From cleanroom to desktop: emerging micro-nanofabrication technology for biomedical applications.

    PubMed

    Pan, Tingrui; Wang, Wei

    2011-02-01

    This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities.

  14. The impact of sex as a biological variable in the search for novel antidepressants.

    PubMed

    Williams, Alexia V; Trainor, Brian C

    2018-05-31

    A roadblock to successful treatment for anxiety and depression is the high proportion of individuals that do not respond to existing treatments. Different underlying neurobiological mechanisms may drive similar symptoms, so a more personalized approach to treatment could be more successful. There is increasing evidence that sex is an important biological variable modulating efficacy of antidepressants and anxiolytics. We review evidence for sex-specific effects of traditional monoamine based antidepressants and newer pharmaceuticals targeting kappa opioid receptors (KOR), oxytocin receptors (OTR), and N-methyl-D-aspartate receptors (ketamine). In some cases, similar behavioral effects are observed in both sexes while in other cases strong sex-specific effects are observed. Most intriguing are cases such as ketamine which has similar behavioral effects in males and females, perhaps through sex-specific neurobiological mechanisms. These results show how essential it is to include both males and females in both clinical and preclinical evaluations of novel antidepressants and anxiolytics. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Fuel Cell Balance-of-Plant Reliability Testbed Project

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

    Sproat, Vern; LaHurd, Debbie

    Reliability of the fuel cell system balance-of-plant (BoP) components is a critical factor that needs to be addressed prior to fuel cells becoming fully commercialized. Failure or performance degradation of BoP components has been identified as a life-limiting factor in fuel cell systems.1 The goal of this project is to develop a series of test beds that will test system components such as pumps, valves, sensors, fittings, etc., under operating conditions anticipated in real Polymer Electrolyte Membrane (PEM) fuel cell systems. Results will be made generally available to begin removing reliability as a roadblock to the growth of the PEMmore » fuel cell industry. Stark State College students participating in the project, in conjunction with their coursework, have been exposed to technical knowledge and training in the handling and maintenance of hydrogen, fuel cells and system components as well as component failure modes and mechanisms. Three test beds were constructed. Testing was completed on gas flow pumps, tubing, and pressure and temperature sensors and valves.« less

  16. Challenges associated with drunk driving measurement: combining police and self-reported data to estimate an accurate prevalence in Brazil.

    PubMed

    Sousa, Tanara; Lunnen, Jeffrey C; Gonçalves, Veralice; Schmitz, Aurinez; Pasa, Graciela; Bastos, Tamires; Sripad, Pooja; Chandran, Aruna; Pechansky, Flavio

    2013-12-01

    Drunk driving is an important risk factor for road traffic crashes, injuries and deaths. After June 2008, all drivers in Brazil were subject to a "Zero Tolerance Law" with a set breath alcohol concentration of 0.1 mg/L of air. However, a loophole in this law enabled drivers to refuse breath or blood alcohol testing as it may self-incriminate. The reported prevalence of drunk driving is therefore likely a gross underestimate in many cities. To compare the prevalence of drunk driving gathered from police reports to the prevalence gathered from self-reported questionnaires administered at police sobriety roadblocks in two Brazilian capital cities, and to estimate a more accurate prevalence of drunk driving utilizing three correction techniques based upon information from those questionnaires. In August 2011 and January-February 2012, researchers from the Centre for Drug and Alcohol Research at the Universidade Federal do Rio Grande do Sul administered a roadside interview on drunk driving practices to 805 voluntary participants in the Brazilian capital cities of Palmas and Teresina. Three techniques which include measures such as the number of persons reporting alcohol consumption in the last six hours but who had refused breath testing were used to estimate the prevalence of drunk driving. The prevalence of persons testing positive for alcohol on their breath was 8.8% and 5.0% in Palmas and Teresina respectively. Utilizing a correction technique we calculated that a more accurate prevalence in these sites may be as high as 28.2% and 28.7%. In both cities, about 60% of drivers who self-reported having drank within six hours of being stopped by the police either refused to perform breathalyser testing; fled the sobriety roadblock; or were not offered the test, compared to about 30% of drivers that said they had not been drinking. Despite the reduction of the legal limit for drunk driving stipulated by the "Zero Tolerance Law," loopholes in the legislation permit many drivers under the influence of alcohol to act with impunity. In this context the police/traffic officers are often powerless to enforce the law and thus drunk driving continues to go unchecked. Strong legislation and effective enforcement are necessary to reduce the prevalence of this dangerous behaviour. Correction techniques allow calculation of a truer prevalence of drunk driving, which can assist police and policymakers alike to redirect resources and align strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Natural language processing: state of the art and prospects for significant progress, a workshop sponsored by the National Library of Medicine.

    PubMed

    Friedman, Carol; Rindflesch, Thomas C; Corn, Milton

    2013-10-01

    Natural language processing (NLP) is crucial for advancing healthcare because it is needed to transform relevant information locked in text into structured data that can be used by computer processes aimed at improving patient care and advancing medicine. In light of the importance of NLP to health, the National Library of Medicine (NLM) recently sponsored a workshop to review the state of the art in NLP focusing on text in English, both in biomedicine and in the general language domain. Specific goals of the NLM-sponsored workshop were to identify the current state of the art, grand challenges and specific roadblocks, and to identify effective use and best practices. This paper reports on the main outcomes of the workshop, including an overview of the state of the art, strategies for advancing the field, and obstacles that need to be addressed, resulting in recommendations for a research agenda intended to advance the field. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  18. One-Step Preservation and Decalcification of Bony Tissue for Molecular Profiling.

    PubMed

    Mueller, Claudius; Harpole, Michael G; Espina, Virginia

    2017-01-01

    Bone metastasis from primary cancer sites creates diagnostic and therapeutic challenges. Calcified bone is difficult to biopsy due to tissue hardness and patient discomfort, thus limiting the frequency and availability of bone/bone marrow biopsy material for molecular profiling. In addition, bony tissue must be demineralized (decalcified) prior to histomorphologic analysis. Decalcification processes rely on three main principles: (a) solubility of calcium salts in an acid, such as formic or nitric acid; (b) calcium chelation with ethylenediaminetetraacetic acid (EDTA); or (c) ion-exchange resins in a weak acid. A major roadblock in molecular profiling of bony tissue has been the lack of a suitable demineralization process that preserves histomorphology of calcified and soft tissue elements while also preserving phosphoproteins and nucleic acids. In this chapter, we describe general issues relevant to specimen collection and preservation of osseous tissue for molecular profiling. We provide two protocols: (a) one-step preservation of tissue histomorphology and proteins and posttranslational modifications, with simultaneous decalcification of bony tissue, and (b) ethanol-based tissue processing for TheraLin-fixed bony tissue.

  19. Mechanochemical coupling and bi-phasic force-velocity dependence in the ultra-fast ring ATPase SpoIIIE

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

    Liu, Ninning; Chistol, Gheorghe; Cui, Yuanbo

    Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motor’s mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore,more » we find that SpoIIIE’s velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.« less

  20. Hospital marketing and the Internet: the adoption of an innovation.

    PubMed

    Shepherd, C David; Fell, Daniel

    2003-01-01

    Given the manner in which the Internet permeates today's society, it is easy to forget that the Internet as we know it is only about a decade old. Due to its newness, the Internet has provided an opportunity to view the manner in which marketers move to adopt such an innovation. To that end, since 1995 a series of studies has tracked the adoption and use of the Internet by hospital marketers. In addition to simply investigating the number of hospitals that utilize the Internet in their marketing efforts, the studies have addressed such questions as: How are hospitals using the Internet to market themselves?, What roadblocks have held hospitals back from adopting the Internet as a marketing tool?, and How happy are hospitals with their Internet investment? This manuscript details the most recent in this series of research studies. In addition, the authors compare the results of this study, conducted in the fall of 2002, with the results from the previous studies. As a result, this study provides a unique opportunity to observe the actual adoption of an innovation, the Internet, by hospital marketing professionals.

  1. Reconstructing the ideal results of a perturbed analog quantum simulator

    NASA Astrophysics Data System (ADS)

    Schwenk, Iris; Reiner, Jan-Michael; Zanker, Sebastian; Tian, Lin; Leppäkangas, Juha; Marthaler, Michael

    2018-04-01

    Well-controlled quantum systems can potentially be used as quantum simulators. However, a quantum simulator is inevitably perturbed by coupling to additional degrees of freedom. This constitutes a major roadblock to useful quantum simulations. So far there are only limited means to understand the effect of perturbation on the results of quantum simulation. Here we present a method which, in certain circumstances, allows for the reconstruction of the ideal result from measurements on a perturbed quantum simulator. We consider extracting the value of the correlator 〈Ôi(t ) Ôj(0 ) 〉 from the simulated system, where Ôi are the operators which couple the system to its environment. The ideal correlator can be straightforwardly reconstructed by using statistical knowledge of the environment, if any n -time correlator of operators Ôi of the ideal system can be written as products of two-time correlators. We give an approach to verify the validity of this assumption experimentally by additional measurements on the perturbed quantum simulator. The proposed method can allow for reliable quantum simulations with systems subjected to environmental noise without adding an overhead to the quantum system.

  2. How to Tackle the Challenge of siRNA Delivery with Sequence-Defined Oligoamino Amides.

    PubMed

    Reinhard, Sören; Wagner, Ernst

    2017-01-01

    RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid-phase-assisted synthesis of sequence-defined cationic oligomers. These medium-sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence-defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Photoluminescence Intermittency and Photo-Bleaching of Single Colloidal Quantum Dot.

    PubMed

    Qin, Haiyan; Meng, Renyang; Wang, Na; Peng, Xiaogang

    2017-04-01

    Photoluminescence (PL) blinking of single colloidal quantum dot (QD)-PL intensity switching between different brightness states under constant excitation-and photo-bleaching are roadblocks for most applications of QDs. This progress report shall treat PL blinking and photo-bleaching both as photochemical events, namely, PL blinking as reversible and photo-bleaching being irreversible ones. Most studies on single-molecule spectroscopy of QDs in literature are related to PL blinking, which invites us to concentrate our discussions on the PL blinking, including its brief history in 20 years, analysis methods, competitive mechanisms and different strategies to battle it. In terms of suppression of the PL blinking, wavefunction confinement-confining photo-generated electron and hole within the core and inner portion of the shell of a core/shell QD-demonstrates significant advantages. This strategy yields nearly non-blinking QDs with their emission peaks covering most part of the visible window. As expected, the resulting QDs from this new strategy also show substantially improved anti-bleaching features. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Future Automotive Aftertreatment Solutions: The 150°C Challenge Workshop Report

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

    Zammit, Michael; DiMaggio, Craig L.; Kim, Chang H.

    2013-10-15

    With future fuel economy standards enacted, the U.S. automotive manufacturers (OEMs) are committed to pursuing a variety of high risk/highly efficient stoichiometric and lean combustion strategies to achieve superior performance. In recognition of this need, the U.S. Department of Energy (DOE) has partnered with domestic automotive manufacturers through U.S. DRIVE to develop these advanced technologies. However, before these advancements can be introduced into the U.S. market, they must also be able to meet increasingly stringent emissions requirements. A significant roadblock to this implementation is the inability of current catalyst and aftertreatment technologies to provide the required activity at the muchmore » lower exhaust temperatures that will accompany highly efficient combustion processes and powertrain strategies. Therefore, the goal of this workshop and report is to create a U.S. DRIVE emission control roadmap that will identify new materials and aftertreatment approaches that offer the potential for 90% conversion of emissions at low temperature (150°C) and are consistent with highly efficient combustion technologies currently under investigation within U.S. DRIVE Advanced Combustion and Emission Control (ACEC) programs.« less

  5. Carbon nanotube transistor based high-frequency electronics

    NASA Astrophysics Data System (ADS)

    Schroter, Michael

    At the nanoscale carbon nanotubes (CNTs) have higher carrier mobility and carrier velocity than most incumbent semiconductors. Thus CNT based field-effect transistors (FETs) are being considered as strong candidates for replacing existing MOSFETs in digital applications. In addition, the predicted high intrinsic transit frequency and the more recent finding of ways to achieve highly linear transfer characteristics have inspired investigations on analog high-frequency (HF) applications. High linearity is extremely valuable for an energy efficient usage of the frequency spectrum, particularly in mobile communications. Compared to digital applications, the much more relaxed constraints for CNT placement and lithography combined with already achieved operating frequencies of at least 10 GHz for fabricated devices make an early entry in the low GHz HF market more feasible than in large-scale digital circuits. Such a market entry would be extremely beneficial for funding the development of production CNTFET based process technology. This talk will provide an overview on the present status and feasibility of HF CNTFET technology will be given from an engineering point of view, including device modeling, experimental results, and existing roadblocks. Carbon nanotube transistor based high-frequency electronics.

  6. Carbon nanotube transistor based high-frequency electronics

    NASA Astrophysics Data System (ADS)

    Schroter, Michael

    At the nanoscale carbon nanotubes (CNTs) have higher carrier mobility and carrier velocity than most incumbent semiconductors. Thus CNT based field-effect transistors (FETs) are being considered as strong candidates for replacing existing MOSFETs in digital applications. In addition, the predicted high intrinsic transit frequency and the more recent finding of ways to achieve highly linear transfer characteristics have inspired investigations on analog high-frequency (HF) applications. High linearity is extremely valuable for an energy efficient usage of the frequency spectrum, particularly in mobile communications. Compared to digital applications, the much more relaxed constraints for CNT placement and lithography combined with already achieved operating frequencies of at least 10 GHz for fabricated devices make an early entry in the low GHz HF market more feasible than in large-scale digital circuits. Such a market entry would be extremely beneficial for funding the development of production CNTFET based process technology. This talk will provide an overview on the present status and feasibility of HF CNTFET technology will be given from an engineering point of view, including device modeling, experimental results, and existing roadblocks.

  7. What is it like to be a patient with apperceptive agnosia?

    PubMed

    Vecera, S P; Gilds, K S

    1997-01-01

    Neuropsychological deficits have been widely used to elucidate normal cognitive functioning. Can patients with such deficits also be used to understand conscious visual experience? In this paper, we ask what it would be like to be a patient with apperceptive agnosia (a deficit in object recognition). Philosophical analyses of such questions have suggested that subjectively experiencing what another person experiences would be impossible. Although such roadblocks into the conscious experience of others exist, the experimental study of both patients and neurologically normal subjects can be used to understand visual processing mechanisms. In order to understand the visual processes damaged in apperceptive agnosia, we first review this syndrome and present a case study of one such patient, patient J.W. We then review several theoretical accounts of apperceptive agnosia, and we conclude that studies of the patients themselves may not allow us to discriminate between the various explanations of the syndrome. To test these accounts, we have simulated apperceptive agnosia in neurologically normal subjects. The implications of our results for understanding both apperceptive agnosia and normal visual processing are discussed.

  8. Criminal justice coercion in the treatment of alcohol problems: an examination of two client subgroups.

    PubMed

    Polcin, D L

    1999-01-01

    An increasing number of individuals are being referred to alcohol treatment programs under coercion from the criminal justice system. While a substantial number of investigations have addressed coercive treatment for illicit drug-related offenses, fewer studies have focused on mandated treatment for alcohol-related problems. This article examines the treatment of two subgroups of clients coerced into alcohol treatment from criminal justice institutions. The article begins with an overview of the literature on clients coerced into treatment as a result of "driving under the influence" (DUI) charges. The characteristics of a subgroup that has received less attention are then described: lower socioeconomic clients who are coerced into alcohol treatment from the courts for non-DUI offenses, such as public inebriation, disorderly conduct, trespassing, assault, and theft. This subgroup of non-DUI coerced-treatment offenders depends primarily upon underfunded public services, although their treatment requires careful assessment and triage for multiple problem areas. The article addresses some potential political and economic roadblocks to comprehensive treatment and closes with questions and recommendations for further research.

  9. Out of Academics: Education, Entrepreneurship and Enterprise.

    PubMed

    Banes, Albert J

    2013-06-25

    The author started a niche biotech company in 1985 called Flexcell ® to distribute an enabling technology, mechanobiology devices, to the field. He was the first University of North Carolina faculty member to start a company and stay with it as he pursued his career in academics. That was an unpopular route at that time, but a path he was driven to navigate. Those interests, merged with his training, led to the design and manufacture of mechanobiology devices such as the Flexercell ® Strain Unit and the BioFlex ® flexible bottom culture plates to study fundamental responses of cells to strain. Principles in these devices were also incorporated into bioreactors for tissue engineering, which are standard in the marketplace today. In this article, the major roadblocks will be chronicled that were overcome to help build the field of mechanobiology and create a small biotechnology company. Through example, the author's formula for achieving milestones will be discussed including, the DRIVE it takes to get there ["DRIVE": Determination (Confidence), Research and Development (R&D) and Risk-Taking, Innovation (Imagination) and Intellectual Property, achieving Victory, and Enterprise].

  10. Advanced intermediate temperature sodium–nickel chloride batteries with ultra-high energy density

    PubMed Central

    Li, Guosheng; Lu, Xiaochuan; Kim, Jin Y.; Meinhardt, Kerry D.; Chang, Hee Jung; Canfield, Nathan L.; Sprenkle, Vincent L.

    2016-01-01

    Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium–nickel chloride batteries can be operated at an intermediate temperature of 190 °C with ultra-high energy density. A specific energy density of 350 Wh kg−1, higher than that of conventional tubular sodium–nickel chloride batteries (280 °C), is obtained for planar sodium–nickel chloride batteries operated at 190 °C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium–nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs. PMID:26864635

  11. Isolation of Human Colon Stem Cells Using Surface Expression of PTK7.

    PubMed

    Jung, Peter; Sommer, Christian; Barriga, Francisco M; Buczacki, Simon J; Hernando-Momblona, Xavier; Sevillano, Marta; Duran-Frigola, Miquel; Aloy, Patrick; Selbach, Matthias; Winton, Douglas J; Batlle, Eduard

    2015-12-08

    Insertion of reporter cassettes into the Lgr5 locus has enabled the characterization of mouse intestinal stem cells (ISCs). However, low cell surface abundance of LGR5 protein and lack of high-affinity anti-LGR5 antibodies represent a roadblock to efficiently isolate human colonic stem cells (hCoSCs). We set out to identify stem cell markers that would allow for purification of hCoSCs. In an unbiased approach, membrane-enriched protein fractions derived from in vitro human colonic organoids were analyzed by quantitative mass spectrometry. Protein tyrosine pseudokinase PTK7 specified a cell population within human colonic organoids characterized by highest self-renewal and re-seeding capacity. Antibodies recognizing the extracellular domain of PTK7 allowed us to isolate and expand hCoSCs directly from patient-derived mucosa samples. Human PTK7+ cells display features of canonical Lgr5+ ISCs and include a fraction of cells that undergo differentiation toward enteroendocrine lineage that resemble crypt label retaining cells (LRCs). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Drosophila and experimental neurology in the post-genomic era.

    PubMed

    Shulman, Joshua M

    2015-12-01

    For decades, the fruit fly, Drosophila melanogaster, has been among the premiere genetic model systems for probing fundamental neurobiology, including elucidation of mechanisms responsible for human neurologic disorders. Flies continue to offer virtually unparalleled versatility and speed for genetic manipulation, strong genomic conservation, and a nervous system that recapitulates a range of cellular and network properties relevant to human disease. I focus here on four critical challenges emerging from recent advances in our understanding of the genomic basis of human neurologic disorders where innovative experimental strategies are urgently needed: (1) pinpointing causal genes from associated genomic loci; (2) confirming the functional impact of allelic variants; (3) elucidating nervous system roles for novel or poorly studied genes; and (4) probing network interactions within implicated regulatory pathways. Drosophila genetic approaches are ideally suited to address each of these potential translational roadblocks, and will therefore contribute to mechanistic insights and potential breakthrough therapies for complex genetic disorders in the coming years. Strategic collaboration between neurologists, human geneticists, and the Drosophila research community holds great promise to accelerate progress in the post-genomic era. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Mechanochemical coupling and bi-phasic force-velocity dependence in the ultra-fast ring ATPase SpoIIIE

    DOE PAGES

    Liu, Ninning; Chistol, Gheorghe; Cui, Yuanbo; ...

    2018-03-05

    Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motor’s mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore,more » we find that SpoIIIE’s velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.« less

  14. Engineering management consideration for an integrated aeronautical mobile satellite service

    NASA Astrophysics Data System (ADS)

    Belcher, John M.

    In order to meet local air traffic control terminal requirements as well as national and transborder requirements, countries have developed communications, navigation, and surveillance (CNS) systems having little systems integration and a solely ground-based solution to air traffic control problems. It is believed that the application of satellite technology is the only currently viable solution that will enable international civil aviation to overcome the shortcomings of the presently available CNS systems. If properly implemented, available satellite system technology integrated with avionics and ground based capabilities, can be used to meet new global aviation demands. A clear transition plan has to be implemented so as to ensure continuity of service, recognize user-borne costs, and satisfy institutional and national objectives in the progress toward a universal air traffic management (ATM) system. ATM systems design should rely on a modular approach for flexibility and upgrading. An aeronautical mobile satellite service is intended to provide a worldwide satellite data link and direct air/ground voice communication. Institutional and financial roadblocks for implemetation of a global based approach will likely be far greater than technical constraints.

  15. Canadian mock juror attitudes and decisions in domestic violence cases involving asian and white interracial and intraracial couples.

    PubMed

    Maeder, Evelyn M; Mossière, Annik; Cheung, Liann

    2013-03-01

    This study manipulated the race of the defendant and the victim (White/White, White/Asian, Asian/Asian, and Asian/White) in a domestic violence case to examine the potential prejudicial impact of race on juror decision making. A total of 181 undergraduate students read a trial transcript involving an allegation of spousal abuse in which defendant and victim race were manipulated using photographs. They then provided a verdict and confidence rating, a sentence, and responsibility attributions, and completed various scales measuring attitudes toward wife abuse and women. Findings revealed that female jurors were harsher toward the defendant than were male jurors. When controlling for attitudes toward Asians, jurors found the defendant guilty more often in cases involving interracial couples, as compared to same-race couples. Path analyses revealed various factors and attitudes involved in domestic violence trial outcomes. Findings contribute to the scarce literature on legal proceedings involving Asians, particularly in domestic violence cases. Outcomes also provide a model for relevant factors and characteristics of jurors in domestic violence cases. Roadblocks inherent in jury research are also discussed.

  16. Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein

    NASA Astrophysics Data System (ADS)

    Chaurasiya, Kathy R.; McCauley, Micah J.; Wang, Wei; Qualley, Dominic F.; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S. B.; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C.

    2014-01-01

    The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.

  17. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    PubMed

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  18. Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink

    PubMed Central

    Yu, Yin; Moncal, Kazim K.; Li, Jianqiang; Peng, Weijie; Rivero, Iris; Martin, James A.; Ozbolat, Ibrahim T.

    2016-01-01

    Recent advances in bioprinting have granted tissue engineers the ability to assemble biomaterials, cells, and signaling molecules into anatomically relevant functional tissues or organ parts. Scaffold-free fabrication has recently attracted a great deal of interest due to the ability to recapitulate tissue biology by using self-assembly, which mimics the embryonic development process. Despite several attempts, bioprinting of scale-up tissues at clinically-relevant dimensions with closely recapitulated tissue biology and functionality is still a major roadblock. Here, we fabricate and engineer scaffold-free scalable tissue strands as a novel bioink material for robotic-assisted bioprinting technologies. Compare to 400 μm-thick tissue spheroids bioprinted in a liquid delivery medium into confining molds, near 8 cm-long tissue strands with rapid fusion and self-assemble capabilities are bioprinted in solid form for the first time without any need for a scaffold or a mold support or a liquid delivery medium, and facilitated native-like scale-up tissues. The prominent approach has been verified using cartilage strands as building units to bioprint articular cartilage tissue. PMID:27346373

  19. Compliance with HIPAA security standards in U.S. Hospitals.

    PubMed

    Davis, Diane; Having, Karen

    2006-01-01

    With the widespread use of computer networks, the amount of information stored electronically has grown exponentially, resulting in increased concern for privacy and security of information. The healthcare industry has been put to the test with the federally mandated Health Insurance Portability and Accountability Act (HIPAA) of 1996. To assess the compliance status of HIPAA security standards, a random sample of 1,000 U.S. hospitals was surveyed in January 2004, yielding a return rate of 29 percent. One year later, a follow-up survey was sent to all previous respondents, with 50 percent replying. HIPAA officers'perceptions of security compliance in 2004 and 2005 are compared in this article. The security standards achieving the highest level of compliance in both 2004 and 2005 were obtaining required business associate agreements and physical safeguards to limit access to electronic information systems. Respondents indicated least compliance both years in performing periodic evaluation of security practices governed by the Security Rule. Roadblocks, threats, problems and solutions regarding HIPAA compliance are discussed. This information may be applied to current and future strategies toward maintaining security of information systems throughout the healthcare industry.

  20. "History had taken such a large piece out of my life" - Neuroscientist refugees from Hamburg during National Socialism.

    PubMed

    Zeidman, Lawrence A; von Villiez, Anna; Stellmann, Jan-Patrick; van den Bussche, Hendrik

    2016-01-01

    Approximately 9,000 physicians were uprooted for so-called "racial" or "political" reasons by the Nazi regime and 6,000 fled Germany. These refugees are often seen as survivors who contributed to a "brain drain" from Germany. About 432 doctors (all specialties, private and academic) were dismissed from the major German city of Hamburg. Of these, 16 were Hamburg University faculty members dismissed from their government-supported positions for "racial" reasons, and, of these, five were neuroscientists. In a critical analysis, not comprehensively done previously, we will demonstrate that the brain drain did not equal a "brain gain." The annihilation of these five neuroscientists' careers under different but similar auspices, their shameful harassment and incarceration, financial expropriation by Nazi ransom techniques, forced migration, and roadblocks once reaching destination countries stalled and set back any hopes of research and quickly continuing once-promising careers. A major continuing challenge is finding ways to repair an open wound and obvious vacuum in the German neuroscience community created by the largely collective persecution of colleagues 80 years ago.

  1. Galerkin Models Enhancements for Flow Control

    NASA Astrophysics Data System (ADS)

    Tadmor, Gilead; Lehmann, Oliver; Noack, Bernd R.; Morzyński, Marek

    Low order Galerkin models were originally introduced as an effective tool for stability analysis of fixed points and, later, of attractors, in nonlinear distributed systems. An evolving interest in their use as low complexity dynamical models, goes well beyond that original intent. It exposes often severe weaknesses of low order Galerkin models as dynamic predictors and has motivated efforts, spanning nearly three decades, to alleviate these shortcomings. Transients across natural and enforced variations in the operating point, unsteady inflow, boundary actuation and both aeroelastic and actuated boundary motion, are hallmarks of current and envisioned needs in feedback flow control applications, bringing these shortcomings to even higher prominence. Building on the discussion in our previous chapters, we shall now review changes in the Galerkin paradigm that aim to create a mathematically and physically consistent modeling framework, that remove what are otherwise intractable roadblocks. We shall then highlight some guiding design principles that are especially important in the context of these models. We shall continue to use the simple example of wake flow instabilities to illustrate the various issues, ideas and methods that will be discussed in this chapter.

  2. Cross-industry Performance Modeling: Toward Cooperative Analysis

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

    Reece, Wendy Jane; Blackman, Harold Stabler

    One of the current unsolved problems in human factors is the difficulty in acquiring information from lessons learned and data collected among human performance analysts in different domains. There are several common concerns and generally accepted issues of importance for human factors, psychology and industry analysts of performance and safety. Among these are the need to incorporate lessons learned in design, to carefully consider implementation of new designs and automation, and the need to reduce human performance-based contributions to risk. In spite of shared concerns, there are several roadblocks to widespread sharing of data and lessons learned from operating experiencemore » and simulation, including the fact that very few publicly accessible data bases exist (Gertman & Blackman, 1994, and Kirwan, 1997). There is a need to draw together analysts and analytic methodologies to comprise a centralized source of data with sufficient detail to be meaningful while ensuring source anonymity. We propose that a generic source of performance data and a multi-domain data store may provide the first steps toward cooperative performance modeling and analysis across industries.« less

  3. Elasto-inertial microfluidics for bacteria separation from whole blood for sepsis diagnostics.

    PubMed

    Faridi, Muhammad Asim; Ramachandraiah, Harisha; Banerjee, Indradumna; Ardabili, Sahar; Zelenin, Sergey; Russom, Aman

    2017-01-04

    Bloodstream infections (BSI) remain a major challenge with high mortality rate, with an incidence that is increasing worldwide. Early treatment with appropriate therapy can reduce BSI-related morbidity and mortality. However, despite recent progress in molecular based assays, complex sample preparation steps have become critical roadblock for a greater expansion of molecular assays. Here, we report a size based, label-free, bacteria separation from whole blood using elasto-inertial microfluidics. In elasto-inertial microfluidics, the viscoelastic flow enables size based migration of blood cells into a non-Newtonian solution, while smaller bacteria remain in the streamline of the blood sample entrance and can be separated. We first optimized the flow conditions using particles, and show continuous separation of 5 μm particles from 2 μm at a yield of 95% for 5 µm particle and 93% for 2 µm particles at respective outlets. Next, bacteria were continuously separated at an efficiency of 76% from undiluted whole blood sample. We demonstrate separation of bacteria from undiluted while blood using elasto-inertial microfluidics. The label-free, passive bacteria preparation method has a great potential for downstream phenotypic and molecular analysis of bacteria.

  4. CASMI TSCC Launch Event, Paris, France, July 2013: An Assessment of the Key Barriers to the Commercialization and Clinical Adoption of Pluripotent Stem Cell Therapies*

    PubMed Central

    Bure, Kim; Brindley, David A.

    2014-01-01

    Abstract The high incidence of unmet medical needs in combination with the rising burden of chronic diseases, linked to an increasingly aging population, necessitates new approaches to therapeutic intervention. One potential class of health care innovation that may offer an alternative approach to addressing current shortfalls is stem cell therapies. The CASMI Translational Stem Cell Consortium (CTSCC) was formed to elucidate the key hurdles to the commercialization and clinical adoption of stem cell technologies, with a particular focus on pluripotent stem cell (PSC) technologies. As a global pre-competitive academic–industry consortium, the CTSCC unites thought leaders from a range of sectors and technical specialties in defining and discovering solutions to roadblocks that will impede the field. Targeted toward stakeholder requirements at the delivery end of the translational spectrum, the CTSCC aims to provide mechanisms for multidirectional dialogue and to produce academically rigorous and commercially practicable research outputs to accelerate industry progress. On the 30th and 31st of July, 2013, the CASMI Translational Stem Cell Consortium (CTSCC) held a launch event at the Saint James Club, Paris, France. PMID:24392658

  5. Using FT-IR Spectroscopy to Measure Charge Organization in Ionic Liquids

    PubMed Central

    Burba, Christopher M.; Janzen, Jonathan; Butson, Eric D.; Coltrain, Gage L.

    2013-01-01

    A major goal in the field of ionic liquids is correlating transport property trends with the underlying liquid structure of the compounds, such as the degree of charge organization among the constituent ions. Traditional techniques for experimentally assessing charge organization are specialized and not readily available for routine measurements. This represents a significant roadblock in elucidating these correlations. We use a combination of transmission and polarized-ATR infrared spectroscopy to measure the degree of charge organization for ionic liquids. The technique is illustrated with a family of 1-alkyl-3-methylimidazolium trifluoromethansulfonate ionic liquids at 30°C. As expected, the amount of charge organization decreases as the alkyl side chain is lengthened, highlighting the important role of short-range repulsive interactions in defining quasilattice structure. Inherent limitations of the method are identified and discussed. The quantitative measurements of charge organization are then correlated with trends in the transport properties of the compounds to highlight the relationship between charge and momentum transport and the underlying liquid structure. Most research laboratories possess infrared spectrometers capable of conducting these measurements, thus, the proposed method may represent a cost-effective solution for routinely measuring charge organization in ionic liquids. PMID:23781877

  6. Propulsion Health Management System Development for Affordable and Reliable Operation of Space Exploration Systems

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.; Maul, William A.; Garg, Sanjay

    2007-01-01

    The constraints of future Exploration Missions will require unique integrated system health management capabilities throughout the mission. An ambitious launch schedule, human-rating requirements, long quiescent periods, limited human access for repair or replacement, and long communication delays, all require an integrated approach to health management that can span distinct, yet interdependent vehicle subsystems, anticipate failure states, provide autonomous remediation and support the Exploration Mission from beginning to end. Propulsion is a critical part of any space exploration mission, and monitoring the health of the propulsion system is an integral part of assuring mission safety and success. Health management is a somewhat ubiquitous technology that encompasses a large spectrum of physical components and logical processes. For this reason, it is essential to develop a systematic plan for propulsion health management system development. This paper provides a high-level perspective of propulsion health management systems, and describes a logical approach for the future planning and early development that are crucial to planned space exploration programs. It also presents an overall approach, or roadmap, for propulsion health management system development and a discussion of the associated roadblocks and challenges.

  7. Human Mut T Homolog 1 (MTH1): a roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS.

    PubMed

    Rai, Priyamvada

    2012-01-01

    Oncogenic RAS-induced reactive oxygen species (ROS) trigger barriers to cell transformation and cancer progression through tumor-suppressive responses such as cellular senescence or cell death. We have recently shown that oncogenic RAS-induced DNA damage and attendant premature senescence can be prevented by overexpressing human MutT Homolog 1 (MTH1), the major mammalian detoxifier of the oxidized DNA precursor, 8-oxo-dGTP. Paradoxically, RAS-induced ROS are also able to participate in tumor progression via transformative processes such as mitogenic signaling, the epithelial-mesenchymal transition (EMT), anoikis inhibition, and PI3K/Akt-mediated survival signaling. Here we provide a preliminary insight into the influence of MTH1 levels on the EMT phenotype and Akt activation in RAS-transformed HMLE breast epithelial cells. Within this context, we will discuss the implications of MTH1 upregulation in oncogenic RAS-sustaining cells as a beneficial adaptive change that inhibits ROS-mediated cell senescence and participates in the maintenance of ROS-associated tumor-promoting mechanisms. Accordingly, targeting MTH1 in RAS-transformed tumor cells will not only induce proliferative defects but also potentially enhance therapeutic cytotoxicity by shifting cellular response away from pro-survival mechanisms.

  8. Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection.

    PubMed

    Sack, Brandon; Kappe, Stefan H I; Sather, D Noah

    2017-05-01

    An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.

  9. Anti-Diabetic Potential of Noni: The Yin and the Yang.

    PubMed

    Nerurkar, Pratibha V; Hwang, Phoebe W; Saksa, Erik

    2015-09-25

    Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni's several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni's exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their "natural" origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation "from bench side to bedside". In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni's health benefits.

  10. Withania somnifera: from prevention to treatment of cancer

    PubMed Central

    Palliyaguru, Dushani L.; Singh, Shivendra V.; Kensler, Thomas W.

    2016-01-01

    The identification of bioactive molecules that have potential to interrupt carcinogenesis continues to garner research interest. In particular, molecules that have dietary origin are most attractive because of their safety, cost-effectiveness and feasibility of oral administration. Nutraceuticals have played an important role in the overall well-being of humans for many years, with or without rigorous evidence backing their health claims. Traditional medicine systems around the world have utilized plants for millennia that have medicinal properties, providing an opportunity for modern day researchers to assess their efficacies against ailments such as cancer. Withania somnifera (WS) is a plant that has been used in Ayurveda (an ancient form of medicine in Asia) and in the recent past, has been demonstrated to have anti-tumorigenic properties in experimental models. While scientific research performed on WS has exploded in the past decade, much regarding the mode of action and molecular targets involved remains unknown. In this review, we discuss the traditional uses of the plant, the experimental evidence supporting its chemopreventive potential as well as roadblocks that need to be overcome in order for WS to be evaluated as a chemopreventive agent in humans. PMID:26718910

  11. Andiamo, a Graphical User Interface for Ohio University's Hauser-Feshbach Implementation

    NASA Astrophysics Data System (ADS)

    Brooks, Matthew

    2017-09-01

    First and foremost, I am not a physicist. I am an undergraduate computer science major/Japanese minor at Ohio University. However, I am working for Zach Meisel, in the Ohio University's physics department. This is the first software development project I've ever done. My charge is/was to create a graphical program that can be used to more easily set up Hauser-Feshbach equation input files. The input files are of the format expected by the Hauser-Feshbach 2002 code developed by a handful of people at the university. I regularly attend group meetings with Zach and his other subordinates, but these are mostly used as a way for us to discuss our progress and any troubles or roadblocks we may have encountered. I was encouraged to try to come with his group to this event because it could help expose me to the scientific culture of astrophysics research. While I know very little about particles and epic space events, my poster would be an informative and (hopefully) inspiring one that could help get other undergraduates interested in doing object oriented programming. This could be more exposure for them, as I believe a lot of physics majors only learn scripting languages.

  12. Successfully accelerating translational research at an academic medical center: the University of Michigan-Coulter translational research partnership program.

    PubMed

    Pienta, Kenneth J

    2010-12-01

    Translational research encompasses the effective movement of new knowledge and discoveries into new approaches for prevention, diagnosis, and treatment of disease. There are many roadblocks to successful bench to bedside research, but few have received as much recent attention as the "valley of death". The valley of death refers to the lack of funding and support for research that moves basic science discoveries into diagnostics, devices, and treatments in humans, and is ascribed to be the result of companies unwilling to fund research development that may not result in a drug or device that will be utilized in the clinic and conversely, the fact that researchers have no access to the funding needed to carry out preclinical and early clinical development to demonstrate potential efficacy in humans. The valley of death also exists because bridging the translational gap is dependent on successfully managing an additional four risks: scientific, intellectual property, market, and regulatory. The University of Michigan (UM) has partnered with the Wallace H. Coulter Foundation (CF) to create a model providing an infrastructure to overcome these risks. This model is easily adoptable to other academic medical centers (AMCs). © 2010 Wiley Periodicals, Inc.

  13. Low temperature processing of dielectric perovskites for energy storage

    NASA Astrophysics Data System (ADS)

    Singh, N. B.; Schreib, Ben; Devilbiss, Michael; Loiacono, Julian; Arnold, Bradley; Choa, Fow-Sen; Mandal, K. D.

