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Sample records for overcome steric barriers

  1. Overcoming Barriers.

    PubMed

    Neal-Boylan, Leslie; Schmidt, Kari L

    2015-01-01

    Dr. Neal-Boylan's program of scholarship has always focused on nurse workforce issues. She recently published two books related to how nurses work. One (The Nurse's Reality Gap: Overcoming Barriers Between Academic Achievement and Clinical Success; Neal-Boylan, 2013) focused on the experience of new graduates from baccalaureate, master's, and doctoral programs. The second book, The Nurse's Reality Shift: Using Our History to Transform Our Future (Neal-Boylan, 2014), focuses on the problems nursing continues to face throughout our history and has failed to correct. PMID:26200309

  2. Overcoming Language Barriers

    PubMed Central

    De Buda, Yvonne

    1976-01-01

    Many family physicians in Canada experience language and cultural barriers between themselves and their patients. Several aspects of the ensuing problems are described and some practical suggestions for solutions are made. The importance of health education for new Canadians in the family physician's office as well as through the media and community projects is stressed. Imagesp68-ap68-bp70-a PMID:21308059

  3. Toward overcoming cisplatin resistance via sterically hindered platinum(II) complexes.

    PubMed

    Yu, Haiyan; Gou, Shaohua; Wang, Zhimei; Chen, Feihong; Fang, Lei

    2016-05-23

    A number of platinum(II) complexes with steric hindrance derived from (1R,2R)-N(1)-benzylcyclohexane-1,2-diamine derivatives were designed and prepared. Biological assay indicated that most complexes showed antitumor activity against the tested cancer cell lines, especially those with chloride anions as leaving groups had compatible or superior activity to cisplatin and oxaliplatin. Complex 2a, as the most potent agent, is also sensitive to cisplatin resistant SGC7901/CDDP cancer cell line, which has been subsequently studied by cellular uptake, flow cytometry, gel electrophoresis and western blot assays. The steric hindrance resulting from a pending 2-fluorobenzyl moiety of the ligand might be the key factor for its ability to overcome cisplatin resistant cancer cells. PMID:26974381

  4. Overcoming Barriers: Women in Superintendency

    ERIC Educational Resources Information Center

    Miller, Claire M.

    2009-01-01

    Women currently represent the largest number of teachers in the United States but remain underrepresented in the superintendent position. This suggests that the superintendency has been influenced by patriarchy. If women are to break through the barriers that prevent them from attaining a superintendency, we will need to understand the social…

  5. Overcome barriers to career success

    SciTech Connect

    Raudsepp, E.

    1983-04-01

    A test is given to determine if an engineer suffers from one of the three barriers to technical success: fear of success, fear of failure, or perfectionism. As in most such tests, the middle way is best. Successful engineers know that perfection cannot be attained, that they don't have time to worry about failure or success, and that by aiming and perservering in doing things well, success can be achieved.

  6. Overcoming Barriers in Working with Families

    ERIC Educational Resources Information Center

    Heru, Alison M.; Drury, Laura

    2006-01-01

    Objective: The Accreditation Council for Graduate Medical Education and the Residency Review Committee for psychiatry outline the expected competencies for residents. These competencies include working with families. This article describes barriers that residents face when working with families, and offers ways to overcome these barriers. Method:…

  7. Overcoming cultural barriers to change.

    PubMed

    Hill, S; McNulty, D

    1998-01-01

    This article is a case study which focuses on organisational and cultural change associated with the incorporation of a college which provided pre- and post-registration nursing and midwifery education into a much larger institution within the university sector. Among the issues addressed is whether transformational change, such as that represented by incorporation or merger, can be used by managers to successfully refashion the culture of the organisation, making more effective than traditional or discipline-based management structures. It examines the barriers to change and the various considerations that arose in determining the fit of managerial styles and assesses the outcomes of the process of change. PMID:10346302

  8. Overcoming biological barriers with ultrasound

    NASA Astrophysics Data System (ADS)

    Thakkar, Dhaval; Gupta, Roohi; Mohan, Praveena; Monson, Kenneth; Rapoport, Natalya

    2012-10-01

    Effect of ultrasound on the permeability of blood vessels and cell membranes to macromolecules and nanodroplets was investigated using mouse carotid arteries and tumor cells. Model macromolecular drug, FITC-dextran with molecular weight of 70,000 Da was used in experiments with carotid arteries. The effect of unfocused 1-MHz ultrasound and and perfluoro-15-crown-5-ether nanodroplets stabilized with the poly(ethylene oxide)-co-poly(D, L-lactide) block copolymer shells was studied. In cell culture experiments, ovarian carcinoma cells and Doxorubicin (DOX) loaded poly(ethylene oxide)-co-polycaprolactone nanodroplets were used. The data showed that the application of ultrasound resulted in permeabilization of all biological barriers tested. Under the action of ultrasound, not only FITC-dextran but also nanodroplets effectively penetrated through the arterial wall; the effect of continuous wave ultrasound was stronger than that of pulsed ultrasound. In cell culture experiments, ultrasound triggered DOX penetration into cell nuclei, presumably due to releasing the drug from the carrier. Detailed mechanisms of the observed effects require further study.

  9. Overcoming Barriers in the Media Center

    ERIC Educational Resources Information Center

    Winter, Clint

    2011-01-01

    Web 2.0 has revolutionized one's ability to teach students in new and exciting ways. Students with disabilities can now overcome many barriers that once kept them from being successful in the regular education classroom. Media specialists can effectively advocate for students with disabilities. School library media specialists have the ability to…

  10. Overcoming Barriers to Engaging in College Academics

    ERIC Educational Resources Information Center

    Hensley, Lauren; Shaulskiy, Stephanie; Zircher, Andrew; Sanders, Megan

    2015-01-01

    Underprepared college students face transition issues that prevent full academic engagement. The written responses of 176 students in a learning-strategies course were used to develop a grounded model of overcoming barriers to academic engagement. Findings revealed contexts in which academic engagement involved high costs (i.e., effort, trade-off,…

  11. Explaining and overcoming barriers to climate change adaptation

    NASA Astrophysics Data System (ADS)

    Eisenack, Klaus; Moser, Susanne C.; Hoffmann, Esther; Klein, Richard J. T.; Oberlack, Christoph; Pechan, Anna; Rotter, Maja; Termeer, Catrien J. A. M.

    2014-10-01

    The concept of barriers is increasingly used to describe the obstacles that hinder the planning and implementation of climate change adaptation. The growing literature on barriers to adaptation reveals not only commonly reported barriers, but also conflicting evidence, and few explanations of why barriers exist and change. There is thus a need for research that focuses on the interdependencies between barriers and considers the dynamic ways in which barriers develop and persist. Such research, which would be actor-centred and comparative, would help to explain barriers to adaptation and provide insights into how to overcome them.

  12. Overcoming Barriers to Shared Decision Making

    MedlinePlus

    ... American Heart area Search by State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 (Simplified Chinese) ... to interfere with your daily life, you may benefit from counseling, medication or both. Barrier: Difficulty understanding ...

  13. Dos Hermanas Chicanas: Overcoming Barriers to Professional Advancement

    ERIC Educational Resources Information Center

    Prospero, Moises

    2007-01-01

    Women and ethnic minorities face steep barriers to professional advancement, and those who rise to the executive level typically use a variety of strategies to overcome obstacles in their way. This study first reviewed the literature on barriers to professional advancement for women and ethnic minorities and the strategies that they report using…

  14. Overcoming immunological barriers in regenerative medicine

    PubMed Central

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2015-01-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  15. Overcoming immunological barriers in regenerative medicine.

    PubMed

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2014-08-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  16. Overcoming physical barriers in cancer therapy

    PubMed Central

    Beyer, Ines; van Rensburg, Ruan; Lieber, André

    2013-01-01

    Most solid tumors are of epithelial origin and, although malignant cells are de-differentiated, they maintain intercellular junctions, a key feature of epithelial cells, both in the primary tumor as well as in metastatic lesions. These intercellular junctions represent a protective mechanism against attacks by the host’s immune system and pose as physical barriers that prevent intratumoral penetration and dissemination of cancer therapeutics. A key protein of epithelial junctions is desmoglein 2 (DSG2). DSG2 is consistently upregulated in all cancers analyzed. Recently, we demonstrated that a group of human adenoviruses (Ad serotypes 3, 7, 11 and 14) use DSG2 as a primary attachment receptor for the infection of cells. We subsequently created a small recombinant protein derived from Ad serotype 3, which binds to DSG2 and triggers transient opening of epithelial intercellular junctions. We named the protein “JO-1” (“junction opener -1”). JO-1 is a small protein that can easily be produced in E. coli. JO-1 binding to and clustering of DSG2 triggers an epithelial-to-mesenchymal-transition that results in transient opening of epithelial junctions. We have shown in over 25 xenograft tumor models that the intravenous injection of JO-1 increased the efficacy of monoclonal and chemotherapy, subsequently reducing the required treatment dose and concomitantly reducing the toxic side effect of these treatments. The application of JO-1 has not been associated with toxicities in safety studies performed in human DSG2-transgenic mice and monkeys. PMID:24665377

  17. Establishing a statewide mammography database in Arkansas: overcoming the barriers.

    PubMed

    Jazieh, Abdul Rahman

    2003-01-01

    To determine patterns of mammography utilization in Arkansas, the Arkansas Mammography Data Collection Project (MDCP) was established. The project's objective was to compile into one database statewide information about mammograms performed. All mammography centers were invited to participate in the project. Many barriers were encountered that were center related, data related, or personnel related; different interventions were implemented for each barrier. At the conclusion of the project, 92 out of 112 centers (82%) participated in the project, creating a database of 157,976 mammography data sets. Identifying and overcoming many of the barriers were crucial steps in the project's success. PMID:12552932

  18. Overcoming health literacy barriers: a model for action.

    PubMed

    Mancuso, Lorraine

    2011-01-01

    A large influx of Indonesian immigrants seeking asylum from racial and religious persecution into our hospital service area alerted providers to the need for specific cultural knowledge about this ethnic group, and to develop new skill sets to effectively care for this population. Health education programs that provide knowledge and tools to overcome misunderstandings that arise from differences between provider and client expectations for behavior will be most effective in overcoming the health literacy barriers that so often contribute to health disparities. A framework to understand factors that affect health literacy for local Indonesian asylum seekers guided community health education, while the written educational materials for programs informed providers about health literacy barriers for this population. Community outreach engaged local pastors and interpreters as cultural brokers to collaborate with nurses to develop and implement culturally sensitive programs that are socially sensitive to the local Indonesian refugee population. PMID:21744676

  19. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier

    PubMed Central

    Hersh, David S.; Wadajkar, Aniket S.; Roberts, Nathan B.; Perez, Jimena G.; Connolly, Nina P.; Frenkel, Victor; Winkles, Jeffrey A.; Woodworth, Graeme F.; Kim, Anthony J.

    2016-01-01

    The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

  20. Overcoming barriers to health care access for medically underserved children.

    PubMed

    Redlener, I

    1993-01-01

    The NYCHP was designed to serve the special needs of medically underserved, extremely disadvantaged children in New York City. As a model, and as the flagship program of a national network, the NYCHP demonstrates that it is possible to provide a medical home for children in a variety of challenging situations where access to traditional providers is limited. It is clear, however, that mobile units or other creative ways to overcome barriers to access to care are an insufficient long-term answer. Ultimately, the public sector must take steps to ensure that all American children have regular access to a true medical home regardless of their social or economic situation. In the interim, special initiatives such as the NYCHP must continue to fill the gap. PMID:10123427

  1. Overcoming barriers to development of cooperative medical decision support models.

    PubMed

    Hudson, Donna L; Cohen, Maurice E

    2012-01-01

    Attempts to automate the medical decision making process have been underway for the at least fifty years, beginning with data-based approaches that relied chiefly on statistically-based methods. Approaches expanded to include knowledge-based systems, both linear and non-linear neural networks, agent-based systems, and hybrid methods. While some of these models produced excellent results none have been used extensively in medical practice. In order to move these methods forward into practical use, a number of obstacles must be overcome, including validation of existing systems on large data sets, development of methods for including new knowledge as it becomes available, construction of a broad range of decision models, and development of non-intrusive methods that allow the physician to use these decision aids in conjunction with, not instead of, his or her own medical knowledge. None of these four requirements will come easily. A cooperative effort among researchers, including practicing MDs, is vital, particularly as more information on diseases and their contributing factors continues to expand resulting in more parameters than the human decision maker can process effectively. In this article some of the basic structures that are necessary to facilitate the use of an automated decision support system are discussed, along with potential methods for overcoming existing barriers. PMID:23366358

  2. Overcoming the barriers to xenotransplantation: prospects for the future

    PubMed Central

    Ekser, Burcin; Cooper, David KC

    2010-01-01

    Cross-species transplantation (xenotransplantation) has immense potential to solve the critical need for organs, tissues and cells for clinical transplantation. The increasing availability of genetically engineered pigs is enabling progress to be made in pig-to-nonhuman primate experimental models. Potent pharmacologic immunosuppressive regimens have largely prevented T-cell rejection and a T-cell-dependent elicited antibody response. However, coagulation dysfunction between the pig and primate is proving to be a major problem, and this can result in life-threatening consumptive coagulopathy. This complication is unlikely to be overcome until pigs expressing a human ‘antithrombotic’ or ‘anticoagulant’ gene, such as thrombomodulin, tissue factor pathway inhibitor or CD39, become available. Progress in islet xenotransplantation has been more encouraging, and diabetes has been controlled in nonhuman primates for periods in excess of 6 months, although this has usually been achieved using immunosuppressive protocols that might not be clinically applicable. Further advances are required to overcome the remaining barriers. PMID:20402385

  3. Overcoming the Confucian psychological barrier in government cyberspace.

    PubMed

    Lee, Ook; Gong, Sung Jin

    2004-02-01

    The Confucian tradition still dictates the behavior of many people in East Asian countries such as South Korea. Even in e-mail communication, people try their best to show signs of respect which is required by the Confucian tradition. This psychological barrier can be detrimental to the development of democracy as people are educated not to challenge opinions of elders or bosses. After a long military dictatorship, South Korea has emerged as a newly democratized nation where the Confucian tradition is less emphasized. However, this tradition dies hard, and citizens are still afraid of offending government officials who have the power to affect lives of citizens. In light of creating a more democratic society, the e-government project has been implemented, and one of the features of cyber-government is to give citizens a place in cyberspace to express their concerns. Even though citizens have to use their real names, it is found that those who wrote messages in the bulletin board of the city of Seoul government's web pages tend not to use terms that are often used in e-mails for the purpose of expressing respect. A survey was conducted, and results show that people were able to overcome the Confucian psychological barrier in government cyberspace. Self-efficacy is proposed to explain this phenomenon. PMID:15006165

  4. Immunotherapy and complexity: overcoming barriers to control of advanced cancer.

    PubMed

    Lage, Agustin

    2014-01-01

    Recent advances in fundamental immunology are changing paradigms for management of advanced cancer, now acknowledged as a chronic disease whose prevalence will increase, and one whose complexity makes it difficult to control. Immunotherapy is emerging as an alternative, with new monoclonal antibodies, therapeutic vaccines and deeper understanding of fundamental phenomena in the interaction between tumor and immune system. These novel insights concern mechanisms of programmed contraction of the immune response, characterization of molecular and cellular markers of immunosenescence, the dual role of inflammation, characterization of myeloid-derived suppressor cells and cancer stem cells, and the phenomena of immunogenic apoptosis and oncogene addiction. Additionally, new data drive a deeper understanding of four barriers to overcome in control of advanced cancer: the complexity of biological systems, tumor heterogeneity, tumor mutation rates, and human genome-environment mismatch. The new landscape points to six main strategies: manage advanced cancer as a chronic disease, find relevant molecular markers for patient stratification, develop a rationale for therapeutic combinations, target regulatory control loops in the immune system, expand mathematical modeling capacity, and evaluate complex health intervention packages in real-world conditions. These transitions in cancer immunotherapy research are illustrated in this paper through description of ongoing projects at Cuba's Molecular Immunology Center. PMID:25208123

  5. 75 FR 58347 - Information Collection; Overcoming Barriers to Wildland Fire Defensible Space Behaviors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Overcoming Barriers to Wildland Fire... Fire Defensible Space Behaviors. DATES: Comments must be received in writing on or before November 23...: Overcoming Barriers to Wildland Fire Defensible Space Behaviors. OMB Number: 0596-New. Type of Request:...

  6. Overcoming Barriers to Wind Development in Appalachian Coal Country

    SciTech Connect

    Brent Bailey; Evan Hansen

    2012-10-09

    This research project synthesizes existing data and communication from experts to assess barriers to wind development in Pennsylvania, Maryland, West Virginia, Virginia, and Kentucky, and makes recommendations where feasible to reduce or eliminate those barriers.

  7. Steric repulsions, rotation barriers, and stereoelectronic effects: a real space perspective.

    PubMed

    Pendás, A Martín; Blanco, M A; Francisco, E

    2009-01-15

    Widely used chemical concepts like Pauli repulsion or hyperconjugation, and their role in determining rotation barriers or stereoelectronic effects, are analyzed from the real space perspective of the interacting quantum atoms approach (IQA). IQA emerges from the quantum theory of atoms in molecules (QTAIM), but is free from the equilibrium geometry constraint of the former. A framework with both electronically unrelaxed and relaxed wavefunctions is presented that leads to an approximate correspondence between the IQA concepts and those used in the EDA (energy decomposition analysis) or NBO (natural bond orbital) procedures. We show that no net force acts upon the electrons in an electronically relaxed system, so that any reasonable definition of Pauli repulsion must involve unrelaxed state functions. Using antisymmetrized fragments clarifies that Pauli repulsions are energetically connected to the IQA deformation energies, leaving footprints in the finally relaxed states. Similarly, EDA or NBO hyperconjugative stabilizations are found to be naturally related to the IQA electron delocalization patterns. Applications to the rotation barrier of ethane and other simple systems are presented, and the very often forgotten role of electrostatic contributions in determining preferred conformations is highlighted. PMID:18536054

  8. Service use among low-income minority elderly: strategies for overcoming barriers.

    PubMed

    Yeatts, D E; Crow, T; Folts, E

    1992-02-01

    The 1987 amendments to the Older Americans Act mandate a special effort to serve low-income minority elderly persons. A literature review showed that "practice-oriented" research on service use has focused primarily on identifying barriers with much less attention to identification of strategies for overcoming the barriers. This paper identifies and describes strategies used throughout Texas. Strategies addressing the "lack of knowledge" barrier included use of influential groups, working with significant individuals, and the media. Strategies addressing the "lack of access" barrier included transportation, affordability, and availability. Strategies addressing the "lack of intent" barrier focused on cultural differences, making services attractive, and overcoming negative attitudes toward service use. PMID:1740252

  9. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    EPA Science Inventory

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  10. Provider barriers to telemental health: obstacles overcome, obstacles remaining.

    PubMed

    Brooks, Elizabeth; Turvey, Carolyn; Augusterfer, Eugene F

    2013-06-01

    Many providers are hesitant to use telemental health technologies. When providers are queried, various barriers are presented, such as the clinician's skepticism about the effectiveness of telemental health (TMH), viewing telehealth technologies as inconvenient, or reporting difficulties with medical reimbursement. Provider support for TMH is critical to its diffusion because clinicians often serve as the initial gatekeepers to telehealth implementation and program success. In this article, we address provider concerns in three broad domains: (1) personal barriers, (2) clinical workflow and technology barriers, and (3) licensure, credentialing, and reimbursement barriers. We found evidence that, although many barriers have been discussed in the literature for years, advancements in TMH have rapidly reduced obstacles for its use. Improvements include extensive opportunities for training, a growing evidence base supporting positive TMH outcomes, and transformations in technologies that improve provider convenience and transmission quality. Recommendations for further change are discussed within each domain. In particular, it is important to grow and disseminate data underscoring the promise and effectiveness of TMH, integrate videoconferencing capabilities into electronic medical record platforms, expand TMH reimbursement, and modify licensure standards. PMID:23590176

  11. Teaching English Language Learners: Strategies for Overcoming Barriers

    ERIC Educational Resources Information Center

    Helfrich, Sara R.; Bosh, Amy J.

    2011-01-01

    The number of English language learners (ELLs) in today's classrooms is increasing. In this article, the authors identify four perceived barriers beginning and veteran teachers face in teaching literacy to ELLs: the lack of understanding of the role of literacy in other cultures, the teacher's inability to differentiate instruction to meet the…

  12. Automation U.S.A.: Overcoming Barriers to Automation.

    ERIC Educational Resources Information Center

    Brody, Herb

    1985-01-01

    Although labor unions and inadequate technology play minor roles, the principal barrier to factory automation is "fear of change." Related problems include long-term benefits, nontechnical executives, and uncertainty of factory cost accounting. Industry support for university programs is helping to educate engineers to design, implement, and…

  13. Women in School Administration: Overcoming the Barriers to Advancement.

    ERIC Educational Resources Information Center

    WEEA Digest, 1990

    1990-01-01

    This digest examines three prominent theories that attempt to explain why women are underrepresented in educational administration and develops a three-dimensional matrix as an empowerment perspective. Each of the theories--resocialization, structural barriers, and male dominance--is based on deficiencies in the woman, the system, or the society.…

  14. Barriers to Effective Counseling with Blacks and Therapeutic Strategies for Overcoming Them.

    ERIC Educational Resources Information Center

    Tucker, Carolyn M.; And Others

    1981-01-01

    Presents strategies for counselors working with Black clients. Suggests awareness of potential barriers to effective counseling enables the therapist to gear the initial sessions toward overcoming these obstacles and thus make early observations of tangible therapeutic gains. Proposes such advances are important in overcoming client skepticism and…

  15. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    ERIC Educational Resources Information Center

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  16. Implementing District Energy Systems: Municipal Approaches To Overcoming Barriers

    NASA Astrophysics Data System (ADS)

    Simpson, Kevin George

    Climate change and energy security are issues facing municipalities throughout the world. Efficient, resilient, sustainable, community-based energy systems, such as district energy systems (DES), fuelled mostly by renewables, are an important tool for addressing both climate change and energy security at the municipal level. In spite of their benefits, DES are not widely adopted in Canada (CDEA, 2011). This is due to the complex nature of the barriers which project proponents face. This thesis examines the experience of the City of Prince George in adopting and implementing the Downtown DES. Using a case study methodology, data was collected through a review of relevant municipal documents and a series of semi-structured, open-ended interviews. A thematic analysis revealed unexpected barriers related to lack of adequate public consultation and negative perceptions regarding biomass as a fuel for the DES. These `lessons learned' were then developed into recommendations for other municipalities considering DES.

  17. No One Is Unemployable: Creative Solutions for Overcoming Barriers to Employment.

    ERIC Educational Resources Information Center

    Harney, Elisabeth E.

    The goal of the WorkNet Model Career Development & Job Placement for people with barriers is to help even the most challenged job seekers begin and advance in careers they enjoy. This paper presents one key component of the WorkNet Model, a practical process for creatively overcoming any barrier a candidate faces. The chapter includes: the…

  18. Overcoming barriers to public understanding of climate change

    NASA Astrophysics Data System (ADS)

    Hayhoe, K.

    2012-12-01

    Humans are interfering with global climate, increasing the risk of serious consequences for human society and the natural environment. As the scientific evidence builds, however, so does the public controversy surrounding this issue. Why is climate change so contentious? What makes it so hard to comprehend? I argue that there is no single reason for this, but rather a perfect storm of multiple confounding factors; scientific, historical, ideological, psychological and even physiological in nature. Education—of both the messengers and the audience—can play a critical role in surmounting many of the common barriers to understanding, accepting, and acting this important issue.

  19. Newborn screening progress in developing countries--overcoming internal barriers.

    PubMed

    Padilla, Carmencita D; Krotoski, Danuta; Therrell, Bradford L

    2010-04-01

    Newborn screening is an important public health measure aimed at early identification and management of affected newborns thereby lowering infant morbidity and mortality. It is a comprehensive system of education, screening, follow-up, diagnosis, treatment/management, and evaluation that must be institutionalized and sustained within public health systems often challenged by economic, political, and cultural considerations. As a result, developing countries face unique challenges in implementing and expanding newborn screening that can be grouped into the following categories: (1) planning, (2) leadership, (3) medical support, (4) technical support, (5) logistical support, (6) education, (7) protocol and policy development, (8) administration, (9) evaluation, and (10) sustainability. We review some of the experiences in overcoming implementation challenges in developing newborn screening programs, and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in 2 regions-the Asia Pacific and the Middle East/North Africa. PMID:20207264

  20. Barriers to overcome for effective cancer control in Africa.

    PubMed

    Harford, Joe B

    2015-08-01

    Cancer control in Africa is complicated due to large differences in cancer incidence between countries caused by differences in exposure to known risk factors. For example, substantial differences are seen when selected cancers in north Africa are compared with those in sub-Saharan Africa. In the future, population growth and demographic shifts are likely to have profound effects on the prevalence of cancer across the continent. Likewise, many factors outside of health care such as language differences, conflict, and poverty can affect cancer control efforts. Although cooperation in cancer control efforts is desirable, differences in cultural and geopolitical factors that characterise African countries and their populations, together with the sheer size of the continent, present unique challenges to effective cancer control. This Series paper discusses factors related to the size, diversity, and conditions within Africa that present barriers to optimal collaboration in cancer control efforts across the continent. PMID:26248846

  1. Staff resistance to restraint reduction: identifying & overcoming barriers.

    PubMed

    Curran, Staci Silver

    2007-05-01

    Professional organizations, regulating agencies, and hospital administrators have taken a strong stance on restraint reduction policies. When implementing a restraint reduction initiative, it is important to identify the barriers to restraint reduction, such as concern for personal safety, lack of knowledge about and practice using alternate de-escalation skills, and fear of disrupting the therapeutic milieu by using a variety of de-escalation methods. Education aimed to reduce the use of restraints needs to do more than simply provide information. It is important to acknowledge the emotional response of the nursing staff and the culture of the current practice. A variety of educational strategies, including role-playing, and case studies will help identify attitudes, beliefs, and behaviors that are congruent with reducing the use of restraints. If the ultimate goal of restraint reduction is philosophical change, it will eventually lead to a new culture of practice. PMID:17526330

  2. Strategies to overcome the ABO barrier in kidney transplantation.

    PubMed

    Böhmig, Georg A; Farkas, Andreas M; Eskandary, Farsad; Wekerle, Thomas

    2015-12-01

    Kidney transplantation across the ABO blood group barrier was long considered a contraindication for transplantation, but in an effort to increase donor pools, specific regimens for ABO-incompatible (ABOi) transplantation have been developed. These regimens are now widely used as an integral part of the available treatment options. Various desensitization protocols, commonly based on transient depletion of preformed anti-A and/or anti-B antibodies and modulation of B-cell immunity, enable excellent transplant outcomes, even in the long-term. Nevertheless, the molecular mechanisms behind transplant acceptance facilitated by a short course of anti-humoral treatment are still incompletely understood. With the evolution of efficient clinical programmes, tailoring of recipient preconditioning based on individual donor-recipient blood type combinations and the levels of pretransplant anti-A/B antibodies has become possible. In the context of low antibody titres and/or donor A2 phenotype, immunomodulation and/or apheresis might be dispensable. A concern still exists, however, that ABOi kidney transplantation is associated with an increased risk of surgical and infectious complications, partly owing to the effects of extracorporeal treatment and intensified immunosuppression. Nevertheless, a continuous improvement in desensitization strategies, with the aim of minimizing the immunosuppressive burden, might pave the way to clinical outcomes that are comparable to those achieved in ABO-compatible transplantation. PMID:26324199

  3. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed

    Hoover, Eddie L

    2006-09-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented. PMID:17019926

  4. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed Central

    Hoover, Eddie L.

    2006-01-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented. PMID:17019926

  5. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

    PubMed Central

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research. PMID:26465757

  6. Strategies for Overcoming Key Barriers to Development of a National Security Workforce

    SciTech Connect

    2008-06-30

    This report documents the strategies for overcoming identified key barriers to development of an adequate national security workforce as part of the National Security Preparedness Project (NSPP) being performed under a Department of Energy (DOE) National Nuclear Security Administration (NNSA) grant. Many barriers currently exist that prevent the development of an adequate number of properly trained national security personnel. The identified strategies to address the barriers will focus on both short-term and long-term efforts, as well as strategies to capture legacy knowledge of retiring national security workforce personnel.

  7. Powering Your Community With Solar: Overcoming Market and Implementation Barriers (Fact Sheet)

    SciTech Connect

    Not Available

    2012-06-01

    This document introduces the Energy Department's new Solarize Guidebook: A Community Guide to Collective Purchasing of Residential PV Systems. The guide is designed for 'green' consumers, utilities, local governments, and community groups who want to replicate the success of the Solarize Portland model, overcome barriers to implementation, and permanently transform the market for solar energy in their communities.

  8. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    ERIC Educational Resources Information Center

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  9. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, P. C.; Halverson, M. A.

    2013-09-01

    This guidance document was prepared using the input from the meeting summarized in the draft CSI Roadmap to provide Building America research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America innovations arising in and/or stemming from codes, standards, and rating methods.

  10. Open access for the non-English-speaking world: overcoming the language barrier

    PubMed Central

    Fung, Isaac CH

    2008-01-01

    This editorial highlights the problem of language barrier in scientific communication in spite of the recent success of Open Access Movement. Four options for English-language journals to overcome the language barrier are suggested: 1) abstracts in alternative languages provided by authors, 2) Wiki open translation, 3) international board of translator-editors, and 4) alternative language version of the journal. The Emerging Themes in Epidemiology announces that with immediate effect, it will accept translations of abstracts or full texts by authors as Additional files. Editorial note: In an effort towards overcoming the language barrier in scientific publication, ETE will accept translations of abstracts or the full text of published articles. Each translation should be submitted separately as an Additional File in PDF format. ETE will only peer review English-language versions. Therefore, translations will not be scrutinized in the review-process and the responsibility for accurate translation rests with the authors. PMID:18173854

  11. Overcoming barriers to exercise among parents: a social cognitive theory perspective.

    PubMed

    Mailey, Emily L; Phillips, Siobhan M; Dlugonski, Deirdre; Conroy, David E

    2016-08-01

    Parents face numerous barriers to exercise and exhibit high levels of inactivity. Examining theory-based determinants of exercise among parents may inform interventions for this population. The purpose of this study was to test a social-cognitive model of parental exercise participation over a 12-month period. Mothers (n = 226) and fathers (n = 70) of children <16 completed measures of exercise, barriers self-efficacy, perceived barriers, and exercise planning at baseline and 1 year later. Panel analyses were used to test the hypothesized relationships. Barriers self-efficacy was related to exercise directly and indirectly through perceived barriers and prioritization/planning. Prioritization and planning also mediated the relationship between perceived barriers and exercise. These paths remained significant at 12 months. These results suggest efforts to increase exercise in parents should focus on improving confidence to overcome exercise barriers, reducing perceptions of barriers, and helping parents make specific plans for prioritizing and engaging in exercise. PMID:27108160

  12. Overcoming terminology barrier using Web resources for cross-language medical information retrieval.

    PubMed

    Lu, Wen-Hsiang; Lin, Ray Shih-Jui; Chan, Yi-Che; Chen, Kuan-Hsi

    2006-01-01

    A number of authoritative medical websites, such as PubMed and MedlinePlus, provide consumers with the most up-to-date health information. However, non-English speakers often encounter not only language barriers (from other languages to English) but also terminology barriers (from laypersons inverted exclamation mark| terms to professional medical terms) when retrieving information from these websites. Our previous work address language barriers by developing a multilingual medical thesaurus, Chinese-English MeSH, while this study presents an approach to overcome terminology barriers based on Web resources. Two techniques were utilized in our approach: monolingual concept mapping using approximate string matching and crosslingual concept mapping using Web resources. The evaluation shows that our approach can significantly improve the performance on MeSH concept mapping and cross-language medical information retrieval. PMID:17238395

  13. Emergency department crowding, part 2--barriers to reform and strategies to overcome them.

    PubMed

    Moskop, John C; Sklar, David P; Geiderman, Joel M; Schears, Raquel M; Bookman, Kelly J

    2009-05-01

    Part 1 of this 2-article series reviews serious moral problems created by emergency department (ED) crowding. In this second part of the series, we identify and describe operational and financial barriers to resolving the crisis of ED crowding, along with a variety of institutional and public policy strategies proposed or implemented to overcome those barriers. Finally, the article evaluates 2 additional actions designed to address the problem of ED crowding, namely, distribution of a warning statement to ED patients and implementation of a "reverse triage" system for safe early discharge of hospital inpatients. PMID:19027194

  14. Overcoming transport barriers for interstitial-, lymphatic-, and lymph node-targeted drug delivery

    PubMed Central

    Thomas, Susan N.; Schudel, Alex

    2015-01-01

    Despite drug formulation improving circulation times and targeting, efficacy is stymied by inadequate penetration into and retention within target tissues. This review highlights the barriers restricting delivery to the connective tissue interstitium, lymphatics, and lymph nodes as well as advances in engineering drug carriers to overcome these delivery challenges. Three-dimensional tissue physiology is discussed in the context of providing material design principles for delivery to these tissues; in particular the influence of interstitial and lymphatic flows as well as differential permeabilities of the blood and lymphatic capillaries. Key examples of materials with different characteristics developed to overcome these transport barriers are discussed as well as potential areas for further development. PMID:25745594

  15. Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

    PubMed Central

    Tu, Haohua; Boppart, Stephen A.

    2015-01-01

    Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring. An optimal scheme of clinical CARS micro-spectroscopy for thin ex vivo tissues. PMID:23674234

  16. Public Health in the Emergency Department: Overcoming Barriers to Implementation and Dissemination

    PubMed Central

    McKay, Mary Pat; Vaca, Federico E.; Field, Craig; Rhodes, Karin

    2011-01-01

    This article is the outcome of a consensus building workshop entitled, “Overcoming Barriers to Implementation and Dissemination” convened at the 2009 Academic Emergency Medicine Consensus Conference, “Public Health in the ED: Surveillance, Screening, and Intervention.” The participants were asked to address potential methods for overcoming barriers to the dissemination and implementation in the emergency department (ED) of evidenced-based practices to improve public health. The panel discussed three broad areas of interest including methods for disseminating evidence-based practices, barriers encountered during the process of implementation, and the importance of involvement in activities outside the ED including engagement in policy development and improvement. Four recommendations were discussed in detail and consensus was reached. The recommendations included 1) researchers and advocates should disseminate findings through multiple forums beyond peer-reviewed publications when an ED-based public health intervention has enough evidence to support integration into the routine practice of emergency care; 2) local barriers to implementation of public health interventions should be recognized and well understood from multiple perspectives prior to implementation; 3) innovation must be put into place and adapted based on local institutional context and culture as barriers and the best methods for overcoming them will vary across institutions; and 4) use of legislation, regulation, and incentives outside of the ED should support and strengthen ED-based interventions. For each area of interest, research dimensions to extend the current understanding of methods for effectively and efficiently implementing evidence-based public health interventions in the ED were discussed and consensus was achieved. PMID:20053233

  17. Overcoming the Cystic Fibrosis Sputum Barrier to Leading Adeno-associated Virus Gene Therapy Vectors

    PubMed Central

    Schuster, Benjamin S; Kim, Anthony J; Kays, Joshua C; Kanzawa, Mia M; Guggino, William B; Boyle, Michael P; Rowe, Steven M; Muzyczka, Nicholas; Suk, Jung Soo; Hanes, Justin

    2014-01-01

    Gene therapy has not yet improved cystic fibrosis (CF) patient lung function in human trials, despite promising preclinical studies. In the human CF lung, inhaled gene vectors must penetrate the viscoelastic secretions coating the airways to reach target cells in the underlying epithelium. We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials. Using multiple particle tracking, we found that sputum strongly impeded diffusion of AAV, regardless of serotype, by adhesive interactions and steric obstruction. Approximately 50% of AAV vectors diffused >1,000-fold more slowly in sputum than in water, with large patient-to-patient variation. We thus tested two strategies to improve AAV diffusion in sputum. We showed that an AAV2 mutant engineered to have reduced heparin binding diffused twice as fast as AAV2 on average, presumably because of reduced adhesion to sputum. We also discovered that the mucolytic N-acetylcysteine could markedly enhance AAV diffusion by altering the sputum microstructure. These studies underscore that sputum is a major barrier to CF gene delivery, and offer strategies for increasing AAV penetration through sputum to improve clinical outcomes. PMID:24869933

  18. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers. PMID:26675218

  19. How to overcome barriers and establish a successful home HD program.

    PubMed

    Young, Bessie A; Chan, Christopher; Blagg, Christopher; Lockridge, Robert; Golper, Thomas; Finkelstein, Fred; Shaffer, Rachel; Mehrotra, Rajnish

    2012-12-01

    Home hemodialysis (HD) is an underused dialysis modality in the United States, even though it provides an efficient and probably cost-effective way to provide more frequent or longer dialysis. With the advent of newer home HD systems that are easier for patients to learn, use, and maintain, patient and provider interest in home HD is increasing. Although barriers for providers are similar to those for peritoneal dialysis, home HD requires more extensive patient training, nursing education, and infrastructure support in order to maintain a successful program. In addition, because many physicians and patients do not have experience with home HD, reluctance to start home HD programs is widespread. This in-depth review describes barriers to home HD, focusing on patients, individual physicians and practices, and dialysis facilities, and offers suggestions for how to overcome these barriers and establish a successful home HD program. PMID:23037981

  20. Cancer cells remodel themselves and vasculature to overcome the endothelial barrier.

    PubMed

    Shenoy, Anitha K; Lu, Jianrong

    2016-10-01

    Metastasis refers to the spread of cancer cells from a primary tumor to distant organs mostly via the bloodstream. During the metastatic process, cancer cells invade blood vessels to enter circulation, and later exit the vasculature at a distant site. Endothelial cells that line blood vessels normally serve as a barrier to the movement of cells into or out of the blood. It is thus critical to understand how metastatic cancer cells overcome the endothelial barrier. Epithelial cancer cells acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT), which enables them to move toward vasculature. Cancer cells also express a variety of adhesion molecules that allow them to attach to vascular endothelium. Finally, cancer cells secrete or induce growth factors and cytokines to actively prompt vascular hyperpermeability that compromises endothelial barrier function and facilitates transmigration of cancer cells through the vascular wall. Elucidation of the mechanisms underlying metastatic dissemination may help develop new anti-metastasis therapeutics. PMID:25449784

  1. How to Overcome Barriers and Establish a Successful Home HD Program

    PubMed Central

    Chan, Christopher; Blagg, Christopher; Lockridge, Robert; Golper, Thomas; Finkelstein, Fred; Shaffer, Rachel; Mehrotra, Rajnish

    2012-01-01

    Summary Home hemodialysis (HD) is an underused dialysis modality in the United States, even though it provides an efficient and probably cost-effective way to provide more frequent or longer dialysis. With the advent of newer home HD systems that are easier for patients to learn, use, and maintain, patient and provider interest in home HD is increasing. Although barriers for providers are similar to those for peritoneal dialysis, home HD requires more extensive patient training, nursing education, and infrastructure support in order to maintain a successful program. In addition, because many physicians and patients do not have experience with home HD, reluctance to start home HD programs is widespread. This in-depth review describes barriers to home HD, focusing on patients, individual physicians and practices, and dialysis facilities, and offers suggestions for how to overcome these barriers and establish a successful home HD program. PMID:23037981

  2. Mental health care for irregular migrants in Europe: Barriers and how they are overcome

    PubMed Central

    2012-01-01

    Background Irregular migrants (IMs) are exposed to a wide range of risk factors for developing mental health problems. However, little is known about whether and how they receive mental health care across European countries. The aims of this study were (1) to identify barriers to mental health care for IMs, and (2) to explore ways by which these barriers are overcome in practice. Methods Data from semi-structured interviews with 25 experts in the field of mental health care for IMs in the capital cities of 14 European countries were analysed using thematic analysis. Results Experts reported a range of barriers to mental health care for IMs. These include the absence of legal entitlements to health care in some countries or a lack of awareness of such entitlements, administrative obstacles, a shortage of culturally sensitive care, the complexity of the social needs of IMs, and their fear of being reported and deported. These barriers can be partly overcome by networks of committed professionals and supportive services. NGOs have become important initial points of contact for IMs, providing mental health care themselves or referring IMs to other suitable services. However, these services are often confronted with the ethical dilemma of either acting according to the legislation and institutional rules or providing care for humanitarian reasons, which involves the risk of acting illegally and providing care without authorisation. Conclusions Even in countries where access to health care is legally possible for IMs, various other barriers remain. Some of these are common to all migrants, whilst others are specific for IMs. Attempts at improving mental health care for IMs should consider barriers beyond legal entitlement, including communicating information about entitlement to mental health care professionals and patients, providing culturally sensitive care and ensuring sufficient resources. PMID:22607386

  3. "Closing the Loop": Overcoming barriers to locally sourcing food in Fort Collins, Colorado

    NASA Astrophysics Data System (ADS)

    DeMets, C. M.

    2012-12-01

    Environmental sustainability has become a focal point for many communities in recent years, and restaurants are seeking creative ways to become more sustainable. As many chefs realize, sourcing food locally is an important step towards sustainability and towards building a healthy, resilient community. Review of literature on sustainability in restaurants and the local food movement revealed that chefs face many barriers to sourcing their food locally, but that there are also many solutions for overcoming these barriers that chefs are in the early stages of exploring. Therefore, the purpose of this research is to identify barriers to local sourcing and investigate how some restaurants are working to overcome those barriers in the city of Fort Collins, Colorado. To do this, interviews were conducted with four subjects who guide purchasing decisions for restaurants in Fort Collins. Two of these restaurants have created successful solutions and are able to source most of their food locally. The other two are interested in and working towards sourcing locally but have not yet been able to overcome barriers, and therefore only source a few local items. Findings show that there are four barriers and nine solutions commonly identified by each of the subjects. The research found differences between those who source most of their food locally and those who have not made as much progress in local sourcing. Based on these results, two solution flowcharts were created, one for primary barriers and one for secondary barriers, for restaurants to assess where they are in the local food chain and how they can more successfully source food locally. As there are few explicit connections between this research question and climate change, it is important to consider the implicit connections that motivate and justify this research. The question of whether or not greenhouse gas emissions are lower for locally sourced food is a topic of much debate, and while there are major developments

  4. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    PubMed Central

    Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. Results Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. Conclusions A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders. PMID:26262941

  5. Geothermal(Ground-Source)Heat Pumps: Market Status, Barriers to Adoption, and Actions to Overcome Barriers

    SciTech Connect

    Hughes, Patrick

    2008-12-01

    More effective stewardship of our resources contributes to the security, environmental sustainability, and economic well-being of the nation. Buildings present one of the best opportunities to economically reduce energy consumption and limit greenhouse gas emissions. Geothermal heat pumps (GHPs), sometimes called ground-source heat pumps, have been proven capable of producing large reductions in energy use and peak demand in buildings. However, GHPs have received little attention at the policy level as an important component of a national strategy. Have policymakers mistakenly overlooked GHPs, or are GHPs simply unable to make a major contribution to the national goals for various reasons? This brief study was undertaken at DOE's request to address this conundrum. The scope of the study includes determining the status of global GHP markets and the status of the GHP industry and technology in the United States, assembling previous estimates of GHP energy savings potential, identifying key barriers to application of GHPs, and identifying actions that could accelerate market adoption of GHPs. The findings are documented in this report along with conclusions and recommendations.

  6. Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers.

    PubMed

    McErlean, Emma M; McCrudden, Cian M; McCarthy, Helen O

    2016-09-01

    The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration. PMID:27582234

  7. Overcoming barriers to high performance seismic design using lessons learned from the green building industry

    NASA Astrophysics Data System (ADS)

    Glezil, Dorothy

    NEHRP's Provisions today currently governing conventional seismic resistant design. These provisions, though they ensure the life-safety of building occupants, extensive damage and economic losses may still occur in the structures. This minimum performance can be enhanced using the Performance-Based Earthquake Engineering methodology and passive control systems like base isolation and energy dissipation systems. Even though these technologies and the PBEE methodology are effective reducing economic losses and fatalities during earthquakes, getting them implemented into seismic resistant design has been challenging. One of the many barriers to their implementation has been their upfront costs. The green building community has faced some of the same challenges that the high performance seismic design community currently faces. The goal of this thesis is to draw on the success of the green building industry to provide recommendations that may be used overcome the barriers that high performance seismic design (HPSD) is currently facing.

  8. Overcoming Codes and Standards Barriers to Innovations in Building Energy Efficiency

    SciTech Connect

    Cole, Pamala C.; Gilbride, Theresa L.

    2015-02-15

    In this journal article, the authors discuss approaches to overcoming building code barriers to energy-efficiency innovations in home construction. Building codes have been a highly motivational force for increasing the energy efficiency of new homes in the United States in recent years. But as quickly as the codes seem to be changing, new products are coming to the market at an even more rapid pace, sometimes offering approaches and construction techniques unthought of when the current code was first proposed, which might have been several years before its adoption by various jurisdictions. Due to this delay, the codes themselves can become barriers to innovations that might otherwise be helping to further increase the efficiency, comfort, health or durability of new homes. . The U.S. Department of Energy’s Building America, a program dedicated to improving the energy efficiency of America’s housing stock through research and education, is working with the U.S. housing industry through its research teams to help builders identify and remove code barriers to innovation in the home construction industry. The article addresses several approaches that builders use to achieve approval for innovative building techniques when code barriers appear to exist.

  9. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials. PMID:26192479

  10. Overcoming Barriers: Adolescents’ Experiences Using a Mobile Phone Dietary Assessment App

    PubMed Central

    Svensson, Åsa; Magnusson, Maria

    2016-01-01

    Background The use of new technology has the potential to increase participation rates in dietary studies and improve the validity of collected dietary data. However, to evaluate the usability of developed dietary methods, qualitative studies of participants’ experiences and perceptions are needed. Objective To explore adolescents’ experiences using a newly developed mobile phone dietary assessment app, with a focus on factors that could affect their recording of dietary intake. Methods Focus group interviews were conducted with 75 participants who had used a newly developed mobile phone dietary assessment app in a quantitative evaluation study. The interviews were analyzed using qualitative content analysis and the theoretical framework of Self Determination Theory was applied. Results The adolescents’ use of the mobile phone dietary assessment app was characterized by their struggle to overcome several perceived barriers. Facilitators that helped adolescents complete the method were also identified. Motivation was found to be an important facilitator, and intrinsically motivated participants completed the method because they found it fun to use. The autonomous extrinsically motivated participants completed the method for the greater good, in order to contribute to the study. The controlled extrinsically motivated participants completed the method to get a reward or avoid punishment. Amotivated participants did not complete the method. More motivated participants were assumed to be more able to overcome barriers and needed less facilitators. Conclusions Future studies that examine the recording of food intake should include systematic efforts that aim to minimize identified barriers and promote identified facilitators. Further research should specifically aim at studying methods for (and effects of) increasing intrinsic motivation by supporting autonomy, competence, and relatedness among adolescents asked to participate in dietary studies. PMID:27473462

  11. Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection.

    PubMed

    Namvar, Ali; Bolhassani, Azam; Khairkhah, Niloofardokht; Motevalli, Fatemeh

    2015-07-01

    Delivery of the macromolecules including DNA, miRNA, and antisense oligonucleotides is typically mediated by carriers due to the large size and negative charge. Different physical (e.g., gene gun or electroporation), and chemical (e.g., cationic polymer or lipid) vectors have been already used to improve the efficiency of gene transfer. Polymer-based DNA delivery systems have attracted special interest, in particular via intravenous injection with many intra- and extracellular barriers. The recent progress has shown that stimuli-responsive polymers entitled as multifunctional nucleic acid vehicles can act to target specific cells. These nonviral carriers are classified by the type of stimulus including reduction potential, pH, and temperature. Generally, the physicochemical characterization of DNA-polymer complexes is critical to enhance the transfection potency via protection of DNA from nuclease digestion, endosomal escape, and nuclear localization. The successful clinical applications will depend on an exact insight of barriers in gene delivery and development of carriers overcoming these barriers. Consequently, improvement of novel cationic polymers with low toxicity and effective for biomedical use has attracted a great attention in gene therapy. This article summarizes the main physicochemical and biological properties of polyplexes describing their gene transfection behavior, in vitro and in vivo. In this line, the relative efficiencies of various cationic polymers are compared. PMID:25761628

  12. Barriers to the Uptake of Human-based Test Methods, and How to Overcome Them.

    PubMed

    Archibald, Kathy; Drake, Tamara; Coleman, Robert

    2015-11-01

    Although there is growing concern as to the questionable value of animal-based methods for determining the safety and efficacy of new medicines, which has in turn led to many groups developing innovative human-based methods, there are many barriers to their adoption for regulatory submissions. The reasons for this are various, and include a lack of confidence that the available human-based methods, be they in vivo, in silico or in vitro, can be sufficiently predictive of clinical outcomes. However, this is not the only problem: the issue of validation presents a serious impediment to progress, a particularly frustrating situation, in view of the fact that the existing animal-based methods have never themselves been formally validated. Superimposed upon this is the issue of regulatory requirements, where, although regulators may be willing to accept non-animal approaches in place of particular animal tests, nowhere is this explicitly stated in their guidelines. Such problems are far from trivial, and represent major hurdles to be overcome. In addition, there are a range of other barriers, real or self-imposed, that are hindering a more-predictive approach to establishing a new drug's clinical safety and efficacy profiles. Some of these barriers are identified, and ways forward are suggested. PMID:26551287

  13. Teams, tribes and patient safety: overcoming barriers to effective teamwork in healthcare.

    PubMed

    Weller, Jennifer; Boyd, Matt; Cumin, David

    2014-03-01

    Modern healthcare is delivered by multidisciplinary, distributed healthcare teams who rely on effective teamwork and communication to ensure effective and safe patient care. However, we know that there is an unacceptable rate of unintended patient harm, and much of this is attributed to failures in communication between health professionals. The extensive literature on teams has identified shared mental models, mutual respect and trust and closed-loop communication as the underpinning conditions required for effective teams. However, a number of challenges exist in the healthcare environment. We explore these in a framework of educational, psychological and organisational challenges to the development of effective healthcare teams. Educational interventions can promote a better understanding of the principles of teamwork, help staff understand each other's roles and perspectives, and help develop specific communication strategies, but may not be sufficient on their own. Psychological barriers, such as professional silos and hierarchies, and organisational barriers such as geographically distributed teams, can increase the chance of communication failures with the potential for patient harm. We propose a seven-step plan to overcome the barriers to effective team communication that incorporates education, psychological and organisational strategies. Recent evidence suggests that improvement in teamwork in healthcare can lead to significant gains in patient safety, measured against efficiency of care, complication rate and mortality. Interventions to improve teamwork in healthcare may be the next major advance in patient outcomes. PMID:24398594

  14. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, Pamala C.; Halverson, Mark A.

