WorldWideScience

Sample records for act opportunity knocks

  1. EPA and the Federal Technology Transfer Act: Opportunity knocks

    Energy Technology Data Exchange (ETDEWEB)

    Gatchett, A.M.; Fradkin, L.; Moore, M.; Gorman, T.; Ehrlich, A. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    In 1986, the Federal Technology Transfer Act (FTTA) was established to promote a closer, collaborative relationship between federal government agencies and the private sector. With the increasing need for new cost-effective technologies to prevent and control pollution, both the US Environmental Protection Agency (EPA) and private industry are encouraged to facilitate the transfer of knowledge and technology under this Act. The FTTA removed several of the legal and institutional barriers to cooperative research that existed before the Act`s passage. Through the FTTA, the government strives to promote the movement of its products, processes, skills, and knowledge into the private sector for further development and commercialization by encouraging the exchange of technical personnel and the sharing of facilities and other resources. Collaborative efforts between industry, federal agencies, and academia are made possible through cooperative research and development agreements (CRADAs). Forty-two CRADAs and five licensing agreements have been initiated with EPA under this program. This paper provides an overview of this new and innovative program within the EPA. 1 fig., 2 tabs.

  2. Biosimilars lining up to compete with Herceptin--opportunity knocks.

    Science.gov (United States)

    Nelson, Kevin M; Gallagher, Patrick C

    2014-11-01

    Trastuzumab is a monoclonal antibody developed by Genentech as a treatment for breast cancer and gastric cancer when the cancer cells overexpress HER2, a membrane-bound receptor activated by epidermal growth factor. Now marketed by Roche under the trade name Herceptin, trastuzumab has been readily adopted as treatment for some of the most invasive types of breast cancer. The cost for Herceptin is over $50,000 for a full course of treatment. With the development of regulatory pathways for biosimilar products, and the imminent expiry of patents covering Herceptin, several companies have developed biosimilar trastuzumab products. As biosimilar manufacturers look for opportunities to market biosimilar trastuzumab products, Roche has positioned itself to protect its market by developing additional anti-HER2 products complementary to Herceptin. The advent of competition from biosimilars should bring some opportunity for cost savings for patients, as well as incentive for continued advancement in development of better treatments to fight breast cancer.

  3. Opportunities knock: Mediation of peer-relations during meal-time in toddler groups

    Directory of Open Access Journals (Sweden)

    Ellen Os

    2013-11-01

    Full Text Available According to socio-cultural perspectives, adults are seen as mediators of cultural believes, values and practices. Qualitative analyses of teachers’ mediation of peer relations based on video-recordings in 9 toddler-groups indicate that meal-time represents opportunities for teachers to facilitate togetherness and peer-relations between toddlers. The teachers might facilitate sharing, passing food, routinized practices such as singing, and conversations. The results indicate variations between child- and group-oriented approaches, and accomplishing meals in an effective way. The child- and group-oriented approaches are marked by encouragement of toddlers’ initiatives and teachers supporting peer-interactions. Raising teachers’ consciousness about their contributions to children’s development of peer-relations and togetherness in group settings might contribute to enhance reflected practices in working with toddlers in groups.

  4. Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks

    Energy Technology Data Exchange (ETDEWEB)

    Pfestroff, A.; Luster, M. [University Hospital Marburg, Department of Nuclear Medicine, Marburg (Germany); Jilg, C.A. [University Hospital Freiburg, Department of Urology, Freiburg (Germany); Olbert, P.J. [University Hospital Marburg, Department of Urology, Marburg (Germany); Ohlmann, C.H. [Saarland University Hospital, Department of Urology, Homburg/Saar (Germany); Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maecke, H.R. [University Hospital Freiburg, Department of Nuclear Medicine and Radiopharmacy, Freiburg (Germany); Ezziddin, S. [Saarland University Hospital, Department of Nuclear Medicine, Homburg/Saar (Germany); Bodei, L. [European Institute of Oncology, Department of Nuclear Medicine, Milan (Italy); Collaboration: on behalf of the Radionuclide Therapy Committee of the European Association of Nuclear Medicine

    2015-12-15

    {sup 177}Lu-based PSMA-targeted therapy appears to be a promising treatment for advanced PCA. However, lessons should be learned from PRRT of neuroendocrine tumours, which was referred to as a ''promising'' tool for 15 years before the advent of evidence-based comparative studies. This experience strongly suggests that the communities involved with PSMA-targeted therapy, namely nuclear medicine, urology, radiochemistry, and medical physics, should capitalize without delay on the great opportunity to conduct well-designed prospective studies. Doing so should advance this modality from the proof-of principle stage to the potential standard-of-Care-stage. From our perspective, crucial components of this process are: - Harmonization of therapy protocols - Implementation of a patient selection algorithm into clinical routine - Standardization of toxicity assessment - Establishment of standardized dosimetry protocols to assess safety and efficacy - Transfer of expertise in PSMA therapy throughout Europe - Regulatory approval of {sup 177}Lu-PSMA-targeted compounds.

  5. When Opportunity Knocks Twice: Dual Living Kidney Donation, Autonomy and the Public Interest.

    Science.gov (United States)

    Bailey, Phillippa; Huxtable, Richard

    2016-02-01

    Living kidney transplantation offers the best treatment in terms of life-expectancy and quality of life for those with end-stage renal disease. The long-term risks of living donor nephrectomy, although real, are very small, with evidence of good medium-term outcomes. Who should be entitled to donate, and in which circumstances, is nevertheless a live question. We explore the ethical dimensions of a request by an individual to donate both of their kidneys during life: 'dual living kidney donation'. Our ethical analysis is tethered to a hypothetical case study in which a father asks to donate a kidney to each of his twin boys. We explore the autonomy of the protagonists, alongside different dimensions of the public interest, such as the need to protect not only the recipients, but also the donor and even the wider community. Whilst acknowledging objections to 'dual-donation', not least by reference to the harms that the donor might be expected to endure, we suggest there is a prima facie case for permitting this, provided that both donor and recipients are willing and that due attention is paid to such considerations as the autonomy and welfare of all parties, as well as to the wider ramifications of acting on such a request. We argue for broader interpretations of the concepts of autonomy and welfare, recognizing the importance of relationships and the relevance of more than merely physical well-being. Equipped with such a holistic assessment, we suggest there is a prima facie case for allowing 'dual living kidney donation'. © 2015 The Authors. Bioethics Published by John Wiley & Sons Ltd.