    2016-05-01

    Since the report of high dielectric value was published for the calcium copper titanate of the stoichiometry CaCu3Ti4O12 (CCTO), several of its analogs such as Yittrium copper titanate Y2/3Cu3Ti4O12 (YCTO), Pr2/3Cu3Ti4O12 (PCTO) and several other compounds have been studied extensively. Most of these materials have demonstrated very high dielectric constants. However, the roadblock is their low resistivity. To overcome this problem, several approaches have been considered, including doping and substitution. In order to solve this problem, we have synthesized the stoichiometric composition and used low temperature processing to grow grains of La2/3Cu3Ti4O12 (LCTO) stoichiometric compound. LCTO with excess copper oxide was also prepared to determine its effect on the morphology and dielectric constant of the stoichiometric LCTO compound. In spite of the low melting point of copper oxide, we observed that excess copper oxide did not show any faster grain growth. Also, the dielectric constant of LCTO was lower than CCTO and unlike CCTO, LCTO showed significant changes as the function of frequency. The measured resistivity was slightly higher than CCTO.

  14. Applications in Nuclear Energy Security

    NASA Astrophysics Data System (ADS)

    Sheffield, Richard

    2009-05-01

    A key roadblock to development of additional nuclear power capacity is a concern over management of nuclear waste. Nuclear waste is predominantly comprised of used fuel discharged from operating nuclear reactors. The roughly 100 operating US reactors currently produce about 20% of the US electricity and will create about 87,000 tons of such discharged or ``spent'' fuel over the course of their lifetimes. The long-term radioactivity of the spent fuel drives the need for deep geologic storage that remains stable for millions of years. Nearly all issues related to risks to future generations arising from long-term disposal of such spent nuclear fuel is attributable to approximately the 1% made up primarily of minor actinides. If we can reduce or eliminate this 1% of the spent fuel, then within a few hundred years the toxic nature of the spent fuel drops below that of the natural uranium ore that was originally mined for nuclear fuel. The minor actinides can be efficiently eliminated through nuclear transmutation using as a driver fast-neutrons produced by a spallation process initiated with a high-energy proton beam. This presentation will cover the system design considerations and issues of an accelerator driven transmutation system.

  15. Overcoming roadblocks: current and emerging reimbursement strategies for integrated mental health services in primary care.

    PubMed

    O'Donnell, Allison N; Williams, Mark; Kilbourne, Amy M

    2013-12-01

    The Chronic Care Model (CCM) has been shown to improve medical and psychiatric outcomes for persons with mental disorders in primary care settings, and has been proposed as a model to integrate mental health care in the patient-centered medical home under healthcare reform. However, the CCM has not been widely implemented in primary care settings, primarily because of a lack of a comprehensive reimbursement strategy to compensate providers for day-to-day provision of its core components, including care management and provider decision support. Drawing upon the existing literature and regulatory guidelines, we provide a critical analysis of challenges and opportunities in reimbursing CCM components under the current fee-for-service system, and describe an emerging financial model involving bundled payments to support core CCM components to integrate mental health treatment into primary care settings. Ultimately, for the CCM to be used and sustained over time to integrate physical and mental health care, effective reimbursement models will need to be negotiated across payers and providers. Such payments should provide sufficient support for primary care providers to implement practice redesigns around core CCM components, including care management, measurement-based care, and mental health specialist consultation.

  16. The stability of cellulose: a statistical perspective from a coarse-grained model of hydrogen-bond networks.

    PubMed

    Shen, Tongye; Gnanakaran, S

    2009-04-22

    A critical roadblock to the production of biofuels from lignocellulosic biomass is the efficient degradation of crystalline microfibrils of cellulose to glucose. A microscopic understanding of how different physical conditions affect the overall stability of the crystalline structure of microfibrils could facilitate the design of more effective protocols for their degradation. One of the essential physical interactions that stabilizes microfibrils is a network of hydrogen (H) bonds: both intrachain H-bonds between neighboring monomers of a single cellulose polymer chain and interchain H-bonds between adjacent chains. We construct a statistical mechanical model of cellulose assembly at the resolution of explicit hydrogen-bond networks. Using the transfer matrix method, the partition function and the subsequent statistical properties are evaluated. With the help of this lattice-based model, we capture the plasticity of the H-bond network in cellulose due to frustration and redundancy in the placement of H-bonds. This plasticity is responsible for the stability of cellulose over a wide range of temperatures. Stable intrachain and interchain H-bonds are identified as a function of temperature that could possibly be manipulated toward rational destruction of crystalline cellulose.

  17. A Genetically Optimized Predictive System for Success in General Chemistry Using a Diagnostic Algebra Test

    NASA Astrophysics Data System (ADS)

    Cooper, Cameron I.; Pearson, Paul T.

    2012-02-01

    In higher education, many high-enrollment introductory courses have evolved into "gatekeeper" courses due to their high failure rates. These courses prevent many students from attaining their educational goals and often become graduation roadblocks. At the authors' home institution, general chemistry has become a gatekeeper course in which approximately 25% of students do not pass. This failure rate in chemistry is common, and often higher, at many other institutions of higher education, and mathematical deficiencies are perceived to be a large contributing factor. This paper details the development of a highly accurate predictive system that identifies students at the beginning of the semester who are "at-risk" for earning a grade of C- or below in chemistry. The predictive accuracy of this system is maximized by using a genetically optimized neural network to analyze the results of a diagnostic algebra test designed for a specific population. Once at-risk students have been identified, they can be helped to improve their chances of success using techniques such as concurrent support courses, online tutorials, "just-in-time" instructional aides, study skills, motivational interviewing, and/or peer mentoring.

  18. The blood-brain barrier: an engineering perspective

    PubMed Central

    Wong, Andrew D.; Ye, Mao; Levy, Amanda F.; Rothstein, Jeffrey D.; Bergles, Dwight E.; Searson, Peter C.

    2013-01-01

    It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases. PMID:24009582

  19. Running With an Elastic Lower Limb Exoskeleton.

    PubMed

    Cherry, Michael S; Kota, Sridhar; Young, Aaron; Ferris, Daniel P

    2016-06-01

    Although there have been many lower limb robotic exoskeletons that have been tested for human walking, few devices have been tested for assisting running. It is possible that a pseudo-passive elastic exoskeleton could benefit human running without the addition of electrical motors due to the spring-like behavior of the human leg. We developed an elastic lower limb exoskeleton that added stiffness in parallel with the entire lower limb. Six healthy, young subjects ran on a treadmill at 2.3 m/s with and without the exoskeleton. Although the exoskeleton was designed to provide ~50% of normal leg stiffness during running, it only provided 24% of leg stiffness during testing. The difference in added leg stiffness was primarily due to soft tissue compression and harness compliance decreasing exoskeleton displacement during stance. As a result, the exoskeleton only supported about 7% of the peak vertical ground reaction force. There was a significant increase in metabolic cost when running with the exoskeleton compared with running without the exoskeleton (ANOVA, P < .01). We conclude that 2 major roadblocks to designing successful lower limb robotic exoskeletons for human running are human-machine interface compliance and the extra lower limb inertia from the exoskeleton.

  20. Analysis of Economic and Environmental Aspects of Microalgae Biorefinery for Biofuels Production: A Review.

    PubMed

    Chia, Shir Reen; Chew, Kit Wayne; Show, Pau Loke; Yap, Yee Jiun; Ong, Hwai Chyuan; Ling, Tau Chuan; Chang, Jo-Shu

    2018-06-01

    Microalgae are considered promising feedstock for the production of biofuels and other bioactive compounds, yet there are still challenges on commercial applications of microalgae-based products. This review focuses on the economic analysis, environmental impact, and industrial potential of biofuels production from microalgae. The cost of biofuels production remains higher compared to conventional fuel sources. However, integration of biorefinery pathways with biofuels production for the recovery of value-added products (such as antioxidants, natural dyes, cosmetics, nutritional supplements, polyunsaturated fatty acids, and so forth) could substantially reduce the production costs. It also paves the way for sustainable energy resources by significantly reducing the emissions of CO 2 , NO x , SO x , and heavy metals. Large-scale biofuels production has yet to be successfully commercialized with many roadblocks ahead and heavy competition with conventional fuel feedstock as well as technological aspects. One of the prominent challenges is to develop a cost-effective method to achieve high-density microalgal cultivation on an industrial scale. The biofuels industry should be boosted by Government's support in the form of subsidies and incentives, for addressing the pressing climate change issues, achieving sustainability, and energy security. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. α-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease.

    PubMed

    Spencer, Brian; Kim, Changyoun; Gonzalez, Tania; Bisquertt, Alejandro; Patrick, Christina; Rockenstein, Edward; Adame, Anthony; Lee, Seung-Jae; Desplats, Paula; Masliah, Eliezer

    2016-03-15

    α-Synuclein (α-syn) has been implicated in neurological disorders with parkinsonism, including Parkinson's disease and Dementia with Lewy body. Recent studies have shown α-syn oligomers released from neurons can propagate from cell-to-cell in a prion-like fashion exacerbating neurodegeneration. In this study, we examined the role of the endosomal sorting complex required for transport (ESCRT) pathway on the propagation of α-syn. α-syn, which is transported via the ESCRT pathway through multivesicular bodies for degradation, can also target the degradation of the ESCRT protein-charged multivesicular body protein (CHMP2B), thus generating a roadblock of endocytosed α-syn. Disruption of the ESCRT transport system also resulted in increased exocytosis of α-syn thus potentially increasing cell-to-cell propagation of synuclein. Conversely, delivery of a lentiviral vector overexpressing CHMP2B rescued the neurodegeneration in α-syn transgenic mice. Better understanding of the mechanisms of intracellular trafficking of α-syn might be important for understanding the pathogenesis and developing new treatments for synucleinopathies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Reengineering Biomedical Translational Research with Engineering Ethics.

    PubMed

    Sunderland, Mary E; Nayak, Rahul Uday

    2015-08-01

    It is widely accepted that translational research practitioners need to acquire special skills and knowledge that will enable them to anticipate, analyze, and manage a range of ethical issues. While there is a small but growing literature that addresses the ethics of translational research, there is a dearth of scholarship regarding how this might apply to engineers. In this paper we examine engineers as key translators and argue that they are well positioned to ask transformative ethical questions. Asking engineers to both broaden and deepen their consideration of ethics in their work, however, requires a shift in the way ethics is often portrayed and perceived in science and engineering communities. Rather than interpreting ethics as a roadblock to the success of translational research, we suggest that engineers should be encouraged to ask questions about the socio-ethical dimensions of their work. This requires expanding the conceptual framework of engineering beyond its traditional focus on "how" and "what" questions to also include "why" and "who" questions to facilitate the gathering of normative, socially-situated information. Empowering engineers to ask "why" and "who" questions should spur the development of technologies and practices that contribute to improving health outcomes.

  3. Direct Aqueous-Phase Synthesis of Sub-10 nm “Luminous Pearls” with Enhanced in Vivo Renewable Near-Infrared Persistent Luminescence

    DOE PAGES

    Li, Zhanjun; Zhang, Yuanwei; Wu, Xiang; ...

    2015-04-02

    Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs), possessing unique NIR PL properties, have recently emerged as important materials for a wide variety of applications in chemistry and biology, for which they must endure high-temperature solid-state annealing reactions and subsequent complicated physical post-treatments. Herein, we report on a first direct aqueous-phase chemical synthesis route to NIR PLNPs and present their enhanced in vivo renewable NIR PL. Our method leads to monodisperse PLNPs as small as ca. 8 nm. Such sub-10 nm nanocrystals are readily dispersed and functionalized, and can form stable colloidal solutions in aqueous solution and cell culture medium for biologicalmore » applications. Under biotissue-penetrable red-light excitation, we found that such nanocrystals possess superior renewable PL photoluminescence in vitro and in vivo compared to their larger counterparts currently made by existing methods. In conclusion, we believe that this solid-state-reaction-free chemical approach overcomes the current key roadblock in regard to PLNP development, and thus will pave the way to broad use of these advanced miniature “luminous pearls” in photonics and biophotonics.« less

  4. Analysis of chain saw lubricating oils commonly used in Thailand's southern border provinces for forensic science purpose.

    PubMed

    Choodum, Aree; Tripuwanard, Kijja; Daeid, Niamh Nic

    2014-08-01

    In recent years, Thailand's southern border provinces (Malay-Muslim-majority border provinces) have become the scene of violence and insurgency. One of the attack patterns is the blocking of roads with perennial plants followed by planned attacks using improvised explosive devices (IEDs) or weapons on first responders. Containers of viscous dark lubricating oil and traces of lubricants on the felled trees were usually found at the scene. These were suspected to be chain oil lubricant from the chainsaws used to cut down the trees used for the roadblock. This work aimed to differentiate the chromatographic patterns of used lubricating oils available in automobile repair shops from various locations across Thailand's southern border provinces. Lubricating oils were analyzed using gas chromatography/flame ionization detector (GC/FID) every two weeks to study their variation in chemical compositions over time. The results obtained from GC/FID were normalized for differentiation. This included four two-stroke, six four-stroke, and three recycled oils. Two lubricating oils found at an incident scene were also analyzed and the results compared with the chain oil from five seized chainsaws. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Advocating for equitable science-learning opportunities for girls in an urban city youth club and the roadblocks faced by women science educators

    NASA Astrophysics Data System (ADS)

    Davis, Kathleen S.

    2002-02-01

    This article reports on a study that examined the obstacles women science educators faced as they facilitated Explorers, an after-school science program for girls aged 6-12. The program aimed to provide girls with opportunities to legitimately participate in science activity. Explorers was one of several programs offered by the Foothills City Youth Club (FCYC) in a racially diverse urban center in the Southwestern United States. The youth club was meant to serve the needs of children and youth in that community. Through analysis of field notes, interviews, and documents, the social structures and forces that impeded the implementation of practices and the acquisition of capital are described. They include: (a) inadequate funding and community support, (b) conflicting beliefs between FCYC leaders and community leaders about the needs of boys and girls, and 3) inequitable decision-making structures of the community. Underlying beliefs, structures, and practices within the community weakened the FCYC in many ways, interrupted the leadership's attempts to meet their goals as they worked with the community's children, and brought to the surface issues of bias and oppression.

  6. Control of Surface Segregation in Bimetallic NiCr Nanoalloys Immersed in Ag Matrix

    PubMed Central

    Bohra, Murtaza; Singh, Vidyadhar; Grammatikopoulos, Panagiotis; Toulkeridou, Evropi; Diaz, Rosa E.; Bobo, Jean-François; Sowwan, Mukhles

    2016-01-01

    Cr-surface segregation is a main roadblock encumbering many magneto-biomedical applications of bimetallic M-Cr nanoalloys (where M = Fe, Co and Ni). To overcome this problem, we developed Ni95Cr5:Ag nanocomposite as a model system, consisting of non-interacting Ni95Cr5 nanoalloys (5 ± 1 nm) immersed in non-magnetic Ag matrix by controlled simultaneous co-sputtering of Ni95Cr5 and Ag. We employed Curie temperature (TC) as an indicator of phase purity check of these nanocomposites, which is estimated to be around the bulk Ni95Cr5 value of 320 K. This confirms prevention of Cr-segregation and also entails effective control of surface oxidation. Compared to Cr-segregated Ni95Cr5 nanoalloy films and nanoclusters, we did not observe any unwanted magnetic effects such as presence Cr-antiferromagnetic transition, large non-saturation, exchange bias behavior (if any) or uncompensated higher TC values. These nanocomposites films also lose their unique magnetic properties only at elevated temperatures beyond application requirements (≥800 K), either by showing Ni-type behavior or by a complete conversion into Ni/Cr-oxides in vacuum and air environment, respectively. PMID:26750659

  7. Methodology for the analysis of transcription and translation in transcription-coupled-to-translation systems in vitro.

    PubMed

    Castro-Roa, Daniel; Zenkin, Nikolay

    2015-09-15

    The various properties of RNA polymerase (RNAP) complexes with nucleic acids during different stages of transcription involve various types of regulation and different cross-talk with other cellular entities and with fellow RNAP molecules. The interactions of transcriptional apparatus with the translational machinery have been focused mainly in terms of outcomes of gene expression, whereas the study of the physical interaction of the ribosome and the RNAP remains obscure partly due to the lack of a system that allows such observations. In this article we will describe the methodology needed to set up a pure, transcription-coupled-to-translation system in which the translocation of the ribosome can be performed in a step-wise manner towards RNAP allowing investigation of the interactions between the two machineries at colliding and non-colliding distances. In the same time RNAP can be put in various types of states, such as paused, roadblocked, backtracked, etc. The experimental system thus allows studying the effects of the ribosome on different aspects of transcription elongation and the effects by RNAP on translation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Crossing boundaries in interprofessional education: A call for instructional integration of two script concepts.

    PubMed

    Kiesewetter, Jan; Kollar, Ingo; Fernandez, Nicolas; Lubarsky, Stuart; Kiessling, Claudia; Fischer, Martin R; Charlin, Bernard

    2016-09-01

    Clinical work occurs in a context which is heavily influenced by social interactions. The absence of theoretical frameworks underpinning the design of collaborative learning has become a roadblock for interprofessional education (IPE). This article proposes a script-based framework for the design of IPE. This framework provides suggestions for designing learning environments intended to foster competences we feel are fundamental to successful interprofessional care. The current literature describes two script concepts: "illness scripts" and "internal/external collaboration scripts". Illness scripts are specific knowledge structures that link general disease categories and specific examples of diseases. "Internal collaboration scripts" refer to an individual's knowledge about how to interact with others in a social situation. "External collaboration scripts" are instructional scaffolds designed to help groups collaborate. Instructional research relating to illness scripts and internal collaboration scripts supports (a) putting learners in authentic situations in which they need to engage in clinical reasoning, and (b) scaffolding their interaction with others with "external collaboration scripts". Thus, well-established experiential instructional approaches should be combined with more fine-grained script-based scaffolding approaches. The resulting script-based framework offers instructional designers insights into how students can be supported to develop the necessary skills to master complex interprofessional clinical situations.

  9. Standardisation of digital human models.

    PubMed

    Paul, Gunther; Wischniewski, Sascha

    2012-01-01

    Digital human models (DHM) have evolved as useful tools for ergonomic workplace design and product development, and found in various industries and education. DHM systems which dominate the market were developed for specific purposes and differ significantly, which is not only reflected in non-compatible results of DHM simulations, but also provoking misunderstanding of how DHM simulations relate to real world problems. While DHM developers are restricted by uncertainty about the user need and lack of model data related standards, users are confined to one specific product and cannot exchange results, or upgrade to another DHM system, as their previous results would be rendered worthless. Furthermore, origin and validity of anthropometric and biomechanical data is not transparent to the user. The lack of standardisation in DHM systems has become a major roadblock in further system development, affecting all stakeholders in the DHM industry. Evidently, a framework for standardising digital human models is necessary to overcome current obstructions. Practitioner Summary: This short communication addresses a standardisation issue for digital human models, which has been addressed at the International Ergonomics Association Technical Committee for Human Simulation and Virtual Environments. It is the outcome of a workshop at the DHM 2011 symposium in Lyon, which concluded steps towards DHM standardisation that need to be taken.

  10. An Error-Reduction Algorithm to Improve Lidar Turbulence Estimates for Wind Energy

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

    Newman, Jennifer F.; Clifton, Andrew

    2016-08-01

    Currently, cup anemometers on meteorological (met) towers are used to measure wind speeds and turbulence intensity to make decisions about wind turbine class and site suitability. However, as modern turbine hub heights increase and wind energy expands to complex and remote sites, it becomes more difficult and costly to install met towers at potential sites. As a result, remote sensing devices (e.g., lidars) are now commonly used by wind farm managers and researchers to estimate the flow field at heights spanned by a turbine. While lidars can accurately estimate mean wind speeds and wind directions, there is still a largemore » amount of uncertainty surrounding the measurement of turbulence with lidars. This uncertainty in lidar turbulence measurements is one of the key roadblocks that must be overcome in order to replace met towers with lidars for wind energy applications. In this talk, a model for reducing errors in lidar turbulence estimates is presented. Techniques for reducing errors from instrument noise, volume averaging, and variance contamination are combined in the model to produce a corrected value of the turbulence intensity (TI), a commonly used parameter in wind energy. In the next step of the model, machine learning techniques are used to further decrease the error in lidar TI estimates.« less

  11. The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances.

    PubMed

    Hill, Jennifer W; Faulkner, Latrice D

    2017-01-01

    Obesity is increasing in prevalence across all sectors of society, and with it a constellation of associated ailments including hypertension, type 2 diabetes, and eating disorders. The melanocortin system is a critical neural system underlying the control of body weight and other functions. Deficits in the melanocortin system may promote or exacerbate the comorbidities of obesity. This system has therefore generated great interest as a potential target for treatment of obesity. However, drugs targeting melanocortin receptors are plagued by problematic side effects, including undesirable increases in sympathetic nervous system activity, heart rate, and blood pressure. Circumnavigating this roadblock will require a clearer picture of the precise neural circuits that mediate the functions of melanocortins. Recent, novel experimental approaches have significantly advanced our understanding of these pathways. We here review the latest advances in our understanding of the role of melanocortins in food intake, reward pathways, blood pressure, glucose control, and energy expenditure. The evidence suggests that downstream melanocortin-responsive circuits responsible for different physiological actions do diverge. Ultimately, a more complete understanding of melanocortin pathways and their myriad roles should allow treatments tailored to the mix of metabolic disorders in the individual patient. © 2016 The Author(s) Published by S. Karger AG, Basel.

  12. Reproductive Rights without Resources or Recourse.

    PubMed

    Mutcherson, Kimberly

    2017-12-01

    The U.S. Supreme Court declared procreation to be a fundamental right in the early twentieth century in a case involving Oklahoma's Habitual Criminal Sterilization Act, an act that permitted unconsented sterilization of individuals convicted of certain crimes. The right that the Court articulated in that case is a negative right: it requires that the government not place unjustified roadblocks in the way of people seeking to procreate, but it does not require the government to take positive steps to help people procreate if they wish to. I argue that a positive legal right is morally necessary in the United States, given the profound significance of procreation, the current barriers to access to care, and the related issues of individual and societal justice. I assume at the outset that the right to procreate should be expansive enough to include a right to noncoital reproduction. The absence of a positive right to procreate reflects not just constitutional tradition but also a governmental and societal commitment to a longstanding set of reproductive hierarchies by which those who fall outside of the traditional framing of family too frequently find their procreative dreams hindered. Reconceiving procreative rights to include a positive right would create greater opportunities to argue and lobby for increased access to technologies that are out of reach for many. © 2017 The Hastings Center.

  13. Views on Researcher-Community Engagement in Autism Research in the United Kingdom: A Mixed-Methods Study

    PubMed Central

    Pellicano, Elizabeth; Dinsmore, Adam; Charman, Tony

    2014-01-01

    There has been a substantial increase in research activity on autism during the past decade. Research into effective ways of responding to the immediate needs of autistic people is, however, less advanced, as are efforts at translating basic science research into service provision. Involving community members in research is one potential way of reducing this gap. This study therefore investigated the views of community involvement in autism research both from the perspectives of autism researchers and of community members, including autistic adults, family members and practitioners. Results from a large-scale questionnaire study (n = 1,516) showed that researchers perceive themselves to be engaged with the autism community but that community members, most notably autistic people and their families, did not share this view. Focus groups/interviews with 72 participants further identified the potential benefits and remaining challenges to involvement in research, especially regarding the distinct perspectives of different stakeholders. Researchers were skeptical about the possibilities of dramatically increasing community engagement, while community members themselves spoke about the challenges to fully understanding and influencing the research process. We suggest that the lack of a shared approach to community engagement in UK autism research represents a key roadblock to translational endeavors. PMID:25303222

  14. Random breath testing in Australia: getting it to work according to specifications.

    PubMed

    Homel, R

    1993-01-01

    After reading the deterrence literature, particularly the work of H. Laurence Ross, I concluded in the late 1970's that many road accidents could be prevented through the wholehearted implementation of random breath testing (RBT). RBT is a system of drink-drive law enforcement which aims to increase the perceived likelihood of apprehension through the use of mass breath testing techniques at roadblocks which are highly visible, are unpredictable in their locations and give the impression of ubiquity. As the result of public pressure, RBT was introduced in NSW in December 1982, with spectacular results. The law was intensively enforced and extensively advertised, partly due to the advocacy of researchers such as myself, but also because ther was an acute political need for instant results. Since RBT is a difficult enforcement technique for police to sustain in effective form, researchers must strive to improve their understanding of what works, and remain in close contact with police, policy makers and politicians. Although this process is costly in terms of time and, possibly, academic 'pay-off', it is essential if the fragile understanding of deterrence principles amongst these groups is not to lead to superficially attractive, but probably ineffective techniques such as low visibility mobile RBT.

  15. oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes

    PubMed Central

    Ho Sui, Shannan J.; Mortimer, James R.; Arenillas, David J.; Brumm, Jochen; Walsh, Christopher J.; Kennedy, Brian P.; Wasserman, Wyeth W.

    2005-01-01

    Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective. Creation of a system for the efficient identification of common regulatory mechanisms in a subset of co-expressed human genes promises to break a roadblock in functional genomics research. We have developed an integrated system that searches for evidence of co-regulation by one or more transcription factors (TFs). oPOSSUM combines a pre-computed database of conserved TFBSs in human and mouse promoters with statistical methods for identification of sites over-represented in a set of co-expressed genes. The algorithm successfully identified mediating TFs in control sets of tissue-specific genes and in sets of co-expressed genes from three transcript profiling studies. Simulation studies indicate that oPOSSUM produces few false positives using empirically defined thresholds and can tolerate up to 50% noise in a set of co-expressed genes. PMID:15933209

  16. A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

    PubMed

    Shelton, Laura M; Mukherjee, Purna; Huysentruyt, Leanne C; Urits, Ivan; Rosenberg, Joshua A; Seyfried, Thomas N

    2010-09-01

    Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

  17. Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research

    PubMed Central

    Austin, Christopher P.; Balapure, Anil K.; Birnbaum, Linda S.; Bucher, John R.; Fentem, Julia; Fitzpatrick, Suzanne C.; Fowle, John R.; Kavlock, Robert J.; Kitano, Hiroaki; Lidbury, Brett A.; Muotri, Alysson R.; Peng, Shuang-Qing; Sakharov, Dmitry; Seidle, Troy; Trez, Thales; Tonevitsky, Alexander; van de Stolpe, Anja; Whelan, Maurice; Willett, Catherine

    2015-01-01

    Summary Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved. PMID:26523530

  18. Highly Efficient Broadband Multiplexed Millimeter-Wave Vortices from Metasurface-Enabled Transmit-Arrays of Subwavelength Thickness

    NASA Astrophysics Data System (ADS)

    Jiang, Zhi Hao; Kang, Lei; Hong, Wei; Werner, Douglas H.

    2018-06-01

    Structured electromagnetic waves carrying nonvanishing orbital angular momentum (OAM) have recently opened up alternative frontiers in the field of wave physics, holding great promise for a wide range of potential applications. By leveraging geometric phases originating from spin-to-orbital interactions, spin-dependent wave phenomena can be created, leading to a more versatile realm of dispersionless wave-front manipulation. However, the currently available transmissive vortex-beam generators suffer from a narrow bandwidth, require an optically thick device profile, or are limited by a low efficiency, severely restricting their integration into systems and/or widespread usage for practical applications. We present the design methodology and a physical analysis and complete experimental characterization of a class of millimeter-wave Pancharatnam-Berry transmit-arrays with a thickness of about λ0/3 , which enables highly efficient generation and separation of spin-controlled vortex beams over a broad bandwidth, achieving an unprecedented peak efficiency of 88% for a single vortex beam and 71% for dual vortex beams. The proposed transmit-array, which is capable of providing two-dimensional OAM multiplexing and demultiplexing without normal-mode background interference, overcomes all previous roadblocks and paves the way for high-efficiency electromagnetic vortex-beam generation as well as other wave-front-shaping devices from microwave frequencies to optical wavelengths.

  19. Quantitative imaging for discovery and assembly of the metabo-regulome

    PubMed Central

    Okumoto, Sakiko; Takanaga, Hitomi; Frommer, Wolf B.

    2009-01-01

    Summary Little is known about regulatory networks that control metabolic flux in plant cells. Detailed understanding of regulation is crucial for synthetic biology. The difficulty of measuring metabolites with cellular and subcellular precision is a major roadblock. New tools have been developed for monitoring extracellular, cytosolic, organellar and vacuolar ion and metabolite concentrations with a time resolution of milliseconds to hours. Genetically encoded sensors allow quantitative measurement of steady-state concentrations of ions, signaling molecules and metabolites and their respective changes over time. Fluorescence resonance energy transfer (FRET) sensors exploit conformational changes in polypeptides as a proxy for analyte concentrations. Subtle effects of analyte binding on the conformation of the recognition element are translated into a FRET change between two fused green fluorescent protein (GFP) variants, enabling simple monitoring of analyte concentrations using fluorimetry or fluorescence microscopy. Fluorimetry provides information averaged over cell populations, while microscopy detects differences between cells or populations of cells. The genetically encoded sensors can be targeted to subcellular compartments or the cell surface. Confocal microscopy ultimately permits observation of gradients or local differences within a compartment. The FRET assays can be adapted to high-throughput analysis to screen mutant populations in order to systematically identify signaling networks that control individual steps in metabolic flux. PMID:19138219

  20. 2014 Trans-Atlantic Research and Development Interchange ...

    EPA Pesticide Factsheets

    The Trans-Atlantic Research and Development Interchange on Sustainability (TARDIS) has been bringing together a select group of scientists and engineers for in-depth discussions on sustainability on a bi-annual basis since 2004. TARDIS 2014 included twenty eight individuals from across the globe discussing issues related to progress towards sustainability. The discussion included policies, technologies, societal structure and norms, business practices and culture, and time-frames. As discussed later, the focus was on four questions: (1) what progress has been accomplished in sustainability? (2) why has there not been more progress in moving societies towards sustainability? (3) what are the road-blocks to progress towards sustainability? (4) what are the policies, technologies, and other changes that are needed to make further progress towards sustainability? One salient conclusion from TARDIS 2014 is that while sustainability has entered mainstream thinking, significant social, economic, technological, and business barriers remain to further progress towards a sustainable path as discussed throughout this report. The Trans-Atlantic Research and Development Interchange on Sustainability is a bi-annual workshop alternatively held in the United States and Austria. The purpose is to bring the best thinkers from across the globe to discuss, explore, and clarify major issues related to sustainability. A report summarizing teh finding and discussions is prepared and d

  1. Biomarkers to guide clinical therapeutics in rheumatology?

    PubMed

    Robinson, William H; Mao, Rong

    2016-03-01

    The use of biomarkers in rheumatology can help identify disease risk, improve diagnosis and prognosis, target therapy, assess response to treatment, and further our understanding of the underlying pathogenesis of disease. Here, we discuss the recent advances in biomarkers for rheumatic disorders, existing impediments to progress in this field, and the potential of biomarkers to enable precision medicine and thereby transform rheumatology. Although significant challenges remain, progress continues to be made in biomarker discovery and development for rheumatic diseases. The use of next-generation technologies, including large-scale sequencing, proteomic technologies, metabolomic technologies, mass cytometry, and other single-cell analysis and multianalyte analysis technologies, has yielded a slew of new candidate biomarkers. Nevertheless, these biomarkers still require rigorous validation and have yet to make their way into clinical practice and therapeutic development. This review focuses on advances in the biomarker field in the last 12 months as well as the challenges that remain. Better biomarkers, ideally mechanistic ones, are needed to guide clinical decision making in rheumatology. Although the use of next-generation techniques for biomarker discovery is making headway, it is imperative that the roadblocks in our search for new biomarkers are overcome to enable identification of biomarkers with greater diagnostic and predictive utility. Identification of biomarkers with robust diagnostic and predictive utility would enable precision medicine in rheumatology.

  2. Triple surveillance: a proposal for an integrated strategy to support and accelerate birth defect prevention

    PubMed Central

    Mastroiacovo, Pierpaolo

    2018-01-01

    Abstract Preventing neural tube defects (NTDs) easily qualifies as a high‐value opportunity to improve childhood survival and health: the unmet need is significant (major preventable burden), the intervention is transformative (providing sufficient folic acid), and delivery strategies (e.g., fortification) are effective in low‐resource countries. Yet, NTD prevention is lagging. Can public health surveillance help fix this problem? Critics contend that surveillance is largely unnecessary, that limited resources are best spent on interventions, and that surveillance is unrealistic in developing countries. The counterargument is twofold: (1) in the absence of surveillance, interventions will provide fewer benefits and cost more and (2) effective surveillance is likely possible nearly everywhere, with appropriate strategies. As a base strategy, we propose “triple surveillance:” integrating surveillance of cause (folate insufficiency), of disease occurrence (NTD prevalence), and of health outcomes (morbidity, mortality, and disability). For better sustainability and usefulness, it is crucial to refocus and streamline surveillance activities (no recreational data collection), weave surveillance into clinical care (integrate in clinical workflow), and, later, work on including additional risk factors and pediatric outcomes (increase benefits at low marginal cost). By doing so, surveillance becomes not a roadblock but a preferential path to prevention and better care. PMID:29532515

  3. MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures.

    PubMed

    Muraoka, Naoto; Yamakawa, Hiroyuki; Miyamoto, Kazutaka; Sadahiro, Taketaro; Umei, Tomohiko; Isomi, Mari; Nakashima, Hanae; Akiyama, Mizuha; Wada, Rie; Inagawa, Kohei; Nishiyama, Takahiko; Kaneda, Ruri; Fukuda, Toru; Takeda, Shu; Tohyama, Shugo; Hashimoto, Hisayuki; Kawamura, Yoshifumi; Goshima, Naoki; Aeba, Ryo; Yamagishi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

    2014-07-17

    Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming. © 2014 The Authors.

  4. MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures

    PubMed Central

    Muraoka, Naoto; Yamakawa, Hiroyuki; Miyamoto, Kazutaka; Sadahiro, Taketaro; Umei, Tomohiko; Isomi, Mari; Nakashima, Hanae; Akiyama, Mizuha; Wada, Rie; Inagawa, Kohei; Nishiyama, Takahiko; Kaneda, Ruri; Fukuda, Toru; Takeda, Shu; Tohyama, Shugo; Hashimoto, Hisayuki; Kawamura, Yoshifumi; Goshima, Naoki; Aeba, Ryo; Yamagishi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

    2014-01-01

    Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming. PMID:24920580

  5. Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies

    PubMed Central

    Hunsberger, Joshua; Harrysson, Ola; Shirwaiker, Rohan; Starly, Binil; Wysk, Richard; Cohen, Paul; Allickson, Julie; Yoo, James

    2015-01-01

    Summary The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014, had a vision of assisting with translating tissue engineering and regenerative medicine (TERM)-based technologies closer to the clinic. This vision was achieved by assembling leaders in the field to cover critical areas. Some of these critical areas included regulatory pathways for regenerative medicine therapies, strategic partnerships, coordination of resources, developing standards for the field, government support, priorities for industry, biobanking, and new technologies. The final day of this conference featured focused sessions on manufacturing, during which expert speakers were invited from industry, government, and academia. The speakers identified and accessed roadblocks plaguing the field where improvements in advanced manufacturing offered many solutions. The manufacturing sessions included (a) product development toward commercialization in regenerative medicine, (b) process challenges to scale up manufacturing in regenerative medicine, and (c) infrastructure needs for manufacturing in regenerative medicine. Subsequent to this, industry was invited to participate in a survey to further elucidate the challenges to translation and scale-up. This perspective article will cover the lessons learned from these manufacturing sessions and early results from the survey. We also outline a road map for developing the manufacturing infrastructure, resources, standards, capabilities, education, training, and workforce development to realize the promise of TERM. PMID:25575525

  6. Exploration of suitable dry etch technologies for directed self-assembly

    NASA Astrophysics Data System (ADS)

    Yamashita, Fumiko; Nishimura, Eiichi; Yatsuda, Koichi; Mochiki, Hiromasa; Bannister, Julie

    2012-03-01

    Directed self-assembly (DSA) has shown the potential to replace traditional resist patterns and provide a lower cost alternative for sub-20-nm patterns. One of the possible roadblocks for DSA implementation is the ability to etch the polymers to produce quality masks for subsequent etch processes. We have studied the effects of RF frequency and etch chemistry for dry developing DSA patterns. The results of the study showed a capacitively-coupled plasma (CCP) reactor with very high frequency (VHF) had superior pattern development after the block co-polymer (BCP) etch. The VHF CCP demonstrated minimal BCP height loss and line edge roughness (LER)/line width roughness (LWR). The advantage of CCP over ICP is the low dissociation so the etch rate of BCP is maintained low enough for process control. Additionally, the advantage of VHF is the low electron energy with a tight ion energy distribution that enables removal of the polymethyl methacrylate (PMMA) with good selectivity to polystyrene (PS) and minimal LER/LWR. Etch chemistries were evaluated on the VHF CCP to determine ability to treat the BCPs to increase etch resistance and feature resolution. The right combination of RF source frequencies and etch chemistry can help overcome the challenges of using DSA patterns to create good etch results.

  7. The Quest for an Effective Treatment for an Intractable Cancer: Established and Novel Therapies for Pancreatic Adenocarcinoma.

    PubMed

    Quinn, Bridget A; Lee, Nathaniel A; Kegelman, Timothy P; Bhoopathi, Praveen; Emdad, Luni; Das, Swadesh K; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

    2015-01-01

    With therapies that date back to the 1950s, and few newly approved treatments in the last 20 years, pancreatic cancer remains a significant challenge for the development of novel therapeutics. Current regimens have successfully extended patient survival, although they still lead to prognoses measured in months rather than years. The genetic diversity inherent in pancreatic tumors forms the roadblocks that must be overcome in future therapeutics. Recent insight into the genetic patterns found in tumor cells may provide clues leading to better understanding of the challenges hindering the development of treatments. Here, we review currently used drugs and established combination therapies that comprise the standard of care for a highly recalcitrant disease. Novel approaches can improve upon current therapies in a variety of ways. Enhancing specificity, such that growth inhibition and cytotoxic effects act preferentially on tumor cells, is one approach to advance treatments. This can be accomplished through the targeting of extracellular markers specific to cancer cells. Additionally, enlisting natural defenses and overcoming tumor-driven immune suppression could prove to be a useful tactic. Recent studies utilizing these approaches have yielded promising results and could contribute to an ongoing effort battling a particularly difficult cancer. © 2015 Elsevier Inc. All rights reserved.