    2013-09-01

    The U.S. Department of Energy’s (DOE) Building America program implemented a new Codes and Standards Innovation (CSI) Team in 2013. The Team’s mission is to assist Building America (BA) research teams and partners in identifying and resolving conflicts between Building America innovations and the various codes and standards that govern the construction of residences. A CSI Roadmap was completed in September, 2013. This guidance document was prepared using the information in the CSI Roadmap to provide BA research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America (BA) innovations arising in and/or stemming from codes, standards, and rating methods. For more information on the BA CSI team, please email: CSITeam@pnnl.gov

  15. Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

    PubMed

    Almajed, Faisal S; Forsythe, Stephen J

    2016-01-01

    Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly. PMID:26616163

  16. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption.

    PubMed

    Sheng, Jianyong; Han, Limei; Qin, Jing; Ru, Ge; Li, Ruixiang; Wu, Lihong; Cui, Dongqi; Yang, Pei; He, Yuwei; Wang, Jianxin

    2015-07-22

    Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics. PMID:26111015

  17. Overcoming barriers to the implementation of a pharmacy bar code scanning system for medication dispensing: a case study.

    PubMed

    Nanji, Karen C; Cina, Jennifer; Patel, Nirali; Churchill, William; Gandhi, Tejal K; Poon, Eric G

    2009-01-01

    Technology has great potential to reduce medication errors in hospitals. This case report describes barriers to, and facilitators of, the implementation of a pharmacy bar code scanning system to reduce medication dispensing errors at a large academic medical center. Ten pharmacy staff were interviewed about their experiences during the implementation. Interview notes were iteratively reviewed to identify common themes. The authors identified three main barriers to pharmacy bar code scanning system implementation: process (training requirements and process flow issues), technology (hardware, software, and the role of vendors), and resistance (communication issues, changing roles, and negative perceptions about technology). The authors also identified strategies to overcome these barriers. Adequate training, continuous improvement, and adaptation of workflow to address one's own needs mitigated process barriers. Ongoing vendor involvement, acknowledgment of technology limitations, and attempts to address them were crucial in overcoming technology barriers. Staff resistance was addressed through clear communication, identifying champions, emphasizing new information provided by the system, and facilitating collaboration. PMID:19567797

  18. Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

    PubMed

    Linde, Peter G; Archdeacon, Patrick; Breyer, Matthew D; Ibrahim, Tod; Inrig, Jula K; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y; Roy-Chaudhury, Prabir; Sloand, James A; Meyer, Rachel; Smith, Kimberly A; Snook, Jennifer; West, Melissa; Falk, Ronald J

    2016-07-01

    Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology. PMID:27127187

  19. Creating sustainable local health information exchanges: can barriers to stakeholder participation be overcome?

    PubMed

    Grossman, Joy M; Kushner, Kathryn L; November, Elizabeth A

    2008-02-01

    Local health information exchanges (HIEs) hold the promise of collecting patient clinical data across sites of care to provide more complete and timely information for treatment, as well as supporting quality improvement and reporting, public health activities, and clinical research. Findings from a study of stakeholder perspectives on participation in four HIEs by the Center for Studying Health System Change (HSC) and the National Institute for Health Care Management (NIHCM) Foundation suggest, however, that barriers to achieving data exchange remain high. Concerns about loss of competitive advantage and data misuse impede provider and health plan willingness to contribute patient data. Additionally, uncertainty about who benefits from HIEs is affecting stakeholder willingness to fund the exchanges. The more mature exchanges--Cincinnati-based HealthBridge and the Indiana Health Information Exchange (IHIE)--have achieved some viability by meeting a specific business need--more efficient delivery of hospital test results to physicians. The newer exchanges--CareSpark, serving northeast Tennessee and southwest Virginia, and the Tampa Bay Regional Health Information Organization (RHIO)--have struggled to identify and finance initial services without a similar critical mass of hospital participation. While narrow data exchange efforts that improve transaction efficiency may be a pragmatic first step to overcome barriers to stakeholder participation, expanding HIEs to achieve the broad-based data exchange necessary for quality reporting and pay-for-performance (P4P) activities raises more challenges. PMID:18496926

  20. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery.

    PubMed

    Wong, Tin Wui

    2014-11-10

    Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described. PMID:24801250

  1. Understanding and Overcoming Barriers to Upper Limb Surgical Reconstruction After Tetraplegia: The Need for Interdisciplinary Collaboration.

    PubMed

    Punj, Vandana; Curtin, Catherine

    2016-06-01

    There are approximately 300,000 persons with spinal cord injury living in the United States, and nearly 60% of these persons have suffered tetraplegia with resultant alterations in body function, activity, and therefore participation. Restoring hand function can improve independence, and various studies have shown that persons with tetraplegia rate restoration of arm and hand function higher than bowel and bladder control, walking, or sexuality. There are conservative options to improve upper limb function in this population (eg, orthoses, neuroprostheses). Surgical interventions are also available, and 70% of surgical patients report satisfaction and improvement in various activities of daily living after surgery to restore arm and hand function. Despite these positive surgical outcomes, <10% of the eligible population of 60% to 70% undergo tendon transfer surgery to restore function. Underutilization of surgical interventions can be explained by population-, provider-, and health care systems-specific barriers. With further education of providers and patients and team building across disciplines these barriers can be overcome, ultimately leading to reduced disability and improved quality of life for persons with tetraplegia. PMID:27233595

  2. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

    PubMed

    Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane; Song, Eric; Choi, Won Kyu; Boyle, Michael P; Morales, Marcelo M; Hanes, Justin; Suk, Jung Soo

    2015-07-14

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration. PMID:26124127

  3. Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report.

    PubMed

    Harle, Christopher A; Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried Of; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

    2016-01-01

    In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden. PMID:26159464

  4. Evidence for Health II: Overcoming barriers to using evidence in policy and practice.

    PubMed

    Andermann, Anne; Pang, Tikki; Newton, John N; Davis, Adrian; Panisset, Ulysses

    2016-01-01

    Even the highest quality evidence will have little impact unless it is incorporated into decision-making for health. It is therefore critical to overcome the many barriers to using evidence in decision-making, including (1) missing the window of opportunity, (2) knowledge gaps and uncertainty, (3) controversy, irrelevant and conflicting evidence, as well as (4) vested interests and conflicts of interest. While this is certainly not a comprehensive list, it covers a number of main themes discussed in the knowledge translation literature on this topic, and better understanding these barriers can help readers of the evidence to be more savvy knowledge users and help researchers overcome challenges to getting their evidence into practice. Thus, the first step in being able to use research evidence for improving population health is ensuring that the evidence is available at the right time and in the right format and language so that knowledge users can take the evidence into consideration alongside a multitude of other factors that also influence decision-making. The sheer volume of scientific publications makes it difficult to find the evidence that can actually help inform decisions for health. Policymakers, especially in low- and middle-income countries, require context-specific evidence to ensure local relevance. Knowledge synthesis and dissemination of policy-relevant local evidence is important, but it is still not enough. There are times when the interpretation of the evidence leads to various controversies and disagreements, which act as barriers to the uptake of evidence. Research evidence can also be influenced and misused for various aims and agendas. It is therefore important to ensure that any new evidence comes from reliable sources and is interpreted in light of the overall body of scientific literature. It is not enough to simply produce evidence, nor even to synthesize and package evidence into a more user-friendly format. Particularly at the policy

  5. Overcoming Barriers to Eye Care: Patient Response to a Medical Social Worker in a Glaucoma Service.

    PubMed

    Fudemberg, Scott J; Amarasekera, Dilru C; Silverstein, Marlee H; Linder, Kathryn M; Heffner, Paul; Hark, Lisa A; Waisbourd, Michael

    2016-08-01

    This paper investigates the patient response to a medical social worker in a glaucoma clinic. The literature suggests that medical social workers are effective in a variety of health care settings, yet the efficacy of a medical social worker in an adult ophthalmic setting has not been studied. We present the results of a retrospective chart review of 50 patients with glaucoma referred to a medical social worker between January 5, 2015 and June 31, 2015 in an outpatient clinic of an urban eye hospital. Clinical and demographic data, as well as the data from a quality of care questionnaire, were collected for each patient. Patients rated their interaction with the medical social worker as highly positive (mean = 4.75, 5-point Likert scale), and nearly 90 % of patients expressed interest in future contact with the social worker. Additionally, most patients reported that the social worker resolved the issues they were facing (61.1 %), supported them in seeing their ophthalmologist (70.6 %), and helped them to manage their glaucoma (69.7 %). Reported barriers to glaucoma care were emotional distress; cost of office visits and medications; lack of medical insurance; transportation; poor medication adherence; impairment of daily activities; follow-up adherence; and language. As vision loss from glaucoma is irreversible, it is important to detect and treat patients at early stages of the disease. Therefore, it is imperative for patients to regularly visit their eye care providers and adhere to treatment and follow-up recommendations. This study suggests that a medical social worker could play a pivotal role in helping patients with glaucoma overcome barriers to treatment and facilitate disease management. PMID:26860278

  6. Nano-carrier systems: Strategies to overcome the mucus gel barrier.

    PubMed

    Dünnhaupt, S; Kammona, O; Waldner, C; Kiparissides, C; Bernkop-Schnürch, A

    2015-10-01

    The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal, buccal and pulmonary mucus layer without destroying them. It focuses on the one hand on strategies to improve the mucus permeation behavior of particles and on the other hand on systems avoiding the back-diffusion of particles out of the mucus gel layer. Nanocarriers with improved mucus permeation behavior either exhibit a high density of positive and negative charges, bearing mucolytic enzymes such as papain and bromelain on their surface or display a slippery surface due to PEG-ylation. Furthermore, self-nanoemulsifying-drug-delivery-systems (SNEDDS) turned out to exhibit comparatively high mucus permeating properties. Strategies in order to avoid back-diffusion are based on thiolated polymers reacting to a higher extent with cysteine subunits of the mucus at pH 7 in deeper mucus regions than at pH 5 being prevalent in luminal mucus regions of the intestinal and vaginal mucosa. Furthermore, particles changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising carriers. The summarized knowledge should provide a good starting point for further developments in this field. PMID:25712487

  7. Lung Gene Therapy with Highly Compacted DNA Nanoparticles that Overcome the Mucus Barrier

    PubMed Central

    Suk, Jung Soo; Kim, Anthony J.; Trehan, Kanika; Schneider, Craig S.; Cebotaru, Liudmila; Woodward, Owen M.; Boylan, Nicholas J.; Boyle, Michael P.; Lai, Samuel K.; Guggino, William B.; Hanes, Justin

    2014-01-01

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  8. Adenovirus i-Leader Truncation Bioselected Against Cancer-associated Fibroblasts to Overcome Tumor Stromal Barriers

    PubMed Central

    Puig-Saus, Cristina; Gros, Alena; Alemany, Ramon; Cascalló, Manel

    2012-01-01

    Tumor-associated stromal cells constitute a major hurdle in the antitumor efficacy with oncolytic adenoviruses. To overcome this biological barrier, an in vitro bioselection of a mutagenized AdwtRGD stock in human cancer-associated fibroblasts (CAFs) was performed. Several rounds of harvest at early cytopathic effect (CPE) followed by plaque isolation led us to identify one mutant with large plaque phenotype, enhanced release in CAFs and enhanced cytotoxicity in CAF and several tumor cell lines. Whole genome sequencing and functional mapping identified the truncation of the last 17 amino acids in C-terminal end of the i-leader protein as the mutation responsible for this phenotype. Similar mutations have been previously isolated in two independent bioselection processes in tumor cell lines. Importantly, our results establish the enhanced antitumor activity in vivo of the i-leader C-terminal truncated mutants, especially in a desmotic fibroblast-embedded lung carcinoma model in mice. These results indicate that the i-leader truncation represents a promising trait to improve virotherapy with oncolytic adenoviruses. PMID:21863000

  9. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier.

    PubMed

    Suk, Jung Soo; Kim, Anthony J; Trehan, Kanika; Schneider, Craig S; Cebotaru, Liudmila; Woodward, Owen M; Boylan, Nicholas J; Boyle, Michael P; Lai, Samuel K; Guggino, William B; Hanes, Justin

    2014-03-28

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in the mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  10. Helping Our Most Vulnerable Families Overcome Barriers to Work and Achieve Financial Success. KIDS COUNT 2005 Essay

    ERIC Educational Resources Information Center

    Annie E. Casey Foundation, 2005

    2005-01-01

    This essay, taken from the 2005 KIDS COUNT Data Book, examines four employment barriers that policymakers and others consider among the most difficult to overcome: substance abuse, domestic violence, a history of incarceration, and depression. These burdens can diminish a person's motivation and ability to find work. Furthermore, they can make it…

  11. Overcoming Relationship-Initiation Barriers: The Impact of a Computer-Dating System on Sex Role, Shyness, and Appearance Inhibitions.

    ERIC Educational Resources Information Center

    Scharlott, Bradford W.; Christ, William G.

    1995-01-01

    A survey of the users of an online computer-mediated matchmaking service showed that their communication patterns and objectives varied by their sex, shyness level, and appearance. Intrinsic aspects of this system helped some users overcome relationship-initiation barriers rooted in sex role, shyness, and appearance inhibitions. (Author)

  12. Translating Research to Practice: Overcoming Barriers to Implementing Effective Off-Campus Party Intervention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on overcoming barriers in implementing effective off-campus party intervention. This issue contains the following articles: (1) Confronting the Problems Associated With Off-Campus Parties With Evidence-Based Strategies (John D. Clapp); (2) Overview of Research on Effective Off-Campus Party…

  13. All Health Plans Need CLAMS: Culturally and Linguistically Appropriate Materials for Diverse Populations Can Overcome Language Barriers to Effective Treatment.

    ERIC Educational Resources Information Center

    Smith, Sandra; Gonzales, Virginia

    2000-01-01

    CLAMs are "Culturally and Linguistically Appropriate Materials" designed for diverse populations to help them overcome language barriers to effective treatment. The demographic shift underway in the United States is making the country more linguistically diverse. Health plans need to accommodate this shift, because without information patients…

  14. Overcoming the Fundamental Barrier Thickness Limits of Ferroelectric Tunnel Junctions through BaTiO3/SrTiO3 Composite Barriers.

    PubMed

    Wang, Lingfei; Cho, Myung Rae; Shin, Yeong Jae; Kim, Jeong Rae; Das, Saikat; Yoon, Jong-Gul; Chung, Jin-Seok; Noh, Tae Won

    2016-06-01

    Ferroelectric tunnel junctions (FTJs) have attracted increasing research interest as a promising candidate for nonvolatile memories. Recently, significant enhancements of tunneling electroresistance (TER) have been realized through modifications of electrode materials. However, direct control of the FTJ performance through modifying the tunneling barrier has not been adequately explored. Here, adding a new direction to FTJ research, we fabricated FTJs with BaTiO3 single barriers (SB-FTJs) and BaTiO3/SrTiO3 composite barriers (CB-FTJs) and reported a systematic study of FTJ performances by varying the barrier thicknesses and compositions. For the SB-FTJs, the TER is limited by pronounced leakage current for ultrathin barriers and extremely small tunneling current for thick barriers. For the CB-FTJs, the extra SrTiO3 barrier provides an additional degree of freedom to modulate the barrier potential and tunneling behavior. The resultant high tunability can be utilized to overcome the barrier thickness limits and enhance the overall CB-FTJ performances beyond those of SB-FTJ. Our results reveal a new paradigm to manipulate the FTJs through designing multilayer tunneling barriers with hybrid functionalities. PMID:27195918

  15. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier.

    PubMed

    Pereira de Sousa, Irene; Cattoz, Beatrice; Wilcox, Matthew D; Griffiths, Peter C; Dalgliesh, Robert; Rogers, Sarah; Bernkop-Schnürch, Andreas

    2015-11-01

    The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems. PMID:25661320

  16. Overcoming the Meter Barrier and The Formation of Systems with Tightly-packed Inner Planets (STIPs)

    NASA Astrophysics Data System (ADS)

    Boley, Aaron C.; Morris, Melissa A.; Ford, Eric B.

    2014-11-01

    The Kepler space mission has revealed numerous planetary types and systems, shaping our understanding of planet formation. Among the quickly-growing data is a subclass of multi-planet configurations referred to as Systems with Tightly-packed Inner Planets (STIPs). Their large abundance (>10% of stars) suggests that they are one of the principal outcomes of planet formation. The prototype STIP is Kepler-11, which hosts six known transiting planets, five of which have measured masses in the super-Earth and mini-Neptune regimes. The known planetary orbits in this system are spaced between a=0.09 and 0.47 AU, with small eccentricities and mutual inclinations. The lack of low-order mean motion resonances among planets in STIPs suggests that migration may have not played a dominant role in placing all of these planets on short orbital periods. While the formation of massive planetary systems on the hot side of the water ice line may be difficult to reconcile under the current paradigm of planet formation, we must explore whether many STIP planets formed by and large in situ. We discuss an overlooked mechanism that may allow the in situ formation of planetary systems on very short orbital periods. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can reduce net evaporation of incoming material, which could promote collisions between partially molten solids, allowing rapid growth and overcoming the classic meter barrier.

  17. Overcoming Barriers to Implementation of Evidence-Based Practice Concepts in Athletic Training Education: Perceptions of Select Educators

    PubMed Central

    Manspeaker, Sarah; Van Lunen, Bonnie

    2011-01-01

    Context: The need to include evidence-based practice (EBP) concepts in entry-level athletic training education is evident as the profession transitions toward using evidence to inform clinical decision making. Objective: To evaluate athletic training educators' experience with implementation of EBP concepts in Commission on Accreditation of Athletic Training Education (CAATE)-accredited entry-level athletic training education programs in reference to educational barriers and strategies for overcoming these barriers. Design: Qualitative interviews of emergent design with grounded theory. Setting: Undergraduate CAATE-accredited athletic training education programs. Patients or Other Participants: Eleven educators (3 men, 8 women). The average number of years teaching was 14.73 ± 7.06. Data Collection and Analysis: Interviews were conducted to evaluate perceived barriers and strategies for overcoming these barriers to implementation of evidence-based concepts in the curriculum. Interviews were explored qualitatively through open and axial coding. Established themes and categories were triangulated and member checked to determine trustworthiness. Results: Educators identified 3 categories of need for EBP instruction: respect for the athletic training profession, use of EBP as part of the decision-making toolbox, and third-party reimbursement. Barriers to incorporating EBP concepts included time, role strain, knowledge, and the gap between clinical and educational practices. Suggested strategies for surmounting barriers included identifying a starting point for inclusion and approaching inclusion from a faculty perspective. Conclusions: Educators must transition toward instruction of EBP, regardless of barriers present in their academic programs, in order to maintain progress with other health professions' clinical practices and educational standards. Because today's students are tomorrow's clinicians, we need to include EBP concepts in entry-level education to promote

  18. Can Self-Prediction Overcome Barriers to Hepatitis B Vaccination? A Randomized Controlled Trial

    PubMed Central

    Cox, Anthony D.; Cox, Dena; Cyrier, Rosalie; Graham-Dotson, Yolanda; Zimet, Gregory D.

    2011-01-01

    Objective Hepatitis B virus (HBV) infection remains a serious public health problem, due in part to low vaccination rates among high-risk adults, many of whom decline vaccination because of barriers such as perceived inconvenience or discomfort. This study evaluates the efficacy of a self-prediction intervention to increase HBV vaccination rates among high-risk adults. Method Randomized controlled trial of 1175 adults recruited from three STD clinics in the United States over 28 months. Participants completed an audio-computer-assisted self-interview (A-CASI), which presented information about HBV infection and vaccination, and measured relevant beliefs, behaviors and demographics. Half of participants were assigned randomly to a "self-prediction" intervention, asking them to predict their future acceptance of HBV vaccination. The main outcome measure was subsequent vaccination behavior. Other measures included perceived barriers to HBV vaccination, measured prior to the intervention. Results There was a significant interaction between the intervention and vaccination barriers, indicating the effect of the intervention differed depending on perceived vaccination barriers. Among high-barriers patients, the intervention significantly increased vaccination acceptance. Among low-barrier patients, the intervention did not influence vaccination acceptance. Conclusions The self-prediction intervention significantly increased vaccination acceptance among "high-barriers" patients, who typically have very low vaccination rates. This brief intervention could be a useful tool in increasing vaccine uptake among high-barriers patients. PMID:21875205

  19. Energy management action plan: Developing a strategy for overcoming institutional barriers to municipal energy conservation

    SciTech Connect

    Not Available

    1992-12-31

    Energy offices working to improve efficiency of local government facilities face not only technical tasks, but institutional barriers, such as budget structures that do not reward efficiency, a low awareness of energy issues, and purchasing procedures based only on minimizing initial cost. The bureau, in working to remove such barriers in San Francisco, has identified 37 institutional barriers in areas such as operations & maintenance, purchasing, and facility design; these barriers were then reorganized into three groupings-- policy & attitudes, budget & incentives, and awareness & information-- and mapped. This map shows that the barriers mutually reinforce each other, and that a holistic approach is required for permanent change. The city`s recreation & parks department was used as a model department, and information about facility energy use was compiled into a departmental energy review. Staff interviews showed how barriers affect conservation. The bureau then generated ideas for projects to remove specific barriers and rated them according to potential impact and the resources required to implement them. Four of the six projects selected focused on maintenance staff: a cost- sharing lighting retrofit program, a boiler efficiency program, a departmental energy tracking system, and a budgetary incentive program for conservation. The other two projects are city-wide: promotion of a new term contract supplying energy-efficient light materials, and publication/distribution of ENERGY NEWS newsletter. A general methodology, the EMAP Strategy Guide, has been created to assist other energy offices in developing EMAPs.

  20. Principles of nanoparticle design for overcoming biological barriers to drug delivery

    PubMed Central

    Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

    2016-01-01

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

  1. Overcoming Career Barriers: A Model of Cognitive and Emotional Processes for Realistic Appraisal and Constructive Coping.

    ERIC Educational Resources Information Center

    London, Manuel

    1997-01-01

    A model of reactions to career barriers explains how people differ in appraising situations and establishing coping strategies based on a mix of emotional and cognitive processes, appraisal styles, and predispositions. (SK)

  2. Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

    PubMed Central

    Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

    2014-01-01

    Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided

  3. Ground-Source Heat Pumps. Overview of Market Status, Barriers to Adoption, and Options for Overcoming Barriers

    SciTech Connect

    Goetzler, William; Zogg, Robert; Lisle, Heather; Burgos, Javier

    2009-02-03

    February 2009 final report submitted to DOE by Navigant Consulting, Inc. This report summarizes the status of ground-source heat pump (GSHP) technology and market penetration globally, estimates the energy saving potential of GSHPs in the U.S., identifies key market barriers that are inhibiting wider market adoption of GSHPs, and recommends initiatives that can be implemented or facilitated by the DOE to accelerate market adoption.

  4. Writing for Publication: An Intervention to Overcome Barriers to Scholarly Writing

    ERIC Educational Resources Information Center

    Kapp, C. A.; Albertyn, R. M.; Frick, B. L.

    2011-01-01

    Academics are actively encouraged to disseminate new knowledge to the scientific community by publishing in scholarly journals. External and internal barriers to writing, however, prevent many authors from writing for publication. This article gives an account of an intervention to provide hands-on coaching to inexperienced academic authors.…

  5. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    ERIC Educational Resources Information Center

    Justice, Laura M.; Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their…

  6. Overcoming Barriers to the Sexual Expression of Women with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Stinson, Jennifer; Christian, LeeAnn; Dotson, Lori Ann

    2002-01-01

    This article discusses barriers to sexual fulfillment faced by women with developmental disabilities, including: access to gynecological healthcare, limited choices regarding reproductive issues, lack of sex education, and prevailing negative stereotypes that affect the way women are viewed by others and the way they view themselves.…

  7. Strategies for Overcoming Barriers to Training and Education for Canadians with Disabilities. Lessons in Learning

    ERIC Educational Resources Information Center

    Canadian Council on Learning, 2009

    2009-01-01

    If stronger skills and more education are key to greater labour force participation, then it is important to identify critical barriers to education and training for Canadians with disabilities. In 2008, the Canadian Council on Learning's Adult Learning Knowledge Centre funded a "Community Outreach Initiative for Learner's with Disabilities" that…

  8. Learning from the Best: Overcoming Barriers to Reforms-Based Elementary Science Teaching

    ERIC Educational Resources Information Center

    Banchi, Heather May

    2009-01-01

    This study explored the characteristics of elementary science teachers who employ reforms-based practices. Particular attention was paid to the consistency of teachers' practices and their beliefs, the impact of professional development experiences on practices, and how teachers mitigated barriers to reforms-based instruction. Understanding how…

  9. Overcoming Barriers to the Market Access of Biosimilars in the European Union: The Case of Biosimilar Monoclonal Antibodies

    PubMed Central

    Moorkens, Evelien; Jonker-Exler, Clara; Huys, Isabelle; Declerck, Paul; Simoens, Steven; Vulto, Arnold G.

    2016-01-01

    Background: In 2014, six of the top ten blockbuster medicines were monoclonal antibodies. This multibillion-dollar market with expiring patents is the main driver for the development of biosimilar mAbs. With the ever-increasing cost of healthcare and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing costs for medication and increasing patient access to treatment. Objectives: The aim of this study is to identify and describe the barriers to market access of biosimilar mAbs in the European Union and to analyze how these barriers could be overcome. Methods: A narrative literature review was carried out using the databases PubMed, Embase, and EconLit. Studies were published in English or Dutch. Additionally, the reference list of the articles was checked for relevant studies. Articles and conference papers known to the authors were included as well. Articles were also identified by searching on the website of the Generics and Biosimilars Initiative (GaBI) journal. Results: Six barriers were identified based on available literature: The manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator's reach. These six barriers are presented as a possible framework to study the market access of biosimilar mAbs. Based on the literature search, recommendations can be made to overcome these barriers: (i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing (ii) gain experience with the regulatory process and establish alignment between stakeholders (iii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU (iv) create demand-side policies, disseminate objective information (v) change attitude toward biosimilar switching/substitution, starting with physician, and patient

  10. ECR heating power modulation as a means to ease the overcoming of the radiation barrier in fusion devices

    SciTech Connect

    Morozov, D. Kh.; Pshenov, A. A.; Mineev, A. B.

    2010-06-15

    A method is proposed to ease the overcoming of the impurity radiation barrier during current drive in tokamaks, as well as in alternative fusion and plasmochemical systems with ECR plasma heating. The method is based on the fact that the dependence of the ionization rate on the electron temperature is strongly nonlinear and the dependence of the recombination rate on the latter is weaker. The result is that, during temperature oscillations, the effective temperature for ionization-recombination processes is higher than that in a steady state, so the ionization equilibrium is shifted and strongly emitting ions are stripped more rapidly. Thereby, ECR plasma heating in the initial discharge stage can be made more efficient by modulating the heating power at a low frequency. The evolution of the electron temperature in a homogeneous hydrogen plasma with a carbon impurity and in small ISX-scale tokamaks is simulated numerically, as well as the evolution of the electron and ion temperatures and of the current during discharge startup in the ITER device. Numerical simulations of the effect of modulation of the ECR heating power on the rate of heating of nitrogen, oxygen, and argon plasmas were also carried out. The assumption of coronal equilibrium is not used. It is shown that the low-frequency modulation of the heating power can substantially ease the overcoming of the radiation barrier.

  11. A possible mechanism for overcoming the electrostatic barrier against dust growth in protoplanetary disks

    NASA Astrophysics Data System (ADS)

    Akimkin, V. V.

    2015-08-01

    The coagulation of dust particles under the conditions in protoplanetary disks is investigated. The study focuses on the repulsive electrostatic barrier against growth of charged dust grains. Taking into account the photoelectric effect leads to the appearance of a layer at intermediate heights where the dust has a close to zero charge, enabling the dust grains to grow efficiently. An increase in the coagulation rate comes about not only due to the lowering of the Coulomb barrier, but also because of the electrostatic attraction between grains of opposite charge due to the non-zero dispersion of the near-zero charge. Depending on the efficiency of mixing in the disk, the acceleration of the evolution of the dust in this layer could be important, both in the quasi-stationary stage of the disk evolution and during its dispersal.

  12. Overcoming barriers to the mobilisation of patients in an intensive care unit.

    PubMed

    Dafoe, S; Chapman, M J; Edwards, S; Stiller, K

    2015-11-01

    We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients. PMID:26603796

  13. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

    PubMed Central

    Sun, Yujia; Nien, Chung-Yi; Chen, Kai; Liu, Hsiao-Yun; Johnston, Jeff; Zeitlinger, Julia; Rushlow, Christine

    2015-01-01

    The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner. PMID:26335633

  14. Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence.

    PubMed

    Geoghegan, Jemma L; Senior, Alistair M; Holmes, Edward C

    2016-08-31

    Emerging diseases are a major challenge to public health. Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence. In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission. To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus. We considered the possibility of acquiring the necessary host adaptive mutations both before ('off-the-shelf' emergence) and after ('tailor-made' emergence) a virus is transmitted from a donor to a new recipient species. Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier. In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow. Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species. PMID:27581875

  15. Overcoming barriers in care for the dying: Theoretical analysis of an innovative program model.

    PubMed

    Wallace, Cara L

    2016-08-01

    This article explores barriers to end-of-life (EOL) care (including development of a death denying culture, ongoing perceptions about EOL care, poor communication, delayed access, and benefit restrictions) through the theoretical lens of symbolic interactionism (SI), and applies general systems theory (GST) to a promising practice model appropriate for addressing these barriers. The Compassionate Care program is a practice model designed to bridge gaps in care for the dying and is one example of a program offering concurrent care, a recent focus of evaluation though the Affordable Care Act. Concurrent care involves offering curative care alongside palliative or hospice care. Additionally, the program offers comprehensive case management and online resources to enrollees in a national health plan (Spettell et al., 2009).SI and GST are compatible and interrelated theories that provide a relevant picture of barriers to end-of-life care and a practice model that might evoke change among multiple levels of systems. These theories promote insight into current challenges in EOL care, as well as point to areas of needed research and interventions to address them. The article concludes with implications for policy and practice, and discusses the important role of social work in impacting change within EOL care. PMID:27332743

  16. AccessAbility: Overcoming Information Barriers. Proceedings from the 1987 Spring Meeting of the Nebraska Library Association, College and University Section (Omaha, Nebraska, May 29, 1987).

    ERIC Educational Resources Information Center

    Kacena, Barbara J., Ed.

    Various aspects of the theme, "AccessAbility: Overcoming Information Barriers," are considered in the conference papers collected in this document. They include: (1) "The Library Image: A Barrier to Accessibility" (Janice S. Boyer); (2) "The Educationally Disadvantaged Student: How Can the Library Help?" (Michael Poma and Richard Jehlik); (3)…

  17. Oculocutaneous albinism: identifying and overcoming barriers to vision care in a Nigerian population.

    PubMed

    Udeh, N N; Eze, B I; Onwubiko, S N; Arinze, O C; Onwasigwe, E N; Umeh, R E

    2014-06-01

    To assess eye care service utilization, and identify access barriers in a south-eastern Nigerian albino population. The study was a population-based, cross-sectional survey conducted in Enugu state between August, 2011 and January, 2012. Using the data base of the state's Albino Foundation and tailored awareness creation, persons living with albinism were identified and recruited at two study centres. Data on participants' socio-demographics, perception of vision, visual needs, previous eye examination and or low vision assessment, use of glasses or low vision devices were collected. Reasons for non-utilisation of available vision care services were also obtained. Descriptive and comparative statistics were performed. A p < 0.05 was considered statistically significant. The participants (n = 153; males 70; females 83; sex ratio: 1:1.1) were aged 23.46 + 10.44 SD years (range 6-60 years). Most--95.4 % of the participants had no previous low vision assessment and none--0.0% had used low vision device. Of the participants, 82.4% reported previous eye examination, 33.3% had not used spectacles previously, despite the existing need. Ignorance--88.9% and poor access--8.5% were the main barriers to uptake of vision care services. In Enugu, Nigeria, there is poor awareness and low utilization of vision care services among people with albinism. The identified barriers to vision care access are amenable to awareness creation and logistic change in the provision of appropriate vision care services. PMID:24198136

  18. OVERCOMING THE METER BARRIER AND THE FORMATION OF SYSTEMS WITH TIGHTLY PACKED INNER PLANETS (STIPs)

    SciTech Connect

    Boley, A. C.; Morris, M. A.; Ford, E. B.

    2014-09-10

    We present a solution to the long outstanding meter barrier problem in planet formation theory. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can suppress solid evaporation, and promote collisions between partially molten solids, allowing rapid growth. This process should be ubiquitous in planet-forming disks, which may be evidenced by the abundant class of Systems with Tightly packed Inner Planets discovered by the NASA Kepler Mission.

  19. "Take your own path": minority leaders encountering and overcoming barriers in cultural community centers.

    PubMed

    Flores, Kevin Lynn; Matkin, Gina Sue

    2014-01-01

    Minority leaders face workplace issues not experienced by white leaders including lack of support, discrimination, racism, and stereotyping. The purpose of this study was to explore how racial/ethnic minority leaders encountered and overcame barriers as leaders of cultural community centers. Three racial/ethnic minority executive directors of cultural community centers located in a Midwestern city were interviewed and their responses were hand-coded to develop themes. Six themes emerged from this process: finding "inspiration", "developing thick skin", "stereotypes", "damage from within", "take your path", and "hope". Their stories help us understand the complexities of inter-racial relations in the workplace. PMID:24855809

  20. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways.

    PubMed

    Li, Man; Zhao, Mengnan; Fu, Yao; Li, You; Gong, Tao; Zhang, Zhirong; Sun, Xun

    2016-04-28

    Facing the threat of highly variable virus infection, versatile vaccination systems are urgently needed. Intranasal mRNA vaccination provides a flexible and convenient approach. However, the nasal epithelium remains a major biological barrier to deliver antigens to nasal associated lymphoid tissue (NALT). To address this issue, a potent polymer-based intranasal mRNA vaccination system for HIV-1 treatment was synthesized using cationic cyclodextrin-polyethylenimine 2k conjugate (CP 2k) complexed with anionic mRNA encoding HIV gp120. The delivery vehicle containing CP 2k and mRNA overcame the epithelial barrier by reversibly opening the tight junctions, enhanced the paracellular delivery of mRNA and consequently minimized absorption of toxins in the nasal cavity. Together with the excellent intracellular delivery and prolonged nasal residence time, strong system and mucosal anti-HIV immune responses as well as cytokine productions were achieved with a balanced Th1/Th2/Th17 type. Our study provided the first proof of evidence that cationic polymers can be used as safe and potent intranasal mRNA vaccine carriers to overcome the nasal epithelial barrier. The safe and versatile polymeric delivery system represents a promising vaccination platform for infectious diseases. PMID:26941035

  1. Overcoming barriers to health-care access: A qualitative study among African migrants in Guangzhou, China.

    PubMed

    Lin, Lavinia; Brown, Katherine B; Hall, Brian J; Yu, Fan; Yang, Jingqi; Wang, Jason; Schrock, Joshua M; Bodomo, Adams B; Yang, Ligang; Yang, Bin; Nehl, Eric J; Tucker, Joseph D; Wong, Frank Y

    2016-10-01

    Guangzhou is China's third most populous city, and the region's burgeoning manufacturing economy has attracted many young African businessmen and entrepreneurs to the city. The aims of this study were to examine strategies that African migrants in Guangzhou have adopted in response to health-care barriers, and explore their perceptions of how to address their needs. Twenty-five semi-structured interviews and two focus groups were conducted among African migrants residing in Guangzhou, China. Facing multiple barriers to care, African migrants have adopted a number of suboptimal and unsustainable approaches to access health care. These included: using their Chinese friends or partners as interpreters, self-medicating, using personal connections to medical doctors, and travelling to home countries or countries that offer English-speaking doctors for health care. Health-care providers and health organisations in Guangzhou have not yet acquired sufficient cultural competence to address the needs of African migrants residing in the city. Introducing linguistically and culturally competent health-care services in communities concentrated with African migrants may better serve the population. With the growing international migration to China, it is essential to develop sustainable approaches to improving health-care access for international migrants, particularly those who are marginalised. PMID:26400191

  2. Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy.

    PubMed

    Marshall, Merville C

    2007-08-01

    A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African-American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID:17722663

  3. Overcoming Workplace Barriers: A Focus Group Study Exploring African American Mothers' Needs for Workplace Breastfeeding Support

    PubMed Central

    Johnson, Angela Marie; Kirk, Rosalind; Muzik, Maria

    2015-01-01

    Background Persistent racial disparities in breastfeeding show that African American women breastfeed at the lowest rates. Return to work is a critical breastfeeding barrier for African American women who return to work sooner than other ethnic groups and more often encounter unsupportive work environments. They also face psychosocial burdens that make breastfeeding at work uniquely challenging. Participants share personal struggles with combining paid employment and breastfeeding and suggest workplace and personal support strategies that they believe will help continue breastfeeding after a return to work. Objective To explore current perspectives on ways to support African American mothers' workplace breastfeeding behavior. Methods Pregnant African American women (n = 8), African American mothers of infants (n = 21), and lactation support providers (n = 9) participated in 1 of 6 focus groups in the Greater Detroit area. Each focus group audiotape was transcribed verbatim. Thematic analysis was used to inductively analyze focus group transcripts and field notes. Focus groups explored thoughts, perceptions, and behavior on interventions to support African American women's breastfeeding. Results Participants indicate that they generally believed breastfeeding was a healthy option for the baby; however, paid employment is a critical barrier to successful breastfeeding for which mothers receive little help. Participants felt breastfeeding interventions that support working African American mothers should include education and training for health care professionals, regulation and enforcement of workplace breastfeeding support policies, and support from peers who act as breastfeeding role models. Conclusion Culturally appropriate interventions are needed to support breastfeeding among working African American women. PMID:25714345

  4. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment.

    PubMed

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism--17 of them with autism-specific employment--participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems--problems with organizational and practical process-related aspects of the job entry--most frequently while individuals in non-autism-specific employment mentioned social problems--obstacles concerning communication and human interaction--most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  5. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment

    PubMed Central

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism–17 of them with autism-specific employment–participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems–problems with organizational and practical process-related aspects of the job entry–most frequently while individuals in non-autism-specific employment mentioned social problems–obstacles concerning communication and human interaction–most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  6. Overcoming restriction as a barrier to DNA transformation in Caldicellulosiruptor species results in efficient marker replacement

    PubMed Central

    2013-01-01

    Background Thermophilic microorganisms have special advantages for the conversion of plant biomass to fuels and chemicals. Members of the genus Caldicellulosiruptor are the most thermophilic cellulolytic bacteria known. They have the ability to grow on a variety of non-pretreated biomass substrates at or near ~80°C and hold promise for converting biomass to bioproducts in a single step. As for all such relatively uncharacterized organisms with desirable traits, the ability to genetically manipulate them is a prerequisite for making them useful. Metabolic engineering of pathways for product synthesis is relatively simple compared to engineering the ability to utilize non-pretreated biomass. Results Here we report the construction of a deletion of cbeI (Cbes2438), which encodes a restriction endonuclease that is as a major barrier to DNA transformation of C. bescii. This is the first example of a targeted chromosomal deletion generated by homologous recombination in this genus and the resulting mutant, JWCB018 (ΔpyrFA ΔcbeI), is readily transformed by DNA isolated from E. coli without in vitro methylation. PCR amplification and sequencing suggested that this deletion left the adjacent methyltransferase (Cbes2437) intact. This was confirmed by the fact that DNA isolated from JWCB018 was protected from digestion by CbeI and HaeIII. Plasmid DNA isolated from C. hydrothermalis transformants were readily transformed into C. bescii. Digestion analysis of chromosomal DNA isolated from seven Caldicellulosiruptor species by using nine different restriction endonucleases was also performed to identify the functional restriction-modification activities in this genus. Conclusion Deletion of the cbeI gene removes a substantial barrier to routine DNA transformation and chromosomal modification of C. bescii. This will facilitate the functional analyses of genes as well as metabolic engineering for the production of biofuels and bioproducts from biomass. An analysis of

  7. Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses.

    PubMed

    Strauss, J; Alewine, C; Figg, W D; Duffy, A

    2016-07-01

    Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer. PMID:26661112

  8. Personal health records: definitions, benefits, and strategies for overcoming barriers to adoption.

    PubMed

    Tang, Paul C; Ash, Joan S; Bates, David W; Overhage, J Marc; Sands, Daniel Z

    2006-01-01

    Recently there has been a remarkable upsurge in activity surrounding the adoption of personal health record (PHR) systems for patients and consumers. The biomedical literature does not yet adequately describe the potential capabilities and utility of PHR systems. In addition, the lack of a proven business case for widespread deployment hinders PHR adoption. In a 2005 working symposium, the American Medical Informatics Association's College of Medical Informatics discussed the issues surrounding personal health record systems and developed recommendations for PHR-promoting activities. Personal health record systems are more than just static repositories for patient data; they combine data, knowledge, and software tools, which help patients to become active participants in their own care. When PHRs are integrated with electronic health record systems, they provide greater benefits than would stand-alone systems for consumers. This paper summarizes the College Symposium discussions on PHR systems and provides definitions, system characteristics, technical architectures, benefits, barriers to adoption, and strategies for increasing adoption. PMID:16357345

  9. Overcoming barriers to osteoporosis care in vulnerable elderly patients with hip fractures.

    PubMed

    Switzer, Julie A; Jaglal, Susan; Bogoch, Earl R

    2009-07-01

    Indications for and benefits of providing osteoporosis (OP) care for hip fracture patients have become widely understood. The hip fracture patient is frequently over age 80 years, minimally ambulatory, has multiple medical comorbidities, and has cognitive impairment. Patient barriers to initiation of effective OP treatment include: age, dementia, medical comorbidities, polypharmacy, lack of adherence with treatment, alcohol abuse, postoperative delirium, language barriers, inadequate social support, and socioeconomic status. In a large teaching hospital, 244 patients presented with hip fracture over 2 years: 72% were female and 64% were over age 80. Forty percent had been diagnosed with dementia; another 29% had other severe medical comorbidities.Opportunities for OP diagnosis and treatment are numerous. In acute care hospitals, coordinator facilitated programs are effective for identification, education, assessment, referral, and treatment of underlying OP in fracture patients. System modifications may include an automated care path or automatic specialist referral for hip fracture patients. In the rehabilitation hospital, the patients are in a more stable condition, there is a focus on the recent fracture, and there are opportunities to initiate OP treatment and to promote adherence. In long-term care, dietary intake including calcium and vitamin D supplementation and persistence with pharmacotherapy can be monitored. Patient education and referral to the family physician for osteoporosis investigation and treatment have improved patient knowledge and diagnosis, but the reported impact on treatment has been limited.Effective OP care for the vulnerable hip fracture patient should be initiated early but may be complex and require coordination. In addition to calcium and vitamin D supplementation, most patients in this category have an indication for aminobisphosphonate therapy. Liaison between the orthopaedic team and the discharge destination caregivers, an

  10. Learning from the best: Overcoming barriers to reforms-based elementary science teaching

    NASA Astrophysics Data System (ADS)

    Banchi, Heather May

    This study explored the characteristics of elementary science teachers who employ reforms-based practices. Particular attention was paid to the consistency of teachers' practices and their beliefs, the impact of professional development experiences on practices, and how teachers mitigated barriers to reforms-based instruction. Understanding how successful elementary science teachers develop fills a gap in the science reforms literature. Participants included 7 upper elementary science teachers from six different schools. All schools were located within two suburban school districts in the south-Atlantic United States and data was collected during the spring of 2008. Data collection included use of the Reformed Teaching Observation Protocol (RTOP) to evaluate the level of reforms-based instruction, as well as 35 hours of classroom observation field notes and 21 hours of audio-taped teacher interviews. The variety of data sources allowed for triangulation of evidence. The RTOP was analyzed using descriptive statistics and classroom observations and interview data were analyzed using Erickson's (1986) guidelines for analytic induction. Findings indicated (a) reforms-based elementary science teaching was attainable, (b) beliefs and practices were consistent and both reflected reforms-based philosophies and practices, (c) formal professional development experiences were limited and did not foster reforms-based practices, (d) informal professional development pursued by teachers had a positive impact on practices, (e) barriers to reforms-based instruction were present but mitigated by strong beliefs and practical strategies like curriculum integration. These findings suggest that there are common, salient characteristics of reforms-based teachers' beliefs, practices, and professional development experiences. These commonalities contribute to an understanding of how reforms-based teachers develop, and inform efforts to move all elementary teachers in the direction of

  11. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers

    PubMed Central

    Bruce, Alex; Faunce, Thomas

    2015-01-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen–consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  12. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers.

    PubMed

    Bruce, Alex; Faunce, Thomas

    2015-06-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen-consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  13. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    NASA Astrophysics Data System (ADS)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  14. Supramolecular association via Sb...S and C-H...S interactions in dimeric tris(N,N-dimethyldithiocarbamato-S,S')antimony(III): an approach to overcome the concept of steric bulk on such interactions.

    PubMed

    Chauhan, H P S; Carpenter, Jaswant

    2013-12-01

    Tris(N,N-dimethyldithiocarbamato-S,S')antimony(III) has been isolated as a dimer in acetonitrile. Single-crystal X-ray analysis shows that the molecule possesses both Sb···S and C-H···S interactions, which results in a supramolecular association in the absence of hydrogen-bonding functionality on the R group. The co-existence in the title compound of such interactions is a unique character of known dimeric antimony(III) alkyl and/or aryl dithiocarbamate complexes. The literature reveals that the species where the alkyl and/or aryl dithiocarbamates carry the following groups: R = methyl (chloroform solvated), ethyl, n-propyl, pyrrolidine, morpholine, piperidine, azepane, benzyl, methylphenyl, are not capable of forming significant hydrogen-bonding interactions. However, either Sb···S or C-H···S intermolecular interactions dominate between two centrosymmetrically related molecules leading to a supramolecular aggregation. In the species where the R group carries hydrogen-bonding functionality, i.e. 2-hydroxylethyl, the C-H···S interactions are subverted by O-H···O hydrogen bonding. In addition, the title compound does not have steric hindrance or any hydrogen-bonding group but is stabilized with the co-existence of Sb···S and C-H···S interactions. Analysis of the secondary interactions of a series of analogues previously reported reveals that steric bulk is unnecessary for the mitigation of Sb···S interactions and for the establishment of C-H···S secondary bonding. PMID:24253087

  15. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    PubMed

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed. PMID:27208862

  16. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic. PMID:26647486

  17. 'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

    PubMed

    Muñoz, M; Gómez-Ramírez, S; Kozek-Langeneker, S; Shander, A; Richards, T; Pavía, J; Kehlet, H; Acheson, A G; Evans, C; Raobaikady, R; Javidroozi, M; Auerbach, M

    2015-07-01

    In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources. PMID:26089443

  18. Identifying and Overcoming Critical Barriers to Widespread Second Use of PEV Batteries

    SciTech Connect

    Neubauer, J.; Smith, K.; Wood, E.; Pesaran, A.

    2015-02-01

    Both the market penetration of plug-in electric vehicles (PEVs) and deployment of grid-connected energy storage systems are presently restricted by the high cost of batteries. Battery second use (B2U) strategies--in which a single battery first serves an automotive application, then is redeployed into a secondary market--could help address both issues by reducing battery costs to the primary (automotive) and secondary (electricity grid) users. This study investigates the feasibility of and major barriers to the second use of lithium-ion PEV batteries by posing and answering the following critical B2U questions: 1. When will used automotive batteries become available, and how healthy will they be? 2. What is required to repurpose used automotive batteries, and how much will it cost? 3. How will repurposed automotive batteries be used, how long will they last, and what is their value? Advanced analysis techniques are employed that consider the electrical, thermal, and degradation response of batteries in both the primary (automotive) and secondary service periods. Second use applications are treated in detail, addressing operational requirements, economic value, and market potential. The study concludes that B2U is viable and could provide considerable societal benefits due to the large possible supply of repurposed automotive batteries and substantial remaining battery life following automotive service. However, the only identified secondary market large enough to consume the supply of these batteries (utility peaker plant replacement) is expected to be a low margin market, and thus B2U is not expected to affect the upfront cost of PEVs.

  19. Applying Risk Science and Stakeholder Engagement to Overcome Environmental Barriers to Marine and Hydrokinetic Energy Projects

    SciTech Connect

    Copping, Andrea E.; Anderson, Richard M.; Van Cleve, Frances B.