  6. 78 FR 42103 - Agency Information Collection Activities: African Growth and Opportunity Act Certificate of Origin

    Science.gov (United States)

    2013-07-15

    ... Opportunity Act Certificate of Origin AGENCY: U.S. Customs and Border Protection, Department of Homeland... accordance with the Paperwork Reduction Act: African Growth and Opportunity Act Certificate of Origin (AGOA...: African Growth and Opportunity Act Certificate of Origin. OMB Number: 1651-0082. Form Number: None...

  7. 75 FR 9423 - Agency Information Collection Activities: African Growth and Opportunity Act Certificate of Origin

    Science.gov (United States)

    2010-03-02

    ... Opportunity Act Certificate of Origin AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland... requirement concerning the African Growth and Opportunity Act Certificate of Origin (AGOA). This request for...: Title: African Growth and Opportunity Act Certificate of Origin. OMB Number: 1651-0082. Form Number...

  8. 78 FR 26650 - Agency Information Collection Activities: African Growth and Opportunity Act Certificate of Origin

    Science.gov (United States)

    2013-05-07

    ... Opportunity Act Certificate of Origin AGENCY: U.S. Customs and Border Protection, Department of Homeland... Certificate of Origin (AGOA). This request for comments is being made pursuant to the Paperwork Reduction Act...: Title: African Growth and Opportunity Act Certificate of Origin. OMB Number: 1651-0082. Form Number...

  9. Statistical Engine Knock Control

    DEFF Research Database (Denmark)

    Stotsky, Alexander A.

    2008-01-01

    A new statistical concept of the knock control of a spark ignition automotive engine is proposed . The control aim is associated with the statistical hy pothesis test which compares the threshold value to the average value of the max imal amplitud e of the knock sensor signal at a given freq uency...... which includ es generation of the amplitud e signals, a threshold value d etermination and a knock sound mod el is d eveloped for evaluation of the control concept....

  10. Higher Education Opportunity Act (Public Law 110-315)

    Science.gov (United States)

    US Congress, 2008

    2008-01-01

    This purpose of this Act is to amend and extend the Higher Education Act of 1965, and for other purposes. This Act includes the following titles: (1) General Provisions; (2) Teacher Quality Enhancement; (3) Institutional Aid; (4) Student Assistance (Grants to Students in Attendance at Institutions of Higher Education, Federal Family Education Loan…

  11. 75 FR 26974 - Agency Information Collection Activities: African Growth and Opportunity Act Certificate of Origin

    Science.gov (United States)

    2010-05-13

    ... Opportunity Act Certificate of Origin AGENCY: U.S. Customs and Border Protection, Department of Homeland... Certificate of Origin (AGOA). This is a proposed extension of an information collection that was previously... forms of information. Title: African Growth and Opportunity Act Certificate of Origin. OMB Number: 1651...

  12. Equal Protection of the Law: The Persons with Disabilities (Equal Opportunities Act, 2014, Bahamas

    Directory of Open Access Journals (Sweden)

    Bernadette Bain

    2016-10-01

    This analysis of the Persons with Disabilities (Equal Opportunities Act, 2014, examines the nature and scope of equal rights and whether the Act provides adequate enforcement. The aim of the provisions is to restrict discrimination against persons with disabilities by providing opportunities on an equal basis and to require persons having dealings with the disabled to accommodate their needs. It is questionable whether the Act fulfils its purpose and whether penalties for failure to comply with the Act are adequate, as there is a lacuna or gap in the law, which hinders purposeful rights.

  13. The Mental Health Care Act: challenges and opportunities

    African Journals Online (AJOL)

    Adele

    The Mental Health Care Act was promulgated in December 2004. Although this was not unexpected, the timing had certainly not been anticipated. Overnight the mental health care landscape was transformed. Not only had all of our professional designations been collapsed into a single entity of “mental health.

  14. 75 FR 70342 - Privacy Act; System of Records: Equal Employment Opportunity Records

    Science.gov (United States)

    2010-11-17

    ... disabled. RETENTION AND DISPOSAL: Records are retired or destroyed in accordance with published records... Act; System of Records: Equal Employment Opportunity Records SUMMARY: Notice is hereby given that the Department of State proposes to amend an existing system of records, Equal Employment Opportunity Records...

  15. 76 FR 41434 - Removal of Certain Requirements Related to the Prescription Drug Marketing Act; Opportunity for...

    Science.gov (United States)

    2011-07-14

    ... the Prescription Drug Marketing Act; Opportunity for Public Comment AGENCY: Food and Drug... remove a section of the Prescription Drug Marketing Act (PDMA) regulations requiring that prior to the... the purchaser ``a statement identifying each prior sale, purchase, or trade of such drug,'' starting...

  16. Education Issues Raised by S.744: The Border Security, Economic Opportunity, and Immigration Modernization Act

    Science.gov (United States)

    Murphy, Garrett

    2014-01-01

    This brief report summarizes the requirements for undocumented immigrants set forth by the Border Security, Economic Opportunity, and Immigration Modernization Act (S.744). Assuming that S.744 will move forward in Congress, the report also examines issues having to do with certain language, civics and government, and education/training provisions…

  17. When a Leadership Opportunity Knocks, Answer!

    Science.gov (United States)

    DelGuidice, Margaux

    2011-01-01

    In the fall of 2010 the author received an e-mail informing her that she has been selected as a Gale/Cengage New Leader, which was a true honor. Not only would she be joining four dynamic school librarians from around the country at the School Library Journal Summit on the Future of Reading, she was also being paired with a mentor to navigate her…

  18. Opportunities for social work under the Affordable Care Act: A call for action.

    Science.gov (United States)

    Lynch, Sean; Greeno, Catherine; Teich, Judith; Delany, Peter

    2016-10-01

    The Affordable Care Act (ACA) has profoundly restructured American health care. Numerous social work authors have commented on the importance of the ACA's reforms to social work practice, education, and research. This article summarizes the literature, adds relevant information, and makes recommendations for future actions. The policy, opinion, and peer-reviewed literatures were systematically reviewed. Sixty-three publications appeared between 2010 and 2015 are included. Five themes emerged, as follows: 1) the crucial provisions of the ACA, 2) the natural affinity of social work and the ACA reforms, 3) curricular adaptations needed to address changing workforce needs, 4) areas for continued social work advocacy, and 5) opportunities for high-impact social work research. This article provides a comprehensive introduction to the ACA, its reforms, and opportunities for social work to assume a high visibility leadership role in implementing the reforms, with particular emphasis on needed curricular changes and opportunities for research.