  8. Alzheimer’s Prevention Initiative: a proposal to evaluate presymptomatic treatments as quickly as possible

    PubMed Central

    Reiman, Eric M; Langbaum, Jessica BS; Tariot, Pierre N

    2010-01-01

    Now is the time to launch the era of Alzheimer’s disease (AD) prevention research, establish the methods and infrastructure to rapidly evaluate presymptomatic AD treatments and evaluate them rigorously and rapidly in randomized clinical trials. This article is a call to arms. It contends that the evaluation of presymptomatic AD treatments must become an urgent priority, it identifies what is holding us back and proposes new public policies and scientific strategies to overcome these roadblocks. It defines the term ‘presymptomatic AD treatment,’ notes the best established biomarkers of AD progression and pathology and suggests how they could be used to rapidly evaluate presymptomatic AD treatments in the people at risk. It introduces an approach to evaluate presymptomatic AD treatments in asymptomatic people at the highest risk of imminent clinical onset and determines the extent to which the treatment’s biomarker predicts a clinical outcome. We propose an Alzheimer’s Prevention Initiative, which is now being reviewed and refined in partnership with leading academic and industry investigators. It is intended to evaluate the most promising presymptomatic AD treatments, help develop a regulatory pathway for their accelerated approval using reasonably likely surrogate end points and find demonstrably effective presymptomatic AD treatments as quickly as possible. PMID:20383319

  9. Open and Lys–His Hexacoordinated Closed Structures of a Globin with Swapped Proximal and Distal Sites

    PubMed Central

    Teh, Aik-Hong; Saito, Jennifer A.; Najimudin, Nazalan; Alam, Maqsudul

    2015-01-01

    Globins are haem-binding proteins with a conserved fold made up of α-helices and can possess diverse properties. A putative globin-coupled sensor from Methylacidiphilum infernorum, HGbRL, contains an N-terminal globin domain whose open and closed structures reveal an untypical dimeric architecture. Helices E and F fuse into an elongated helix, resulting in a novel site-swapped globin fold made up of helices A–E, hence the distal site, from one subunit and helices F–H, the proximal site, from another. The open structure possesses a large cavity binding an imidazole molecule, while the closed structure forms a unique Lys–His hexacoordinated species, with the first turn of helix E unravelling to allow Lys52(E10) to bind to the haem. Ligand binding induces reorganization of loop CE, which is stabilized in the closed form, and helix E, triggering a large conformational movement in the open form. These provide a mechanical insight into how a signal may be relayed between the globin domain and the C-terminal domain of HGbRL, a Roadblock/LC7 domain. Comparison with HGbI, a closely related globin, further underlines the high degree of structural versatility that the globin fold is capable of, enabling it to perform a diversity of functions. PMID:26094577

  10. Effects of in situ dual ion beam (He+ and D+) irradiation with simultaneous pulsed heat loading on surface morphology evolution of tungsten-tantalum alloys

    NASA Astrophysics Data System (ADS)

    Gonderman, S.; Tripathi, J. K.; Sinclair, G.; Novakowski, T. J.; Sizyuk, T.; Hassanein, A.

    2018-02-01

    The strong thermal and mechanical properties of tungsten (W) are well suited for the harsh fusion environment. However, increasing interest in using tungsten as plasma-facing components (PFCs) has revealed several key issues. These potential roadblocks necessitate more investigation of W and other alternative W based materials exposed to realistic fusion conditions. In this work, W and tungsten-tantalum (W-Ta) alloys were exposed to single (He+) and dual (He+  +  D+) ion irradiations with simultaneous pulsed heat loading to elucidate PFCs response under more realistic conditions. Laser only exposer revealed significantly more damage in W-Ta samples as compared to pure W samples. This was due to the difference in the mechanical properties of the two different materials. Further erosion studies were conducted to evaluate the material degradation due to transient heat loading in both the presence and absence of He+ and/or D+ ions. We concluded that erosion of PFC materials was significantly enhanced due to the presence of ion irradiation. This is important as it demonstrates that there are key synergistic effects resulting from more realistic fusion loading conditions that need to be considered when evaluating the response of plasma facing materials.

  11. Shared Opportunities on Institutional Lands: On-Site Food Production, Its Benefits, Barriers, and Opportunities.

    PubMed

    Knezevic, Irena; Mount, Phil; Clement, Chantal

    2016-10-01

    This article outlines preliminary findings of a 3-year project that explored on-site food production on institutional properties, primarily healthcare facilities. There are growing pressures on healthcare facilities to improve their food offerings and incorporate food gardens into their health programs. While several healthcare facilities produce food on-site, there are few studies that explore opportunities, capacities, and institutional barriers related to on-site food production. The study employed mixed methods including historical review, case studies, surveys, interviews, pilot garden projects, and Geographic Information System mapping. The number of participating institutions varied by method. Benefits associated with on-site food production can be health, economic, environmental, and social. There are also institutional barriers including administrative roadblocks, perceived obstacles, and the difficulty in quantitatively, measuring the qualitatively documented benefits. The benefits of food gardens far outweigh the challenges. On-site food production has tremendous potential to improve nutrition for staff and patients, offer healing spaces, better connect institutions with the communities in which they are located, and provide the long-professed benefits of gardening for all involved-from therapeutic benefits and outdoor physical activities to developing skills and social relationships in ways that few other activities do. © The Author(s) 2016.

  12. 'Taking X-ray phase contrast imaging into mainstream applications' and its satellite workshop 'Real and reciprocal space X-ray imaging'.

    PubMed

    Olivo, Alessandro; Robinson, Ian

    2014-03-06

    A double event, supported as part of the Royal Society scientific meetings, was organized in February 2013 in London and at Chicheley Hall in Buckinghamshire by Dr A. Olivo and Prof. I. Robinson. The theme that joined the two events was the use of X-ray phase in novel imaging approaches, as opposed to conventional methods based on X-ray attenuation. The event in London, led by Olivo, addressed the main roadblocks that X-ray phase contrast imaging (XPCI) is encountering in terms of commercial translation, for clinical and industrial applications. The main driver behind this is the development of new approaches that enable XPCI, traditionally a synchrotron method, to be performed with conventional laboratory sources, thus opening the way to its deployment in clinics and industrial settings. The satellite meeting at Chicheley Hall, led by Robinson, focused on the new scientific developments that have recently emerged at specialized facilities such as third-generation synchrotrons and free-electron lasers, which enable the direct measurement of the phase shift induced by a sample from intensity measurements, typically in the far field. The two events were therefore highly complementary, in terms of covering both the more applied/translational and the blue-sky aspects of the use of phase in X-ray research. 

  13. Grand challenges in mass storage: A systems integrators perspective

    NASA Technical Reports Server (NTRS)

    Lee, Richard R.; Mintz, Daniel G.

    1993-01-01

    Within today's much ballyhooed supercomputing environment, with its CFLOPS of CPU power, and Gigabit networks, there exists a major roadblock to computing success; that of Mass Storage. The solution to this mass storage problem is considered to be one of the 'Grand Challenges' facing the computer industry today, as well as long into the future. It has become obvious to us, as well as many others in the industry, that there is no clear single solution in sight. The Systems Integrator today is faced with a myriad of quandaries in approaching this challenge. He must first be innovative in approach, second choose hardware solutions that are volumetric efficient; high in signal bandwidth; available from multiple sources; competitively priced, and have forward growth extendibility. In addition he must also comply with a variety of mandated, and often conflicting software standards (GOSIP, POSIX, IEEE, MSRM 4.0, and others), and finally he must deliver a systems solution with the 'most bang for the buck' in terms of cost vs. performance factors. These quandaries challenge the Systems Integrator to 'push the envelope' in terms of his or her ingenuity and innovation on an almost daily basis. This dynamic is explored further, and an attempt to acquaint the audience with rational approaches to this 'Grand Challenge' is made.

  14. Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

    PubMed

    Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

    2016-06-01

    Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Electromagnetic metamaterials: Engineering the physics of light

    NASA Astrophysics Data System (ADS)

    Driscoll, Tom

    Structures engineered to give a specific response to light are certainly nothing new. The long history of engineering materials response to light encompasses seemingly disparate structures from antennas to stained glass, lighting rods to mirrors. It is only in the recent decade, however, that we have appreciated the full gamut of possibilities this field holds, and envisioned paths towards realizing these possibilities. The new field of electromagnetic metamaterials has given us the potential to create devices that manipulate light in nearly any way we can envision. The work of this thesis is involved principally with the study of metamaterials and their unique properties. Using a wide array of developed apparatus and techniques - spanning microwave frequencies through the infrared - we investigate metamaterial behavior, and the ways they differ from conventional materials. Applications are always kept in the forefront of thought. The demonstration of a graded negative-index lens, fabricated from metamaterial fiberglass composite, highlights the potential of these structures. Characterization procedures and instruments suitable for metamaterial samples, developed in the course of this work, enable not only our investigation of the physics of metamaterials, but also facilitate the full design cycle critical to engineering. Our demonstration of dynamic tuning directly addresses the role bandwidth plays as a major roadblock to metamaterial devices. Finally a demonstrated novel use as a sensor/detector adds to the growing list of metamaterial roles in emerging technology.

  16. Losses, gain, and lasing in organic and perovskite active materials (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pourdavoud, Neda; Riedl, Thomas J.

    2016-09-01

    Organic solid state lasers (OSLs) based on semiconducting polymers or small molecules have seen some significant progress over the past decade. Highly efficient organic gain materials combined with high-Q resonator geometries (distributed feedback (DFB), VCSEL, etc.) have enabled OSLs, optically pumped by simple inorganic laser diodes or even LEDs. However, some fundamental goals remain to be reached, like continuous wave (cw) operation and injection lasing. I will address various loss mechanisms related to accumulated triplet excitons or long-lived polarons that in combination with the particular photo-physics of organic gain media state the dominant road-blocks on the way to reach these goals. I will discuss the recent progress in fundamental understanding of these loss processes, which now provides a solid basis for modelling, e.g. of laser dynamics. Avenues to mitigate these fundamental loss mechanisms, e.g. by alternative materials will be presented. In this regard, a class of gain materials based on organo-lead halide perovskites re-entered the scene as light emitters, recently. Enjoying a tremendous lot of attention as active material for solution processed solar cells with a 20+% efficiency, they have recently unveiled their exciting photo-physics for lasing applications. Optically pumped lasing in these materials has been achieved. I will discuss some of the unique properties that render this class of materials a promising candidate to overcome some of the limitations of "classical" organic gain media.

  17. CuPt and CuPtRu Nanostructures for Ammonia Oxidation Reaction

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

    Manso, R H.; Song, L.; Liang, Z.

    Liquid fuels, such as methanol, ethanol, and ammonia, are attractive alternative to hydrogen for fuel cells due to their lower costs for storage and distribution. However, lack of sufficiently active catalysts for their oxidation reactions is a roadblock. Our previous study found that Pt 3Cu nanodendrites yielded higher activity and durability than Pt nanoparticles for methanol oxidation reaction (MOR) in acid. In this study, we synthesized two types of nanostructures of CuPt and CuPtRu catalysts via seed-mediated growth of Pt and Ru on Cu and tested their performance for ammonia oxidation reaction (AOR) in alkaline solution. Unlike for MOR, themore » nanodendrites do not promote AOR activity - CuPt performs similar to Pt and CuPtRu is less active than Pt. Interestingly, the AOR peak current is increased by 64% on CuPt nanowires and 330% on CuPtRu nanowires as compared to Pt nanoparticles. These results suggest that AOR prefers extended surface on long nanowires, distinctly differing from MOR. This can be contributed to two factors: NH 3 oxidization to N 2 involves dimerization of two N-containing intermediates to form the N-N bond and diffusion batters for adsorbed intermediates are generally lower on terrace than at low-coordination sites. This demonstrated strong effect of surface morphology will be further studied and utilized in developing advanced AOR nanocatalysts.« less

  18. Advances in Atmospheric Radiation Measurements and Modeling Needed to Improve Air Safety

    NASA Astrophysics Data System (ADS)

    Tobiska, W. Kent; Atwell, William; Beck, Peter; Benton, Eric; Copeland, Kyle; Dyer, Clive; Gersey, Brad; Getley, Ian; Hands, Alex; Holland, Michael; Hong, Sunhak; Hwang, Junga; Jones, Bryn; Malone, Kathleen; Meier, Matthias M.; Mertens, Chris; Phillips, Tony; Ryden, Keith; Schwadron, Nathan; Wender, Stephen A.; Wilkins, Richard; Xapsos, Michael A.

    2015-04-01

    Air safety is tied to the phenomenon of ionizing radiation from space weather, primarily from galactic cosmic rays but also from solar energetic particles. A global framework for addressing radiation issues in this environment has been constructed, but more must be done at international and national levels. Health consequences from atmospheric radiation exposure are likely to exist. In addition, severe solar radiation events may cause economic consequences in the international aviation community due to exposure limits being reached by some crew members. Impacts from a radiation environment upon avionics from high-energy particles and low-energy, thermalized neutrons are now recognized as an area of active interest. A broad community recognizes that there are a number of mitigation paths that can be taken relative to the human tissue and avionics exposure risks. These include developing active monitoring and measurement programs as well as improving scientific modeling capabilities that can eventually be turned into operations. A number of roadblocks to risk mitigation still exist, such as effective pilot training programs as well as monitoring, measuring, and regulatory measures. An active international effort toward observing the weather of atmospheric radiation must occur to make progress in mitigating radiation exposure risks. Stakeholders in this process include standard-making bodies, scientific organizations, regulatory organizations, air traffic management systems, aircraft owners and operators, pilots and crew, and even the public.

  19. Triple surveillance: a proposal for an integrated strategy to support and accelerate birth defect prevention.

    PubMed

    Botto, Lorenzo D; Mastroiacovo, Pierpaolo

    2018-02-01

    Preventing neural tube defects (NTDs) easily qualifies as a high-value opportunity to improve childhood survival and health: the unmet need is significant (major preventable burden), the intervention is transformative (providing sufficient folic acid), and delivery strategies (e.g., fortification) are effective in low-resource countries. Yet, NTD prevention is lagging. Can public health surveillance help fix this problem? Critics contend that surveillance is largely unnecessary, that limited resources are best spent on interventions, and that surveillance is unrealistic in developing countries. The counterargument is twofold: (1) in the absence of surveillance, interventions will provide fewer benefits and cost more and (2) effective surveillance is likely possible nearly everywhere, with appropriate strategies. As a base strategy, we propose "triple surveillance:" integrating surveillance of cause (folate insufficiency), of disease occurrence (NTD prevalence), and of health outcomes (morbidity, mortality, and disability). For better sustainability and usefulness, it is crucial to refocus and streamline surveillance activities (no recreational data collection), weave surveillance into clinical care (integrate in clinical workflow), and, later, work on including additional risk factors and pediatric outcomes (increase benefits at low marginal cost). By doing so, surveillance becomes not a roadblock but a preferential path to prevention and better care. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  20. Fast segmentation and high-quality three-dimensional volume mesh creation from medical images for diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Jermyn, Michael; Ghadyani, Hamid; Mastanduno, Michael A.; Turner, Wes; Davis, Scott C.; Dehghani, Hamid; Pogue, Brian W.

    2013-08-01

    Multimodal approaches that combine near-infrared (NIR) and conventional imaging modalities have been shown to improve optical parameter estimation dramatically and thus represent a prevailing trend in NIR imaging. These approaches typically involve applying anatomical templates from magnetic resonance imaging/computed tomography/ultrasound images to guide the recovery of optical parameters. However, merging these data sets using current technology requires multiple software packages, substantial expertise, significant time-commitment, and often results in unacceptably poor mesh quality for optical image reconstruction, a reality that represents a significant roadblock for translational research of multimodal NIR imaging. This work addresses these challenges directly by introducing automated digital imaging and communications in medicine image stack segmentation and a new one-click three-dimensional mesh generator optimized for multimodal NIR imaging, and combining these capabilities into a single software package (available for free download) with a streamlined workflow. Image processing time and mesh quality benchmarks were examined for four common multimodal NIR use-cases (breast, brain, pancreas, and small animal) and were compared to a commercial image processing package. Applying these tools resulted in a fivefold decrease in image processing time and 62% improvement in minimum mesh quality, in the absence of extra mesh postprocessing. These capabilities represent a significant step toward enabling translational multimodal NIR research for both expert and nonexpert users in an open-source platform.

  1. Evaluation of the American college of surgeons thyroid and parathyroid ultrasound course: Results of a web-based survey.

    PubMed

    Sharma, Giriraj K; Sofferman, Robert A; Armstrong, William B

    2017-08-01

    The American College of Surgeons Thyroid and Parathyroid Ultrasound Skills-Oriented Course (TPUSC) was designed to teach surgeons how to interpret and perform office-based head and neck ultrasound (HNUS). The objective of this study was to survey attendees of the TPUSC to evaluate the usefulness of the course, to track surgeon performed HNUS practice patterns, and to help identify potential roadblocks to incorporation of HNUS into a surgeon's practice. Cross-sectional survey. A Web-based survey was sent to 952 surgeons who completed the TPUSC between 2010 and 2014. Questions included surgeon specialty, practice type, Likert scale rating of the TPUSC, competency with different HNUS procedures, and current HNUS practice patterns. The response rate was 24%. On a scale from 1 (not useful) to 5 (extremely valuable), the mean course usefulness rating was 4.2. Educational goals were met for 194 (92%) surgeons, and 162 (77%) surgeons reported performing HNUS in their practice. Of 48 surgeons not performing HNUS, 24 (50%) attributed insufficient time in their clinic schedule, and 21 (44%) attributed high equipment costs. The TPUSC is a valuable educational experience for surgeons seeking to gain proficiency in HNUS. The majority of TPUSC graduates gain competency with at least one type of HNUS procedure following the course. NA Laryngoscope, 127:1950-1958, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Induced pluripotent stem cells (iPSC)-derived retinal cells in disease modeling and regenerative medicine.

    PubMed

    Rathod, Reena; Surendran, Harshini; Battu, Rajani; Desai, Jogin; Pal, Rajarshi

    2018-02-12

    Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Issues and Solutions for Bringing Heterogeneous Water Cycle Data Sets Together

    NASA Technical Reports Server (NTRS)

    Acker, James; Kempler, Steven; Teng, William; Belvedere, Deborah; Liu, Zhong; Leptoukh, Gregory

    2010-01-01

    The water cycle research community has generated many regional to global scale products using data from individual NASA missions or sensors (e.g., TRMM, AMSR-E); multiple ground- and space-based data sources (e.g., Global Precipitation Climatology Project [GPCP] products); and sophisticated data assimilation systems (e.g., Land Data Assimilation Systems [LDAS]). However, it is often difficult to access, explore, merge, analyze, and inter-compare these data in a coherent manner due to issues of data resolution, format, and structure. These difficulties were substantiated at the recent Collaborative Energy and Water Cycle Information Services (CEWIS) Workshop, where members of the NASA Energy and Water cycle Study (NEWS) community gave presentations, provided feedback, and developed scenarios which illustrated the difficulties and techniques for bringing together heterogeneous datasets. This presentation reports on the findings of the workshop, thus defining the problems and challenges of multi-dataset research. In addition, the CEWIS prototype shown at the workshop will be presented to illustrate new technologies that can mitigate data access roadblocks encountered in multi-dataset research, including: (1) Quick and easy search and access of selected NEWS data sets. (2) Multi-parameter data subsetting, manipulation, analysis, and display tools. (3) Access to input and derived water cycle data (data lineage). It is hoped that this presentation will encourage community discussion and feedback on heterogeneous data analysis scenarios, issues, and remedies.

  4. Translational physiology: from molecules to public health.

    PubMed

    Seals, Douglas R

    2013-07-15

    The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

  5. Translational physiology: from molecules to public health

    PubMed Central

    Seals, Douglas R

    2013-01-01

    The term ‘translational research’ was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by ‘reverse translation’ in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise. PMID:23732641

  6. CuPt and CuPtRu Nanostructures for Ammonia Oxidation Reaction

    DOE PAGES

    Manso, R H.; Song, L.; Liang, Z.; ...

    2018-04-01

    Liquid fuels, such as methanol, ethanol, and ammonia, are attractive alternative to hydrogen for fuel cells due to their lower costs for storage and distribution. However, lack of sufficiently active catalysts for their oxidation reactions is a roadblock. Our previous study found that Pt 3Cu nanodendrites yielded higher activity and durability than Pt nanoparticles for methanol oxidation reaction (MOR) in acid. In this study, we synthesized two types of nanostructures of CuPt and CuPtRu catalysts via seed-mediated growth of Pt and Ru on Cu and tested their performance for ammonia oxidation reaction (AOR) in alkaline solution. Unlike for MOR, themore » nanodendrites do not promote AOR activity - CuPt performs similar to Pt and CuPtRu is less active than Pt. Interestingly, the AOR peak current is increased by 64% on CuPt nanowires and 330% on CuPtRu nanowires as compared to Pt nanoparticles. These results suggest that AOR prefers extended surface on long nanowires, distinctly differing from MOR. This can be contributed to two factors: NH 3 oxidization to N 2 involves dimerization of two N-containing intermediates to form the N-N bond and diffusion batters for adsorbed intermediates are generally lower on terrace than at low-coordination sites. This demonstrated strong effect of surface morphology will be further studied and utilized in developing advanced AOR nanocatalysts.« less

  7. Silencing the roadblocks to effective triple-negative breast cancer treatments by siRNA nanoparticles.

    PubMed

    Parvani, Jenny G; Jackson, Mark W

    2017-04-01

    Over the past decade, RNA interference (RNAi) has been ubiquitously utilized to study biological function in vitro ; however, limitations were associated with its utility in vivo More recently, small interfering RNA (siRNA) nanoparticles with improved biocompatibility have gained prevalence as a potential therapeutic option for the treatment of various diseases. The adaptability of siRNA nanoparticles enables the delivery of virtually any siRNA, which is especially advantageous for therapeutic applications in heterogeneous diseases that lack unifying molecular features, such as triple-negative breast cancer (TNBC). TNBC is an aggressive subtype of breast cancer that is stratified by the lack of estrogen receptor/progesterone receptor expression and HER2 amplification. There are currently no FDA-approved targeted therapies for the treatment of TNBCs, making cytotoxic chemotherapy the only treatment option available to these patients. In this review, we outline the current status of siRNA nanoparticles in clinical trials for cancer treatment and discuss the promising preclinical approaches that have utilized siRNA nanoparticles for TNBC treatment. Next, we address TNBC subtype-specific therapeutic interventions and highlight where and how siRNA nanoparticles fit into these strategies. Lastly, we point out ongoing challenges in the field of siRNA nanoparticle research that, if addressed, would significantly improve the efficacy of siRNA nanoparticles as a therapeutic option for cancer treatment. © 2017 Society for Endocrinology.

  8. ClpXP protease targets long-lived DNA translocation states of a helicase-like motor to cause restriction alleviation

    PubMed Central

    Simons, Michelle; Diffin, Fiona M.; Szczelkun, Mark D.

    2014-01-01

    We investigated how Escherichia coli ClpXP targets the helicase-nuclease (HsdR) subunit of the bacterial Type I restriction–modification enzyme EcoKI during restriction alleviation (RA). RA is a temporary reduction in endonuclease activity that occurs when Type I enzymes bind unmodified recognition sites on the host genome. These conditions arise upon acquisition of a new system by a naïve host, upon generation of new sites by genome rearrangement/mutation or during homologous recombination between hemimethylated DNA. Using recombinant DNA and proteins in vitro, we demonstrate that ClpXP targets EcoKI HsdR during dsDNA translocation on circular DNA but not on linear DNA. Protein roadblocks did not activate HsdR proteolysis. We suggest that DNA translocation lifetime, which is elevated on circular DNA relative to linear DNA, is important to RA. To identify the ClpX degradation tag (degron) in HsdR, we used bioinformatics and biochemical assays to design N- and C-terminal mutations that were analysed in vitro and in vivo. None of the mutants produced a phenotype consistent with loss of the degron, suggesting an as-yet-unidentified recognition pathway. We note that an EcoKI nuclease mutant still produces cell death in a clpx− strain, consistent with DNA damage induced by unregulated motor activity. PMID:25260590

  9. A rational design for hepatitis B virus X protein refolding and bioprocess development guided by second virial coefficient studies.

    PubMed

    Basu, Anindya; Chen, Wei Ning; Leong, Susanna Su Jan

    2011-04-01

    The hepatitis B virus X (HBx) protein is well known for its role in hepatitis B virus infection that often leads to hepatocellular carcinoma. Despite the clinical importance of HBx, there is little progress in anti-HBx drug development strategies due to shortage of HBx from native sources. Consistent expression of HBx as insoluble inclusion bodies within various expression systems has largely hindered HBx manufacturing via economical biosynthesis routes. Confronted by this roadblock, this study aims to quantitatively understand HBx protein behaviour in solution that will guide the rational development of a refolding-based bioprocess for HBx production. Second virial coefficient (SVC) measurements were employed to study the effects of varying physicochemical parameters on HBx intermolecular protein interaction. The SVC results suggest that covalent HBx aggregates play a key role in protein destabilisation during refolding. The use of an SVC-optimised refolding environment yielded bioactive and soluble HBx proteins from the denatured-reduced inclusion body state. This study provides new knowledge on HBx solubility behaviour in vitro, which is important in structure-function elucidation behaviour of this hydrophobic protein. Importantly, a rational refolding-based Escherichia coli bioprocess that can deliver purified and soluble HBx at large scale is successfully developed, which opens the way for rapid preparation of soluble HBx for further clinical and characterisation studies.

  10. A systematic investigation of SO2 removal dynamics by coal-based activated cokes: The synergic enhancement effect of hierarchical pore configuration and gas components

    NASA Astrophysics Data System (ADS)

    Sun, Fei; Gao, Jihui; Liu, Xin; Tang, Xiaofan; Wu, Shaohua

    2015-12-01

    For the aim to break through the long-term roadblock to porous carbon based SO2 removal technology, typical coal-based activated cokes differing in terms of surface area, pore configuration and surface functional properties, were employed to investigate the SO2 removal dynamics. Among the employed activated cokes, the one with a hierarchically porous structure greatly enhanced the SO2 removal dynamics under the simulated flue gas compositions. More detailedly, SO2 separate adsorption property under normal temperature and pressure evidenced that monolayer SO2 molecules anchoring on micropore surface is the main adsorption pattern. The catalytic oxidation of SO2 follows the Eley-Rideal mechanism by which SO2 was firstly oxidized by molecular oxygen into SO3 which could depart partially to release the active sites for further adsorption. For the role of hierarchical pore configuration, it was proposed that micropores serve as gas adsorption and reaction accommodation, meso-/macropores act as byproduct H2SO4 transport and buffing reservoirs, which may in turn gives rise to the recovery of active sites in micropores and guarantees the continuous proceeding of sulfur-containing species transformation in the micropores. The present results suggest that pore configuration or interconnecting pattern, but not mere surface area or pore volume, should be favourably considered for optimizing heterogeneous gas-solid adsorption and reaction.

  11. Quality of Type II Diabetes Care in Primary Health Care Centers in Kuwait: Employment of a Diabetes Quality Indicator Set (DQIS).

    PubMed

    Badawi, Dalia; Saleh, Shadi; Natafgi, Nabil; Mourad, Yara; Behbehani, Kazem

    2015-01-01

    Diabetes Mellitus is one of the major public health challenges, affecting more than 347 million adults worldwide. The impact of diabetes necessitates assessing the quality of care received by people with diabetes, especially in countries with a significant diabetes burden such as Kuwait. This paper aimed at piloting an approach for measuring Type II diabetes care performance through the use of a diabetes quality indicator set (DQIS) in primary health care. The DQIS for Kuwait was adapted from that developed by the National Diabetes Quality Improvement Alliance and the International Diabetes Federation. Five key care domains/measures were employed: (1) Blood glucose level measurement, (2) Cholesterol level measurement, (3) Blood pressure measurement, (4) Kidney function testing and (5) Smoking status check. The sample included the four major primary health care centers with the highest case load in Kuwait City, 4,241 patients in 2012 and 3,211 in 2010. Findings revealed the applicability and utility of employing performance indicators for diabetes care in Kuwait. Furthermore, findings revealed that many of the primary health care centers have achieved noteworthy improvement in diabetes care between 2010 and 2012, with the exception of smoking status check. The DQIS can help policymakers identify performance gaps and investigate key system roadblocks related to diabetes care in Kuwait.

  12. Overexpression of Thiamin Biosynthesis Genes in Rice Increases Leaf and Unpolished Grain Thiamin Content But Not Resistance to Xanthomonas oryzae pv. oryzae

    PubMed Central

    Dong, Wei; Thomas, Nicholas; Ronald, Pamela C.; Goyer, Aymeric

    2016-01-01

    Thiamin diphosphate (ThDP), also known as vitamin B1, serves as an enzymatic cofactor in glucose metabolism, the Krebs cycle, and branched-chain amino acid biosynthesis in all living organisms. Unlike plants and microorganisms, humans are not able to synthesize ThDP de novo and must obtain it from their diet. Staple crops such as rice are poor sources of thiamin. Hence, populations that mainly consume rice commonly suffer thiamin deficiency. In addition to thiamin’s nutritional function, studies in rice have shown that some thiamin biosynthesis genes are involved in resistance to Xanthomonas oryzae, which causes a serious disease in rice fields. This study shows that overexpression of two thiamin biosynthesis genes, 4-methyl-5-β-hydroxyethylthiazole phosphate synthase and 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate synthase, involved in the first steps of the thiazole and pyrimidine synthesis branches, respectively, increased thiamin content up to fivefold in unpolished seeds that retain the bran. However, thiamin levels in polished seeds with removed bran were similar to those found in polished control seeds. Plants with higher accumulation of thiamin did not show enhanced resistance to X. oryzae. These results indicate that stacking of two traits can enhance thiamin accumulation in rice unpolished grain. We discuss potential roadblocks that prevent thiamin accumulation in the endosperm. PMID:27242822

  13. Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription

    PubMed Central

    Majumder, Parijat; Banerjee, Amrita; Shandilya, Jayasha; Senapati, Parijat; Chatterjee, Snehajyoti; Kundu, Tapas K.; Dasgupta, Dipak

    2013-01-01

    The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as “chromatin remodeling”. In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance. PMID:23460895

  14. What fosters concern for inequality among American adolescents?

    PubMed

    Cech, Erin A

    2017-01-01

    Understanding cultural beliefs about social and economic inequality is vital to discerning the roadblocks and pathways to addressing that inequality. The foundation of concern for inequality is laid during adolescence, yet scholars understand little about the factors that influence whether and how adolescents come to express such concern. Arguing that structural and cultural contexts are just as consequential as whether adolescents themselves are members of disadvantaged groups, I draw on four theoretical perspectives to identify factors that influence adolescents' concern for addressing inequality: the underdog thesis, intergroup contact theory, the education enlightens thesis, and ideological buttressing. Using representative restricted-use Educational Longitudinal Survey data, I find that 12th-graders' beliefs are indeed influenced by more than their own demography: the diversity of their social milieu, the content of education in and out of the classroom, and ideological buttressing via political region and entertainment all influence whether they express concern for addressing inequality. These findings suggest extensions and amendments to the four theoretical perspectives and underscore the importance of studying structural and cultural factors that shape beliefs about inequality. The results also point to several interventions that may increase students' concern for inequality: involvement in civic-oriented extracurricular activities, more education in academic subjects that consider inequality, nurturing of cross-race friendships, and increased leisure reading. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Implementing the new clinical nurse leader role while gleaning insights from the past.

    PubMed

    Moore, Linda Weaver; Leahy, Cathy

    2012-01-01

    This qualitative study explored the experiences of clinical nurse leaders (CNLs) as they implemented this new role. Twenty-four CNLs participated. Data were collected via an e-mail-distributed questionnaire. Data from open-ended questions were used to conduct a qualitative content analysis. Data were categorized according to question, key thoughts and phrases were established, and themes were determined. Findings revealed that nonsystematic role introduction was common. Two challenges to role implementation included role confusion and being overworked. The most positive aspect of the role was remaining close to the point of care. Participants noted that the overall response of the health care team to the role was positive despite participants' belief that the greatest roadblock to role success was the lack of support by nurse administrators. The support of nurse administrators and clear role expectations were viewed as essential for role sustain-ability. Understanding the experiences of CNLs as they launch this new role can provide insights for educators, administrators, CNLs, and other health care providers regarding the success and sustainability of the role. In addition, understanding the similarities between the clinical nurse specialist (CNS) role initiation in the past and the CNL role initiation today can foster the development of strategies for confronting the challenges of new role implementation. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. How small can MOSFETs get?

    NASA Astrophysics Data System (ADS)

    Risch, Lothar

    2001-10-01

    Scaling of CMOS technology made possible the key appliances of our information technology society, like the PC, mobile communication, and the internet. Reduction of feature sizes for semiconductor devices continued according to Moore's law for the last 25 years in order to achieve higher integration densities, higher speed, lower power consumption, and lower costs. But now, as we approach the sub 100 nm regime, several roadblocks have been predicted for the next generations down to 35 nm. The latest ITRS roadmap 99 describes in detail the challenges which have to be addressed for the future CMOS technology nodes, regarding lithography, metallization, power dissipation, and circuit design. Also for the MOSFET, performance degradation is a big issue. Because this is not a limitation from basic physical laws, novel architectures for MOSFETs will be needed to improve again the electrical characteristics and thus pave the way to much smaller transistors than expected in the past. 25 nm CMOS seems to be feasible using very thin silicon substrates on insulator. Further improvements down to 10 nm are very likely with two gates for the control of the charge carriers. So, it is very likely that CMOS will not end with today's roadmap at 35 nm or even before, but may continue with non bulk devices and fully depleted channels. Finally, tunnelling from source to drain will set an end to the reduction of channel length, which is estimated to be below 5 nm.

  17. Terahertz-Regime, Micro-VEDs: Evaluation of Micromachined TWT Conceptual Designs

    NASA Technical Reports Server (NTRS)

    Booske, John H.; Kory, Carol L.; Gallagher, D.; van der Weide, Daniel W.; Limbach, S; Gustafson, P; Lee, W.-J.; Gallagher, S.; Jain, K.

    2001-01-01

    Summary form only given. The Terahertz (THz) region of the electromagnetic spectrum (approx.300-3000 GHz) has enormous potential for high-data-rate communications, spectroscopy, astronomy, space research, medicine, biology, surveillance, remote sensing, industrial process control, etc. The most critical roadblock to full exploitation of the THz band is lack of coherent radiation sources that are powerful (0.01-10.0 W continuous wave), efficient (>1 %), frequency agile (instantaneously tunable over 1% bandwidths or more), reliable, and relatively inexpensive. Micro-machined Vacuum Electron Devices (micro-VEDs) represent a promising solution. We describe prospects for miniature, THz-regime TWTs fabricated using micromachining techniques. Several approx.600 GHz conceptual designs are compared. Their expected performance has been analyzed using SD, 2.51), and 3D TWT codes. A folded waveguide (FWG) TWT forward-wave amplifier design is presented based on a Northrop Grumman (NGC) optimized design procedure. This conceptual device is compared to the simulated performance of a novel, micro-VED helix TWT. Conceptual FWG TWT backward-wave amplifiers and oscillators are also discussed. A scaled (100 GHz) FWG TWT operating at a relatively low voltage (-12 kV) is under development at NGC. Also, actual-size micromachining experiments are planned to evaluate the feasibility of arrays of micro-VED TWTs. Progress and results of these efforts are described. This work was supported, in part by AFOSR, ONR, and NSF.

  18. To be or not to be alive: How recent discoveries challenge the traditional definitions of viruses and life.

    PubMed

    Forterre, Patrick

    2016-10-01

    Three major discoveries have recently profoundly modified our perception of the viral world: molecular ecologists have shown that viral particles are more abundant than cells in natural environments; structural biologists have shown that some viruses from the three domains of life, Bacteria, Eukarya and Archaea, are evolutionarily related, and microbiologists have discovered giant viruses that rival with cells in terms of size and gene content. I discuss here the scientific and philosophical impact of these discoveries on the debates over the definition, nature (living or not), and origin of viruses. I suggest that viruses have often been considered non-living, because they are traditionally assimilated to their virions. However, the term virus describes a biological process and should integrate all aspects of the viral reproduction cycle. It is especially important to focus on the intracellular part of this cycle, the virocell, when viral information is actively expressed and reproduced, allowing the emergence of new viral genes. The virocell concept theoretically removes roadblocks that prevent defining viruses as living organisms. However, defining a "living organism" remains challenging, as indicated by the case of organelles that evolved from intracellular bacteria. To bypass this problem, I suggest considering that all biological entities that actively participate in the process of life are living. Copyright © 2016. Published by Elsevier Ltd.

  19. Dissecting the evolution of dark matter subhaloes in the Bolshoi simulation

    NASA Astrophysics Data System (ADS)

    van den Bosch, Frank C.

    2017-06-01

    We present a comprehensive analysis of the evolution of dark matter subhaloes in the cosmological Bolshoi simulation. We identify a complete set of 12 unique evolution channels by which subhaloes evolve in between simulation outputs, and study their relative importance and demographics. We show that instantaneous masses and maximum circular velocities of individual subhaloes are extremely noisy, despite the use of a sophisticated, phase-space-based halo finder. We also show that subhaloes experience frequent penetrating encounters with other subhaloes (on average about one per dynamical time), and that subhaloes whose apo-centre lies outside the virial radius of their host (the 'ejected' or 'backsplash' haloes) experience tidal forces that modify their orbits. This results in an average fractional subhalo exchange rate among host haloes of ˜0.01 Gyr-1 (at the present time). In addition, we show that there are three distinct disruption channels; one in which subhaloes drop below the mass resolution limit of the simulation, one in which subhaloes 'merge' with their host halo largely driven by dynamical friction, and one in which subhaloes abruptly disintegrate. We estimate that roughly 80 per cent of all subhalo disruption in the Bolshoi simulation is numerical, rather than physical. This 'overmerging' is a serious road-block for the use of numerical simulations to interpret small-scale clustering, or for any other study that is sensitive to the detailed demographics of dark matter substructure.

  20. Opportunities and roadblocks in utilizing forages and small grains for liquid fuels.

    PubMed

    Sarath, Gautam; Mitchell, Robert B; Sattler, Scott E; Funnell, Deanna; Pedersen, Jeffery F; Graybosch, Robert A; Vogel, Kenneth P

    2008-05-01

    This review focuses on the potential advantages and disadvantages of forages such as switchgrass (Panicum virgatum), and two small grains: sorghum (Sorghum bicolor), and wheat (Triticum aesitvum), as feedstocks for biofuels. It highlights the synergy provided by applying what is known from forage digestibility and wheat and sorghum starch properties studies to the biofuels sector. Opportunities therefore, exist to improve biofuel qualities in these crops via genetics and agronomics. In contrast to cereal crops, switchgrass still retains tremendous exploitable genetic diversity, and can be specifically improved to fit a particular agronomic, management, and conversion platform. Combined with emerging studies on switchgrass genomics, conversion properties and management, the future for genetic modification of this species through conventional and molecular breeding strategies appear to be bright. The presence of brown-midrib mutations in sorghum that alter cell wall composition by reducing lignin and other attributes indicate that sorghum could serve as an important model species for C(4)-grasses. Utilization of the brown-midrib traits could lead to the development of forage and sweet sorghums as novel biomass crops. Additionally, wheat crop residue, and wheat and sorghum with improved starch content and composition represent alternate biofuel sources. However, the use of wheat starch as a biofuel is unlikely but its value as a model to study starch properties on biofuel yields holds significant promise.