    2010-09-20

    The production of electricity from the moving waters of the ocean has the potential to be a viable addition to the portfolio of renewable energy sources worldwide. The marine and hydrokinetic (MHK) industry faces many hurdles, including technology development, challenges of offshore deployments, and financing; however, the barrier most commonly identified by industry, regulators, and stakeholders is the uncertainty surrounding potential environmental effects of devices placed in the water and the permitting processes associated with real or potential impacts. Regulatory processes are not well positioned to judge the severity of harm due to turbines or wave generators. Risks from MHK devices to endangered or protected animals in coastal waters and rivers, as well as the habitats that support them, are poorly understood. This uncertainty raises concerns about catastrophic interactions between spinning turbine blades or slack mooring lines and marine mammals, birds and fish. In order to accelerate the deployment of tidal and wave devices, there is a need to sort through the extensive list of potential interactions that may cause harm to marine organisms and ecosystems, to set priorities for regulatory triggers, and to direct future research. Identifying the risk of MHK technology components on specific marine organisms and ecosystem components can separate perceived from real risk-relevant interactions. Scientists from Pacific Northwest National Laboratory (PNNL) are developing an Environmental Risk Evaluation System (ERES) to assess environmental effects associated with MHK technologies and projects through a systematic analytical process, with specific input from key stakeholder groups. The array of stakeholders interested in the development of MHK is broad, segmenting into those whose involvement is essential for the success of the MHK project, those that are influential, and those that are interested. PNNL and their partners have engaged these groups, gaining

  20. Performance of some new Niño3.4 predictors at overcoming the spring predictability barrier.

    NASA Astrophysics Data System (ADS)

    Miguel, Tasambay-Salazar; Jose, Ortizbevia Maria; Francisco Jose, Alvarez-Garcia; Antonio, Ruizdeelvira

    2016-04-01

    The El Niño-Southern Oscillation (ENSO) phenomenon is the main source of predictability skill in many regions of the world, at seasonal and interannual timescales. Improving ENSO understanding and forecast skill is still one of the main goals of the international seasonal forecast programs. A common feature found in ENSO forecast is the skill predictability barrier, that is the skill drop for forecast across the spring season. In this study ENSO variability is represented by the Niño3.4 Index. Here we will use different seasonal linear stochastic models to test the performance of some new ENSO predictors at overcoming the spring predictability barrier. The benchmarkt is the performance scored by the same predictive scheme when the variables are those of a basic equatorial model representing the 'recharge-discharge' oscillator paradigm. Some of the new predictors, like the Tropical South Atlantic Index, the Tropical North Atlantic Index, the Indian Ocean Dipole Mode or the Pacific Meridional Model have been pointed at by recent studies. Additionally, we propose two new predictors, that take into account the zonal sea surface temperature gradients across the tropical Pacific, the North Tropical Pacific Zonal Gradient and the South Tropical Pacific Zonal Gradient Indexes. We intercompare the performance of the new predictors, by introducing them, one at a time, in a simple, three variables, stochastic predictive scheme. For some seasons and lags, the differences between the skill scored by some of the models that include one of these predictors are important. However, these are diminished when a Full Stochastic Mode set-up is adopted. References. Tasambay Salazar, M.; Ortiz Beviá, M. J.; Alvarez García, F. J.; Ruiz de Elvira Serra, A. The Niño3.4 region predictability beyond the persistence barrier. Tellus A. 2015, 67. doi: 10.3402/tellusa.v67.27457,

  1. Barriers to integration of behavioral and social sciences in the general medicine curriculum and recommended strategies to overcome them: A systematic review

    PubMed Central

    TABATABAEI, ZAHRA; YAZDANI, SHAHRAM; SADEGHI, RAMIN

    2016-01-01

    Introduction The integration of behavioral and social sciences (BSS) into the curriculum of medical students in order to equip them with the necessary knowledge, skills and attitudes is an essential issue, emphasized in many researches. Our aim is to investigate the barriers to integrate BSS into the general medicine curriculum as well as the recommended strategies to overcome such barriers through a systematic review of literature. Methods PubMed, ERIC, Scopus, CINAHL, Google Scholar, and OPENGREY were searched for studies on the barriers to integration of BSS into the general medicine curriculum as well as the strategies employed to overcome them until August 28, 2015. Results Sixteen relevant studies were included and the related domains were categorized as barriers and some strategies were recommended to overcome them. In addition, the quality of the included studies was assessed. Conclusion Despite the prominent role of BSS in the effectiveness of health care, these sciences have not been included in the curriculum of medical students effectively. The identified barriers and the strategies used to overcome them should be considered for all integration programs. Future studies should focus on the process of BSS integration in the medical curricula and should evaluate the efficacy of this integration in more detail. PMID:27382578

  2. The GEOFAR Project - Geothermal Finance and Awareness in Europeans Regions - Development of new schemes to overcome non-technical barriers, focusing particularly on financial barriers

    NASA Astrophysics Data System (ADS)

    Poux, Adeline; Wendel, Marco; Jaudin, Florence; Hiegl, Mathias

    2010-05-01

    Numerous advantages of geothermal energy like its widespread distribution, a base-load power and availability higher than 90%, a small footprint and low carbon emissions, and the growing concerns about climate changes strongly promote the development of geothermal projects. Geothermal energy as a local energy source implies needs on surface to be located close to the geothermal resource. Many European regions dispose of a good geothermal potential but it is mostly not sufficiently developed due to non-technical barriers occurring at the very early stages of the project. The GEOFAR Project carried out within the framework of EU's "Intelligent Energy Europe" (IEE) program, gathers a consortium of European partners from Germany, France, Greece, Spain and Portugal. Launched in September 2008, the aim of this research project is to analyze the mentioned non-technical barriers, focusing most particularly on economic and financial aspects. Based on this analysis GEOFAR aims at developing new financial and administrative schemes to overcome the main financial barriers for deep geothermal projects (for electricity and direct use, without heat pumps). The analysis of the current situation and the future development of geothermal energy in GEOFAR target countries (Germany, France, Greece, Spain, Portugal, Slovakia, Bulgaria and Hungary) was necessary to understand and expose the diverging status of the geothermal sector and the more and less complicated situation for geothermal projects in different Europeans Regions. A deeper analysis of 40 cases studies (operating, planned and failed projects) of deep geothermal projects also contributed to this detailed view. An exhaustive analysis and description of financial mechanisms already existing in different European countries and at European level to support investors completed the research on non-technical barriers. Based on this profound analysis, the GEOFAR project has made an overview of the difficulties met by project

  3. Overcoming the Illiteracy Barrier.

    ERIC Educational Resources Information Center

    Park, Rosemarie J.

    1984-01-01

    This article asks "How literate do workers need to be?" and suggests such measures as the widespread use of technical materials written in "plain language" and employers' offering job-related reading programs. (JB)

  4. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia

    PubMed Central

    Saha, Somen; Annear, Peter Leslie

    2015-01-01

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor. PMID:25685728

  5. Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression

    PubMed Central

    Zheng, Li; Dai, Huifang; Zhou, Mian; Li, Xiaojin; Liu, Changwei; Guo, Zhigang; Wu, Xiwei; Wu, Jun; Wang, Charles; Zhong, John; Huang, Qin; Garcia-Aguilar, Julio; Pfeifer, Gerd P.; Shen, Binghui

    2012-01-01

    Mutations in genes involved in DNA replication such as FEN1, can cause single-stranded DNA breaks (SSBs) and subsequent collapse of DNA replication forks leading to DNA replication stresses. Persistent replication stresses normally induce p53-mediated senescence or apoptosis to prevent tumor progression. It is unclear how some mutant cells can overcome persistent replication stresses and bypass the p53-mediated pathways to develop malignancy. Here we show that formation of polyploidy, which is often observed in human cancers, leads to overexpression of BRCA1, p19arf and other DNA repair genes in FEN1 mutant cells. This overexpression triggers SSB repair and non-homologous end joining pathways to increase DNA repair activity, but at the cost of frequent chromosomal translocations. Meanwhile, DNA methylation silences p53 target genes, to bypass the p53-mediated senescence and apoptosis. These molecular changes rewire DNA damage response and repair gene networks in polyploid tumor cells, enabling them to escape replication stress-induced senescence barriers. PMID:22569363

  6. The role of "blebbing" in overcoming the hydrophobic barrier during biooxidation of elemental sulfur by Thiobacillus thiooxidans

    USGS Publications Warehouse

    Knickerbocker, C.; Nordstrom, D.K.; Southam, G.

    2000-01-01

    Brimstone Basin, in southeastern Yellowstone National Park, Wyoming is an ancient hydrothermal area containing solfataric alteration. Drainage waters flowing from Brimstone Basin had pH values as low as 1.23 and contained up to 1.7×106 MPN/ml acidophilic sulfur-oxidizing bacteria. Thiobacillus thiooxidans was the dominant sulfur-oxidizing bacterium recovered from an enrichment culture and was used in a structural examination of bacterial sulfur oxidation. Growth in these sulfur cultures occurred in two phases with cells in association with the macroscopic sulfur grains and in suspension above these grains. Colonization of sulfur grains by individual cells and microcolonies was facilitated by organic material that appeared to be responsible for bacterial adhesion. Transmission electron microscopy of negatively stained (2% [wt./vol.] uranyl acetate), sulfur-grown T. thiooxidans revealed extensive membrane blebbing (sloughing of outer membrane vesicles) and the presence of approximately 100 nm sized sulfur particles adsorbed to membrane material surrounding individual bacteria. Sulfite-grown bacteria did not possess membrane blebs. The amphipathic nature of these outer membrane vesicles appear to be responsible for overcoming the hydrophobic barrier necessary for the growth of T. thiooxidans on elemental sulfur.

  7. Overcoming the barriers to effective treatment for attention-deficit/hyperactivity disorder: a neuro-educational approach.

    PubMed

    Monastra, Vincent J

    2005-10-01

    Despite specific diagnostic criteria, published practice guidelines for assessing patients, and the availability of effective pharmacological treatments for children diagnosed with attention-deficit/hyperactivity disorder (AD/HD), a review of prescription practices in the United States indicates that as few as 25-50% of these patients receive even minimal medical treatment for this condition. Because untreated children with AD/HD are at increased risk for psychoactive substance abuse, criminal behavior, and other social problems as adults, the provision of effective care during childhood is essential. In order to clarify the factors impeding treatment during childhood and develop a targeted intervention to overcome these barriers, two studies involving 1514 families were conducted. Each family included one child diagnosed with AD/HD. Factors associated with treatment failure or non-compliance with medical advice included: dissatisfaction with a diagnostic process limited to brief observation, interview, and review of behavior rating scales; fear of stimulant medication; lack of medication response within the first month; development of side-effects during the first month; lack of understanding of the reasons stimulants were being prescribed for a child, and insufficient clinical response. Based on these findings, an intervention program consisting of a comprehensive evaluation process (that included neuropsychological and neurophysiological tests of attention, and medical screening for other health problems associated with inattention and hyperactivity) and parent education about the medical causes of AD/HD, the biochemical action of medications, the relationship between dietary habits and attention, and the educational rights of children with AD/HD was conducted. Following completion of this three session intervention, 95% of patients complied with medical recommendations, initiated pharmacological treatment, and continued medication for a 2-year follow-up period

  8. "My hair or my health:" Overcoming barriers to physical activity in African American women with a focus on hairstyle-related factors.

    PubMed

    Huebschmann, Amy G; Campbell, Lucille Johnson; Brown, Candace S; Dunn, Andrea L

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n = 51) were AA women aged 19-73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from November 2012 to February 2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was "lack of money" (27%) and among non-exercisers was "lack of self-discipline" (57%). A hairstyle-related barrier of "sweating out my hairstyle" was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier. PMID:26495938

  9. Sequence-Specific, RNA–Protein Interactions Overcome Electrostatic Barriers Preventing Assembly of Satellite Tobacco Necrosis Virus Coat Protein

    PubMed Central

    Ford, Robert J.; Barker, Amy M.; Bakker, Saskia E.; Coutts, Robert H.; Ranson, Neil A.; Phillips, Simon E.V.; Pearson, Arwen R.; Stockley, Peter G.

    2013-01-01

    We have examined the roles of RNA–coat protein (CP) interactions in the assembly of satellite tobacco necrosis virus (STNV). The viral genomic RNA encodes only the CP, which comprises a β-barrel domain connected to a positively charged N-terminal extension. In the previous crystal structures of this system, the first 11 residues of the protein are disordered. Using variants of an RNA aptamer sequence isolated against the CP, B3, we have studied the sequence specificity of RNA-induced assembly. B3 consists of a stem–loop presenting the tetra-loop sequence ACAA. There is a clear preference for RNAs encompassing this loop sequence, as measured by the yield of T = 1 capsids, which is indifferent to sequences within the stem. The B3-containing virus-like particle has been crystallised and its structure was determined to 2.3 Å. A lower-resolution map encompassing density for the RNA has also been calculated. The presence of B3 results in increased ordering of the N-terminal helices located at the particle 3-fold axes, which extend by roughly one and a half turns to encompass residues 8–11, including R8 and K9. Under assembly conditions, STNV CP in the absence of RNA is monomeric and does not self-assemble. These facts suggest that a plausible model for assembly initiation is the specific RNA-induced stabilisation of a trimeric capsomere. The basic nature of the helical extension suggests that electrostatic repulsion between CPs prevents assembly in the absence of RNA and that this barrier is overcome by correct placement of appropriately orientated helical RNA stems. Such a mechanism would be consistent with the data shown here for assembly with longer RNA fragments, including an STNV genome. The results are discussed in light of a first stage of assembly involving compaction of the genomic RNA driven by multiple RNA packaging signal–CP interactions. PMID:23318955

  10. What are the barriers which discourage 15-16 year-old girls from participating in team sports and how can we overcome them?

    PubMed

    Wetton, Abigail R; Radley, Rebecca; Jones, Angela R; Pearce, Mark S

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  11. What Are the Barriers Which Discourage 15-16 Year-Old Girls from Participating in Team Sports and How Can We Overcome Them?

    PubMed Central

    Wetton, Abigail R.; Jones, Angela R.; Pearce, Mark S.

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  12. Advocating for responsible oil and natural gas extraction policies; FracTracker as a mechanism for overcoming the barriers to scientific advocacy for academics and communities

    NASA Astrophysics Data System (ADS)

    Ferrar, K. J.; Malone, S.; Kelso, M.; Lenker, B.

    2013-12-01

    The inability to translate data to scientific information that can readily be incorporated by citizens into the public arena is an obstacle for science-based advocacy. This issue is particularly poignant for shale oil and natural gas development via hydraulic fracturing, as the issue has become highly politicized. Barriers to engaging in policy debate are different but highly related for community members and scientists. For citizens and interest groups, barriers including accessibility, public awareness and data presentation limit the motivation for community involvement in political interactions. To overcome such barriers, social researchers call for public engagement to move upstream and many call for a broad engagement of scientists in science-based advocacy. Furthermore surveys have shown that citizens, interest groups, and decision-makers share a broad desire for scientists to engage in environmental policy development. Regardless, scientists face a number of perceived barriers, with academics expressing the most resistance to overcoming the tension created by adherence to the scientific method and the need to engage with the broader society, described by Schneider (1990) as the 'double ethical bind'. For the scientific community the appeal of public dissemination of information beyond the scope of academic journals is limited for a number of reasons. Barriers include preservation of credibility, peer attitudes, training, and career trajectory. The result is a lack of translated information available to the public. This systematic analysis of the FracTracker platform provides an evaluation of where the features of the public engagement, GIS platform has been successful at overcoming these barriers to public dissemination, where the platform needs further development or is ill-suited to address these issues, and the development of FracTracker as an outlet for scientific researchers to engage with citizens. The analysis will also provide insight into what

  13. Strategies to Overcome Barriers to Implementation of Alcohol Screening and Brief Intervention in General Practice: a Delphi Study Among Healthcare Professionals and Addiction Prevention Experts.

    PubMed

    Abidi, L; Oenema, A; Nilsen, P; Anderson, P; van de Mheen, D

    2016-08-01

    Despite the evidence base, alcohol screening and brief intervention (ASBI) have rarely been integrated into routine clinical practice. The aim of this study is to identify strategies that could tackle barriers to ASBI implementation in general practice by involving primary healthcare professionals and addiction prevention experts. A three-round online Delphi study was carried out in the Netherlands. The first-round questionnaire consisted of open-ended questions to generate ideas about strategies to overcome barriers. In the second round, participants were asked to indicate how applicable they found each strategy. Items without consensus were systematically fed back with group median ratings and interquartile range (IQR) scores in the third-round questionnaire. In total, 39 out of 69 (57 %) invited participants enrolled in the first round, 214 participants completed the second round, and 144 of these (67 %) completed the third-round questionnaire. Results show that participants reached consensus on 59 of 81 strategies, such as the following: (1) use of E-learning technology, (2) symptom-specific screening by general practitioners (GPs) and/or universal screening by practice nurses, (3) reimbursement incentives, (4) supportive materials, (5) clear guidelines, (6) service provision of addiction care centers, and (7) more publicity in the media. This exploratory study identified a broad set of strategies that could potentially be used for overcoming barriers to ASBI implementation in general practice and paves the way for future research to experimentally test the identified implementation strategies using multifaceted approaches. PMID:27167074

  14. Steric effects on geminate recombinations

    SciTech Connect

    Traylor, T.G.; Taube, D.; Jongeward, K.A.; Magde, D. )

    1990-09-12

    Steric effects on the binding of isonitrile ligands to iron(II) porphyrins were investigated by picosecond flash photolysis. Two different types of steric effects were distinguished and characterized: (1) steric restrictions to porphyrin planarity and (2) blocking of the pathway for ligand approach. Heme planarity was restricted by coordinating 1,2-dimethylimidazole trans to the ligand binding site being investigated. Blocking of the binding site was explored by using adamantane heme 6,6-cyclophane, in which the adamantane moiety forms a cap over the binding site. Results of picosecond kinetic measurements demonstrate that the first effect, heme nonplanarity or trans strain, influences the bond-making step, whereas the second effect, ligand blocking, involves a conformational preequilibrium prior to bond making. Relevance of these findings for contact pair recombination, in general, and for heme protein ligation, in particular, are discussed.

  15. "We Don't Want to Talk about That": Overcoming Barriers to Rural Aging Research and Interventions on Sensitive Topics

    ERIC Educational Resources Information Center

    Zanjani, Faika; Rowles, Graham D.

    2012-01-01

    Geographical, economic, social and cultural barriers to accessing services in rural areas are widely reported. Less widely discussed are dilemmas posed by individual and community reluctance to address sensitive health issues. This article, focusing on the highly sensitive area of mental health, and employing a participatory action approach,…

  16. Fisher information and steric effect

    NASA Astrophysics Data System (ADS)

    Nagy, Á.

    2007-11-01

    A modified Fisher information, the sum of the one-electron Fisher information, is proposed. It is shown that the modified Fisher information is the original Fisher information plus a sum of differences of quantum and classical variances. A generalization of the Stam's inequality is derived. It is argued that Fisher information provides a measure of steric effect.

  17. Overcoming barriers to effectiveness in a health care operational environment: building on the lessons of American industry.

    PubMed

    Zimmerer, L W; Zimmerer, T W; Yasin, M M

    1999-01-01

    Several of the manufacturing-based philosophies, techniques and tools, such as Total Quality Management (TQM), Continuous Improvement (CI), Business Process Reengineering (BPR) and Time-based Competition (TBC) have been successfully adapted for use within the service sector. Diverse service industries including airlines, insurance, food services and hospitality have increased customer satisfaction and performance through the use of the quality driven, manufacturing-based philosophies. This article explores the reasons for the limited success of TQM/CI, BPR, TBC and benchmarking within the health care industry. Sixteen barriers to change are identified, possible counter-measures to these barriers are outlined and two conceptual frameworks are offered as possible facilitators of change for the health care industry. PMID:11066723

  18. Being "chill" with teachers and "frozen" by peers in science: overcoming social and educational barriers in a learning community

    NASA Astrophysics Data System (ADS)

    Kim, Hannah; Scantlebury, Kathryn

    2013-09-01

    This forum discusses the issue of `othering' and how intersectionality is a useful analytical framework for understanding the students' immigrant experiences in, and out of, the science classroom. We use a feminist perspective to discuss Minjung's study because gender is a key aspect of one's identity other aspects such as race, religion, socio-economic status, and age have assumed a significant status in gender studies. Lastly we examine the supports and barriers that cliques can produce and propose the importance of building a learning community in the science classroom to engage all students.

  19. Do we need to overcome barriers to learning in the workplace for foundation trainees rotating in neurosurgery in order to improve training satisfaction?

    PubMed

    Phan, Pho Nh; Patel, Keyur; Bhavsar, Amar; Acharya, Vikas

    2016-01-01

    Junior doctors go through a challenging transition upon qualification; this repeats every time they start a rotation in a new department. Foundation level doctors (first 2 years postqualification) in neurosurgery are often new to the specialty and face various challenges that may result in significant workplace dissatisfaction. The neurosurgical environment is a clinically demanding area with a high volume of unwell patients and frequent emergencies - this poses various barriers to learning in the workplace for junior doctors. We identify a number of key barriers and review ideas that can be trialed in the department to overcome them. Through an evaluation of current suggestions in the literature, we propose that learning opportunities need to be made explicit to junior doctors in order to encourage them to participate as a member of the team. We consider ideas for adjustments to the induction program and the postgraduate medical curriculum to shift the focus from medical knowledge to improving confidence and clinical skills in newly qualified doctors. Despite being a powerful window for opportunistic learning, the daily ward round is unfortunately not maximized and needs to be more learner focused while maintaining efficiency and time consumption. Finally, we put forward the idea of an open forum where trainees can talk about their learning experiences, identify subjective barriers, and suggest solutions to senior doctors. This would be achieved through departmental faculty development. These interventions are presented within the context of the neurosurgical ward; however, they are transferable and can be adapted in other specialties and departments. PMID:27099543

  20. Do we need to overcome barriers to learning in the workplace for foundation trainees rotating in neurosurgery in order to improve training satisfaction?

    PubMed Central

    Phan, Pho NH; Patel, Keyur; Bhavsar, Amar; Acharya, Vikas

    2016-01-01

    Junior doctors go through a challenging transition upon qualification; this repeats every time they start a rotation in a new department. Foundation level doctors (first 2 years postqualification) in neurosurgery are often new to the specialty and face various challenges that may result in significant workplace dissatisfaction. The neurosurgical environment is a clinically demanding area with a high volume of unwell patients and frequent emergencies – this poses various barriers to learning in the workplace for junior doctors. We identify a number of key barriers and review ideas that can be trialed in the department to overcome them. Through an evaluation of current suggestions in the literature, we propose that learning opportunities need to be made explicit to junior doctors in order to encourage them to participate as a member of the team. We consider ideas for adjustments to the induction program and the postgraduate medical curriculum to shift the focus from medical knowledge to improving confidence and clinical skills in newly qualified doctors. Despite being a powerful window for opportunistic learning, the daily ward round is unfortunately not maximized and needs to be more learner focused while maintaining efficiency and time consumption. Finally, we put forward the idea of an open forum where trainees can talk about their learning experiences, identify subjective barriers, and suggest solutions to senior doctors. This would be achieved through departmental faculty development. These interventions are presented within the context of the neurosurgical ward; however, they are transferable and can be adapted in other specialties and departments. PMID:27099543

  1. Exploring the role of social interactions and supports in overcoming accessibility barriers while undertaking health tours in India.

    PubMed

    Jana, Arnab; Harata, Noboru; Kiyoshi, Takami; Ohmori, Nobuaki

    2014-01-01

    This article explores the phenomenon of companionship as an adaptation strategy to counter the existing barriers to health care access in developing nations. Companionship is argued to be an outcome of "inter" and "intra" household collaboration to offer diverse supports in addition to altruism. The analysis of the household survey conducted in West Bengal, India, exhibited different patterns of health care tours and the associated dependencies. In addition to support in terms of mobility while traveling and companionship while waiting for the opportunity, support in terms of refuge is also found to be essential, especially for the poor while they undertake regional tours. Causal models focusing on aggregated general health tours and specific regional tours were estimated separately to comprehend the implicit social interactions and their effects on the patient as well as the companions. The research demonstrated that accessibility barriers affect not only the ill, but also those associated with them and at times adversely. Segregation of regional tours illustrated the gaps, which instigated such tours and also might aid in health infrastructure planning as a whole. PMID:24871773

  2. Overcoming barriers to effective early parenting interventions for attention-deficit hyperactivity disorder (ADHD): parent and practitioner views

    PubMed Central

    Smith, E; Koerting, J; Latter, S; Knowles, M M; McCann, D C; Thompson, M; Sonuga-Barke, E J

    2015-01-01

    Background The importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low ‘take-up’ and high ‘drop-out’ rates compromise the effectiveness of such programmes within the community. Methods This qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. Results and conclusions Many of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented. PMID:24814640

  3. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer.

    PubMed

    Davis, Ruth J; Van Waes, Carter; Allen, Clint T

    2016-07-01

    A significant subset of head and neck cancers display a T-cell inflamed phenotype, suggesting that patients with these tumors should respond to therapeutic approaches aimed at strengthening anti-tumor immune responses. A major barrier to the development of an effective anti-tumor immune response, at baseline or in response to immunotherapy, is the development of an immunosuppressive tumor microenvironment. Several well described mechanisms of effector immune cell suppression in the head and neck cancer microenvironment are discussed here, along with updates on current trials designed to translate what we have learned from pre-clinical and correlative clinical studies into improved responses in patients with head and neck cancer following immune activating therapies. PMID:27215705

  4. Overcoming language and cultural barriers: a graphical communication tool to perform a parasitological screening in two vulnerable populations from Argentina.

    PubMed

    Buyayisqui, María Pía; Bordoni, Noemí; Garbossa, Graciela

    2013-01-01

    This is an exploratory study of the application of a support tool for the detection of asymptomatic subjects carrying enteric parasites in two vulnerable populations in Argentina: a shantytown in the city of Buenos Aires and a rural Wichí indigenous community in the province of Chaco. The ethnic and cultural diversity, high illiteracy rate, and language barriers called for the development of an auxiliary resource to explain stool sample collection procedures. In individual interviews with each family, the authors used two instructional guidance leaflets in comic strip format depicting the procedures. They evaluated the acceptance of the graphical communication tool on the basis of the number of retrieved samples. Percentages of respondent families were 72.2% and 66.7%, respectively. Definitive validation of these instruments would allow their use in community studies, community service learning experiences, and research on aboriginal communities that would otherwise be excluded from studies on health status. PMID:23066862

  5. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds.

    PubMed

    Elgar, Amelia T; Freebody, Kylie; Pohlman, Catherine L; Shoo, Luke P; Catterall, Carla P

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of "new forests" more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  6. PLANET FORMATION IN STELLAR BINARIES. II. OVERCOMING THE FRAGMENTATION BARRIER IN α CENTAURI AND γ CEPHEI-LIKE SYSTEMS

    SciTech Connect

    Rafikov, Roman R.; Silsbee, Kedron

    2015-01-10

    Planet formation in small-separation (∼20 AU) eccentric binaries such as γ Cephei or α Centauri is believed to be adversely affected by the presence of the stellar companion. Strong dynamical excitation of planetesimals by the eccentric companion can result in collisional destruction (rather than growth) of 1-100 km objects, giving rise to the ''fragmentation barrier'' for planet formation. We revise this issue using a novel description of secular dynamics of planetesimals in binaries, which accounts for the gravity of the eccentric, coplanar protoplanetary disk, as well as gas drag. By studying planetesimal collision outcomes, we show, in contrast to many previous studies, that planetesimal growth and subsequent formation of planets (including gas giants) in AU-scale orbits within ∼20 AU separation binaries may be possible, provided that the protoplanetary disks are massive (≳ 10{sup –2} M {sub ☉}) and only weakly eccentric (disk eccentricity ≲ 0.01). These requirements are compatible with both the existence of massive (several M{sub J} ) planets in γ Cep-like systems and the results of recent simulations of gaseous disks in eccentric binaries. Terrestrial and Neptune-like planets can also form in lower-mass disks at small (sub-AU) radii. We find that the fragmentation barrier is less of a problem in eccentric disks that are apsidally aligned with the binary orbit. Alignment gives rise to special locations, where (1) relative planetesimal velocities are low and (2) the timescale of their drag-induced radial drift is long. This causes planetesimal pileup at such locations in the disk and promotes their growth locally, helping to alleviate the timescale problem for core formation.

  7. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds

    PubMed Central

    Elgar, Amelia T.; Freebody, Kylie; Pohlman, Catherine L.; Shoo, Luke P.; Catterall, Carla P.

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of “new forests” more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  8. Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

    PubMed

    Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

    2006-12-15

    The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

  9. The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

    PubMed Central

    2014-01-01

    Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen. PMID:25537314

  10. In vitro affinity maturation of a natural human antibody overcomes a barrier to in vivo affinity maturation

    PubMed Central

    Li, Bing; Fouts, Ashley E; Stengel, Katharina; Luan, Peng; Dillon, Michael; Liang, Wei-Ching; Feierbach, Becket; Kelley, Robert F; Hötzel, Isidro

    2014-01-01

    Antibodies isolated from human donors are increasingly being developed for anti-infective therapeutics. These antibodies undergo affinity maturation in vivo, minimizing the need for engineering of therapeutic leads for affinity. However, the affinities required for some therapeutic applications may be higher than the affinities of the leads obtained, requiring further affinity maturation in vitro. To improve the neutralization potency of natural human antibody MSL-109 targeting human cytomegalovirus (CMV), we affinity matured the antibody against the gH/gL glycoprotein complex. A phage display library where most of the six complementary-determining regions (CDRs) were allowed to vary in only one amino acid residue at a time was used to scan for mutations that improve binding affinity. A T55R mutation and multiple mutations in position 53 of the heavy chain were identified that, when present individually or in combination, resulted in higher apparent affinities to gH/gL and improved CMV neutralization potency of Fab fragments expressed in bacterial cells. Three of these mutations in position 53 introduced glycosylation sites in heavy chain CDR 2 (CDR H2) that impaired binding of antibodies expressed in mammalian cells. One high affinity (KD < 10 pM) variant was identified that combined the D53N and T55R mutations while avoiding glycosylation of CDR H2. However, all the amino acid substitutions identified by phage display that improved binding affinity without introducing glycosylation sites required between two and four simultaneous nucleotide mutations to avoid glycosylation. These results indicate that the natural human antibody MSL-109 is close to a local affinity optimum. We show that affinity maturation by phage display can be used to identify and bypass barriers to in vivo affinity maturation of antibodies imposed by glycosylation and codon usage. These constraints may be relatively prevalent in human antibodies due to the codon usage and the amino acid

  11. Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities

    PubMed Central

    Salihu, Hamisu M.; Wilson, Ronee E.; King, Lindsey M.; Marty, Phillip J.; Whiteman, Valerie E.

    2015-01-01

    Background: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. Methods: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. Results: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. Conclusions and Global Health Implications: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials.

  12. Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening†

    PubMed Central

    Alcaraz, Jordi; Mori, Hidetoshi; Ghajar, Cyrus M.; Brownfield, Doug; Galgoczy, Roland; Bissell, Mina J.

    2013-01-01

    Collective cell invasion (CCI) through interstitial collagenous extracellular matrix (ECM) is crucial to the initial stages of branching morphogenesis, and a hallmark of tissue repair and dissemination of certain tumors. The collagenous ECM acts as a mechanical barrier against CCI. However, the physical nature of this barrier and how it is overcome by cells remains incompletely understood. To address these questions, we performed theoretical and experimental analysis of mammary epithelial branching morphogenesis in 3D type I collagen (collagen-I) gels. We found that the mechanical resistance of collagen-I is largely due to its elastic rather than its viscous properties. We also identified two strategies utilized by mammary epithelial cells that can independently minimize ECM mechanical resistance during CCI. First, cells adopt a narrow tube-like geometry during invasion, which minimizes the elastic opposition from the ECM as revealed by theoretical modeling of the most frequent invasive shapes and sizes. Second, the stiffness of the collagenous ECM is reduced at invasive fronts due to its degradation by matrix metalloproteinases (MMPs), as indicated by direct measurements of collagen-I microelasticity by atomic force microscopy. Molecular techniques further specified that the membrane-bound MMP14 mediates degradation of collagen-I at invasive fronts. Thus, our findings reveal that MMP14 is necessary to efficiently reduce the physical restraints imposed by collagen-I during branching morphogenesis, and help our overall understanding of how forces are balanced between cells and their surrounding ECM to maintain collective geometry and mechanical stability during CCI. PMID:21993836

  13. Increasing Rural Adults' Participation in Collegial Programs: Exemplary Programs. Proceedings of the Rural Action Conference "Programs and Activities to Overcome Barriers to Rural Adult Participation in Postsecondary Education" (Blacksburg, Virginia, June 1-3, 1987).

    ERIC Educational Resources Information Center

    Sullins, W. Robert, Ed.; And Others

    Approximately 85 educators from six states participated in a regional conference designed to showcase exemplary and collaborative programs to overcome many of the barriers faced by rural adults in pursuing higher education. After the keynote address, "The Role of Adult Learning in Revitalizing Rural Communities," by Cornelia Butler Flora, the…

  14. Sterically and electrosterically stabilized emulsion polymerization. Kinetics and preparation.

    PubMed

    Capek, Ignác

    2002-10-21

    The principal subject discussed in the current paper is the radical polymerization in the aqueous emulsions of unsaturated monomers (styrene, alkyl (meth)acrylates, etc.) stabilized by non-ionic and ionic/non-ionic emulsifiers. The sterically and electrosterically stabilized emulsion polymerization is a classical method which allows to prepare polymer lattices with large particles and a narrow particle size distribution. In spite of the similarities between electrostatically and sterically stabilized emulsion polymerizations, there are large differences in the polymerization rate, particle size and nucleation mode due to varying solubility of emulsifiers in oil and water phases, micelle sizes and thickness of the interfacial layer at the particle surface. The well-known Smith-Ewart theory mostly applicable for ionic emulsifier, predicts that the number of particles nucleated is proportional to the concentration of emulsifier up to 0.6. The thin interfacial layer at the particle surface, the large surface area of relatively small polymer particles and high stability of small particles lead to rapid polymerization. In the sterically stabilized emulsion polymerization the reaction order is significantly above 0.6. This was ascribed to limited flocculation of polymer particles at low concentration of emulsifier, due to preferential location of emulsifier in the monomer phase. Polymerization in the large particles deviates from the zero-one approach but the pseudo-bulk kinetics can be operative. The thick interfacial layer can act as a barrier for entering radicals due to which the radical entry efficiency and also the rate of polymerization are depressed. The high oil-solubility of non-ionic emulsifier decreases the initial micellar amount of emulsifier available for particle nucleation, which induces non-stationary state polymerization. The continuous release of emulsifier from the monomer phase and dismantling of the non-micellar aggregates maintained a high level of

  15. A Progress Report of Activities in "To Study a Program to Overcome Sex Bias Barriers in Women's Qualifications for Vocational Administration Posts."

    ERIC Educational Resources Information Center

    Legg, Marilyn R.

    One of four phases has been completed in a study conducted at Kansas State University of sex-bias barriers in women's qualifications for vocational administration posts. The project's objective is to improve the probability that women may be able to move into vocational administration. The first phase, a field survey in the form of a mail…

  16. A Change Agent's Facilitation Process for Overcoming the Barriers of ICT Adoption for Educational Administration--The Case of a Rural-Bangladesh Vocational Institution

    ERIC Educational Resources Information Center

    Khalid, Md. Saifuddin; Nyvang, Tom

    2014-01-01

    The factors influencing the use of information and communication technologies (ICT) as a professional and management tool outside the classroom have received little research attention. The two objectives of this research were: how do stakeholders of educational administration experience the barriers of ICT adoption, and how can they facilitate the…

  17. Women bound to be active (years 3 and 4): can a book club help women overcome barriers to physical activity and improve self-worth?

    PubMed

    Huberty, Jennifer L; Vener, Jamie; Ransdell, Lynda; Schulte, Laura; Budd, Melissa A; Gao, Yong

    2010-01-01

    Little progress has been made toward increasing physical activity in women. This study aimed to determine if an 8-month theory-based book club intervention (Women Bound to Be Active) was effective in increasing: (a) self-worth, (b) benefits relative to barriers to physical activity, and (c) physical activity in women (n = 51). Findings suggested a book club was effective for improving: self-worth, the benefits relative to barriers to physical activity, and possibly participation in physical activity. This is an innovative model to help women become more active and learn skills that may enable them to be active on their own long after a physical activity program has ended. PMID:20349397

  18. You can teach an old dog new tricks: a qualitative analysis of how residents of senior living communities may use the web to overcome spatial and social barriers.

    PubMed

    Winstead, Vicki; Anderson, William A; Yost, Elizabeth A; Cotten, Shelia R; Warr, Amanda; Berkowsky, Ronald W

    2013-08-01

    For adults in senior living communities, information and communication technologies (ICTs) can be used to increase and expand communication for a population that is often spatially and socially separated from the general public. Using qualitative observational data from a longitudinal study of the impact of ICT usage on the quality of life among residents in assisted and independent living communities, the authors examine whether ICTs can mitigate the effects of social and spatial barriers. The authors find that ICTs have the potential to allow individuals to transcend social and spatial barriers, providing residents with the ability to maintain and enhance social networks as well as provide a greater sense of connection to the world at large. PMID:25474761

  19. Overcoming prejudice.

    PubMed

    Da Silva, J M; Correa, J; Terto, V

    1998-02-01

    People of African descent comprise a large proportion of Brazil's population. While racism exists in the country, it is commonly denied. Most Afro-Brazilians live in poor areas, with poor health care services, sanitation, schools, and transport. Since HIV is linked to poverty, Afro-Brazilians are more affected by HIV than is the overall population. Although Afro-Brazilians contribute to Brazil's culture, they do not benefit from that contribution. Recognizing this considerable social problem, Project Araye was created in 1996 to address issues of race and HIV. Building upon religious and cultural traditions, the project is staffed by Afro-Brazilians who are knowledgeable in both health issues and Afro-Brazilian culture. Project Araye supports a wide range of diverse community leaders in linking sexual health and HIV with other health concerns which affect Afro-Brazilians such as sickle-cell anemia, diabetes, and leprosy. One important challenge has been overcoming the target population's denial of HIV and encouraging Afro-Brazilians to accept that HIV also affects them. Community leaders include religious leaders, rap musicians, artists, and other people respected by various communities. Activities include visits to samba dance schools, Umbanda and Candomble temples, and street youth groups to provide HIV-related information. PMID:12293758

  20. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion. PMID:26667208

  1. Community-based antiretroviral therapy programs can overcome barriers to retention of patients and decongest health services in sub-Saharan Africa: a systematic review.

    PubMed

    Decroo, Tom; Rasschaert, Freya; Telfer, Barbara; Remartinez, Daniel; Laga, Marie; Ford, Nathan

    2013-09-01

    In sub-Saharan Africa models of care need to adapt to support continued scale up of antiretroviral therapy (ART) and retain millions in care. Task shifting, coupled with community participation has the potential to address the workforce gap, decongest health services, improve ART coverage, and to sustain retention of patients on ART over the long-term. The evidence supporting different models of community participation for ART care, or community-based ART, in sub-Saharan Africa, was reviewed. In Uganda and Kenya community health workers or volunteers delivered ART at home. In Mozambique people living with HIV/AIDS (PLWHA) self-formed community-based ART groups to deliver ART in the community. These examples of community ART programs made treatment more accessible and affordable. However, to achieve success some major challenges need to be overcome: first, community programs need to be driven, owned by and embedded in the communities. Second, an enabling and supportive environment is needed to ensure that task shifting to lay staff and PLWHA is effective and quality services are provided. Finally, a long term vision and commitment from national governments and international donors is required. Exploration of the cost, effectiveness, and sustainability of the different community-based ART models in different contexts will be needed. PMID:24030268

  2. Increased Chondroitin Sulfate Proteoglycan Expression in Denervated Brainstem Targets Following Spinal Cord Injury Creates a Barrier to Axonal Regeneration Overcome by Chondroitinase ABC and Neurotrophin-3

    PubMed Central

    Massey, James M.; Amps, Jeremy; Viapiano, Mariano S.; Matthews, Russell. T.; Wagoner, Michelle R.; Whitaker, Christopher M.; Alilain, Warren; Yonkof, Alicia L.; Khalyfa, Abdelnaby; Cooper, Nigel G. F.; Silver, Jerry; Onifer, Stephen M.

    2008-01-01

    Increased chondroitin sulfate proteoglycan (CSPG) expression in the vicinity of a spinal cord injury (SCI) is a primary participant in axonal regeneration failure. However, the presence of similar increases of CSPG expression in denervated synaptic targets well away from the primary lesion and the subsequent impact on regenerating axons attempting to approach deafferented neurons has not been studied. Constitutively expressed CSPGs within the extracellular matrix and perineuronal nets of the adult rat dorsal column nuclei (DCN) were characterized using real-time PCR, western blot analysis and immunohistochemistry. We show for the first time that by 2 days and through 3 weeks following SCI, the levels of NG2, neurocan and brevican associated with reactive glia throughout the DCN were dramatically increased throughout the DCN despite being well beyond areas of trauma-induced blood brain barrier breakdown. Importantly, regenerating axons from adult sensory neurons microtransplanted 2 weeks following SCI between the injury site and the DCN were able to regenerate rapidly within white matter (as shown previously by Davies et al., 1999) but were unable to enter the denervated DCN. Application of chondroitinase ABC or neurotrophin 3-expressing lentivirus in the DCN partially overcame this inhibition. When the treatments were combined, entrance by regenerating axons into the DCN was significantly augmented. These results demonstrate both an additional challenge and potential treatment strategy for successful functional pathway reconstruction after SCI. PMID:17540369

  3. Screening for Asymptomatic Extragenital Gonorrhea and Chlamydia in Men Who Have Sex with Men: Significance, Recommendations, and Options for Overcoming Barriers to Testing.

    PubMed

    Lutz, Anthony R

    2015-03-01

    Men who have sex with men (MSM) have a disproportionately greater risk than other populations of acquiring Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC), the two most commonly reported notifiable diseases in the United States according to the Centers for Disease Control and Prevention (CDC). The presence of either of these diseases is a significant risk factor for the acquisition and transmission of human immunodeficiency virus (HIV). Recent studies have shown that significant rates of asymptomatic GC and CT infection are found at the extragenital oropharygeal and rectal sites in MSM, with or without concurrent urogenital infection. However, extragenital sites are not being routinely screened and, thus, many asymptomatic GC and CT infections at the oropharyngeal and rectal sites may go undiagnosed. This review will begin with the current evidence-based screening recommendations for extragenital GC and CT in MSM. This will be followed by recently reported extragenital GC and CT infection rates in asymptomatic MSM, and a discussion of the risks and potential implications of undiagnosed extragenital GC and CT infections. Finally, a discussion on the frequency of, and potential barriers to, screening will be presented with a summary of potential interventions for increasing screening frequency found in the literature. The scope of this review will focus primarily on U.S. recommendations, infection rates, and screening frequencies, with the inclusion of relevant international recommendations and studies for comparative and illustrative purposes. PMID:26790015

  4. Adaptation to Ephemeral Habitat May Overcome Natural Barriers and Severe Habitat Fragmentation in a Fire-Dependent Species, the Bachman's Sparrow (Peucaea aestivalis)

    PubMed Central

    Cerame, Blain; Cox, James A.; Brumfield, Robb T.; Tucker, James W.; Taylor, Sabrina S.

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat. PMID:25180939

  5. Overcoming barriers to validation of non-animal partial replacement methods/Integrated Testing Strategies: the report of an EPAA-ECVAM workshop.

    PubMed

    Kinsner-Ovaskainen, Agnieszka; Akkan, Zerrin; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Dal Negro, Gianni; De Bruijn, Jack; De Silva, Odile; Gribaldo, Laura; Griesinger, Claudius; Jaworska, Joanna; Kreysa, Joachim; Maxwell, Gavin; McNamee, Pauline; Price, Anna; Prieto, Pilar; Schubert, Roland; Tosti, Luca; Worth, Andrew; Zuang, Valerie

    2009-09-01

    The use of Integrated Testing Strategies (ITS) in toxicological hazard identification and characterisation is becoming increasingly common as a method for enabling the integration of diverse types of toxicology data. At present, there are no existing procedures and guidelines for the construction and validation of ITS, so a joint EPAA WG5-ECVAM workshop was held with the following objectives: a) to investigate the role of ITS and the need for validation of ITS in the different industry sectors (pharmaceuticals, cosmetics, chemicals); b) to formulate a common definition of ITS applicable across different sectors; c) to explore how and when Three Rs methods are used within ITS; and d) to propose a validation rationale for ITS and for alternative methods that are foreseen to be used within ITS. The EPAA provided a platform for comparing experiences with ITS across different industry sectors. It became clear that every ITS has to be adapted to the product type, R&D stage, and regulatory context. However, common features of ITS were also identified, and this permitted the formulation of a general definition of ITS in a regulatory context. The definition served as a basis for discussing the needs, rationale and process of formal ITS validation. One of the main conclusions was that a formal validation should not be required, unless the strategy will serve as full replacement of an in vivo study used for regulatory purposes. Finally, several challenges and bottlenecks to the ITS validation were identified, and it was agreed that a roadmap on how to address these barriers would be established by the EPAA partners. PMID:19807215

  6. Enhanced clickability of doubly sterically-hindered aryl azides

    NASA Astrophysics Data System (ADS)

    Yoshida, Suguru; Shiraishi, Akira; Kanno, Kimiyuki; Matsushita, Takeshi; Johmoto, Kohei; Uekusa, Hidehiro; Hosoya, Takamitsu

    2011-09-01

    Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group. Experimental and computational studies have indicated that the steric hindrance eliciting the inhibition of resonance between azido group and the aromatic ring is the primary cause of this apparently-paradoxical phenomenon. This is the first type of steric acceleration, indicating a possibility of designing a highly reactive functional group by strategically locating it in the sterically-congested environment.

  7. Zero Steric Potential and bond order

    NASA Astrophysics Data System (ADS)

    Ghasemi, S.; Noorizadeh, S.

    2016-05-01

    The variation of Zero Steric Potential (ZSP) through a C-C bond shows two maximums, which their values depend on the bond order (BO). A good relationship (R2 = 1) is observed between the mean values of maximum ZSPs and the bond orders of C-C bonds in ethane, ethylene and acetylene, as reference molecules (Ln BO = 1.956ZSP‾max - 0.898). The obtained equation is used to predict the C-C bond orders of more than twenty aromatic and aliphatic hydrocarbons. The results show that the obtained bond orders from ZSP‾max are more reliable than those which are evaluated using NBO and Laplacian methods.

  8. Steric Effects Govern the Photoactivation of Phytochromes.

    PubMed

    Falklöf, Olle; Durbeej, Bo

    2016-04-01

    Phytochromes constitute a superfamily of photoreceptor proteins existing in two forms that absorb red (Pr) and far-red (Pfr) light. Although it is well-known that the conversion of Pr into Pfr (the biologically active form) is triggered by a Z→E photoisomerization of the linear tetrapyrrole chromophore, direct evidence is scarce as to why this reaction always occurs at the methine bridge between pyrrole rings C and D. Here, we present hybrid quantum mechanics/molecular mechanics calculations based on a high-resolution Pr crystal structure of Deinococcus radiodurans bacteriophytochrome to investigate the competition between all possible photoisomerizations at the three different (AB, BC and CD) methine bridges. The results demonstrate that steric interactions with the protein are a key discriminator between the different reaction channels. In particular, it is found that such interactions render photoisomerizations at the AB and BC bridges much less probable than photoisomerization at the CD bridge. PMID:26756452

  9. Temporary Restraints to Overcome Steric Obstacles—Efficient Strategy for the Synthesis of Mycalamide B**

    PubMed Central

    Jewett, John C.; Rawal, Viresh H.

    2014-01-01

    Restrain and Release: An efficient synthesis of mycalamide B is reported. The synthetic route features (a) a one-pot Mukaiyama–Michael/epoxidation sequence to introduce three of the stereocenters found in the natural product, (b) an intramolecular isocyanate trapping to produce a rigid 10-membered cyclic carbamate, and (c) the selective opening of the cyclic carbamate to reveal the fully constructed natural product. PMID:20931583

  10. Steric interactions between two grafted polymer brushes

    NASA Astrophysics Data System (ADS)

    Ruckenstein, Eli; Li, Buqiang

    1997-07-01

    A lattice model and a generator-matrix method are employed to calculate the interaction force profile between two grafted polymer brushes. The correlation between neighboring bonds and the interdigitation between the two brushes are taken into account. The calculations show that the effect of incorporating the bond correlations is equivalent to an increase in the value of the polymer-solvent interaction parameter when the bond correlations are ignored. The interdigitation between the two brushes decreases the free energy of the system and consequently results in a smaller steric repulsion. A complete interdigitation occurs at a separation close to half the separation between the two plates for which the interaction force is zero. The model is compared with the experimental interaction force profiles for ten systems which involve poly(2-vinylpyridine)-polyisoprene (PVP-PI), poly(2-vinylpyridine)-polystyrene (PVP-PS) block copolymers as well as end-functionalized polystyrenes (PS-X). For most of the systems, the theoretical predictions are in good agreement with experiment. In addition, the present results are compared with the equations proposed by de Gennes, based on the assumption of a step distribution function for the segment density, and by Milner et al., based on the parabolic distribution of the segment density. Both equations neglected interdigitation. It is shown in this paper that the interdigitation is not negligible and that it can decrease by an order of magnitude the repulsive force.

  11. Sterically stabilized colloids with tunable repulsions.

    PubMed

    van Gruijthuijsen, Kitty; Obiols-Rabasa, Marc; Heinen, Marco; Nägele, Gerhard; Stradner, Anna

    2013-09-10

    When studying tunable electrostatic repulsions in aqueous suspensions of charged colloids, irreversible colloid aggregation or gelation may occur at high salt concentrations. For many commonly used synthetic colloids, such as polystyrene and silica particles, the reason for coagulation is the presence of unbalanced, strongly attractive, and short-ranged van der Waals (VDW) forces. Here, we present an aqueous polystyrene model colloid that is sterically stabilized against VDW attractions. We show that the synthesis procedure, based on a neutral initiator couple and a nonionic surfactant, introduces surface charges that can be further increased by the addition of charged comonomer methacrylic acid. Thus, the interactions between the polystyrene spheres can be conveniently tuned from hard-sphere-like to charge-stabilized with long-ranged electrostatic repulsions described by a Yukawa-type pair potential. The particle size, grafting density, core-shell structure, and surface charge are characterized by light and neutron scattering. Using X-ray and neutron scattering in combination with an accurate analytic integral equation scheme for the colloidal static structure factor, we deduce effective particle charges for colloid volume fractions ≥0.1 and salt concentrations in the range of 1.5 to 50 mM. PMID:23937718

  12. Overcoming the Adoption Barrier to Electric Flight

    NASA Technical Reports Server (NTRS)

    Borer, Nicholas K.; Nickol, Craig L.; Jones, Frank P.; Yasky, Richard J.; Woodham, Kurt; Fell, Jared S.; Litherland, Brandon L.; Loyselle, Patricia L.; Provenza, Andrew J.; Kohlman, Lee W.; Samuel, Aamod G.