  19. Granite Rock Company; Proposed Settlement of Clean Water Act Class II Administrative Penalty Matter and Opportunity to Comment

    Science.gov (United States)

    Public Notice of Proposed Settlement of Clean Water Act Class II Administrative Penalty Matter and Opportunity to Comment In the Matter of Granite Rock Company, 350 Technology Drive, Watsonville, CA 95076

  20. Workplace Discrimination and Visual Impairment: A Comparison of Equal Employment Opportunity Commission Charges and Resolutions under the Americans with Disabilities Act and Americans with Disabilities Amendments Act

    Science.gov (United States)

    Victor, Callie M.; Thacker, Leroy R.; Gary, Kelli W.; Pawluk, Dianne T. V.; Copolillo, Al

    To guarantee equal opportunities and treatment in employment for individuals with disabilities, Congress enacted Title I of the Americans with Disabilities Act (ADA) in 1992. This law states, "No covered entity shall discriminate against a qualified individual on the basis of disability in regard to job application procedures, the hiring,…

  1. The Science of Hard Knocks

    Science.gov (United States)

    Vance, Erik

    2007-01-01

    Head injuries in sports are nothing new, but in recent years, college athletes have reported a steady rise in concussions. Football players still get the most knocks to the head. Women have managed to keep up with, and often surpass, men in sports-related concussions in the last few years. In basketball, women reported 24 percent more concussions…

  2. Healthy, Hunger-Free Kids Act of 2010: An Opportunity for School Nurses to Make a Difference

    Science.gov (United States)

    Prokop, Jessica L.; Galon, Patricia

    2011-01-01

    Implementation of the Healthy Hunger-Free Kids Act of 2010 will provide an opportunity for school nurses to intervene in the serious childhood obesity problem in the United States. Major changes in the management of the National School Lunch Program (NSLP) will likely challenge schools yet may provide the impetus for a collaborative effort by the…

  3. School to Work Opportunities Act Policy--An Effort at Backward Mapping

    Directory of Open Access Journals (Sweden)

    Arthur M. Recesso

    1999-03-01

    Full Text Available This study examined the intent of federal policy and the actual implementation within local school districts. Specifically, the focus is on the Federal School to Work Opportunities Act of 1994 and its implementation in 47 school districts in upstate New York as part of a consortium during the 1995-96 school year. The purpose of the study was to determine 1 the extent to which an agreement to participate in a consortium arrangement designed to facilitate the implementation of a specific Federal or state policy resulted in the active implementation efforts by individual consortium members, and 2 how a high school setting where School to Work activities were perceived by local stakeholders as having great specific and important effects differed from a high school setting where School to Work activities were perceived by local stakeholders as having some or no effect. A bottom-up backward mapping policy analysis model was used for the purposes of this study. Local level data was used to create performance, environment, technology implementation, and School to Work implementation profiles of local high schools. Regression and correlation analyses were used to determine the relationship between stakeholder perceptions and local high school characteristics. Results of the study were reported and interpreted with the aim of furthering research and knowledge of policy analysis and the use of local level data to determine the success of policy implementation. This study found that variation between federal intent and local adaptation is explained by characteristics of the high school and perceptions of stakeholders. School to Work policy implementation, perceived by the high school administrator as a stakeholder, varied significantly by high school student performance, environment in which the high school operates, and level of technology implementation in the high school. Results indicated that the backward mapping policy analysis model is effective in

  4. Exclusivity strategies and opportunities in view of the Biologics Price Competition and Innovation Act.

    Science.gov (United States)

    Gaudry, Kate S

    2011-01-01

    Government-provided exclusivity periods provide pharmaceutical companies with incentives to invest in new drugs. Meanwhile, encouraging competition serves another worthy goal of improving the affordability of medications. Decades ago, the Hatch-Waxman Act set forth provisions attempting to balance these objectives in the context of small-molecule drugs. Recently, the Biologics Price Competition and Innovation Act was enacted to meet similar aims in the context of biologic drugs. This article presents a detailed comparison of these two Acts. While the Acts share many global similarities (e.g., providing exclusivity terms and abbreviated approval processes), many differences are also apparent when analyzing details of the provisions. One area of great departure between the Acts is the requirements of how a generic or follow-on applicant must address patents covering a reference product. After describing these differences, the article presents predictions of how reference product sponsors will adapt their patent-prosecution strategies in view of the new Biologics Act.

  5. 78 FR 76212 - Patient Protection and Affordable Care Act; Maximizing January 1, 2014 Coverage Opportunities

    Science.gov (United States)

    2013-12-17

    ... enacted on March 23, 2010. The Health Care and Education Reconciliation Act of 2010 (Pub. L. 111-152... CMS's belief that this interim final rule does not reach this economic threshold and thus is not..., Sunshine Act, Technical Assistance, Women, and Youth. For the reasons set forth in the preamble, the...

  6. Opportunities and Accountability To Leave No Child Behind in the Middle Grades: An Examination of the "No Child Left Behind Act of 2001."

    Science.gov (United States)

    Brown, Cynthia G.

    The No Child Left Behind Act of 2001 reauthorized and significantly expanded the Elementary and Secondary Education Act. The Act and its accompanying fund increases offer numerous opportunities to improve teaching and achievement of young adolescents, targeting federal money more than ever to high poverty schools and districts and including…

  7. CRISPR/Cas9-Mediated Zebrafish Knock-in as a Novel Strategy to Study Midbrain-Hindbrain Boundary Development

    Science.gov (United States)

    Kesavan, Gokul; Chekuru, Avinash; Machate, Anja; Brand, Michael

    2017-01-01

    The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns. In contrast, CRISPR/Cas9-mediated genome editing technology now provides a great opportunity to efficiently knock-in or knock-out genes. We have generated four CRISPR/Cas9-based knock-in fluorescent reporter lines for two crucial genes involved in MHB development, namely otx2 and pax2a. The coding sequences of the reporters were knocked-in upstream of the corresponding ATG and are, thus, under the control of the endogenous promoter/enhancer elements. Interestingly, this strategy does not disturb endogenous gene expression. Using the fast maturing fluorescent protein reporter, Venus, enabled us to follow MHB development using cell tracking and live imaging. In addition, we show that these reporter lines label various neuronal and glial cell types in the adult zebrafish brain, making them highly suitable for investigating embryonic and adult midbrain, hindbrain, and MHB development. PMID:28713249

  8. Protein-tyrosine kinase activity profiling in knock down zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Simone Lemeer