  1. Flow cytometry-assisted rapid isolation of recombinant Plasmodium berghei parasites exemplified by functional analysis of aquaglyceroporin

    PubMed Central

    Kenthirapalan, Sanketha; Waters, Andrew P.; Matuschewski, Kai; Kooij, Taco W.A.

    2012-01-01

    The most critical bottleneck in the generation of recombinant Plasmodium berghei parasites is the mandatory in vivo cloning step following successful genetic manipulation. This study describes a new technique for rapid selection of recombinant P. berghei parasites. The method is based on flow cytometry to isolate isogenic parasite lines and represents a major advance for the field, in that it will speed the generation of recombinant parasites as well as cut down on animal use significantly. High expression of GFP during blood infection, a prerequisite for robust separation of transgenic lines by flow cytometry, was achieved. Isogenic recombinant parasite populations were isolated even in the presence of a 100-fold excess of wild-type (WT) parasites. Aquaglyceroporin (AQP) loss-of-function mutants and parasites expressing a tagged AQP were generated to validate this approach. aqp− parasites grow normally within the WT phenotypic range during blood infection of NMRI mice. Similarly, colonization of the insect vector and establishment of an infection after mosquito transmission were unaffected, indicating that AQP is dispensable for life cycle progression in vivo under physiological conditions, refuting its use as a suitable drug target. Tagged AQP localized to perinuclear structures and not the parasite plasma membrane. We suggest that flow-cytometric isolation of isogenic parasites overcomes the major roadblock towards a genome-scale repository of mutant and transgenic malaria parasite lines. PMID:23137753

  2. Differential regulation of ROMK (Kir1.1) in distal nephron segments by dietary potassium.

    PubMed

    Wade, James B; Fang, Liang; Coleman, Richard A; Liu, Jie; Grimm, P Richard; Wang, Tong; Welling, Paul A

    2011-06-01

    ROMK channels are well-known to play a central role in renal K secretion, but the absence of highly specific and avid-ROMK antibodies has presented significant roadblocks toward mapping the extent of expression along the entire distal nephron and determining whether surface density of these channels is regulated in response to physiological stimuli. Here, we prepared new ROMK antibodies verified to be highly specific, using ROMK knockout mice as a control. Characterization with segmental markers revealed a more extensive pattern of ROMK expression along the entire distal nephron than previously thought, localizing to distal convoluted tubule regions, DCT1 and DCT2; the connecting tubule (CNT); and cortical collecting duct (CD). ROMK was diffusely distributed in intracellular compartments and at the apical membrane of each tubular region. Apical labeling was significantly increased by high-K diet in DCT2, CNT1, CNT2, and CD (P < 0.05) but not in DCT1. Consistent with the large increase in apical ROMK, dramatically increased mature glycosylation was observed following dietary potassium augmentation. We conclude 1) our new antibody provides a unique tool to characterize ROMK channel localization and expression and 2) high-K diet causes a large increase in apical expression of ROMK in DCT2, CNT, and CD but not in DCT1, indicating that different regulatory mechanisms are involved in K diet-regulated ROMK channel functions in the distal nephron.

  3. Taking stock of Myanmar's progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead.

    PubMed

    Saw, Yu Mon; Win, Khine Lae; Shiao, Laura Wen-Shuan; Thandar, Moe Moe; Amiya, Rachel M; Shibanuma, Akira; Tun, Soe; Jimba, Masamine

    2013-09-11

    Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar's progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar's government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar's government should invest greater efforts into health system strengthening to pave the road to universal health coverage.

  4. Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

    PubMed

    Robinson, J M; Henderson, W A

    2018-01-12

    We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

  5. Flexibility Matters: Cooperative Active Sites in Covalent Organic Framework and Threaded Ionic Polymer.

    PubMed

    Sun, Qi; Aguila, Briana; Perman, Jason; Nguyen, Nicholas; Ma, Shengqian

    2016-12-07

    The combination of two or more reactive centers working in concert on a substrate to facilitate the reaction is now considered state of the art in catalysis, yet there still remains a tremendous challenge. Few heterogeneous systems of this sort have been exploited, as the active sites spatially separated within the rigid framework are usually difficult to cooperate. It is now shown that this roadblock can be surpassed. The underlying principle of the strategy presented here is the integration of catalytic components with excellent flexibility and porous heterogeneous catalysts, as demonstrated by the placement of linear ionic polymers in close proximity to surface Lewis acid active sites anchored on the walls of a covalent organic framework (COF). Using the cycloaddition of the epoxides and CO 2 as a model reaction, dramatic activity improvements have been achieved for the composite catalysts in relation to the individual catalytic component. Furthermore, they also clearly outperform the benchmark catalytic systems formed by the combination of the molecular organocatalysts and heterogeneous Lewis acid catalysts, while affording additional recyclability. The extraordinary flexibility and enriched concentration of the catalytically active moieties on linear polymers facilitate the concerted catalysis, thus leading to superior catalytic performance. This work therefore uncovers an entirely new strategy for designing bifunctional catalysts with double-activation behavior and opens a new avenue in the design of multicapable systems that mimic biocatalysis.

  6. Guidelines for research recruitment of underserved populations (EERC).

    PubMed

    Matsuda, Yui; Brooks, Jada L; Beeber, Linda S

    2016-11-01

    Despite concerted efforts to establish health equity, significant disparities persist. One roadblock to eliminating health disparities is the inadequate recruitment of underserved populations, which prevents researchers from creating culturally-tailored interventions. To further develop the science of recruitment, we argue that a systematic approach should be applied to research participant recruitment. Given the lack of practical and comprehensive recruitment conceptual frameworks or guidelines in the literature, the authors propose newly synthesized guidelines for research recruitment of underserved populations: EERC (evaluate, engage, reflect, and carefully match). The EERC guidelines are delineated, and the application of these guidelines is illustrated through a study recently conducted by the authors. The guidelines consist of the following four components: 1. Evaluate the composition of the research team; 2. Engage fully with the community by working with key informants and cultural insiders; 3. Reflect the unique cultural characteristics of the community in the research conduct; and 4. Carefully use a matching technique. The application component of the article demonstrates concrete examples of how the guidelines can enhance research recruitment for an underserved population. The authors intend these guidelines to be broadly applicable for research teams regardless of research design or characteristics of the underserved population. Application of these guidelines in nursing and health science will contribute to increasing research recruitment of underserved populations, with the goal of reducing health disparities and achieving health equity for all persons. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cost-effective Expression and Purification of Antimicrobial and Host Defense Peptides in Escherichia coli

    PubMed Central

    Bommarius, B.; Jenssen, H.; Elliott, M.; Kindrachuk, J.; Pasupuleti, Mukesh; Gieren, H; Jaeger, K.-E.; Hancock, R.E. W.

    2010-01-01

    Cationic antimicrobial host defense peptides (HDPs) combat infection by directly killing a wide variety of microbes, and/or modulating host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites, but there are substantial roadblocks to their therapeutic application. High manufacturing costs associated with amino acid precursors have limited the delivery of inexpensive therapeutics through industrial-scale chemical synthesis. Conversely, the production of peptides in bacteria by recombinant DNA technology has been impeded by the antimicrobial activity of these peptides and their susceptibility to proteolytic degradation, while subsequent purification of recombinant peptides often requires multiple steps and has not been cost-effective. Here we have developed methodologies appropriate for large-scale industrial production of HDPs; in particular, we describe (i) a method, using fusions to SUMO, for producing high yields of intact recombinant HDPs in bacteria without significant toxicity; and (ii) a simplified 2-step purification method appropriate for industrial use. We have used this method to produce seven HDPs to date (IDR1, MX226, LL37, CRAMP, HHC-10, E5 and E6). Using this technology, pilot-scale fermentation (10 L) was performed to produce large quantities of biologically active cationic peptides. Together, these data indicate that this new method represents a cost-effective means to enable commercial enterprises to produce HDPs in large-scale under Good Laboratory Manufacturing Practice (GMP) conditions for therapeutic application in humans. PMID:20713107

  8. Career Opportunities for Physicists in the Micro Electronics Industry

    NASA Astrophysics Data System (ADS)

    Bourianoff, George

    1997-10-01

    The US micro electronics industry anticipates growth of 20 to 30 percent per year for the next five years. The need for engineers and scientists poses a critical problem for the industry but conversely presents great opportunities for those in closely related fields such as physics where career opportunities may be more limited. There is no shortage of important and challenging problems on the Semiconductor Institute of America (SIA) roadmap which will require solution in the next 10 years and which require expertise in the physical sciences. However, significant cultural differences exist between the physics community and the engineering oriented semiconductor community which must be understood and addressed in order for a physicist to successfully contribute in this environment. This talk will identify some of those cultural differences and describe some of the critical physics related problems which must be solved. Critical roadblocks include lithographic patterning below 0.18m. and design of Very Large Scale Integrated (VLSI) circuits in the deep submicron regime. The former will require developing radiation sources and optical elements for the EUV or XRAY part of the spectrum. The latter will require incorporating electromagnetic field equations with traditional lumped element circuit design methods. The cultural barriers alluded to earlier involve the manner in which engineering detail is approached. A physicist's basic instinct is to strip off the detail in order to make a problem mathematically tractable. This enables understanding of the underlying physical relationships but does not yield the quantitative detail necessary in semiconductor production.

  9. Issues in Forecasting CMEs

    NASA Astrophysics Data System (ADS)

    Pizzo, V. J.

    2017-12-01

    I will present my view of the current status of space weather forecasting abilities related to CMEs. This talk will address the large-scale aspects, but specifically not energetic particle phenomena. A key point is that all models, whether sophisticated numerical contraptions or quasi-empirical ones, are only as good as the data you feed them. Hence the emphasis will be on observations and analysis methods. First I will review where we stand with regard to the near-Sun quantitative data needed to drive any model, no matter how complex or simple-minded, and I will discuss technological roadblocks that suggest it may be some time before we see any meaningful improvements beyond what we have today. Then I cover issues related to characterizing CME propagation out through the corona and into interplanetary space, as well as to observational limitations in the vicinity of 1 AU. Since none of these observational constraints are likely to be resolved anytime soon, the real challenge is to make more informed use of what is available. Thus, this talk will focus on how we may identify and pursue the most profitable approaches, for both forecast and research applications. The discussion will highlight a number of promising leads, including those related to inclusion of solar backside information, joint magnetograph observations from L5 and Earth, how to use (not just run) ensembles, more rational use of HI observations, and suggestions for using cube-sats for deep space observations of CMEs and MCs.

  10. p53 and Mdm2 act synergistically to maintain cardiac homeostasis and mediate cardiomyocyte cell cycle arrest through a network of microRNAs.

    PubMed

    Stanley-Hasnain, Shanna; Hauck, Ludger; Grothe, Daniela; Aschar-Sobbi, Roozbeh; Beca, Sanja; Butany, Jagdish; Backx, Peter H; Mak, Tak W; Billia, Filio

    2017-01-01

    Defining the roadblocks responsible for cell cycle arrest in adult cardiomyocytes lies at the core of developing cardiac regenerative therapies. p53 and Mdm2 are crucial mediators of cell cycle arrest in proliferative cell types, however, little is known about their function in regulating homeostasis and proliferation in terminally differentiated cell types, like cardiomyocytes. To explore this, we generated a cardiac-specific conditional deletion of p53 and Mdm2 (DKO) in adult mice. Herein we describe the development of a dilated cardiomyopathy, in the absence of cardiac hypertrophy. In addition, DKO hearts exhibited a significant increase in cardiomyocyte proliferation. Further evaluation showed that proliferation was mediated by a significant increase in Cdk2 and cyclin E with downregulation of p21 Cip1 and p27 Kip1 . Comparison of miRNA expression profiles from DKO mouse hearts and controls revealed 11 miRNAs that were downregulated in the DKO hearts and enriched for mRNA targets involved in cell cycle regulation. Knockdown of these miRNAs in neonatal rat cardiomyocytes significantly increased cytokinesis with an upregulation in the expression of crucial cell cycle regulators. These results illustrate the importance of the cooperative activities of p53 and Mdm2 in a network of miRNAs that function to impose a barrier against aberrant cardiomyocyte cell cycle re-entry to maintain cardiac homeostasis.

  11. Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment.

    PubMed

    Apostoli, Anthony J; Ailles, Laurie

    2016-01-01

    Human cancer is not a uniform disease but a plethora of disparate tumor types and subtypes. The differences that exist between individual tumors (intertumoral heterogeneity) present a significant roadblock to the eradication of cancer. It has also become increasingly clear that variations across individual tumors (intratumoral heterogeneity) have important implications to cancer progression and treatment efficacy. Therefore, in order to improve patient care and develop novel chemotherapeutics, the evolving tumor landscape needs to be further explored. Next-generation sequencing (NGS) technologies are revolutionizing the cancer research arena by providing state-of-the-art, high-speed methods of genome sequencing at single-nucleotide resolution, thus enabling an unprecedented detection of tumor-specific genetic abnormalities. These anomalies can be quantified to reveal specific frequencies of DNA alterations that correspond to distinct clonal populations within a given tumor. As such, NGS approaches have also been utilized to explore the heterogeneous landscape of patient tumors as well as to match metastatic and/or recurrent growths and patient-derived engrafts. By sequencing in this manner--through time so to speak--cancer researchers can track shifting clonal populations, make important inferences about tumor evolution and potentially identify tumor subclones that could be viably targeted. This exciting new territory has important implications for the competing clonal evolution and cancer stem cell models of tumor heterogeneity, and also offers a new dimension for cancer treatment and profound hope for patients in the coming years.

  12. MISTICA: Minimum Spanning Tree-based Coarse Image Alignment for Microscopy Image Sequences

    PubMed Central

    Ray, Nilanjan; McArdle, Sara; Ley, Klaus; Acton, Scott T.

    2016-01-01

    Registration of an in vivo microscopy image sequence is necessary in many significant studies, including studies of atherosclerosis in large arteries and the heart. Significant cardiac and respiratory motion of the living subject, occasional spells of focal plane changes, drift in the field of view, and long image sequences are the principal roadblocks. The first step in such a registration process is the removal of translational and rotational motion. Next, a deformable registration can be performed. The focus of our study here is to remove the translation and/or rigid body motion that we refer to here as coarse alignment. The existing techniques for coarse alignment are unable to accommodate long sequences often consisting of periods of poor quality images (as quantified by a suitable perceptual measure). Many existing methods require the user to select an anchor image to which other images are registered. We propose a novel method for coarse image sequence alignment based on minimum weighted spanning trees (MISTICA) that overcomes these difficulties. The principal idea behind MISTICA is to re-order the images in shorter sequences, to demote nonconforming or poor quality images in the registration process, and to mitigate the error propagation. The anchor image is selected automatically making MISTICA completely automated. MISTICA is computationally efficient. It has a single tuning parameter that determines graph width, which can also be eliminated by way of additional computation. MISTICA outperforms existing alignment methods when applied to microscopy image sequences of mouse arteries. PMID:26415193

  13. MISTICA: Minimum Spanning Tree-Based Coarse Image Alignment for Microscopy Image Sequences.

    PubMed

    Ray, Nilanjan; McArdle, Sara; Ley, Klaus; Acton, Scott T

    2016-11-01

    Registration of an in vivo microscopy image sequence is necessary in many significant studies, including studies of atherosclerosis in large arteries and the heart. Significant cardiac and respiratory motion of the living subject, occasional spells of focal plane changes, drift in the field of view, and long image sequences are the principal roadblocks. The first step in such a registration process is the removal of translational and rotational motion. Next, a deformable registration can be performed. The focus of our study here is to remove the translation and/or rigid body motion that we refer to here as coarse alignment. The existing techniques for coarse alignment are unable to accommodate long sequences often consisting of periods of poor quality images (as quantified by a suitable perceptual measure). Many existing methods require the user to select an anchor image to which other images are registered. We propose a novel method for coarse image sequence alignment based on minimum weighted spanning trees (MISTICA) that overcomes these difficulties. The principal idea behind MISTICA is to reorder the images in shorter sequences, to demote nonconforming or poor quality images in the registration process, and to mitigate the error propagation. The anchor image is selected automatically making MISTICA completely automated. MISTICA is computationally efficient. It has a single tuning parameter that determines graph width, which can also be eliminated by the way of additional computation. MISTICA outperforms existing alignment methods when applied to microscopy image sequences of mouse arteries.

  14. Alcohol use in an academic medical school environment: A UC San Diego Healer Education Assessment and Referral (HEAR) Report.

    PubMed

    Martinez, Stephanie; Tal, Ilanit; Norcross, William; Newton, Isabel Gala; Downs, Nancy; Seay, Kathryn; McGuire, Tara; Kirby, Brittany; Chidley, Brittany; Tiamson-Kassab, Maria; Lee, Daniel; Hadley, Allison; Doran, Neal; Jong, Pam; Lee, Kelly; Moutier, Christine; Norman, Marc; Zisook, Sidney

    2016-05-01

    Medical students and physicians in training and in practice are at risk for excessive alcohol use and abuse, potentially impacting the affected individuals as well as their family members, trainees, and patients. However, several roadblocks to care, including stigma, often keep them from seeking treatment. We analyzed data from anonymous questionnaires completed by medical students, house staff, and faculty from 2009 to 2014 as part of a depression awareness and suicide prevention program at a state-supported medical school in the United States. The authors explored associations between self-reported "drinking too much" and depression, suicidal ideation, substance use, intense affective states, and mental health treatment. Approximately one-fifth of the respondents reported "drinking too much." "Drinking too much" was associated with more severe depression and impairment, past suicide attempts and current suicidal ideation, intense affective states, and other substance use. Those who were "drinking too much" were more likely than others to accept referrals for mental health treatment through the anonymous interactive screening program, suggesting that this program may be effective in skirting the stigma barrier for accessing mental health care for this at-risk population. The self-reported prevalence of "drinking too much" among medical students, house staff, and faculty is high and associated with negative mental health outcomes. Targeted, anonymous screenings may identify at-risk individuals and provide mental health care referrals to those in need.

  15. Rice fortification: its potential for improving micronutrient intake and steps required for implementation at scale.

    PubMed

    Piccoli, Nina Beretta; Grede, Nils; de Pee, Saskia; Singhkumarwong, Anusara; Roks, Eveline; Moench-Pfanner, Regina; Bloem, Martin W

    2012-12-01

    Micronutrient deficiencies affect over 2 billion people worldwide, with profound implications for health, cognitive development, education, economic development, and productivity. Fortification of staple foods is a cost-effective strategy to increase vitamin and mineral intake among the general population. Rice is consumed by billions of people (> 440 million MT/year) but is as yet rarely fortified. To discuss the untapped opportunity of rice fortification. Review literature and experience with rice fortification and compare to fortification of other staple foods. Most technologies used to fortify rice first produce the fortified kernels and then blend them with regular, polished rice. Technologies differ with regard to how nutrients are added to the rice kernels, required investment, production cost, and degree of resemblance to unfortified rice. There are, so far, limited success stories for rice fortification. Some of the main roadblocks appear to be high initial investment and associated cost; lack of government leadership; and consumer hesitation to accept variations in the characteristics of rice, or a higher price, without good understanding of the benefits. In countries with a large centralized rice milling industry, starting rice fortification is easier than in countries with many small mills. Countries with large safety nets that supply rice to the poorest, for free or subsidized, have a good channel to reach those most in need. Furthermore, key players from the public and private sectors should establish a coalition to support the use of fortified rice and address some of the barriers to its implementation.

  16. High productivity chromatography refolding process for Hepatitis B Virus X (HBx) protein guided by statistical design of experiment studies.

    PubMed

    Basu, Anindya; Leong, Susanna Su Jan

    2012-02-03

    The Hepatitis B Virus X (HBx) protein is a potential therapeutic target for the treatment of hepatocellular carcinoma. However, consistent expression of the protein as insoluble inclusion bodies in bacteria host systems has largely hindered HBx manufacturing via economical biosynthesis routes, thereby impeding the development of anti-HBx therapeutic strategies. To eliminate this roadblock, this work reports the development of the first 'chromatography refolding'-based bioprocess for HBx using immobilised metal affinity chromatography (IMAC). This process enabled production of HBx at quantities and purity that facilitate their direct use in structural and molecular characterization studies. In line with the principles of quality by design (QbD), we used a statistical design of experiments (DoE) methodology to design the optimum process which delivered bioactive HBx at a productivity of 0.21 mg/ml/h at a refolding yield of 54% (at 10 mg/ml refolding concentration), which was 4.4-fold higher than that achieved in dilution refolding. The systematic DoE methodology adopted for this study enabled us to obtain important insights into the effect of different bioprocess parameters like the effect of buffer exchange gradients on HBx productivity and quality. Such a bioprocess design approach can play a pivotal role in developing intensified processes for other novel proteins, and hence helping to resolve validation and speed-to-market challenges faced by the biopharmaceutical industry today. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells.

    PubMed

    Tsai, Yihuan; Cutts, Josh; Kimura, Azuma; Varun, Divya; Brafman, David A

    2015-07-01

    Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery. Copyright © 2015. Published by Elsevier B.V.

  18. From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function.

    PubMed

    Bernard, Daniel J; Brûlé, Emilie; Smith, Courtney L; Joustra, Sjoerd D; Wit, Jan M

    2018-03-01

    Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo , failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes.

  19. New Wavelet Neurovascular Bundle for Bedside Evaluation of Cerebral Autoregulation and Neurovascular Coupling in Newborns with Hypoxic-Ischemic Encephalopathy.

    PubMed

    Chalak, Lina F; Zhang, Rong

    2017-01-01

    Neonatal encephalopathy (NE) resulting from birth asphyxia constitutes a major global public health burden for millions of infants every year, and despite therapeutic hypothermia, half of these neonates have poor neurological outcomes. As new neuroprotective interventions are being studied in clinical trials, there is a critical need to establish physiological surrogate markers of therapeutic efficacy, to guide patient selection and/or to modify the therapeutic intervention. The challenge in the field of neonatal brain injury has been the difficulty of clinically discerning NE severity within the short therapeutic window after birth or of analyzing the dynamic aspects of the cerebral circulation in sick NE newborns. To address this roadblock, we have recently developed a new "wavelet neurovascular bundle" analytical system that can measure cerebral autoregulation (CA) and neurovascular coupling (NVC) at multiple time scales under dynamic, nonstationary clinical conditions. This wavelet analysis may allow noninvasive quantification at the bedside of (1) CA (combining metrics of blood pressure and cerebral near-infrared spectroscopy, NIRS) and (2) NVC (combining metrics obtained from NIRS and EEG) in newborns with encephalopathy without mathematical assumptions of linear and stationary systems. In this concept paper, we present case examples of NE using the proposed physiological wavelet metrics of CA and NVC. The new approach, once validated in large NE studies, has the potential to optimize the selection of candidates for therapeutic decision-making, and the prediction of neurocognitive outcomes. © 2017 S. Karger AG, Basel.

  20. A DNA replicon system for rapid high-level production of virus-like particles in plants.

    PubMed

    Huang, Zhong; Chen, Qiang; Hjelm, Brooke; Arntzen, Charles; Mason, Hugh

    2009-07-01

    Recombinant virus-like particles (VLPs) represent a safe and effective vaccine strategy. We previously described a stable transgenic plant system for inexpensive production and oral delivery of VLP vaccines. However, the relatively low-level antigen accumulation and long-time frame to produce transgenic plants are the two major roadblocks in the practical development of plant-based VLP production. In this article, we describe the optimization of geminivirus-derived DNA replicon vectors for rapid, high-yield plant-based production of VLPs. Co-delivery of bean yellow dwarf virus (BeYDV)-derived vector and Rep/RepA-supplying vector by agroinfiltration of Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within 5 days. Co-expression of the P19 protein of tomato bush stunt virus, a gene silencing inhibitor, further enhanced VLP accumulation by stabilizing the mRNA. With this system, hepatitis B core antigen (HBc) and Norwalk virus capsid protein (NVCP) were produced at 0.80 and 0.34 mg/g leaf fresh weight, respectively. Sedimentation analysis and electron microscopy of transiently expressed antigens verified the efficient assembly of VLPs. Furthermore, a single replicon vector containing a built-in Rep/RepA cassette without P19 drove protein expression at similar levels as the three-component system. These results demonstrate the advantages of fast and high-level production of VLP-based vaccines using the BeYDV-derived DNA replicon system for transient expression in plants. (c) 2009 Wiley Periodicals, Inc.

  1. A DNA replicon system for rapid high-level production of virus-like particles in plants

    PubMed Central

    Huang, Zhong; Chen, Qiang; Hjelm, Brooke; Arntzen, Charles

    2009-01-01

    Recombinant virus-like particles (VLPs) represent a safe and effective vaccine strategy. We previously described a stable transgenic plant system for inexpensive production and oral delivery of VLP vaccines. However, the relatively low level antigen accumulation and long time frame to produce transgenic plants are the two major roadblocks in the practical development of plant-based VLP production. In this paper, we describe the optimization of geminivirus-derived DNA replicon vectors for rapid, high-yield plant-based production of VLPs. Co-delivery of bean yellow dwarf virus (BeYDV)-derived vector and Rep/RepA-supplying vector by agroinfiltration of Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within five days. Co-expression of the P19 protein of tomato bush stunt virus, a gene silencing inhibitor, further enhanced VLP accumulation by stabilizing the mRNA. With this system, hepatitis B core antigen (HBc) and Norwalk virus capsid protein (NVCP) were produced at 0.80 and 0.34 mg/g leaf fresh weight, respectively. Sedimentation analysis and electron microscopy of transiently expressed antigens verified the efficient assembly of VLPs. Furthermore, a single replicon vector containing a built-in Rep/RepA cassette without p19 drove protein expression at similar levels as the three-component system. These results demonstrate the advantages of fast and high-level production of VLP-based vaccines using the BeYDV-derived DNA replicon system for transient expression in plants. PMID:19309755

  2. Coevolving advances in animal flight and aerial robotics

    PubMed Central

    Lentink, David

    2017-01-01

    Our understanding of animal flight has inspired the design of new aerial robots with more effective flight capacities through the process of biomimetics and bioinspiration. The aerodynamic origin of the elevated performance of flying animals remains, however, poorly understood. In this themed issue, animal flight research and aerial robot development coalesce to offer a broader perspective on the current advances and future directions in these coevolving fields of research. Together, four reviews summarize and 14 reports contribute to our understanding of low Reynolds number flight. This area of applied aerodynamics research is challenging to dissect due to the complicated flow phenomena that include laminar–turbulent flow transition, laminar separation bubbles, delayed stall and nonlinear vortex dynamics. Our mechanistic understanding of low Reynolds number flight has perhaps been advanced most by the development of dynamically scaled robot models and new specialized wind tunnel facilities: in particular, the tiltable Lund flight tunnel for animal migration research and the recently developed AFAR hypobaric wind tunnel for high-altitude animal flight studies. These world-class facilities are now complemented with a specialized low Reynolds number wind tunnel for studying the effect of turbulence on animal and robot flight in much greater detail than previously possible. This is particular timely, because the study of flight in extremely laminar versus turbulent flow opens a new frontier in our understanding of animal flight. Advancing this new area will offer inspiration for developing more efficient high-altitude aerial robots and removes roadblocks for aerial robots operating in turbulent urban environments.

  3. High p-type doping, mobility, and photocarrier lifetime in arsenic-doped CdTe single crystals

    NASA Astrophysics Data System (ADS)

    Nagaoka, Akira; Kuciauskas, Darius; McCoy, Jedidiah; Scarpulla, Michael A.

    2018-05-01

    Group-V element doping is promising for simultaneously maximizing the hole concentration and minority carrier lifetime in CdTe for thin film solar cells, but there are roadblocks concerning point defects including the possibility of self-compensation by AX metastability. Herein, we report on doping, lifetime, and mobility of CdTe single crystals doped with As between 1016 and 1020 cm-3 grown from the Cd solvent by the travelling heater method. Evidence consistent with AX instability as a major contributor to compensation in samples doped below 1017 cm-3 is presented, while for higher-doped samples, precipitation of a second phase on planar structural defects is also observed and may explain spatial variation in properties such as lifetime. Rapid cooling after crystal growth increases doping efficiency and mobility for times up to 20-30 days at room temperature with the highest efficiencies observed close to 45% and a hole mobility of 70 cm2/Vs at room temperature. A doping limit in the low 1017/cm3 range is observed for samples quenched at 200-300 °C/h. Bulk minority carrier lifetimes exceeding 20 ns are observed for samples doped near 1016 cm-3 relaxed in the dark and for unintentionally doped samples, while a lifetime of nearly 5 ns is observed for 1018 cm-3 As doping. These results help us to establish limits on properties expected for group-V doped CdTe polycrystalline thin films for use in photovoltaics.

  4. Towards Comprehensive Variation Models for Designing Vehicle Monitoring Systems

    NASA Technical Reports Server (NTRS)

    McAdams, Daniel A.; Tumer, Irem Y.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    When designing vehicle vibration monitoring systems for aerospace devices, it is common to use well-established models of vibration features to determine whether failures or defects exist. Most of the algorithms used for failure detection rely on these models to detect significant changes in a flight environment. In actual practice, however, most vehicle vibration monitoring systems are corrupted by high rates of false alarms and missed detections. This crucial roadblock makes their implementation in real vehicles (e.g., helicopter transmissions and aircraft engines) difficult, making their operation costly and unreliable. Research conducted at the NASA Ames Research Center has determined that a major reason for the high rates of false alarms and missed detections is the numerous sources of statistical variations that are not taken into account in the modeling assumptions. In this paper, we address one such source of variations, namely, those caused during the design and manufacturing of rotating machinery components that make up aerospace systems. We present a novel way of modeling the vibration response by including design variations via probabilistic methods. Using such models, we develop a methodology to account for design and manufacturing variations, and explore the changes in the vibration response to determine its stochastic nature. We explore the potential of the methodology using a nonlinear cam-follower model, where the spring stiffness values are assumed to follow a normal distribution. The results demonstrate initial feasibility of the method, showing great promise in developing a general methodology for designing more accurate aerospace vehicle monitoring systems.

  5. Gamification in Action: Theoretical and Practical Considerations for Medical Educators.

    PubMed

    Rutledge, Chrystal; Walsh, Catharine M; Swinger, Nathan; Auerbach, Marc; Castro, Danny; Dewan, Maya; Khattab, Mona; Rake, Alyssa; Harwayne-Gidansky, Ilana; Raymond, Tia T; Maa, Tensing; Chang, Todd P

    2018-02-20

    Gamification involves the application of game design elements to traditionally non-game contexts. It is increasingly being used as an adjunct to traditional teaching strategies in medical education to engage the millennial learner and enhance adult learning. The extant literature has focused on determining whether the implementation of gamification results in better learning outcomes, leading to a dearth of research examining its theoretical underpinnings within the medical education context. The authors define gamification, explore how gamification works within the medical education context using self-determination theory as an explanatory mechanism for enhanced engagement and motivation, and discuss common roadblocks and challenges to implementing gamification.While previous gamification research has largely focused on determining whether implementation of gamification in medical education leads to better learning outcomes, the authors recommend that future research should explore how and under what conditions gamification is likely to be effective. Selective, purposeful gamification that aligns with learning goals has the potential to increase learner motivation and engagement and, ultimately, learning. In line with self-determination theory, game design elements can be used to enhance learners' feelings of relatedness, autonomy, and competence to foster learners' intrinsic motivation. Poorly applied game design elements, however, may undermine these basic psychological needs by the overjustification effect or through negative effects of competition. Educators must, therefore, clearly understand the benefits and pitfalls of gamification in curricular design, take a thoughtful approach when integrating game design elements, and consider the types of learners and overarching learning objectives.

  6. Translocation by T7 RNA polymerase: a sensitively poised Brownian ratchet.

    PubMed

    Guo, Qing; Sousa, Rui

    2006-04-21

    Studies of halted T7 RNA polymerase (T7RNAP) elongation complexes (ECs) or of T7RNAP transcription against roadblocks due to DNA-bound proteins indicate that T7RNAP translocates via a passive Brownian ratchet mechanism. Crystal structures of T7RNAP ECs suggest that translocation involves an active power-stroke. However, neither solution studies of halted or slowed T7RNAP ECs, nor crystal structures of static complexes, are necessarily relevant to how T7RNAP translocates during rapid elongation. A recent single molecule study of actively elongating T7RNAPs provides support for the Brownian ratchet mechanism. Here, we obtain additional evidence for the existence of a Brownian ratchet during active T7RNAP elongation by showing that both rapidly elongating and halted complexes are equally sensitive to pyrophosphate. Using chemical nucleases tethered to the polymerase we achieve sub-ångström resolution in measuring the average position of halted T7RNAP ECs and find that the positional equilibrium of the EC is sensitively poised between pre-translocated and post-translocated states. This may be important in maximizing the sensitivity of the polymerase to sequences that cause pausing or termination. We also confirm that a crystallographically observed disorder to order transition in a loop formed by residues 589-612 also occurs in solution and is coupled to pyrophosphate or NTP release. This transition allows the loop to make interactions with the DNA that help stabilize the laterally mobile, ligand-free EC against dissociation.

  7. Detergent-associated solution conformations of helical and beta-barrel membrane proteins.

    PubMed

    Mo, Yiming; Lee, Byung-Kwon; Ankner, John F; Becker, Jeffrey M; Heller, William T

    2008-10-23

    Membrane proteins present major challenges for structural biology. In particular, the production of suitable crystals for high-resolution structural determination continues to be a significant roadblock for developing an atomic-level understanding of these vital cellular systems. The use of detergents for extracting membrane proteins from the native membrane for either crystallization or reconstitution into model lipid membranes for further study is assumed to leave the protein with the proper fold with a belt of detergent encompassing the membrane-spanning segments of the structure. Small-angle X-ray scattering was used to probe the detergent-associated solution conformations of three membrane proteins, namely bacteriorhodopsin (BR), the Ste2p G-protein coupled receptor from Saccharomyces cerevisiae, and the Escherichia coli porin OmpF. The results demonstrate that, contrary to the traditional model of a detergent-associated membrane protein, the helical proteins BR and Ste2p are not in the expected, compact conformation and associated with detergent micelles, while the beta-barrel OmpF is indeed embedded in a disk-like micelle in a properly folded state. The comparison provided by the BR and Ste2p, both members of the 7TM family of helical membrane proteins, further suggests that the interhelical interactions between the transmembrane helices of the two proteins differ, such that BR, like other rhodopsins, can properly refold to crystallize, while Ste2p continues to prove resistant to crystallization from an initially detergent-associated state.

  8. Breast Cancer: A Molecular and Redox Snapshot.

    PubMed

    Raman, Deepika; Foo, Chuan Han Jonathan; Clement, Marie-Veronique; Pervaiz, Shazib

    2016-08-20

    Breast cancer is a unique disease characterized by heterogeneous cell populations causing roadblocks in therapeutic medicine, owing to its complex etiology and primeval understanding of the biology behind its genesis, progression, and sustenance. Globocan statistics indicate over 1.7 million new breast cancer diagnoses in 2012, accounting for 25% of all cancer morbidities. Despite these dismal statistics, the introduction of molecular gene signature platforms, progressive therapeutic approaches in diagnosis, and management of breast cancer has led to more effective treatment strategies and control measures concurrent with an equally reassuring decline in the mortality rate. However, an enormous body of research in this area is requisite as high mortality associated with metastatic and/or drug refractory tumors continues to present a therapeutic challenge. Despite advances in systemic chemotherapy, the median survival of patients harboring metastatic breast cancers continues to be below 2 years. Hence, a massive effort to scrutinize and evaluate chemotherapeutics on the basis of the molecular classification of these cancers is undertaken with the objective to devise more attractive and feasible approaches to treat breast cancers and improve patients' quality of life. This review aims to summarize the current understanding of the biology of breast cancer as well as challenges faced in combating breast cancer, with special emphasis on the current battery of treatment strategies. We will also try and gain perspective from recent encounters on novel findings responsible for the progression and metastatic transformation of breast cancer cells in an endeavor to develop more targeted treatment options. Antioxid. Redox Signal. 25, 337-370.

  9. Human milk oligosaccharides: every baby needs a sugar mama.

    PubMed

    Bode, Lars

    2012-09-01

    Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic "bifidus factor" that serves as a metabolic substrate for desired bacteria and shapes an intestinal microbiota composition with health benefits for the breast-fed neonate. Today, HMOs are known to be more than just "food for bugs". An accumulating body of evidence suggests that HMOs are antiadhesive antimicrobials that serve as soluble decoy receptors, prevent pathogen attachment to infant mucosal surfaces and lower the risk for viral, bacterial and protozoan parasite infections. In addition, HMOs may modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, lower the risk for necrotizing enterocolitis and provide the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Most data, however, stem from in vitro, ex vivo or animal studies and occasionally from association studies in mother-infant cohorts. Powered, randomized and controlled intervention studies will be needed to confirm relevance for human neonates. The first part of this review introduces the pioneers in HMO research, outlines HMO structural diversity and describes what is known about HMO biosynthesis in the mother's mammary gland and their metabolism in the breast-fed infant. The second part highlights the postulated beneficial effects of HMO for the breast-fed neonate, compares HMOs with oligosaccharides in the milk of other mammals and in infant formula and summarizes the current roadblocks and future opportunities for HMO research.

  10. Adherence Barriers to Chronic Dialysis in the United States

    PubMed Central

    Thadhani, Ravi I.; Maddux, Franklin W.