    2016-01-01

    Electrically-powered aircraft can enable dramatic increases in efficiency and reliability, reduced emissions, and reduced noise as compared to today's combustion-powered aircraft. This paper describes a novel flight demonstration concept that will enable the benefits of electric propulsion, while keeping the extraordinary convenience and utility of common fuels available at today's airports. A critical gap in airborne electric propulsion research is addressed by accommodating adoption at the integrated aircraft-airport systems level, using a confluence of innovative but proven concepts and technologies in power generation and electricity storage that need to reside only on the airframe. Technical discriminators of this demonstrator concept include (1) a novel, high-efficiency power system that utilizes advanced solid oxide fuel cells originally developed for ultra-long-endurance aircraft, coupled with (2) a high-efficiency, high-power electric propulsion system selected from mature products to reduce technical risk, assembled into (3) a modern, high-performance demonstration platform to provide useful and compelling data, both for the targeted early adopters and the eventual commercial market.

  13. Overcoming Learning Barriers through Knowledge Management

    ERIC Educational Resources Information Center

    Dror, Itiel E.; Makany, Tamas; Kemp, Jonathan

    2011-01-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and…

  14. Overcoming Barriers to Classroom Technology Integration

    ERIC Educational Resources Information Center

    Kelly, Daniel P.

    2015-01-01

    Technology-savvy teachers are often the "go to" staff members in schools for their colleagues' technology issues. These teachers are seen as leaders within their schools with respect to technology and often do not understand their peers' difficulties when bringing technology into the classroom. Understanding both the reasons teachers may…

  15. Overcoming barriers to physician adoption of EHRs.

    PubMed

    Hochron, Stuart M; Goldberg, Paul

    2014-02-01

    A hospital's success in implementing an electronic health record will depend largely on physicians' willingness to adopt the new technology. Therefore, before embarking on such an initiative, finance leaders should conduct a targeted survey to assess the likelihood that the initiative will meet with physician resistance. The survey results can provide a basis for developing an outreach program that will bring physicians on board by helping them understand the initiative's purpose and giving them a stake in its success. PMID:24611225

  16. Overcoming Disaster Barriers To Service All Children.

    ERIC Educational Resources Information Center

    Tramonte, Michael R.

    This paper contains an outline of a workshop designed for the disaster mental health worker. The goal of the workshop is to describe how disaster services are different from other mental health services and to provide suggestions on how to make these services more effective. The types of disasters, the anatomy of a disaster, and time phases of a…

  17. Overcoming the cutaneous barrier with microemulsions.

    PubMed

    Lopes, Luciana B

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  18. Overcoming the barriers to effective clinical supervision.

    PubMed

    Bush, Tony

    Clinical supervision remains one of the most misunderstood practices in modern nursing. It provides a nurturing and supportive service for nurses, helping them to reflect critically on their actions in the provision of patient care. The aim of this article is to explore and examine the current role and status of clinical supervision in the NHS. PMID:15688921

  19. Overcoming Barriers to Exercise: No More Excuses

    MedlinePlus

    ... cost exercise programs in your area. Increasing your energy Regular, moderate physical activity can help reduce fatigue ... become active, you’re likely to have more energy than before. As you do more, you also ...

  20. Childhood lymphoedema and 'Lymphaletics': overcoming barriers.

    PubMed

    Todd, Marie

    2016-07-14

    Primary lymphoedema is a complex condition that causes tissue swelling, usually in one or more of the limbs, but lymphatic drainage of the head, trunk or deeper organs may also be affected. It can manifest in swelling at any time from birth meaning there are a number of children affected by this condition. While it is rare in childhood there are too few professionals experienced in diagnosis and treatment, which results in delays in identification and referral to appropriate services for diagnosis and treatment. The Children's Lymphoedema Special Interest Group (CLSIG) was formed in 2010 by a group of lymphoedema specialists in a bid to raise awareness, improve service provision, and enhance practitioner knowledge. One of the aims of the group was to deliver a 'fun day' (Lymphaletics) for children with lymphoedema and their families to encourage physical activity and social interaction with children who have similar problems, and to provide a source of parent-to-parent support. This article discusses the issues for children and their families, and the aims and format of the event. PMID:27409777

  1. Overcoming the Cutaneous Barrier with Microemulsions

    PubMed Central

    Lopes, Luciana B.

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  2. Overcoming Barriers to Progress in Exercise Genomics

    PubMed Central

    Bouchard, Claude

    2011-01-01

    This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. PMID:21697717

  3. Drastic alteration of diffusioosmosis due to steric effects.

    PubMed

    Hoshyargar, Vahid; Ashrafizadeh, Seyed Nezameddin; Sadeghi, Arman

    2015-11-21

    The inclusion of the ionic size (steric) effects into the steady and locally developed diffusioosmotic flow inside a uniformly charged slit microchannel through a theoretical analysis is the subject of this study. The results indicate essential quantitative and qualitative distinctions between the steric effects on classical electrokinetic phenomena like electroosmosis and on diffusioosmosis. For example, although the steric effect on electroosmotic flow is always unfavorable, it may have a positive influence on diffusioosmosis and even double the mean velocity under certain conditions. Moreover, finite ionic sizes can even change the flow direction with a tendency to increase the chance of flow toward higher concentrations. Another interesting finding is that, unlike electroosmosis, the steric effects on diffusioosmotic flow do not vanish even when the EDL is very thin. The main quantitative difference between the ionic size effects on diffusioosmosis and the other electrokinetic phenomena is the critical zeta potential above which these effects become important which is here found to be only about several tens of millivolts. The more sensitivity of diffusioosmosis to the steric effects and also the above-mentioned surprisingly different trends are attributed to the induced electric field which may drastically get influenced by the steric factor. PMID:26465606

  4. Overcoming Breastfeeding Challenges

    MedlinePlus Videos and Cool Tools

    ... and Human Services Office on Women's Health Skip Navigation Skip top navigation Home A-Z Health Topics ePublications News About Us Contact Us Text size | Print | Skip left navigation It's Only Natural Planning ahead Overcoming challenges Overcoming ...

  5. From information theory to quantitative description of steric effects.

    PubMed

    Alipour, Mojtaba; Safari, Zahra

    2016-07-21

    Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems. PMID:27321125

  6. Density functional steric analysis of linear and branched alkanes.

    PubMed

    Ess, Daniel H; Liu, Shubin; De Proft, Frank

    2010-12-16

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (E(s)[ρ]), an electrostatic energy term (E(e)[ρ]), and a fermionic quantum energy term (E(q)[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes. PMID:21086970

  7. Density Functional Steric Analysis of Linear and Branched Alkanes

    SciTech Connect

    Ess, Daniel H.; Liu, Shubin; De Proft, Frank

    2010-11-18

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (Ee[[ρ]), an electrostatic energy term (Ee[ρ]), and a fermionic quantum energy term (Eq[[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes.

  8. Overcoming: A Concept Analysis

    PubMed Central

    Brush, Barbara L.; Kirk, Keri; Gultekin, Laura; Baiardi, Janet M.

    2011-01-01

    This article provides an operational definition of overcoming as a first step in the systematic analysis of the concept. Using the method described by Walker and Avant (2005), the authors identify the attributes and characteristics of overcoming and its theoretical and practical application to nursing. Sample cases from clinical research illustrate the concept further. Further nursing research needs to test the theoretical relationships between overcoming and outcome variables. PMID:21806626

  9. Unlocking the Sugar ‘Steric Gate’ of DNA Polymerases†

    PubMed Central

    Brown, Jessica A.; Suo, Zucai

    2011-01-01

    To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2′-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the ‘steric gate’, establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review article. PMID:21226515

  10. Understanding and Overcoming "Bottlenecks" in Student Learning

    ERIC Educational Resources Information Center

    Sturts, Jill R.; Mowatt, Rasul A.

    2012-01-01

    Pedagogically, the term "bottleneck" refers to a moment when students may face barriers to understanding content in the process of learning. As instructors identify "bottlenecks" within their courses, they are faced with the challenge of how to best assist students in overcoming them. Further, most instructors want to know what selected teaching…

  11. Shock initiation sensitivity of PETN: A steric hindrance model

    SciTech Connect

    Dick, J.J.

    1991-01-01

    In this report, shock initiation sensitivity of PETN crystals is discussed. A new molecular model for shock sensitivity in crystalline solids is proposed in terms of steric hindrance to edge dislocation motion. This model is successful in predicting the relative shock sensitivities of the four PETN orientations studied, especially at low stresses. (JL)

  12. Origin of anomeric effect: A density functional steric analysis

    SciTech Connect

    Huang, Ying; Zhong, Ai-Guo; Yang, Qinsong; Liu, Shubin

    2011-01-01

    The anomeric effect (the tendency of heteroatomic substituents adjacent to a heteroatom within the cyclohexane ring to prefer the axial orientation instead of the sterically less hindered equatorial position) is traditionally explained through either the dipole moment repulsion or the hyperconjugation effect. In this work, by employing our recent work in density functional steric analysis, we provide a novel two-component explanation, which is consistent with the common belief in chemistry that the effect has a stereoelectronic origin. With α-D-glucopyranose as the prototype, we systematically explore its conformational space and generate 32 isomers, leading to a total of 80 axial–equatorial conformation pairs. The energy difference analysis of these pairs shows that while statistically speaking the tendency is valid, the anomeric effect is not always true and can be violated. Three energy components, exchange–correlation, classical electrostatic, and density functional steric, are found to be directly proportional to the total energy difference between axial and equatorial isomers. We also found that the total dipole moment change, not the hyperconjugation effect, is a reasonable indicator of the total energy difference. However, all these correlations alone are not strong enough to provide a compellingly convincing explanation for the general validity of the effect. With the help of strong correlations between energy components, an explanation with two energy components, steric and electrostatic, was proposed in this work. We show that the axial–equatorial energy difference in general, with the anomeric effect as a special case, is dictated by two factors of the stereoelectronic origin, steric hindrance and classical electrostaticinteractions, synchronously working together. Another explanation in terms of exchange–correlation and electrostaticinteractions has also been obtained in this work.

  13. Overcoming job stress

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000884.htm Overcoming job stress To use the sharing features on this ... you stay healthy and feel better. Causes of Job Stress Although the cause of job stress is ...

  14. Overcoming breastfeeding problems

    MedlinePlus

    Plugged milk ducts; Nipple soreness when breastfeeding; Breastfeeding - overcoming problems; Let-down reflex ... Breastfeeding (nursing) your baby can be a good experience for both the mother and the baby. It ...

  15. General theory of asymmetric steric interactions in electrostatic double layers.

    PubMed

    Maggs, A C; Podgornik, R

    2016-01-28

    We study the mean-field Poisson-Boltzmann equation in the context of dense ionic liquids where steric effects become important. We generalise lattice gas theory by introducing a Flory-Huggins entropy for ions of differing volumes and then compare the effective free energy density to other existing lattice gas approximations, not based on the Flory-Huggins Ansatz. Within the methodology presented we also invoke more realistic equations of state, such as the Carnahan-Starling approximation, that are not based on the lattice gas approximation and lead to thermodynamic functions and properties that differ strongly from the lattice gas case. We solve the Carnahan-Starling model in the high density limit, and demonstrate a slow, power-law convergence at high potentials. We elucidate how equivalent convex free energy functions can be constructed that describe steric effects in a manner which is more convenient for numerical minimisation. PMID:26584630

  16. Sterically-hindered amines for acid-gas absorption

    SciTech Connect

    Sartori, G.; Ho, W.S.; Savage, D.W.; Chludzinski, G.R.; Wiechert, S. )

    1988-01-01

    This paper describes sterically hindered amines for removal of acid gases such as CO/sub 2/ and H/sub 2/S from gaseous streams. Steric hindrance of amines reduces carbamate stability. Moderately hindered amines are characterized by high rates of CO/sub 2/ absorption and high capacities for CO/sub 2/. The moderately hindered amine in use with organic solvent has considerably higher capacity than the conventional amine-solvent system for simultaneous removal of CO/sub 2/ and H/sub 2/S from synthesis gas and natural gas. A severely-hindered-amine absorbent, characterized by a very low rate of CO/sub 2/ absorption, has much higher capacity and selectivity than the current industry standard absorbent, using the conventional methyldiethanolamine for selective removal of H/sub 2/S from CO/sub 2/-containing streams.

  17. Interactions of triazine herbicides with biochar: Steric and electronic effects.

    PubMed

    Xiao, Feng; Pignatello, Joseph J

    2015-09-01

    We studied the adsorption of triazine herbicides and several reference heteroaromatic amines from water onto a temperature series of hardwood biochars (300-700 °C, labeled B300-B700). Adsorption on biochars correlated poorly with pyrolysis temperature, H/C, O/C, mean minimum fused ring size, surface area (N2 or CO2), microporosity, and mesoporosity, but correlated well with a weighted sum of microporosity and mesoporosity. Steric effects were evident by the negative influence of solute molecular volume on adsorption rate. For a given compound, adsorption rate maximized for the biochar with the greatest mesoporosity-to-total-porosity ratio, suggesting that mesopores are important for facilitating diffusion into pore networks. The cationic forms of amines adsorb more slowly than the neutral forms. To further probe steric and electronic effects, adsorption on a biochar (B400) was compared to adsorption on graphite-a nonporous reference material with an unhindered, unfunctionalized graphene surface-and in comparison with reference compounds (benzene, naphthalene, pyridine, quinoline and 1,3-triazine). Relative to benzene, the surface area-normalized adsorption of the triazine herbicides was disfavored on B400 (favored on graphite) by 11-19 kJ/mol, depending on concentration. It is estimated that steric suppression of B400 adsorption comprises 6.2 kJ/mol of this difference, the remainder being the difference in polar electronic effects. Based on the behavior of the reference amines, the difference in polar effects is dominated by π-π electron donor-acceptor (EDA) interactions with sites on polyaromatic surfaces, which are more electropositive and/or more abundant on graphite. Overall, our results show that mesoporosity is critical, that adsorption rate is a function of solute molecular size and charge, that steric bulk in the solute suppresses equilibrium adsorption, and that π-π EDA forces play a role in triazine polar interactions with biochar. PMID:26001283

  18. Collective overcoming of point defects by dislocations in the dynamic region

    NASA Astrophysics Data System (ADS)

    Malashenko, V. V.

    2014-08-01

    A mechanism of collective overcoming of point defects by dislocations during the over-barrier slip has been proposed. It has been shown that the interaction between dislocations promotes the overcoming of point defects at a high dislocation density.

  19. Steric Effects in the Reaction of Aryl Radicals on Surfaces

    SciTech Connect

    Combellas, Catherine; Jiang, Deen; Kanoufi, Frederic; Pinson, Jean; Podvorica, Fetah

    2009-01-01

    Steric effects are investigated in the reaction of aryl radicals with surfaces. The electrochemical reduction of 2-, 3-, 4-methyl, 2-methoxy, 2-ethyl, 2,6-, 2,4-, and 3,5-dimethyl, 4-tert-butyl, 3,5-bis-tert-butyl benzenediazonium, 3,5-bis(trifluoromethyl), and pentafluoro benzenediazonium tetrafluoroborates is examined in acetonitrile solutions. It leads to the formation of grafted layers only if the steric hindrance at the 2- or 2,6-position(s) is small. When the 3,5-positions are crowded with tert-butyl groups, the growth of the organic layer is limited by steric effects and a monolayer is formed. The efficiency of the grafting process is assessed by cyclic voltammetry, X-ray photoelectron spectroscopy, infrared, and ellipsometry. These experiments, together with density functional computations of bonding energies of substituted phenyl groups on a copper surface, are discussed in terms of the reactivity of aryl radicals in the electrografting reaction and in the growth of the polyaryl layer.

  20. Overcoming the Polyester Image.

    ERIC Educational Resources Information Center

    Regan, Dorothy

    1988-01-01

    Urges community colleges to overcome their image problem by documenting the colleges' impact on their communities. Suggests ways to determine what data should be collected, how to collect the information, and how it can be used to empower faculty, staff, and alumni to change the institution's image. (DMM)

  1. Deterministic folding: The role of entropic forces and steric specificities

    NASA Astrophysics Data System (ADS)

    da Silva, Roosevelt A.; da Silva, M. A. A.; Caliri, A.

    2001-03-01

    The inverse folding problem of proteinlike macromolecules is studied by using a lattice Monte Carlo (MC) model in which steric specificities (nearest-neighbors constraints) are included and the hydrophobic effect is treated explicitly by considering interactions between the chain and solvent molecules. Chemical attributes and steric peculiarities of the residues are encoded in a 10-letter alphabet and a correspondent "syntax" is provided in order to write suitable sequences for the specified target structures; twenty-four target configurations, chosen in order to cover all possible values of the average contact order χ (0.2381⩽χ⩽0.4947 for this system), were encoded and analyzed. The results, obtained by MC simulations, are strongly influenced by geometrical properties of the native configuration, namely χ and the relative number φ of crankshafts-type structures: For χ<0.35 the folding is deterministic, that is, the syntax is able to encode successful sequences: The system presents larger encodability, minimum sequence-target degeneracies and smaller characteristic folding time τf. For χ⩾0.35 the above results are not reproduced any more: The folding success is severely reduced, showing strong correlation with φ. Additionally, the existence of distinct characteristic folding times suggests that different mechanisms are acting at the same time in the folding process. The results (all obtained from the same single model, under the same "physiological conditions") resemble some general features of the folding problem, supporting the premise that the steric specificities, in association with the entropic forces (hydrophobic effect), are basic ingredients in the protein folding process.

  2. Thin Filament Structure and the Steric Blocking Model.

    PubMed

    Lehman, William

    2016-04-01

    By interacting with the troponin-tropomyosin complex on myofibrillar thin filaments, Ca2+ and myosin govern the regulatory switching processes influencing contractile activity of mammalian cardiac and skeletal muscles. A possible explanation of the roles played by Ca2+ and myosin emerged in the early 1970s when a compelling "steric model" began to gain traction as a likely mechanism accounting for muscle regulation. In its most simple form, the model holds that, under the control of Ca2+ binding to troponin and myosin binding to actin, tropomyosin strands running along thin filaments either block myosin-binding sites on actin when muscles are relaxed or move away from them when muscles are activated. Evidence for the steric model was initially based on interpretation of subtle changes observed in X-ray fiber diffraction patterns of intact skeletal muscle preparations. Over the past 25 years, electron microscopy coupled with three-dimensional reconstruction directly resolved thin filament organization under many experimental conditions and at increasingly higher resolution. At low-Ca2+, tropomyosin was shown to occupy a "blocked-state" position on the filament, and switched-on in a two-step process, involving first a movement of tropomyosin away from the majority of the myosin-binding site as Ca2+ binds to troponin and then a further movement to fully expose the site when small numbers of myosin heads bind to actin. In this contribution, basic information on Ca2+-regulation of muscle contraction is provided. A description is then given relating the voyage of discovery taken to arrive at the present understanding of the steric regulatory model. PMID:27065174

  3. Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Stronach, M. W.; Ketner, R. J.; Hurley, T. B.

    1995-01-01

    Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

  4. A Steric Block in Translation Caused by the Antibiotic Spectinomycin

    PubMed Central

    Holton, James M.; Fredrick, Kurt; Cate, Jamie H. D.

    2015-01-01

    The widely used antibiotic spectinomycin inhibits bacterial protein synthesis by blocking translocation of messenger RNA and transfer RNAs on the ribosome. Here, we show that in crystals of the Escherichia coli 70S ribosome spectinomycin binding traps a distinct swiveling state of the head domain of the small ribosomal subunit. Spectinomycin also alters the rate and completeness of reverse translocation in vitro. These structural and biochemical data indicate that in solution spectinomycin sterically blocks swiveling of the head domain of the small ribosomal subunit and thereby disrupts the translocation cycle. PMID:17696316

  5. Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

    SciTech Connect

    Tomasello, Gaia; Altoe, Piero; Stenta, Marco; Olaso-Gonzalez, Gloria; Garavelli, Marco; Orlandi, Giorgio

    2007-12-26

    Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutral GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.

  6. Optimized steric stabilization of aqueous ferrofluids and magnetic nanoparticles.

    PubMed

    Jain, Nirmesh; Wang, Yanjun; Jones, Stephen K; Hawkett, Brian S; Warr, Gregory G

    2010-03-16

    The preparation and properties of an aqueous ferrofluid consisting of a concentrated (>65 wt %) dispersion of sterically stabilized superparamagnetic, iron oxide (maghemite) nanoparticles stable for several months at high ionic strength and over a broad pH range is described. The 6-8 nm diameter nanoparticles are individually coated with a short poly(acrylic acid)-b-poly(acrylamide) copolymer, designed to form the thinnest possible steric stabilizing layer while remaining strongly attached to the iron oxide surface over a wide range of nanoparticle concentrations. Thermogravimetric analysis yields an iron oxide content of 76 wt % in the dried particles, consistent with a dry polymer coating of approximately 1 nm in thickness, while the poly(acrylamide) chain length indicated by electrospray mass spectrometry is consistent with the 4-5 nm increase in the hydrodynamic radius observed by light scattering when the poly(acrylamide) stabilizing chains are solvated. Saturation magnetization experiments indicate nonmagnetic surface layers resulting from the strong chemical attachment of the poly(acrylic acid) block to the particle surface, also observed by Fourier transform infrared spectroscopy. PMID:19950943

  7. Steric-electronic effects in malarial peptides inducing sterile immunity

    SciTech Connect

    Moreno-Vranich, Armando; Patarroyo, Manuel E.

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer Is it evident that the residues position are relevant regarding of {phi} angular value. Black-Right-Pointing-Pointer The geometry considered for detailing the alterations undergone by HABPs. Black-Right-Pointing-Pointer The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.

  8. Steric effects and preferential interactions in supercritical carbon dioxide

    SciTech Connect

    Saquing, C.D.; Lucien, F.P.; Foster, N.R

    1998-10-01

    Solubility data are presented for a mixture of o-hydroxybenzoic acid (o-HBA) and m-HBA in supercritical CO{sub 2} doped with 3.5 mol% methanol. The data were measured at 318 and 328 K and for pressures in the range of 101--201 bar. Some new data for the solubility of pure m-HBA in methanol-doped supercritical CO{sub 2} are also presented. The solubilities of the HBA isomers are enhanced considerably with the addition of methanol to supercritical CO{sub 2}. However, the solubility enhancement is strongly affected by the spatial arrangement of their functional groups (steric effect). There appears to be preferential interaction between the solutes and the cosolvent in the quaternary system, and this phenomenon is consistent with thermodynamic modeling of the system.

  9. Blocking cyclobutane pyrimidine dimer formation by steric hindrance.

    PubMed

    Vendrell-Criado, Victoria; Lhiaubet-Vallet, Virginie; Yamaji, Minoru; Cuquerella, M Consuelo; Miranda, Miguel A

    2016-04-26

    The efficiency of thymine (Thy) and uracil (Ura) to form cyclobutane pyrimidine dimers (CPDs) in solution, upon UV irradiation differs by one order of magnitude. This could to be partially related to the steric hindrance induced by the methyl at C5 in thymine. The aim of the present work is to establish the influence of a bulky moiety at this position on the photoreactivity of pyrimidines. With this purpose, photosensitization with benzophenone and acetone of a 5-tert-butyl uracil derivative () and the equivalent Thy () has been compared. Introduction of the tert-butyl group completely blocks CPD formation. Moreover, the mechanistic insight obtained by laser flash photolysis is in accordance with the observed photoreactivity. PMID:27112630

  10. Modulations in restricted amide rotation by steric induced conformational trapping

    NASA Astrophysics Data System (ADS)

    Krishnan, V. V.; Thompson, William B.; Goto, Joy J.; Maitra, Kalyani; Maitra, Santanu

    2012-01-01

    The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.

  11. Sterically stabilized water based magnetic fluids: Synthesis, structure and properties

    NASA Astrophysics Data System (ADS)

    Bica, Doina; Vékás, Ladislau; Avdeev, Mikhail V.; Marinică, Oana; Socoliuc, Vlad; Bălăsoiu, Maria; Garamus, Vasil M.

    2007-04-01

    Magnetic fluids (MFs), prepared by chemical co-precipitation followed by double layer steric and electrostatic (combined) stabilization of magnetite nanoparticles dispersed in water, are presented. Several combinations of surfactants with different chain lengths (lauric acid (LA), myristic acid (MA), oleic acid (OA) and dodecyl-benzene-sulphonic acid (DBS)) were used, such as LA+LA, MA+MA, LA+DBS, MA+DBS, OA+DBS, OA+OA and DBS+DBS. Static light scattering, transmission electron microscopy, small angle neutron scattering, magnetic and magneto-rheological measurements revealed that MFs with MA+MA or LA+LA biocompatible double layer covered magnetite nanoparticles are the most stable colloidal systems among the investigated samples, and thus suitable for biomedical applications.

  12. Overcoming associative learning.

    PubMed

    Haselgrove, Mark

    2016-08-01

    Thorndike (1898, 1911) rejected the idea that animal behavior was the consequence of reasoning, and suggested instead that the gradual acquisition of associations formed the basis of behavior-a contention that has had a significant impact on the development of animal learning theory. Despite this, comparative psychology provides a number of examples of behaviors that have been considered to be above and beyond the explanation of associative-, or reinforcement-learning mechanisms. These behaviors have motivated some researchers to propose higher-order cognitive abilities in animals, including (but not limited to) reasoning, sensitivity to ambiguity, and metacognition. However, other authors have questioned this claim, and provided alternative explanations for these behaviors from an associative perspective. With relevant examples, the steps that must be taken in order to overcome an associative explanation of behavior are described. (PsycINFO Database Record PMID:26986019

  13. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  14. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  15. Psychological Barriers to Behavior Change

    PubMed Central

    Olson, James M.

    1992-01-01

    Adopting a healthy lifestyle often requires changing patterns of behavior. This article describes three categories of psychological barriers to behavior change: those that prevent the admission of a problem, those that interfere with initial attempts to change behavior, and those that make long-term change difficult. Strategies are identified that family physicians can use to overcome the barriers. PMID:21221258

  16. Modulated nematic structures induced by chirality and steric polarization

    NASA Astrophysics Data System (ADS)

    Longa, Lech; PajÄ k, Grzegorz

    2016-04-01

    What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (NLP) and transverse (NTP) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (NTB) and the splay-bend nematic phase (NSB), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral NTP and NSB into new NTB phases. Surprisingly, the nonchiral NLP phase can stay stable even in the presence of intrinsic chirality.

  17. Lis1 regulates dynein by sterically blocking its mechanochemical cycle

    PubMed Central

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-01-01

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein–Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the ‘linker’, from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle. DOI: http://dx.doi.org/10.7554/eLife.03372.001 PMID:25380312

  18. Sterically allowed configuration space for amino acid dipeptides

    NASA Astrophysics Data System (ADS)

    Caballero, Diego; Maatta, Jukka; Sammalkorpi, Maria; O'Hern, Corey; Regan, Lynne

    2014-03-01

    Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic propensities for amino acids to be in particular backbone or side-chain conformations. This question has remained unsettled for years because of the discrepancies between different experimental approaches. To address it, I performed all-atom hard-sphere simulations of hydrophobic residues with stereo-chemical constraints and non-attractive steric interactions between non-bonded atoms for ALA, ILE, LEU and VAL dipeptide mimetics. For these hard-sphere MD simulations, I show that transitions between α-helix and β-sheet structures only occur when the bond angle τ(N -Cα - C) >110° , and the probability distribution of bond angles for structures in the `bridge' region of ϕ- ψ space is shifted to larger angles compared to that in other regions. In contrast, the relevant bond-angle distributions obtained from most molecular dynamics packages are broader and shifter to larger values. I encounter similar correlations between bond angles and side-chain dihedral angles. The success of these studies is an argument for re-incorporating local stereochemical constraints into computational protein design methodology.

  19. Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia.

    PubMed

    Dobramysl, Ulrich; Papoian, Garegin A; Erban, Radek

    2016-05-10

    Filopodia are ubiquitous fingerlike protrusions, spawned by many eukaryotic cells, to probe and interact with their environments. Polymerization dynamics of actin filaments, comprising the structural core of filopodia, largely determine their instantaneous lengths and overall lifetimes. The polymerization reactions at the filopodial tip require transport of G-actin, which enter the filopodial tube from the filopodial base and diffuse toward the filament barbed ends near the tip. Actin filaments are mechanically coupled into a tight bundle by cross-linker proteins. Interestingly, many of these proteins are relatively short, restricting the free diffusion of cytosolic G-actin throughout the bundle and, in particular, its penetration into the bundle core. To investigate the effect of steric restrictions on G-actin diffusion by the porous structure of filopodial actin filament bundle, we used a particle-based stochastic simulation approach. We discovered that excluded volume interactions result in partial and then full collapse of central filaments in the bundle, leading to a hollowed-out structure. The latter may further collapse radially due to the activity of cross-linking proteins, hence producing conical-shaped filament bundles. Interestingly, electron microscopy experiments on mature filopodia indeed frequently reveal actin bundles that are narrow at the tip and wider at the base. Overall, our work demonstrates that excluded volume effects in the context of reaction-diffusion processes in porous networks may lead to unexpected geometric growth patterns and complicated, history-dependent dynamics of intermediate metastable configurations. PMID:27166814

  20. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases

    PubMed Central

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs’ unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a “water-soluble” amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug’s therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  1. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases.

    PubMed

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  2. Nano- and microfabrication for overcoming drug delivery challenges

    PubMed Central

    Kam, Kimberly R.

    2013-01-01

    This highlight article describes current nano- and microfabrication techniques for creating drug delivery devices. We first review the main physiological barriers to delivering therapeutic agents. Then, we describe how novel fabrication methods can be utilized to combine many features into a single physiologically relevant device to overcome drug delivery challenges. PMID:23730504

  3. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Lynn Sparling; Bruce C. Buckheit; Daniel LoBue; and Richard P. Bowers

    2012-06-29

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  4. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Richard P. Bowers; Dr. Lynn Sparling; Bruce Buckheit; Daniel LoBue

    2012-05-31

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  5. Perspective: Vibrational-induced steric effects in bimolecular reactions

    SciTech Connect

    Liu, Kopin

    2015-02-28

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C–H stretch-excited CHD{sub 3}(v{sub 1} = 1) with F, Cl, and O({sup 3}P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O({sup 3}P) + CHD{sub 3}(v{sub 1} = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical “negative” lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD{sub 3}. On the contrary, the interaction between O({sup 3}P) and CHD{sub 3}(v{sub 1} = 1) behaves as a “positive” lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD{sub 3}(v{sub 1} = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi’s rules, are made.

  6. Comparative investigation of antimutagenic activity of sterically hindered phenols

    SciTech Connect

    Pashin, Yu.V.; Bakhitova, L.M.; Bentkhen, T.I.

    1985-07-01

    Mutagenic properties of primarily inactive carcinogenic polycyclic aromatic hydrocarbons (PAH) are manifested after metabolic oxidation by microsomal enzymes. It has been established that activation of carcinogens in biological systems is accompanied by intensification of free-radical processes, effective inhibition of which is achieved by sterically hindered phenols (SHP). The authors studied the effect of SHP on the mutagenic activity of benzo(a)pyrene (BP) using estimation of induced direct gene mutation at the locus for hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) in somatic Chinese hamster cells of line V-79 cultured in vitro and with estimation of the induction of micronuclei in polychromatophilic erythrocytes of mouse bone marrow in vivo. The reference mutagen was BP from Fluka and the following SHP were used: dibunol, F-800, and F-804. Genetic activity of each substance tested and their combination was studied in an in vitro system under conditions of metabolic activation by mouse liver microsomes and in vivo according to induction of micronuclei in polychromatophilic bone marrow erythrocytes in (CBA x C57B1/6J)F/sub 1/ mice 60-80 days old, which reflects gross defects of chromosomes at the erythroblast stage. In order to establish optimal time for recording the frequency of induction of micronuclei, bone marrow samples were taken from the animals, 24, 48, 72, and 96 h after a single intraperitoneal injection of the agents. The BP was dissolved in sunflower oil and used in a concentration constituting 1/3 of the lowest lethal dose in mice. The SHP was then dissolved in water or dimethyl sulfoxide and administered in a ratio with BP of 1:1 or 1:0.5. The smears were then stained in methanol, washed with twice-distilled water, and stained in 7% Giemsa solution.

  7. Overcoming Barriers to Student Participation in Online Discussions

    ERIC Educational Resources Information Center

    Goodell, Joanne; Yusko, Brian

    2005-01-01

    This paper is an analysis of the issues encountered in the process of building a community of practice amongst students through engaging in online dialogue using WebCT. The analysis is guided by an educational change framework, proposed by Goodell, Parker, and Kahle (2005), which includes Technical, Political, Cultural, Moral, and Personal…

  8. Overcoming barriers to priority setting using interdisciplinary methods.

    PubMed

    Peacock, Stuart; Mitton, Craig; Bate, Angela; McCoy, Bonnie; Donaldson, Cam

    2009-10-01

    Ten years ago, Holm's highly influential paper "Goodbye to the simple solutions: the second phase of priority setting" was published [Holm S. Goodbye to the simple solutions: the second phase of priority setting in health care. British Medical Journal 1998;317:1000-7]. Whilst attending the 2nd International Conference on Priorities in Health Care in London, Holm argued that the search for a rational set of decision-making rules was no longer adequate. Instead, the priority setting process itself was now thought to be more complex. Ten years later, the Conference returns to the UK for the first time, and it is timely to describe some new tools intended to assist both researchers and decision-makers seeking to develop both rational and fair and legitimate priority setting processes. In this paper we argue that to do so, researchers and decision-makers need to adopt an interdisciplinary and collaborative approach to priority setting. We focus on program budgeting and marginal analysis (PBMA) and bring together three hitherto separate interdisciplinary strands of the PBMA literature. Our aim is to assist researchers and decision-makers seeking to effectively develop and implement PBMA in practice. Specifically, we focus on the use of multi-criteria decision analysis, participatory action research, and accountability for reasonableness, drawn from the disciplines of decision analysis, sociology, and ethics respectively. PMID:19346024

  9. HIV/HCV Co-infection: Overcoming Barriers to Treatment.

    PubMed

    Gross, Chloe; Akoth, Elizabeth; Price, Angie; Kattakuzhy, Sarah; Silk, Rachel; Rosenthal, Elana

    2016-01-01

    A critical step in the eradication of hepatitis C virus (HCV) infection is access to effective therapy. With the advent of interferon-free regimens, HCV providers and patients gained hope that the success seen in clinical trials could be translated to the real world. However, the exorbitant cost of the new direct-acting antivirals limits access to these medications to the general HCV population, especially underserved patients with public insurance. We used a descriptive qualitative approach to detail the measures necessary and challenges faced by an inner-city nursing team in Washington, DC to obtain the new direct-acting antivirals. Significant time and dedication on the part of providers and staff was required to assist patients with the process of obtaining direct-acting antivirals. PMID:26996983

  10. Overcoming Barriers: Personal and Organizational Development in Schools.

    ERIC Educational Resources Information Center

    Hunsaker, Johanna S.; Hunsaker, Phillip L.

    1979-01-01

    Freedom from material insecurity brings with it new human expectations. Demands for personal fulfillment and development of human potential will increasingly be placed on schools, and change will be necessary for organizational success and individual self-actualization. The authors present ten principles for bringing about desired changes.…

  11. Barriers to Effective Inclusion and Strategies to Overcome Them

    ERIC Educational Resources Information Center

    Darrow, Alice-Ann

    2009-01-01

    Much progress has been made in the past three decades to improve the quality of education for students with disabilities. Schools have had to undergo complex changes in order to implement the special education laws regarding access to and structure of educational services. Although services have dramatically improved, there remain frequent…

  12. Overcoming Barriers: Engaging Younger Students in an Online Intercultural Exchange

    ERIC Educational Resources Information Center

    Peiser, Gillian

    2015-01-01

    This paper reports on a small-scale project involving an online school exchange between two classes of 12-/13-year olds located in the North of England and the Ruhr area of Germany. The overarching aim of the project was to develop intercultural understanding in foreign language learning through communication in an online environment. Analysing…

  13. Wind Power in Australia: Overcoming Technological and Institutional Barriers

    ERIC Educational Resources Information Center

    Healey, Gerard; Bunting, Andrea

    2008-01-01

    Until recently, Australia had little installed wind capacity, although there had been many investigations into its potential during the preceding decades. Formerly, state-owned monopoly utilities showed only token interest in wind power and could dictate the terms of energy debates. This situation changed in the late 1990s: Installed wind capacity…

  14. Overcoming Defensive Barriers to Communication: A Transactional Analysis Approach

    ERIC Educational Resources Information Center

    Carr-Smith, Norma

    1978-01-01

    Discusses executives' behaviors that create both defensive and supportive climates for workers, indicating ways in which transactional analysis can be used to interpret these behaviors and their effects. (RL)

  15. Overcoming Barriers to Intercultural Relationships: A Culturally Competent Approach.

    ERIC Educational Resources Information Center

    Osher, David; Mejia, Brenda

    1999-01-01

    Profiles programs of two youth centers that are successfully bridging cultural differences through the development of cultural competence. Both centers acknowledge that actualizing cross-cultural competency means providing a way for their ethnic groups to interact with the larger population without losing their cultural heritage. Programs include…

  16. Overcoming the Financial Aid Barrier for E-Learners

    ERIC Educational Resources Information Center

    Chaloux, Bruce

    2008-01-01

    Financial aid systems help make higher education available to all who can benefit. To "adjust" the existing financial aid system to make it more student friendly and open doors currently closed to many part-time learners and students with the greatest financial challenges, state policy changes and greater private sector initiatives targeted at…

  17. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial maintenance workers…

  18. Virtual states introduced for overcoming entropic barriers in conformational space

    PubMed Central

    Higo, Junichi; Nakamura, Haruki

    2012-01-01

    Free-energy landscape is an important quantity to study large-scale motions of a biomolecular system because it maps possible pathways for the motions. When the landscape consists of thermodynamically stable states (low-energy basins), which are connected by narrow conformational pathways (i.e., bottlenecks), the narrowness slows the inter-basin round trips in conformational sampling. This results in inaccuracy of free energies for the basins. This difficulty is not cleared out even when an enhanced conformational sampling is fairly performed along a reaction coordinate. In this study, to enhance the inter-basin round trips we introduced a virtual state that covers the narrow pathways. The probability distribution function for the virtual state was controlled based on detailed balance condition for the inter-state transitions (transitions between the real-state basins and the virtual state). To mimic the free-energy landscape of a real biological system, we introduced a simple model where a wall separates two basins and a narrow hole is pierced in the wall to connect the basins. The sampling was done based on Monte Carlo (MC). We examined several hole-sizes and inter-state transition probabilities. For a small hole-size, a small inter-state transition probability produced a sampling efficiency 100 times higher than a conventional MC does. This result goes against ones intuition, because one considers generally that the sampling efficiency increases with increasing the transition probability. The present method is readily applicable to enhanced conformational sampling such as multi-canonical or adaptive umbrella sampling, and extendable to molecular dynamics.

  19. Telecollaborative Networks in University Higher Education: Overcoming Barriers to Integration

    ERIC Educational Resources Information Center

    O'Dowd, Robert

    2013-01-01

    Foreign language telecollaboration refers to virtual intercultural interaction and exchange projects between classes of learners in geographically distant locations. While research findings on telecollaboration have confirmed its valuable contribution to students' foreign language, intercultural and electronic competences, a preliminary research…

  20. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    NASA Astrophysics Data System (ADS)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  1. Postsecondary Correctional Education: Recognizing and Overcoming Barriers to Success

    ERIC Educational Resources Information Center

    Palmer, Shelby M.

    2012-01-01

    Postsecondary programs offering vocational training and college credit to eligible inmates have had difficulty finding a place in the U.S. correctional system. Politically motivated restrictions preventing inmates from receiving federal funds for college resulted in drastic program closures. Although new laws restored funding to select inmates,…

  2. Overcoming barriers to residential conservation: do energy audits help

    SciTech Connect

    Hoffman, W.L.

    1982-12-01

    A study on the effects of energy audits on the pace and choice of household investment in energy-saving improvements in the home is reported. An evaluation based on the household's assessment of the usefulness of the audit which was provided for their home was performed. The number and types of recent conservation actions among audited and unaudited samples of households are compared. The audit's effect on household knowledge about the economically attractive options for their home and on the choice of recent improvements is assessed. Possible reasons are suggested for the weak effect of audits in stimulating activity and reorienting investment choices. (LEW)

  3. But Can She Cook? Overcoming the Barriers to Women's Education.

    ERIC Educational Resources Information Center

    Antler, Joyce

    1985-01-01

    Reviews Barbara Miller Solomon's "In the Company of Educated Women," a comprehensive survey of the history of collegiate women. Asserts that this history successfully describes the subtle interplay between women's possibilities within higher education and their shifting roles in the larger society. (KH)

  4. What Changes Education? An Action Research to Overcome Barriers

    ERIC Educational Resources Information Center

    Eskicioglu, Yeser Eroglu

    2016-01-01

    According to the National Disabled People Data Base within Ministry of Family and Social Policies (Özveri), there are 1.559.222 disabled people in Turkey. If this rate would be linked to the families of the disabled people, the number of people who spend time with disabled individuals would increase to 10 million. This number corresponds to 12.5%…

  5. Acceleration: Overcoming the Vector Barrier with Simple Practical Models.

    ERIC Educational Resources Information Center

    Whitworth, R.

    1988-01-01

    Describes five basic concepts, such as displacement, velocity, momentum, force, and moment of force. Discusses an experimental model to improve the intuitive understanding of acceleration in a straight line and a non-linear situation. (YP)

  6. Overcoming Barriers for "Niche" Learners through Distance Learning.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; And Others

    For over 15 years, Tennessee's Chattanooga State Technical Community College has been offering non-traditional, distance education to reach "niches" of students who would otherwise find it difficult to attain a college education. Begun in 1979 with a laboratory-based independent study program offering a mix of purchased and locally-developed…

  7. Improving The Perfect Storm: Overcoming Barriers To Climate Literacy

    NASA Astrophysics Data System (ADS)

    Tillinger, D.

    2015-12-01

    Students and scientists are trained to speak different languages. Climate science, and the geosciences more broadly, are strictly classroom topics, not subjects appropriate for casual conversation, social media, or creative projects. When students are aware of climate change through the mainstream media, it is nearly always in a political or technological context rather than a scientific one. However, given the opportunity, students are perfectly capable of not only understanding the science behind climate change, but communicating it to their peers. At the American Museum of Natural History, a group of underprivileged high school students visited Nature's Fury: The Science of Natural Disasters to learn about volcanoes, earthquakes, and climate change impacts. They were then able to write pitches and develop trailers for scientifically accurate, but still compelling, disaster movies. Arts in Parts, a creative outreach group formed as a response to Hurricane Sandy, facilitated a workshop in which younger children made mobiles from beach debris they collected while learning about the the threat of sea level rise locally and globally. Participants in an undergraduate natural disasters class wrote guides to understanding climate change that remained factual while showing great creativity and reflecting the personality of each student. Art, humor, and popular culture are the languages that society chooses to use; scientific literacy might benefit from their inclusion.

  8. Viscoelastic properties of sterically stabilised emulsions and their stability.

    PubMed

    Tadros, Tharwat

    2015-08-01

    The interaction forces between emulsion droplets containing adsorbed polymeric surfactants and the theory of steric stabilisation are briefly described. The results for the viscoelastic properties of O/W emulsions that are stabilised with partially hydrolysed poly(vinyl acetate) that is commonly referred to as poly(vinyl alcohol) (PVA) with 4% vinyl acetate are given. The effect of the oil volume fraction, addition of electrolytes and increasing temperature is described. This allows one to obtain various parameters such as the adsorbed layer thickness, the critical flocculation concentration of electrolyte (CFC) and critical flocculation temperature (CFT) at constant electrolyte concentration. The viscoelastic properties of O/W emulsions stabilised with an A-B-A block copolymer of polyethylene oxide (A) and polypropylene oxide (B) are described. These emulsions behave as viscoelastic liquids showing a cross-over-point between G' (the elastic component of the complex modulus) and G″ (the viscous component of the complex modulus) at a characteristic frequency. Plots of G' and G″ versus oil volume fraction ϕ show the transition from predominantly viscous to predominantly elastic response at a critical volume fraction ϕ(c). The latter can be used to estimate the adsorbed layer thickness of the polymeric surfactants. Results are also shown for W/O emulsions stabilised with an A-B-A block copolymer of polyhydroxystearic acid (PHS, A) and polyethylene oxide (PEO, B). The viscosity volume fraction curves could be fitted to the Dougherty-Krieger equation for hard-spheres. The results could be applied to give an estimate of the adsorbed layer thickness Δ which shows a decrease with increase of the water volume fraction. This is due to the interpenetration and/or compression of the PHS layers on close approach of the water droplets on increasing the water volume fraction. The last section of the review gives an example of O/W emulsion stability using an AB(n) graft

  9. Sterically encumbered tin and phosphorus peri-substituted acenaphthenes.

    PubMed

    Chalmers, Brian A; Athukorala Arachchige, Kasun S; Prentis, Joanna K D; Knight, Fergus R; Kilian, Petr; Slawin, Alexandra M Z; Woollins, J Derek

    2014-08-18

    A group of sterically encumbered peri-substituted acenaphthenes have been prepared, containing tin moieties at the 5,6-positions in 1-3 ([Acenap(SnR3)2], Acenap = acenaphthene-5,6-diyl; R3 = Ph3 (1), Me3 (2); [(Acenap)2(SnMe2)2] (3)) and phosphorus functional groups at the proximal peri-positions in 4 and 5 ([Acenap(PR2)(P(i)Pr2)] R2 = Ph2 (4), Ph((i)Pr) (5)). Bis(stannane) structures 1-3 are dominated by repulsive interactions between the bulky tin groups, leading to peri-distances approaching the sum of van der Waals radii. Conversely, the quasi-linear CPh-P···P three-body fragments found in bis(phosphine) 4 suggest the presence of a lp(P)-σ*(P-C) donor-acceptor 3c-4e type interaction, supported by a notably short intramolecular P···P distance and notably large JPP through-space coupling (180 Hz). Severely strained bis(sulfides) 4-S and 5-S, experiencing pronounced in-plane and out-of-plane displacements of the exocyclic peri-bonds, have also been isolated following treatment of 4 and 5 with sulfur. The resulting nonbonded intramolecular P···P distances, ∼4.05 Å and ∼12% longer than twice the van der Waals radii of P (3.60 Å), are among the largest ever reported peri-separations, independent of the heteroatoms involved, and comparable to the distance found in 1 containing the larger Sn atoms (4.07 Å). In addition we report two metal complexes with square planar [(4)PtCl2] (4-Pt) and octahedral cis-[(4)Mo(CO)4] (4-Mo) geometries. In both complexes the bis(phosphine) backbone is distorted, but notably less so than in bis(sulfide) 4-S. All compounds were fully characterized, and except for bis(phosphine) 5, crystal structures were determined. PMID:25080308

  10. Photocleavage control of nucleated DNA nanosystems--the influence of surface strand sterics.

    PubMed

    Hanna, Morcos; Munshi, Moorsalin; Kedzierski, Nancy A; Chung, Paul N; Huang, Terry; Mok, Allen K; Lukeman, Philip S

    2014-02-21

    We use sterically inaccessible 'seed' strands, released from a surface into solution by photocleavage to initiate a nucleated DNA polymerization reaction. We demonstrate control of the quantity of 'seed' release and that hairpin steric protection of the 'seed' leads to less 'leaky' surfaces. This polymerization is a model system for surface-photocleavage initiation of sub-stoichiometric reaction cascades; these cascades should find use as a component of labs-on-chips capable of bioanalytical and DNA-computing tasks. PMID:24402244

  11. In Vivo Gene Delivery by Nonviral Vectors: Overcoming Hurdles?

    PubMed Central

    Zhang, Yuan; Satterlee, Andrew; Huang, Leaf

    2012-01-01

    The promise of cancer gene therapeutics is hampered by difficulties in the in vivo delivery to the targeted tumor cells, and systemic delivery remains to be the biggest challenge to be overcome. Here, we concentrate on systemic in vivo gene delivery for cancer therapy using nonviral vectors. In this review, we summarize the existing delivery barriers together with the requirements and strategies to overcome these problems. We will also introduce the current progress in the design of nonviral vectors, and briefly discuss their safety issues. PMID:22525514

  12. Unfavorable electrostatic and steric interactions in DNA polymerase β E295K mutant interfere with the enzyme’s pathway

    PubMed Central

    Li, Yunlang; Gridley, Chelsea L.; Jaeger, Joachim; Sweasy, Joann B.; Schlick, Tamar

    2012-01-01

    Mutations in DNA polymerase β (pol β) have been associated with approximately 30% of human tumors. The E295K mutation of pol β has been linked to gastric carcinoma via interference with base excision repair. To interpret the different behavior of E295K compared to wild-type pol β in atomic and energetic detail, we resolve a binary crystal complex of E295K at 2.5 Å and apply transition path sampling (TPS) to delineate the closing pathway of the E295K pol β mutant. Conformational changes are important components in the enzymatic pathway that lead to and ready the enzyme for the chemical reaction. Our analyses show that the closing pathway of E295K mutant differs from the wild-type pol β in terms of the individual transition states along the pathway, associated energies, and the active site conformation in the final closed form of the mutant. In particular, the closed state of E295K has a more distorted active site than the active site in the wild-type pol β. In addition, the total energy barrier in the conformational closing pathway is 65 ± 11 kJ/mol, much higher than that estimated for both correct (e.g., G:C) and incorrect (e.g., G:A) wild-type pol β systems (42 ± 8 kJ/mol and 45 ± 7 kJ/mol, respectively). In particular, the rotation of Arg258 is the rate-limiting step in the conformational pathway of E295K due to unfavorable electrostatic and steric interactions. The distorted active site in the closed relative to open state and the high energy barrier in the conformational pathway may explain in part why the E295K mutant is observed to be inactive. Interestingly, however, following the closing of the thumb but prior to the rotation of Arg258, the E295K mutant complex has a similar energy level compared to the wild-type pol β. This suggests that the E295K mutant may associate with DNA with similar affinity, but it may be hampered in continuing the process of chemistry. Supporting experimental data come from the observation that the catalytic activity

  13. Overcoming Exclusion through Adult Learning.

    ERIC Educational Resources Information Center

    Nash, Ian; Walshe, John

    Strategies for overcoming exclusion through adult learning were identified through case studies of 19 initiatives in the following countries: Belgium; Mexico; the Netherlands; Norway; Portugal; and the United Kingdom. The study programs involved a diverse array of formal, nonformal, and informal public sector, community, and enterprise-based…

  14. Overcoming Roadblocks to Healthy Eating

    MedlinePlus

    ... National Institute on Aging at NIH Search form Search this site Menu Get Started Try These Exercises Go to My Go4Life Get Free Stuff Be a Partner Overcoming Roadblocks to Healthy Eating Sometimes it’s hard to make smart food choices . Here are some suggestions from Go4Life ...