    Full Text Available BACKGROUND: Protein-tyrosine kinases (PTKs regulate virtually all biological processes. PTKs phosphorylate substrates in a sequence-specific manner and relatively short peptide sequences determine selectivity. Here, we developed new technology to determine PTK activity profiles using peptide arrays. The zebrafish is an excellent model system to investigate signaling in the whole organism, given its wealth of genetic tools, including morpholino-mediated knock down technology. We used zebrafish embryo lysates to determine PTK activity profiles, thus providing the unique opportunity to directly compare the effect of protein knock downs on PTK activity profiles on the one hand and phenotypic changes on the other. METHODOLOGY: We used multiplex arrays of 144 distinct peptides, spotted on a porous substrate, allowing the sample to be pumped up and down, optimizing reaction kinetics. Kinase reactions were performed using complex zebrafish embryo lysates or purified kinases. Peptide phosphorylation was detected by fluorescent anti-phosphotyrosine antibody binding and the porous chips allowed semi-continuous recording of the signal. We used morpholinos to knock down protein expression in the zebrafish embryos and subsequently, we determined the effects on the PTK activity profiles. RESULTS AND CONCLUSION: Reproducible PTK activity profiles were derived from one-day-old zebrafiish embryos. Morpholino-mediated knock downs of the Src family kinases, Fyn and Yes, induced characteristic phenotypes and distinct changes in the PTK activity profiles. Interestingly, the peptide substrates that were less phosphorylated upon Fyn and Yes knock down were preferential substrates of purified Fyn and Yes. Previously, we demonstrated that Wnt11 knock down phenocopied Fyn/Yes knock down. Interestingly, Wnt11 knock down induced similar changes in the PTK activity profile as Fyn/Yes knock down. The control Nacre/Mitfa knock down did not affect the PTK activity profile

  9. Superfund Reauthorization 1994: DoD’s Opportunity to Clean Up Its Hazardous Waste Act

    Science.gov (United States)

    1994-04-01

    more mundane utilitarian considerations, it is characteristic of man to bury that which he fears and 36 Albert Schweitzer, quoted in RACHEL CARSON ... SILENT SPRING i (1962). 123 wishes to rid himself of. In today’s industrialized society, however, the routine practice of burying highly toxic chemical...critics have dubbed CERCLA the "full employment act for lawyers." Rachel Giesber, Note, Foolish Consistency? Compliance with the National Contingency Plan

  10. Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Leslie Toby

    2008-12-01

    Full Text Available Abstract Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities.

  11. The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?

    Science.gov (United States)

    Wellman-Labadie, Olivier; Zhou, Youwen

    2010-05-01

    This study investigates issues associated with the United States Orphan Drug Act. A comprehensive orphan drug database was compiled from FDA data and corporate annual reports of major pharmaceutical companies. Analysis allowed the generation of a descriptive orphan drug portrait as well as documentation of orphan drugs along their lifecycle. Currently, 2002 products have obtained orphan drug designation with 352 drugs obtaining FDA approval. Approximately 33% of orphan drugs are oncology products. On average, products obtain 1.7 orphan designations with approximately 70% obtaining a single designation. At least 9% of orphan drugs have reached blockbuster status with two-thirds having two or more designations. An additional 25 orphan drugs had sales exceeding US$ 100 million in 2008 alone. Since 1983, at least 14 previously discontinued products have been recycled as orphan drugs. The United States Orphan Drug Act has created issues which, in some cases, have led to commercial and ethical abuses. Orphan Drug Act reform is necessary but current incentives, including 7 year market exclusivity, should be maintained in order to favour patients as well as economic prosperity. Suggested reforms include price regulation, subsidy paybacks for profitable drugs and the establishment of an International Orphan Drug Office. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Opportunity knocks - the sustainable energy industry and climate change

    Energy Technology Data Exchange (ETDEWEB)

    Price, B.; Keegan, P. [International Institute for Energy Conservation, Washington, DC (United States)

    1997-12-31

    Climate change mitigation, if intelligently undertaken, can stimulate economic growth. The main tools available for this task are energy efficiency, renewable energy, and clean energy technologies and services, which are collectively known as sustainable energy. To unleash this potential, the US and other governments need the full cooperation of the sustainable energy industry. This industry knows more than most other about turning energy-related pollution prevention into profits. If engaged, they can help: (1) Identify the economic benefits of greenhouse gas mitigation; (2) Identify barriers to the implementation of greenhouse gas mitigation projects; (3) Develop policies and measures to overcome these barriers; and (4) Implement greenhouse gas mitigation projects. 7 refs.

  13. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy.

    Science.gov (United States)

    Owen, Andrew; Rannard, Steve

    2016-08-01

    Advances in solid drug nanoparticle technologies have resulted in a number of long-acting (LA) formulations with the potential for once monthly or longer administration. Such formulations offer great utility for chronic diseases, particularly when a lack of medication compliance may be detrimental to treatment response. Two such formulations are in clinical development for HIV but the concept of LA delivery has its origins in indications such as schizophrenia and contraception. Many terms have been utilised to describe the LA approach and standardisation would be beneficial. Ultimately, definitions will depend upon specific indications and routes of delivery, but for HIV we propose benchmarks that reflect perceived clinical benefits and available data on patient attitudes. Specifically, we propose dosing intervals of ≥1week, ≥1month or ≥6months, for oral, injectable or implantable strategies, respectively. This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications. Key technological challenges such as the need for consistency and ease of administration for drug combinations, are also discussed. Finally, the review explores the gaps in knowledge regarding the pharmacology of drug release from particulate-based LA injectable suspensions. A number of hypotheses are discussed based upon available data relating to local drug metabolism, active transport systems, the lymphatics, macrophages and patient-specific factors. Greater knowledge of the mechanisms that underpin drug release and protracted exposure will help facilitate further development of this strategy to achieve the promising clinical benefits. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Opportunity Design

    DEFF Research Database (Denmark)

    Nielsen, Louise Møller; Lassen, Astrid Heidemann; Tollestrup, Christian

    2012-01-01

    or development oriented, the act of ‘recognition’ is still a central part of the definition. Recently the term “Opportunity Design” has been introduced, suggesting that opportunities can be proactively and intentionally designed. However, the relatedness between the opportunity recognition process...... and opportunity design is not clear. Furthermore, there is still a lack of approaches, methods and tools, which can support entrepreneurs in designing the entrepreneurial opportunities. In this paper, we take steps towards defining opportunity design in respect to the opportunity recognition process, and identify...... some of the specific approaches applicable to the design of opportunities. By looking at industrial designers working with entrepreneurial opportunities, it becomes evident that there is a set of approaches, which can turn the opportunity recognition process into an intentional and proactive process....