    2014-01-01

    Hemodialysis patients often do not attend their scheduled treatment session. We investigated factors associated with missed appointments and whether such nonadherence poses significant harm to patients and increases overall health care utilization in an observational analysis of 44 million hemodialysis treatments for 182,536 patients with ESRD in the United States. We assessed the risk of hospitalization, emergency room visit, or intensive-coronary care unit (ICU-CCU) admission in the 2 days after a missed treatment relative to the risk for patients who received hemodialysis. Over the 5-year study period, the average missed treatment rate was 7.1 days per patient-year. In covariate adjusted logistic regression, the risk of hospitalization (odds ratio [OR], 3.98; 95% confidence interval [95% CI], 3.93 to 4.04), emergency room visit (OR, 2.00; 95% CI, 1.87 to 2.14), or ICU-CCU admission (OR, 3.89; 95% CI, 3.81 to 3.96) increased significantly after a missed treatment. Overall, 0.9 missed treatment days per year associated with suboptimal transportation to dialysis, inclement weather, holidays, psychiatric illness, pain, and gastrointestinal upset. These barriers also associated with excess hospitalization (5.6 more events per patient-year), emergency room visits (1.1 more visits), and ICU-CCU admissions (0.8 more admissions). In conclusion, poor adherence to hemodialysis treatments may be a substantial roadblock to achieving better patient outcomes. Addressing systemic and patient barriers that impede access to hemodialysis care may decrease missed appointments and reduce patient morbidity. PMID:24762400

  11. Detergent-associated Solution Conformations of Helical and Beta-barrel Membrane Proteins

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

    Mo, Yiming; Lee, Byung-Kwon; Ankner, John Francis

    2008-01-01

    Membrane proteins present major challenges for structural biology. In particular, the production of suitable crystals for high-resolution structural determination continues to be a significant roadblock for developing an atomic-level understanding of these vital cellular systems. The use of detergents for extracting membrane proteins from the native membrane for either crystallization or reconstitution into model lipid membranes for further study is assumed to leave the protein with the proper fold with a belt of detergent encompassing the membrane-spanning segments of the structure. Small-angle X-ray scattering was used to probe the detergent-associated solution conformations of three membrane proteins, namely bacteriorhodopsin (BR), themore » Ste2p G-protein coupled receptor from Saccharomyces cerevisiae, and the Escherichia coli porin OmpF. The results demonstrate that, contrary to the traditional model of a detergent-associated membrane protein, the helical proteins BR and Ste2p are not in the expected, compact conformation and associated with detergent micelles, while the ?-barrel OmpF is indeed embedded in a disk-like micelle in a properly folded state. The comparison provided by the BR and Ste2p, both members of the 7TM family of helical membrane proteins, further suggests that the interhelical interactions between the transmembrane helices of the two proteins differ, such that BR, like other rhodopsins, can properly refold to crystallize, while Ste2p continues to prove resistant to crystallization from an initially detergent-associated state.« less

  12. Analytical validation considerations of multiplex mass-spectrometry-based proteomic platforms for measuring protein biomarkers.

    PubMed

    Boja, Emily S; Fehniger, Thomas E; Baker, Mark S; Marko-Varga, György; Rodriguez, Henry

    2014-12-05

    Protein biomarker discovery and validation in current omics era are vital for healthcare professionals to improve diagnosis, detect cancers at an early stage, identify the likelihood of cancer recurrence, stratify stages with differential survival outcomes, and monitor therapeutic responses. The success of such biomarkers would have a huge impact on how we improve the diagnosis and treatment of patients and alleviate the financial burden of healthcare systems. In the past, the genomics community (mostly through large-scale, deep genomic sequencing technologies) has been steadily improving our understanding of the molecular basis of disease, with a number of biomarker panels already authorized by the U.S. Food and Drug Administration (FDA) for clinical use (e.g., MammaPrint, two recently cleared devices using next-generation sequencing platforms to detect DNA changes in the cystic fibrosis transmembrane conductance regulator (CFTR) gene). Clinical proteomics, on the other hand, albeit its ability to delineate the functional units of a cell, more likely driving the phenotypic differences of a disease (i.e., proteins and protein-protein interaction networks and signaling pathways underlying the disease), "staggers" to make a significant impact with only an average ∼ 1.5 protein biomarkers per year approved by the FDA over the past 15-20 years. This statistic itself raises the concern that major roadblocks have been impeding an efficient transition of protein marker candidates in biomarker development despite major technological advances in proteomics in recent years.

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

    Witzel, Wayne; Rudinger, Kenneth Michael; Sarovar, Mohan

    Using a novel formal methods approach, we have generated computer-veri ed proofs of major theorems pertinent to the quantum phase estimation algorithm. This was accomplished using our Prove-It software package in Python. While many formal methods tools are available, their practical utility is limited. Translating a problem of interest into these systems and working through the steps of a proof is an art form that requires much expertise. One must surrender to the preferences and restrictions of the tool regarding how mathematical notions are expressed and what deductions are allowed. Automation is a major driver that forces restrictions. Our focus,more » on the other hand, is to produce a tool that allows users the ability to con rm proofs that are essentially known already. This goal is valuable in itself. We demonstrate the viability of our approach that allows the user great exibility in expressing state- ments and composing derivations. There were no major obstacles in following a textbook proof of the quantum phase estimation algorithm. There were tedious details of algebraic manipulations that we needed to implement (and a few that we did not have time to enter into our system) and some basic components that we needed to rethink, but there were no serious roadblocks. In the process, we made a number of convenient additions to our Prove-It package that will make certain algebraic manipulations easier to perform in the future. In fact, our intent is for our system to build upon itself in this manner.« less

  14. Substrate noise coupling: a pain for mixed-signal systems (Keynote Address)

    NASA Astrophysics Data System (ADS)

    Wambacq, Piet; Van der Plas, Geert; Donnay, Stephane; Badaroglu, Mustafa; Soens, Charlotte

    2005-06-01

    Crosstalk from digital to analog in mixed-signal ICs is recognized as one of the major roadblocks for systems-on-chip (SoC) in future CMOS technologies. This crosstalk mainly happens via the semiconducting silicon substrate, which is usually treated as a ground node by analog and RF designers. The substrate noise coupling problem leads more and more to malfunctioning or extra design iterations. One of the reasons is that the phenomenon of substrate noise coupling is difficult to model and hence difficult to understand. It can be caused by the switching of thousands or millions of gates and depends on layout details. From the generation side (the digital domain), coping with the large amount of noise generators can be solved by macromodeling. On the other hand, the impact of substrate noise on the analog circuits requires careful modeling at the level of transistors and parasitics of layout, power supply, package, PCB, Comparison to measurements of macromodeling at the digital side and careful modeling at the analog side, shows that both the generation and the impact of substrate noise can be predicted with an accuracy of a few dB. In addition, this combination of macromodeling at the digital side and careful modeling at the analog side leads to an understanding of the problem, which can be used for digital low-noise design techniques to minimize the generation of noise, and substrate noise immune design of analog/RF circuits.

  15. Dual-beam laser welding of AZ31B magnesium alloy in zero-gap lap joint configuration

    NASA Astrophysics Data System (ADS)

    Harooni, Masoud; Carlson, Blair; Kovacevic, Radovan

    2014-03-01

    Porosity within laser welds of magnesium alloys is one of the main roadblocks to achieving high quality joints. One of the causes of pore formation is the presence of pre-existing coatings on the surface of magnesium alloy such as oxide or chromate layers. In this study, single-beam and dual-beam laser heat sources are investigated in relation to mitigation of pores resulting from the presence of the as-received oxide layer on the surface of AZ31B-H24 magnesium alloy during the laser welding process. A fiber laser with a power of up to 4 kW is used to weld samples in a zero-gap lap joint configuration. The effect of dual-beam laser welding with different beam energy ratios is studied on the quality of the weld bead. The purpose of this paper is to identify the beam ratio that best mitigates pore formation in the weld bead. The laser molten pool and the keyhole condition, as well as laser-induced plasma plume are monitored in real-time by use of a high speed charge-coupled device (CCD) camera assisted with a green laser as an illumination source. Tensile and microhardness tests were used to measure the mechanical properties of the laser welded samples. Results showed that a dual-beam laser configuration can effectively mitigate pore formation in the weld bead by a preheating-welding mechanism.

  16. Taking stock of Myanmar’s progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead

    PubMed Central

    2013-01-01

    Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar’s progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar’s achievements toward MDG 6 targets – in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar’s government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar’s government should invest greater efforts into health system strengthening to pave the road to universal health coverage. PMID:24025845

  17. Facilitating the selection and creation of accurate interatomic potentials with robust tools and characterization

    NASA Astrophysics Data System (ADS)

    Trautt, Zachary T.; Tavazza, Francesca; Becker, Chandler A.

    2015-10-01

    The Materials Genome Initiative seeks to significantly decrease the cost and time of development and integration of new materials. Within the domain of atomistic simulations, several roadblocks stand in the way of reaching this goal. While the NIST Interatomic Potentials Repository hosts numerous interatomic potentials (force fields), researchers cannot immediately determine the best choice(s) for their use case. Researchers developing new potentials, specifically those in restricted environments, lack a comprehensive portfolio of efficient tools capable of calculating and archiving the properties of their potentials. This paper elucidates one solution to these problems, which uses Python-based scripts that are suitable for rapid property evaluation and human knowledge transfer. Calculation results are visible on the repository website, which reduces the time required to select an interatomic potential for a specific use case. Furthermore, property evaluation scripts are being integrated with modern platforms to improve discoverability and access of materials property data. To demonstrate these scripts and features, we will discuss the automation of stacking fault energy calculations and their application to additional elements. While the calculation methodology was developed previously, we are using it here as a case study in simulation automation and property calculations. We demonstrate how the use of Python scripts allows for rapid calculation in a more easily managed way where the calculations can be modified, and the results presented in user-friendly and concise ways. Additionally, the methods can be incorporated into other efforts, such as openKIM.

  18. Improvements in resist performance towards EUV HVM

    NASA Astrophysics Data System (ADS)

    Yildirim, Oktay; Buitrago, Elizabeth; Hoefnagels, Rik; Meeuwissen, Marieke; Wuister, Sander; Rispens, Gijsbert; van Oosten, Anton; Derks, Paul; Finders, Jo; Vockenhuber, Michaela; Ekinci, Yasin

    2017-03-01

    Extreme ultraviolet (EUV) lithography with 13.5 nm wavelength is the main option for sub-10nm patterning in the semiconductor industry. We report improvements in resist performance towards EUV high volume manufacturing. A local CD uniformity (LCDU) model is introduced and validated with experimental contact hole (CH) data. Resist performance is analyzed in terms of ultimate printing resolution (R), line width roughness (LWR), sensitivity (S), exposure latitude (EL) and depth of focus (DOF). Resist performance of dense lines at 13 nm half-pitch and beyond is shown by chemical amplified resist (CAR) and non-CAR (Inpria YA Series) on NXE scanner. Resolution down to 10nm half pitch (hp) is shown by Inpria YA Series resist exposed on interference lithography at the Paul Sherrer Institute. Contact holes contrast and consequent LCDU improvement is achieved on a NXE:3400 scanner by decreasing the pupil fill ratio. State-of-the-art imaging meets 5nm node requirements for CHs. A dynamic gas lock (DGL) membrane is introduced between projection optics box (POB) and wafer stage. The DGL membrane will suppress the negative impact of resist outgassing on the projection optics by 100%, enabling a wider range of resist materials to be used. The validated LCDU model indicates that the imaging requirements of the 3nm node can be met with single exposure using a high-NA EUV scanner. The current status, trends, and potential roadblocks for EUV resists are discussed. Our results mark the progress and the improvement points in EUV resist materials to support EUV ecosystem.

  19. Magnetic defects in chemically converted graphene nanoribbons: electron spin resonance investigation

    NASA Astrophysics Data System (ADS)

    Singamaneni, Srinivasa Rao; Stesmans, Andre; van Tol, Johan; Kosynkin, D. V.; Tour, James M.

    2014-04-01

    Electronic spin transport properties of graphene nanoribbons (GNRs) are influenced by the presence of adatoms, adsorbates and edge functionalization. To improve the understanding of the factors that influence the spin properties of GNRs, local (element) spin-sensitive techniques such as electron spin resonance (ESR) spectroscopy are important for spintronics applications. Here, we present results of multi-frequency continuous wave (CW), pulse and hyperfine sublevel correlation (HYSCORE) ESR spectroscopy measurements performed on oxidatively unzipped graphene nanoribbons (GNRs), which were subsequently chemically converted (CCGNRs) with hydrazine. ESR spectra at 336 GHz reveal an isotropic ESR signal from the CCGNRs, of which the temperature dependence of its line width indicates the presence of localized unpaired electronic states. Upon functionalization of CCGNRs with 4-nitrobenzene diazonium tetrafluoroborate, the ESR signal is found to be 2 times narrower than that of pristine ribbons. NH3 adsorption/desorption on CCGNRs is shown to narrow the signal, while retaining the signal intensity and g value. The electron spin-spin relaxation process at 10 K is found to be characterized by slow (163 ns) and fast (39 ns) components. HYSCORE ESR data demonstrate the explicit presence of protons and 13C atoms. With the provided identification of intrinsic point magnetic defects such as proton and 13C has been reported, which are roadblocks to spin travel in graphene-based materials, this work could help in advancing the present fundamental understanding on the edge-spin (or magnetic)-based transport properties of CCGNRs.

  20. Prosthetic Jamming Terminal Device: A Case Study of Untethered Soft Robotics

    PubMed Central

    Amend, John; Farrell, Todd; Latour, Debra; Martinez, Carlos; Johansson, Jen; McNicoll, Anthony; Wartenberg, Marek; Naseef, Samuel; Hanson, William; Culley, William

    2016-01-01

    Abstract This article illuminates the major and often overlooked challenge of untethering soft robotic systems through the context of recent work, in which soft robotic gripper technology enabled by jamming of granular media was applied to a prosthetic jamming terminal device (PJTD). The PJTD's technical and market feasibility was evaluated in a pilot study with two upper-limb amputees. A PJTD prototype was tested against a commercial device (Motion Control electric terminal service with a one degree-of-freedom pinching mechanism) using two existing hand function tests: the first quantified the device's speed in picking and placing small blocks and the second evaluated a person's ability to perform activities of daily living (ADLs). The PJTD prototype performed slightly slower than its commercial counterpart in the first test. While both participants successfully completed all the ADLs with both devices in the second test, the commercial device scored marginally higher. Results suggested that PJTD can have potential benefits over existing terminal devices, such as providing the capability to firmly grasp tools due to the ability of PJTD to conform to arbitrary surfaces and reducing compensatory shoulder movements due to its axisymmetric design. Some downsides were that users reported fatigue while operating the PJTD, as most operations require pushing the PJTD against target objects to adequately conform to them. The greatest drawback for the PJTD is also a major roadblock preventing a number of soft robotic research projects from making an impact in real-world applications: pneumatic technology required for operating the PJTD is currently too large and heavy to enable compact untethered operation. PMID:28078196

  1. Adherence barriers to chronic dialysis in the United States.

    PubMed

    Chan, Kevin E; Thadhani, Ravi I; Maddux, Franklin W

    2014-11-01

    Hemodialysis patients often do not attend their scheduled treatment session. We investigated factors associated with missed appointments and whether such nonadherence poses significant harm to patients and increases overall health care utilization in an observational analysis of 44 million hemodialysis treatments for 182,536 patients with ESRD in the United States. We assessed the risk of hospitalization, emergency room visit, or intensive-coronary care unit (ICU-CCU) admission in the 2 days after a missed treatment relative to the risk for patients who received hemodialysis. Over the 5-year study period, the average missed treatment rate was 7.1 days per patient-year. In covariate adjusted logistic regression, the risk of hospitalization (odds ratio [OR], 3.98; 95% confidence interval [95% CI], 3.93 to 4.04), emergency room visit (OR, 2.00; 95% CI, 1.87 to 2.14), or ICU-CCU admission (OR, 3.89; 95% CI, 3.81 to 3.96) increased significantly after a missed treatment. Overall, 0.9 missed treatment days per year associated with suboptimal transportation to dialysis, inclement weather, holidays, psychiatric illness, pain, and gastrointestinal upset. These barriers also associated with excess hospitalization (5.6 more events per patient-year), emergency room visits (1.1 more visits), and ICU-CCU admissions (0.8 more admissions). In conclusion, poor adherence to hemodialysis treatments may be a substantial roadblock to achieving better patient outcomes. Addressing systemic and patient barriers that impede access to hemodialysis care may decrease missed appointments and reduce patient morbidity. Copyright © 2014 by the American Society of Nephrology.

  2. Prospects for the Comparative Study of International Migration using quasi-longitudinal micro-data

    PubMed Central

    Liu, Mao-Mei; Creighton, Mathew J.; Riosmena, Fernando; Baizán Mun͂oz, Pau

    2017-01-01

    BACKGROUND Longitudinal micro-level data about international migration behavior are notoriously difficult to collect, but data collection efforts have become more frequent in recent years. Comparative research of the patterns and processes of international migration, however, remains quite rare, especially that which compares across regions. OBJECTIVE We highlight the promises and difficulties of comparative international migration research, by offering a detailed comparison of two prominent data collection efforts. METHODS We systematically review existing sources of longitudinal and quasi-longitudinal individual-level and household-level data of international migration. We then compare two widely-used data sources: the Mexican Migration Project (MMP) and the Migration between Africa and Europe project (MAFE). RESULTS Data collection efforts are increasingly diverse, yet public accessibility of data remains limited. Also, comparability of data collected across settings can be complicated. In our MMP-MAFE analysis, we show some ways in which comparability can be achieved. CONCLUSIONS A primary roadblock to international comparative research is that, with some exceptions, the public accessibility of data remains low. Even when data is public and surveys are modeled after one another, comparability is not easy due to necessary trade-offs in adapting surveys to local settings and to developments in the field. CONTRIBUTION We demonstrate that, despite great strides in collecting quasi-longitudinal data of international migration, data accessibility still hinders the study of migration. With regards to comparability, our article provides important lessons for future data collection and analysis efforts that could improve comparability and thus advance understanding of the complex dynamics of international migration. PMID:29276429

  3. Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens

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

    Elfenbein, Johanna R.; Knodler, Leigh A.; Nakayasu, Ernesto S.

    Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking itsmore » retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.« less

  4. Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens

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

    Elfenbein, Johanna R.; Knodler, Leigh A.; Nakayasu, Ernesto S.

    Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking itsmore » retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.« less

  5. Human milk oligosaccharides: Every baby needs a sugar mama

    PubMed Central

    Bode, Lars

    2012-01-01

    Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic “bifidus factor” that serves as a metabolic substrate for desired bacteria and shapes an intestinal microbiota composition with health benefits for the breast-fed neonate. Today, HMOs are known to be more than just “food for bugs”. An accumulating body of evidence suggests that HMOs are antiadhesive antimicrobials that serve as soluble decoy receptors, prevent pathogen attachment to infant mucosal surfaces and lower the risk for viral, bacterial and protozoan parasite infections. In addition, HMOs may modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, lower the risk for necrotizing enterocolitis and provide the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Most data, however, stem from in vitro, ex vivo or animal studies and occasionally from association studies in mother–infant cohorts. Powered, randomized and controlled intervention studies will be needed to confirm relevance for human neonates. The first part of this review introduces the pioneers in HMO research, outlines HMO structural diversity and describes what is known about HMO biosynthesis in the mother's mammary gland and their metabolism in the breast-fed infant. The second part highlights the postulated beneficial effects of HMO for the breast-fed neonate, compares HMOs with oligosaccharides in the milk of other mammals and in infant formula and summarizes the current roadblocks and future opportunities for HMO research. PMID:22513036

  6. Translational research in infectious disease: current paradigms and challenges ahead

    PubMed Central

    Fontana, Judith M.; Alexander, Elizabeth; Salvatore, Mirella

    2012-01-01

    In recent years, the biomedical community has witnessed a rapid scientific and technological evolution following the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology, to the “holistic” approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics and other “omics” have become the predominant tools by which large amounts of data are amassed, analyzed and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been steadily decreasing, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this paper we will review, in a non-inclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field. PMID:22633095

  7. Contextual processing in unpredictable auditory environments: the limited resource model of auditory refractoriness in the rhesus

    PubMed Central

    Gurnsey, Kate; Salisbury, Dean; Sweet, Robert A.

    2016-01-01

    Auditory refractoriness refers to the finding of smaller electroencephalographic (EEG) responses to tones preceded by shorter periods of silence. To date, its physiological mechanisms remain unclear, limiting the insights gained from findings of abnormal refractoriness in individuals with schizophrenia. To resolve this roadblock, we studied auditory refractoriness in the rhesus, one of the most important animal models of auditory function, using grids of up to 32 chronically implanted cranial EEG electrodes. Four macaques passively listened to sounds whose identity and timing was random, thus preventing animals from forming valid predictions about upcoming sounds. Stimulus onset asynchrony ranged between 0.2 and 12.8 s, thus encompassing the clinically relevant timescale of refractoriness. Our results show refractoriness in all 8 previously identified middle- and long-latency components that peaked between 14 and 170 ms after tone onset. Refractoriness may reflect the formation and gradual decay of a basic sensory memory trace that may be mirrored by the expenditure and gradual recovery of a limited physiological resource that determines generator excitability. For all 8 components, results were consistent with the assumption that processing of each tone expends ∼65% of the available resource. Differences between components are caused by how quickly the resource recovers. Recovery time constants of different components ranged between 0.5 and 2 s. This work provides a solid conceptual, methodological, and computational foundation to dissect the physiological mechanisms of auditory refractoriness in the rhesus. Such knowledge may, in turn, help develop novel pharmacological, mechanism-targeted interventions. PMID:27512021

  8. Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens

    DOE PAGES

    Elfenbein, Johanna R.; Knodler, Leigh A.; Nakayasu, Ernesto S.; ...

    2015-09-14

    Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking itsmore » retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.« less

  9. Critical care medicine in the hospital: lessons from the EURICUS-studies.

    PubMed

    Miranda, D Reis; Rivera-Fernández, R; Nap, R E

    2007-05-01

    We have performed a retrospective analysis of the EURICUS-studies using their database at the Foundation for Research on Intensive Care in Europe (FRICE) and other related documents, among which the various reports produced to the European Union which granted the studies, with the following purposes: a) to select and describe the most relevant observational and experimental results of the EURICUS studies; b) to inventory the main obstacles to the appropriate organization of intensive care medicine in the Hospital and c) to highlight amid the acquired knowledge those subjects which could have a direct and primary impact for improving the organization and management of intensive care units (ICUs). The EURICUS-studies have shown a rather non-systematic variation on the variables of the organization and management, resulting in a significant waste of resources and in a generally perceived insufficient performance of ICUs in Europe. Three major roadblocks were found: a) the lack of a clear concept of Critical Care Medicine; b) the lack of defined objectives both regarding the planning of the facilities and the activities to be developed in the ICU and c) the lack of a purposeful organization and management of work in the ICU. The further development and integration of each ICU in the Hospital should consider the following: a) the system approach to the analysis and standardization of processes of care; b) the redefinition of all jobs in each ICU; c) the definition of patient/nurse ratios in each ICU and sibling departments and d) to professionalize the organization and management of the ICU.

  10. A verotoxin 1 B subunit-lambda CRO chimeric protein specifically binds both DNA and globotriaosylceramide (Gb(3)) to effect nuclear targeting of exogenous DNA in Gb(3) positive cells.

    PubMed

    Facchini, L M; Lingwood, C A

    2001-09-10

    Inefficient nuclear incorporation of foreign DNA remains a critical roadblock in the development of effective nonviral gene delivery systems. DNA delivered by traditional protocols remains within endosomal/lysosomal vesicles, or is rapidly degraded in the cytoplasm. Verotoxin I (VT), an AB(5) subunit toxin produced by enterohaemorrhagic Escherichia coli, binds to the cell surface glycolipid, globotriaosylceramide (Gb(3)) and is internalized into preendosomes. VT is then retrograde transported to the Golgi, endoplasmic reticulum (ER), and nucleus of highly VT-sensitive cells. We have utilized this nuclear targeting of VT to design a unique delivery system which transports exogenous DNA via vesicular traffic to the nucleus. The nontoxic VT binding subunit (VTB) was fused to the lambda Cro DNA-binding repressor, generating a 14-kDa VTB-Cro chimera. VTB-Cro binds specifically via the Cro domain to a 25-bp DNA fragment containing the consensus Cro operator. VTB-Cro demonstrates simultaneous specific binding to Gb(3). Treatment of Vero cells with fluorescent-labeled Cro operator DNA in the presence of VTB-Cro, results in DNA internalization to the Golgi, ER, and nucleus, whereas fluorescent DNA alone is incorporated poorly and randomly within the cytoplasm. VTB-Cro mediated nuclear DNA transport is prevented by brefeldin A, consistent with Golgi/ER intracellular routing. Pretreatment with filipin had no effect, indicating that caveoli are not involved. This novel VTB-Cro shuttle protein may find practical applications in the fields of intracellular targeting, gene delivery, and gene therapy. Copyright 2001 Academic Press.

  11. Who goes, who stays?

    PubMed

    Light, D A

    2001-01-01

    The merger announcement between DeWaal Pharmaceuticals and BioHealth Labs was front-page news. Pictures of CEO Steve Lindell and chairman Kaspar van de Velde had appeared in newspapers around the world. Two months later, the press had moved on to a new story, and the hard labor of integration loomed. Steve had worked tirelessly to clear regulatory hurdles, and all signs pointed toward approval in the near future. Now Steve was feeling pressure to attack the real challenge of the merger: bringing together two very different cultures as quickly and efficiently as possible. DeWaal was an established drug-maker based in the Netherlands, and BioHealth, headquartered just north of New York City, had in recent years become competitive at the highest tier of the market. The first step in integrating the two companies was to select the top layers of management for the new company. At the moment, there were some 120 people on two continents for about 65 senior-level jobs. Steve's urgency was not without cause: talented people from both sides were jumping ship, and BioHealth's stock price had dipped 20% after the initial euphoria over the deal had worn off. Complicating matters was confusion over who was really in charge: Steve wanted to take leadership and move ahead rapidly, but he was often disarmed by Kaspar's charming persuasiveness. As the two men attempt to work through the important personnel issues during a lunch meeting, they quickly hit a roadblock. How can they come to agreement about who goes and who stays? Four commentators offer advice in response to this fictional case.

  12. High p-type doping, mobility, and photocarrier lifetime in arsenic-doped CdTe single crystals

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

    Nagaoka, Akira; Kuciauskas, Darius; McCoy, Jedidiah

    Here, Group-V element doping is promising for simultaneously maximizing the hole concentration and minority carrier lifetime in CdTe for thin film solar cells, but there are roadblocks concerning point defects including the possibility of self-compensation by AX metastability. Herein, we report on doping, lifetime, and mobility of CdTe single crystals doped with As between 10 16 and 10 20 cm –3 grown from the Cd solvent by the travelling heater method. Evidence consistent with AX instability as a major contributor to compensation in samples doped below 10 17 cm –3 is presented, while for higher-doped samples, precipitation of a secondmore » phase on planar structural defects is also observed and may explain spatial variation in properties such as lifetime. Rapid cooling after crystal growth increases doping efficiency and mobility for times up to 20–30 days at room temperature with the highest efficiencies observed close to 45% and a hole mobility of 70 cm 2/Vs at room temperature. A doping limit in the low 10 17/cm 3 range is observed for samples quenched at 200–300 °C/h. Bulk minority carrier lifetimes exceeding 20 ns are observed for samples doped near 10 16 cm –3 relaxed in the dark and for unintentionally doped samples, while a lifetime of nearly 5 ns is observed for 10 18 cm –3 As doping. These results help us to establish limits on properties expected for group-V doped CdTe polycrystalline thin films for use in photovoltaics.« less

  13. Intrinsic and extrinsic defects in a family of coal-derived graphene quantum dots

    NASA Astrophysics Data System (ADS)

    Singamaneni, Srinivasa Rao; van Tol, Johan; Ye, Ruquan; Tour, James M.

    2015-11-01

    In this letter, we report on the high frequency (239.2 and 336 GHz) electron spin resonance (ESR) studies performed on graphene quantum dots (GQDs), prepared through a wet chemistry route from three types of coal: (a) bituminous, (b) anthracite, and (c) coke; and from non-coal derived GQDs. The microwave frequency-, power-, and temperature-dependent ESR spectra coupled with computer-aided simulations reveal four distinct magnetic defect centers. In bituminous- and anthracite-derived GQDs, we have identified two of them as intrinsic carbon-centered magnetic defect centers (a broad signal of peak to peak width = 697 (10-4 T), g = 2.0023; and a narrow signal of peak to peak width = 60 (10-4 T), g = 2.003). The third defect center is Mn2+ (6S5/2, 3d5) (signal width = 61 (10-4 T), g = 2.0023, Aiso = 93(10-4 T)), and the fourth defect is identified as Cu2+ (2D5/2, 3d9) (g⊥ = 2.048 and g‖ = 2.279), previously undetected. Coke-derived and non-coal derived GQDs show Mn2+ and two-carbon related signals, and no Cu2+ signal. The extrinsic impurities most likely originate from the starting coal. Furthermore, Raman, photoluminescence, and ESR measurements detected no noticeable changes in the properties of the bituminous GQDs after one year. This study highlights the importance of employing high frequency ESR spectroscopy in identifying the (magnetic) defects, which are roadblocks for spin relaxation times of graphene-based materials. These defects would not have been possible to probe by other spin transport measurements.

  14. The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

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

    Rosenthal, Liana S.; Drake, Daniel; Alcalay, Roy N.

    Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projectsmore » also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.« less

  15. A National Program for Analysis of the Climate System

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried; Arkin, Phil; Kalnay, Eugenia; Laver, James; Trenberth, Kevin

    2002-01-01

    Perhaps the single greatest roadblock to fundamental advances in our understanding of climate variability and climate change is the lack of robust and unbiased long-term global observations of the climate system. Such observations are critical for the identification and diagnosis of climate variations, and provide the constraints necessary for developing and validating climate models. The first generation of reanalysis efforts, by using fixed analysis systems, eliminated the artificial climate signals that occurred in analyses generated at the operational numerical weather prediction centers. These datasets are now widely used by the scientific community in a variety of applications including atmosphere-ocean interactions, seasonal prediction, climate monitoring, the hydrological cycle, and a host of regional and other diagnostic studies. These reanalyses, however, had problems that made them sub-optimal or even unusable for some applications. Perhaps the most serious problem for climate applications was that, while the assimilation system remained fixed, changes in the observing systems did produce spurious changes in the perceived climate. The first generation reanalysis products also exposed problems with physical consistency of the products and the accurate representation of physical processes in the climate system. Examples are bias in the estimates of ocean surface fluxes, and inadequate representation of polar hydrology. In this talk, I will describe some initial plans for a national program on reananlysis. The program is envisioned to be part of an on-going activity to maintain, improve, and reprocess our record of climate observations. I will discuss various issues affecting the quality of reanalyses, with a special focus on those relevant to the ocean.

  16. Hurdles in tissue engineering/regenerative medicine product commercialization: a survey of North American academia and industry.

    PubMed

    Johnson, Peter C; Bertram, Timothy A; Tawil, Bill; Hellman, Kiki B

    2011-01-01

    The Tissue Engineering and Regenerative Medicine International Society-North America (TERMIS-NA) Industry Committee was formed in February 2009 to address the common roadblocks (i.e., hurdles) in the commercialization of tissue engineering/regenerative medicine products for its members. A semiquantitative online opinion survey instrument that delineated potentially sensitive hurdles to commercialization in each of the TERMIS constituency groups that generally participate in the stream of technology commercialization (academia, startup companies, development-stage companies, and established companies) was developed. The survey was opened to each of the 863 members of TERMIS-NA for a period of 5 weeks from October to November 2009. By its conclusion, 215 members (25%) had responded. Their proportionate numbers were closely representative of TERMIS-NA constituencies. The resulting data delineate what each group considers to be its most difficult and also its easiest hurdles in taking a technology to full product development. In addition, each group ranked its perception of the difficult and easy hurdles for all other groups, enabling an assessment of the degree of understanding between groups. The data depict not only critical hurdles in the path to commercialization at each stage in product development but also a variable understanding of perceptions of hurdles between groups. This assessment has provided the Industry Committee with activity foci needed to assist individual groups in the technology-commercialization stream. Moreover, the analysis suggests that enhanced communication between groups engaged in commercialization will be critical to the successful development of products in the tissue engineering/regenerative medicine sector.

  17. A new generation of cancer genome diagnostics for routine clinical use: overcoming the roadblocks to personalized cancer medicine.

    PubMed

    Heuckmann, J M; Thomas, R K

    2015-09-01

    The identification of 'druggable' kinase gene alterations has revolutionized cancer treatment in the last decade by providing new and successfully targetable drug targets. Thus, genotyping tumors for matching the right patients with the right drugs have become a clinical routine. Today, advances in sequencing technology and computational genome analyses enable the discovery of a constantly growing number of genome alterations relevant for clinical decision making. As a consequence, several technological approaches have emerged in order to deal with these rapidly increasing demands for clinical cancer genome analyses. Here, we describe challenges on the path to the broad introduction of diagnostic cancer genome analyses and the technologies that can be applied to overcome them. We define three generations of molecular diagnostics that are in clinical use. The latest generation of these approaches involves deep and thus, highly sensitive sequencing of all therapeutically relevant types of genome alterations-mutations, copy number alterations and rearrangements/fusions-in a single assay. Such approaches therefore have substantial advantages (less time and less tissue required) over PCR-based methods that typically have to be combined with fluorescence in situ hybridization for detection of gene amplifications and fusions. Since these new technologies work reliably on routine diagnostic formalin-fixed, paraffin-embedded specimens, they can help expedite the broad introduction of personalized cancer therapy into the clinic by providing comprehensive, sensitive and accurate cancer genome diagnoses in 'real-time'. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Low-voltage back-gated atmospheric pressure chemical vapor deposition based graphene-striped channel transistor with high-κ dielectric showing room-temperature mobility > 11,000 cm(2)/V·s.

    PubMed

    Smith, Casey; Qaisi, Ramy; Liu, Zhihong; Yu, Qingkai; Hussain, Muhammad Mustafa

    2013-07-23

    Utilization of graphene may help realize innovative low-power replacements for III-V materials based high electron mobility transistors while extending operational frequencies closer to the THz regime for superior wireless communications, imaging, and other novel applications. Device architectures explored to date suffer a fundamental performance roadblock due to lack of compatible deposition techniques for nanometer-scale dielectrics required to efficiently modulate graphene transconductance (gm) while maintaining low gate capacitance-voltage product (CgsVgs). Here we show integration of a scaled (10 nm) high-κ gate dielectric aluminum oxide (Al2O3) with an atmospheric pressure chemical vapor deposition (APCVD)-derived graphene channel composed of multiple 0.25 μm stripes to repeatedly realize room-temperature mobility of 11,000 cm(2)/V·s or higher. This high performance is attributed to the APCVD graphene growth quality, excellent interfacial properties of the gate dielectric, conductivity enhancement in the graphene stripes due to low tox/Wgraphene ratio, and scaled high-κ dielectric gate modulation of carrier density allowing full actuation of the device with only ±1 V applied bias. The superior drive current and conductance at Vdd = 1 V compared to other top-gated devices requiring undesirable seed (such as aluminum and poly vinyl alcohol)-assisted dielectric deposition, bottom gate devices requiring excessive gate voltage for actuation, or monolithic (nonstriped) channels suggest that this facile transistor structure provides critical insight toward future device design and process integration to maximize CVD-based graphene transistor performance.

  19. Characterizability of metabolic pathway systems from time series data.

    PubMed

    Voit, Eberhard O

    2013-12-01

    Over the past decade, the biomathematical community has devoted substantial effort to the complicated challenge of estimating parameter values for biological systems models. An even more difficult issue is the characterization of functional forms for the processes that govern these systems. Most parameter estimation approaches tacitly assume that these forms are known or can be assumed with some validity. However, this assumption is not always true. The recently proposed method of Dynamic Flux Estimation (DFE) addresses this problem in a genuinely novel fashion for metabolic pathway systems. Specifically, DFE allows the characterization of fluxes within such systems through an analysis of metabolic time series data. Its main drawback is the fact that DFE can only directly be applied if the pathway system contains as many metabolites as unknown fluxes. This situation is unfortunately rare. To overcome this roadblock, earlier work in this field had proposed strategies for augmenting the set of unknown fluxes with independent kinetic information, which however is not always available. Employing Moore-Penrose pseudo-inverse methods of linear algebra, the present article discusses an approach for characterizing fluxes from metabolic time series data that is applicable even if the pathway system is underdetermined and contains more fluxes than metabolites. Intriguingly, this approach is independent of a specific modeling framework and unaffected by noise in the experimental time series data. The results reveal whether any fluxes may be characterized and, if so, which subset is characterizable. They also help with the identification of fluxes that, if they could be determined independently, would allow the application of DFE. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Characterizability of Metabolic Pathway Systems from Time Series Data

    PubMed Central

    Voit, Eberhard O.

    2013-01-01

    Over the past decade, the biomathematical community has devoted substantial effort to the complicated challenge of estimating parameter values for biological systems models. An even more difficult issue is the characterization of functional forms for the processes that govern these systems. Most parameter estimation approaches tacitly assume that these forms are known or can be assumed with some validity. However, this assumption is not always true. The recently proposed method of Dynamic Flux Estimation (DFE) addresses this problem in a genuinely novel fashion for metabolic pathway systems. Specifically, DFE allows the characterization of fluxes within such systems through an analysis of metabolic time series data. Its main drawback is the fact that DFE can only directly be applied if the pathway system contains as many metabolites as unknown fluxes. This situation is unfortunately rare. To overcome this roadblock, earlier work in this field had proposed strategies for augmenting the set of unknown fluxes with independent kinetic information, which however is not always available. Employing Moore-Penrose pseudo-inverse methods of linear algebra, the present article discusses an approach for characterizing fluxes from metabolic time series data that is applicable even if the pathway system is underdetermined and contains more fluxes than metabolites. Intriguingly, this approach is independent of a specific modeling framework and unaffected by noise in the experimental time series data. The results reveal whether any fluxes may be characterized and, if so, which subset is characterizable. They also help with the identification of fluxes that, if they could be determined independently, would allow the application of DFE. PMID:23391489

  1. High p-type doping, mobility, and photocarrier lifetime in arsenic-doped CdTe single crystals

    DOE PAGES

    Nagaoka, Akira; Kuciauskas, Darius; McCoy, Jedidiah; ...