  15. Overcoming Prejudices: An Invitational Approach.

    ERIC Educational Resources Information Center

    Reed, Charlotte

    1996-01-01

    Offers an invitational model for overcoming prejudices. The model, based on the five-step approach of M. Haberman (1994) and the conflict management plan of W. W. Purkey (1992) proposes an effective and sensitive method for dealing with prejudice and discrimination in the schools. (SLD)

  16. Helping Young Children Overcome Shyness.

    ERIC Educational Resources Information Center

    Malouff, John

    This paper examines shyness--its causes and its impact on children--and presents several strategies based on social learning theory for parents and teachers to help young children overcome shyness. The paper also describes a personal application of these strategies on a young girl. The strategies presented for parents and teachers are: (1) tell…

  17. Measuring Transmembrane Helix Interaction Strengths in Lipid Bilayers Using Steric Trapping

    PubMed Central

    Hong, Heedeok; Chang, Yu-Chu; Bowie, James U.

    2016-01-01

    We have developed a method to measure strong transmembrane (TM) helix interaction affinities in lipid bilayers that are difficult to measure by traditional dilution methods. The method, called steric trapping, couples dissociation of biotinylated TM helices to a competitive binding by monovalent streptavidin (mSA), so that dissociation is driven by the affinity of mSA for biotin and mSA concentration. By adjusting the binding affinity of mSA through mutation, the method can obtain dissociation constants of TM helix dimers (Kd,dimer) over a range of six orders of magnitudes. The Kd,dimer limit of measurable target interaction is extended 3–4 orders of magnitude lower than possible by dilution methods. Thus, steric trapping opens up new opportunities to study the folding and assembly of α-helical membrane proteins in lipid bilayer environments. Here we provide detailed methods for applying steric trapping to a TM helix dimer. PMID:23975771

  18. Bis(oxazolines) based on glycopyranosides - steric, configurational and conformational influences on stereoselectivity.

    PubMed

    Minuth, Tobias; Boysen, Mike M K

    2010-01-01

    In previous studies we found that the asymmetric induction of bis(oxazolines) based on D-glucosamine strongly depended on the steric demand of the 3-O-substituents. To further probe the impact of the 3-position of the pyranose scaffold, we prepared 3-epimerised and 3-defunctionalised versions of these ligands as well as a 3-O-formyl derivative. Application of these new ligands in asymmetric cyclopropanation revealed strong steric and configurational effects of position 3 on asymmetric induction, further dramatic effects of the pyranose conformation were also observed. PMID:20502606

  19. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  20. Overcoming Stereotypes, Discovering Hidden Capitals

    ERIC Educational Resources Information Center

    Beckett, Lori; Wrigley, Terry

    2014-01-01

    This article presents a model of teacher research supported by academic partners to develop a better understanding of the barriers to education faced by young people growing up in poverty. It critiques politicians' demands for teachers to "close the gap" for ignoring the cumulative intergenerational effects of deprivation. The…

  1. Implications of sterically constrained n-butane oxidation reactions on the reaction mechanism and selectivity to 1-butanol

    NASA Astrophysics Data System (ADS)

    Dix, Sean T.; Gómez-Gualdrón, Diego A.; Getman, Rachel B.

    2016-11-01

    Density functional theory (DFT) is used to analyze the reaction network in n-butane oxidation to 1-butanol over a Ag/Pd alloy catalyst under steric constraints, and the implications on the ability to produce 1-butanol selectively using MOF-encapsulated catalysts are discussed. MOFs are porous crystalline solids comprised of metal nodes linked by organic molecules. Recently, they have been successfully grown around metal nanoparticle catalysts. The resulting porous networks have been shown to promote regioselective chemistry, i.e., hydrogenation of trans-1,3-hexadiene to 3-hexene, presumably by forcing the linear alkene to stand "upright" on the catalyst surface and allowing only the terminal C-H bonds to be activated. In this work, we extend this concept to alkane oxidation. Our goal is to determine if a MOF-encapsulated catalyst could be used to selectively produce 1-butanol. Reaction energies and activation barriers are presented for more than 40 reactions in the pathway for n-butane oxidation. We find that C-H bond activation proceeds through an oxygen-assisted pathway and that butanal and 1-butanol are some of the possible products.

  2. Understanding the Effects of Pre-Organization, Rigidity, and Steric Interactions in Synthetic Barbiturate Receptors

    PubMed Central

    McGrath, Jacqueline M.

    2014-01-01

    Synthetic barbiturate receptors have been utilized for many applications due to their high binding affinities for complementary guests. Although interest in this class of receptors spans from supramolecular to materials chemistry, the effects of receptor steric bulk and pre-organization on guest binding affinity has not been studied systematically. To investigate the roles that steric bulk and pre-organization play in guest binding, we prepared a series of 12 deconstructed Hamilton receptors with varying degrees of steric bulk and pre-organization. Both diethylbarbital and 3-methyl-7-propylxanthine were investigated as guests for the synthetic receptors. The stoichiometry of guest binding was investigated using Job plots for each host-guest pair, and 1H NMR titrations were performed to measure the guest binding affinities. To complement the solution-state studies, DFT calculations at the B3LYP/6-31+G(d,p) level of theory employing the IEF-PCM CHCl3 solvation model were also performed. Calculated guest binding energies correlated well with the experimental findings and provided additional insight into the factors influencing guest binding. Taken together, the results presented highlight the interplay between pre-organization and steric interactions establishing favorable interactions for self-assembled hydrogen-bonded systems. PMID:24377967

  3. The applicapility of the steric height criteria of the Antarctic Circumpolar Current jets

    NASA Astrophysics Data System (ADS)

    Tarakanov, Roman

    2016-04-01

    According to the steric height criteria of the jets of the Antarctic Circumpolar Current (ACC) the cores of these jets are kept in time and in a whole circumpolar circle at the same isolines of the steric height. The applicability of these criteria was analyzed on the basis of two databases. The first one is the data of several hydrophysical sections carried out south of Africa which were executed in 2004-2010 along the same track. The second one is the series of daily digital maps of the sea level anomaly (SLA) published by the French CLS agency (www.aviso.oceanobs.com). The analysis was executed by comparing two types of curves along the track. The first one is the differences in the steric heights at the same points between two sections. The second one is the differences in SLA at the same points. The analysis revealed an example of a lack of geometric similarity of these curves for the sections in December 2009 and October 2010 in the southern half of the ACC. This lack is up to 10 cm in the SLA values. This fact points to inapplicability of the steric height criteria of the ACC jets in general. In the other words there is no permanent no-motion surface (depth) in the ACC even in time.

  4. Steric and mass-induced sea level variations in the Mediterranean Sea revisited

    NASA Astrophysics Data System (ADS)

    GarcíA-GarcíA, D.; Chao, B. F.; Boy, J.-P.

    2010-12-01

    The total sea level variation (SLV) is the combination of steric and mass-induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of "altimetry minus GRACE" agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

  5. OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

    EPA Science Inventory

    Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


    Thomas M. Becker, Michael A. Gonzalez*

    United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

  6. Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

    NASA Technical Reports Server (NTRS)

    Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

    1990-01-01

    The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

  7. Epistemological barriers to radical behaviorism

    PubMed Central

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  8. Barriers to Physical Activity Among Gay Men.

    PubMed

    Cary, Miranda A; Brittain, Danielle R; Dinger, Mary K; Ford, Melissa L; Cain, Meagan; Sharp, Teresa A

    2016-09-01

    Gay men may not be physically active at recommended levels to achieve health benefits. Thus, a need exists to identify general (i.e., common across populations) and population-specific barriers that hinder or stop gay men from participating in physical activity (PA). Salient barriers may be identified through the extent each barrier limits PA (i.e., barrier limitation) and the level of one's confidence to overcome barriers and engage in PA (i.e., self-regulatory efficacy). The purposes of this study were to (1) provide a description of general and population-specific barriers to PA among sufficiently and insufficiently active gay men, (2) identify barrier limitation and self-regulatory efficacy for the reported barriers, and (3) examine the associations between meeting the current PA recommendation, barrier limitation, and self-regulatory efficacy. Participants were 108 self-identified gay males aged 21 to 64 years who completed a web-based survey. A total of 35 general barriers and no population-specific barriers were identified by the sufficiently and insufficiently active groups. The sufficiently active group reported higher self-regulatory efficacy and lower barrier limitation for nearly all reported barriers. A binary logistic regression used to examine the associations between PA, barrier limitation, and self-regulatory efficacy was statistically significant, χ(2)(2, N = 108) = 19.26, p < .0001, R(2) = .16. Only barrier limitation significantly contributed to the model. Future research should continue to examine barriers to PA among gay men to determine whether an intervention needs to be designed specifically for gay men or whether a one-size-fits-all intervention would be effective in helping all men overcome common barriers to engaging in PA. PMID:25643585

  9. Adsorption of sterically stabilized latex particles at liquid surfaces: effects of steric stabilizer surface coverage, particle size, and chain length on particle wettability.

    PubMed

    Reed, K M; Borovicka, J; Horozov, T S; Paunov, V N; Thompson, K L; Walsh, A; Armes, S P

    2012-05-01

    A series of five near-monodisperse sterically stabilized polystyrene (PS) latexes were synthesized using three well-defined poly(glycerol monomethacrylate) (PGMA) macromonomers with mean degrees of polymerization (DP) of 30, 50, or 70. The surface coverage and grafting density of the PGMA chains on the particle surface were determined using XPS and (1)H NMR spectroscopy, respectively. The wettability of individual latex particles adsorbed at the air-water and n-dodecane-water interfaces was studied using both the gel trapping technique and the film calliper method. The particle equilibrium contact angle at both interfaces is relatively insensitive to the mean DP of the PGMA stabilizer chains. For a fixed stabilizer DP of 30, particle contact angles were only weakly dependent on the particle size. The results are consistent with a model of compact hydrated layers of PGMA stabilizer chains at the particle surface over a wide range of grafting densities. Our approach could be utilized for studying the adsorption behavior of a broader range of sterically stabilized inorganic and polymeric particles of practical importance. PMID:22502638

  10. Overcoming "the Valley of Death".

    PubMed

    McIntyre, Robin A

    2014-01-01

    On a global level there are major challenges arising from climate change, resource use and changing age demographics. These issues have created a global marketplace for novel innovative products and solutions which can help to combat and overcome these challenges which have created significant commercial opportunities for companies, particularly for small and medium size enterprises or SMEs. Companies most likely to take advantage of these opportunities will be those which can innovate in a timely manner. Innovation significantly contributes to higher productivity and economic growth, and is core to a company's competitiveness within often challenging marketplaces. However, many factors can stifle innovation. Companies can struggle to identify finance for early-stage development, the returns can be difficult to predict, and the innovation 'landscape' is often complex and unclear. This brief review describes some of the main issues with commercialising innovative ideas and provides guidance with respect to the often complicated funding landscape both on a National and European level. PMID:25549408

  11. Overcoming challenges in improvement work.

    PubMed

    Crisp, Helen

    2013-09-01

    The Health Foundation is an independent charity working to improve healthcare in the UK, so that we have a system of the highest possible quality-safe, effective, person-centred, timely, efficient and equitable. We believe that in order to achieve this, health services need to continually improve the way they work. The Foundation conducts research and evaluation, puts ideas into practice through improvement programmes, develops leaders and shares evidence to drive wider change. The work is a focused around two priority areas: patient safety and person-centred care. The Foundation has supported work to improve services for patients with kidney disease and, in common with other quality improvement projects, there have been challenges to overcome. Awareness of these common challenges can help others to be more prepared when planning service improvements. PMID:23941702

  12. Vehicle barrier

    DOEpatents

    Hirsh, Robert A.

    1991-01-01

    A vehicle security barrier which can be conveniently placed across a gate opening as well as readily removed from the gate opening to allow for easy passage. The security barrier includes a barrier gate in the form of a cable/gate member in combination with laterally attached pipe sections fixed by way of the cable to the gate member and lateral, security fixed vertical pipe posts. The security barrier of the present invention provides for the use of cable restraints across gate openings to provide necessary security while at the same time allowing for quick opening and closing of the gate areas without compromising security.

  13. Electrocatalytic Alcohol Oxidation with TEMPO and Bicyclic Nitroxyl Derivatives: Driving Force Trumps Steric Effects.

    PubMed

    Rafiee, Mohammad; Miles, Kelsey C; Stahl, Shannon S

    2015-11-25

    Bicyclic nitroxyl derivatives, such as 2-azaadamantane N-oxyl (AZADO) and 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), have emerged as highly effective alternatives to TEMPO-based catalysts for selective oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-1-piperidine N-oxyl). Their efficacy is widely attributed to their smaller steric profile; however, electrocatalysis studies described herein show that the catalytic activity of nitroxyls is more strongly affected by the nitroxyl/oxoammonium redox potential than by steric effects. The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols. Mechanistic studies provide insights into the origin of these unexpected reactivity trends. The superior activity of ACT is especially noteworthy at high pH, where bicyclic nitroxyls are inhibited by formation of an oxoammonium hydroxide adduct. PMID:26505317

  14. Effect of Sterical Shielding on the Redox Properties of Imidazoline and Imidazolidine Nitroxides.

    PubMed

    Kirilyuk, Igor A; Bobko, Andrey A; Semenov, Sergey V; Komarov, Denis A; Irtegova, Irina G; Grigor'ev, Igor A; Bagryanskaya, Elena

    2015-09-18

    The oxidant properties of the series of 2,2,5,5-tetraalkyl imidazoline and imidazolidine nitroxides were investigated. An increase in the number of bulky alkyl substituents leads to a decrease in the rate of reduction with ascorbate, which makes the electrochemical reduction potential more negative and shifts the equilibrium in the mixture of nitroxide and reference hydroxylamine (3-carboxy-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl-1-(15)N) toward the starting compounds. The effect of structural factors on these reactions was analyzed by means of multiple regression using the Fujita steric constant Es and the inductive Hammett constant σI. Satisfactory statistical outputs were obtained in all of the biparameter correlations, denoting that the oxidant properties of the nitroxides are determined by steric and electronic effects of the substituents. The data imply that bulky substituents can stabilize nitroxide and/or destabilize hydroxylamine. PMID:26302173

  15. The Role of Aryne Distortions, Steric Effects, and Charges in Regioselectivities of Aryne Reactions

    PubMed Central

    2015-01-01

    The distortion/interaction model has been used to explain and predict reactivity in a variety of reactions where more common explanations, such as steric and electronic factors, do not suffice. This model has also provided new fundamental insight into regioselectivity trends in reactions of unsymmetrical arynes, which in turn has fueled advances in aryne methodology and natural product synthesis. This article describes a systematic experimental and computational study of one particularly important class of arynes, 3-halobenzynes. 3-Halobenzynes are useful synthetic building blocks whose regioselectivities have been explained by several different models over the past few decades. Our efforts show that aryne distortion, rather than steric factors or charge distribution, are responsible for the regioselectivities observed in 3-haloaryne trapping experiments. We also demonstrate the synthetic utility of 3-halobenzynes for the efficient synthesis of functionalized heterocycles, using a tandem aryne-trapping/cross-coupling sequence involving 3-chlorobenzyne. PMID:25303232

  16. Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact.

    PubMed

    Shaw, Paul; Kennedy, Alan R; Nelson, David J

    2016-08-01

    The synthesis and co-ordination chemistry of a new 'bulky yet flexible' N-heterocyclic carbene ("IPaul") is reported. This carbene has spatially-defined steric impact; steric maps show that two quadrants are very bulky while the other two are quite open. The electronic properties of this carbene are very similar to those of other 1,3-diarylimidazol-2-ylidenes. Copper, silver, iridium, and nickel complexes of the new ligand have been prepared. In solution, the ligand adopts two different conformations, while X-ray crystallographic analyses of the transition metal complexes suggest that the syn-conformer is preferred in the solid state due to intermolecular interactions. The copper(i) chloride complex of this new ligand has been shown to be highly-active in the hydrosilylation of carbonyl compounds, when compared to the analogous IPr, IMes, IPr* and IPr*(OMe) complexes. PMID:27335266

  17. Using steric hindrance to design new inhibitors of class C beta-lactamases

    SciTech Connect

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K.

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  18. Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds.

    PubMed

    Zimmermann, Bettina; Dzik, Wojciech I; Himmler, Thomas; Goossen, Lukas J

    2011-10-01

    A catalyst system generated in situ from Pd(dba)(2) and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromide as a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives. PMID:21863787

  19. Structural peculiarities of configurational isomers of 1-styrylpyrroles according to 1Н, 13С and 15N NMR spectroscopy and density functional theory calculations: electronic and steric hindrance for planar structure.

    PubMed

    Afonin, Andrei V; Ushakov, Igor A; Pavlov, Dmitry V; Schmidt, Elena Yu; Dvorko, Marina Yu

    2013-06-01

    Comparative analysis of the (1)Н and (13)С NMR data for a series of the E and Z-1-styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene suggests that the conjugation between the unsaturated fragments in the former compounds is reduced. This is the result of the mutual influence of the donor p-π and π-π conjugation having opposite directions. According to the NMR data combined with the density functional theory calculations, the Z isomer of 1-styrylpyrrole has essentially a nonplanar structure because of the steric hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane structure despite the absence of a sterical barrier for the planar one. Deviation of the E isomer from the planar structure seems to be caused by an electronic hindrance produced by a mutual influence of the p-π and π-π conjugation. The structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral angle between planes of the pyrrole ring and double bond. PMID:23558848

  20. Steric contribution to the long-term sea level variations within the Gulf of Cadiz continental shelf

    NASA Astrophysics Data System (ADS)

    Laiz, Irene; Tejedor, Begoña; Gómez-Enri, Jesús; Aboitiz, Alazne; Villares, Pilar

    2015-04-01

    The response of the long-term coastal sea level variations to the steric contribution has been explored within the Gulf of Cadiz (GoC) for the period 1997-2008 using tide gauge data as well as altimeter-derived sea level anomaly maps (AVISO). In order to remove the atmospheric pressure contribution, tide gauge data were corrected using the inverted barometer (IB) method. The AVISO maps were initially de-corrected using the Dynamic Atmospheric Correction product and then corrected using the same IB method. Steric height (ssh) time series were computed by combining a high resolution climatology (0.1° x 0.1°) with monthly maps of AVHRR sea surface temperature considering a reference depth of 500 m at the open ocean and the bottom depth for shallower areas. In order to evaluate the steric effect on the long-term sea level changes, four types of steric contribution were defined: (1) The ssh values interpolated to the AVISO grid resolution were considered as the local steric effect. (2) The open ocean steric effect was computed by averaging all the steric heights corresponding to grid points located over the 500 m isobath and deeper. (3) The Eastern / Western continental shelf steric contribution was obtained by averaging over those grid points located within each continental shelf. (4) Finally, a basin-wide steric effect was computed by averaging the steric heights all over the GoC. The potential contribution of each of the defined steric effects on the pressure-adjusted sea level was evaluated. The open ocean contribution explained the highest percentage of variance all over the basin with the exception of the western shelf, where the best results were obtained with the local contribution, supporting the idea that the cell of cyclonic circulation found off Cape San Vicente is a local quasi-permanent feature. The fact that the open ocean steric effect explained the highest percentage of variance within the eastern shelf suggested that the deep ocean thermosteric

  1. Low-ppm-Level colorimetric acid detection using gold nanoparticles with electro-steric stabilization.

    PubMed

    Bae, Doo Ri; Lee, You-Jin; Lee, Sung Woo; Han, Young-Kyu; Yoon, Jae-Sik; Lee, Ji-Hyun; Lee, Sang-Gil; Chang, Ki Soo; Yi, Gi-Ra; Lee, Gaehang

    2014-12-01

    Electro-sterically stabilized gold suspensions were employed in a colorimetric system for the detection of strong acid in water. Using oleyamine and oleic acid as steric stabilizer in 1,2-dichlorobenzene, hydrophobic gold nanoparticles were first synthesized by a reduction reaction of gold salts and were then transferred into water with a cationic surfactant. When the hydrochlo- ric acid solution higher than critical concentration was injected, particles were quickly aggregated and precipitated, creating a clear solution from the colored suspension. The particles were stable against chemical etching by corrosive ion such as chloride. Critical concentration was dependent of the size and concentration of the particles. The minimum concentration of dramatic color change was at 5 ppm level of hydrochloric acid, in which the largest colloidal gold nanoparticles (54 nm) were used. Furthermore, because of their steric repulsive soft layer on particles, particles could be reused for further detection experiments after regeneration by the simple pH-neutralization and washing process. PMID:25971086

  2. Sea surface height and steric height increases in the Southern Hemisphere

    NASA Astrophysics Data System (ADS)

    Tretkoff, Ernie

    2011-06-01

    Sea surface height has increased by 3 millimeters per year, globally averaged, since 1993. Some fraction of sea surface height change is due to added water from melting glaciers, for instance, and some is due to increasing heat and salinity changes (steric effects). Focusing on the Southern Hemisphere, Sutton and Roemmich analyzed temperature and salinity data from the Argo float array in relation to earlier data from the World Ocean Circulation Experiment (WOCE) to estimate the steric changes. These were compared with the total sea surface height changes over the same period seen in satellite altimetric data. They found that on decadal time scales, about half of the rise in sea surface height in the Southern Ocean is due to steric effects, with the proportion increasing southward. The accompanying increase in ocean heat content south of 30°S can account for most of the global heat content change during this period. (Geophysical Research Letters, doi:10.1029/ 2011GL046802, 2011)

  3. How Warming and Steric Sea Level Rise Relate to Cumulative Carbon Emissions After Many Centuries

    NASA Astrophysics Data System (ADS)

    Williams, R. G.; Goodwin, P.; Ridgwell, A. J.

    2014-12-01

    Surface warming and steric sea level rise over the global ocean nearly linearly increase with cumulative carbon emissions for an atmosphere-ocean equilibrium, reached many centuries after emissions cease. Surface warming increases with cumulative emissions with a proportionality factor, ΔT2xCO2 /(IB ln 2), ranging from 0.8 to 1.9 K (1000 PgC)-1 for surface air temperature, depending on the climate sensitivity for a doubling of CO2, ΔT2xCO2 (in degrees K), and the buffered carbon inventory, IB (in Pg of carbon). Steric sea level rise similarly increases with cumulative emissions and depends on the climate sensitivity of the bulk ocean, ranging from 0.4 K to 2.7 K; a factor 0.4±0.2 smaller than that for surface temperature based on diagnostics of two Earth System models. The implied steric sea level rise ranges from 0.7 m to 5 m for a cumulative emission of 5000 PgC, approached perhaps 500 years or more after emissions cease.

  4. Does Size Really Matter? The Steric Isotope Effect in a Supramolecular Host?Guest Exchange Reaction

    SciTech Connect

    Mugridge, Jeffrey; Bergman, Robert; Raymond, Kenneth

    2010-01-29

    Isotope effects (IEs), which arise from differences in zero point energies (ZPEs) between a parent and isotopically substituted bond, have been used extensively by chemists to probe molecular interactions and reactivity. Due to the anharmonicity of the C-H/D vibrational potential energy function and the lower ZPE of a C-D bond, the average C-D bond length is typically {approx}0.005 {angstrom} shorter than an equivalent C-H bond. It is this difference in size that is often invoked to explain the observation of secondary, inverse kinetic isotope effects (KIEs) in chemical processes which proceed through a sterically strained transition state. This so-called 'steric isotope effect' (SIE) has been observed in processes such as the racemization of ortho-substituted biphenyls[6] and phenanthrenes, ring flipping of cyclophanes, and more recently in the deslipping of rotaxanes, where substitution of the sterically less demanding deuterium for protium results in rate accelerations for these processes. Herein, we use deuterium substitution in a cationic guest molecule to probe the sensitivity limits of the guest exchange process from a highly-charged supramolecular host.

  5. Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase.

    PubMed

    Colby, Jennifer M; Krantz, Bryan A

    2015-11-01

    Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. PMID:26363343

  6. Steric and Mass-Induced Sea Level Variations in the Mediterranean Sea, Revisited

    NASA Astrophysics Data System (ADS)

    Garcia-Garcia, D.; Chao, B. F.; Boy, J.-P.

    2009-04-01

    Observed by radar altimetry satellites such as TOPEX/Poseidon (T/P) and Jason-1/2, the total Sea Level Variations (SLV) are produced by a combination of the steric and mass-induced components. The steric SLV can be computed from in situ measurements of temperature and salinity profiles, or from Ocean General Circulation Models (OGCM) that can assimilate those measurements. Mass-induced SLV can be estimated, since 2002, from Time-Variable Gravity (TVG) measurements by the GRACE satellite mission. This methodology has been successfully applied in estimation of the global ocean mass-induced SLV. However, some difficulties arise when studying semi-enclosed basins due to land aliasing of the GRACE TVG signal. The problem is specially complicated in the Mediterranean Sea as reported in previous studies. We revisit this problem analyzing release 4 of the GRACE data set, which represents a time series 3 times longer than in previous studies, by means of new and more efficient filters to reduce the noise in the high degree and order spherical harmonics coefficients. The seasonal and non-seasonal signals are analyzed. From the comparison of GRACE with altimetry data a general underestimation of the steric term is observed in the OGCMs used.

  7. Overcoming Degeneracies in Exoplanet Spectra

    NASA Astrophysics Data System (ADS)

    Benneke, Björn

    2015-08-01

    Spectroscopic observations of exoplanets can provide invaluable insights into the planets’ compositions, their formation and evolution histories, and even their habitability. Obtaining exoplanet spectra is observationally challenging; however, and we are generally limited to relatively low signal-to-noise, low spectral resolution, disk-integrated observations , often with relatively narrow wavelength coverage. This low data situation results in strong correlations and degeneracies between the different planet and atmospheric parameters of interest. In this talk, I will present a conceptual picture of how vital information about the planet is encoded in its observable spectrum. I will then give an overview about the wide range of correlations and degeneracies relevant to today’s exoplanet observations. Finally, I will demonstrate how some degeneracies can be overcome and improved constraints can be obtained by including prior knowledge of atmospheric chemistry and physics in the retrieval. I present a new atmospheric retrieval framework, SCARLET, that combines observational data and our prior (limited) knowledge of atmospheric processes in a statistical robust Bayesian framework. New results for hot Jupiters will be presented.

  8. Steric Sea Level Trends in the Northeast Pacific Ocean: Possible Evidence of Global Sea Level Rise.

    NASA Astrophysics Data System (ADS)

    Thomson, Richard E.; Tabata, Susumu

    1989-06-01

    Thirty-year time series of hydrographic observations from Ocean Station PAPA and Line P' are used to estimate secular trends in monthly mean steric sea level heights relative to depths of 100 and 1000 decibars in the northeast Pacific Ocean. Linear trends at station P' (50°N, 145°W) indicate that steric heights relative to the 1000 db (approx. 1000 m) level are rising at a rate of 1.1 mm yr1, comparable with the Order 1 mm yr1 global trends suggested by analysis of selected long-term coastal tide gauge records. Approximately 67% of the increase in steric levels is due to thermosteric change at depths below 100 m, the smaller 33% contribution from the halosteric component apeasrs to be confined to the upper 100 m. Steric height trends at fine P' locations are also of order 1 mm yr1 but, in contrast to station P' trends, arise mainly through the halosteric component.Confidence levels for the linear trends an calculated in two ways. (i) using the Student-t test assuming that cub monthly observation is a statistically independent sample; and (ii) using the Student-t test in conjunction with the effective number of degrees of freedom derived from integral time scales. For station P', trends based on (i) are reliable to the 99% confidence level while for line P' only stations on the eastern portion of the fine have significant trends relative to the 1000 db level. Confidence levels obtained from (i) fail to take into consideration the long-term fluctuations in steric level records. To obtain more reliable estimates of the confidence intervals, we use integral time scales to determine the effective number of degrees of freedom for each monthly time series. Subsequent recalculation of trend-line confidence intervals indicates that the total steric height trends at Station P' remain significant at the 90% confidence level. The halosteric trend relative to 100 db is significant at 90% while the thermosteric trend relative to 1000 db is marginally significant at 70 to 80

  9. Glucocorticosteroids in Nano-Sterically Stabilized Liposomes Are Efficacious for Elimination of the Acute Symptoms of Experimental Cerebral Malaria

    PubMed Central

    Waknine-Grinberg, Judith H.; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K.; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage. PMID:23991146

  10. Bioenergetic Progress and Heat Barriers

    NASA Astrophysics Data System (ADS)

    Zotin, A. A.; Lamprecht, I.; Zotin, A. I.

    2001-07-01

    Progressing biological evolution is discussed in the framework of nonequilibrium thermodynamics. It is connected with an increase of the mass specific standard metabolism given by coefficient a in the allometric relation (1) between oxygen consumption rate and body mass of an animal. Three “heat barriers” are found in the course of such a bioenergetic evolution. The first heat barrier concerns an animal's overheating during active movement and is overcome by the development of thermoregulation and the appearance of homeothermic animals. A second barrier arises when the coefficient a reaches values connected with lethal body temperatures. The transition across this second heat barrier occurs as result of reasonable activities and the appearance of civilization. The third heat barrier will arise during the further development of human civilization, connected with a highly increased energy production and a fatal warming of the Earth atmosphere. The manner to overcome this barrier will probably depend on the assimilation of space and the establishment of energy consuming industries outside the Earth. The bioenergetic evolution discussed in this paper does not exclude other trends of evolution, e.g. increase of size, and does not mean to be the only aspect of biological evolution.

  11. Nucleophilic substitution in ionizable Fischer thiocarbene complexes: steric effect of the alkyl substituent on the heteroatom.

    PubMed

    Andrada, Diego M; Zoloff Michoff, Martin E; de Rossi, Rita H; Granados, Alejandro M

    2015-03-28

    A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene complexes (CO)5M[double bond, length as m-dash]C(SR)CH3 (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one secondary amine in aqueous acetonitrile solutions (50% MeCN-50% water (v/v)). The observed rate constants for the reaction with primary amines showed a first-order dependence on the amine concentration, while with morpholine, the rate constant has second-order dependence. The general base catalysis process was confirmed by the variation of the rate constants with the concentration of an external catalyst and the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene carbon to produce a tetrahedral intermediate (T±) is the first step, followed by a rapid deprotonation of to form the anion T- which leads to the products by general-acid catalysed leaving group (-SR) expulsion. In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The obtained Brønsted parameters for the nucleophilic addition (βnuc) indicate that C-N bond formation has made little progress at the transition state. By using Charton's correlation, the role that the steric factor plays throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sensitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely, the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst and the metal centre. On the basis of the structure-reactivity coefficients β and ψ and comparison with alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in terms of transition state imbalances are discussed. PMID:25698135

  12. Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

    NASA Astrophysics Data System (ADS)

    Storto, Andrea; Masina, Simona; Balmaseda, Magdalena; Guinehut, Stéphanie; Xue, Yan; Szekely, Tanguy; Fukumori, Ichiro; Forget, Gael; Chang, You-Soon; Good, Simon A.; Köhl, Armin; Vernieres, Guillaume; Ferry, Nicolas; Peterson, K. Andrew; Behringer, David; Ishii, Masayoshi; Masuda, Shuhei; Fujii, Yosuke; Toyoda, Takahiro; Yin, Yonghong; Valdivieso, Maria; Barnier, Bernard; Boyer, Tim; Lee, Tony; Gourrion, Jérome; Wang, Ou; Heimback, Patrick; Rosati, Anthony; Kovach, Robin; Hernandez, Fabrice; Martin, Matthew J.; Kamachi, Masafumi; Kuragano, Tsurane; Mogensen, Kristian; Alves, Oscar; Haines, Keith; Wang, Xiaochun

    2015-03-01

    Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003-2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993-2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread.

  13. The role of Argo steric sea level within the global sea level budget

    NASA Astrophysics Data System (ADS)

    von Schuckmann, K.; Sallée, J.-B.; Cabanes, C.; Le Traon, P.-Y.; Gaillard, F.; Speich, S.; Hamon, M.

    2012-04-01

    Precise estimations of global ocean indicators (GOIs) such as global ocean heat content (GOHC) and global steric sea level (GSSL) are necessary to observe the ocean's role in the Earth's climate system. To improve accuracy of these estimations, our knowledge of deep ocean and regional contributions to GOIs needs to be quantified. Data from the global Argo array are used here to analyze these contributionsduring the period 2005 to 2010. GOHC/GMSH rise increases by 25% /35% for the upper 2000m depth compared to the upper ocean 700m depth. A comparison of Argo steric sea level to total sea level from satellite altimetry (AVISO) and ocean mass (GRACE) is performed during this period. We could close the global and regional sea level budgets for 2005 to 2010 in terms of 6-year trends. Results show that largest correlation of global GSSL, ocean mass and global total sea level can be observed in the global tropical basin. Differences of the 6-year trend between global mean total sea level and GSSL in this basin are mostly explained by Argo sampling issues, especially in the - by Argo under sampled - Indonesian Archipelago. The differences of the 6-year trend in the Southern Ocean can be attributed to mass changes and deep ocean steric changes, whereas in the Northern Ocean mass changes clearly dominate decadal and longer-term variability. The results are only valid under the assumption that no systematic errors remain in either one of the global observing systems, although the comparison of all three observing systems indicates that these errors appear to be small during the years 2005 to 2010.

  14. On the energetics of P-P bond dissociation of sterically strained tetraamino-diphosphanes.

    PubMed

    Blum, M; Puntigam, O; Plebst, S; Ehret, F; Bender, J; Nieger, M; Gudat, D

    2016-02-01

    The homolytic P-P bond fission in a series of sterically congested tetraaminodiphosphanes (R2N)2P-P(NR2)2 ({4}2-{9}2, two of which were newly synthesized and fully characterized) into diaminophosphanyl radicals (R2N)2P˙ (4-9) was monitored by VT EPR spectroscopy. Determination of the radical concentration from the EPR spectra permitted to calculate free dissociation energies ΔGDiss(295) as well as dissociation enthalpies ΔHDiss and entropies ΔSDiss, respectively. Large positive values of ΔGDiss(295) indicate that the degree of dissociation is in most cases low, and the concentration of persistent radicals--even if they are spectroscopically observable at ambient temperature--remains small. Appreciable dissociation was established only for the sterically highly congested acyclic derivative {9}2. Analysis of the trends in experimental data in connection with DFT studies indicate that radical formation is favoured by large entropy contributions and the energetic effect of structural relaxation (geometrical distortions and conformational changes in acyclic derivatives) in the radicals, and disfavoured by attractive dispersion forces. Comparison of the energetics of formation for CC-saturated N-heterocyclic diphosphanes and the 7π-radical 3c indicates that the effect of energetic stabilization by π-electron delocalization in the latter is visible, but stands back behind those of steric and entropic contributions. Evaluation of spectroscopic and computational data indicates that diaminophosphanyl radicals exhibit, in contrast to aminophosphenium cations, no strong energetic preference for a planar arrangement of the (R2N)2P unit. PMID:26337501

  15. Electronic and steric effects in gold(i) phosphine thiolate complexes.

    PubMed

    Foley, J; Fort, R C; McDougal, K; Bruce, M R; Bruce, A E

    1994-01-01

    The unusual yellow color of Au(2)(dppm)(SR)(2) (R = 4-tolyl; dppm = diphenylphosphinomethane) is attributed to a red-shift in the S-->Au charge transfer caused by destabilization of the sulfur highest occupied molecular orbital (HOMO). Variable temperature experiments show two broad bands at -80 degrees C in the (31)P{(1)H} NMR spectrum of Au(2)(dppm)(SR)(2) and the activation energy for interconversion is 10 kcal/mol. Only one sharp band is observed down to -80 degrees C in the spectrum of the white complex, Au(2)(dppe)(SR)(2) (dppe = diphenylphosphinoethane). Molecular mechanics calculations on Au(2)(dppm)(SR)(2) and Au(2)(dppe)(SR)(2) reveal that, for Au(2)(dppe)(SR)(2), a series of maxima and minima, separated by 2.5 kcal/mol, occur every 120 degrees which is consistent with rotation around an unhindered carbon-phosphorus single bond. The Au atoms are not within bonding distance in any conformation. Computational results for Au(2)(dppm)(SR)(2) indicate one minimum energy structure in which the Au-P bonds are anti. There is a high energy conformation (9 kcal/mol above the global minimum) where overlap between golds is maximized. The implications of gold-gold bonding in this complex are discussed. The steric influence of the thiolate ligand has been examined by synthesizing a series of dinuclear gold(I) complexes in which the steric properties of the thiolate are varied: Au(2)(dppm)(SR)(2) (R = 2,6-dichlorophenyl; 2,6-dimethylphenyl; 3,5-dimethylphenyl). The 2,6-disubstituted complexes are white, while the 3,5-dimethyl complex is yellow. These results, along with VT-NMR experiments, are consistent with the conclusion that the more sterically-bulky thiolates hinder the close approach of the golds in the dinuclear complexes. PMID:18476259

  16. Determining the Effective Density and Stabilizer Layer Thickness of Sterically Stabilized Nanoparticles

    PubMed Central

    2016-01-01

    A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMAx–PTFEMAy nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100–1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g

  17. Sterically controlled azomethine ylide cycloaddition polymerization of phenyl-C61-butyric acid methyl ester.

    PubMed

    Stephen, Meera; Ramanitra, Hasina H; Santos Silva, Hugo; Dowland, Simon; Bégué, Didier; Genevičius, Kristijonas; Arlauskas, Kęstutis; Juška, Gytis; Morse, Graham E; Distler, Andreas; Hiorns, Roger C

    2016-05-01

    Phenyl-C61-butyric acid methyl ester (PCBM) is polymerized simply using a one-pot reaction to yield soluble, high molecular weight polymers. The sterically controlled azomethine ylide cycloaddition polymerization (SACAP) is demonstrated to be highly adaptable and yields polymers with probable Mn≈ 24 600 g mol(-1) and Mw≈ 73 800 g mol(-1). Products are metal-free and of possible benefit to organic and hybrid photovoltaics and electronics as they form thin films from solution and have raised LUMOs. The promising electronic properties of this new polymer are discussed. PMID:27066898

  18. Math Is Like a Scary Movie? Helping Young People Overcome Math Anxiety

    ERIC Educational Resources Information Center

    Kulkin, Margaret

    2016-01-01

    Afterschool teachers who tutor students or provide homework help have a unique opportunity to help students overcome the social or emotional barriers that so often block learning. They can embrace a creative and investigative approach to math learning. Margaret Kulkin's interest in being a math attitude "myth-buster" led her to apply to…

  19. Steric stabilization of "charge-free" cellulose nanowhiskers by grafting of poly(ethylene glycol).

    PubMed

    Araki, Jun; Mishima, Shiho

    2015-01-01

    A sterically stabilized aqueous suspension of "charge-free" cellulose nanowhiskers was prepared by hydrochloric acid hydrolysis of cotton powders and subsequent surface grafting of monomethoxy poly(ethylene glycol) (mPEG). The preparation scheme included carboxylation of the terminal hydroxyl groups in mPEG via oxidation with silica gel particles carrying 2,2,6,6-tetramethyl-1-pyperidinyloxyl (TEMPO) moieties and subsequent esterification between terminal carboxyls in mPEG and surface hydroxyl groups of cellulose nanowhiskers, mediated by 1,1'-carbonyldiimidazole (CDI) in dimethyl sulfoxide or dimethylacetamide. Some of the prepared PEG-grafted samples showed remarkable flow birefringence and enhanced stability after 24 h, even in 0.1 M NaCl, suggesting successful steric stabilization by efficient mPEG grafting. Actual PEG grafting via ester linkages was confirmed by attenuated total reflectance-Fourier transform infrared spectrometry. In a typical example, the amount of grafted mPEG was estimated as ca. 0.3 g/g cellulose by two measurements, i.e., weight increase after grafting and weight loss after alkali cleavage of ester linkages. Transmission electron microscopy indicated unchanged nanowhisker morphology after mPEG grafting. PMID:25547722

  20. Steric stabilization of thermally responsive N-isopropylacrylamide particles by poly(vinyl alcohol).

    PubMed

    Lee, A; Tsai, H-Y; Yates, M Z

    2010-12-01

    Poly(vinyl alcohol) (PVA) was used as a steric stabilizer for the dispersion polymerization of cross-linked poly(N-isopropylacrylamide) (PNIPAM) in water. A series of reactions were carried out using PVA of varying molecular weight and degree of hydrolysis. Under appropriate conditions, PNIPAM particles of uniform and controllable size were produced using PVA as the stabilizer. The colloidal stability was investigated by measuring changes in particle size with temperature in aqueous suspensions of varying ionic strength. For comparison, parallel colloidal stability measurements were conducted on PNIPAM particles synthesized with low-molecular-weight ionic surfactants. PVA provides colloidal stability over a wide range of temperature and ionic strength, whereas particles produced with ionic surfactants flocculate in moderate ionic strength solutions upon collapse of the hydrogel as the temperature is increased. Experimental results and theoretical consideration indicate that sterically stabilized PNIPAM particles resulted from the grafting of PVA to the PNIPAM particle surface. The enhanced colloidal stability afforded by PVA allows the temperature-responsive PNIPAM particles to be used under physiological conditions where electrostatic stability is ineffective. PMID:21050003

  1. Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity

    NASA Astrophysics Data System (ADS)

    Wensink, H. H.; Morales-Anda, L.

    2015-10-01

    We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or "soft" chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly.

  2. Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity.

    PubMed

    Wensink, H H; Morales-Anda, L

    2015-10-14

    We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or "soft" chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly. PMID:26472398

  3. From soft to hard rod behavior in liquid crystalline suspensions of sterically stabilized colloidal filamentous particles.

    PubMed

    Grelet, Eric; Rana, Richa

    2016-05-18

    The liquid crystalline phase behavior of a colloidal system of sterically stabilized rods is reported. Our colloidal suspensions consist of highly monodisperse, semi-flexible filamentous viruses which have been coated with neutral hydrophilic polymers by irreversibly binding poly(ethylene glycol) (PEG) to the surface of the virus particles. Depending on the size of the grafted polymer, up to three different phase transitions are observed (isotropic-to-chiral nematic, chiral nematic-to-smectic, and smectic-to-columnar). Each phase transition is shown to be independent of ionic strength, confirming the steric stabilization of the viral colloids. A direct, i.e. without any free parameters, comparison with theory and computer simulations of the volume fraction associated with the phase transition can be performed, showing a quantitative agreement with hard rod behavior at a low polymer chain size, and some deviation stemming from soft repulsion by increasing the polymer thickness coating of the rod. Specifically, we demonstrate that the columnar mesophase is not stabilized by electrostatic repulsion, and we discuss the conditions of its existence. PMID:27108523

  4. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    SciTech Connect

    Monine, Michael; Posner, Richard; Savage, Paul; Faeder, James; Hlavacek, William S

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  5. Role of water and steric constraints in the kinetics of cavity–ligand unbinding

    PubMed Central

    Tiwary, Pratyush; Mondal, Jagannath; Morrone, Joseph A.; Berne, B. J.

    2015-01-01

    A key factor influencing a drug’s efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity–ligand system using a metadynamics-based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, the unbinding time is found to be on the order of 4,000 s. In accordance with previous studies, we find that the cavity must pass through a region of sharp wetting transition manifested by sudden and high fluctuations in solvent density. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp wetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent MD studies at timescales previously unattainable, to our knowledge, obtaining direct and reliable pictures of the underlying physiochemical factors including free energies and rate constants. PMID:26371312

  6. Elaboration of Sterically Stabilized Liposomes for S-Nitrosoglutathione Targeting to Macrophages.

    PubMed

    Diab, R; Virriat, A S; Ronzani, C; Fontanay, S; Grandemange, S; Elaissari, A; Foliguet, B; Maincent, P; Leroy, P; Duvaj, R E; Rihn, B H; Joubert, O

    2016-01-01

    S-nitrosoglutathione (GSNO) is a potential therapeutic for infectious disease treatment because of its pivotal role in macrophage-mediated inflammatory responses and host defense in addition to direct antibacterial activities. In this study, sterically stabilized cationic liposomes (SSCL) and sterically stabilized anionic liposomes (SSAL) were developed as nanocarriers for macrophage targeting. Elaborated liposomes were characterized in terms of size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and cytotoxicity. Their versatility in targeting monocytes/macrophages was determined by confocal laser scanning microscopy and transmission electron microscopy. Flow cytometry revealed that cellular uptake of both SSCL and SSAL was governed by several endocytic clathrin- and caveolae-dependent mechanisms. Quantitative assessments of intracellular nitric oxide demonstrated highly efficient uptake of GSNO-loaded SSCL that was twenty-fold higher than that of GSNO-free molecules. GSNO-loaded SSCL displayed strong bacteriostatic effects on Staphylococcus aureus and Pseudomonas aeruginosa, which can be involved in pulmonary infectious diseases. These results reveal the potential of liposomal GSNO as an anti-infective therapeutic due to its macrophage targeting capacity and direct antibacterial effects. PMID:27301185

  7. Temporal and steric analysis of ionic permeation and binding in SERCA via molecular dynamic simulations.

    PubMed

    Fonseca, J E; Kaya, S; Rakowski, R F

    2007-10-24

    The availability of the crystal structure of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) has allowed atomic-level molecular dynamic (MD) simulations of this membrane transport protein to be done. The biomedical and nanotechnological implications of this work are discussed as well as the methods of performing the simulations and analysis. We have performed nanosecond timescale simulations of SERCA for several of its known conformations in a lipid/water environment. One simulation contained Ca(2+) ions, while others without ions were analyzed by techniques such as steric pathway determination. We discuss details of the resulting putative cytoplasmic and lumenal pathways, along with experimental evidence from the literature to support our conclusions. Finally, we give a brief overview of future research directions, as they pertain to MD simulations and their analysis. The methodology used in this work shows that significant insight into the structure-function relationship of ion-motive transmembrane pumps can be derived by a combination of simulation tools and analysis techniques including MD trajectories, steric analysis and electrostatic potentials. PMID:21730455

  8. Conformational effects of peripheral substituents and axial ligands in sterically crowded porphyrins

    SciTech Connect

    Nurco, D.J.; Smith, K.M.; Fajer, J.

    1997-12-31

    Crystallographic results for peripherally substituted porphyrins illustrate effects of steric crowding, axial ligation and {pi}-{pi} interactions on the structures of metalloporphyrins that begin to resemble the architectures found for porphyrinic prosthetic groups and chromophores in vivo. (1) Metalloporphyrins with multiple peripheral substituents can adopt planar, saddled, ruffled or {open_quotes}wavy{close_quotes} conformations that persist upon axial ligation of the metal. (2) In porphyrins with substituents at all peripheral positions, the substituents form pockets that force the axial ligands to align in specific orientations relative to each other and to the axes defined by the porphyrin estrogens. (3) The enforced alignment of the axial ligands caused by the substituent pocket prevents aromatic ligands from rotating around the coordination axis with intriguing consequences: the axial ligands can be forced to tip off axis because of steric crowding by adjacent molecules in the crystal lattice. (4) In porphyrins with meso substituents only, the axial ligands are free to rotate but {pi}-{pi} interactions and collacial stacking between adjacent molecules in the crystal also induce off-axis ligand tilts.

  9. Structural consequences of spin conversion in a sterically encumbered Ni(II) porphyrin

    SciTech Connect

    Barkigia, K.M.; Nelson, N.Y.; Renner, M.W.; Smith, K.M.; Fajer, J.

    1999-10-14

    The crystal structure of a pyridine-ligated, high-spin Ni(II) complex of 2,3,7,8,12,13,17,18-octabromo-5, 15-bis(isopropyl)-10,20-bis(isopropylidenyl) porphyrin, is reported and compared to the unligated, low-spin Ni(II) complex previously reported. The results demonstrate that conversion to high-spin Ni(II) in nonplanar, sterically encumbered porphyrins induces a significant core expansion about the Ni while nonplanarity is still retained. The expansion of the core parameters (Ni-N, Ct-C{alpha}, Ct-Cmexo) and the Ni-N{sub axial} distances are characteristic of the d{sub x{sup 2}{minus}y{sup 2}} orbital occupancies in high-spin Ni(II) porphyrins and document the structural consequences of the spin conversion in severely nonplanar Ni(II) porphyrins. The stereochemical results are particularly relevant to ligation effects in nonplanar Ni biomolecules and synthetic porphyrins increasingly used as biomimetic models of conformational effects in chromophores and prosthetic groups in vivo, and to the remarkably wide range of lifetimes observed for excited (d,d) states in nonplanar, sterically constrained Ni(II) porphyrins in which the d{sub x{sup 2}{minus}y{sup 2}} and d{sub z{sup 2}} orbitals are also populated.

  10. Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity

    SciTech Connect

    Wensink, H. H. Morales-Anda, L.

    2015-10-14

    We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or “soft” chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly.

  11. Overcoming challenges to adoption of shared medical appointments.

    PubMed

    McCuistion, Mary Honodel; Stults, Cheryl D; Dohan, Daniel; Frosch, Dominick L; Hung, Dorothy Y; Tai-Seale, Ming

    2014-04-01

    Although research has shown many benefits of Shared Medical Appointments (SMAs) or group visits, uptake by physicians has been quite limited. The objective of this study was to explore the facilitators and barriers to implementing SMAs in a large multispecialty medical group. This was a comparative analysis of SMAs at 3 geographically distinct, semiautonomous divisions of the medical group based on qualitative themes identified in audio recorded key informant interviews with medical and administrative staff (n=12) involved with the implementation of SMAs. Data were collected by conducting key informant interviews focusing on the SMA implementation process, including motivations, history, barriers, and facilitators. Uptake at the 3 divisions was predicated by differing motivations, facilitators, and barriers. Divisions 1 and 2 allocated necessary resources including management support, a physician champion, expert consults, and support staff. These divisions also overcame physician reluctance and financial sustainability challenges. Despite early interest, Division 3 did not devote the time or resources to overcome initial resistance. Without the impetus of management mandate or a champion's enthusiasm, early attempts of SMA implementation faltered and were abandoned. In these cases, a physician champion, management support, and financial sustainability were judged to be the primary enablers of successful implementations of SMAs. Without these enablers and other contributing factors, implementing SMAs was challenging. PMID:24156662

  12. Study on steric transition in asymmetrical flow field-flow fractionation and application to characterization of high-energy material.