  15. Dual Acting Neuraminidase Inhibitors Open New Opportunities to Disrupt the Lethal Synergism between Streptococcus pneumoniae and Influenza Virus

    Directory of Open Access Journals (Sweden)

    Elisabeth eWalther

    2016-03-01

    Full Text Available Secondary infections with Streptococcus pneumoniae cause severe pneumonia and enhance lethality during influenza epidemics and pandemics. Structural and functional similarities with viral neuraminidase (NA suggest that the highly prevalent pneumococcal NAs, NanA and NanB, might contribute to this lethal synergism by supporting viral replication and that dual acting NA inhibitors (NAIs will disrupt it. To verify this hypothesis, NanA and NanB were expressed in E. coli. After confirming their activity in enzyme assays, in vitro models with influenza virus A/Jena/8178/09 (Jena/8178 and the recombinant NanA or NanB (rNanA and rNanB were established in A549 and MDCK cells to mimic the role of these pneumococcal NAs during co-infection. Studies on the influence of both NAs on viral receptor expression, spread, and yield revealed a distinct effect of NanA and NanB on viral replication in these in vitro models. Both enzymes were able to support Jena/8178 replication at certain concentrations. This synergism was disrupted by the NAIs oseltamivir, DANA, katsumadain A, and artocarpin exerting an inhibitory effect on viral NA and NanA. Interestingly, katsumadain A and artocarpin inhibited rNanA and rNanB similarly. Zanamivir did not show activity. These results demonstrate a key role of pneumococcal NAs in the lethal synergism with influenza viruses and reveal opportunities for its effective disruption.

  16. Knocking in an Internal-combustion Engine

    Science.gov (United States)

    Sokolik, A; Voinov, A

    1940-01-01

    The question remains open of the relation between the phenomena of knocking in the engine and the explosion wave. The solution of this problem is the object of this paper. The tests were conducted on an aircraft engine with a pyrex glass window in the cylinder head. Photographs were then taken of various combinations of fuels and conditions.

  17. The Cost-Effectiveness of Baccalaureate Programs at Two-Year Public Colleges: A Policy Option to Support the Virginia Higher Education Opportunity Act of 2011

    Science.gov (United States)

    Davis, Christopher Scott

    2012-01-01

    The unanimous passing of the Virginia Higher Education Opportunity Act of 2011 highlights the need to create a cost-effective pathway to baccalaureate degree growth. Using an exploratory case study design, this study compared the cost-effectiveness of two baccalaureate degree programs offered by institutions in the State University System of…

  18. The Clean Air Act Amendments of 1990: Opportunities for Promoting Renewable Energy; Final Report: December 11, 2000

    Energy Technology Data Exchange (ETDEWEB)

    Wooley, D.R.; Morss, E.M. (Young, Sommer, Ward, Ritzenberg, Wooley, Baker and Moore, LLC, Albany, New York)

    2001-01-08

    This report explores key aspects of the intersection between the nation's clean air and energy goals and proposes alternatives for encouraging renewable energy in the context of the federal Clean Air Act (CAA). As with most environmental statutes enacted in the early 1970s, the 1970 CAA embraced a somewhat rigid ''command-and-control'' approach to achieving its clean air goals. Although effective, this approach has been criticized for discouraging creative and cost-effective solutions to reducing air emissions. In response to this concern, Congress included the first significant market-based program to address an environmental problem-in this case, acid rain caused by sulfur dioxide (SO2) emissions from power plants-in the 1990 CAA Amendments. This program prompted the federal government and various state governments to pursue other market-based programs to address air pollution problems. Ten years have elapsed since the passage of the 1990 CAA Amendments, so the time is ripe to consider expanding opportunities for renewable energy development in the reform of clean air policies. A significant potential for renewables exists in conjunction with international efforts to reduce emissions of greenhouse gases (GHG), including CO2. Unfortunately, Congressional opposition to international GHG reduction agreements makes it difficult to develop GHG emission-reduction programs, including a cap-and-trade alternative, that would enable the renewables industry to harness this potential. The renewable industry can, however, track developments both nationally and internationally to ensure that the programs developed adequately address renewables.

  19. Knock characteristics of dual-fuel combustion in diesel engines ...

    Indian Academy of Sciences (India)

    This paper investigates the combustion knock characteristics of diesel engines running on natural gas using pilot injection as means of initiating combustion. The diesel engines knock under normal operating conditions but the knock referred to in this paper is an objectionable one. In the dual-fuel combustion process we ...

  20. The validity of knock-for-knock clauses in comparative perspective

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    This article discusses the validity of so-called knock-for-knock clauses, by which parties to offshore oil and gas or maritime contracts agree that each of them will cover its own losses regardless of who caused them. The issue of validity of such clauses and of the liability exclusions they cont......This article discusses the validity of so-called knock-for-knock clauses, by which parties to offshore oil and gas or maritime contracts agree that each of them will cover its own losses regardless of who caused them. The issue of validity of such clauses and of the liability exclusions...... they contain is analyzed in a comparative perspective between the law of their tradition of origin (common law, especially UK law) and Nordic civil law, where such agreements are also frequently used, namely in the context of oil extraction activities in the North Sea. Based on an assessment of the different...... on the efficiency of mechanisms supposed to replace the deterrence effect of tort or contractual liability....

  1. 76 FR 54772 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

    Science.gov (United States)

    2011-09-02

    ... Funding, Funding Opportunity Announcement CDC-RFA-DP08-805 AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This notice provides notice of CDC's intent to fund continuation cooperative agreement applications under the Nutrition...

  2. 76 FR 54774 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

    Science.gov (United States)

    2011-09-02

    ... Funding, Funding Opportunity Announcement CDC-RFA-DP10-1014 AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This notice provides notice of CDC's intent to fund continuation cooperative agreement applications under REACH CORE...

  3. 76 FR 54773 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

    Science.gov (United States)

    2011-09-02

    ... Funding, Funding Opportunity Announcement CDC-RFA-DP07-707 AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This notice provides notice of CDC's intent to fund continuation cooperative agreement applications under REACH US...

  4. A window of opportunity: maximizing the effectiveness of new HCV regimens in the United States with the expansion of the Affordable Care Act.