    2018-05-07

    Here, Group-V element doping is promising for simultaneously maximizing the hole concentration and minority carrier lifetime in CdTe for thin film solar cells, but there are roadblocks concerning point defects including the possibility of self-compensation by AX metastability. Herein, we report on doping, lifetime, and mobility of CdTe single crystals doped with As between 10 16 and 10 20 cm –3 grown from the Cd solvent by the travelling heater method. Evidence consistent with AX instability as a major contributor to compensation in samples doped below 10 17 cm –3 is presented, while for higher-doped samples, precipitation of a secondmore » phase on planar structural defects is also observed and may explain spatial variation in properties such as lifetime. Rapid cooling after crystal growth increases doping efficiency and mobility for times up to 20–30 days at room temperature with the highest efficiencies observed close to 45% and a hole mobility of 70 cm 2/Vs at room temperature. A doping limit in the low 10 17/cm 3 range is observed for samples quenched at 200–300 °C/h. Bulk minority carrier lifetimes exceeding 20 ns are observed for samples doped near 10 16 cm –3 relaxed in the dark and for unintentionally doped samples, while a lifetime of nearly 5 ns is observed for 10 18 cm –3 As doping. These results help us to establish limits on properties expected for group-V doped CdTe polycrystalline thin films for use in photovoltaics.« less

  2. Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder.

    PubMed

    Uddin, L Q; Dajani, D R; Voorhies, W; Bednarz, H; Kana, R K

    2017-08-22

    Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

  3. Personality and Gambling Involvement: A Person-Centered Approach

    PubMed Central

    Savage, Jeanne E.; Slutske, Wendy S.; Martin, Nicholas G.

    2014-01-01

    Individual differences in personality are likely to play an important role in explaining the propensity to gamble. One of the potential roadblocks to elucidating the relation between personality and gambling may be inadequately accounting for the diversity of gambling activities. The goal of the present study was to provide a comprehensive and nuanced portrait of the relation between personality and gambling by taking a multivariate approach to the co-use of multiple gambling activities and employing a broad inventory of potentially-relevant personality dimensions. Participants were 4,669 individuals from a national Australian twin registry. Structured interviews including an extensive assessment of gambling behaviors were conducted, and personality questionnaires that included the tidimensional Personality Questionnaire, the Sensation Seeking Scale, and the Magical Ideation Scale were completed. A latent class analysis of past-year involvement in 10 different gambling activities was performed to classify the participants into five groups. Unique personality configurations characterized the three more gambling-involved latent classes. Low behavioral control in the context of high negative emotionality and magical thinking typified extensive, versatile gamblers at high risk of gambling problems. Average behavioral control in the context of high negative emotionality and magical thinking typified those who primarily gambled on non-strategic games of chance. Low behavioral control in the context of high positive emotionality and low magical ideation typified those who primarily gambled on strategic games of skill. This study illustrates the value of using a multivariate person-centered approach for characterizing the personality correlates of the multi-faceted phenomenon that is gambling. PMID:25134059

  4. Personality and gambling involvement: a person-centered approach.

    PubMed

    Savage, Jeanne E; Slutske, Wendy S; Martin, Nicholas G

    2014-12-01

    Individual differences in personality are likely to play an important role in explaining the propensity to gamble. One of the potential roadblocks to elucidating the relation between personality and gambling may be inadequately accounting for the diversity of gambling activities. The goal of the present study was to provide a comprehensive and nuanced portrait of the relation between personality and gambling by taking a multivariate approach to the co-use of multiple gambling activities and employing a broad inventory of potentially relevant personality dimensions. Participants were 4,669 individuals from a national Australian twin registry. Structured interviews including an extensive assessment of gambling behaviors were conducted, and personality questionnaires that included the Multidimensional Personality Questionnaire, the Sensation Seeking Scale, and the Magical Ideation Scale were completed. A latent class analysis of past-year involvement in 10 different gambling activities was performed to classify the participants into 5 groups. Unique personality configurations characterized the 3 more gambling-involved latent classes: (a) low behavioral control in the context of high negative emotionality and magical thinking typified extensive, versatile gamblers at high risk of gambling problems; (b) average behavioral control in the context of high negative emotionality and magical thinking typified those who primarily gambled on non-strategic games of chance; (c) low behavioral control in the context of high positive emotionality and low magical ideation typified those who primarily gambled on strategic games of skill. This study illustrates the value of using a multivariate person-centered approach for characterizing the personality correlates of the multifaceted phenomenon that is gambling.

  5. General Motors and the University of Michigan smart materials and structures collaborative research laboratory

    NASA Astrophysics Data System (ADS)

    Brei, Diann; Luntz, Jonathan; Shaw, John; Johnson, Nancy L.; Browne, Alan L.; Alexander, Paul W.; Mankame, Nilesh D.

    2007-04-01

    The field of Smart Materials and Structures is evolving from high-end, one-of-a-kind products for medical, military and aerospace applications to the point of viability for mainstream affordable high volume products for automotive applications. For the automotive industry, there are significant potential benefits to be realized including reduction in vehicle mass, added functionality and design flexibility and decrease in component size and cost. To further accelerate the path from basic research and development to launched competitive products, General Motors (GM) has teamed with the College of Engineering at the University of Michigan (UM) to establish a $2.9 Million Collaborative Research Laboratory (CRL) in Smart Materials and Structures. Researchers at both GM and UM are working closely together to create leap-frog technologies which start at conceptualization and proceed all the way through demonstration and handoff to product teams, thereby bridging the traditional technology gap between industry and academia. In addition to Smart Device Technology Innovation, other thrust areas in the CRL include Smart Material Maturity with a basic research focus on overcoming material issues that form roadblocks to commercialism and Mechamatronic System Design Methodology with an applied focus on development tools (synthesis and analysis) to aid the engineer in application of smart materials to system engineering. This CRL is a global effort with partners across the nation and world from GM's Global Research Network such as HRL Laboratories in California and GM's India Science Lab in Bangalore, India. This paper provides an overview of this new CRL and gives examples of several of the projects underway.

  6. "Lack of knowledge is no excuse" HIV positive patient with progressive multifocal leukoencephalopathy. Case report from Kenya.

    PubMed

    Kafkova, Jirina; Silharova, Barbora

    2017-11-01

    Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease that affects the central nervous system, which has high morbidity and mortality and no effective, targeted therapies are available. According to the data from developing countries, it affects about 3 to 5% patients who are HIV positive. We present a case of a 27-year-old patient, who got infected with the HIV virus from his mother. The patient had poor compliance to the therapy since its initiation. Due to poor compliance and immunological and virological failure of the first line ARVs, the patient developed PML. Despite confirmed diagnosis of PML and change of the regimen to the second line ARVs, due to progression of the condition, he sought care of an unknown physician, who prescribed therapy with azathioprine 150 mg twice daily, which the patient used for more than 2 weeks. Despite immediate virological suppression, the condition significantly worsened, until the patient developed paraparesis, postural tremor, head tremor, severe dysarthria; he was not able to walk, eat or express himself. The major roadblocks to diagnosis of PML include poor access to health care in general, as well as poor knowledge of the rare condition among the health care professionals. Therapy with azathioprine has been proved to be associated with the development of PML. Thus, in resource limited settings, there is an urgent need for improved access to health care and imaging and laboratory diagnostic means, which would decrease the economic and social burden of severe conditions, such as PML.

  7. Ceramic Single Phase High-Level Nuclear Waste Forms: Hollandite, Perovskite, and Pyrochlore

    NASA Astrophysics Data System (ADS)

    Vetter, M.; Wang, J.

    2017-12-01

    The lack of viable options for the safe, reliable, and long-term storage of nuclear waste is one of the primary roadblocks of nuclear energy's sustainable future. The method being researched is the incorporation and immobilization of harmful radionuclides (Cs, Sr, Actinides, and Lanthanides) into the structure of glasses and ceramics. Borosilicate glasses are the main waste form that is accepted and used by today's nuclear industry, but they aren't the most efficient in terms of waste loading, and durability is still not fully understood. Synroc-phase ceramics (i.e. hollandite, perovskite, pyrochlore, zirconolite) have many attractive qualities that glass waste forms do not: high waste loading, moderate thermal expansion and conductivity, high chemical durability, and high radiation stability. The only downside to ceramics is that they are more complex to process than glass. New compositions can be discovered by using an Artificial Neural Network (ANN) to have more options to optimize the composition, loading for performance by analyzing the non-linear relationships between ionic radii, electronegativity, channel size, and a mineral's ability to incorporate radionuclides into its structure. Cesium can be incorporated into hollandite's A-site, while pyrochlore and perovskite can incorporate actinides and lanthanides into their A-site. The ANN is used to predict new compositions based on hollandite's channel size, as well as the A-O bond distances of pyrochlore and perovskite, and determine which ions can be incorporated. These new compositions will provide more options for more experiments to potentially improve chemical and thermodynamic properties, as well as increased waste loading capabilities.

  8. Controlled Hydrogen Fleet and Infrastructure Demonstration Project

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

    Dr. Scott Staley

    2010-03-31

    This program was undertaken in response to the US Department of Energy Solicitation DE-PS30-03GO93010, resulting in this Cooperative Agreement with the Ford Motor Company and BP to demonstrate and evaluate hydrogen fuel cell vehicles and required fueling infrastructure. Ford initially placed 18 hydrogen fuel cell vehicles (FCV) in three geographic regions of the US (Sacramento, CA; Orlando, FL; and southeast Michigan). Subsequently, 8 advanced technology vehicles were developed and evaluated by the Ford engineering team in Michigan. BP is Ford's principal partner and co-applicant on this project and provided the hydrogen infrastructure to support the fuel cell vehicles. BP ultimatelymore » provided three new fueling stations. The Ford-BP program consists of two overlapping phases. The deliverables of this project, combined with those of other industry consortia, are to be used to provide critical input to hydrogen economy commercialization decisions by 2015. The program's goal is to support industry efforts of the US President's Hydrogen Fuel Initiative in developing a path to a hydrogen economy. This program was designed to seek complete systems solutions to address hydrogen infrastructure and vehicle development, and possible synergies between hydrogen fuel electricity generation and transportation applications. This project, in support of that national goal, was designed to gain real world experience with Hydrogen powered Fuel Cell Vehicles (H2FCV) 'on the road' used in everyday activities, and further, to begin the development of the required supporting H2 infrastructure. Implementation of a new hydrogen vehicle technology is, as expected, complex because of the need for parallel introduction of a viable, available fuel delivery system and sufficient numbers of vehicles to buy fuel to justify expansion of the fueling infrastructure. Viability of the fuel structure means widespread, affordable hydrogen which can return a reasonable profit to the fuel provider, while viability of the vehicle requires an expected level of cost, comfort, safety and operation, especially driving range, that consumers require. This presents a classic 'chicken and egg' problem, which Ford believes can be solved with thoughtful implementation plans. The eighteen Ford Focus FCV vehicles that were operated for this demonstration project provided the desired real world experience. Some things worked better than expected. Most notable was the robustness and life of the fuel cell. This is thought to be the result of the full hybrid configuration of the drive system where the battery helps to overcome the performance reduction associated with time related fuel cell degradation. In addition, customer satisfaction surveys indicated that people like the cars and the concept and operated them with little hesitation. Although the demonstrated range of the cars was near 200 miles, operators felt constrained because of the lack of a number of conveniently located fueling stations. Overcoming this major concern requires overcoming a key roadblock, fuel storage, in a manner that permits sufficient quantity of fuel without sacrificing passenger or cargo capability. Fueling infrastructure, on the other hand, has been problematic. Only three of a planned seven stations were opened. The difficulty in obtaining public approval and local government support for hydrogen fuel, based largely on the fear of hydrogen that grew from past disasters and atomic weaponry, has inhibited progress and presents a major roadblock to implementation. In addition the cost of hydrogen production, in any of the methodologies used in this program, does not show a rapid reduction to commercially viable rates. On the positive side of this issue was the demonstrated safety of the fueling station, equipment and process. In the Ford program, there were no reported safety incidents.« less

  9. The 90 90 90 strategy to end the HIV Pandemic by 2030: Can the supply chain handle it?

    PubMed Central

    Jamieson, David

    2016-01-01

    Introduction UNAIDS “90-90-90” strategy calls for 90% of HIV-infected individuals to be diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and 90% of whom will achieve sustained virologic suppression. Reaching these targets by 2020 will reduce the HIV epidemic to a low-level endemic disease by 2030. However, moving the global response towards this universal test and treat model will pose huge challenges to public health systems in resource-limited settings, including global and local supply chain systems. These challenges are especially acute in Africa, which accounts for over 70% of the persons affected by HIV. Discussion From a supply chain perspective, each of the “90's” has possible complications and roadblocks towards realizing the promise envisioned by 90-90-90. For instance, ensuring that 90% of HIV-infected persons know their status will require a large increase in access to HIV tests compared with what is currently available. To ensure that there are enough anti-retrovirals available to treat the nearly 25 million people that will require them by 2020 represents a near doubling of the ARV supplied to treat the 13 million currently on treatment. Similarly, to monitor those on treatment means an unprecedented scale-up of viral load testing throughout Africa. Conclusions Larger issues include whether the capacity exists at the local level to handle these commodities when they arrive in the most severely affected countries, including considerations of the human resources and costs needed to make this strategy effective. We believe that such “real world” analysis of proposed strategies and policies is essential to ensure their most effective implementation. PMID:27370169

  10. International Collaborations in Large Geophysical Experiments: A Win-Win Situation

    NASA Astrophysics Data System (ADS)

    Keller, G. R.

    2007-12-01

    It has been my privilege to be involved in a significant number of large international cooperative geophysical experiments. These logistically challenging efforts all took place in developing or under-developed countries and were co-driven at least to some extent by scientists in the host country. A team of scientists from developed countries were involved in each case but were not always the leaders of the effort. The host countries were all supportive and played roles ranging from simply facilitating the effort to providing most of the funding. Some lessons learned from these efforts were the following: 1) permissions for large efforts must come from very high levels in the host government; 2) the host scientists should never be overlooked or underestimated; 3) involving students from both the host country and developed countries produces big educational and cultural dividends for all involved (it is a life experience for the visitors and a chance to widen perspectives and even acquire advanced degrees for the students from the host countries); 4) providing funds for scientists and students from the host country to visit their international partners to participate in the data processing and analysis and to attend scientific meetings is extremely important; 5) return trips to the host country to collaborate on data processing and analysis and to consolidate partnerships are also important; 6) the partnership with the host country should be viewed as a long term commitment to scientific cooperation and education that benefits all involved. Our experiences have encountered only a few roadblocks and have been ultimately universally positive. Lifelong relationships have been forged, students have been educated and enriched, and excellent scientific results have been produced.

  11. Online quantitative monitoring of live cell engineered cartilage growth using diffuse fiber-optic Raman spectroscopy.

    PubMed

    Bergholt, Mads S; Albro, Michael B; Stevens, Molly M

    2017-09-01

    Tissue engineering (TE) has the potential to improve the outcome for patients with osteoarthritis (OA). The successful clinical translation of this technique as part of a therapy requires the ability to measure extracellular matrix (ECM) production of engineered tissues in vitro, in order to ensure quality control and improve the likelihood of tissue survival upon implantation. Conventional techniques for assessing the ECM content of engineered cartilage, such as biochemical assays and histological staining are inherently destructive. Raman spectroscopy, on the other hand, represents a non-invasive technique for in situ biochemical characterization. Here, we outline current roadblocks in translational Raman spectroscopy in TE and introduce a comprehensive workflow designed to non-destructively monitor and quantify ECM biomolecules in large (>3 mm), live cell TE constructs online. Diffuse near-infrared fiber-optic Raman spectra were measured from live cell cartilaginous TE constructs over a 56-day culturing period. We developed a multivariate curve resolution model that enabled quantitative biochemical analysis of the TE constructs. Raman spectroscopy was able to non-invasively quantify the ECM components and showed an excellent correlation with biochemical assays for measurement of collagen (R 2  = 0.84) and glycosaminoglycans (GAGs) (R 2  = 0.86). We further demonstrated the robustness of this technique for online prospective analysis of live cell TE constructs. The fiber-optic Raman spectroscopy strategy developed in this work offers the ability to non-destructively monitor construct growth online and can be adapted to a broad range of TE applications in regenerative medicine toward controlled clinical translation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Mixtures Research at NIEHS: An Evolving Program

    PubMed Central

    Rider, Cynthia V; Carlin, Danielle J; DeVito, Micheal J; Thompson, Claudia L; Walker, Nigel J

    2014-01-01

    The National Institute of Environmental Health Sciences (NIEHS) has a rich history in evaluating the toxicity of mixtures. The types of mixtures assessed by the Division of the National Toxicology Program (DNTP) and the extramural community (through the Division of Extramural Research and Training (DERT)) have included a broad range of chemicals and toxicants, with each study having a unique set of questions and design considerations. Some examples of the types of mixtures studied include: groundwater contaminants, pesticides/fertilizers, dioxin-like chemicals (assessing the toxic equivalency approach), drug combinations, air pollution, metals, polycyclic aromatic hydrocarbons, technical mixtures (e.g. pentachlorophenol, flame retardants), and mixed entities (e.g. herbals, asbestos). These endeavors have provided excellent data on the toxicity of specific mixtures and have been informative to the human health risk assessment process in general (e.g. providing data on low dose exposures to environmental chemicals). However, the mixtures research effort at NIEHS, to date, has been driven by test article nominations to the DNTP or by investigator-initiated research through DERT. Recently, the NIEHS has embarked upon an effort to coordinate mixtures research across both intramural and extramural divisions in order to maximize mixtures research results. A path forward for NIEHS mixtures research will be based on feedback from a Request for Information (RFI) designed to gather up-to-date views on the knowledge gaps and roadblocks to evaluating mixtures and performing cumulative risk assessment, and a workshop organized to bring together mixtures experts from risk assessment, exposure science, biology, epidemiology, and statistics. The future of mixtures research at NIEHS will include projects from nominations to DNTP, studies by extramural investigators, and collaborations across government agencies that address high-priority questions in the field of mixtures research. PMID:23146757

  13. Knowledge barriers to PACS adoption and implementation in hospitals.

    PubMed

    Paré, Guy; Trudel, Marie-Claude

    2007-01-01

    Drawing on the classical theory of diffusion of innovations advanced by Rogers [E.M. Rogers, Diffusion of Innovations, 4th ed., Free Press, New York, NY, 1995] and on the theory of barriers to innovation [P. Attewell, Technology diffusion and organizational learning: the case of business computing. Organ. Sci. 3 (1992) 1-19; H. Tanriverdi, C.S. Iacono, Knowledge barriers to diffusion of telemedicine. Proceedings of the 20th International Conference on Information Systems, Charlotte, NC, 1999, pp. 39-50; S. Nambisan, Y.-M. Wang, Roadblocks to web technology adoption? Commun. ACM, 42 (1) (1999) 98-101], this study seeks a better understanding of challenges faced in PACS implementations in hospitals and of the strategies required to ensure their success. To attain this objective, we describe and analyze the process used to adopt and implement PACS at two Canadian hospitals. Our findings clearly demonstrate the importance of treating any PACS deployment not simply as a rollout of new technology but as a project that will transform the organization. Proponents of these projects must not lose sight of the fact that, even if technological complexity represents a significant issue, it must not garner all the project team's attention. This situation is even more dangerous, inasmuch as the greatest risk to the implementation often lies elsewhere. It would also appear to be crucial to anticipate and address organizational and behavioral challenges from the very first phase of the innovation process, in order to ensure that all participants will be committed to the project. In order to maximize the likelihood of PACS success, it appears crucial to adopt a proactive implementation strategy, one that takes into consideration all the technical, economic, organizational, and human factors, and does so from the first phase of the innovation process.

  14. Functionalization of carbon nanotubes: Characterization, modeling and composite applications

    NASA Astrophysics Data System (ADS)

    Wang, Shiren

    Carbon nanotubes have demonstrated exceptional mechanical, thermal and electrical properties, and are regarded as one of the most promising reinforcement materials for the next generation of high performance structural and multifunctional composites. However, to date, most application attempts have been hindered by several technical roadblocks, such as poor dispersion and weak interfacial bonding. In this dissertation, several innovative functionalization methods were proposed, studied to overcome these technical issues in order to realize the full potential of nanotubes as reinforcement. These functionalization methods included precision sectioning of nanotubes using an ultra-microtome, electron-beam irradiation, amino and epoxide group grafting. The characterization results of atomic force microscope, transmission electronic microscope and Raman suggested that aligned carbon nanotubes can be precisely sectioned with controlled length and minimum sidewall damage. This study also designed and demonstrated new covalent functionalization approaches through unique epoxy-grafting and one-step amino-grafting, which have potential of scale-up for composite applications. In addition, the dissertation also successfully tailored the structure and properties of the thin nanotube film through electron beam irradiation. Significant improvement of both mechanical and electrical conducting properties of the irradiated nanotube films or buckypapers was achieved. All these methods demonstrated effectiveness in improving dispersion and interfacial bonding in the epoxy resin, resulting in considerable improvements in composite mechanical properties. Modeling of functionalization methods also provided further understanding and offered the reasonable explanations of SWNTs length distribution as well as carbon nanostructure transformation upon electron-beam irradiation. Both experimental and modeling results provide important foundations for the further comprehensively investigation of nanotube functionalization, and hence facilitate realization of the full potential of nanotube-reinforced nanocomposites.

  15. Transcription arrest by a G quadruplex forming-trinucleotide repeat sequence from the human c-myb gene.

    PubMed

    Broxson, Christopher; Beckett, Joshua; Tornaletti, Silvia

    2011-05-17

    Non canonical DNA structures correspond to genomic regions particularly susceptible to genetic instability. The transcription process facilitates formation of these structures and plays a major role in generating the instability associated with these genomic sites. However, little is known about how non canonical structures are processed when encountered by an elongating RNA polymerase. Here we have studied the behavior of T7 RNA polymerase (T7RNAP) when encountering a G quadruplex forming-(GGA)(4) repeat located in the human c-myb proto-oncogene. To make direct correlations between formation of the structure and effects on transcription, we have taken advantage of the ability of the T7 polymerase to transcribe single-stranded substrates and of G4 DNA to form in single-stranded G-rich sequences in the presence of potassium ions. Under physiological KCl concentrations, we found that T7 RNAP transcription was arrested at two sites that mapped to the c-myb (GGA)(4) repeat sequence. The extent of arrest did not change with time, indicating that the c-myb repeat represented an absolute block and not a transient pause to T7 RNAP. Consistent with G4 DNA formation, arrest was not observed in the absence of KCl or in the presence of LiCl. Furthermore, mutations in the c-myb (GGA)(4) repeat, expected to prevent transition to G4, also eliminated the transcription block. We show T7 RNAP arrest at the c-myb repeat in double-stranded DNA under conditions mimicking the cellular concentration of biomolecules and potassium ions, suggesting that the G4 structure formed in the c-myb repeat may represent a transcription roadblock in vivo. Our results support a mechanism of transcription-coupled DNA repair initiated by arrest of transcription at G4 structures.

  16. SEORious business: structural proteins in sieve tubes and their involvement in sieve element occlusion.

    PubMed

    Knoblauch, Michael; Froelich, Daniel R; Pickard, William F; Peters, Winfried S

    2014-04-01

    The phloem provides a network of sieve tubes for long-distance translocation of photosynthates. For over a century, structural proteins in sieve tubes have presented a conundrum since they presumably increase the hydraulic resistance of the tubes while no potential function other than sieve tube or wound sealing in the case of injury has been suggested. Here we summarize and critically evaluate current speculations regarding the roles of these proteins. Our understanding suffers from the suggestive power of images; what looks like a sieve tube plug on micrographs may not actually impede translocation very much. Recent reports of an involvement of SEOR (sieve element occlusion-related) proteins, a class of P-proteins, in the sealing of injured sieve tubes are inconclusive; various lines of evidence suggest that, in neither intact nor injured plants, are SEORs determinative of translocation stoppage. Similarly, the popular notion that P-proteins serve in the defence against phloem sap-feeding insects is unsupported by empirical facts; it is conceivable that in functional sieve tubes, aphids actually could benefit from inducing a plug. The idea that rising cytosolic Ca(2+) generally triggers sieve tube blockage by P-proteins appears widely accepted, despite lacking experimental support. Even in forisomes, P-protein assemblages restricted to one single plant family and the only Ca(2+)-responsive P-proteins known, the available evidence does not unequivocally suggest that plug formation is the cause rather than a consequence of translocation stoppage. We conclude that the physiological roles of structural P-proteins remain elusive, and that in vivo studies of their dynamics in continuous sieve tube networks combined with flow velocity measurements will be required to (hopefully) resolve this scientific roadblock.

  17. Applications of "Integrated Data Viewer'' (IDV) in the classroom

    NASA Astrophysics Data System (ADS)

    Nogueira, R.; Cutrim, E. M.

    2006-06-01

    Conventionally, weather products utilized in synoptic meteorology reduce phenomena occurring in four dimensions to a 2-dimensional form. This constitutes a road-block for non-atmospheric-science majors who need to take meteorology as a non-mathematical and complementary course to their major programs. This research examines the use of Integrated Data Viewer-IDV as a teaching tool, as it allows a 4-dimensional representation of weather products. IDV was tested in the teaching of synoptic meteorology, weather analysis, and weather map interpretation to non-science students in the laboratory sessions of an introductory meteorology class at Western Michigan University. Comparison of student exam scores according to the laboratory teaching techniques, i.e., traditional lab manual and IDV was performed for short- and long-term learning. Results of the statistical analysis show that the Fall 2004 students in the IDV-based lab session retained learning. However, in the Spring 2005 the exam scores did not reflect retention in learning when compared with IDV-based and MANUAL-based lab scores (short term learning, i.e., exam taken one week after the lab exercise). Testing the long-term learning, seven weeks between the two exams in the Spring 2005, show no statistically significant difference between IDV-based group scores and MANUAL-based group scores. However, the IDV group obtained exam score average slightly higher than the MANUAL group. Statistical testing of the principal hypothesis in this study, leads to the conclusion that the IDV-based method did not prove to be a better teaching tool than the traditional paper-based method. Future studies could potentially find significant differences in the effectiveness of both manual and IDV methods if the conditions had been more controlled. That is, students in the control group should not be exposed to the weather analysis using IDV during lecture.

  18. The Empire strikes back. Counterrevolutionary strategies for industry leaders.

    PubMed

    D'Aveni, Richard

    2002-11-01

    Industry leaders frequently worry that their companies will fall victim to some revolutionary business model or disruptive technology. But new research shows that it's strategically better for incumbents to counter a revolution than to ignore or fully embrace it. Successful incumbents rely on one or more of five approaches to restrain, modify, or, if necessary, neutralize a revolutionary threat. A company that perceives a revolution in its earliest stages can use containment strategies. By throwing up roadblocks--raising switching costs, perhaps, or launching discrediting PR efforts--an incumbent can often limit the degree to which customers and competitors accept a nascent insurgency. And, sometimes, revolutions die there. If not, early containment buys a company some time to shape the revolution so that it complements, rather than supersedes, the incumbent's strengths. And even if shaping efforts fail, they can give an industry leader more time to work out how to absorb the threat by bringing the new competencies or technologies inside the firm in such a way that they don't destroy its existing strengths and capabilities. When revolutions have progressed too far to slow them down, incumbents must take a more aggressive tack. Neutralizing strategies meet a revolution head-on and terminate it--by, say, temporarily giving away the benefits offered by the challenger for free. Annulment strategies allow the market leader to leapfrog over or sidestep the threat. These five strategic approaches need not be used in isolation, as a detailed case study of the way Anheuser-Busch countered the craft-beer revolution dramatically demonstrates. Sensible industry leaders do not lead revolutions; they know they may not survive the attempt. Instead, they prefer to lead counterrevolutions.

  19. Environmental literacy framework with a focus on climate change (ELF): a framework and resources for teaching climate change

    NASA Astrophysics Data System (ADS)

    Huffman, L. T.; Blythe, D.; Dahlman, L. E.; Fischbein, S.; Johnson, K.; Kontar, Y.; Rack, F. R.; Kulhanek, D. K.; Pennycook, J.; Reed, J.; Youngman, B.; Reeves, M.; Thomas, R.

    2010-12-01

    The challenges of communicating climate change science to non-technical audiences present a daunting task, but one that is recognized in the science community as urgent and essential. ANDRILL's (ANtarctic geological DRILLing) international network of scientists, engineers, technicians and educators work together to convey a deeper understanding of current geoscience research as well as the process of science to non-technical audiences. One roadblock for educators who recognize the need to teach climate change has been the lack of a comprehensive, integrated set of resources and activities that are related to the National Science Education Standards. Pieces of the climate change puzzle can be found in the excellent work of the groups of science and education professionals who wrote the Essential Principles of Ocean Sciences, Climate Literacy: The Essential Principles of Climate Science, Earth Science Literacy Principles: The Big Ideas and Supporting Concepts of Earth Science, and Essential Principals and Fundamental Concepts for Atmospheric Science Literacy, but teachers have precious little time to search out the climate change goals and objectives in those frameworks and then find the resources to teach them. Through NOAA funding, ANDRILL has created a new framework, The Environmental Literacy Framework with a Focus on Climate Change (ELF), drawing on the works of the aforementioned groups, and promoting an Earth Systems approach to teaching climate change through five units: Atmosphere, Biosphere, Geosphere, Hydrosphere/Cryosphere, and Energy as the driver of interactions within and between the “spheres.” Each key concept in the framework has a hands-on, inquiry activity and matching NOAA resources for teaching the objectives. In its present form, we present a ‘road map’ for teaching climate change and a set of resources intended to continue to evolve over time.

  20. Self-heating and scaling of thin body transistors

    NASA Astrophysics Data System (ADS)

    Pop, Eric

    The most often cited technological roadblock of nanoscale electronics is the "power problem," i.e. power densities and device temperatures reaching levels that will prevent their reliable operation. Technology roadmap (ITRS) requirements are expected to lead to more heat dissipation problems, especially with the transition towards geometrically confined device geometries (SOI, FinFET, nanowires), and new materials with poor thermal properties. This work examines the physics of heat generation in silicon, and in the context of nanoscale CMOS transistors. A new Monte Carlo code (MONET) is introduced which uses analytic descriptions of both the electron bands and the phonon dispersion. Detailed heat generation statistics are computed in bulk and strained silicon, and within simple device geometries. It is shown that non-stationary transport affects heat generation near strongly peaked electric fields, and that self-heating occurs almost entirely in the drain end of short, quasi-ballistic devices. The dissipated power is spectrally distributed between the (slow) optical and (fast) acoustic phonon modes approximately by a ratio of two to one. In addition, this work explores the limits of device design and scaling from an electrical and thermal point of view. A self-consistent electro-thermal compact model for thin-body (SOI, GOI) devices is introduced for calculating operating temperature, saturation current and intrinsic gate delay. Self-heating is sensitive to several device parameters, such as raised source/drain height and material boundary thermal resistance. An experimental method is developed for extracting via/contact thermal resistance from electrical measurements. The analysis suggests it is possible to optimize device geometry in order to simultaneously minimize operating temperature and intrinsic gate delay. Electro-thermal contact and device design are expected to become more important with continued scaling.

  1. The Energy Crisis

    NASA Astrophysics Data System (ADS)

    Hoefflinger, Bernd

    Chip-based electronics in 2010 consumed about 10% of the world's total electric power of ˜2 TW. We have seen throughout the book that all segments, processing, memory and communication, are expected to increase their performance or bandwidth by three orders of magnitude in the decade until 2020. If this progress would be realized, the world semiconductor revenue could grow by 50-100%, and the ICT industry by 43-66% in this decade (Fig. 6.1). Progress sustained at these levels certainly depends on investments and qualified manpower, but energy has become another roadblock almost overnight. In this chapter, we touch upon the life-cycle energy of chips by assessing the energy of Si wafer manufacturing, needed to bring the chips to life, and the power efficiencies in their respective operations. An outstanding segment of power-hungry chip operations is that of operating data centers, often called server farms. Their total operating power was ˜36 GW in 2010, and we look at their evolution under the prospect of a 1,000× growth in performance by 2020. One feasible scenario is that we succeed in improving the power efficiency of Processing 1,000×, Memory 1,000×, Communication 100×, within a decade. In this case, the total required power for the world's data centers would still increase 4× to 144 GW by 2020, equivalent to 40% of the total electrical power available in all of Europe. The power prospects for mobile/wireless as well as long-line cable/radio/satellite are equally serious. Any progression by less than the factors listed above will lead to economic growth smaller than the projections given above. This demands clearly that sustainable nanoelectronics must be minimum-energy (femtojoule) electronics.

  2. Genomics and relative expression analysis identifies key genes associated with high female to male flower ratio in Jatropha curcas L.

    PubMed

    Gangwar, Manali; Sood, Hemant; Chauhan, Rajinder Singh

    2016-04-01

    Jatropha curcas, has been projected as a major source of biodiesel due to high seed oil content (42 %). A major roadblock for commercialization of Jatropha-based biodiesel is low seed yield per inflorescence, which is affected by low female to male flower ratio (1:25-30). Molecular dissection of female flower development by analyzing genes involved in phase transitions and floral organ development is, therefore, crucial for increasing seed yield. Expression analysis of 42 genes implicated in floral organ development and sex determination was done at six floral developmental stages of a J. curcas genotype (IC561235) with inherently higher female to male flower ratio (1:8-10). Relative expression analysis of these genes was done on low ratio genotype. Genes TFL1, SUP, AP1, CRY2, CUC2, CKX1, TAA1 and PIN1 were associated with reproductive phase transition. Further, genes CUC2, TAA1, CKX1 and PIN1 were associated with female flowering while SUP and CRY2 in female flower transition. Relative expression of these genes with respect to low female flower ratio genotype showed up to ~7 folds increase in transcript abundance of SUP, TAA1, CRY2 and CKX1 genes in intermediate buds but not a significant increase (~1.25 folds) in female flowers, thereby suggesting that these genes possibly play a significant role in increased transition towards female flowering by promoting abortion of male flower primordia. The outcome of study has implications in feedstock improvement of J. curcas through functional validation and eventual utilization of key genes associated with female flowering.

  3. The 90 90 90 strategy to end the HIV Pandemic by 2030: Can the supply chain handle it?

    PubMed

    Jamieson, David; Kellerman, Scott E

    2016-01-01

    UNAIDS "90-90-90" strategy calls for 90% of HIV-infected individuals to be diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and 90% of whom will achieve sustained virologic suppression. Reaching these targets by 2020 will reduce the HIV epidemic to a low-level endemic disease by 2030. However, moving the global response towards this universal test and treat model will pose huge challenges to public health systems in resource-limited settings, including global and local supply chain systems. These challenges are especially acute in Africa, which accounts for over 70% of the persons affected by HIV. From a supply chain perspective, each of the "90's" has possible complications and roadblocks towards realizing the promise envisioned by 90-90-90. For instance, ensuring that 90% of HIV-infected persons know their status will require a large increase in access to HIV tests compared with what is currently available. To ensure that there are enough anti-retrovirals available to treat the nearly 25 million people that will require them by 2020 represents a near doubling of the ARV supplied to treat the 13 million currently on treatment. Similarly, to monitor those on treatment means an unprecedented scale-up of viral load testing throughout Africa. Larger issues include whether the capacity exists at the local level to handle these commodities when they arrive in the most severely affected countries, including considerations of the human resources and costs needed to make this strategy effective. We believe that such "real world" analysis of proposed strategies and policies is essential to ensure their most effective implementation.

  4. Red vertical cavity surface emitting lasers (VCSELs) for consumer applications

    NASA Astrophysics Data System (ADS)

    Duggan, Geoffrey; Barrow, David A.; Calvert, Tim; Maute, Markus; Hung, Vincent; McGarvey, Brian; Lambkin, John D.; Wipiejewski, Torsten

    2008-02-01

    There are many potential applications of visible, red (650nm - 690nm) vertical cavity surface emitting lasers (VCSELs) including high speed (Gb) communications using plastic optical fiber (POF), laser mouse sensors, metrology, position sensing. Uncertainty regarding the reliability of red VCSELs has long been perceived as the most significant roadblock to their commercialization. In this paper we will present data on red VCSELs optimized for performance and reliability that will allow exploitation of this class of VCSEL in a wide range of high volume consumer, communication and medical applications. VCSELs operating at ~665nm have been fabricated on 4" GaAs substrates using MOCVD as the growth process and using standard VCSEL processing technology. The active region is AlGaInP-based and the DBR mirrors are made from AlGaAs. Threshold currents are typically less than 2mA, the devices operate up to >60C and the light output is polarized in a stable, linear characteristic over all normal operating conditions. The 3dB modulation bandwidth of the devices is in excess of 3GHz and we have demonstrated the operation of a transceiver module operating at 1.25Gb/s over both SI-POF and GI-POF. Ageing experiments carried out using a matrix of current and temperature stress conditions allows us to estimate that the time to failure of 1% of devices (TT1%F) is over 200,000h for reasonable use conditions - making these red VCSELs ready for commercial exploitation in a variety of consumer-type applications. Experiments using appropriate pulsed driving conditions have resulted in operation of 665nm VCSELs at a temperature of 85°C whilst still offering powers useable for eye-safe free space and POF communications.

  5. Cloud-Based Tools to Support High-Resolution Modeling (Invited)

    NASA Astrophysics Data System (ADS)

    Jones, N.; Nelson, J.; Swain, N.; Christensen, S.

    2013-12-01

    The majority of watershed models developed to support decision-making by water management agencies are simple, lumped-parameter models. Maturity in research codes and advances in the computational power from multi-core processors on desktop machines, commercial cloud-computing resources, and supercomputers with thousands of cores have created new opportunities for employing more accurate, high-resolution distributed models for routine use in decision support. The barriers for using such models on a more routine basis include massive amounts of spatial data that must be processed for each new scenario and lack of efficient visualization tools. In this presentation we will review a current NSF-funded project called CI-WATER that is intended to overcome many of these roadblocks associated with high-resolution modeling. We are developing a suite of tools that will make it possible to deploy customized web-based apps for running custom scenarios for high-resolution models with minimal effort. These tools are based on a software stack that includes 52 North, MapServer, PostGIS, HT Condor, CKAN, and Python. This open source stack provides a simple scripting environment for quickly configuring new custom applications for running high-resolution models as geoprocessing workflows. The HT Condor component facilitates simple access to local distributed computers or commercial cloud resources when necessary for stochastic simulations. The CKAN framework provides a powerful suite of tools for hosting such workflows in a web-based environment that includes visualization tools and storage of model simulations in a database to archival, querying, and sharing of model results. Prototype applications including land use change, snow melt, and burned area analysis will be presented. This material is based upon work supported by the National Science Foundation under Grant No. 1135482

  6. Disruption of Type I Interferon Induction by HIV Infection of T Cells

    PubMed Central

    Sanchez, David Jesse; Miranda, Daniel; Marsden, Matthew D.; Dizon, Thomas Michael A.; Bontemps, Johnny R.; Davila, Sergio J.; Del Mundo, Lara E.; Ha, Thai; Senaati, Ashkon; Zack, Jerome A.; Cheng, Genhong

    2015-01-01

    Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-β promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host. PMID:26375588

  7. Disruption of Type I Interferon Induction by HIV Infection of T Cells.

    PubMed

    Sanchez, David Jesse; Miranda, Daniel; Marsden, Matthew D; Dizon, Thomas Michael A; Bontemps, Johnny R; Davila, Sergio J; Del Mundo, Lara E; Ha, Thai; Senaati, Ashkon; Zack, Jerome A; Cheng, Genhong

    2015-01-01

    Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-β promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host.