    PubMed

    Dou, Haiyang; Lee, Yong-Ju; Jung, Euo Chang; Lee, Byung-Chul; Lee, Seungho

    2013-08-23

    In field-flow fractionation (FFF), there is the 'steric transition' phenomenon where the sample elution mode changes from the normal to steric/hyperlayer mode. Accurate analysis by FFF requires understanding of the steric transition phenomenon, particularly when the sample has a broad size distribution, for which the effect by combination of different modes may become complicated to interpret. In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4) was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually decreases as the particle size increases (normal mode) and reaches a minimum (Ri) at diameter around 0.5μm, after which R increases with increasing diameter (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends to increase as the channel thickness (w) increases. The retention behavior of cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department explosive' (RDX)) particles in AF4 was investigated by varying experimental parameters including w and flow rates. AF4 showed a good reproducibility in size determination of RDX particles with the relative standard deviation of 4.1%. The reliability of separation obtained by AF4 was evaluated by transmission electron microscopy (TEM). PMID:23871284

  13. Barriers to HIV Cure.

    PubMed

    Stein, J; Storcksdieck Genannt Bonsmann, M; Streeck, H

    2016-10-01

    Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers. PMID:27620852

  14. Language barriers

    PubMed Central

    Ngwakongnwi, Emmanuel; Hemmelgarn, Brenda R.; Musto, Richard; King-Shier, Kathryn M.; Quan, Hude

    2012-01-01

    Abstract Objective To assess use of regular medical doctors (RMDs), as well as awareness and use of telephone health lines or telehealth services, by official language minorities (OLMs) in Canada. Design Analysis of data from the 2006 postcensal survey on the vitality of OLMs. Setting Canada. Participants In total, 7691 English speakers in Quebec and 12 376 French speakers outside Quebec, grouped into those who experienced language barriers and those with no language barriers. Main outcome measures Health services utilization (HSU) by the presence of language barriers; HSU measures included having an RMD, use of an RMD’s services, and awareness of and use of telephone health lines or telehealth services. Multivariable models examined the associations between HSU and language barriers. Results After adjusting for age and sex, English speakers residing in Quebec with limited proficiency in French were less likely to have RMDs (adjusted odds ratio [AOR] 0.66, 95% CI 0.50 to 0.87) and to use the services of their RMDs (AOR 0.65, 95% CI 0.50 to 0.86), but were more likely to be aware of the existence of (AOR 1.50, 95% CI 1.16 to 1.93) and to use (AOR 1.43, 95% CI 0.97 to 2.11) telephone health lines or telehealth services. This pattern of having and using RMDs and telehealth services was not observed for French speakers residing outside of Quebec. Conclusion Overall we found variation in HSU among the language barrier populations, with lower use observed in Quebec. Age older than 45 years, male sex, being married or in common-law relationships, and higher income were associated with having RMDs for OLMs. PMID:23242902

  15. Barriers to Asthma Management as Identified by School Nurses.

    PubMed

    Quaranta, Judith E; Spencer, Gale A

    2016-10-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors, and (c) determined the impact of barriers on importance ratings of asthma management behaviors, asthma self-efficacy, and asthma attitudes (N = 537). Results revealed 72% of the nurses reported at least one barrier. As numbers of barriers increased, performance of asthma management behaviors decreased. Significant relationships were found between specific asthma management behaviors and specific barriers. No significant relationships were found between barriers and asthma self-efficacy, asthma attitude, or importance ratings of asthma management behaviors. Removing barriers may allow the nurse to perform at greatest effectiveness, enhancing the positive outcomes that result from appropriate asthma management. PMID:27044669

  16. Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

    PubMed Central

    Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

    2015-01-01

    Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

  17. Promoting Physical Activity: Addressing Barriers and Moving Forward

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  18. The Gendered International School: Barriers to Women Managers' Progression

    ERIC Educational Resources Information Center

    Sanderson, Ruth Elizabeth; Whitehead, Stephen

    2016-01-01

    Purpose: The purpose of this paper is to examine the barriers women identify to their promotion in international schools and also the ways in which women can overcome these barriers. Design/methodology/approach: The field of enquiry is international schools, with the study drawing on qualitative research. The researchers interviewed 11 women from…

  19. Enantiospecific photoresponse of sterically hindered diarylethenes for chiroptical switches and photomemories

    PubMed Central

    Li, Wenlong; Li, Xin; Xie, Yongshu; Wu, Yue; Li, Mengqi; Wu, Xin-Yan; Zhu, Wei-Hong; Tian, He

    2015-01-01

    Light-driven transcription, replication and enzyme catalysis are critically dependent upon a delicate transfer between molecular and supramolecular chirality. Chemists have well realized the impressive stereospecificity over many thermally accessible cycloaddition with chiral catalysts, but making light work in the enantiomer control of diarylethene photocyclization has proved to be more challenging. Here, we report a unique sterically hindered diarylethene (BBTE) system with absolute enantiospecific photocyclization and cycloreversion. Moreover, we have fully separated all the five thermally stable isomers, consisting of one achiral parallel conformer, one pair of anti-parallel ring-open enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral configurations are entirely elucidated by single X-ray crystallographic analyses. The photo-responsive feature exhibits a reversible, complete enantio-control transformation without racemism, offering an unrivaled unimolecular enantiospecific platform for potential applications as bistable chiroptical switches and all-photonic photomemories with optical rotation as non-destructive readout. PMID:25777985

  20. Providing Oligonucleotides with Steric Selectivity by Brush-Polymer-Assisted Compaction.

    PubMed

    Lu, Xueguang; Tran, Thanh-Huyen; Jia, Fei; Tan, Xuyu; Davis, Sage; Krishnan, Swathi; Amiji, Mansoor M; Zhang, Ke

    2015-10-01

    Difficult biopharmaceutical characteristics of oligonucleotides, such as poor enzymatic stability, rapid clearance by reticuloendothelial organs, immunostimulation, and coagulopathies, limit their application as therapeutics. Many of these side effects are initiated via sequence-specific or nonsequence-specific interactions with proteins. Herein, we report a novel form of brush-polymer/DNA conjugate that provides the DNA with nanoscale steric selectivity: Hybridization kinetics with complementary DNA remains nearly unaffected, but interactions with proteins are significantly retarded. The relative lengths of the brush side chain and the DNA strand are found to play a critical role in the degree of selectivity. Being able to evade protein adhesion also improves in vivo biodistribution, thus making these molecular nanostructures promising materials for oligonucleotide-based therapies. PMID:26378378

  1. Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril.

    PubMed

    Schmidt, Andreas; Annamalai, Karthikeyan; Schmidt, Matthias; Grigorieff, Nikolaus; Fändrich, Marcus

    2016-05-31

    Amyloid fibrils are proteinaceous aggregates associated with diseases in humans and animals. The fibrils are defined by intermolecular interactions between the fibril-forming polypeptide chains, but it has so far remained difficult to reveal the assembly of the peptide subunits in a full-scale fibril. Using electron cryomicroscopy (cryo-EM), we present a reconstruction of a fibril formed from the pathogenic core of an amyloidogenic immunoglobulin (Ig) light chain. The fibril density shows a lattice-like assembly of face-to-face packed peptide dimers that corresponds to the structure of steric zippers in peptide crystals. Interpretation of the density map with a molecular model enabled us to identify the intermolecular interactions between the peptides and rationalize the hierarchical structure of the fibril based on simple chemical principles. PMID:27185936

  2. A Steric Antagonism of Actin Polymerization by a Salmonella Virulence Protein

    SciTech Connect

    Margarit,S.; Davidson, W.; Frego, L.; Stebbins, F.

    2006-01-01

    Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein for intracellular growth and systemic virulence. SpvB covalently modifies actin, causing cytoskeletal disruption and apoptosis. We report here the crystal structure of the catalytic domain of SpvB, and we show by mass spectrometric analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We also describe two crystal structures of SpvB-modified, polymerization-deficient actin. These structures reveal that ADP-ribosylation does not lead to dramatic conformational changes in actin, suggesting a model in which this large family of toxins inhibits actin polymerization primarily through steric disruption of intrafilament contacts.

  3. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols

    NASA Astrophysics Data System (ADS)

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W.; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J.

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  4. Steric trapping reveals a cooperativity network in the intramembrane protease GlpG.

    PubMed

    Guo, Ruiqiong; Gaffney, Kristen; Yang, Zhongyu; Kim, Miyeon; Sungsuwan, Suttipun; Huang, Xuefei; Hubbell, Wayne L; Hong, Heedeok

    2016-05-01

    Membrane proteins are assembled through balanced interactions among proteins, lipids and water. Studying their folding while maintaining the native lipid environment is necessary but challenging. Here we present methods for analyzing key elements of membrane protein folding including thermodynamic stability, compactness of the unfolded state and folding cooperativity under native conditions. The methods are based on steric trapping, which couples the unfolding of a doubly biotinylated protein to the binding of monovalent streptavidin (mSA). We further advanced this technology for general application by developing versatile biotin probes possessing spectroscopic reporters that are sensitized by mSA binding or protein unfolding. By applying these methods to the Escherichia coli intramembrane protease GlpG, we elucidated a widely unraveled unfolded state, subglobal unfolding of the region encompassing the active site, and a network of cooperative and localized interactions to maintain stability. These findings provide crucial insights into the folding energy landscape of membrane proteins. PMID:26999782

  5. Peptide length and prime-side sterics influence potency of peptide phosphonate protease inhibitors

    PubMed Central

    Brown, Christopher M.; Ray, Manisha; Eroy-Reveles, Aura A.; Egea, Pascal; Tajon, Cheryl; Craik, Charles S.

    2010-01-01

    Summary The ability to follow enzyme activity in a cellular context represents a challenging technological frontier that impacts fields ranging from disease pathogenesis to epigenetics. Activity-based probes (ABPs) label the active form of an enzyme via covalent modification of catalytic residues. Here we present an analysis of parameters influencing potency of peptide phosphonate ABPs for trypsin-fold S1A proteases, an abundant and important class of enzymes with similar substrate specificities. We find that peptide length and stability influence potency more than sequence composition and present structural evidence that steric interactions at the prime-side of the substrate-binding cleft affect potency in a protease-dependent manner. We introduce guidelines for the design of peptide phosphonate ABPs and demonstrate their utility in a live-cell labeling application that specifically targets active S1A proteases at the cell surface of cancer cells. PMID:21276938

  6. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, T.A.; Okamoto, Yoshiyuki; Lee, H.S.

    1989-11-21

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10[sup [minus]4] to 10[sup [minus]7] S cm[sup [minus]1] at room temperature.

  7. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, Terje A.; Okamoto, Yoshiyuki; Lee, Hung S.

    1989-01-01

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10.sup.-4 to 10.sup.-7 S cm.sup.-1 at room temperature.

  8. Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides.

    PubMed

    Henriksen, Gjermund; Schoultz, B W; Michaelsen, T E; Bruland, Ø S; Larsen, R H

    2004-05-01

    The alpha-particle emitting radionuclides (223)Ra (t(1/2) = 11.4 d), (224)Ra (t(1/2) = 3.6 d), and (225)Ac(t(1/2) = 10.0 d) may have a broad application in targeted radiotherapy provided that they could be linked to vehicles with tumor affinity. The potential usefulness of liposomes as carriers was studied in the present work. Radium and actinium radionuclides could be loaded in good yields into sterically stabilized liposomes. Subsequent coating of the liposomes with a folate-F(ab')(2) construct yielded a product with affinity towards tumor cells expressing folate receptors. Radionuclide loaded liposomes showed excellent stability in serum in vitro. PMID:15093814

  9. Effect of Structural Modifications on the Self-Assembly of Oligoprolines Conjugated with Sterically Demanding Chromophores.

    PubMed

    Lewandowska, Urszula; Zajaczkowski, Wojciech; Pisula, Wojciech; Ma, Yingjie; Li, Chen; Müllen, Klaus; Wennemers, Helma

    2016-03-01

    Conjugates between oligoprolines and sterically demanding perylene monoimides (PMIs) form hierarchical supramolecular self-assemblies. The influence of the length and stereochemistry at the attachment site between the peptide backbone and the chromophore on the self-assembly properties of the conjugates was explored. Comparison between oligoprolines bearing 4R- or 4S-configured azidoprolines (Azp) for the conjugation with the PMIs revealed that diastereoisomers with 4R configuration guide the self-assembly consistently better than conjugates with 4S configuration. Elongating the peptide chain beyond nine proline residues or introducing structural "errors", by altering the absolute configuration of one stereogenic center at the outside of the functionalizable oligoproline helix, lowered the efficacy of self-assembly significantly, both in solution phase and in the solid state. The results showed how subtle structural modifications allow for tuning the self-assembly of chromophores and provided further design principles for the development of peptide-chromophore conjugates into nanostructured materials. PMID:26891419

  10. Enantiospecific photoresponse of sterically hindered diarylethenes for chiroptical switches and photomemories

    NASA Astrophysics Data System (ADS)

    Li, Wenlong; Li, Xin; Xie, Yongshu; Wu, Yue; Li, Mengqi; Wu, Xin-Yan; Zhu, Wei-Hong; Tian, He

    2015-03-01

    Light-driven transcription, replication and enzyme catalysis are critically dependent upon a delicate transfer between molecular and supramolecular chirality. Chemists have well realized the impressive stereospecificity over many thermally accessible cycloaddition with chiral catalysts, but making light work in the enantiomer control of diarylethene photocyclization has proved to be more challenging. Here, we report a unique sterically hindered diarylethene (BBTE) system with absolute enantiospecific photocyclization and cycloreversion. Moreover, we have fully separated all the five thermally stable isomers, consisting of one achiral parallel conformer, one pair of anti-parallel ring-open enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral configurations are entirely elucidated by single X-ray crystallographic analyses. The photo-responsive feature exhibits a reversible, complete enantio-control transformation without racemism, offering an unrivaled unimolecular enantiospecific platform for potential applications as bistable chiroptical switches and all-photonic photomemories with optical rotation as non-destructive readout.

  11. Coarse-grained modeling of protein second osmotic virial coefficients: sterics and short-ranged attractions.

    PubMed

    Grünberger, Alexander; Lai, Pin-Kuang; Blanco, Marco A; Roberts, Christopher J

    2013-01-24

    A series of coarse-grained models, with different levels of structural resolution, were tested to calculate the steric contributions to protein osmotic second virial coefficients (B(22,S)) for proteins ranging from small single-domain molecules to large multidomain molecules, using the recently developed Mayer sampling method. B(22,S) was compared for different levels of coarse-graining: four-beads-per-amino-acid (4bAA), one-bead-per-amino-acid (1bAA), one-sphere-per-domain (1sD), and one-sphere-per-protein (1sP). Values for the 1bAA and 4bAA models were quantitatively indistinguishable for both spherical and nonspherical proteins, and the agreement with values from all-atom models improved with increasing protein size, making the CG approach attractive for large proteins of biotechnological interest. Interestingly, in the absence of detailed structural information, the hydrodynamic radius (R(h)) along with a simple 1sP approximation provided reasonably accurate values for B(22,S) for both globular and highly asymmetric protein structures, while other 1sP approximations gave poorer agreement; this helps to justify the currently empirical practice of estimating B(22,S) from R(h) for large proteins such as antibodies. The results also indicate that either 1bAA or 4bAA CG models may be good starting points for incorporating short-range attractions. Comparison of gD-crystallin B(22) values including both sterics and short-range attractions shows that 1bAA and 4bAA models give equivalent results when properly scaled to account for differences in the number of surface beads in the two CG descriptions. This provides a basis for future work that will also incorporate long-ranged electrostatic attractions and repulsions. PMID:23245189

  12. Role of steric effects in protein-directed enediyne cycloaromatization of neocarzinostatin.

    PubMed

    Chi, Hung-Wen; Chien, Yi-Chih; Liu, Cheng-Yun; Tseng, Chin-Jui; Lee, Yan-Jiun; Chan, Ja-Lin; Chu, Yu-Ru; Chin, Der-Hang

    2011-02-01

    The antibiotic neocarzinostatin comprises a carrier protein with a well-defined cavity for accommodating an active enediyne chromophore. The protein has two disulfides, one (Cys(37)-Cys(47)) lies on the cavity bottom and the other (Cys(88)-Cys(93)) in a constrained short loop. When the chromophore is not bound to the protein, a thiol-induced cycloaromatization of the enediyne into a tetrahydroindacene derivative is responsible for the potent antitumor activity. When it is protein-bound, the protein diverts the cycloaromatization pathway to form a distinct hydroxyisochromene-type product. How the protein directs the enediyne chemistry is an interesting puzzle, and various suggestions have been proposed in the past. We screened more than fifty thiols and manipulated conditions to locate reaction features and search for factors that could influence the protein directing strength. Thiol- and oxygen-concentration-dependence studies suggested that disulfides, which maintain the steric rigidity of the protein, could play a key role in diverting the cycloaromatization pathway. For direct proofs, we made mutations at each of the two disulfides by replacing sulfur atoms with oxygen. Circular dichroism and two-dimensional NMR spectroscopy studies suggested that the mutations changed neither the protein conformation nor the ligand interactions. Analyses of the thiol-induced cycloaromatization revealed that rupture of Cys(37)-Cys(47) made the protein almost completely lose its chemical directing ability, whereas rupture of Cys(88)-Cys(93) had only a minor influence. The results demonstrated that the steric rigidity of the binding cavity, but not necessary the whole protein, played an important role in the protein-directed mechanism. PMID:21268152

  13. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

    PubMed Central

    LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.

    2012-01-01

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence–specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. PMID:22622039

  14. A sterically demanding organo-superbase avoids decomposition of a naked trifluoromethyl carbanion directly generated from fluoroform.

    PubMed

    Kawai, Hiroyuki; Yuan, Zhe; Tokunaga, Etsuko; Shibata, Norio

    2013-03-01

    A simple strategy avoiding the decomposition of a naked trifluoromethyl anion to difluorocarbene by a sterically very demanding organo-superbase without the help of a trifluoromethyl anion reservoir such as DMF is reported. The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded trifluoromethyl alcohols in high yields. PMID:23344691

  15. Comment on "Rabbit-Ears Hybrids, VSEPR Sterics, and Other Orbital Anachronisms": A Reply to a Criticism

    ERIC Educational Resources Information Center

    Hiberty, Philippe C.; Danovich, David; Shaik, Sason

    2015-01-01

    This commentary summarizes the authors' basic disagreements with the paper, "Rabbit-Ears, VSEPR Sterics, and Other Orbital Anachronisms," which criticizes the authors' usage of the hybrid orbitals for H[subscript 2]O in their book, "A Chemist's Guide to Valence Bond Theory" (Shaik and Hiberty, 2008). The current article shows…

  16. Barrier Formation

    PubMed Central

    Lyaruu, D.M.; Medina, J.F.; Sarvide, S.; Bervoets, T.J.M.; Everts, V.; DenBesten, P.; Smith, C.E.; Bronckers, A.L.J.J.

    2014-01-01

    Enamel fluorosis is an irreversible structural enamel defect following exposure to supraoptimal levels of fluoride during amelogenesis. We hypothesized that fluorosis is associated with excess release of protons during formation of hypermineralized lines in the mineralizing enamel matrix. We tested this concept by analyzing fluorotic enamel defects in wild-type mice and mice deficient in anion exchanger-2a,b (Ae2a,b), a transmembrane protein in maturation ameloblasts that exchanges extracellular Cl− for bicarbonate. Defects were more pronounced in fluorotic Ae2a,b−/− mice than in fluorotic heterozygous or wild-type mice. Phenotypes included a hypermineralized surface, extensive subsurface hypomineralization, and multiple hypermineralized lines in deeper enamel. Mineral content decreased in all fluoride-exposed and Ae2a,b−/− mice and was strongly correlated with Cl−. Exposure of enamel surfaces underlying maturation-stage ameloblasts to pH indicator dyes suggested the presence of diffusion barriers in fluorotic enamel. These results support the concept that fluoride stimulates hypermineralization at the mineralization front. This causes increased release of protons, which ameloblasts respond to by secreting more bicarbonates at the expense of Cl− levels in enamel. The fluoride-induced hypermineralized lines may form barriers that impede diffusion of proteins and mineral ions into the subsurface layers, thereby delaying biomineralization and causing retention of enamel matrix proteins. PMID:24170372

  17. Addressing language barriers to healthcare in India.

    PubMed

    Narayan, Lalit

    2013-01-01

    In spite of a growing recognition of the importance of doctor-patient communication, the issue of language barriers to healthcare has received very little attention in India. The Indian population speaks over 22 major languages with English used as the lingua franca for biomedicine. Large-scale internal migration has meant that health workers are encountering increasing instances of language discordance within clinical settings. Research done predominantly in the West has shown language discordance to significantly affect access to care, cause problems of comprehension and adherence, and decrease the satisfaction and quality of care. Addressing language barriers to healthcare in India requires a stronger political commitment to providing non-discriminatory health services, especially to vulnerable groups such as illiterate migrant workers. Research will have to address three broad areas: the ways in which language barriers affect health and healthcare, the efficacy of interventions to overcome language barriers, and the costs of language barriers and efforts to overcome them. There is a need to address such barriers in health worker education and clinical practice. Proven strategies such as hiring multilingual healthcare workers, providing language training to health providers, employing in situ translators or using telephone interpretation services will have to be evaluated for their appropriateness to the Indian context. Internet-based initiatives, the proliferation of mobile phones and recent advances in machine translation promise to contribute to the solution. PMID:24758452

  18. Unusually Efficient Pyridine Photodissociation from Ru(II) Complexes with Sterically Bulky Bidentate Ancillary Ligands

    PubMed Central

    2015-01-01

    The introduction of steric bulk to the bidentate ligand in [Ru(tpy)(bpy)(py)]2+ (1; tpy = 2,2′:2′,6″-terpyridine; bpy = 2,2′-bipyridine; py = pyridine) to provide [Ru(tpy)(Me2bpy)(py)]2+ (2; Me2bpy = 6,6′-dimethyl-2,2′-bipyridine) and [Ru(tpy)(biq)(py)]2+ (3; biq = 2,2′-biquinoline) facilitates photoinduced dissociation of pyridine with visible light. Upon irradiation of 2 and 3 in CH3CN (λirr = 500 nm), ligand exchange occurs to produce the corresponding [Ru(tpy)(NN)(NCCH3)]2+ (NN = Me2bpy, biq) complex with quantum yields, Φ500, of 0.16(1) and 0.033(1) for 2 and 3, respectively. These values represent an increase in efficiency of the reaction by 2–3 orders of magnitude as compared to that of 1, Φ500 < 0.0001, under similar experimental conditions. The photolysis of 2 and 3 in H2O with low energy light to produce [Ru(tpy)(NN)(OH2)]2+ (NN = Me2bpy, biq) also proceeds rapidly (λirr > 590 nm). Complexes 1–3 are stable in the dark in both CH3CN and H2O under similar experimental conditions. X-ray crystal structures and theoretical calculations highlight significant distortion of the planes of the bidentate ligands in 2 and 3 relative to that of 1. The crystallographic dihedral angles defined by the bidentate ligand, Me2bpy in 2 and biq in 3, and the tpy ligand were determined to be 67.87° and 61.89°, respectively, whereas only a small distortion from the octahedral geometry is observed between bpy and tpy in 1, 83.34°. The steric bulk afforded by Me2bpy and biq also result in major distortions of the pyridine ligand in 2 and 3, respectively, relative to 1, which are believed to weaken its σ-bonding and π-back-bonding to the metal and play a crucial role in the efficiency of the photoinduced ligand exchange. The ability of 2 and 3 to undergo ligand exchange with λirr > 590 nm makes them potential candidates to build photochemotherapeutic agents for the delivery of drugs with pyridine binding groups. PMID:25027458

  19. Toward understanding the nature of internal rotation barriers with a new energy partition scheme: ethane and n-butane.

    PubMed

    Liu, Shubin; Govind, Niranjan

    2008-07-24

    On the basis of an alternative energy partition scheme where density-based quantification of the steric effect was proposed [Liu, S. B. J. Chem. Phys. 2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane and n-butane is systematically investigated in this work. Within the new scheme, the total electronic energy is decomposed into three independent components, steric, electrostatic, and fermionic quantum. The steric energy defined in this way is repulsive, exclusive, and extensive and intrinsically linked to Bader's atoms in molecules approach. Two kinds of differences, adiabatic (with optimal structure) and vertical (with fixed geometry), are considered for the molecules in this work. We find that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer for both molecules, but in the vertical cases the staggered conformer retains a larger steric repulsion. For ethane, a linear relationship between the total energy difference and the fermionic quantum energy difference is discovered. This linear relationship, however, does not hold for n-butane, whose behaviors in energy component differences are found to be more complicated. The impact of basis set and density functional choices on energy components from the new energy partition scheme has been investigated, as has its comparison with another definition of the steric effect in the literature in terms of the natural bond orbital analysis through the Pauli Exclusion Principle. In addition, profiles of conceptual density functional theory reactivity indices as a function of dihedral angle changes have been examined. Put together, these results suggest that the new energy partition scheme provides insights from a different perspective of internal rotation barriers. PMID:18563887

  20. Overcoming Resistance to Culture Change: Nursing Home Administrators’ Use of Education, Training and Communication

    PubMed Central

    Tyler, Denise A.; Lepore, Michael; Shield, Renee R.; Looze, Jessica; Miller, Susan C.

    2014-01-01

    Nursing home culture change is becoming more prevalent and research has demonstrated its benefits for nursing home residents and staff, but little is known about the role of nursing home administrators in culture change implementation. The purpose of this study was to determine what barriers nursing home administrators faced in implementing culture change practices and to identify the strategies used to overcome these. We conducted in-depth individual interviews with 64 administrators identified through a nationally representative survey. Results showed that a key barrier to culture change implementation reported by administrators was staff, resident and family member resistance to change. Most nursing home administrators stressed the importance of using communication, education and training to overcome this resistance. Themes emerging around the concepts of communication and education indicate that these efforts should be ongoing, communication should be reciprocal, and that all stakeholders should be included. PMID:24266678

  1. Overcoming Anarchy in the Advanced Language Class.

    ERIC Educational Resources Information Center

    Gutierrez, John R.

    1990-01-01

    The coordination, articulation, and implementation of informed teaching techniques and objectives will help to overcome the anarchy and confusion that characterize higher education advanced-level foreign language classes, and will begin to produce a pool of highly competent foreign language speakers and writers. (33 references) (CB)

  2. Overcoming the Limitations of Learning Objects

    ERIC Educational Resources Information Center

    Wiley, David; Waters, Sandie; Dawson, Deonne; Lambert, Brent; Barclay, Matthew; Wade, David; Nelson, Laurie

    2004-01-01

    There are a number of issues that face individuals who would use learning objects for instructional purposes. These issues include problems with decontextualization, enabling meaningful reusability, and overcoming biases toward didactic approaches in the use of learning objects. We discuss these problems in some detail, and present a project-based…

  3. Overcoming Xenophobia: Learning to Accept Differences.

    ERIC Educational Resources Information Center

    Baker, Judith A.

    1990-01-01

    Quality health education requires that health educators engage in the professional and personal development necessary to overcome xenophobia when working with special populations (obese, elderly, indigent, minorities, etc.). This article describes strategies employed in a university community health education class to help students overcome…

  4. Learn to Avoid or Overcome Leadership Obstacles

    ERIC Educational Resources Information Center

    D'Auria, John

    2015-01-01

    Leadership is increasingly recognized as an important factor in moving schools forward, yet we have been relatively random in how we prepare and support them. Four obstacles often block or diminish their effectiveness. Avoiding or overcoming each of these requires an underlying set of skills and knowledge that we believe can be learned and…

  5. 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…

  6. Students Write to Overcome Learning Blocks.

    ERIC Educational Resources Information Center

    Lavoie, Dan; Backus, Ann

    1990-01-01

    Discussed is the use of writing as a tool to monitor student growth and development. The value of writing to help overcome obstacles such as misconceptions and preconceptions is stressed. A concept map of a hierarchy of writing strategies is provided. Stressed is the value of writing in the development of process skills. (CW)

  7. First Davis Strait discovery overcomes offshore hazards

    SciTech Connect

    Munro, R.G.

    1982-04-01

    In spite of icebergs umpredictable currents and brief drilling seasons, the first discovery well was completed recently in the Davis Strait. The success of this well, known as Hekja 0-71, has opened the waters off the northeastern coast of Canada to more exploration. A discussion is presented of how the well was drilled, the problems encountered and how they were overcome.

  8. The BARRIERS scale -- the barriers to research utilization scale: A systematic review

    PubMed Central

    2010-01-01

    Background A commonly recommended strategy for increasing research use in clinical practice is to identify barriers to change and then tailor interventions to overcome the identified barriers. In nursing, the BARRIERS scale has been used extensively to identify barriers to research utilization. Aim and objectives The aim of this systematic review was to examine the state of knowledge resulting from use of the BARRIERS scale and to make recommendations about future use of the scale. The following objectives were addressed: To examine how the scale has been modified, to examine its psychometric properties, to determine the main barriers (and whether they varied over time and geographic locations), and to identify associations between nurses' reported barriers and reported research use. Methods Medline (1991 to September 2009) and CINHAL (1991 to September 2009) were searched for published research, and ProQuest® digital dissertations were searched for unpublished dissertations using the BARRIERS scale. Inclusion criteria were: studies using the BARRIERS scale in its entirety and where the sample was nurses. Two authors independently assessed the study quality and extracted the data. Descriptive and inferential statistics were used. Results Sixty-three studies were included, with most using a cross-sectional design. Not one study used the scale for tailoring interventions to overcome identified barriers. The main barriers reported were related to the setting, and the presentation of research findings. Overall, identified barriers were consistent over time and across geographic locations, despite varying sample size, response rate, study setting, and assessment of study quality. Few studies reported associations between reported research use and perceptions of barriers to research utilization. Conclusions The BARRIERS scale is a nonspecific tool for identifying general barriers to research utilization. The scale is reliable as reflected in assessments of internal

  9. Sterically stabilized superparamagnetic liposomes for MR imaging and cancer therapy: pharmacokinetics and biodistribution.

    PubMed

    Plassat, V; Martina, M S; Barratt, G; Ménager, C; Lesieur, S

    2007-11-01

    Pharmacokinetics of magnetic-fluid-loaded liposomes (MFLs) with mean hydrodynamic diameter of 200 nm sterically stabilized by poly(ethylene glycol) (PEG) and labelled by a fluorescent lipid probe, N-(lissamine rhodamine B sulfonyl) phosphatidylethanolamine (Rho-PE) was studied. The loading consisted in an aqueous suspension of maghemite nanocrystals close to 8 nm in size at 1.7 Fe(III)mol/mol total lipids ratio. Double tracking of MFL in blood was performed versus time after intravenous administration in mice. Lipids constituting vesicle membrane were followed by Rho-PE fluorescence spectroscopy while iron oxide was determined independently by relaxometry. MFLs circulating in the vascular compartment conserved their vesicle structure and content. The pharmacokinetic profile was characterized by two first-order kinetics of elimination with distinct plasmatic half-lives of 70 min and 12.5 h. Iron biodistribution and organ histology clearly highlighted preferential MFL accumulation within liver and spleen. The pathway in spleen supported that elimination was governed by the mononuclear phagocyte system (MPS). PEG coating was essential to prolong MFL circulation time whereas iron oxide loading tends to favour uptake by the MPS. Despite partial uptake in the earlier times after administration, MFLs exhibited long circulation behaviour over a 24-h period that, coupled to magnetic targeting, encourages further use in drug delivery. PMID:17583452

  10. The interaction of sterically stabilized magnetic nanoparticles with fresh human red blood cells

    PubMed Central

    Pham, Binh TT; Jain, Nirmesh; Kuchel, Philip W; Chapman, Bogdan E; Bickley, Stephanie A; Jones, Stephen K; Hawkett, Brian S

    2015-01-01

    Sterically stabilized superparamagnetic iron oxide nanoparticles (SPIONs) were incubated with fresh human erythrocytes (red blood cells [RBCs]) to explore their potential application as magnetic resonance imaging contrast agents. The chemical shift and linewidth of 133Cs+ resonances from inside and outside the RBCs in 133Cs nuclear magnetic resonance spectra were monitored as a function of time. Thus, we investigated whether SPIONs of two different core sizes and with three different types of polymeric stabilizers entered metabolically active RBCs, consuming glucose at 37°C. The SPIONs broadened the extracellular 133Cs+ nuclear magnetic resonance, and brought about a small change in its chemical shift to a higher frequency; while the intracellular resonance remained unchanged in both amplitude and chemical shift. This situation pertained over incubation times of up to 90 minutes. If the SPIONs had entered the RBCs, the intracellular resonance would have become broader and possibly even shifted. Therefore, we concluded that our SPIONs did not enter the RBCs. In addition, the T2 relaxivity of the small and large particles was 368 and 953 mM−1 s−1, respectively (three and nine times that of the most effective commercially available samples). This suggests that these new SPIONs will provide a superior performance to any others reported thus far as magnetic resonance imaging contrast agents. PMID:26604741

  11. Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential.

    PubMed Central

    Woodle, M C; Collins, L R; Sponsler, E; Kossovsky, N; Papahadjopoulos, D; Martin, F J

    1992-01-01

    The electrophoretic mobility of liposomes containing a negatively charged derivative of phosphatidylethanolamine with a large headgroup composed of the hydrophilic polymer polyethylene glycol (PEG-PE) was determined by Doppler electrophoretic light scattering. The results show that this method is improved by the use of measurements at multiple angles to eliminate artifacts and that very small mobilities can be measured. The electrophoretic mobility of liposomes with 5 to 10 mol% PEG-PE is approximately -0.5 mu ms-1/Vcm-1 regardless of PEG-PE content compared with approximately -2 mu ms-1/Vcm-1 for similar liposomes but containing 7.5% phosphatidylglycerol (PG) instead of PEG-PE. Measurements of surface potential by distribution of an anionic fluorescent probe show that the PEG-PE imparts a negative charge identical to that by PG, consistent with the expectation of similar locations of the ionized phosphate responsible for the charge. The reduced mobility imparted by the surface bound PEG is attributed to a mechanism similar to that described for colloidal steric stabilization: hydrodynamic drag moves the hydrodynamic plane of shear, or the hydrodynamic radius, away from the charge-bearing plane, that of the phosphate moities. An extended length of approximately 50 A for the 2,000 molecular weight PEG is estimated from the reduction in electrophoretic mobility. PMID:1581503

  12. Grafting zwitterionic polymer onto cryogel surface enhances protein retention in steric exclusion chromatography on cryogel monolith.

    PubMed

    Tao, Shi-Peng; Zheng, Jie; Sun, Yan

    2015-04-10

    Cryogel monoliths with interconnected macropores (10-100μm) and hydrophilic surfaces can be employed as chromatography media for protein retention in steric exclusion chromatography (SXC). SXC is based on the principle that the exclusion of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a protein favors their association, leading to the protein retention on the chromatography surface. Elution of the retained protein can be achieved by reducing PEG concentration. In this work, the surface of polyacrylamide-based cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine methacrylate) (pCBMA), leading the increase in the surface hydrophilicity. Observation by scanning electron microscopy revealed the presence of the grafted pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in the changes of the physical properties of the monolith column, and the columns maintained good recyclability in SXC. The effect of the surface grafting on the SXC behavior of γ-globulin was investigated in a wide flow rate range (0.6-12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8 times by the zwitterionic polymer grafting in the flow rate range of 1.5-12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer-grafted surface was proposed. The research proved that zwitterionic polymer modification was promising for the development of new materials for SXC applications. PMID:25757821

  13. The effect of chirality and steric hindrance on intrinsic backbone conformational propensities: tools for protein design.

    PubMed

    Childers, Matthew Carter; Towse, Clare-Louise; Daggett, Valerie

    2016-07-01

    The conformational propensities of amino acids are an amalgamation of sequence effects, environmental effects and underlying intrinsic behavior. Many have attempted to investigate neighboring residue effects to aid in our understanding of protein folding and improve structure prediction efforts, especially with respect to difficult to characterize states, such as disordered or unfolded states. Host-guest peptide series are a useful tool in examining the propensities of the amino acids free from the surrounding protein structure. Here, we compare the distributions of the backbone dihedral angles (φ/ψ) of the 20 proteogenic amino acids in two different sequence contexts using the AAXAA and GGXGG host-guest pentapeptide series. We further examine their intrinsic behaviors across three environmental contexts: water at 298 K, water at 498 K, and 8 M urea at 298 K. The GGXGG systems provide the intrinsic amino acid propensities devoid of any conformational context. The alanine residues in the AAXAA series enforce backbone chirality, thereby providing a model of the intrinsic behavior of amino acids in a protein chain. Our results show modest differences in φ/ψ distributions due to the steric constraints of the Ala side chains, the magnitudes of which are dependent on the denaturing conditions. One of the strongest factors modulating φ/ψ distributions was the protonation of titratable side chains, and the largest differences observed were in the amino acid propensities for the rarely sampled αL region. PMID:27284086

  14. Steric hindrance and the enhanced stability of light rare-earth elements in hydrothermal fluids

    SciTech Connect

    Mayanovic, Robert A.; Anderson, Alan J.; Bassett, William A.; Chou, I-Ming

    2009-10-05

    A series of X-ray absorption spectroscopy (XAS) experiments were made to determine the structure and stability of aqueous REE (La, Nd, Gd, and Yb) chloride complexes to 500 C and 520 MPa. The REE{sup 3+} ions exhibit inner-sphere chloroaqua complexation with a steady increase of chloride coordination with increasing temperature in the 150 to 500 C range. Furthermore, the degree of chloride coordination of REE{sup 3+} inner-sphere chloroaqua complexes decreases significantly from light to heavy REE. These results indicate that steric hindrance drives the reduction of chloride coordination of REE{sup 3+} inner-sphere chloroaqua complexes from light to heavy REE. This results in greater stability and preferential transport of light REE{sup 3+} over heavy REE{sup 3+} ions in saline hydrothermal fluids. Accordingly, the preferential mobility of light REE directly influences the relative abundance of REE in rocks and minerals and thus needs to be considered in geochemical modeling of petrogenetic and ore-forming processes affected by chloride-bearing hydrothermal fluids.

  15. A sterically congested cis-stilbene and its phosphonium salt precursor.

    PubMed

    Shivaprakash, Shivanna; Reddy, G Chandrasekara; Jasinski, Jerry P; Millikan, Sean P; Duff, Courtney E; Glidewell, Christopher

    2015-06-01

    Triphenyl(2,4,5-trimethoxybenzyl)phosphonium chloride is formed in solvent-free form by the reaction under anhydrous conditions between triphenylphosphane and 2,4,5-trimethoxybenzyl chloride, but when it is crystallized from a mixture of ethyl acetate and chloroform in the presence of air it forms a stoichiometric monohydrate, C28H28O3P(+)·Cl(-)·H2O, (I). The reactions between the anhydrous phosphonium salt and alkoxy-substituted benzaldehydes, using Wittig reactions in the presence of potassium tert-butoxide, provide a series of multiply substituted stilbenes, most of which were assigned the Z configuration on the basis of their NMR spectra. However, no such deduction could be made for the symmetrically substituted (Z)-2,2',4,4',5,5'-hexamethoxystilbene, C20H24O6, (II). Compound (II) does in fact have the Z configuration and the molecular geometry provides evidence for steric congestion around the central double bond; in particular, the central alkene fragment is nonplanar, with a C-C=C-C torsion angle of 7.8 (4)°. In hydrated salt (I), the chloride anions and water molecules are linked by O-H···Cl hydrogen bonds to form C2(1)(4) chains; each cation is linked by C-H···O hydrogen bonds to two different chains, so forming a sheet structure. There are no direction-specific intermolecular interactions in the structure of (II). PMID:26044330

  16. The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres☆

    PubMed Central

    Gref, R.; Domb, A.; Quellec, P.; Blunk, T.; Müller, R.H.; Verbavatz, J.M.; Langer, R.

    2014-01-01

    Injectable blood persistent particulate carriers have important therapeutic application in site-specific drug delivery or medical imaging. However, injected particles are generally eliminated by the reticuloendothelial system within minutes after administration and accumulate in the liver and spleen. To obtain a coating that might prevent opsonization and subsequent recognition by the macrophages, sterically stabilized nanospheres were developed using amphiphilic diblock or multiblock copolymers. The nanospheres are composed of a hydrophilic polyethylene glycol coating and a biodegradable core in which various drugs were encapsulated. Hydrophobic drugs, such as lidocaine, were entrapped up to 45 wt% and the release kinetics were governed by the polymer physico-chemical characteristics. Plasma protein adsorption was drastically reduced on PEG-coated particles compared to non-coated ones. Relative protein amounts were time-dependent. The nanospheres exhibited increased blood circulation times and reduced liver accumulation, depending on the coating polyethylene glycol molecular weight and surface density. They could be freeze-dried and redispersed in aqueous solutions and possess good shelf stability. It may be possible to tailor “optimal” polymers for given therapeutic applications. PMID:25170183

  17. Electrochromic sensing platform based on steric hindrance effects for CEA detection.

    PubMed

    Zhai, Qingfeng; Zhang, Xiaowei; Xia, Yong; Li, Jing; Wang, Erkang

    2016-06-20

    In this work, an electrochromic sensing platform with prussian blue (PB) as the indicator was proposed for signaling carcinoembryonic antigen (CEA) using the bipolar electrode (BPE) system. The CEA aptamer was pre-anchored on the anode pole of the BPE for capturing CEA through strong binding affinity. The presence of CEA induced the increase of steric hindrance and led to lower electrochemical currents. Due to the quantitative relationship between the two reactions occurring at both ends of the BPE, the amount of deposited PB in situ can be used as an indicator for reporting target protein concentration. Using CEA concentration in normal human serum as a reference (5 ng mL(-1)), this electrochromic sensing platform can be used for distinguishing persons with cancer from normal humans easily and quickly, which is very important for subsequent treatment of patients. This novel electrochromic platform has great selectivity for target tumor proteins and provides a fast, visual method for CEA detection. Finally, the proposed biosensor can be applied to detect CEA in human serum, which holds great potential for point-of-care diagnostics combined with the advantage of the closed BPE system. PMID:27160521

  18. Effect of fullerene on the dispersibility of nanostructured lipid particles and encapsulation in sterically stabilized emulsions.

    PubMed

    Kulkarni, Chandrashekhar V; Moinuddin, Zeinab; Agarwal, Yash

    2016-10-15

    We report on the effect of fullerenes (C60) on the stability of nanostructured lipid emulsions. These (oil-in-water) emulsions are essentially aqueous dispersions of lipid particles exhibiting self-assembled nanostructures at their cores. The majority of previous studies on fullerenes were focused on planar and spherical lipid bilayer systems including pure lipids and liposomes. In this work, fullerenes were interacted with a lipid that forms nanostructured dispersions of non-lamellar self-assemblies. A range of parameters including the composition of emulsions and sonication parameters were examined to determine the influence of fullerenes on in-situ and pre-stabilized lipid emulsions. We found that fullerenes mutually stabilize very low concentrations of lipid molecules, while other concentration emulsions struggle to stay stable or even to form at first instance; we provide hypotheses to support these observations. Interestingly though, we were able to encapsulate varying amounts of fullerenes in sterically stabilized emulsions. This step has a significant positive impact, as we could effectively control an inherent aggregation tendency of fullerenes in aqueous environments. These novel hybrid nanomaterials may open a range of avenues for biotechnological and biomedical applications exploiting properties of both lipid and fullerene nanostructures. PMID:27416287

  19. An investigation of some sterically hindered amines as potential carbon dioxide scrubbing compounds

    SciTech Connect

    Hook, R.J.

    1997-05-01

    In order to improve the efficiency of the carbon dioxide cycling process and to reduce amine emissions, a series of nonvolatile amino acid salts with sterically hindered amine groups were investigated to determine their potential as direct replacements for monoethanolamine (MEA) in submarine-based CO{sub 2} scrubbers. Absorption from atmospheres containing various levels of CO{sub 2} was measured to assess the total capacities and absorption rates of amine solutions. The regeneration rates and extent of CO{sub 2} desorption were established by heating these solutions. {sup 13}C NMR spectroscopy was used to establish reaction products and solution compositions after both absorption and desorption. Methyl groups substituted adjacent to the amine were found to increase solution absorption capacities but with an overall reduction in absorption rate. Poor absorption rates at low CO{sub 2} levels and precipitation problems would prevent the {alpha}-dimethylamines examined from being used in existing submarine scrubbers. These amines, however, show potential as replacements in industrial CO{sub 2} scrubbing processes.

  20. Design, Synthesis, and Biological Features of Platinum(II) Complexes with Rigid Steric Hindrance.

    PubMed

    Wang, Zhimei; Yu, Haiyan; Gou, Shaohua; Chen, Feihong; Fang, Lei

    2016-05-01

    A series of platinum(II) complexes, with N-monosubstituted 1R,2R-diaminocyclohexane bearing methoxy-substituted benzyl groups as carrier ligands, were designed and synthesized. The newly prepared compounds, with chloride anions as leaving groups, were found to be very active against the tested cancer cell lines, including a cisplatin-resistant cell line. Despite their efficacy against tumor cells, they also showed low toxicity to a human normal liver cell line. Among them, complex 1 had superior cytotoxic activity against A549, HCT-116, MCF-7, SGC7901, and SGC7901/CDDP cancer cell lines. The DNA binding assay is of further special interest, as an unusual monofunctional binding mode was found, due to the introduction of a rigid substituted aromatic ring in the 1R,2R-diaminocyclohexane framework as steric hindrance. The linkage of complex 1 with DNA was stable and insensitive to nucleophilic attack. Moreover, studies including cellular uptake, gel electrophoresis, apoptosis and cell cycle, and Western blot analysis have provided insight into the high potency of this compound. PMID:27074104

  1. Barriers to participation in mental health research: are there specific gender, ethnicity and age related barriers?

    PubMed Central

    2010-01-01

    Background It is well established that the incidence, prevalence and presentation of mental disorders differ by gender, ethnicity and age, and there is evidence that there is also differential representation in mental health research by these characteristics. The aim of this paper is to a) review the current literature on the nature of barriers to participation in mental health research, with particular reference to gender, age and ethnicity; b) review the evidence on the effectiveness of strategies used to overcome these barriers. Method Studies published up to December 2008 were identified using MEDLINE, PsycINFO and EMBASE using relevant mesh headings and keywords. Results Forty-nine papers were identified. There was evidence of a wide range of barriers including transportation difficulties, distrust and suspicion of researchers, and the stigma attached to mental illness. Strategies to overcome these barriers included the use of bilingual staff, assistance with travel, avoiding the use of stigmatising language in marketing material and a focus on education about the disorder under investigation. There were very few evaluations of such strategies, but there was evidence that ethnically matching recruiters to potential participants did not improve recruitment rates. Educational strategies were helpful and increased recruitment. Conclusion Mental health researchers should consider including caregivers in recruitment procedures where possible, provide clear descriptions of study aims and describe the representativeness of their sample when reporting study results. Studies that systematically investigate strategies to overcome barriers to recruitment are needed. PMID:21126334

  2. Rationally designed nanovehicles to overcome cancer chemoresistance.

    PubMed

    Livney, Yoav D; Assaraf, Yehuda G

    2013-11-01

    Drug resistance is a primary hindrance towards curative cancer chemotherapy. Nanotechnology holds great promise in establishing efficacious and innovative strategies to overcome chemoresistance, and markedly facilitate complementary treatments and cancer diagnostics. Various nanomedical devices are being introduced and evaluated, demonstrating encouraging results. While stealth liposomes serve as a benchmark, astonishing progress is witnessed in polymeric nanovehicles, sometimes combined with low molecular weight surfactants, some of which inhibit drug resistance in addition to solubilizing drugs. Cutting edge multifunctional or quadrugnostic nanoparticles currently developed offer simultaneous targeted delivery of chemotherapeutics and chemosensitizers or drug-resistance gene silencing cargo, along with diagnostic imaging agents, like metallic NPs. Viral and cellular components offer exciting new routes for cancer targeting and treatment. Targeting intracellular compartments is another challenging frontier spawning pioneering approaches and results. To further enhance rational design of nanomedicine for overcoming drug resistance, we review the latest thoughts and accomplishments in recent literature. PMID:23954781

  3. [Cancer immunotherapy. Importance of overcoming immune suppression].

    PubMed

    Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

    2010-01-01

    Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors. PMID:21163748

  4. Studies on the synthesis of (-)-spinosyn a: application of the steric directing group strategy to transannular Diels-Alder reactions.

    PubMed

    Frank, Scott A; Roush, William R

    2002-06-14

    A highly diastereoselective and enantioselective synthesis of the decahydro-as-indacene nucleus 12 of (-)-spinosyn A (1) is reported. By implementing the steric directing group strategy, tricyclic lactone 37 was produced from a remarkably diastereoselective transannular Diels-Alder reaction of lactone 9. The tricyclic core of the natural product was then obtained by using an Ireland-Claisen ring contraction of 37. Reversal of the order of these two steps resulted in an almost complete loss of diastereoselectivity. PMID:12054969

  5. Correlation of the solubility of several aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin with steric and hydrophobicity parameters.

    PubMed

    Demian, B A

    2000-10-01

    The solubility isotherms of nineteen aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin were determined to be straight lines. This is explained by the host-guest complexation which is characteristic for the whole class of cyclodextrins and derivatives. The slopes of the solubility isotherms correlate with Sterimol L and log P(ow) as descriptors of the steric fit and hydrophobicity match, in accord with the qualitative representation of the phenomenon. PMID:11093722

  6. Viscoelastic properties of polystyrene and poly(methyl methacrylate) dispersions sterically stabilized by hydrophobically modified inulin (polyfructose) polymeric surfactant.