    Science.gov (United States)

    Haley, Sean J; Kreek, Mary Jeanne

    2015-03-01

    Patients with chronic HCV have predictable overlapping comorbidities that reduce access to care. The Affordable Care Act (ACA) presents an opportunity to focus on the benefits of the medical home model for integrated chronic disease management. New, highly effective HCV treatment regimens in combination with the medical home model could reduce disease prevalence. We sought to address challenges posed by comorbidities in patients with chronic HCV infection and limitations within our health care system, and recommend solutions to maximize the public benefit from ACA and the new drug regimen.

  5. Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA); interpretation of "federal means-tested public benefit"--HHS. Notice with comment period.

    Science.gov (United States)

    1997-08-26

    This notice with comment period interprets the term "Federal means-tested public benefit[s]" as used in Title IV of the Personal Responsibility and work Opportunity Reconciliation Act of 1996 (PRWORA), Pub. L. 104-193, to include only mandatory spending programs of the Federal Government in which eligibility for the program's benefits, or the amount of such benefits or both, are determined on the basis of income or resources of the eligibility unit seeking the benefit. At HHS, the benefit programs that fall within this definition (and are not explicitly excerted from the definition by Section 403 (c)) are Medicaid and Temporary Assistance for Needy Families (TANF).

  6. knock characteristics analysis of a supercharged spark ignition

    African Journals Online (AJOL)

    user

    The power output of a spark ignition engine could be improved by boosting the intake pressure and compression ratio; however the applications of these are limited by knock in engines. This study examined the knocking behaviours of three commercially available fuels for spark ignition engines operated at engine intake ...

  7. Knock characteristics analysis of a supercharged spark Ignition ...

    African Journals Online (AJOL)

    This study examined the knocking behaviours of three commercially available fuels for spark ignition engines operated at engine intake pressures of 1.6 and 2.0 bar. The pressure data for the fuels tested were grouped into three: the fast cycle, medium cycle and slow cycles. Knock intensities from the pressure data were ...

  8. knock characteristics analysis of a supercharged spark ignition

    African Journals Online (AJOL)

    user

    and manufacturing of spark ignition engines with improved performance. Understanding factors influencing knock in spark ignition engines will help designers understand how to manage knock in engines. Various designs over the years have been introduced in internal combustion engines with the aim of improving.

  9. Characteristics of Knock in Hydrogen-Oxygen-Argon SI Engine

    Energy Technology Data Exchange (ETDEWEB)

    Killingsworth, N; Rapp, V; Flowers, D; Aceves, S; Chen, J; Dibble, R

    2010-02-23

    A promising approach for improving the efficiency of internal combustion engines is to employ a working fluid with a high specific heat ratio such as the noble gas argon. Moreover, all harmful emissions are eliminated when the intake charge is composed of oxygen, nonreactive argon, and hydrogen fuel. Previous research demonstrated indicated thermal efficiencies greater than 45% at 5.5 compression ratio in engines operating with hydrogen, oxygen, and argon. However, knock limits spark advance and increasing the efficiency further. Conditions under which knock occurs in such engines differs from typical gasoline fueled engines. In-cylinder temperatures using hydrogen-oxygen-argon are higher due to the high specific heat ratio and pressures are lower because of the low compression ratio. Better understanding of knock under these conditions can lead to operating strategies that inhibit knock and allow operation closer to the knock limit. In this work we compare knock with a hydrogen, oxygen, and argon mixture to that of air-gasoline mixtures in a variable compression ratio cooperative fuels research (CFR) engine. The focus is on stability of knocking phenomena, as well as, amplitude and frequency of the resulting pressure waves.

  10. Challenges and opportunities in building a sustainable rural primary care workforce in alignment with the Affordable Care Act: the WWAMI program as a case study.

    Science.gov (United States)

    Allen, Suzanne M; Ballweg, Ruth A; Cosgrove, Ellen M; Engle, Kellie A; Robinson, Lawrence R; Rosenblatt, Roger A; Skillman, Susan M; Wenrich, Marjorie D

    2013-12-01

    The authors examine the potential impact of the Patient Protection and Affordable Care Act (ACA) on a large medical education program in the Northwest United States that builds the primary care workforce for its largely rural region. The 42-year-old Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) program, hosted by the University of Washington School of Medicine, is one of the nation's most successful models for rural health training. The program has expanded training and retention of primary care health professionals for the region through medical school education, graduate medical education, a physician assistant training program, and support for practicing health professionals.The ACA and resulting accountable care organizations (ACOs) present potential challenges for rural settings and health training programs like WWAMI that focus on building the health workforce for rural and underserved populations. As more Americans acquire health coverage, more health professionals will be needed, especially in primary care. Rural locations may face increased competition for these professionals. Medical schools are expanding their positions to meet the need, but limits on graduate medical education expansion may result in a bottleneck, with insufficient residency positions for graduating students. The development of ACOs may further challenge building a rural workforce by limiting training opportunities for health professionals because of competing demands and concerns about cost, efficiency, and safety associated with training. Medical education programs like WWAMI will need to increase efforts to train primary care physicians and increase their advocacy for student programs and additional graduate medical education for rural constituents.

  11. Opportunities for Energy Development in Water Conduits: A Report Prepared in Response to Section 7 of the Hydropower Regulatory Efficiency Act of 2013

    Energy Technology Data Exchange (ETDEWEB)

    Sale, Michael J. [BCS, Incorporated, Laurel, MD (United States); Bishop, Norman A. [Knight Piesold, Chicago, IL (United States); Reiser, Sonya L. [Knight Piesold, Chicago, IL (United States); Johnson, Kurt [Telluride Energy LLC, Grand Junction, CO (United States); Bailey, Andrea C. [BCS, Incorporated, Laurel, MD (United States); Frank, Anthony [BCS, Incorporated, Laurel, MD (United States); Smith, Brennan T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Environmental Sciences Division

    2014-09-01

    In Section 7 of the Hydropower Regulatory Efficiency Act (HREA) of 2013 (P.L. 113-23), Congress directed the U.S. Department of Energy (DOE) to prepare an analysis of conduit hydropower opportunities available in the United States and to present case studies that describe the potential energy generation from these types of hydropower projects. Those analyses have been included in a new DOE report to Congress, and this ORNL/TM provides additional technical details supporting that report. Conduit hydropower offers important new ways to enhance renewable energy portfolios in the United States, as well as to increase the energy efficiency of water delivery systems. Conduit hydropower projects are constructed on existing water-conveyance structures, such as irrigation canals or pressurized pipelines that deliver water to municipalities, industry, or agricultural water users. Although water conveyance infrastructures are usually designed for non-power purposes, new renewable energy can often be harvested from them without affecting their original purpose and without the need to construct new dams or diversions. Conduit hydropower differs from more conventional hydropower development in that it is generally not located on natural rivers or waterways and therefore does not involve the types of environmental impacts that are associated with hydropower. The addition of hydropower to existing water conduits can provide valuable new revenue sources from clean, renewable energy. The new energy can be used within the existing water distribution systems to offset other energy demands, or it can be sold into regional transmission systems.