  8. Automatically identifying, counting, and describing wild animals in camera-trap images with deep learning.

    PubMed

    Norouzzadeh, Mohammad Sadegh; Nguyen, Anh; Kosmala, Margaret; Swanson, Alexandra; Palmer, Meredith S; Packer, Craig; Clune, Jeff

    2018-06-19

    Having accurate, detailed, and up-to-date information about the location and behavior of animals in the wild would improve our ability to study and conserve ecosystems. We investigate the ability to automatically, accurately, and inexpensively collect such data, which could help catalyze the transformation of many fields of ecology, wildlife biology, zoology, conservation biology, and animal behavior into "big data" sciences. Motion-sensor "camera traps" enable collecting wildlife pictures inexpensively, unobtrusively, and frequently. However, extracting information from these pictures remains an expensive, time-consuming, manual task. We demonstrate that such information can be automatically extracted by deep learning, a cutting-edge type of artificial intelligence. We train deep convolutional neural networks to identify, count, and describe the behaviors of 48 species in the 3.2 million-image Snapshot Serengeti dataset. Our deep neural networks automatically identify animals with >93.8% accuracy, and we expect that number to improve rapidly in years to come. More importantly, if our system classifies only images it is confident about, our system can automate animal identification for 99.3% of the data while still performing at the same 96.6% accuracy as that of crowdsourced teams of human volunteers, saving >8.4 y (i.e., >17,000 h at 40 h/wk) of human labeling effort on this 3.2 million-image dataset. Those efficiency gains highlight the importance of using deep neural networks to automate data extraction from camera-trap images, reducing a roadblock for this widely used technology. Our results suggest that deep learning could enable the inexpensive, unobtrusive, high-volume, and even real-time collection of a wealth of information about vast numbers of animals in the wild. Copyright © 2018 the Author(s). Published by PNAS.

  9. Electrochemical Conversion of Biologically Produced Muconic Acid: Key Considerations for Scale-Up and Corresponding Technoeconomic Analysis

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

    Matthiesen, John E.; Suástegui, Miguel; Wu, Yutong

    We present muconic acid, an unsaturated diacid that can be produced from cellulosic sugars and lignin monomers by fermentation, emerges as a promising intermediate for the sustainable manufacture of commodity polyamides and polyesters including Nylon-6,6 and polyethylene terephthalate (PET). Current conversion schemes consist in the biological production of cis,cis-muconic acid using metabolically engineered yeasts and bacteria, and the subsequent diversification to adipic acid, terephthalic acid, and their derivatives using chemical catalysts. In some instances, conventional precious metal catalysts can be advantageously replaced by base metal electrocatalysts. Here, we show the economic relevance of utilizing a hybrid biological–electrochemical conversion scheme tomore » convert glucose to trans-3-hexenedioic acid (t3HDA), a monomer used for the synthesis of bioadvantaged Nylon-6,6. Potential roadblocks to biological and electrochemical integration in a single reactor, including electrocatalyst deactivation due to biogenic impurities and low faradaic efficiency inherent to side reactions in complex media, have been studied and addressed. In this study, t3HDA was produced with 94% yield and 100% faradaic efficiency. With consideration of the high t3HDA yield and faradaic efficiency, a technoeconomic analysis was developed on the basis of the current yield and titer achieved for muconic acid, the figures of merit defined for industrial electrochemical processes, and the separation of the desired product from the medium. On the basis of this analysis, t3HDA could be produced for approximately $2.00 kg –1. The low cost for t3HDA is a primary factor of the electrochemical route being able to cascade biological catalysis and electrocatalysis in one pot without separation of the muconic acid intermediate from the fermentation broth.« less

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

    PubMed

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

    2015-06-01

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

  11. Multicultural issues in test interpretation.

    PubMed

    Langdon, Henriette W; Wiig, Elisabeth H

    2009-11-01

    Designing the ideal test or series of tests to assess individuals who speak languages other than English is difficult. This article first describes some of the roadblocks-one of which is the lack of identification criteria for language and learning disabilities in monolingual and bilingual populations in most countries of the non-English-speaking world. This lag exists, in part, because access to general education is often limited. The second section describes tests that have been developed in the United States, primarily for Spanish-speaking individuals because they now represent the largest first-language majority in the United States (80% of English-language learners [ELLs] speak Spanish at home). We discuss tests developed for monolingual and bilingual English-Spanish speakers in the United States and divide this coverage into two parts: The first addresses assessment of students' first language (L1) and second language (L2), usually English, with different versions of the same test; the second describes assessment of L1 and L2 using the same version of the test, administered in the two languages. Examples of tests that fit a priori-determined criteria are briefly discussed throughout the article. Suggestions how to develop tests for speakers of languages other than English are also provided. In conclusion, we maintain that there will never be a perfect test or set of tests to adequately assess the communication skills of a bilingual individual. This is not surprising because we have yet to develop an ideal test or set of tests that fits monolingual Anglo speakers perfectly. Tests are tools, and the speech-language pathologist needs to know how to use those tools most effectively and equitably. The goal of this article is to provide such guidance. Thieme Medical Publishers.

  12. Barriers and perceptions regarding code status discussion with families of critically ill patients in a tertiary care hospital of a developing country: A cross-sectional study.

    PubMed

    Syed, Ahsan A; Almas, Aysha; Naeem, Quratulain; Malik, Umer F; Muhammad, Tariq

    2017-02-01

    In Asian societies including Pakistan, a complex background of illiteracy, different familial dynamics, lack of patient's autonomy, religious beliefs, and financial constraints give new dimensions to code status discussion. Barriers faced by physicians during code status discussion in these societies are largely unknown. To determine the barriers and perceptions in discussion of code status by physicians. Questionnaire-based cross-sectional study. This study was conducted in the Department of Medicine of The Aga Khan University Hospital, Karachi, Pakistan. A total of 134 physicians who had discussed at least five code statuses in their lifetime were included. A total of 77 (57.4%) physicians responded. Family-related barriers were found to be the most common barriers. They include family denial (74.0%), level of education of family (66.2%), and conflict between individual family members (66.2%). Regarding personal barriers, lack of knowledge regarding prognosis (44.1%), personal discomfort in discussing death (29.8%), and fear of legal consequences (28.5%) were the top most barriers. In hospital-related barriers, time constraint (57.1%), lack of hospital administration support (48.0%), and suboptimal nursing care after do not resuscitate (48.0%) were the most frequent. There were significant differences among opinions of trainees when compared to those of attending physicians. Family-related barriers are the most frequent roadblocks in the end-of-life care discussions for physicians in Pakistan. Strengthening communication skills of physicians and family education are the potential strategies to improve end-of-life care. Large multi-center studies are needed to better understand the barriers of code status discussion in developing countries.

  13. Avoidance of tearing mode locking with electro-magnetic torque introduced by feedback-based mode rotation control in DIII-D and RFX-mod

    DOE PAGES

    Okabayashi, M.; Zanca, P.; Strait, E. J.; ...

    2016-11-25

    Disruptions caused by tearing modes (TMs) are considered to be one of the most critical roadblocks to achieving reliable, steady-state operation of tokamak fusion reactors. We have demonstrated a promising scheme to avoid mode locking by utilizing the electro-magnetic (EM) torque produced with 3D coils that are available in many tokamaks. In this scheme, the EM torque is delivered to the modes by a toroidal phase shift between the externally applied field and the excited TM fields, compensating for the mode momentum loss through the interaction with the resistive wall and uncorrected error fields. Fine control of torque balance ismore » provided by a feedback scheme. We have explored this approach in two widely different devices and plasma conditions: DIII-D and RFX-mod operated in tokamak mode. In DIII-D, the plasma target was high β N in a non-circular divertor tokamak. We define β N as β N = β/(I p /aB t) (%Tm/MA), where β, I p, a, B t are the total stored plasma pressure normalized by the magnetic pressure, plasma current, plasma minor radius and toroidal magnetic field at the plasma center, respectively. The RFX-mod plasma was ohmically-heated with ultra-low safety factor in a circular limiter discharge with active feedback coils outside the thick resistive shell. The DIII-D and RFX-mod experiments showed remarkable consistency with theoretical predictions of torque balance. The application to ignition-oriented devices such as the International Thermonuclear Experimental Reactor (ITER) would expand the horizon of its operational regime. Finally, the internal 3D coil set currently under consideration for edge localized mode suppression in ITER would be well suited for this purpose.« less

  14. Effects of proton irradiation on the performance of InP/GaAs solar cells

    NASA Technical Reports Server (NTRS)

    Weinberg, Irving; Swartz, C. K.; Brinker, David J.; Wilt, D. M.

    1991-01-01

    InP solar cells are known to be more radiation resistant than either GaAs or Si. In addition, AMO total area efficiencies approaching 19 percent were attained for InP. However, the present high substrate cost presents a barrier to the eventual widespread use of InP cells in space. In addition, if cell thinning becomes desirable, their relative fragility presents a problem. For these reasons, the NASA Lewis Research Center has initiated a program, aimed at producing thin InP cells, by heteroepitaxial deposition of InP on cheaper, more durable substrates. To date, a short term feasibility study as Spire has resulted in cells processed from InP heteroepitaxially deposited on Si substrates with an intervening thin GaAs layer (InP/GaAs/Si) and cells produced from InP deposited on GaAs (InP/GaAs). As a result of this short study efficiencies of over 7 and 9 percent were achieved for InP/GaAs/Si and InP/GaAs respectively. Although these efficiencies are low, they represent a modest and encouraging starting point for a more intensive program. Obviously, when considering economy and mechanical strength, cells processed on silicon substrates are preferred. However, although the InP/GaAs cells are not the final desirable products of this program, their properties serve to highlight several roadblocks to be overcome in producing cells with the more desirable cost and strength properties. Hence, in the present case, the properties of the InP/GaAs cells before and after irradiation by 10 MeV protons are examined. A similar study of InP/GaAs/Si cells will be reported on at a later date.

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

    Branda, Steven S.; Lane, Todd W.; Misra, Milind

    Bioweapons and emerging infectious diseases pose formidable and growing threats to our national security. Rapid advances in biotechnology and the increasing efficiency of global transportation networks virtually guarantee that the United States will face potentially devastating infectious disease outbreaks caused by novel ('unknown') pathogens either intentionally or accidentally introduced into the population. Unfortunately, our nation's biodefense and public health infrastructure is primarily designed to handle previously characterized ('known') pathogens. While modern DNA assays can identify known pathogens quickly, identifying unknown pathogens currently depends upon slow, classical microbiological methods of isolation and culture that can take weeks to produce actionable information.more » In many scenarios that delay would be costly, in terms of casualties and economic damage; indeed, it can mean the difference between a manageable public health incident and a full-blown epidemic. To close this gap in our nation's biodefense capability, we will develop, validate, and optimize a system to extract nucleic acids from unknown pathogens present in clinical samples drawn from infected patients. This system will extract nucleic acids from a clinical sample, amplify pathogen and specific host response nucleic acid sequences. These sequences will then be suitable for ultra-high-throughput sequencing (UHTS) carried out by a third party. The data generated from UHTS will then be processed through a new data assimilation and Bioinformatic analysis pipeline that will allow us to characterize an unknown pathogen in hours to days instead of weeks to months. Our methods will require no a priori knowledge of the pathogen, and no isolation or culturing; therefore it will circumvent many of the major roadblocks confronting a clinical microbiologist or virologist when presented with an unknown or engineered pathogen.« less

  16. Aramid Nanofiber Composites for Energy Storage Applications

    NASA Astrophysics Data System (ADS)

    Tung, Siu on

    Lithium ion batteries and non-aqueous redox flow batteries represent two of the most important energy storage technologies to efficient electric vehicles and power grid, which are essential to decreasing U.S. dependence on fossil fuels and sustainable economic growth. Many of the developmental roadblocks for these batteries are related to the separator, an electrically insulating layer between the cathode and anode. Lithium dendrite growth has limited the performance and threatened the safety of lithium ion batteries by piercing the separator and causing internal shorts. In non-aqueous redox flow batteries, active material crossover through microporous separators and the general lack of a suitable ion conducting membrane has led to low operating efficiencies and rapid capacity fade. Developing new separators for these batteries involve the combination of different and sometimes seemingly contradictory properties, such as high ionic conductivity, mechanical stability, thermal stability, chemical stability, and selective permeability. In this dissertation, I present work on composites made from Kevlar-drived aramid nanofibers (ANF) through rational design and fabrication techniques. For lithium ion batteries, a dendrite suppressing layer-by-layer composite of ANF and polyethylene oxide is present with goals of high ionic conductivity, improved safety and thermal stability. For non-aqueous redox flow batteries, a nanoporous ANF separator with surface polyelectrolyte modification is used to achieve high coulombic efficiencies and cycle life in practical flow cells. Finally, manufacturability of ANF based separators is addressed through a prototype machine for continuous ANF separator production and a novel separator coated on anode assembly. In combination, these studies serve as a foundation for addressing the challenges in separator engineering for lithium ion batteries and redox flow batteries.

  17. International magnetic pulse compression

    NASA Astrophysics Data System (ADS)

    Kirbie, H. C.; Newton, M. A.; Siemens, P. D.

    1991-04-01

    Although pulsed-power engineering traditionally has been practiced by a fairly small, close community in the areas of defense and energy research, it is becoming more common in high-power, high-energy commercial pursuits such as material processing and lasers. This paper is a synopsis of the Feb. 12-14, 1990 workshop on magnetic switching as it applies primarily to pulse compression (power transformation). During the course of the Workshop at Granlibakken, a great deal of information was amassed and a keen insight into both the problems and opportunities as to the use of this switching approach was developed. The segmented workshop format proved ideal for identifying key aspects affecting optimum performance in a variety of applications. Individual groups of experts addressed network and system modeling, magnetic materials, power conditioning, core cooling and dielectrics, and finally circuits and application. At the end, they came together to consolidate their input and formulate the workshop's conclusions, identifying roadblocks or suggesting research projects, particularly as they apply to magnetic switching's trump card - its high-average-power-handling capability (at least on a burst-mode basis). The workshop was especially productive both in the quality and quantity of information transfer in an environment conducive to a free and open exchange of ideas. We will not delve into the organization proper of this meeting, rather we wish to commend to the interested reader this volume, which provides the definitive and most up-to-date compilation on the subject of magnetic pulse compression from underlying principles to current state of the art as well as the prognosis for the future of magnetic pulse compression as a consensus of the workshop's organizers and participants.

  18. Proceedings of the International Magnetic Pulse Compression Workshop. Volume 2: Technical summary

    NASA Astrophysics Data System (ADS)

    Kirbie, H. C.; Newton, M. A.; Siemens, P. D.

    1991-04-01

    A few individuals have tried to broaden the understanding of specific and salient pulsed-power topics. One such attempt is this documentation of a workshop on magnetic switching as it applies primarily to pulse compression (power transformation), affording a truly international perspective by its participants under the initiative and leadership of Hugh Kirbie and Mark Newton of the Lawrence Livermore National Laboratory (LLNL) and supported by other interested organizations. During the course of the Workshop at Granlibakken, a great deal of information was amassed and a keen insight into both the problems and opportunities as to the use of this switching approach was developed. The segmented workshop format proved ideal for identifying key aspects affecting optimum performance in a variety of applications. Individual groups of experts addressed network and system modeling, magnetic materials, power conditioning, core cooling and dielectrics, and finally circuits and application. At the end, they came together to consolidate their input and formulate the workshop's conclusions, identifying roadblocks or suggesting research projects, particularly as they apply to magnetic switching's trump card--its high average power handling capability (at least on a burst-mode basis). The workshop was especially productive both in the quality and quantity of information transfer in an environment conducive to a free and open exchange of ideas. We will not delve into the organization proper of this meeting, rather we wish to commend to the interested reader this volume, which provides the definitive and most up-to-date compilation on the subject of magnetic pulse compression from underlying principles to current state of the art as well as the prognosis for the future of magnetic pulse compression as a consensus of the workshop's organizers and participants.

  19. Swollen hexagonal liquid crystals as smart nanoreactors: implementation in materials chemistry for energy applications.

    PubMed

    Ghosh, Srabanti; Ramos, Laurence; Remita, Hynd

    2018-03-29

    Materials are the key roadblocks for the commercialization of energy conversion devices in fuel cells and solar cells. Significant research has focused on tuning the intrinsic properties of materials at the nanometer scale. The soft template mediated controlled fabrication of advanced nanostructured materials is attracting considerable interest due to the promising applications of these materials in catalysis and electrocatalysis. Swollen hexagonal lyotropic liquid crystals (SLCs) consist of oil-swollen surfactant-stabilized 1D, 2D or 3D nanometric assemblies regularly arranged in an aqueous solvent. Interestingly, the characteristic size of the SLCs can be controlled by adjusting the volume ratio of oil to water. The non-polar and/or polar compartments of the SLCs can be doped with guest molecules and used as nanoreactors for the synthesis of various metals (Pt, Pd, Au, etc.), conducting polymers and composite nanostructures with controlled size and shape. 1D, 2D and 3D mono- and bimetallic nanostructures of controlled composition and porosity can also be fabricated. These materials have demonstrated impressive enhancements of their electrochemical properties as compared to their bulk counterparts and have been identified as promising for further implementation in energy harvesting applications. In this review article, recent research materials are described regarding the development of functional materials with much improved performances for catalysis applications. This review addresses a brief overview of swollen hexagonal mesophases as nanoreactors, describes examples of nanostructured materials synthesized in these nanoreactors, shows several examples of the energy conversion applications in solar light harvesting, fuel cells etc. and also summarizes the associated reaction mechanisms developed in the recent literature for enhanced catalytic activity.

  20. Abolished perineuronal nets and altered parvalbumin-immunoreactivity in the nucleus reticularis thalami of wildtype and 3xTg mice after experimental stroke.

    PubMed

    Härtig, Wolfgang; Appel, Simon; Suttkus, Anne; Grosche, Jens; Michalski, Dominik

    2016-11-19

    Treatment strategies for ischemic stroke are still limited, since numerous attempts were successful only in preclinical research but failed under clinical condition. To overcome this translational roadblock, clinical relevant stroke models should consider co-morbidities, age-related effects and the complex neurovascular unit (NVU) concept. The NVU includes neurons, vessels and glial cells with astrocytic endfeet in close relation to the extracellular matrix (ECM). However, the role of the ECM after stroke-related tissue damage is poorly understood and mostly neglected for treatment strategies. This study is focused on alterations of perineuronal nets (PNs) as ECM constituents and parvalbumin-containing GABAergic neurons in mice with emphasis on the nucleus reticularis thalami (NRT) in close proximity to the ischemic lesion as induced by a filament-based stroke model. One day after ischemia onset, immunofluorescence-based quantitative analyses revealed drastically declined PNs in the ischemia-affected NRT from 3- and 12-month-old wildtype and co-morbid triple-transgenic (3xTg) mice with Alzheimer-like alterations. Parvalbumin-positive cells decreased numerically in the ischemia-affected NRT, while staining intensity did not differ between the affected and non-affected hemisphere. Additional qualitative analyses demonstrated ischemia-induced loss of PNs and allocated neuropil ECM immunoreactive for aggrecan and neurocan, and impaired immunoreactivity for calbindin, the potassium channel subunit Kv3.1b and the glutamate decarboxylase isoforms GAD65 and GAD67 in the NRT. In conclusion, these data confirm PNs as highly sensitive constituents of the ECM along with impaired neuronal integrity of GABAergic neurons. Therefore, specific targeting of ECM components might appear as a promising strategy for future treatment strategies in stroke. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. High-Precision and Low Latency RT-GNSS Processed Data for Diverse Geophysical and Natural Hazard Communities.

    NASA Astrophysics Data System (ADS)

    Mencin, David; Hodgkinson, Kathleen; Sievers, Charlie; David, Phillips; Charles, Meertens; Glen, Mattioli

    2017-04-01

    UNAVCO has been providing infrastructure and support for solid-earth sciences and earthquake natural hazards for the past two decades. Recent advances in GNSS technology and data processing are now providing position solutions with centimeter-level precision at high-rate (>1 Hz) and low latency (i.e. the time required for data to arrive for analysis, in this case less than 1 second). These data have the potential to improve our understanding in diverse areas of geophysics including properties of seismic, volcanic, magmatic and tsunami sources, and thus profoundly transform rapid event characterization and warning. Scientific and operational applications also include glacier and ice sheet motions; tropospheric modeling; and space weather. These areas of geophysics represent a spectrum of research fields, including geodesy, seismology, tropospheric weather, space weather and natural hazards. Processed Real-Time GNSS (RT-GNSS) data will require formats and standards that allow this broad and diverse community to use these data and associated meta-data in existing research infrastructure. These advances have critically highlighted the difficulties associated with merging data and metadata between scientific disciplines. Even seemingly very closely related fields such as geodesy and seismology, which both have rich histories of handling large volumes of data and metadata, do not go together well in any automated way. Community analysis strategies, or lack thereof, such as treatment of error prove difficult to address and are reflected in the data and metadata. In addition, these communities have differing security, accessibility and reliability requirements. We propose some solutions to the particular problem of making RT-GNSS processed solution data and metadata accessible to multiply scientific and natural hazard communities. Importantly, we discuss the roadblocks encounter and solved and those that remain to be addressed.

  2. International magnetic pulse compression

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

    Kirbie, H.C.; Newton, M.A.; Siemens, P.D.

    1991-04-01

    Although pulsed-power engineering traditionally has been practiced by a fairly small, close community in the areas of defense and energy research, it is becoming more common in high-power, high-energy commercial pursuits such as material processing and lasers. This paper is a synopsis of the Feb. 12--14, 1990 workshop on magnetic switching as it applies primarily to pulse compression (power transformation). During the course of the Workshop at Granlibakken, a great deal of information was amassed and a keen insight into both the problems and opportunities as to the use of this switching approach was developed. The segmented workshop format provedmore » ideal for identifying key aspects affecting optimum performance in a variety of applications. Individual groups of experts addressed network and system modeling, magnetic materials, power conditioning, core cooling and dielectrics, and finally circuits and application. At the end, they came together to consolidate their input and formulate the workshop's conclusions, identifying roadblocks or suggesting research projects, particularly as they apply to magnetic switching's trump card -- its high-average-power-handling capability (at least on a burst-mode basis). The workshop was especially productive both in the quality and quantity of information transfer in an environment conducive to a free and open exchange of ideas. We will not delve into the organization proper of this meeting, rather we wish to commend to the interested reader this volume, which provides the definitive and most up-to-date compilation on the subject of magnetic pulse compression from underlying principles to current state of the art as well as the prognosis for the future of magnetic pulse compression as a consensus of the workshop's organizers and participants.« less

  3. International magnetic pulse compression workshop: (Proceedings)

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

    Kirbie, H.C.; Newton, M.A.; Siemens, P.D.

    1991-04-01

    A few individuals have tried to broaden the understanding of specific and salient pulsed-power topics. One such attempt is this documentation of a workshop on magnetic switching as it applies primarily to pulse compression (power transformation), affording a truly international perspective by its participants under the initiative and leadership of Hugh Kirbie and Mark Newton of the Lawrence Livermore National Laboratory (LLNL) and supported by other interested organizations. During the course of the Workshop at Granlibakken, a great deal of information was amassed and a keen insight into both the problems and opportunities as to the use of this switchingmore » approach was developed. The segmented workshop format proved ideal for identifying key aspects affecting optimum performance in a variety of applications. Individual groups of experts addressed network and system modeling, magnetic materials, power conditioning, core cooling and dielectrics, and finally circuits and application. At the end, they came together to consolidate their input and formulate the workshop's conclusions, identifying roadblocks or suggesting research projects, particularly as they apply to magnetic switching's trump card--its high-average-power-handling capability (at least on a burst-mode basis). The workshop was especially productive both in the quality and quantity of information transfer in an environment conducive to a free and open exchange of ideas. We will not delve into the organization proper of this meeting, rather we wish to commend to the interested reader this volume, which provides the definitive and most up-to-date compilation on the subject of magnetic pulse compression from underlying principles to current state of the art as well as the prognosis for the future of magnetic pulse compression as a consensus of the workshop's organizers and participants.« less

  4. From Guide to Practice: Improving Your After School Science Program to Increase Student Academic Achievement

    NASA Astrophysics Data System (ADS)

    Taylor, J.

    2013-12-01

    Numerous science organizations, such as NASA, offer educational outreach activities geared towards after school. For some programs, the primary goal is to grow students' love of science. For others, the programs are also intended to increase academic achievement. For those programs looking to support student learning in out-of-school time environments, aligning the program with learning during the classroom day can be a challenge. The Institute for Education Sciences, What Works Clearinghouse, put together a 'Practice Guide' for maximizing learning time beyond the regular school day. These practice guides provide concrete recommendations for educators supported by research. While this guide is not specific to any content or subject-area, the recommendations provided align very well with science education. After school science is often viewed as a fun, dynamic environment for students. Indeed, one of the recommendations to ensure time is structured according to students' needs is to provide relevant and interesting experiences. Given that our after school programs provide such creative environments for students, what other components are needed to promote increased academic achievement? The recommendations provided to academic achievement, include: 1. Align Instruction, 2. Maximize Attendance and Participation, 3. Adapt Instruction, 4. Provide Engaging Experiences, and 5. Evaluate Program. In this session we will examine these five recommendations presented in the Practice Guide, discuss how these strategies align with science programs, and examine what questions each program should address in order to provide experiences that lend themselves to maximizing instruction. Roadblocks and solutions for overcoming challenges in each of the five areas will be presented. Jessica Taylor will present this research based on her role as an author on the Practice Guide, 'Improving Academic Achievement in Out-of-School Time' and her experience working in various informal science programs for NASA.

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

    Okabayashi, M.; Zanca, P.; Strait, E. J.

    Disruptions caused by tearing modes (TMs) are considered to be one of the most critical roadblocks to achieving reliable, steady-state operation of tokamak fusion reactors. We have demonstrated a promising scheme to avoid mode locking by utilizing the electro-magnetic (EM) torque produced with 3D coils that are available in many tokamaks. In this scheme, the EM torque is delivered to the modes by a toroidal phase shift between the externally applied field and the excited TM fields, compensating for the mode momentum loss through the interaction with the resistive wall and uncorrected error fields. Fine control of torque balance ismore » provided by a feedback scheme. We have explored this approach in two widely different devices and plasma conditions: DIII-D and RFX-mod operated in tokamak mode. In DIII-D, the plasma target was high β N in a non-circular divertor tokamak. We define β N as β N = β/(I p /aB t) (%Tm/MA), where β, I p, a, B t are the total stored plasma pressure normalized by the magnetic pressure, plasma current, plasma minor radius and toroidal magnetic field at the plasma center, respectively. The RFX-mod plasma was ohmically-heated with ultra-low safety factor in a circular limiter discharge with active feedback coils outside the thick resistive shell. The DIII-D and RFX-mod experiments showed remarkable consistency with theoretical predictions of torque balance. The application to ignition-oriented devices such as the International Thermonuclear Experimental Reactor (ITER) would expand the horizon of its operational regime. Finally, the internal 3D coil set currently under consideration for edge localized mode suppression in ITER would be well suited for this purpose.« less

  6. Modification of defects and potential fluctuations in slow-cooled and quenched Cu2ZnSnSe4 single crystals

    NASA Astrophysics Data System (ADS)

    Bishop, Douglas M.; McCandless, Brian; Gershon, Talia; Lloyd, Michael A.; Haight, Richard; Birkmire, Robert

    2017-02-01

    Recent literature reports have shown the ability to manipulate Cu-Zn cation ordering for Cu2ZnSnSe4 (CZTSe) via low temperature treatments. Theoretical arguments suggest that one of the major roadblocks to higher VOC—significant band tailing—could be improved with increased cation order; however, few direct measurements have been reported and significant device improvements have not yet been realized. This report investigates electrical properties, defects, and devices from quenched and slow-cooled single crystals of CZTSe. The extent of disorder was characterized by Raman spectroscopy as well as x-ray diffraction, where the change in Cu-Zn order can be detected by a changing c/a ratio. Quenched samples show higher acceptor concentrations, lower hole mobilities, and a lower-energy photoluminescence (PL) peak than crystals cooled at slower rates, consistent with a reduction in the bandgap. In addition, samples quenched at the highest temperatures showed lower PL yield consistent with higher quantities of deep defects. Devices fabricated using slow-cooled CZTSe single crystals showed improved efficiencies, most notably with increased VOC; however, low temperature intensity-dependent photoluminescence measurements continue to indicate the existence of potential fluctuations. We discuss the possibility that potential fluctuations in slow-cooled samples may be related to the inability to achieve a long range order of the Cu-Zn sub-lattice resulting in local regions of high and low levels of cation order, and consequent local variations in the bandgap. The presence of significant potential fluctuations, even after the slow-cooling step, suggests the difficulty in eliminating band-tailing in this system, and thus, additional approaches may be needed for significant reduction of the VOC deficit.

  7. Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling

    PubMed Central

    Singhal, Hari; Greene, Marianne E.; Zarnke, Allison L.; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G.; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B.; Nickisch, Klaus J.; Long, Henry W.; Becker, Lev; Brown, Myles; Greene, Geoffrey L.

    2018-01-01

    Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic. PMID:29435103

  8. Enhancing science education through extracurricular activities: A retrospective study of "Suzy Science and the Whiz Kids(c)"

    NASA Astrophysics Data System (ADS)

    Kralina, Linda M.

    Extracurricular activities (ECA) are informal settings offering free-choice experiences that are generally voluntary, open-ended, non-sequential, self-directed, hands-on, and evaluation-free. This mixed methods study investigates participation in a high school science ECA by collecting the memories of former student members for their perceptions of engagement as well as social positioning. First, this study examines the levels in which the science club engaged these members, particularly females, in science and teaching. Second, the study also ascertains how participation in the club allowed members to explore new identities and fostered the development of new skills, actions and behaviors, expanding possible future trajectories of identification, specifically in science- and education-related career fields. Based on a review of the related literature regarding engagement and identity formation and the reconstructed reality from the memories of these students and sponsor, a theoretical framework has been constructed, based on seven essential elements of informal learning for an engaging as well as a socially constructive high school science ECA. The most significant findings are (1) the high correlation between engagement, specifically, cognitive engagement with social positioning, (2) the important role of emotional engagement in science ECA, (3) the major perception roadblocks to science learning that can be overcome, particularly for females in physical science, and (4) the importance of the teacher-student interactions in science ECA. Articulating a theoretical framework to legitimate the power of informal learning structures may help other educators to understand the potential benefits of science ECA and thus, increase opportunities for such experiential activities in order to enhance engagement and expand positioning of their students in science. More engaging, socially constructive science ECA have the potential to enhance science education.

  9. Electrochemical Conversion of Biologically Produced Muconic Acid: Key Considerations for Scale-Up and Corresponding Technoeconomic Analysis

    DOE PAGES

    Matthiesen, John E.; Suástegui, Miguel; Wu, Yutong; ...

    2016-10-05

    We present muconic acid, an unsaturated diacid that can be produced from cellulosic sugars and lignin monomers by fermentation, emerges as a promising intermediate for the sustainable manufacture of commodity polyamides and polyesters including Nylon-6,6 and polyethylene terephthalate (PET). Current conversion schemes consist in the biological production of cis,cis-muconic acid using metabolically engineered yeasts and bacteria, and the subsequent diversification to adipic acid, terephthalic acid, and their derivatives using chemical catalysts. In some instances, conventional precious metal catalysts can be advantageously replaced by base metal electrocatalysts. Here, we show the economic relevance of utilizing a hybrid biological–electrochemical conversion scheme tomore » convert glucose to trans-3-hexenedioic acid (t3HDA), a monomer used for the synthesis of bioadvantaged Nylon-6,6. Potential roadblocks to biological and electrochemical integration in a single reactor, including electrocatalyst deactivation due to biogenic impurities and low faradaic efficiency inherent to side reactions in complex media, have been studied and addressed. In this study, t3HDA was produced with 94% yield and 100% faradaic efficiency. With consideration of the high t3HDA yield and faradaic efficiency, a technoeconomic analysis was developed on the basis of the current yield and titer achieved for muconic acid, the figures of merit defined for industrial electrochemical processes, and the separation of the desired product from the medium. On the basis of this analysis, t3HDA could be produced for approximately $2.00 kg –1. The low cost for t3HDA is a primary factor of the electrochemical route being able to cascade biological catalysis and electrocatalysis in one pot without separation of the muconic acid intermediate from the fermentation broth.« less

  10. Modeling fine-scale coral larval dispersal and interisland connectivity to help designate mutually-supporting coral reef marine protected areas: Insights from Maui Nui, Hawaii

    USGS Publications Warehouse

    Storlazzi, Curt; van Ormondt, Maarten; Chen, Yi-Leng; Elias, Edwin P. L.

    2017-01-01

    Connectivity among individual marine protected areas (MPAs) is one of the most important considerations in the design of integrated MPA networks. To provide such information for managers in Hawaii, USA, a numerical circulation model was developed to determine the role of ocean currents in transporting coral larvae from natal reefs throughout the high volcanic islands of the Maui Nui island complex in the southeastern Hawaiian Archipelago. Spatially- and temporally-varying wind, wave, and circulation model outputs were used to drive a km-scale, 3-dimensional, physics-based circulation model for Maui Nui. The model was calibrated and validated using satellite-tracked ocean surface current drifters deployed during coral-spawning conditions, then used to simulate the movement of the larvae of the dominant reef-building coral, Porites compressa, from 17 reefs during eight spawning events in 2010–2013. These simulations make it possible to investigate not only the general dispersal patterns from individual coral reefs, but also how anomalous conditions during individual spawning events can result in large deviations from those general patterns. These data also help identify those reefs that are dominated by self-seeding and those where self-seeding is limited to determine their relative susceptibility to stressors and potential roadblocks to recovery. Overall, the numerical model results indicate that many of the coral reefs in Maui Nui seed reefs on adjacent islands, demonstrating the interconnected nature of the coral reefs in Maui Nui and providing a key component of the scientific underpinning essential for the design of a mutually supportive network of MPAs to enhance conservation of coral reefs.

  11. The Warburg effect version 2.0

    PubMed Central

    Menendez, Javier A.; Joven, Jorge; Cufí, Sílvia; Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; Martin-Castillo, Begoña; López-Bonet, Eugeni; Alarcón, Tomás; Vazquez-Martin, Alejandro

    2013-01-01

    When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg’s metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the “metabolic facilitators” and “metabolic impediments” that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper “Warburg effect version 2.0” allowing them to “run” the CSCs’ “software” programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or “hostile” metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity. PMID:23549172

  12. Avoidance of tearing mode locking with electro-magnetic torque introduced by feedback-based mode rotation control in DIII-D and RFX-mod

    NASA Astrophysics Data System (ADS)

    Okabayashi, M.; Zanca, P.; Strait, E. J.; Garofalo, A. M.; Hanson, J. M.; In, Y.; La Haye, R. J.; Marrelli, L.; Martin, P.; Paccagnella, R.; Paz-Soldan, C.; Piovesan, P.; Piron, C.; Piron, L.; Shiraki, D.; Volpe, F. A.; DIII-D, The; RFX-mod Teams

    2017-01-01

    Disruptions caused by tearing modes (TMs) are considered to be one of the most critical roadblocks to achieving reliable, steady-state operation of tokamak fusion reactors. Here we have demonstrated a promising scheme to avoid mode locking by utilizing the electro-magnetic (EM) torque produced with 3D coils that are available in many tokamaks. In this scheme, the EM torque is delivered to the modes by a toroidal phase shift between the externally applied field and the excited TM fields, compensating for the mode momentum loss through the interaction with the resistive wall and uncorrected error fields. Fine control of torque balance is provided by a feedback scheme. We have explored this approach in two widely different devices and plasma conditions: DIII-D and RFX-mod operated in tokamak mode. In DIII-D, the plasma target was high β N in a non-circular divertor tokamak. Here β N is defined as β N  =  β/(I p /aB t) (%Tm/MA), where β, I p, a, B t are the total stored plasma pressure normalized by the magnetic pressure, plasma current, plasma minor radius and toroidal magnetic field at the plasma center, respectively. The RFX-mod plasma was ohmically-heated with ultra-low safety factor in a circular limiter discharge with active feedback coils outside the thick resistive shell. The DIII-D and RFX-mod experiments showed remarkable consistency with theoretical predictions of torque balance. The application to ignition-oriented devices such as the International Thermonuclear Experimental Reactor (ITER) would expand the horizon of its operational regime. The internal 3D coil set currently under consideration for edge localized mode suppression in ITER would be well suited for this purpose.

  13. The physiology of keystroke dynamics

    NASA Astrophysics Data System (ADS)

    Jenkins, Jeffrey; Nguyen, Quang; Reynolds, Joseph; Horner, William; Szu, Harold

    2011-06-01

    A universal implementation for most behavioral Biometric systems is still unknown since some behaviors aren't individual enough for identification. Habitual behaviors which are measurable by sensors are considered 'soft' biometrics (i.e., walking style, typing rhythm), while physical attributes (i.e., iris, fingerprint) are 'hard' biometrics. Thus, biometrics can aid in the identification of a human not only in cyberspace but in the world we live in. Hard biometrics have proven to be a rather successful form of identification, despite a large amount of individual signatures to keep track of. Virtually all soft biometric strategies, however, share a common pitfall. Instead of the classical pass/fail decision based on the measurements used by hard biometrics, a confidence threshold is imposed, increasing False Alarm and False Rejection Rates. This unreliability is a major roadblock for large scale system integration. Common computer security requires users to log-in with a six or more digit PIN (Personal Identification Number) to access files on the disk. Commercially available Keystroke Dynamics (KD) software can separately calculate and keep track of the mean and variance for each time travelled between each key (air time), and the time spent pressing each key (touch time). Despite its apparent utility, KD is not yet a robust, fault-tolerant system. We begin with a simple question: how could a pianist quickly control so many different finger and wrist movements to play music? What information, if any, can be gained from analyzing typing behavior over time? Biology has shown us that the separation of arm and finger motion is due to 3 long nerves in each arm; regulating movement in different parts of the hand. In this paper we wish to capture the underlying behavioral information of a typist through statistical memory and non-linear dynamics. Our method may reveal an inverse Compressive Sensing mapping; a unique individual signature.