    PubMed

    Nestor, Jérémie; Obiols-Rabasa, Marc; Esquena, Jordi; Solans, Conxita; Levecke, Bart; Booten, Karl; Tadros, Tharwat F

    2008-03-01

    Recently, steric repulsive forces induced by a new graft copolymer surfactant, which is based in inulin (polyfructose), have been described. Previous investigations by atomic force microscopy between solid surfaces covered with adsorbed surfactant indicated strong repulsive forces even at high electrolyte concentration, due to the steric repulsion produced by the surfactant hydration. In the present paper, the colloidal stabilization provided by this surfactant is studied by rheology. The measurements were carried out on sterically stabilized polystyrene (PS) and poly(methyl methacrylate) (PMMA) containing adsorbed surfactant (INUTEC SP1). Steady-state shear stress as a function of shear rate curves was established at various latex volume fractions. The viscosity volume fraction curves were compared with those calculated using the Doughtry-Krieger equation for hard sphere dispersions. From the experimental eta r-phi curves the effective volume fraction of the latex dispersions could be calculated and this was used to determine the adsorbed layer thickness Delta. The value obtained was 9.6 nm, which is in good agreement with that obtained using atomic force microscopy (AFM). Viscoelastic measurements of the various latex dispersions were carried out as a function of applied stress (to obtain the linear viscoelastic region) and frequency. The results showed a change from predominantly viscous to predominantly elastic response at a critical volume fraction (phi c). The effective critical volume fraction, phi eff, was calculated using the adsorbed layer thickness (Delta) obtained from steady-state measurements. For PS latex dispersions phi eff was found to be equal to 0.24 whereas for PMMA phi eff=0.12. These results indicated a much softer interaction between the latex dispersions containing hydrated polyfructose loops and tails when compared with latices containing poly(ethylene oxide) (PEO) layers. The difference could be attributed to the stronger hydration of the

  7. Immunobiological barriers to xenotransplantation.

    PubMed

    Cooper, David K C; Ekser, Burcin; Tector, A Joseph

    2015-11-01

    Binding of natural anti-pig antibodies in humans and nonhuman primates to carbohydrate antigens expressed on the transplanted pig organ, the most important of which is galactose-α1,3-galactose (Gal), activate the complement cascade, which results in destruction of the graft within minutes or hours, known as hyperacute rejection. Even if antibody is removed from the recipient's blood by plasmapheresis, recovery of antibody is associated with acute humoral xenograft rejection. If immunosuppressive therapy is inadequate, the development of high levels of T cell-dependent elicited anti-pig IgG similarly results in graft destruction, though classical acute cellular rejection is rarely seen. Vascular endothelial activation by low levels of anti-nonGal antibody, coupled with dysregulation of the coagulation-anticoagulation systems between pigs and primates, leads to a thrombotic microangiopathy in the graft that may be associated with a consumptive coagulopathy in the recipient. The most successful approach to overcoming these barriers is by genetically-engineering the pig to provide it with resistance to the human humoral and cellular immune responses and to correct the coagulation discrepancies between the two species. Organs and cells from pigs that (i) do not express the important Gal antigen, (ii) express a human complement-regulatory protein, and (iii) express a human coagulation-regulatory protein, when combined with an effective immunosuppressive regimen, have been associated with prolonged pig graft survival in nonhuman primates. PMID:26159291

  8. Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

    PubMed Central

    Stern, Avital; Guidotti, Matteo; Shaubi, Eleonora; Popov, Mary; Linder, Charles; Heldman, Eliahu; Grinberg, Sarina

    2014-01-01

    Two bolaamphiphilic compounds with identical acetylcholine (ACh) head groups, but with different lengths of an alkyl chain pendant adjacent to the head group, as well as differences between their hydrophobic skeleton, were investigated for their ability to self-assemble into vesicles that release their encapsulated content upon hydrolysis of their head groups by acetylcholinesterase (AChE). One of these bolaamphiphiles, synthesized from vernolic acid, has an alkyl chain pendant of five methylene groups, while the other, synthesized from oleic acid, has an alkyl chain pendant of eight methylene groups. Both bolaamphiphiles formed stable spherical vesicles with a diameter of about 130 nm. The ACh head groups of both bolaamphiphiles were hydrolyzed by AChE, but the hydrolysis rate was significantly faster for the bolaamphiphile with the shorter aliphatic chain pendant. Likewise, upon exposure to AChE, vesicles made from the bolaamphiphile with the shorter alkyl chain pendant released their encapsulated content faster than vesicles made from the bolaamphiphile with the longer alkyl chain pendant. Our results suggest that the steric environment around the ACh head group of bolaamphiphiles is a major factor affecting the hydrolysis rate of the head groups by AChE. Attaching an alkyl chain to the bolaamphiphile near the ACh head group allows self-assembled vesicles to form with a controlled release rate of the encapsulated materials, whereas shorter alkyl chains enable a faster head group hydrolysis, and consequently faster release, than longer alkyl chains. This principle may be implemented in the design of bolaamphiphiles for the formation of vesicles for drug delivery with desired controlled release rates. PMID:24531296

  9. Interrelationship of Steric Stabilization and Self-Crowding of a Glycosylated Protein

    PubMed Central

    Høiberg-Nielsen, R.; Westh, P.; Skov, L.K.; Arleth, L.

    2009-01-01

    Abstract In the eukaryotic cell, protein glycosylation takes place in the crowded environment of the endoplasmatic reticulum. With the purpose of elucidating the impact of high concentration on the interactions of glycoproteins, we have conducted a series of small-angle x-ray scattering experiments on the heavily glycosylated enzyme Peniophora lycii phytase (Phy) and its deglycosylated counterpart (dgPhy). The small-angle x-ray scattering data were analyzed using an individual numerical form factor for each of the two glycoforms combined with two structure factors, a hard sphere and a screened coulomb potential structure factor, respectively, as determined by ab initio analysis. Based on this data analysis, three main conclusions could be drawn. First, at comparable protein concentrations (mg/ml), the relative excluded volume of Phy was ∼75% higher than that of dgPhy, showing that the glycans significantly increase excluded-volume interactions. Second, the relative excluded volume of dgPhy increased with concentration, as expected; however, the opposite effect was observed for Phy, where the relative excluded volume decreased in response to increasing protein concentration. Third, a clear difference in the effect of salinity on the excluded-volume interactions was observed between the two glycol forms. Although the relative excluded volume of dgPhy decreased with increasing ionic strength, the relative excluded volume of Phy was basically insensitive to increased salinity. We suggest that protrusion forces from the glycans contribute to steric stabilization of the protein, and that glycosylation helps to sustain repulsive electrostatic interactions under crowded conditions. In combination, this aids in stabilizing high concentrations of glycosylated proteins. PMID:19720033

  10. Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs): physicochemical and in vitro evaluations

    PubMed Central

    Sahib, Mohanad Naji; Abdulameer, Shaymaa Abdalwahed; Darwis, Yusrida; Peh, Kok Khiang; Tan, Yvonne Tze Fung

    2012-01-01

    Background The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate. Aim: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs) loaded with beclomethasone dipropionate (BDP) as a carrier for pulmonary delivery. Methods 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000) polymeric micelles containing BDP (BDP-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated. Results BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and −28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs. Conclusion The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids. PMID:22393583

  11. Alteration of steric hindrance modulates glutathione resistance and cytotoxicity of three structurally related Ru(II)-p-cymene complexes.

    PubMed

    Purkait, Kallol; Chatterjee, Saptarshi; Karmakar, Subhendu; Mukherjee, Arindam

    2016-05-28

    The effect of steric hindrance on reactivity towards biomolecules while designing Ru(II)-η(6)-p-cymene based anticancer agents seems to be an important parameter in improving the activity and inducing resistance against glutathione (GSH) deactivation. Herein we present the structure, hydrolysis, anticancer activity and the effect of steric hindrance on deactivation by glutathione for three complexes, [Ru(II)(η(6)-p-cym)(L1)(Cl)](PF6) (1), [Ru(II)(η(6)-p-cym)(L2)(Cl)](PF6) (2) and [Ru(II)(η(6)-p-cym)(L3)(Cl)](PF6) (3). The ligands L1-L3 are Schiff bases which show increasing substitution in a benzene ring, such that two ortho hydrogens are replaced by -methyl in 2 and by -isopropyl in 3. The cytotoxicity results strongly suggest that controlling the rate of hydrolysis through tuning of steric hindrance may be a feasible pathway to derive GSH resistant anticancer agents. The cellular studies show that all the three complexes show good blood compatibility (haemolysis <3%) and induce cellular death through caspase activation via the mitochondrial pathway. They have anti-angiogenic activity and prevent the healing of treated cells. PMID:27120485

  12. Steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer and pyrene for alkaline phosphatase fluorescent sensing

    NASA Astrophysics Data System (ADS)

    Song, Chunxia; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Jianbo; Huang, Jin; Zhou, Maogui; Guo, Xiaochen

    2016-03-01

    We herein report a strategy for sensitive alkaline phosphatase (ALP) fluorescent sensing based on steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer (polyβ-CD) and pyrene. The fluorescence of pyrene was enhanced more than 10 times through supramolecular assembly with polyβ-CD. The 5‧-phosphorylated dsDNA probe with pyrene attached on the 3‧-terminal could be cleaved by λ exonuclease (λ exo), yielding pyrene attached on mononucleotides. Pyrene attached on mononucleotides could easily enter the cavity of polyβ-CD, resulting in fluorescence enhancement. When ALP was introduced, it could remove 5‧-phosphate groups from dsDNA and then prevented the cleavage of dsDNA. Pyrene attached on dsDNA was difficult to enter the cavity of polyβ-CD because of steric hindrance, resulting in an inconspicuous fluorescence enhancement. Owing to the excellent fluorescence enhancement during steric hindrance regulated supramolecular assembly, excellent performance of the assay method was achieved for ALP with a detection limit of 0.04 U mL- 1. The detection limit was superior or comparable with the reported methods. Besides, this method was simple in design, avoiding double-labeling of probe.

  13. Ligand-Based Steric Effects in Ni-Catalyzed Chain-Growth Polymerizations Using Bis(dialkylphosphino)ethanes

    SciTech Connect

    Lanni, Erica L.; Locke, Jonas R.; Gleave, Christine M.; McNeil, Anne J.

    2011-07-12

    The role of ligand-based steric effects was investigated in the polymerization of 4-bromo-2,5-bis(hexyloxy)phenylmagnesium chloride. Three different Ni(L-L)Cl₂ catalysts were synthesized using commercially available bis(dialkylphosphino)ethane ligands with varying steric properties. One of these catalysts (Ni(depe)Cl₂) outperformed the others for this polymerization. The polymer characterization data were consistent with a chain-growth mechanism. Rate and spectroscopic studies revealed a rate-limiting reductive elimination for both initiation and propagation with Ni(depe)Cl₂. In contrast, less hindered Ni(dmpe)Cl₂ and more hindered Ni(dcpe)Cl₂ were ineffective polymerization catalysts; NMR spectroscopic studies indicated that competing decomposition and uncontrolled pathways intervene. For other monomers, Ni(depe)Cl₂ performed similar to the conventional catalysts. Copolymerization studies revealed that block copolymers could be effectively prepared. Overall, these studies indicate that altering the ligand-based steric properties can have a significant impact on the chain-growth polymerization.

  14. Sprache als Barriere (Language as a Barrier)

    ERIC Educational Resources Information Center

    Mattheier, Klaus

    1974-01-01

    The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

  15. Determination of Effective Particle Density for Sterically Stabilized Carbon Black Particles: Effect of Diblock Copolymer Stabilizer Composition.

    PubMed

    Growney, David J; Fowler, Patrick W; Mykhaylyk, Oleksandr O; Fielding, Lee A; Derry, Matthew J; Aragrag, Najib; Lamb, Gordon D; Armes, Steven P

    2015-08-18

    Two poly(styrene-b-hydrogenated isoprene) (PS-PEP) copolymers and a poly(styrene-b-hydrogenated butadiene) (PS-PB) diblock copolymer of differing polystyrene content (20, 28 or 35 mol %) and molecular weight (117-183 kg mol(-1)) are examined. These copolymers form star-like micelles in n-dodecane, as judged by TEM, DLS, and SAXS studies. At ambient temperature, such micelles are known to adsorb intact onto a model colloidal substrate such as carbon black, conferring a high degree of dispersion (Growney, D. J.; Mykhaylyk, O. O.; Armes, S. P. Langmuir 2014, 30, 6047). Isotherms for micellar adsorption on carbon black at 20 °C are constructed using a supernatant depletion assay based on UV spectroscopy by utilizing the aromatic chromophore in the polystyrene block. Perhaps surprisingly, the diblock copolymer with the lowest polystyrene content has the strongest affinity for the carbon black particles. Assuming that the star-like diblock copolymer micelles adsorb onto carbon black to form hemi-micelles with a stabilizer layer thickness equal to the mean micelle radius, the effective particle density of the resulting sterically stabilized carbon black particles in n-dodecane can be estimated from the SAXS micelle dimensions based on geometric considerations. As an approximation, a spherical core-shell morphology was assumed, and the primary grain size of the carbon black particles was determined to be 74 nm diameter as judged by BET surface area analysis. Using this approach, effective particle densities of 0.90, 0.91, and 0.92 g cm(-3) were calculated for sterically stabilized carbon black particles prepared using the PS-PB20, PS-PEP28, and PS-PEP35 diblock copolymers, respectively. These densities are significantly lower than that of carbon black (1.89 g cm(-3)), which indicates that the sterically stabilized carbon black particles are substantially solvated. Since the rate of sedimentation of the sterically stabilized carbon black particles depends on the density

  16. Acute Kidney Injury in Low-Resource Settings: Barriers to Diagnosis, Awareness, and Treatment and Strategies to Overcome These Barriers.

    PubMed

    Lunyera, Joseph; Kilonzo, Kajiru; Lewington, Andrew; Yeates, Karen; Finkelstein, Fredric O

    2016-06-01

    Acute kidney injury (AKI) is increasingly recognized as a major health problem worldwide, responsible for an estimated 1.4 million deaths per year. The occurrence of and approach to AKI in low-resource settings (LRS) present special challenges due to often limited health care resources, including insufficient numbers of trained personnel, diagnostic tools, and treatment options. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in LRS presents major challenges not only because of the lack of resources, but also because of the lack of awareness of the impact of AKI on patient outcomes, factors that are complicated by the challenge of cognitively dissociating the care of patients with AKI from the care of patients with chronic kidney failure. To better understand how to increase the awareness of AKI and develop strategies to improve the identification and treatment of patients with AKI in LRS, we administered an 18-item web-based questionnaire to physicians actively engaged in providing nephrology care in LRS. A checklist was then developed of meaningful and targeted approaches for implementation, with focus on engaging local and regional stakeholders, developing education programs and appropriate guidelines, enhancing training of health care workers, expanding health care resources, linking with other regional health care projects, and broadening research opportunities. PMID:26830256

  17. Overcoming Challenges in Engineering the Genetic Code.

    PubMed

    Lajoie, M J; Söll, D; Church, G M

    2016-02-27

    Withstanding 3.5 billion years of genetic drift, the canonical genetic code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phylogenetic domains. Genome engineering technologies are now making it possible to rationally change the genetic code, offering resistance to viruses, genetic isolation from horizontal gene transfer, and prevention of environmental escape by genetically modified organisms. We discuss the biochemical, genetic, and technological challenges that must be overcome in order to engineer the genetic code. PMID:26348789

  18. Overcoming Scalability Challenges for Tool Daemon Launching

    SciTech Connect

    Ahn, D H; Arnold, D C; de Supinski, B R; Lee, G L; Miller, B P; Schulz, M

    2008-02-15

    Many tools that target parallel and distributed environments must co-locate a set of daemons with the distributed processes of the target application. However, efficient and portable deployment of these daemons on large scale systems is an unsolved problem. We overcome this gap with LaunchMON, a scalable, robust, portable, secure, and general purpose infrastructure for launching tool daemons. Its API allows tool builders to identify all processes of a target job, launch daemons on the relevant nodes and control daemon interaction. Our results show that Launch-MON scales to very large daemon counts and substantially enhances performance over existing ad hoc mechanisms.

  19. Bacterial strategies to overcome insect defences.

    PubMed

    Vallet-Gely, Isabelle; Lemaitre, Bruno; Boccard, Frédéric

    2008-04-01

    Recent genetic and molecular analyses have revealed how several strategies enable bacteria to persist and overcome insect immune defences. Genetic and genomic tools that can be used with Drosophila melanogaster have enabled the characterization of the pathways that are used by insects to detect bacterial invaders and combat infection. Conservation of bacterial virulence factors and insect immune repertoires indicates that there are common strategies of host invasion and pathogen eradication. Long-term interactions of bacteria with insects might ensure efficient dissemination of pathogens to other hosts, including humans. PMID:18327270

  20. Overcoming social segregation in health care in Latin America.

    PubMed

    Cotlear, Daniel; Gómez-Dantés, Octavio; Knaul, Felicia; Atun, Rifat; Barreto, Ivana C H C; Cetrángolo, Oscar; Cueto, Marcos; Francke, Pedro; Frenz, Patricia; Guerrero, Ramiro; Lozano, Rafael; Marten, Robert; Sáenz, Rocío

    2015-03-28

    Latin America continues to segregate different social groups into separate health-system segments, including two separate public sector blocks: a well resourced social security for salaried workers and their families and a Ministry of Health serving poor and vulnerable people with low standards of quality and needing a frequently impoverishing payment at point of service. This segregation shows Latin America's longstanding economic and social inequality, cemented by an economic framework that predicted that economic growth would lead to rapid formalisation of the economy. Today, the institutional setup that organises the social segregation in health care is perceived, despite improved life expectancy and other advances, as a barrier to fulfilling the right to health, embodied in the legislation of many Latin American countries. This Series paper outlines four phases in the history of Latin American countries that explain the roots of segmentation in health care and describe three paths taken by countries seeking to overcome it: unification of the funds used to finance both social security and Ministry of Health services (one public payer); free choice of provider or insurer; and expansion of services to poor people and the non-salaried population by making explicit the health-care benefits to which all citizens are entitled. PMID:25458715

  1. Thermal barrier research

    SciTech Connect

    Moses, K.G.

    1990-03-07

    The thermal barrier region in the TARA device is a complex arrangement combining ion-plugging by sloshing ions with an ECRH-generated thermal barrier plasma. An axisymmetric, high-mirror-ratio magnetic field, adjacent to the central cell, provides the confinement of the thermal barrier plasma and sloshing ions. This paper discusses research being done in this thermal barrier region.

  2. Barriers, Successes and Enabling Practices of Education for Sustainability in Far North Queensland Schools: A Case Study

    ERIC Educational Resources Information Center

    Evans, Neus; Whitehouse, Hilary; Gooch, Margaret

    2012-01-01

    There are many documented barriers to implementing school-based sustainability. This article examines a) the barriers faced by principals and staff in two regional primary schools in Far North Queensland, Australia, well known for their exemplary practice, and b) ways the barriers were overcome. Through interviews conducted with principals and key…

  3. Barriers to Industrial Energy Efficiency - Study (Appendix A), June 2015

    SciTech Connect

    2015-06-01

    This study examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This study also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  4. Barriers to Industrial Energy Efficiency - Report to Congress, June 2015

    SciTech Connect

    2015-06-01

    This report examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This report also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  5. Barriers to access to hepatitis C treatment.

    PubMed

    Yilmaz, Hava; Yilmaz, Esmeray Mutlu; Leblebicioglu, Hakan

    2016-01-01

    Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. Only 1%-30% of patients in need of treatment may get it. In recent years, the availability of direct-acting antiviral agents (DAA) has been an important advancement in treating HCV infection. However, due to cost, it is not possible to receive these drugs in many countries where infection is endemic. In these low- and middle-income countries, the main barriers to controlling HCV infection are lack of knowledge about the infection, constraints on diagnostic testing and treatment, and lack of experts. Both national and international support are essential to overcoming these barriers. In low- and middle-income countries, interferon and ribavirin-based therapies still are the first choices due to their availability and to government payment support. In addition, in developed countries, efforts to provide lower-cost DAA drugs continue. Pharmaceutical companies continue to research manufacture of bio-equivalent drugs to reduce treatment costs. Considering the fake drug market, all developments need to be monitored closely by the institutions involved. This review focuses on barriers to hepatitis C treatment and ways to overcome those barriers. PMID:27130991

  6. Restaurant employees' perceptions of barriers to three food safety practices.

    PubMed

    Howells, Amber D; Roberts, Kevin R; Shanklin, Carol W; Pilling, Valerie K; Brannon, Laura A; Barrett, Betsy B

    2008-08-01

    Limited research has been conducted to assess employees' perceptions of barriers to implementing food safety practices. Focus groups were conducted with two groups of restaurant employees to identify perceived barriers to implementing three food safety practices: handwashing, using thermometers, and cleaning work surfaces. Ten focus groups were conducted with 34 employees who did not receive training (Group A). Twenty focus groups were conducted with 125 employees after they had participated in a formal ServSafe training program (Group B). The following barriers were identified in at least one focus group in both Group A and Group B for all three practices: time constraints, inconvenience, inadequate training, and inadequate resources. In Group A, additional barriers identified most often were a lack of space and other tasks competing with cleaning work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and thermometers in inconvenient locations. Additional barriers identified most often by Group B were no incentive to do it and the manager not monitoring whether employees cleaned work surfaces; inconvenient location of sinks and dry skin from handwashing; and lack of working thermometers and manager not monitoring the use of thermometers. Results will be used to develop and implement interventions to overcome perceived barriers that training appears not to address. Knowledge of perceived barriers among employees can assist food and nutrition professionals in facilitating employees in overcoming these barriers and ultimately improve compliance with food safety practices. PMID:18656574

  7. Overcoming Challenges to Childhood Immunizations Status.

    PubMed

    Sabnis, Svapna S; Conway, James H

    2015-10-01

    Vaccines are one of the greatest public health achievements, preventing both mortality and morbidity. However, overall immunization rates are still below the 90% target for Healthy People 2020. There remain significant disparities in immunization rates between children of different racial/ethnic groups, as well as among economically disadvantaged populations. There are systemic issues and challenges in providing access to immunization opportunities. In addition, vaccine hesitancy contributes to underimmunization. Multiple strategies are needed to improve immunization rates, including improving access to vaccines and minimizing financial barriers to families. Vaccine status should be assessed and vaccines given at all possible opportunities. PMID:26318942

  8. Informed Courage in Local Leadership: Essential in Overcoming Barriers to Change in Education.

    ERIC Educational Resources Information Center

    VanSciver, James H.

    Without fear, there is no courage, only ignorance of a situation's dynamics. Acknowledging a decision's liabilities promotes fear and forces the educational leader to exercise courage in formulating and carrying out a response to that situation. Courage alone is not enough, however, and could lead to professional suicide. Wisdom to marshal that…

  9. Making College Affordable: Five Ways To Overcome Financial Barriers to College.

    ERIC Educational Resources Information Center

    Coles, Ann

    2003-01-01

    Five strategies to make college affordable include: reduce the time it takes for students to earn a college degree; provide families with better information before students enroll in college; facilitate movement of students between lower-cost and higher-cost colleges; reward college readiness and college persistence; and integrate state financial…

  10. Systems approach-based mitigation of postharvest diseases to overcome trade barriers for Washington apples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Speck rot caused by Phacidiopycnis washingtonensis and Sphaeropsis rot caused by S. pyriputrescens were reported as new postharvest fruit rot diseases in Washington State in the mid-2000s. Both diseases can cause significant postharvest losses of fruit if left uncontrolled, and the two fungi have be...

  11. Women Community College Presidents: A Qualitative Approach to Exploring Leadership and Overcoming Potential Barriers

    ERIC Educational Resources Information Center

    O'Roark, Jordan J.

    2015-01-01

    Since the establishment of American higher education, the presidential profile for institutions has lacked the gender diversity in presidential leadership positions. Though women have taken positive strides as senior executive officers in higher education in the past quarter-century, the conventional post-secondary president is a white, married…

  12. Overcoming Barriers in Intimate Partner Violence Education and Training of Graduate Social Work Students

    ERIC Educational Resources Information Center

    Connor, Pamela D.; Nouer, Simonne S.; Mackey, SeeTrail N.; Banet, Megan S.; Tipton, Nathan G.

    2012-01-01

    Intimate partner violence (IPV) is a highly prevalent problem detected frequently in the social work field, and also extends to the personal lives of social workers and students, with compelling evidence that professionals and students are often victims of IPV. However, students continue to lack substantive knowledge of IPV. This article addresses…

  13. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration. PMID:19071202

  14. Overcoming Disciplinary and Institutional Barriers: An Interdisciplinary Course in Economic and Sociological Perspectives on Health Issues

    ERIC Educational Resources Information Center

    Wade, Bruce H.; Stone, Jack H.

    2010-01-01

    The authors describe an interdisciplinary course team-taught by an economist and a sociologist. Historically mindful of the less than amicable relationship between these disciplines, these colleagues developed a course that attempted to illuminate the different perspectives of economics and sociology in relation to selected health themes. Such a…

  15. Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users.

    PubMed

    Edlin, Brian R; Kresina, Thomas F; Raymond, Daniel B; Carden, Michael R; Gourevitch, Marc N; Rich, Josiah D; Cheever, Laura W; Cargill, Victoria A

    2005-04-15

    Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities. PMID:15768335

  16. Mobile "Comfort" Zones: Overcoming Barriers to Enable Facilitated Learning in the Workplace

    ERIC Educational Resources Information Center

    Holley, Debbie; Sentance, Sue

    2015-01-01

    The affordances of mobile technologies are well documented (Vavoula (2004); Wali (2008); Pachler et al (2010); Cook (2011); Sharples (2013). Linked with the rapid expansion of the "SMART" phones, where users access fast/high quality information, new opportunities are offered to engage students at a time/place of their own choosing. Our…

  17. Overcoming Barriers: Tailoring Climate Education for Latino and non-Latino Citizen to Impact Decision Making

    NASA Astrophysics Data System (ADS)

    Estrada, M.; Boudrias, M. A.; Silva-Send, N. J.; Gershunov, A.; Anders, S.

    2013-12-01

    Culture has been shown to be an important determinant of Latino/Hispanic American environmental attitudes (Schultz, Unipan, & Gamba, 2000), which might help to explain the underrepresentation of Latinos in the U.S. 'environmental' movement. With shifting U.S. demographics, however, there is increased urgency to understand how Latinos integrate into the community that is concerned and literate about climate change. As part of the Climate Education Partners (CEP) work in San Diego, we investigated how to address this ethnic group disparity. In this paper, we describe a study of how climate change science knowledge relates to Latino and Non-Latino citizen (a) engagement in conservation behaviors and (b) more informed decision-making. Drawing upon previous work on the Tripartite Integration Model of Social Influence (TIMSI) (Estrada et al., 2011), we hypothesized that climate change knowledge that promotes efficacy (i.e., a sense that one can do something) would relate to greater engagement in conservation behaviors and more informed decision-making (both common of community members concerned about climate change). To test this model, 1001 San Diego residence participated in a telephone survey in which the attitudes towards climate change were assessed using '6 Americas' segmentation (Leiserowitz et al., 2011), in addition to climate change science knowledge, efficacy, values, and engagement in weekly and yearly climate change friendly behaviors (e.g., conservation, transportation, community engagement behaviors). Results showed that there were significant differences in the 6 America segmentation distributions, knowledge, efficacy and behavioral engagement with Latinos significantly more concerned than Non-Latinos, and reporting greater knowledge, efficacy and engagement in behaviors. However, data from both groups showed support for the TIMSI theoretical framework, such that efficacy mediated the relationship between climate change knowledge and behavior. Thus, for both groups, climate change science knowledge was more likely to result in behavioral engagement when the science knowledge was accompanied with the belief that one has the ability to engage in behaviors that mitigate or adapt to climate change (i.e., efficacy). Implications for how to improve both Latino and Non-Latino climate change education that results in informed decision-making and greater integration into the community concerned about climate change will be discussed.

  18. Understanding and overcoming barriers to medication adherence: a review of research priorities.

    PubMed

    Seabury, Seth A; Gupta, Charu N; Philipson, Tomas J; Henkhaus, Laura E

    2014-08-01

    Improving medication adherence has been identified as a crucial step towards improving health outcomes for patients with chronic disease and has provided the motivation for many changes in our health care system. Despite the volume of research done on this topic, however, we still lack important basic information about how to improve adherence in a cost-effective way. There is a need for a better understanding of what areas of research are most likely to produce advances that could be used by policymakers, providers, payers, or other stakeholders to generate real improvements in medication adherence. To address this, we developed a set of research priorities designed to improve understanding about whom to target for adherence interventions and which particular interventions to employ for specific subpopulations. To produce this research agenda, we synthesized information from the existing literature with a series of stakeholder interviews and expert panel meetings. We identified 6 key areas for research: (1) predicting nonadherence, (2) behavioral factors affecting nonadherence, (3) measuring the impact of nonadherence on health and cost outcomes, (4) effectiveness of existing interventions, (5) misaligned incentives between payers and providers, and (6) provider training and coordination of care. We provide detailed descriptions and example topics within each area.  As the health care system continues to embrace reforms designed to improve the value of care, more and better information is needed to guide efforts designed to improve medication adherence. Addressing the topic areas identified here will be an important step towards accomplishing this goal.  PMID:25062070

  19. Older Teens in TANF Families: Overcoming Barriers to Self-Sufficiency.

    ERIC Educational Resources Information Center

    Kaplan, Jan

    2001-01-01

    Older teens living in families receiving Temporary Assistance to Needy Families (TANF) face serious sociodemographic disadvantages. When combined with the characteristic risk-taking behaviors of adolescence, these disadvantages pose a threat to TANF teens' immediate and future physical, psychological, and emotional health and to their long-term…

  20. Black communities' belief in "AIDS as genocide". A barrier to overcome for HIV prevention.

    PubMed

    Guinan, M E

    1993-03-01

    The belief that acquired immunodeficiency syndrome (AIDS) is a form of genocide targeted at the black population is prevalent in black communities in the United States. Public health authorities are distrusted, in part because of the legacy of the Tuskegee Study of untreated syphilis, a perceived racist experiment. For effective interventions to prevent the transmission of human immunodeficiency virus in black communities, genocidal fears and beliefs must be addressed and black community leaders should be involved in planning and implementation. PMID:8269075

  1. Education for All Aspects of the Industry: Overcoming Barriers to Broad-Based Training.

    ERIC Educational Resources Information Center

    Bailey, Thomas; And Others

    This report is designed to help the educational community develop the "all aspects of the industry" (AAI) strategy promoted in the Perkins Vocational Education Act. The introduction describes the current status of AAI and elaborates on three arguments for it: (1) AAI is a pedagogic strategy that promotes more effective learning; (2) better…

  2. Overcoming Barriers to the Remediation of Carbon Tetrachloride Through Manipulation of Competing Reaction Mechanisms

    SciTech Connect

    Tratnyek, Paul G.; Amonette, James E.; Bylaska, Eric J.

    2004-03-29

    Most approaches that have been proposed for the remediation of groundwater contaminated with carbon tetrachloride produce chloroform as the major product and methylene chloride as a minor product. Both of these products are nearly as persistent and problematic as the parent compound, but competing reaction pathways produce the more desirable products carbon monoxide and/or formate. Branching between these reaction pathways is highly variable, but the controlling factors have not been identified. To improve the applicability of reductive remediation technologies to the large plumes of carbon tetrachloride at several DOE sites, we are pursuing the complete characterization of the mechanisms and kinetics of competing degradation reactions of carbon tetrachloride through laboratory experiments closely coordinated with theoretical modeling studies. The results are beginning to suggest strategies for maximizing the yield of desirable products from carbon tetrachloride degradation, which will be tested in column model systems using real site waters and matrix materials.

  3. Identifying, Understanding, and Overcoming Barriers to the Use of Clinical Practice Guidelines in Pediatric Oncology

    ClinicalTrials.gov

    2016-07-25

    B-Cell Non-Hodgkin Lymphoma; Chemotherapy-Related Nausea and/or Vomiting; Childhood Acute Myeloid Leukemia; Childhood Burkitt Lymphoma; Childhood Neoplasm; Febrile Neutropenia; Hematopoietic Cell Transplantation Recipient; Recurrent Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  4. Overcoming the Language Barrier. Third European Congress on Information Systems and Networks, Vol. 1.

    ERIC Educational Resources Information Center

    Commission des Communautes Europeennes (Luxembourg).

    The papers presented here have a double objective: to give those responsible for the Action plan for the improvement of information transfer between European languages a good view of existing and developing systems and to make future users of EURONET acquainted with methods and tools that will soon be available. The papers are arranged under six…

  5. Videos Bridging Asia and Africa: Overcoming Cultural and Institutional Barriers in Technology-Mediated Rural Learning

    ERIC Educational Resources Information Center

    Van Mele, Paul; Wanvoeke, Jonas; Akakpo, Cyriaque; Dacko, Rosaline Maiga; Ceesay, Mustapha; Beavogui, Louis; Soumah, Malick; Anyang, Robert

    2010-01-01

    Will African farmers watch and learn from videos featuring farmers in Bangladesh? Learning videos on rice seed management were made with rural women in Bangladesh. By using a new approach, called zooming-in, zooming-out, the videos were of regional relevance and locally appropriate. When the Africa Rice Center (AfricaRice) introduced them to…

  6. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia

    PubMed Central

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability. PMID:25609917

  7. The energy barrier in singlet fission can be overcome through coherent coupling and entropic gain

    NASA Astrophysics Data System (ADS)

    Chan, Wai-Lun; Ligges, Manuel; Zhu, X.-Y.

    2012-10-01

    One strategy to improve solar-cell efficiency is to generate two excited electrons from just one photon through singlet fission, which is the conversion of a singlet (S1) into two triplet (T1) excitons. For efficient singlet fission it is believed that the cumulative energy of the triplet states should be no more than that of S1. However, molecular analogues that satisfy this energetic requirement do not show appreciable singlet fission, whereas crystalline tetracene displays endothermic singlet fission with near-unity quantum yield. Here we probe singlet fission in tetracene by directly following the intermediate multiexciton (ME) state. The ME state is isoenergetic with 2 × T1, but fission is not activated thermally. Rather, an S1 ⇔ ME superposition formed through a quantum-coherent process allows access to the higher-energy ME. We attribute entropic gain in crystalline tetracene as the driving force for the subsequent decay of S1 ⇔ ME into 2 × T1, which leads to a high singlet-fission yield.

  8. Overcoming Barriers to Improve Breastfeeding Self-Efficacy in Older Adolescent Mothers

    ERIC Educational Resources Information Center

    Beattie-Fairchild, Cindy

    2013-01-01

    A lack of breastfeeding has negative consequences on mother and infant by creating health disparities with a higher incidence of morbidity and mortality. Nationwide, fewer than 60% of mothers younger than age 20 years breastfed exclusively, while fewer than 20% did so in the community being studied. The purpose of this qualitative case study was…

  9. Overcoming the Barrier of Low Efficiency during Genetic Transformation of Streptococcus mitis

    PubMed Central

    Salvadori, Gabriela; Junges, Roger; Morrison, Donald A.; Petersen, Fernanda C.

    2016-01-01

    Objective: Streptococcus mitis is a predominant oral colonizer, but difficulties in genetic manipulation of this species have hampered our understanding of the mechanisms it uses for colonization of oral surfaces. The aim of this study was to reveal optimal conditions for natural genetic transformation in S. mitis and illustrate its application in direct genome editing. Methods: Luciferase reporter assays were used to assess gene expression of the alternative sigma factor (σX) in combination with natural transformation experiments to evaluate the efficiency by which S. mitis activates the competence system and incorporates exogenous DNA. Optimal amounts and sources of donor DNA (chromosomal, amplicon, or replicative plasmid), concentrations of synthetic competence-stimulating peptide, and transformation media were assessed. Results: A semi-defined medium showed much improved results for response to the competence stimulating peptide when compared to rich media. The use of a donor amplicon with large homology flanking regions also provided higher transformation rates. Overall, an increase of transformation efficiencies from 0.001% or less to over 30% was achieved with the developed protocol. We further describe the construction of a markerless mutant based on this high efficiency strategy. Conclusion: We optimized competence development in S. mitis, by use of semi-defined medium and appropriate concentrations of synthetic competence factor. Combined with the use of a large amplicon of donor DNA, this method allowed easy and direct editing of the S. mitis genome, broadening the spectrum of possible downstream applications of natural transformation in this species. PMID:27458432

  10. Overcoming barriers to effective pain management: the use of professionally directed small group discussions.

    PubMed

    Lewis, C Preston; Corley, Donna J; Lake, Norma; Brockopp, Dorothy; Moe, Krista

    2015-04-01

    Inadequate assessment and management of pain among critical care patients can lead to ineffective care delivery and an increased length of stay. Nurses' lack of knowledge regarding appropriate assessment and treatment, as well as negative biases toward specific patient populations, can lead to poor pain control. Our aim was to evaluate the effectiveness of professionally directed small group discussions on critical care nurses' knowledge and biases related to pain management. A quasi-experiment was conducted at a 383-bed Magnet(®) redesignated hospital in the southeastern United States. Critical care nurses (N = 32) participated in the study. A modified Brockopp and Warden Pain Knowledge Questionnaire was administered before and after the small group sessions. These sessions were 45 minutes in length, consisted of two to six nurses per group, and focused on effective pain management strategies. Results indicated that mean knowledge scores differed significantly and in a positive direction after intervention [preintervention mean = 18.28, standard deviation = 2.33; postintervention mean = 22.16, standard deviation = 1.70; t(31) = -8.87, p < .001]. Post-bias scores (amount of time and energy nurses would spend attending to patients' pain) were significantly higher for 6 of 15 patient populations. The strongest bias against treating patients' pain was toward unconscious and mechanically ventilated individuals. After the implementation of professionally directed small group discussions with critical care nurses, knowledge levels related to pain management increased and biases toward specific patient populations decreased. PMID:25439127

  11. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia

    PubMed Central

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, A Duncan

    2013-01-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction. PMID:23955246

  12. Overcoming Barriers to Family Involvement in Title I Schools. Report to Congress.

    ERIC Educational Resources Information Center

    Policy Studies Associates, Inc., Washington, DC.

    Title I of the Elementary and Secondary Education Act as amended by the Improving America's Schools Act (IASA) requires all schools and districts receiving Title I money to engage in an extensive array of activities to build the capacity of parents and school staff to work together in support of students' learning. Title I also requires schools to…

  13. Using Synthetic Biology to Distinguish and Overcome Regulatory and Functional Barriers Related to Nitrogen Fixation

    PubMed Central

    Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

    2013-01-01

    Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ∼100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase–LacI expression system was used to replace the σ54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ∼42% of the nitrogenase activity of the σ54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology. PMID:23935879

  14. Overcoming Barriers to the Remediation of Carbon Tetrachloride through Manipulation of Competing Reaction Mechanisms

    SciTech Connect

    Tratnyek, Paul G.; Amonette, James E.; Bylaska, Eric J. and Szecsody, James E.

    2004-06-01

    Most approaches that have been proposed for the remediation of groundwater contaminated with carbon tetrachloride (CCl4) produce chloroform (CHCl3) as the major product and methylene chloride (CH2Cl2) as a minor product. Both of these products are nearly as persistent and problematic as the parent compound, but competing reaction pathways produce the more desirable products carbon monoxide (CO) and/or formate (HCOO-). Results scattered throughout the chemical and environmental engineering literature show that the branching between these reaction pathways is highly variable, but the controlling factors have not been identified. If we understood the fundamental chemistry that controls the branching among these, and related, product-formation pathways, we could improve the applicability of a host of remediation technologies (both chemical and biological) to the large plumes of CCl4 that contaminate DOE sites across the country. This project will provide the first complete characterization of the mechanisms and kinetics of competing degradation reactions of CCl4 through laboratory experiments in simple model systems closely coordinated with theoretical modeling studies. The results provide strategies for maximizing the yield of desirable products from CCl4 degradation, and the most promising of these will be tested in column model systems using real site waters and matrix materials.

  15. Overcoming Barriers to the Remediation of Carbon Tetrachloride Through Manipulation of Competing Reaction Mechanisms

    SciTech Connect

    Tratnyek, Paul G.

    2003-06-01

    Quantify the kinetics of all competing product-formation pathways, over a range of conditions relevant to groundwater remediation, using well-mixed batch reactors and analysis primarily by chromatography. At OGI, batch experiments were conducted on Fe(0) systems (both Fisher Electrolytic and Nano-sized iron). The experiments were done with and without buffer. The buffered experiments tried to contrast two buffers: an organic buffer (EPPS, presumably a H atom donor), and the inorganic borate. In the buffered experiments, the pH was varied (7.3 and 8.4). For the pre-exposure treatment, after trying a variety of methods, like shaking and not shaking for varied amounts of time, it was decided to stick with not shaking and have a pre-exposure of 24 hours. The unbuffered data did not show any marked trend with increasing mass of Felc. However, 3.5 g of Fe showed about 100% conversion to CHCl3, and 1g of Fe showed 50% conversion. At pHs 8.4 and 7.3, there was no trend observed for branching ratios between EPPS and Borate buffer. kCT (disappearance rate constant of carbon tetrachloride) values were found to be different from CT and CF fits. Experiments with nano-iron (unbuffered, buffered with both buffers at pH 8.3), did not show any trend with respect to Fisher Iron, except for the unbuffered experiments, where the CF ''yield'' was less in the nano iron case. Future experiments involve testing for chloride, formate and CO, and performing experiments over a wider range of pH and buffers. Batch experiments were conducted at PNNL to compare the efficiency and product distribution of representative Fe(II) and Fe(0) systems applied to dechlorination of CCl4. These experiments involved (1) a smectite clay with Fe(III) in its structure that had been reduced to Fe(II) by dithionite treatment, (2) the same clay to which Fe(II) was added as an exchangeable cation, (3) electrolytic Fe(0) from Fisher, and (4) a mixture of the reduced clay and Fe(0). Experiments were conducted in headspace vials at pH 7 in either bicarbonate or bis-tris propane buffers. Reactant and product concentrations were determined by headspace analysis using GC/MS. Results from the first run of this experiment showed relatively little dechlorination by the Fe(II) system, and from 50-80% dechlorination by the Fe(0) system after 48 h. Essentially no CHCl3 was seen in the Fe(II) system, whereas as 30% of the original CCl4 was converted to CHCl3 in the Fe(0) system. Very low amounts of CH2Cl2 were seen in all treatments. Plans are underway to repeat this experiment and use a cryo-GC capability that will allow simultaneous determination of CO as well as the chlorinated methanes. This is important because CO represents the end product of the second hypothetical dechlorination pathway that may compete with the CHCl3 pathway and will aid in mass balance calculations. An additional experiment to evaluate the Henry's Law constant for CCl4 in aqueous solutions in the presence and absence of clay showed no significant difference due to the presence of clay, although slightly higher gas-phase concentrations were seen when clay was present.

  16. Evolving from academic to academic entrepreneur: overcoming barriers to scientific progress and finance.

    PubMed

    Miller, Andrew D

    2016-07-01

    The overall goal of my career as an academic chemist has always been the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the management of chronic diseases. Realising this goal has been an immensely difficult process involving multidisciplinary problem-driven research at the chemistry-biology-medicine interfaces. With success in the laboratory, I started seriously to question the value of remaining an academic whose career is spent in the pursuit of knowledge and understanding alone without making any significant effort to translate knowledge and understanding gained into products of genuine utility for public benefit. Therefore, I elected by choice to become an academic entrepreneur, seeking opportunities wherever possible for the translation of the best of my personal and collaborative academic research work into potentially valuable and useful products. This choice has brought with it many unexpected difficulties and challenges. Nevertheless, progress bas been made and sufficient learnt to suggest that this would be an appropriate moment to take stock and provide some personal reflections on what it takes to design and create advanced therapeutics and diagnostics in the laboratory then seek to develop, innovate and translate the best towards market. PMID:27476702

  17. The Role of Identity Narratives in Overcoming Barriers to Parental Engagement

    ERIC Educational Resources Information Center

    Naqvi, Rahat; Carey, Jennifer; Cummins, Jim; Altidor-Brooks, Alison

    2015-01-01

    This paper describes a qualitative study conducted over the course of one school year in an ethnically diverse school. Aimed at exploring the conditions under which parents of low socioeconomic status (SES) immigrant-background children will engage actively with the school, we involved parents and facilitators in story-telling sessions, sharing…

  18. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia.

    PubMed

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world's children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability. PMID:25609917

  19. The InterpreCare System: overcoming language barriers in long-term care.

    PubMed

    Camp, C J; Burant, C J; Graham, G C

    1996-12-01

    Differences in the language spoken by residents and staff in long-term care create a variety of problems. The InterpreCare System represents an intervention for dealing with this issue. We describe the nature and purpose of this intervention, and provide detailed instructions on the construction of Language Boards. Examples are given from our experience at Menorah Park Center for the Aging in enabling English-speaking staff to use Russian phrases while delivering care. Beneficial effects produced by the intervention are discussed. PMID:8990595

  20. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade.

    PubMed

    Marchini, Antonio; Scott, Eleanor M; Rommelaere, Jean

    2016-01-01

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a "double-edged sword" for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. PMID:26751469

  1. Sexual History-Taking: Using Educational Interventions to Overcome Barriers to Learning

    ERIC Educational Resources Information Center

    Jayasuriya, Ashini N.; Dennick, Reg

    2011-01-01

    Sexual history-taking is a basic medical skill that is traditionally taught poorly in medical school. Practising medical professionals have frequently reported feeling inadequately trained at taking these histories or discussing sexual risk. In order to promote and enhance the learning of this basic skill, those who teach sexual history-taking…

  2. Overcoming Psychosocial Barriers to Maternal Exercise: Intervention Strategies to Improve Participation and Adherence

    ERIC Educational Resources Information Center

    Schoenfeld, Brad; Tiryaki-Sonmez, Gul

    2011-01-01

    Poor adherence to physical activity programmes during pregnancy is a serious national issue, one that has detrimental effects on a large percentage of the population. Not only does a lack of activity result in a decrease in quality of life for women during term, but the effects can carry over well after pregnancy, potentially leading to increased…

  3. Overcoming Language and Literacy Barriers in Safety and Health Training of Agricultural Workers

    PubMed Central

    Arcury, Thomas A.; Estrada, Jorge M.; Quandt, Sara A.

    2010-01-01

    The workforce in all areas of United States agriculture and forestry is becoming increasingly diverse in language, culture, and education. Many agricultural workers are immigrants who have limited English language skills and limited educational attainment. Providing safety and health training to this large, diverse, dispersed, and often transient population of workers is challenging. This review, prepared for the 2010 Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, “Be Safe, Be Profitable: Protecting Workers in Agriculture,” is divided into five sections. First, we describe the occupational and demographic characteristics of agricultural workers in the US to highlight their safety and health training needs. Second, we summarize current research on the social and cultural attributes of agricultural workers and agricultural employers that affect the provision of safety and health training. Worker and employer attributes include language, literacy, financial limitations, work beliefs, and health beliefs. Third, we review current initiatives addressing safety and health training for agricultural workers that consider worker language and literacy. These initiatives are limited to a few specific topics (e.g., pesticides, heat stress); they do not provide general programs of safety training that would help establish a culture of workplace safety. However, several innovative approaches to health and safety training are being implemented, including the use of community-based participatory approaches and lay health promoter programs. Fourth, the limited industry response for safety training with this linguistically diverse and educationally limited workforce is summarized. Finally, gaps in knowledge and practice are summarized and recommendations to develop educationally, culturally, and linguistically appropriate safety and health training are presented. PMID:20665309

  4. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade

    PubMed Central

    Marchini, Antonio; Scott, Eleanor M.; Rommelaere, Jean

    2016-01-01

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a “double-edged sword” for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. PMID:26751469

  5. Working with Schools in Identifying and Overcoming Emotional Barriers to Learning

    ERIC Educational Resources Information Center

    Nash, Poppy; Schlösser, Annette

    2015-01-01

    This paper reports a case study on working closely with a secondary school, to enhance understanding of disruptive behaviour, through the use of bespoke Continuing Professional Development (CPD) materials. This project evolved from the researchers' previous research on the extent to which teachers believe disruptive pupils can control their…

  6. Overcoming Medicaid Reimbursement Barriers to Funding School Nursing Services for Low-Income Children with Asthma

    ERIC Educational Resources Information Center

    Malcarney, Mary-Beth; Horton, Katherine; Seiler, Naomi

    2016-01-01

    Background: School nurses can provide direct services for children with asthma, educate, and reinforce treatment recommendations to children and their families, and coordinate the school-wide response to students' asthma emergencies. Unfortunately, school-based health services today depend on an unreliable patchwork of funding. Limited state and…

  7. Toll free mobile communication: overcoming barriers in maternal and neonatal emergencies in Rural Bangladesh

    PubMed Central

    2014-01-01

    Background Toll free mobile telephone intervention to support mothers in pregnancy and delivery period was tested in one sub district of Bangladesh. Qualitative research was conducted to measure the changes of mobile phone use in increasing communication for maternal and neonatal complications. Methods In-depth interviews were conducted among twelve Community Skilled Birth Attendants and fourteen mothers along with their husbands prior to intervention. At intervention end, six Community Skilled Birth Attendants were purposively selected for in-depth interview. Semi structured interviews were conducted among all 27 Community Skilled Birth Attendants engaged in the intervention. One Focus Group Discussion was conducted with 10 recently delivered mothers. Thematic analysis and triangulation of different responses were conducted. Results Prior to intervention, Community Skilled Birth Attendants reported that mobile communication was not a norm. It was also revealed that poor mothers had poor accessibility to mobile services. Mothers, who communicated through mobile phone with providers noted irritability from Community Skilled Birth Attendants and sometimes found phones switched off. At the end of the project, 85% of mothers who had attended orientation sessions of the intervention communicated with Community Skilled Birth Attendants through mobile phones during maternal health complications. Once a complication is reported or anticipated over phone, Community Skilled Birth Attendants either made a prompt visit to mothers or advised for direct referral. More than 80% Community Skilled Birth Attendants communicated with Solution Linked Group for guidance on maternal health management. Prior to intervention, Solution Linked Group was not used to receive phone call from Community Skilled Birth Attendants. Community Skilled Birth Attendants were valued by the mothers. Mothers viewed that Community Skilled Birth Attendants are becoming confident in managing complication due to communication with Solution Linked Group. Conclusions The use of mobile technology in this intervention took a leap from simply rendering information to providing more rapid services. Active participation of service providers along with mothers’ accessibility motivated both the service providers and mothers to communicate through mobile phone for maternal health issues. These altogether made the shift towards adoption of an innovation. PMID:25015126

  8. Overcoming Language and Cultural Barriers in School: Helping Hispanic Students Acquire Success in Elementary School

    ERIC Educational Resources Information Center

    Ivey, Pauline S.