  12. Commentary: Personalized health planning and the Patient Protection and Affordable Care Act: an opportunity for academic medicine to lead health care reform.

    Science.gov (United States)

    Dinan, Michaela A; Simmons, Leigh Ann; Snyderman, Ralph

    2010-11-01

    The Patient Protection and Affordable Care Act of 2010 (PPACA) mandates the exploration of new approaches to coordinated health care delivery--such as patient-centered medical homes, accountable care organizations, and disease management programs--in which reimbursement is aligned with desired outcomes. PPACA does not, however, delineate a standardized approach to improve the delivery process or a specific means to quantify performance for value-based reimbursement; these details are left to administrative agencies to develop and implement. The authors propose that coordinated care can be implemented more effectively and performance quantified more accurately by using personalized health planning, which employs individualized strategic health planning and care relevant to the patient's specific needs. Personalized health plans, developed by providers in collaboration with their patients, quantify patients' health and health risks over time, identify strategies to mitigate risks and/or treat disease, deliver personalized care, engage patients in their care, and measure outcomes. Personalized health planning is a core clinical process that can standardize coordinated care approaches while providing the data needed for performance-based reimbursement. The authors argue that academic health centers have a significant opportunity to lead true health care reform by adopting personalized health planning to coordinate care delivery while conducting the research and education necessary to enable its broad clinical application.

  13. Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA); interpretation of "federal public benefit"--HHS. Notice with comment period.

    Science.gov (United States)

    1998-08-04

    This notice with comment period interprets the term "Federal public benefit" as used in Title IV of the Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA), Pub. L. 104-193, and identifies the HHS programs that provide such benefits under this interpretation. According to section 401 if PRWORA, aliens who are not "qualified aliens" are not eligible for any "Federal public benefit," unless the "Federal public benefit" falls within a specified exception. A "Federal public benefit" includes "any grant, contract, loan, professional license, or commercial license" provided to an individual, and also "any retirement, welfare, health, disability, public or assisted housing, postsecondary education, food assistance, unemployment benefit, or any other similar benefit for which payments or assistance are provided to an individual, household, or family eligibility unit." Under section 432, providers of a non-exempt "Federal public benefit" must verify that a person applying for the benefit is a qualified alien and is eligible to receive the benefit. The HHS programs that provide "Federal public benefits" and are not otherwise excluded from the definition by the exceptions provided in section 401(b) are: Adoption Assistance Administration on Developmental Disabilities (ADD)-State Developmental Disabilities Councils (direct services only) ADD-Special Projects (direct services only) ADD-University Affiliated Programs (clinical disability assessment services only) Adult Programs/Payments to Territories Agency for Health Care Policy and Research Dissertation Grants Child Care and Development Fund Clinical Training Grant for Faculty Development in Alcohol & Drug Abuse Foster Care Health Profession Education and Training Assistance Independent Living Program Job Opportunities for Low Income Individuals (JOLI) Low Income Home Energy Assistance Program (LIHEAP) Medicare Medicaid (except assistance for an emergency medical condition) Mental Health Clinical

  14. The Computational Complexity of the Parallel Knock-Out Problem

    NARCIS (Netherlands)

    Broersma, Haitze J.; Johnson, M.; Paulusma, Daniël; Stewart, I.A.; Correa, J.R.; Hevia, A.; Kiwi, M.

    2006-01-01

    We consider computational complexity questions related to parallel knock-out schemes for graphs. In such schemes, in each round, each remaining vertex of a given graph eliminates exactly one of its neighbours. We show that the problem of whether, for a given graph, such a scheme can be found that

  15. Knock Prediction Using a Simple Model for Ignition Delay

    KAUST Repository

    Kalghatgi, Gautam

    2016-04-05

    An earlier paper has shown the ability to predict the phasing of knock onset in a gasoline PFI engine using a simple ignition delay equation for an appropriate surrogate fuel made up of toluene and PRF (TPRF). The applicability of this approach is confirmed in this paper in a different engine using five different fuels of differing RON, sensitivity, and composition - including ethanol blends. An Arrhenius type equation with a pressure correction for ignition delay can be found from interpolation of previously published data for any gasoline if its RON and sensitivity are known. Then, if the pressure and temperature in the unburned gas can be estimated or measured, the Livengood-Wu integral can be estimated as a function of crank angle to predict the occurrence of knock. Experiments in a single cylinder DISI engine over a wide operating range confirm that this simple approach can predict knock very accurately. The data presented should enable engineers to study knock or other auto-ignition phenomena e.g. in premixed compression ignition (PCI) engines without explicit chemical kinetic calculations. © Copyright 2016 SAE International.

  16. William Knocke receives 2008 Virginia Outstanding Civil Engineer Award

    OpenAIRE

    Daniilidi, Christina

    2008-01-01

    William R. Knocke, W.C. English Professor and head of the Charles E. Via, Jr. Department of Civil and Environmental Engineering at Virginia Tech, was awarded the 2008 Virginia Outstanding Civil Engineer Award at the Virginia Section of the American Society of Civil Engineers' (ASCE) banquet, held recently in Williamsburg, Va.

  17. Zika virus infection of adult and fetal STAT2 knock-out hamsters.

    Science.gov (United States)

    Siddharthan, Venkatraman; Van Wettere, Arnaud J; Li, Rong; Miao, Jinxin; Wang, Zhongde; Morrey, John D; Julander, Justin G

    2017-07-01

    Zika virus (ZIKV) infection was investigated in adult and fetal STAT2 knock-out (KO) hamsters. Subcutaneous injection of ZIKV of adults resulted in morbidity, mortality, and infection of the uterus, placenta, brain, spinal cord, and testicles, thus providing an opportunity to evaluate congenital ZIKV infection in a second rodent species besides mice. ZIKV-infected cells with morphologies of Sertoli cells and spermatogonia were observed in the testes, which may have implications for sexual transmission and male sterility. Neonates exposed as fetuses to ZIKV at 8 days post-coitus were not smaller than controls. Nevertheless, infectious virus and ZIKV RNA was detected in some, but not all, placentas and fetal brains of KO hamsters. STAT2 KO hamsters may be useful for addressing sexual transmission, pathogenesis, routes of fetal infection, and neurological disease outcomes, and may also be used in antiviral or vaccine studies to identify intervention strategies. Copyright © 2017. Published by Elsevier Inc.