  14. Intrinsic and extrinsic defects in a family of coal-derived graphene quantum dots

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

    Singamaneni, Srinivasa Rao, E-mail: ssingam@ncsu.edu, E-mail: tour@rice.edu; Department of Material Science and Engineering, North Carolina State University, Raleigh, North Carolina 27695; Tol, Johan van

    In this letter, we report on the high frequency (239.2 and 336 GHz) electron spin resonance (ESR) studies performed on graphene quantum dots (GQDs), prepared through a wet chemistry route from three types of coal: (a) bituminous, (b) anthracite, and (c) coke; and from non-coal derived GQDs. The microwave frequency-, power-, and temperature-dependent ESR spectra coupled with computer-aided simulations reveal four distinct magnetic defect centers. In bituminous- and anthracite-derived GQDs, we have identified two of them as intrinsic carbon-centered magnetic defect centers (a broad signal of peak to peak width = 697 (10{sup −4} T), g = 2.0023; and a narrow signal of peak tomore » peak width = 60 (10{sup −4} T), g = 2.003). The third defect center is Mn{sup 2+} ({sup 6}S{sub 5/2}, 3d{sup 5}) (signal width = 61 (10{sup −4} T), g = 2.0023, A{sub iso} = 93(10{sup −4} T)), and the fourth defect is identified as Cu{sup 2+} ({sup 2}D{sub 5/2}, 3d{sup 9}) (g{sub ⊥} = 2.048 and g{sub ‖} = 2.279), previously undetected. Coke-derived and non-coal derived GQDs show Mn{sup 2+} and two-carbon related signals, and no Cu{sup 2+} signal. The extrinsic impurities most likely originate from the starting coal. Furthermore, Raman, photoluminescence, and ESR measurements detected no noticeable changes in the properties of the bituminous GQDs after one year. This study highlights the importance of employing high frequency ESR spectroscopy in identifying the (magnetic) defects, which are roadblocks for spin relaxation times of graphene-based materials. These defects would not have been possible to probe by other spin transport measurements.« less

  15. Promotores de salud and community health workers: an annotated bibliography.

    PubMed

    WestRasmus, Emma K; Pineda-Reyes, Fernando; Tamez, Montelle; Westfall, John M

    2012-01-01

    For underserved and disenfranchised communities in the United States, affordable, effective health care can be nearly inaccessible, which often leads to the exclusion of these communities from relevant medical information and care. Barriers to care are especially salient in minority communities, where language, traditions and customs, socioeconomics, and access to education can serve as additional roadblocks to accessing health care information and services. These factors have contributed to a national health disparity crisis that unnecessarily places some communities in a vulnerable position without adequate prevention and treatment opportunities. One solution to the exclusion some communities face in the health care system may be the promotores de salud (PdS)/community health worker (CHW), an approach to culturally competent health care delivery whose popularity in the mainstream health care system has been steadily growing in recent decades. Known by a wide variety of names and broad in the spectrum of health issues they address, the PdS/CHW serves as cultural brokers between their own community and the formal health care system and can play a crucial role in promoting health and wellness within their community. This annotated bibliography was created to educate the reader about the history, definition, key features, utility, outcomes, and broad potential of the CHW approach in a variety of populations. Intended to serve as a reference point to a vast body of information on the CHW/PdS approach, this document is a resource for those wishing to effect change in the disparities within the health care system, and to improve the access to, quality, and cost of health care for underserved patients and their communities. Promotores de Salud is a Spanish term that translates to Health Promoter. A female health worker may be referred to as a Promotora, a male as a Promotor, and the plural of both is Promotores. For the purposes of this bibliography, the terms community health worker and promotores de salud may be used interchangeably.

  16. Prevalence of alcohol-impaired driving and riding in northern Ghana.

    PubMed

    Damsere-Derry, James; Palk, Gavan; King, Mark

    2016-01-01

    The objective of this study was to determine the roadside prevalence of alcohol-impaired driving among drivers and riders in northern Ghana. The study also verifies motorists' perceptions of their own alcohol use and knowledge of the legal blood alcohol concentration (BAC) limit in Ghana. With the assistance of police, systematic random sampling was used to collect data at roadblocks using a cross-sectional study design. Breathalyzers were used to screen whether motorists had detectable alcohol in their breath and follow-up breath tests were conducted to measure the actual breath alcohol levels among positive participants. In all, 9.7% of the 789 participants had detectable alcohol, among whom 6% exceeded the legal BAC limit of 0.08%. The prevalence of alcohol-impaired driving/riding was highest among cyclists (10% of all cyclists breath-tested) followed by truck drivers (9%) and motorcyclists (7% of all motorcyclists breath-tested). The occurrence of a positive BAC among cyclists was about 8 times higher (odds ratio [OR] = 7.73; P < .001) and it was 2 times higher among motorcyclists (OR = 2.30; P = .039) compared to private car drivers. The likelihood for detecting a positive BAC among male motorists/riders was higher than that among females (OR = 1.67; P = .354). The odds for detecting a positive BAC among weekend motorists/riders was significantly higher than on weekdays (OR = 2.62; P = .001). Alcohol-impaired driving/riding in Ghana is high by international standards. In order to attenuate the harmful effects of alcohol misuse such as alcohol-impaired driving/riding, there is the need to educate road users about how much alcohol they can consume and stay below the legal limit. The police should also initiate random breath testing to instill the deterrence of detection, certainty of apprehension and punishment, and severity and celerity of punishment among drink-driving motorists and riders.

  17. Roadblocks Hampering the Professional Development of Geoscientists in AFRICA.- a Case Study from the Ghanaian Perspective

    NASA Astrophysics Data System (ADS)

    Kabore, A.

    2010-12-01

    Ghana, like many African countries is in a strategic position to promote the development of early-career geoscientist because of the huge potential in terms of geological resources, huge number of interested students, and a number of institutions for training geoscientists. Ghana is often described as the gateway to Africa. As a result, situations that hamper the development of early career geoscientists in Ghana are likely to be replicated in many African countries. Over the last few decades, several institutions have been created to develop the technical-geoscientific expertise, and to deal with the disparity that exists between the amount of work that needs to be done in the geosciences and the small number of geoscientists working in the profession. There are more than four universities in Ghana that offer the study of geosciences. Available statistics indicate that the number of students enrolled in these institutions has seen a distinct increase over the last few decades. However, a significant percentage of the graduates from these institutions do not work in their core profession or even in closely-aligned disciplines. Unfortunately, the problem of a small national geosciences workforce is more pronounced today than it was over the last few decades. This problem is not a result of the lack of trained geoscientists, but rather a combination of several factors which may be socio-economic, cultural, passion, lack of mentorship etc. This presentation will focus on the broad challenges and institutional difficulties that geosciences graduates and early career professional face in Ghana and in Africa. Several recommendations will be proposed to address these problems and foster the establishment of professional development resources to boost the flow of geosciences graduates into the profession. These proposed resources will enable graduates to develop not only the skills and experience needed in the profession, but also the passion to become future leaders within the geosciences community.

  18. Humanized immunoglobulin mice: models for HIV vaccine testing and studying the broadly neutralizing antibody problem

    PubMed Central

    Verkoczy, Laurent

    2018-01-01

    A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broad neutralizing antibody (bnAb) responses. A major technical hurdle towards achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past six years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell tolerance mechanisms limiting bnAb production and evaluation of strategies to circumvent such processes. From these studies, in conjunction with the wealth of information recently obtained regarding the evolutionary pathways and paratopes/epitopes of multiple bnAbs, it has become clear that the very features of bnAbs desired for their function will be problematic to elicit by traditional vaccine paradigms, necessitating more iterative testing of new vaccine concepts. To meet this need, novel bnAb KI models have now been engineered to express either inferred pre-rearranged V(D)J exons (or unrearranged germline V, D, or J segments that can be assembled into functional rearranged V(D)J exons) encoding predecessors of mature bnAbs One encouraging approach that has materialized from studies using such newer models is sequential administration of immunogens designed to bind progressively more mature bnAb predecessors. In this review, insights into the regulation and induction of bnAbs based on the use of KI models will be discussed, as will new Ig KI approaches for higher-throughput production and/or altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb induction studies. PMID:28413022

  19. For Me It Was When I Saw a Simple Chart: Former Climate Contrarians Recount What Changed Their Minds

    NASA Astrophysics Data System (ADS)

    Kirk, K. B.

    2017-12-01

    Efforts to advance climate policy in the US have been hindered by a sector of the public that is reluctant to accept the science of anthropogenic climate change. Climate educators, advocates, and policymakers seek to resolve this roadblock through educational efforts and strategic messaging, while social science research strives to understand the causes of resistance on climate change. A discussion on the social media platform, AskReddit, offered a surprising source of insight when a tantalizing question was posed, "Former climate deniers, what changed your mind?" Responses to the query offered a rare glimpse into the process of how people switched camps, outgrew their parents' values, had transformative experiences, or were worn down by mounting scientific evidence. The posts contained 66 examples of people who were initially uncertain or dismissive of climate change, but came to accept the mainstream science. The commenters provided insightful narratives describing the origins of their skeptical beliefs, the rationales for their changing opinions, and the events that caused them to reverse course. Analysis of the comments revealed the primary reasons that influenced people to change their minds. Those were: science and evidence (cited as a factor in 47% of the comments); stewardship for the Earth and concerns about pollution (29%); unusual weather events (21%); and the untrustworthiness of the messengers who claim that climate change is false (17%). Note that several commenters pointed to more than one factor that contributed to their evolving views. While neither the setting nor the sample size allow a robust scientific analysis, these anecdotal accounts offer useful insights on a vexing problem. Learning about the circumstances that lead people to update their thinking can help us improve efforts to communicate the science and policy around climate change. This work is the topic of an article at Yale Climate Connections, https://www.yaleclimateconnections.org/2017/04/changing-minds-on-a-changing-climate/.

  20. Comprehensive molecular characterization of Methylobacterium extorquens AM1 adapted for 1-butanol tolerance

    DOE PAGES

    Hu, Bo; Yang, Yi -Ming; Beck, David A. C.; ...

    2016-04-11

    In this study, the toxicity of alcohols is one of the major roadblocks of biological fermentation for biofuels production. Methylobacterium extorquens AM1, a facultative methylotrophic α-proteobacterium, has been engineered to generate 1-butanol from cheap carbon feedstocks through a synthetic metabolic pathway. However, M. extorquens AM1 is vulnerable to solvent stress, which impedes further development for 1-butanol production. Only a few studies have reported the general stress response of M. extorquens AM1 to solvent stress. Therefore, it is highly desirable to obtain a strain with ameliorated 1-butanol tolerance and elucidate the molecular mechanism of 1-butnaol tolerance in M. extorquens AM1 formore » future strain improvement. In this work, adaptive laboratory evolution was used as a tool to isolate mutants with 1-butanol tolerance up to 0.5 %. The evolved strains, BHBT3 and BHBT5, demonstrated increased growth rates and higher survival rates with the existence of 1-butanol. Whole genome sequencing revealed a SNP mutation at kefB in BHBT5, which was confirmed to be responsible for increasing 1-butanol tolerance through an allelic exchange experiment. Global metabolomic analysis further discovered that the pools of multiple key metabolites, including fatty acids, amino acids, and disaccharides, were increased in BHBT5 in response to 1-butanol stress. Additionally, the carotenoid synthesis pathway was significantly down-regulated in BHBT5. In conclusion, we successfully screened mutants resistant to 1-butanol and provided insights into the molecular mechanism of 1-butanol tolerance in M. extorquens AM1. This research will be useful for uncovering the mechanism of cellular response of M. extorquens AM1 to solvent stress, and will provide the genetic blueprint for the rational design of a strain of M. extorquens AM1 with increased 1-butanol tolerance in the future.« less

  1. Electron mobility in InGaN channel heterostructure field effect transistor structures with different barriers

    NASA Astrophysics Data System (ADS)

    Xie, J.; Leach, J. H.; Ni, X.; Wu, M.; Shimada, R.; Özgür, Ü.; Morkoç, H.

    2007-12-01

    InGaN possesses higher electron mobility and velocity than GaN, and therefore is expected to lead to relatively better performances for heterostructure field effect transistors (HFETs). However, the reported mobilities for AlGaN /InGaN HFETs are lower than GaN channel HFETs. To address this issue, we studied the effect of different barriers on the Hall mobility for InGaN channel HFETs grown by metal organic chemical vapor deposition. Unlike the conventional AlGaN barrier, the AlInN barrier can be grown at the same temperature as the InGaN channel layer, alleviating some of the technological roadblocks. Specifically, this avoids possible degradation of the thin InGaN channel during AlGaN growth at high temperatures; and paves the way for better interfaces. An undoped In0.18Al0.82N/AlN/In0.04Ga0.96N HFET structure exhibited a μH=820cm2/Vs, with a ns=2.12×1013cm-2 at room temperature. Moreover, with an In-doped AlGaN barrier, namely, Al0.24In0.01Ga0.75N, grown at 900°C, the μH increased to 1230cm2/Vs with a ns of 1.09×1013cm-2 for a similar InGaN channel. Furthermore, when the barrier was replaced by Al0.25Ga0.75N grown at 1030°C, μH dropped to 870cm2/Vs with ns of 1.26×1013cm-2 at room temperature. Our results suggest that to fully realize the potential of the InGaN channel HFETs, AlInN or AlInGaN should be used as the barrier instead of the conventional AlGaN barrier.

  2. Using game authoring platforms to develop screen-based simulated functional assessments in persons with executive dysfunction following traumatic brain injury.

    PubMed

    Martínez-Pernía, David; Núñez-Huasaf, Javier; Del Blanco, Ángel; Ruiz-Tagle, Amparo; Velásquez, Juan; Gomez, Mariela; Robert Blesius, Carl; Ibañez, Agustin; Fernández-Manjón, Baltasar; Slachevsky, Andrea

    2017-10-01

    The assessment of functional status is a critical component of clinical neuropsychological evaluations used for both diagnostic and therapeutic purposes in patients with cognitive brain disorders. There are, however, no widely adopted neuropsychological tests that are both ecologically valid and easily administered in daily clinical practice. This discrepancy is a roadblock to the widespread adoption of functional assessments. In this paper, we propose a novel approach using a serious game authoring platform (eAdventure) for creating screen-based simulated functional assessments. We created a naturalistic functional task that consisted of preparing a cup of tea (SBS-COT) and applied the assessment in a convenience sample of eight dyads of therapists/patients with mild executive dysfunction after traumatic brain injury. We had three main aims. First, we performed a comprehensive review of executive function assessment in activities of daily living. Second, we were interested in measuring the feasibility of this technology with respect to staffing, economic and technical requirements. Third, a serious game was administered to patients to study the feasibility of this technology in the clinical context (pre-screening test). In addition, quantitative (Technology Acceptance Model (TAM) questionnaires) and qualitative (semistructured interviews) evaluations were applied to obtain user input. Our results suggest that the staffing, economic and technical requirements of the SBS-COT are feasible. The outcomes of the pre-screening test provide evidence that this technology is useful in the functional assessment of patients with executive dysfunction. In relation to subjective data, the TAM questionnaire showed good user acceptability from a professional perspective. Interview analyses with professionals and patients showed positive experiences related to the use of the SBS-COT. Our work indicates that the use of these types of authoring platforms could have positive long-term implications for neuropsychological research, opening the door to more reproducible, cooperative and efficient research by allowing the facilitated production, reuse and sharing of neuropsychological assessment tools. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    PubMed Central

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system. PMID:24295207

  4. Nanotube Production Devices Expand Research Capabilities

    NASA Technical Reports Server (NTRS)

    2012-01-01

    In order for the Hubble Space Telescope to take incredible, never-seen-before shots of celestial bodies and then send them back to Earth, the spacecraft needs power. While in orbit, Hubble cannot plug into an electrical outlet or stop at a store for some batteries. One of the ways NASA supplies power aboard a spacecraft is by harnessing energy from the most powerful entity in the solar system: the Sun. Since the 1960s, photovoltaic technology, or technology that converts sunlight into electricity, has been instrumental in the exploration of space. To build upon existing photovoltaic technology, NASA s Glenn Research Center has worked on a variety of innovative designs and materials to incorporate into photovoltaic cells, the building blocks of solar power systems. One of these materials is the carbon nanotube - a tiny structure about 50,000 times finer than the average human hair, with notably high electrical and thermal conductivity and an extreme amount of mechanical strength. Such properties give carbon nanotubes great potential to enhance the reliability of power generation and storage devices in space and on Earth. Dennis J. Flood, the branch chief of the photovoltaic division at Glenn in the 1990s, was looking into using carbon nanotubes to improve the efficiency of solar cells when he ran into a major roadblock - high-quality carbon nanotubes were not readily available. To address this problem, one of the chemists in Flood s group came up with a process and system for growing them. A senior chemist at Glenn, Aloysius F. Hepp, devised an injection chemical vapor deposition process using a specific organometallic catalyst in a two-zone furnace. Hepp's group found the unique process produced high-quality carbon nanotubes with less than 5 percent metal impurity. In addition, the process was more efficient than existing techniques, as it eliminated pre-patterning of the substrate used for growing the nanotubes, a timely and cost-prohibitive step.

  5. Brief history of agricultural systems modeling.

    PubMed

    Jones, James W; Antle, John M; Basso, Bruno; Boote, Kenneth J; Conant, Richard T; Foster, Ian; Godfray, H Charles J; Herrero, Mario; Howitt, Richard E; Janssen, Sander; Keating, Brian A; Munoz-Carpena, Rafael; Porter, Cheryl H; Rosenzweig, Cynthia; Wheeler, Tim R

    2017-07-01

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the "next generation" models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of this history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. The lessons from history should be considered to help avoid roadblocks and pitfalls as the community develops this next generation of agricultural systems models.

  6. WE-AB-BRB-12: Nanoscintillator Fiber-Optic Detector System for Microbeam Radiation Therapy Dosimetry

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

    Rivera, J; Dooley, J; Chang, S

    2015-06-15

    Purpose: Microbeam Radiation Therapy (MRT) is an experimental radiation therapy that has demonstrated a higher therapeutic ratio than conventional radiation therapy in animal studies. There are several roadblocks in translating the promising treatment technology to clinical application, one of which is the lack of a real-time, high-resolution dosimeter. Current clinical radiation detectors have poor spatial resolution and, as such, are unsuitable for measuring microbeams with submillimeter-scale widths. Although GafChromic film has high spatial resolution, it lacks the real-time dosimetry capability necessary for MRT preclinical research and potential clinical use. In this work we have demonstrated the feasibility of using amore » nanoscintillator fiber-optic detector (nanoFOD) system for real-time MRT dosimetry. Methods: A microplanar beam array is generated using a x-ray research irradiator and a custom-made, microbeam-forming collimator. The newest generation nanoFOD has an effective size of 70 µm in the measurement direction and was calibrated against a kV ion chamber (RadCal Accu-Pro) in open field geometry. We have written a computer script that performs automatic data collection with immediate background subtraction. A computer-controlled detector positioning stage is used to precisely measure the microbeam peak dose and beam profile by translating the stage during data collection. We test the new generation nanoFOD system, with increased active scintillation volume, against the previous generation system. Both raw and processed data are time-stamped and recorded to enable future post-processing. Results: The real-time microbeam dosimetry system worked as expected. The new generation dosimeter has approximately double the active volume compared to the previous generation resulting in over 900% increase in signal. The active volume of the dosimeter still provided the spatial resolution that meets the Nyquist criterion for our microbeam widths. Conclusion: We have demonstrated that real-time dosimetry of MRT microbeams is feasible using a nanoscintillator fiber-optic detector with integrated positioning system.« less

  7. Catalyzing healthcare transformation with digital health: Performance indicators and lessons learned from a Digital Health Innovation Group.

    PubMed

    Tseng, Jocelyn; Samagh, Sonia; Fraser, Donna; Landman, Adam B

    2018-06-01

    Despite considerable investment in digital health (DH) companies and a growing DH ecosystem, there are multiple challenges to testing and implementing innovative solutions. Health systems have recognized the potential of DH and have formed DH innovation centers. However, limited information is available on DH innovation center processes, best practices, or outcomes. This case report describes a DH innovation center process that can be replicated across health systems and defines and benchmarks process indicators to assess DH innovation center performance. The Brigham and Women's Hospital's Digital Health Innovation Group (DHIG) accelerates DH innovations from idea to pilot safely and efficiently using a structured process. Fifty-four DH innovations were accelerated by the DHIG process between July 2014 and December 2016. In order to measure effectiveness of the DHIG process, key process indicators were defined as 1) number of solutions that completed each DHIG phase and 2) length of time to complete each phase. Twenty-three DH innovations progressed to pilot stage and 13 innovations were terminated after barriers to pilot implementation were identified by the DHIG process. For 4 DH solutions that executed a pilot, the average time for innovations to proceed from DHIG intake to pilot initiation was 9 months. Overall, the DHIG is a reproducible process that addresses key roadblocks in DH innovation within health systems. To our knowledge, this is the first report to describe DH innovation process indicators and results within an academic health system. Therefore, there is no published data to compare our results with the results of other DH innovation centers. Standardized data collection and indicator reporting could allow benchmark comparisons across institutions. Additional opportunities exist for the validation of DH solution effectiveness and for translational support from pilot to implementation. These are critical steps to advance DH technologies and effectively leverage the DH ecosystem to transform healthcare. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The relationship between health worker stigma and uptake of HIV counseling and testing and utilization of non-HIV health services: the experience of male and female sex workers in Kenya.

    PubMed

    Nyblade, Laura; Reddy, Aditi; Mbote, David; Kraemer, John; Stockton, Melissa; Kemunto, Caroline; Krotki, Karol; Morla, Javier; Njuguna, Stella; Dutta, Arin; Barker, Catherine

    2017-11-01

    The barrier HIV-stigma presents to the HIV treatment cascade is increasingly documented; however less is known about female and male sex worker engagement in and the influence of sex-work stigma on the HIV care continuum. While stigma occurs in all spheres of life, stigma within health services may be particularly detrimental to health seeking behaviors. Therefore, we present levels of sex-work stigma from healthcare workers (HCW) among male and female sex workers in Kenya, and explore the relationship between sex-work stigma and HIV counseling and testing. We also examine the relationship between sex-work stigma and utilization of non-HIV health services. A snowball sample of 497 female sex workers (FSW) and 232 male sex workers (MSW) across four sites was recruited through a modified respondent-driven sampling process. About 50% of both male and female sex workers reported anticipating verbal stigma from HCW while 72% of FSW and 54% of MSW reported experiencing at least one of seven measured forms of stigma from HCW. In general, stigma led to higher odds of reporting delay or avoidance of counseling and testing, as well as non-HIV specific services. Statistical significance of relationships varied across type of health service, type of stigma and gender. For example, anticipated stigma was not a significant predictor of delay or avoidance of health services for MSW; however, FSW who anticipated HCW stigma had significantly higher odds of avoiding (OR = 2.11) non-HIV services, compared to FSW who did not. This paper adds to the growing evidence of stigma as a roadblock in the HIV treatment cascade, as well as its undermining of the human right to health. While more attention is being paid to addressing HIV-stigma, it is equally important to address the key population stigma that often intersects with HIV-stigma.

  9. Innovative farmers and regulatory gatekeepers: Genetically modified crops regulation and adoption in developing countries

    PubMed Central

    Sinebo, Woldeyesus; Maredia, Karim

    2016-01-01

    ABSTRACT The regulation of genetically modified (GM) crops is a topical issue in agriculture and environment over the past 2 decades. The objective of this paper is to recount regulatory and adoption practices in some developing countries that have successfully adopted GM crops so that aspiring countries may draw useful lessons and best practices for their biosafatey regulatory regimes. The first 11 mega-GM crops growing countries each with an area of more than one million hectares in 2014 were examined. Only five out of the 11 countries had smooth and orderly adoption of these crops as per the regulatory requirement of each country. In the remaining 6 countries (all developing countries), GM crops were either introduced across borders without official authorization, released prior to regulatory approval or unapproved seeds were sold along with the approved ones in violation to the existing regulations. Rapid expansion of transgenic crops over the past 2 decades in the developing world was a result of an intense desire by farmers to adopt these crops irrespective of regulatory roadblocks. Lack of workable biosafety regulatory system and political will to support GM crops encouraged unauthorized access to GM crop varieties. In certain cases, unregulated access in turn appeared to result in the adoption of substandard or spurious technology which undermined performance and productivity. An optimal interaction among the national agricultural innovation systems, biosafety regulatory bodies, biotech companies and high level policy makers is vital in making a workable regulated progress in the adoption of GM crops. Factoring forgone opportunities to farmers to benefit from GM crops arising from overregulation into biosafety risk analysis and decision making is suggested. Building functional biosafety regulatory systems that balances the needs of farmers to access and utilize the GM technology with the regulatory imperatives to ensure adequate safety to the environment and human health is recommended. PMID:26954893

  10. Brief history of agricultural systems modeling

    DOE PAGES

    Jones, James W.; Antle, John M.; Basso, Bruno; ...

    2017-06-21

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the "next generation" models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of thismore » history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. Furthermore, the lessons from history should be considered to help avoid roadblocks and pitfalls as the community develops this next generation of agricultural systems models.« less

  11. Differential Absorption Radar: An Emerging Technology for Remote Sounding of Water Vapor Within Clouds

    NASA Astrophysics Data System (ADS)

    Lebsock, M. D.; Millan Valle, L. F.; Cooper, K. B.; Siles, J.; Monje, R.

    2017-12-01

    We present the results of our efforts to build and demonstrate the first Differential Absorption Radar (DAR), which will provide unique capabilities to remotely sound for water vapor within cloudy and precipitating atmospheres. The approach leverages multiple radar channels located near the 183 GHz water vapor absorption feature to simultaneously derive microphysical and water vapor profiles. The DAR technique has the potential to neatly complement existing water vapor sounding techniques such as infrared and microwave sounding and GPS radio occultation. These precisions rival those of existing water vapor remote sensing instruments. The approach works best from above clouds because the water vapor burden and line width increases towards the Earth surface allowing increased sampling from the top-down compared with bottom-up. From an airborne or satellite platform channels can be selected that target either upper-tropospheric or lower-tropospheric clouds. Our theoretical studies suggest that the water vapor concentration can be retrieved to within 1-3 gm-3 and the column integrated water vapor can be retrieved to within 1 kgm-2. The high-frequency radar is only recently enabled by technological advances that have allowed us to demonstrate 0.5 W of continuous power near 183 GHz. We are currently developing an airborne DAR using a Frequency Modulated Continuous Wave (FMCW) architecture with a quasi-optical duplexer providing 80 dB of transmit/receive isolation. A prototype of this instrument recently made the first ever range resolved DAR measurements of humidity out to several hundred meters during a light rain event at JPL. The spectral dependence of the attenuation was in excellent agreement with the predicted attenuation based on nearby weather stations, proving for the first time the feasibility of the concept. A major impediment to implementing DAR is the international regulation of radio-frequency transmissions below 300 GHz. The major roadblocks and potential paths forward towards a spaceborne instruments will be presented.

  12. Tunable Dielectric Materials and Devices for Broadband Wireless Communications

    NASA Technical Reports Server (NTRS)

    Mueller, Carl H.; Miranda, Felix A.; Dayton, James A. (Technical Monitor)

    1998-01-01

    Wireless and satellite communications are a rapidly growing industries which are slated for explosive growth into emerging countries as well as countries with advanced economies. The dominant trend in wireless communication systems is towards broadband applications such as multimedia file transfer, video transmission and Internet access. These applications require much higher data transmission rates than those currently used for voice transmission applications. To achieve these higher data rates, substantially larger bandwidths and higher carrier frequencies are required. A key roadblock to implementing these systems at K-band (18-26.5 GHz) and Ka-band (26.5-40 GHz) is the need to develop hardware which meets the requirements for high data rate transmission in a cost effective manner. In this chapter, we report on the status of tunable dielectric thin films for devices, such as resonators, filters, phased array antennas, and tunable oscillators, which utilize nonlinear tuning in the control elements. Paraelectric materials such as Barium Strontium Titanate ((Ba, Sr)TiO3) have dielectric constants which can be tuned by varying the magnitude of the electric field across the material. Therefore, these materials can be used to control the frequency and/or phase response of various devices such as electronically steerable phased array antennas, oscillators, and filters. Currently, tunable dielectric devices are being developed for applications which require high tunability, low loss, and good RF power-handling capabilities at microwave and millimeter-wave frequencies. These properties are strongly impacted by film microstructure and device design, and considerable developmental work is still required. However, in the last several years enormous progress has occurred in this field, validating the potential of tunable dielectric technology for broadband wireless communication applications. In this chapter we summarize how film processing techniques, microwave test configurations, and prototype devices have combined to drive the field to its current stage of development.

  13. Brief history of agricultural systems modeling

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

    Jones, James W.; Antle, John M.; Basso, Bruno

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the "next generation" models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of thismore » history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. Furthermore, the lessons from history should be considered to help avoid roadblocks and pitfalls as the community develops this next generation of agricultural systems models.« less

  14. Configuring The REU Experience To Maximize Student Collaboration

    NASA Astrophysics Data System (ADS)

    Majkowski, L.; Pullin, M. J.

    2012-12-01

    The New Mexico Tech NSF-funded REU Program, Interdisciplinary Science for the Environment (ISE), hosted six cohorts of students between 2005 and 2010. The program ran for eight weeks during the first cycle and nine weeks during the second cycle, bringing in an average of twelve student participants per year. Students were provided with a stipend, food allowance, travel from home to New Mexico Tech, and free campus housing. The program sponsored weekend group field trips to scientific, environmental, and cultural sites of significance in New Mexico. For the second cycle, the ISE shared some programmatic elements with the New Mexico EPSCoR Undergraduate Research Opportunities Program (UROP). The majority of the research projects focused on the geosciences, with interdepartmental participation from researchers in earth science, hydrology, chemistry, environmental science, and biology. The ISE adopted a non-traditional approach to matching student participants with research projects and faculty mentors. Students were selected from different disciplines to work together in pairs on each project. This model provided the students with a peer collaborator in addition to the guidance of their faculty mentors and support from graduate students associated with the different projects. The focus on cohort, both within the individual research projects and each year's group, enabled and enhanced the students' critical thinking, problem-solving and teamwork skills. Students would routinely seek out the advice of their peers when they hit a roadblock in their research. This collaboration also occurred across the boundaries of the ISE and UROP cohorts. Long-term follow up has shown that a significant number of the student participants have continued on to graduate school. Students credit the program with developing their capacity to work on complex problems in an interdisciplinary group environment. Additionally, many students have continued contact with their research partners, faculty mentors and other members of their REU cohort.

  15. Uptake of enhanced recovery practices by SAGES members: a survey.

    PubMed

    Keller, Deborah S; Delaney, Conor P; Senagore, Anthony J; Feldman, Liane S

    2017-09-01

    The SAGES Surgical Multimodal Accelerated Recovery Trajectory (SMART) Enhanced Recovery Task Force aims to increase awareness and provide tools for members to successfully implement enhanced recovery pathways (ERPs) to improve clinical outcomes and patient satisfaction. An initial step was to survey SAGES member on their knowledge, use, and impediments to enhanced recovery. An online survey designed by SMART committee members to define SAGES member's awareness and use of enhanced recovery principles and practice was emailed to all SAGES members. Reminders were sent 2 and 3 weeks later, encouraging completion of the survey. The web-based survey included 48 questions and took an estimated 20 min to complete. A total of 229 members completed the survey. Respondents were primarily general/MIS surgeons (82.6%) working in an urban location (85.5%), with a bell-shaped age distribution (median 35-44). Almost half regularly used some elements of ERPs (48.7%), but 30% were unfamiliar with the concept. Wide variety in the specific ERP elements used and discharge criteria were reported. The majority had to create and implement their own plan (70.4%). Roadblocks to implementation were inconsistencies with partners/covering physicians (56.3%), nursing education (46.6%), and resources (34.7%). When implemented, members saw improvements in length of stay (88%), patient satisfaction (54.7%), postoperative pain (53.3%), time to return of bowel function (52.7%), and readmissions (16.7%). A need for education and standardization was especially seen in preoperative care, with 74.4% fasting patients from midnight the night before surgery. Wide variations were also reported in pain management practices. An overwhelming majority (89%) reported that having a protocol endorsed by a national organization, such as SAGES, would help with implementation. From this survey of SAGES members, there is a need for education, tools, and standardized protocols to increase awareness, support implementation, and encourage wider utilization of ERP. The overwhelming majority stated having a protocol endorsed by a national organization, such as SAGES, would facilitate implementation.

  16. Brief History of Agricultural Systems Modeling

    NASA Technical Reports Server (NTRS)

    Jones, James W.; Antle, John M.; Basso, Bruno O.; Boote, Kenneth J.; Conant, Richard T.; Foster, Ian; Godfray, H. Charles J.; Herrrero, Mario; Howitt, Richard E.; Janssen, Sandor; hide

    2016-01-01

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the next generation models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of this history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. The lessons from history should be considered to help avoid roadblocks and pitfalls as the community develops this next generation of agricultural systems models.

  17. Development of Millimeter-Wave Velocimetry and Acoustic Time-of-Flight Tomography for Measurements in Densely Loaded Gas-Solid Riser Flow

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

    Fort, James A.; Pfund, David M.; Sheen, David M.

    2007-04-01

    The MFDRC was formed in 1998 to advance the state-of-the-art in simulating multiphase turbulent flows by developing advanced computational models for gas-solid flows that are experimentally validated over a wide range of industrially relevant conditions. The goal was to transfer the resulting validated models to interested US commercial CFD software vendors, who would then propagate the models as part of new code versions to their customers in the US chemical industry. Since the lack of detailed data sets at industrially relevant conditions is the major roadblock to developing and validating multiphase turbulence models, a significant component of the work involvedmore » flow measurements on an industrial-scale riser contributed by Westinghouse, which was subsequently installed at SNL. Model comparisons were performed against these datasets by LANL. A parallel Office of Industrial Technology (OIT) project within the consortium made similar comparisons between riser measurements and models at NETL. Measured flow quantities of interest included volume fraction, velocity, and velocity-fluctuation profiles for both gas and solid phases at various locations in the riser. Some additional techniques were required for these measurements beyond what was currently available. PNNL’s role on the project was to work with the SNL experimental team to develop and test two new measurement techniques, acoustic tomography and millimeter-wave velocimetry. Acoustic tomography is a promising technique for gas-solid flow measurements in risers and PNNL has substantial related experience in this area. PNNL is also active in developing millimeter wave imaging techniques, and this technology presents an additional approach to make desired measurements. PNNL supported the advanced diagnostics development part of this project by evaluating these techniques and then by adapting and developing the selected technology to bulk gas-solids flows and by implementing them for testing in the SNL riser testbed.« less

  18. Comprehensive molecular characterization of Methylobacterium extorquens AM1 adapted for 1-butanol tolerance

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

    Hu, Bo; Yang, Yi -Ming; Beck, David A. C.

    In this study, the toxicity of alcohols is one of the major roadblocks of biological fermentation for biofuels production. Methylobacterium extorquens AM1, a facultative methylotrophic α-proteobacterium, has been engineered to generate 1-butanol from cheap carbon feedstocks through a synthetic metabolic pathway. However, M. extorquens AM1 is vulnerable to solvent stress, which impedes further development for 1-butanol production. Only a few studies have reported the general stress response of M. extorquens AM1 to solvent stress. Therefore, it is highly desirable to obtain a strain with ameliorated 1-butanol tolerance and elucidate the molecular mechanism of 1-butnaol tolerance in M. extorquens AM1 formore » future strain improvement. In this work, adaptive laboratory evolution was used as a tool to isolate mutants with 1-butanol tolerance up to 0.5 %. The evolved strains, BHBT3 and BHBT5, demonstrated increased growth rates and higher survival rates with the existence of 1-butanol. Whole genome sequencing revealed a SNP mutation at kefB in BHBT5, which was confirmed to be responsible for increasing 1-butanol tolerance through an allelic exchange experiment. Global metabolomic analysis further discovered that the pools of multiple key metabolites, including fatty acids, amino acids, and disaccharides, were increased in BHBT5 in response to 1-butanol stress. Additionally, the carotenoid synthesis pathway was significantly down-regulated in BHBT5. In conclusion, we successfully screened mutants resistant to 1-butanol and provided insights into the molecular mechanism of 1-butanol tolerance in M. extorquens AM1. This research will be useful for uncovering the mechanism of cellular response of M. extorquens AM1 to solvent stress, and will provide the genetic blueprint for the rational design of a strain of M. extorquens AM1 with increased 1-butanol tolerance in the future.« less

  19. Raw Sewage Harbors Diverse Viral Populations

    PubMed Central

    Cantalupo, Paul G.; Calgua, Byron; Zhao, Guoyan; Hundesa, Ayalkibet; Wier, Adam D.; Katz, Josh P.; Grabe, Michael; Hendrix, Roger W.; Girones, Rosina; Wang, David; Pipas, James M.

    2011-01-01

    ABSTRACT At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. Importance At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected. PMID:21972239

  20. The health worker recruitment and deployment process in Kenya: an emergency hiring program

    PubMed Central

    Adano, Ummuro

    2008-01-01

    Despite a pool of unemployed health staff available in Kenya, staffing levels at most facilities were only 50%, and maldistribution of staff left many people without access to antiretroviral therapy (ART). Because in the current system it takes one to two years to fill vacant positions, even when funding is available, an emergency approach was needed to fast-track the hiring and deployment process. A stakeholder group was formed to bring together leaders from several sectors to design and implement a fast-track hiring and deployment model that would mobilize 830 additional health workers. This model used the private sector to recruit and deploy new health workers and manage the payroll and employment contracts, with an agreement from the government to transfer these staff to the government payroll after three years. The recruitment process was shortened to less than three months. By providing job orientation and on-time pay checks, the program increased employee retention and satisfaction. Most of the active roadblocks to changes in the health workforce policies and systems are 'human' and not technical, stemming from a lack of leadership, a problem-solving mindset and the alignment of stakeholders from several sectors. It is essential to establish partnerships and foster commitment and collaboration to create needed change in human resource management (HRM). Strengthening appointment on merit is one of the most powerful, yet simplest ways in which the health sector and governments that seek to tackle the challenges of corruption and poor governance can improve their image and efficiency. The quality and integrity of the public health sector can be improved only through professionalizing HRM, reformulating and consolidating the currently fragmented HR functions, and bringing all the pieces together under the authority and influence of HR departments and units with expanded scopes. HR staff must be specialists with strategic HR functions and not generalists who are confined to playing a restricted and bureaucratic role. PMID:18796157

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