    2011-01-01

    Research shows that Hispanic second language students are not as successful as their English-speaking peers in school. The problem is in part due to several factors: curriculum deliverance in a foreign language, cultural differences, and family/school disconnect. Current census reports reveal that Hispanic populations in the United States, and…

  9. Overcoming the organization-practice barrier in sports injury prevention: A nonhierarchical organizational model.

    PubMed

    Dahlström, Ö; Jacobsson, J; Timpka, T

    2015-08-01

    The organization of sports at the national level has seldom been included in scientific discussions of sports injury prevention. The aim of this study was to develop a model for organization of sports that supports prevention of overuse injuries. The quality function deployment technique was applied in seminars over a two-season period to develop a national organizational structure for athletics in Sweden that facilitates prevention of overuse injuries. Three central features of the resulting model for organization of sports at the national level are (a) diminishment of the organizational hierarchy: participatory safety policy design is introduced through annual meetings where actors from different sectors of the sporting community discuss training, injury prevention, and sports safety policy; (b) introduction of a safety surveillance system: a ubiquitous system for routine collection of injury and illness data; and (c) an open forum for discussion of safety issues: maintenance of a safety forum for participants from different sectors of the sport. A nonhierarchical model for organization of sports at the national level - facilitated by modern information technology - adapted for the prevention of overuse injuries has been developed. Further research is warranted to evaluate the new organizational model in prospective effectiveness studies. PMID:25430864

  10. Confidence-Based Learning CME: Overcoming Barriers in Irritable Bowel Syndrome with Constipation

    ERIC Educational Resources Information Center

    Cash, Brooks; Mitchner, Natasha A.; Ravyn, Dana

    2011-01-01

    Introduction: Performance of health care professionals depends on both medical knowledge and the certainty with which they possess it. Conventional continuing medical education interventions assess the correctness of learners' responses but do not determine the degree of confidence with which they hold incorrect information. This study describes…

  11. Overcoming Barriers in the Use of Adaptive and Assistive Technology in Special Education.

    ERIC Educational Resources Information Center

    Bushrow, Kathy M.; Turner, Keith D.

    This paper examines change and change facilitators as they affect full use of adaptive and assistive technology (AAT) in special education, and compares qualitative versus quantitative methods of researching the change process. Four administrators and two teachers from a rural school district completed the Stages of Concern Questionnaire, which…

  12. Overcoming Unintentional Barriers with Intentional Strategies: Educating Faculty about Student Disabilities

    ERIC Educational Resources Information Center

    Forrest, Krista D.

    2003-01-01

    Krista Forrest is an Assistant Professor in the Department of Psychology at the University of Nebraska at Kearney, where she teaches general psychology and life span development as well as advanced courses in adolescent psychology, group dynamics, and psychology and law. A graduate of North Carolina State University with a MS in developmental…

  13. T7 replisome directly overcomes DNA damage

    PubMed Central

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-01-01

    Cells and viruses possess several known ‘restart' pathways to overcome lesions during DNA replication. However, these ‘bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase–DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly. PMID:26675048

  14. T7 replisome directly overcomes DNA damage

    NASA Astrophysics Data System (ADS)

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-12-01

    Cells and viruses possess several known `restart' pathways to overcome lesions during DNA replication. However, these `bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.

  15. Overcoming the effects of intentional forgetting.

    PubMed

    Lehman, Melissa; Malmberg, Kenneth J

    2011-02-01

    The long-term effects of the compartmentalization of task-irrelevant memories were investigated using a directed forgetting procedure. Many models tacitly assume the persistence of the costs and benefits of directed forgetting or otherwise fail to predict what factors might reduce or eliminate them. In contrast, a retrieving effectively from memory model (REM; Lehman & Malmberg, 2009) predicts that intentional forgetting should only be observed for free recall when temporal context is used to probe memory. By manipulating whether study lists were constructed from category exemplars or from a random set of words, and by either providing temporal or category cues at test, we tested the prediction. The effects of directed forgetting were eliminated when categorized lists were studied and category cues were provided. When categorized lists were used but category cues were not provided, the usual costs and benefits of directed forgetting were observed. These results specify the conditions under which the consequences of intentional forgetting can be overcome. PMID:21264615

  16. Innovative Strategies to Overcome Biofilm Resistance

    PubMed Central

    Taraszkiewicz, Aleksandra; Fila, Grzegorz; Grinholc, Mariusz; Nakonieczna, Joanna

    2013-01-01

    We review the recent literature concerning the efficiency of antimicrobial photodynamic inactivation toward various microbial species in planktonic and biofilm cultures. The review is mainly focused on biofilm-growing microrganisms because this form of growth poses a threat to chronically infected or immunocompromised patients and is difficult to eradicate from medical devices. We discuss the biofilm formation process and mechanisms of its increased resistance to various antimicrobials. We present, based on data in the literature, strategies for overcoming the problem of biofilm resistance. Factors that have potential for use in increasing the efficiency of the killing of biofilm-forming bacteria include plant extracts, enzymes that disturb the biofilm structure, and other nonenzymatic molecules. We propose combining antimicrobial photodynamic therapy with various antimicrobial and antibiofilm approaches to obtain a synergistic effect to permit efficient microbial growth control at low photosensitizer doses. PMID:23509680

  17. How to overcome difficulties with reserves replacement

    SciTech Connect

    Brashear, J.P.; Becker, A.B.; Godec, M.L.; Crawford, P.M.

    1997-03-10

    The first part of this article discussed the challenge of replacing reserves while maintaining high levels of profitability. An examination of the 82 largest US-based, publicly traded exploration and production (E and P) companies, grouped by size, suggested a potential conflict between reserves replacement and profitability--a ``devil`s dilemma`` between long term viability and financial performance. The 10 largest companies failed to replace their production in the US or worldwide (although they did in non-US operations). They were, however, the most profitable on a per-barrel-equivalent basis. In general, the smaller the company, the higher its reserves-replacement ratio, reflecting greater relative effort but lower unit profitability. This article examines the difficulties that companies face in reserves replacement planning, the accommodations they make to these difficulties, and the problems caused by these accommodations. It then suggests an analytical structure for reserves replacement planning that contributes to overcoming the difficulties.

  18. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC) transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed. PMID:26649310

  19. Steric and electronic contributions to the core reactivity of monoprotonated 5-phenylporphyrin: A DFT study

    NASA Astrophysics Data System (ADS)

    Presselt, Martin; Wojdyr, Michal; Beenken, Wichard J. D.; Kruk, Mikalai; Martínez, Todd J.

    2014-05-01

    We analyse the behaviour of mono-protonated 5-phenylporphyrin upon por-ph torsion to get insights into torsion-induced reactivity changes. In contrast to the majority of structures, nitrogen-accessibility volume (Vreact) is larger for front-side (exposed nitrogen) than for backside-attacks at the optimised structure. The high reactivity of nitrogen is determined by the electrostatic potential distribution inside the porphyrine core. Even if Vreact at certain structures is smaller for front side than for backside attacks the mean electrostatic-potential-density φ inside Vreact reveals a lower barrier for front side than for backside protonation, and this holds true for the majority of structures.

  20. Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions.

    PubMed

    Liu, Yongmei; Meng, Guangrong; Liu, Ruzhang; Szostak, Michal

    2016-05-21

    Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond nN→πCO* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions. PMID:27139813

  1. Steric and electronic effects of 1,3-disubstituted cyclopentadienyl ligands on metallocene derivatives of Cerium, Titanium, Manganese, and Iron

    SciTech Connect

    Sofield, C.D.

    2000-05-19

    Sterically demanding 1,3-disubstituted cyclopentadienyl ligands were used to modify the physical properties of the corresponding metallocenes. Sterically demanding ligands provided kinetic stabilization for trivalent cerium compounds. Tris(di-t-butylcyclopentadienyl)cerium was prepared and anion competition between halides and cyclopentadienyl groups which had complicated synthesis of the tris(cyclopentadienyl)compound was qualitatively examined. Bis(di-t-butylcyclopentadienyl)cerium methyl was prepared and its rate of decomposition, by ligand redistribution, to tris(di-t-butylcyclopentadienyl)cerium was shown to be slower than the corresponding rate for less sterically demanding ligands. Asymmetrically substituted ligands provided a symmetry label for examination of chemical exchange processes. Tris[trimethylsilyl(t-butyl)cyclopentadienyl]cerium was prepared and the rate of interconversion between the C1 and C3 isomers was examined. The enthalpy difference between the two distereomers is 7.0 kJ/mol. The sterically demanding cyclopentadienyl ligands ansa-di-t-butylcyclopentadiene (Me2Si[(Me3C)2C5H3]2), ansa-bis(trimethylsilyl)cyclopentadiene (Me2Si[(Me3Si)2C5H3]2) and tetra-t-butylfulvalene and metallocene derivatives of the ligands were prepared and their structures were examined by single crystal X-ray crystallography. The effect that substituents on the cyclopentadienyl ring have on the pi-electron system of the ligand was examined through interaction between ligand and metal orbitals. A series of 1,3-disubstituted manganocenes was prepared and their electronic states were determined by solid-state magnetic susceptibility, electron paramagnetic resonance, X-ray crystallography, and variable temperature UV-vis spectroscopy. Spin-equilibria in [(Me3C)2C5H3]2Mn and [(Me3C)(Me3Si)C5H3]2Mn were examined and indicate an enthalpy difference of 15 kJ/mol between the high-spin and low-spin forms. Cyclopentadienyl groups resistant to intramolecular oxidative addition

  2. Overcoming the obstacles: Life stories of scientists with learning disabilities

    NASA Astrophysics Data System (ADS)

    Force, Crista Marie

    Scientific discovery is at the heart of solving many of the problems facing contemporary society. Scientists are retiring at rates that exceed the numbers of new scientists. Unfortunately, scientific careers still appear to be outside the reach of most individuals with learning disabilities. The purpose of this research was to better understand the methods by which successful learning disabled scientists have overcome the barriers and challenges associated with their learning disabilities in their preparation and performance as scientists. This narrative inquiry involved the researcher writing the life stories of four scientists. These life stories were generated from extensive interviews in which each of the scientists recounted their life histories. The researcher used narrative analysis to "make sense" of these learning disabled scientists' life stories. The narrative analysis required the researcher to identify and describe emergent themes characterizing each scientist's life. A cross-case analysis was then performed to uncover commonalities and differences in the lives of these four individuals. Results of the cross-case analysis revealed that all four scientists had a passion for science that emerged at an early age, which, with strong drive and determination, drove these individuals to succeed in spite of the many obstacles arising from their learning disabilities. The analysis also revealed that these scientists chose careers based on their strengths; they actively sought mentors to guide them in their preparation as scientists; and they developed coping techniques to overcome difficulties and succeed. The cross-case analysis also revealed differences in the degree to which each scientist accepted his or her learning disability. While some demonstrated inferior feelings about their successes as scientists, still other individuals revealed feelings of having superior abilities in areas such as visualization and working with people. These individuals revealed

  3. Overcoming Breakdowns and Engaging the Public

    NASA Astrophysics Data System (ADS)

    Bowman, T. E.

    2012-12-01

    With strong climate science evidence readily available, why do major segments of the public remain disengaged? Decades of social science research and practical communications experience indicate that prioritizing and structuring information, choosing appropriate messengers, and adapting to audience interests and learning styles are vital, yet often ignored criteria. This session will explore key differences between communications models within the science community and effective outreach to non-scientist audiences. Here, prioritizing goals, understanding preconceptions and identifying intervention opportunities require careful examination. "Public engagement" is defined as encouraging and enabling people to make informed choices on their own behalf. Crucial barriers identified in economics, political psychology and audience segmentation research will be addressed, and recommendations for more effective engagement will emerge including: defining realistic goals, simplifying science content accurately, avoiding values conflicts that prevent learning, enlisting trusted messengers, and matching a call to action to the scale of the challenge in ways people can embrace.

  4. Steric interactions lead to collective tilting motion in the ribosome during mRNA–tRNA translocation

    PubMed Central

    Nguyen, Kien; Whitford, Paul C.

    2016-01-01

    Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA–tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P–P/E and P/P–E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P–pe/E intermediate, where the 30S head is rotated ∼18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ∼10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements. PMID:26838673

  5. Reactivity versus steric effects in fluorinated ketones as esterase inhibitors: a quantum mechanical and molecular dynamics study

    PubMed Central

    Rayo, Josep; Muñoz, Lourdes; Rosell, Gloria; Hammock, Bruce D.; Guerrero, Angel

    2010-01-01

    Carboxylesterases (CEs) are a family of ubiquitous enzymes with broad substrate specificity, and their inhibition may have important implications in pharmaceutical and agrochemical fields. One of the most potent inhibitors both for mammalian and insect CEs are trifluoromethyl ketones (TFMKs), but the mechanism of action of these chemicals is not completely understood. This study examines the balance between reactivity versus steric effects in modulating the activity against human carboxylesterase 1. The intrinsic reactivity of the ketone moiety is determined from quantum mechanical computations, which combine gas phase B3LYP calculations with hydration free energies estimated with the IEF/MST model. In addition, docking and molecular dynamics simulations are used to explore the binding mode of the inhibitors along the deep gorge that delineates the binding site. The results point out that the activity largely depends on the nature of the fluorinated ketone, since the activity is modulated by the balance between the intrinsic electrophilicity of the carbonyl carbon atom and the ratio between keto and hydrate forms. However, the results also suggest that the correct alignment of the alkyl chain in the binding site can exert a large influence on the inhibitory activity, as this effect seems to override the intrinsic reactivity features of the fluorinated ketone. Overall, the results sustain a subtle balance between reactivity and steric effects in modulating the inhibitory activity of TFMK inhibitors. PMID:20676708

  6. Specific contrast ultrasound using sterically stabilized microbubbles for early diagnosis of thromboembolic disease in a rabbit model

    PubMed Central

    Vlašín, Michal; Lukáč, Robert; Kauerová, Zuzana; Kohout, Pavel; Mašek, Josef; Bartheldyová, Eliška; Koudelka, Štěpán; Korvasová, Zina; Plocková, Jana; Hronová, Nikola; Turánek, Jaroslav

    2014-01-01

    Specific contrast ultrasound is widely applied in diagnostic procedures on humans but remains underused in veterinary medicine. The objective of this study was to evaluate the use of microbubble-based contrast for rapid ultrasonographic diagnosis of thrombosis in small animals, using male New Zealand white rabbits (average weight about 3.5 kg) as a model. It was hypothesized that the use of microbubble-based contrast agents will result in a faster and more precise diagnosis in our model of thrombosis. A pro-coagulant environment had been previously established by combining endothelial denudation and external vessel wall damage. Visualization of thrombi was achieved by application of contrast microbubbles [sterically stabilized, phospholipid-based microbubbles filled with sulfur hexafluoride (SF6) gas] and ultrasonography. As a result, rapid and clear diagnosis of thrombi in aorta abdominalis was achieved within 10 to 30 s (mean: 17.3 s) by applying microbubbles as an ultrasound contrast medium. In the control group, diagnosis was not possible or took 90 to 180 s. Therefore, sterically stabilized microbubbles were found to be a suitable contrast agent for the rapid diagnosis of thrombi in an experimental model in rabbits. This contrast agent could be of practical importance in small animal practice for rapid diagnosis of thrombosis. PMID:24688175

  7. Observation of steric hindrance effect controlling crystal packing structures and physical properties in three new isomeric nitronyl nitroxide radicals

    NASA Astrophysics Data System (ADS)

    Zhao, Hai-Rong; Sun, Jia-Sen; Sui, Yun-Xia; Ren, Xiao-Ming; Yao, Bin-Qian; Shen, Lin-Jiang; Meng, Qing-Jin

    2009-07-01

    Three isomeric nitronyl nitroxide radical compounds, 2-[ n-( N-benzyl)pyridinium]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide bromide ( n = 2, 3 and 4 for 1, 2 and 3, respectively), have been synthesized and structurally characterized. The influence of steric hindrance on the molecular packing structures and physical properties has been observed. In the radical 1, such steric hindrance leads to a folding conformation of the imidazoline and benzene rings and the intramolecular C-H…π interaction between the methyl group and the benzene ring. There is no such effect in 2 and 3. In crystal of 2, there are the intermolecular C-H…π between methyl groups and benzene ring and intermolecular π…π stacking interaction between pyridine and benzene rings. Crystal of 2 with a chiral space group P2 12 12 1 shows the SHG response about 0.4 times as that of urea. In crystal of 3, there are three symmetry-independent radical molecules, which form an unusually six-membered supramolecular ring via intermolecular O…π interactions. For the solid sample of 3, the X-band EPR exhibits an axially symmetric signal and magnetic susceptibility data suggest intermolecular antiferromagnetic (AFM) coupling interactions and very weak intermolecular ferromagnetic (FM) coupling interactions which is more likely caused by magnetic anisotropy, while measurements of both 1 and 2 show isotropic X-band EPR signals and simple Currie-Weiss magnetic behavior.

  8. Density functional theory analysis of the impact of steric interaction on the function of switchable polarity solvents

    SciTech Connect

    McNally, Joshua S.; Noll, Bruce; Orme, Christopher J.; Wilson, Aaron D.

    2015-05-04

    Here, a density functional theory (DFT) analysis has been performed to explore the impact of steric interactions on the function of switchable polarity solvents (SPS) and their implications on a quantitative structure-activity relationship (QSAR) model previously proposed for SPS. An x-ray crystal structure of the N,N-dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an asymmetric unit containing two cation/anion pairs, with a hydrogen bonding interaction observed between the bicarbonate anions, as well as between the cation and anion in each pair. DFT calculations provide an optimized structure of Hdmcha that closely resembles experimental data and reproduces the cation/anion interaction with the inclusion of a dielectric field. Relaxed potential energy surface (PES) scans have been performed on Hdmcha-based computational model compounds, differing in the size of functional group bonded to the nitrogen center, to assess the steric impact of the group on the relative energy and structural properties of the compound. Results suggest that both the length and amount of branching associated with the substituent impact the energetic limitations on rotation of the group along the N-R bond and NC-R bond, and disrupt the energy minimized position of the hydrogen bonded bicarbonate group. The largest interaction resulted from functional groups that featured five bonds between the ammonium proton and a proton on a functional group with the freedom of rotation to form a pseudo-six membered ring which included both protons.

  9. Structural and functional mimic of galactose oxidase by a copper complex of a sterically demanding [N2O2] ligand.

    PubMed

    John, Alex; Shaikh, Mobin M; Ghosh, Prasenjit

    2008-06-01

    A structural and functional mimic of the galactose oxidase (GOase) enzyme active-site by a copper complex supported over a sterically demanding ligand having [N2O2] donor sites is reported. Specifically, the binding of the histidine (496 and 581) and tyrosine (272 and 495) residues to the copper center in a square-pyramidal fashion in the active-site of galactose oxidase (GOase) enzyme has been modeled in a copper complex, ([(3-tert-butyl-5-methyl-2-hydoxybenzyl)(3'-tert-butyl-5'-methyl-2'-oxobenzyl)(2-pyridylmethyl)]amine)Cu(OAc)) (1b), stabilized over a sterically demanding ligand in which the two phenolate-O atoms mimicked the tyrosine binding while an amine-N and pyridyl-N atoms emulated the histidine binding to the metal center, similar to that in the enzyme active-site. Furthermore, the copper complex 1b is found to be an effective functional model of the enzyme as it efficiently catalyzed the chemoselective oxidation of primary alcohols to aldehydes in high turnover numbers under ambient conditions. An insight into the nature of the active-species was obtained by EPR and CV studies, which in conjunction with the DFT studies, revealed that the active-species is an anti-ferromagnetically coupled diamagnetic radical cation, (1)1b+, obtained by one electron oxidation at the equatorial phenolate-O atom of the ligand in the 1b complex. PMID:18478142

  10. Steric effects in the dynamics of electrolytes at large applied voltages. II. Modified Poisson-Nernst-Planck equations.

    PubMed

    Kilic, Mustafa Sabri; Bazant, Martin Z; Ajdari, Armand

    2007-02-01

    In situations involving large potentials or surface charges, the Poisson-Boltzman (PB) equation has shortcomings because it neglects ion-ion interactions and steric effects. This has been widely recognized by the electrochemistry community, leading to the development of various alternative models resulting in different sets "modified PB equations," which have had at least qualitative success in predicting equilibrium ion distributions. On the other hand, the literature is scarce in terms of descriptions of concentration dynamics in these regimes. Here, adapting strategies developed to modify the PB equation, we propose a simple modification of the widely used Poisson-Nernst-Planck (PNP) equations for ionic transport, which at least qualitatively accounts for steric effects. We analyze numerical solutions of these modified PNP equations on the model problem of the charging of a simple electrolyte cell, and compare the outcome to that of the standard PNP equations. Finally, we repeat the asymptotic analysis of Bazant, Thornton, and Ajdari [Phys. Rev. E 70, 021506 (2004)] for this new system of equations to further document the interest and limits of validity of the simpler equivalent electrical circuit models introduced in Part I [Kilic, Bazant, and Ajdari, Phys. Rev. E 75, 021502 (2007)] for such problems. PMID:17358344

  11. Templating an organic layer with the Si(111)-7×7 surface reconstruction using steric constraints

    NASA Astrophysics Data System (ADS)

    Weymouth, A. J.; Edge, G. J. A.; McLean, A. B.; Miwa, R. H.; Srivastava, G. P.

    2011-10-01

    We demonstrate that the Si(111)-7×7 surface reconstruction can be used to template an ordered array of 1,3,5-methyl benzene molecules that are uniformly distributed over both the faulted and the unfaulted halves of the 7×7 unit cell by covalent attachment in vacuo. An intermolecular steric interaction, which hinders nearest-neighbor adsorption, is shown to play an important role in the formation of the ordered array. The stable equilibrium structure is shown to be one where the molecules are located at the corner of the half unit cells maximizing the intermolecular separation. In addition to the intermolecular steric interaction, there is an interaction between the molecule and the surface that plays a important role in reducing disorder in the array. Moreover, as the coverage is increased, there is a switch in site preference, from edge to corner, that mitigates the effect of the intermolecular interaction. To investigate this system we used scanning tunneling microscopy to study site occupancy as a function of coverage, ab initio total energy calculation to study the stability of the attachment sites, and Monte Carlo modeling to examine the emergence of translational order in the overlayer. The switch in site preference from edge to corner is faithfully reproduced by the kinetic Monte Carlo model when an interaction term is included.

  12. Relative contributions of ocean mass and deep steric changes to sea level rise between 1993 and 2013

    NASA Astrophysics Data System (ADS)

    Purkey, Sarah G.; Johnson, Gregory C.; Chambers, Don P.

    2014-11-01

    Regional and global trends of Sea Level Rise (SLR) owing to mass addition centered between 1996 and 2006 are assessed through a full-depth SLR budget using full-depth in situ ocean data and satellite altimetry. These rates are compared to regional and global trends in ocean mass addition estimated directly using data from the Gravity Recovery and Climate Experiment (GRACE) from 2003 to 2013. Despite the two independent methods covering different time periods with differing spatial and temporal resolution, they both capture the same large-scale mass addition trend patterns including higher rates of mass addition in the North Pacific, South Atlantic, and the Indo-Atlantic sector of the Southern Ocean, and lower mass addition trends in the Indian, North Atlantic, South Pacific, and the Pacific sector of the Southern Ocean. The global mean trend of ocean mass addition is 1.5 (±0.4) mm yr-1 for 1996-2006 from the residual method and the same for 2003-2013 from the GRACE method. Furthermore, the residual method is used to evaluate the error introduced into the mass budget if the deep steric contributions below 700, 1000, 2000, 3000, and 4000 m are neglected, revealing errors of 65%, 38%, 13%, 8%, and 4% respectively. The two methods no longer agree within error bars when only the steric contribution shallower than 1000 m is considered.

  13. Density functional theory analysis of the impact of steric interaction on the function of switchable polarity solvents

    DOE PAGESBeta

    McNally, Joshua S.; Noll, Bruce; Orme, Christopher J.; Wilson, Aaron D.

    2015-05-04

    Here, a density functional theory (DFT) analysis has been performed to explore the impact of steric interactions on the function of switchable polarity solvents (SPS) and their implications on a quantitative structure-activity relationship (QSAR) model previously proposed for SPS. An x-ray crystal structure of the N,N-dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an asymmetric unit containing two cation/anion pairs, with a hydrogen bonding interaction observed between the bicarbonate anions, as well as between the cation and anion in each pair. DFT calculations provide an optimized structure of Hdmcha that closely resembles experimental data and reproduces the cation/anion interaction withmore » the inclusion of a dielectric field. Relaxed potential energy surface (PES) scans have been performed on Hdmcha-based computational model compounds, differing in the size of functional group bonded to the nitrogen center, to assess the steric impact of the group on the relative energy and structural properties of the compound. Results suggest that both the length and amount of branching associated with the substituent impact the energetic limitations on rotation of the group along the N-R bond and NC-R bond, and disrupt the energy minimized position of the hydrogen bonded bicarbonate group. The largest interaction resulted from functional groups that featured five bonds between the ammonium proton and a proton on a functional group with the freedom of rotation to form a pseudo-six membered ring which included both protons.« less

  14. Steric effects of CO2 binding to transition metal-benzene complexes: A first-principles study

    NASA Astrophysics Data System (ADS)

    Bae, Hyeonhu; Huang, Bing; Lee, Hoonkyung

    2016-09-01

    Using density functional theory (DFT) calculations, we investigated the adsorption of CO2 molecules on 3d transition metal (TM)-benzene complexes. Our calculations show that the maximum number of CO2 molecules adsorbable on Sc or Ti atoms is three, but the 18-electron rule predicts it should be four. The 18-electron rule is generally successful in predicting the maximum H2 adsorption number for TM atoms including Sc or Ti atoms. We found that the 18-electron rule fails to correctly predict CO2 binding on Sc- or Ti-benzene complexes because CO2 binding, in contrast to H2 binding, requires additional consideration for steric hindrance due to the large bond length of CO2. We calculated the occupation function for CO2 using the Tolman cone angle, which shows that three CO2 molecules fully occupy the available space around Sc- and Ti-benzene complexes. This estimation is the same maximum CO2 adsorption number predicted by DFT calculations. Therefore, we propose that the occupation function for CO2 using the Tolman cone angle is an efficient model for evaluating steric hindrance of CO2 adsorption on a surface.

  15. Steric interactions lead to collective tilting motion in the ribosome during mRNA-tRNA translocation.

    PubMed

    Nguyen, Kien; Whitford, Paul C

    2016-01-01

    Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ∼18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ∼10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements. PMID:26838673

  16. Steric effects in the dynamics of electrolytes at large applied voltages. II. Modified Poisson-Nernst-Planck equations

    NASA Astrophysics Data System (ADS)

    Kilic, Mustafa Sabri; Bazant, Martin Z.; Ajdari, Armand

    2007-02-01

    In situations involving large potentials or surface charges, the Poisson-Boltzman (PB) equation has shortcomings because it neglects ion-ion interactions and steric effects. This has been widely recognized by the electrochemistry community, leading to the development of various alternative models resulting in different sets “modified PB equations,” which have had at least qualitative success in predicting equilibrium ion distributions. On the other hand, the literature is scarce in terms of descriptions of concentration dynamics in these regimes. Here, adapting strategies developed to modify the PB equation, we propose a simple modification of the widely used Poisson-Nernst-Planck (PNP) equations for ionic transport, which at least qualitatively accounts for steric effects. We analyze numerical solutions of these modified PNP equations on the model problem of the charging of a simple electrolyte cell, and compare the outcome to that of the standard PNP equations. Finally, we repeat the asymptotic analysis of Bazant, Thornton, and Ajdari [Phys. Rev. E 70, 021506 (2004)] for this new system of equations to further document the interest and limits of validity of the simpler equivalent electrical circuit models introduced in Part I [Kilic, Bazant, and Ajdari, Phys. Rev. E 75, 021502 (2007)] for such problems.

  17. Steric and Electronic Factors Associated with the Photoinduced Ligand Exchange of Bidentate Ligands Coordinated to Ru(II).

    PubMed

    Albani, Bryan A; Whittemore, Tyler; Durr, Christopher B; Turro, Claudia

    2015-01-01

    In an effort to create a molecule that can absorb low energy visible or near-infrared light for photochemotherapy (PCT), the new complexes [Ru(biq)2 (dpb)](PF6 )2 (1, biq = 2,2'-biquinoline, dpb = 2,3-bis(2-pyridyl)benzoquinoxaline) and [(biq)2 Ru(dpb)Re(CO)3 Cl](PF6 )2 (2) were synthesized and characterized. Complexes 1 and 2 were compared to [Ru(bpy)2 (dpb)](PF6 )2 (3, bpy = 2,2'-bipyridine) and [Ru(biq)2 (phen)](PF6 )2 (4, phen = 1,10-phenanthroline). Distortions around the metal and biq ligands were used to explain the exchange of one biq ligand in 4 upon irradiation. Complex 1, however, undergoes photoinduced dissociation of the dpb ligand rather than biq under analogous experimental conditions. Complex 3 is not photoactive, providing evidence that the biq ligands are crucial for ligand photodissociation in 1. The crystal structures of 1 and 4 are compared to explain the difference in photochemistry between the complexes. Complex 2 absorbs lower energy light than 1, but is photochemically inert although its crystal structure displays significant distortions. These results indicate that both the excited state electronic structure and steric bulk play key roles in bidentate photoinduced ligand dissociation. The present work also shows that it is possible to stabilize sterically hindered Ru(II) complexes by the addition of another metal, a property that may be useful for other applications. PMID:25403564

  18. Steric interactions lead to collective tilting motion in the ribosome during mRNA-tRNA translocation

    NASA Astrophysics Data System (ADS)

    Nguyen, Kien; Whitford, Paul C.

    2016-02-01

    Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ~18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ~10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements.

  19. Barriers to Healthier Eating in a Disadvantaged Community

    ERIC Educational Resources Information Center

    O'Neill, Martin; Rebane, Deanne; Lester, Carolyn

    2004-01-01

    Objective: The research objective was to identify how healthy eating was understood in a disadvantaged community and how barriers to healthy eating might be overcome. Design: Participatory action research. Setting: Communities in Gurnos, Merthyr Tydfil, one of the most deprived areas in the UK. Method: Trainees on a participative methods course…

  20. Industry-College Cooperation: New Components, Barriers and Strategies.

    ERIC Educational Resources Information Center

    Rinehart, Richard L.

    A variety of linkage components that can help build and maintain effective relationships between the worlds of work and education are identified, and barriers to the development of such relationships and techniques for overcoming them are described in this report. The first section lists different forms of industry/education cooperation and their…

  1. Overcoming the force and power of immunity: a history of immunosuppression in kidney transplantation.

    PubMed

    Patel, Paul S

    2006-01-01

    Immunosuppression for organ transplantation is a modern concept. The earliest reports of organ replacement have their roots in mythology and human fantasy. The primacy of overcoming the immunologic barrier for successful transplantation of organs has been influenced by geopolitical conflict, unorthodox ideas, application of knowledge across medical disciplines, and serendipity. The earliest form of chemical immunosuppression had its origin in chemical gas in warfare. Further developments in immunology, cancer therapy and biochemistry helped shape the intellectual basis for the introduction of chemical immunosuppression. PMID:16874728

  2. Barriers to Successful Implementation of Technology Integration in Educational Settings: A Case Study

    ERIC Educational Resources Information Center

    Laferrière, T.; Hamel, C.; Searson, M.

    2013-01-01

    Representing issues discussed at the EduSummIT 2011 relative to essential conditions and barriers to successful technology integration, this article presents a systemic analysis of barriers that needed to be overcome for an information technology initiative (Remote Networked School project) to be successfully implemented. The analysis was…

  3. Development of the Motivators of and Barriers to Health-Smart Behaviors Inventory

    ERIC Educational Resources Information Center

    Tucker, Carolyn M.; Rice, Kenneth G.; Hou, Wei; Kaye, Lillian B.; Nolan, Sarah E. M.; Grandoit, Delphia J.; Gonzales, Lucia; Smith, Mary B.; Desmond, Frederic F.

    2011-01-01

    The Motivators of and Barriers to Health-Smart Behaviors Inventory (MB-HSBI) was developed for use in identifying self-reported motivators of and barriers to the following health-promoting behaviors (called "health-smart behaviors") that should occur daily to help promote health and overcome illnesses/diseases: eating a healthy breakfast, eating…

  4. NANOPREPARATIONS TO OVERCOME MULTIDRUG RESISTANCE IN CANCER

    PubMed Central

    Patel, Niravkumar R.; Pattni, Bhushan S.; Abouzeid, Abraham H.; Torchilin, Vladimir P.

    2013-01-01

    Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing micro tumor tissues in vitro are discussed in detail. PMID:23973912

  5. Overcoming Old in Age-Friendliness

    PubMed Central

    Lindenberg, J.; Westendorp, R.G.J.

    2015-01-01

    In this article, we explore views on an age-friendly space in the Netherlands by analysing the responses of older individuals (N = 54) in focus groups and by examining the perspectives around an age-friendly zone in the Netherlands, Parkstad Limburg. We found that a central issue in the wishes for living at a later age are adjustments to envisioned physical limitations that come with the ageing process; this includes adjustments to ensure safety, accessibility and mobility, in order to facilitate older individuals' efforts to stay engaged with the world around them. In their wishes, the older participants constructed ideal dwelling places that closely resembled a senior home, but at the same time they rejected wishing to live in a place that was identified as a senior home. We explain this paradox by the representation of such a space as being for old people, i.e. needy older individuals, which was not how the older participants wished to be identified. We conclude that the conception of age-friendly environments will have to face the difficult challenge of overcoming the association with old age, while simultaneously taking into account adjustments that signify and relate to the ageing process and that seem inescapably tied to oldness. PMID:26028795

  6. Evaluative pressure overcomes perceptual load effects.

    PubMed

    Normand, Alice; Autin, Frédérique; Croizet, Jean-Claude

    2015-06-01

    Perceptual load has been found to be a powerful bottom-up determinant of distractibility, with high perceptual load preventing distraction by any irrelevant information. However, when under evaluative pressure, individuals exert top-down attentional control by giving greater weight to task-relevant features, making them more distractible from task-relevant distractors. One study tested whether the top-down modulation of attention under evaluative pressure overcomes the beneficial bottom-up effect of high perceptual load on distraction. Using a response-competition task, we replicated previous findings that high levels of perceptual load suppress task-relevant distractor response interference, but only for participants in a control condition. Participants under evaluative pressure (i.e., who believed their intelligence was assessed) showed interference from task-relevant distractor at all levels of perceptual load. This research challenges the assumptions of the perceptual load theory and sheds light on a neglected determinant of distractibility: the self-relevance of the performance situation in which attentional control is solicited. PMID:25233881

  7. Overcoming Current Limitations in Humanized Mouse Research

    PubMed Central

    Brehm, Michael A.; Shultz, Leonard D.; Luban, Jeremy; Greiner, Dale L.

    2013-01-01

    Immunodeficient mice engrafted with human cells and tissues have provided an exciting alternative to in vitro studies with human tissues and nonhuman primates for the study of human immunobiology. A major breakthrough in the early 2000s was the introduction of a targeted mutation in the interleukin 2 (IL-2) receptor common gamma chain (IL2rgnull) into mice that were already deficient in T and B cells. Among other immune defects, natural killer (NK) cells are disrupted in these mice, permitting efficient engraftment with human hematopoietic cells that generate a functional human immune system. These humanized mouse models are becoming increasingly important for preclinical studies of human immunity, hematopoiesis, tissue regeneration, cancer, and infectious diseases. In particular, humanized mice have enabled studies of the pathogenesis of human-specific pathogens, including human immunodeficiency virus type 1, Epstein Barr virus, and Salmonella typhi. However, there are a number of limitations in the currently available humanized mouse models. Investigators are continuing to identify molecular mechanisms underlying the remaining defects in the engrafted human immune system and are generating “next generation” models to overcome these final deficiencies. This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed. PMID:24151318

  8. Overcoming the grand challenges in Quantum Simulations

    NASA Astrophysics Data System (ADS)

    Zhou, Qi

    2010-03-01

    The highly ambitious goal of the ``Quantum Simulation'' program is to simulate the behavior of strongly correlated solid-state systems using cold atoms in optical lattices. It promises to provide insight into a range of long-standing problems in many-body physics. There are, however, significant challenges which need to be overcome in order for these efforts to succeed. The first challenge is that the required temperatures for studying strongly correlated physics in optical lattices are far below those achievable in laboratories today. The second problem concerns the fact that many important thermodynamic qualities, which distribute non-uniformly in the confining trap, are inaccessible by standard imaging methods. In this talk, I will discuss ways to solve these grand challenges. First, I will present schemes which allow for strongly correlated regimes of atoms in optical lattices to be reached. These schemes are based on transferring the entropy out of the region of interest. Examples will be given to demonstrate that these schemes can reach temperature regions down to a few tens of pico-Kelvin. Secondly, I will discuss algorithms to map out the phase diagrams of quantum models and deduce the thermodynamic properties of homogeneous systems, such as the superfluid density and entropy density, which have eluded cold atom experiments for years. Using only the density profile of trapped atoms as input, these algorithms can fulfill the lofty goal of quantum simulation.

  9. Towards an Approach to Overcome Software Brittleness

    SciTech Connect

    OSBOURN,GORDON C.

    1999-11-01

    Development of bug-free, high-surety, complex software is quite difficult using current tools. The brittle nature of the programming constructs in popular languages such as C/C++ is one root cause. Brittle commands force the designer to rigidly specify the minutiae of tasks, e.g. using ''for(index=0;index>total;index++)'', rather than specifying the goals or intent of the tasks, e.g. ''ensure that all relevant data elements have been examined''. Specification of task minutiae makes code hard to comprehend, which in turn encourages design errors/limitations and makes future modifications quite difficult. This report describes an LDRD project to seed the development of a surety computer language, for stand-alone computing environments, to be implemented using the swarm intelligence of autonomous agents. The long term vision of this project was to develop a language with the following surety capabilities: (1) Reliability -- Autonomous agents can appropriate y decide when to act and when a task is complete, provide a natural means for avoiding brittle task specifications, and can overcome many hardware glitches. (2) Safety, security -- Watchdog safety and security agents can monitor other agents to prevent unauthorized or dangerous actions. (3) An immune system -- The small chunks of agent code can have an encryption scheme to enable detection and elimination of unauthorized and corrupted agents. This report describes the progress achieved during this small 9 month project and describes lessons learned.

  10. Cooperative networks overcoming defectors by social influence

    NASA Astrophysics Data System (ADS)

    Gomez Portillo, Ignacio

    2014-01-01

    We address the cooperation problem in structured populations by considering the prisoner’s dilemma game as a metaphor of the social interactions between individuals with imitation capacity. We present a new strategy update rule called democratic weighted update where the individual’s behavior is socially influenced by each one of their neighbors. In particular, the capacity of an individual to socially influence other ones is proportional to its accumulated payoff. When in a neighborhood there are cooperators and defectors, the focal player is contradictorily influenced by them and, therefore, the effective social influence is given by the difference of the accumulated payoff of each strategy in its neighborhood. First, by considering the growing process of the network and neglecting mutations, we show the evolution of highly cooperative systems. Then, we broadly show that the social influence allows to overcome the emergence of defectors into highly cooperative systems. In this way, we conclude that in a structured system formed by a growing process, the cooperation evolves if the individuals have an imitation capacity socially influenced by each one of their neighbors. Therefore, here we present a theoretical solution of the cooperation problem among genetically unrelated individuals.

  11. Puncture detecting barrier materials

    DOEpatents

    Hermes, Robert E.; Ramsey, David R.; Stampfer, Joseph F.; Macdonald, John M.

    1998-01-01

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material.

  12. Puncture detecting barrier materials

    DOEpatents

    Hermes, R.E.; Ramsey, D.R.; Stampfer, J.F.; Macdonald, J.M.

    1998-03-31

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material. 4 figs.

  13. Supports and Barriers to Successful Progression in a DNP Program: Students' and Graduates' Perspectives.

    PubMed

    Hlabse, Mara Lea; Dowling, Donna A; Lindell, Deborah; Underwood, Patricia; Barsman, Sarah Gutin

    2016-01-01

    This study examined the supports, barriers, and strategies to successful progression in a DNP program using a nationwide online survey of DNP students and graduates. Subjects (n = 172) had a mean age of 46.2 years; 83% worked full time. Major barriers were competing demands of work, family, and school. Perseverance was a key element in overcoming barriers; most students reported being overwhelmed, and 37% considered quitting. Mechanisms for programs to consider in addressing this stress are discussed. PMID:26866732

  14. Single-step versus stepwise two-electron reduction of polyarylpyridiniums: insights from the steric switching of redox potential compression.

    PubMed

    Fortage, Jérôme; Peltier, Cyril; Perruchot, Christian; Takemoto, Yohei; Teki, Yoshio; Bedioui, Fethi; Marvaud, Valérie; Dupeyre, Grégory; Pospísil, Lubomír; Adamo, Carlo; Hromadová, Magdaléna; Ciofini, Ilaria; Lainé, Philippe P

    2012-02-01

    Contrary to 4,4'-dipyridinium (i.e., archetypal methyl viologen), which is reduced by two single-electron transfers (stepwise reduction), the 4,1'-dipyridinium isomer (so-called "head-to-tail" isomer) undergoes two electron transfers at apparently the same potential (single-step reduction). A combined theoretical and experimental study has been undertaken to establish that the latter electrochemical behavior, also observed for other polyarylpyridinium electrophores, is due to potential compression originating in a large structural rearrangement. Three series of branched expanded pyridiniums (EPs) were prepared: N-aryl-2,4,6-triphenylpyridiniums (Ar-TP), N-aryl-2,3,4,5,6-pentaphenylpyridiniums (Ar-XP), and N-aryl-3,5-dimethyl-2,4,6-triphenylpyridinium (Ar-DMTP). The intramolecular steric strain was tuned via N-pyridinio aryl group (Ar) phenyl (Ph), 4-pyridyl (Py), and 4-pyridylium (qPy) and their bulky 3,5-dimethyl counterparts, xylyl (Xy), lutidyl (Lu), and lutidylium (qLu), respectively. Ferrocenyl subunits as internal redox references were covalently appended to representative electrophores in order to count the electrons involved in EP-centered reduction processes. Depending on the steric constraint around the N-pyridinio site, the two-electron reduction is single-step (Ar = Ph, Py, qPy) or stepwise (Ar = Xy, Lu, qLu). This steric switching of the potential compression is accurately accounted for by ab initio modeling (Density Functional Theory, DFT) that proposes a mechanism for pyramidalization of the N(pyridinio) atom coupled with reduction. When the hybridization change of this atom is hindered (Ar = Xy, Lu, qLu), the first reduction is a one-electron process. Theory also reveals that the single-step two-electron reduction involves couples of redox isomers (electromers) displaying both the axial geometry of native EPs and the pyramidalized geometry of doubly reduced EPs. This picture is confirmed by a combined UV-vis-NIR spectroelectrochemical and time

  15. Iron(II) complexes featuring κ3- and κ2-bound PNP pincer ligands--the significance of sterics.

    PubMed

    Glatz, Mathias; Bichler, Bernhard; Mastalir, Matthias; Stöger, Berthold; Weil, Matthias; Mereiter, Kurt; Pittenauer, Ernst; Allmaier, Günter; Veiros, Luis F; Kirchner, Karl

    2015-01-01

    Treatment of anhydrous FeX2 (X = Cl, Br) with 2 equiv. of the sterically little demanding N,N'-bisphosphino-2,6-diaminopyridine based PNP ligands--featuring Ph, biphenol (BIPOL), Me, Et, nPr, and nBu substituents at the phosphorus sites and H, Me, and Ph substituents at the N-linkers--afforded diamagnetic cationic octahedral complexes of the general formula [Fe(κ(3)-P,N,P-PNP)(κ(2)-P,N-PNP)X](+) featuring a κ(2)-P,N bound PNP ligand. With the sterically more encumbered N-methylated ligand PNP(Me)-Ph the related complex [Fe(κ(3)-P,N,P-PNP(Me)-Ph)(κ(2)-P,N-PN(HMe)-Ph)Cl](+) rather than [Fe(κ(3)-P,N,P-PNP(Me)-Ph)Cl2] was formed. This reaction was accompanied by P-N bond cleavage, thereby forming the κ(2)-P,N-bound N-diphenylphosphino-N,N'-methyl-2,6-diaminopyridine ligand. In contrast, with the N-phenylated ligands PNP(Ph)-Et and PNP(Ph)-nPr, despite small Et and nPr substituents at the phosphorus sites, complexes [Fe(κ(3)-P,N,P-PNP(Ph)-Et)Cl2] and [Fe(κ(3)-P,N,P-PNP(Ph)-nPr)Cl2] were formed, revealing that sterics can be also controlled by substituent variations at the amino N-sites. Depending on the solvent, complexes featuring κ(2)-P,N-bound ligands undergo facile rearrangement reactions to give dicationic complexes of the type [Fe(κ(3)-P,N,P-PNP)2](2+) where both PNP ligands are bound in a κ(3)-P,N,P-fashion. In the presence of either Ag(+) or Na(+) salts as halide scavengers this reaction takes place within a few minutes. The pendant PR2 arm of the κ(3)-κ(2)-complexes is readily oxidized to the corresponding phosphine sulfides upon treatment with elemental sulfur. This was exemplarily shown for [Fe(κ(3)-P,N,P-PNP-nPr)(κ(2)-P,N-PNS-nPr)Cl](+). Halide abstraction afforded the dicationic bis-chelated octahedral Fe(II) complex [Fe(κ(3)-P,N,P-PNP)2](2+) together with the free SNP ligand rather than [Fe(κ(3)-P,N,P-PNP-nPr)(κ(3)-S,P,N-PNS-nPr)](2+). PMID:25376759

  16. Comparing barrier algorithms

    NASA Technical Reports Server (NTRS)

    Arenstorf, Norbert S.; Jordan, Harry F.

    1987-01-01

    A barrier is a method for synchronizing a large number of concurrent computer processes. After considering some basic synchronization mechanisms, a collection of barrier algorithms with either linear or logarithmic depth are presented. A graphical model is described that profiles the execution of the barriers and other parallel programming constructs. This model shows how the interaction between the barrier algorithms and the work that they synchronize can impact their performance. One result is that logarithmic tree structured barriers show good performance when synchronizing fixed length work, while linear self-scheduled barriers show better performance when synchronizing fixed length work with an imbedded critical section. The linear barriers are better able to exploit the process skew associated with critical sections. Timing experiments, performed on an eighteen processor Flex/32 shared memory multiprocessor, that support these conclusions are detailed.

  17. Comparing barrier algorithms

    NASA Technical Reports Server (NTRS)

    Arenstorf, Norbert S.; Jordan, Harry F.

    1989-01-01

    A barrier is a method for synchronizing a large number of concurrent computer processes. After considering some basic synchronization mechanisms, a collection of barrier algorithms with either linear or logarithmic depth are presented. A graphical model is described that profiles the execution of the barriers and other parallel programming constructs. This model shows how the interaction between the barrier algorithms and the work that they synchronize can impact their performance. One result is that logarithmic tree structured barriers show good performance when synchronizing fixed length work, while linear self-scheduled barriers show better performance when synchronizing fixed length work with an imbedded critical section. The linear barriers are better able to exploit the process skew associated with critical sections. Timing experiments, performed on an eighteen processor Flex/32 shared memory multiprocessor that support these conclusions, are detailed.

  18. Sterically hindered disulfide bridges in cystine diketopiperazine, cysteinyl-cysteine disulfide and derivatives.

    PubMed

    Ottnad, M; Hartter, P; Jung, G

    1975-06-01

    L-Cystine diketopiperazine (1), L-cysteinyl-cysteine disulfide -HCl (2), L-cysteinyl-cysteine disulfide methyl ester -HCl (3), and t-butyloxycarbonyl-L-cysteinyl-cysteine disulfide methyl ester (4) are investigated by CD, ultraviolet, 13C NMR, infrared and laser Raman spectroscopy. The temperature dependence of the 13C NMR signals of 1 reveals an exceptionally high energy barrier of deltaGNo. = 15.8 +/- 0.2 kcal/mol for the reversible change in helicity of the inherently dissymmetric disulfide bridge of 1. The P-helical diastereomer predominates in dimethyl-sulfoxide at 25 degrees C, with 80-85% of the molecules having this configuration. The Cotton effects of 1 are larger and show smaller temperature coefficients than the conformationally more mobile cystine compounds 2 and 3. After dissolving crystals of 1 in 95% ethanol there is a time-dependent decrease of the ellipticity of the negative Cotton effect at 225 nm, indicating a conformational change in going from crystal to solution. Besides 1, 2 and 3 are at present the only known examples of cystine derivatives with C-S-S-C torsional angles around 90 degrees, which do not exhibit optical activity in the long wavelength disulfide absorption, as is predicted for 1 from the Linderberg-Michl model. At 305 nm a new weak Cotton effect was discovered for 1. The solvent dependence of the CD spectra is discussed and the infrared and Raman spectra are assigned. PMID:1181260

  19. Control of the Handedness of Self-assemblies of Dipeptides by the Chirality of Phenylalanine and Steric Hindrance of Phenylglycine.

    PubMed

    Lin, Shuwei; Li, Yi; Li, Baozong; Yang, Yonggang

    2016-07-26

    Eight dipeptides, composed of phenylalanine and phenylglycine, that are able to self-assemble into twisted nanoribbons in deionized water are synthesized. The handedness of the nanoribbons is controlled by the chirality of the phenylalanine and the steric hindrance owing to the phenyl group of the phenylglycine. When the phenylalanine is at the C-terminal, π-π stacking by the phenyl groups, hydrogen bonding by the NH group of the phenylalanine, and hydrophobic associations of the alkyl chains control the stacking of the molecules. When phenylglycine is at the C-terminal, the chiral π-π stacking by the phenyl groups of the phenylalanines is suppressed. The hydrogen bonds formed by the NH groups of the phenylalanines had a greater contribution on forming organic self-assemblies than those formed by the NH groups of the phenylglycines. PMID:27389603

  20. Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

    PubMed Central

    O’Keefe, B. Michael; Simmons, Nicholas

    2011-01-01

    A general and mild protocol for achieving the carbonylative cross-coupling of sterically-hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported. PMID:21712966