  18. Ionization in the Knock Zone of an Internal-combustion Engine

    Science.gov (United States)

    Hasting, Charles E

    1940-01-01

    The ionization in the knock zone of an internal-combustion engine was investigated. A suspected correlation between the intensity of knock and the degree of ionization was verified and an oscillation in the degree of ionization corresponding in frequency to the knock vibrations in the cylinder pressure was observed.

  19. Opportunity versus Necessity

    OpenAIRE

    Calderon, Gabriela; Iacovone, Leonardo; Juarez, Laura

    2016-01-01

    Entrepreneurs that voluntarily choose to start a business because they are able to identify a good business opportunity and act on it -- opportunity entrepreneurs -- might be different along various dimensions from those who are forced to become entrepreneurs because of lack of other alternatives -- necessity entrepreneurs. To provide evidence on these differences, this paper exploits a un...

  20. Evaluation of Knock Behavior for Natural Gas - Gasoline Blends in a Light Duty Spark Ignited Engine

    Energy Technology Data Exchange (ETDEWEB)

    Pamminger, Michael [Argonne National Lab. (ANL), Argonne, IL (United States); Sevik, James [Argonne National Lab. (ANL), Argonne, IL (United States); Scarcelli, Riccardo [Argonne National Lab. (ANL), Argonne, IL (United States); Wallner, Thomas [Argonne National Lab. (ANL), Argonne, IL (United States); Wooldridge, Steven [Ford Motor Co., Detroit, MI (United States); Boyer, Brad [Ford Motor Co., Detroit, MI (United States); Hall, Carrie M. [Illinois Inst. of Technology, Chicago, IL (United States)

    2016-10-17

    The compression ratio is a strong lever to increase the efficiency of an internal combustion engine. However, among others, it is limited by the knock resistance of the fuel used. Natural gas shows a higher knock resistance compared to gasoline, which makes it very attractive for use in internal combustion engines. The current paper describes the knock behavior of two gasoline fuels, and specific incylinder blend ratios with one of the gasoline fuels and natural gas. The engine used for these investigations is a single cylinder research engine for light duty application which is equipped with two separate fuel systems. Both fuels can be used simultaneously which allows for gasoline to be injected into the intake port and natural gas to be injected directly into the cylinder to overcome the power density loss usually connected with port fuel injection of natural gas. Adding natural gas at wide open throttle helps to reduce knock mitigating measures and increases the efficiency and power density compared to the other gasoline type fuels with lower knock resistance. The used methods, knock intensity and number of pressure waves, do not show significant differences in knock behavior for the natural gas - gasoline blends compared to the gasoline type fuels. A knock integral was used to describe the knock onset location of the fuels tested. Two different approaches were used to determine the experimental knock onset and were compared to the knock onset delivered by the knock integral (chemical knock onset). The gasoline type fuels show good agreement between chemical and experimental knock onset. However, the natural gas -gasoline blends show higher discrepancies comparing chemical and experimental knock onset.

  1. When Opportunity Only Knocks Once: Lessons From Gen Petraeus In Iraq And Afghanistan

    Science.gov (United States)

    2016-03-01

    civilian control.32 Firing a capable commander like McChrystal placed pressure on the Obama administration to both select the right commander that...could bring success to an administration with a plummeting approval rating and to bring enough peace to stabilize the country before another major...Commander to ISAF Commander could have been viewed as a demotion but simply was the President’s way of putting forth a last ditch football -like “hail Mary

  2. Chronic disease and ageing in the Caribbean: opportunities knock at the door.

    Science.gov (United States)

    Eldemire-Shearer, D; James, K; Morris, C; Holder-Nevins, D; Lawes, H; Harris, M

    2011-07-01

    Amidst rapid population ageing, the incidence and prevalence of chronic diseases and their sequelae demand reflective and critical looks at the issue and the subsequent development of informed age-sensitive responses. This paper reviews the burden of chronic diseases in the Caribbean, and its relationship to ageing and the demographic transition. Inter-linkages between the social determinants of health, poverty, ageing, and chronic disease are illustrated. Suggestions are made regarding directions to be pursued and the emerging initiative regarding chronic non-communicable diseases being spearheaded at the United Nations by CARICOM countries

  3. Opportunity Knocks: Pipeline Programs Offer Minority Students a Path to Dentistry

    Science.gov (United States)

    Fauteux, Nicole

    2012-01-01

    Minority students have traditionally been underrepresented in dental schools, which is why enrichment and pipeline programs aimed at helping minority students are necessary. That reality is reflected in their woeful underrepresentation among practicing dentists. Hispanics made up only 5.8 percent of practicing dentists in 2011, according to the…

  4. Is Opportunity Knocking or Slipping Away? Racial Diversity and Segregation in Pennsylvania

    Science.gov (United States)

    Kotok, Stephen; Reed, Katherine

    2015-01-01

    Historically, Pennsylvania has struggled to integrate its public schools, especially with much of the racial diversity concentrated in urban regions. Starting in the 1960s, the Pennsylvania Human Relations Commission (PHRC) was the state's enforcing body to combat school desegregation, but since the early 1980s, when it comes to education, the…

  5. Caracterización del 'Knock out' en Boxeo

    OpenAIRE

    Pic-Aguilar, M.; Sánchez-López, C.R.; Blanco Villaseñor, Ángel.

    2016-01-01

    El objetivo de este trabajo es identificar las cuatro últimas acciones motrices emitidas (golpes) por boxeadores campeones del mundo de los pesos pesados y así poder caracterizar el 'Knock out' en boxeo. Para ello, hemos desarrollado una herramienta de observación que consta de cuatro criterios y 35 categorías. Para la selección de la muestra se tuvo en cuenta dos requisitos: haberse proclamado campeón del mundo del peso pesado durante el período que comprende 1921-2007 (desde Jack Dempsey ha...

  6. Act No. 16.045 of 2 June 1989 prohibiting all discrimination that violates the principle of equality of treatment and opportunities for both sexes in all sectors of labor activity.

    Science.gov (United States)

    1989-01-01

    This Uruguayan Act prohibits discrimination in employment with respect to the following areas, among others: 1) advertising for the provision of positions; 2) selection criteria; 3) recruitment and hiring; 4) evaluation of performance criteria; 5) the right to advancement and promotion; 6) labour stability; 7) social benefits; 8) suspension and dismissal, particularly in cases involving a change of civil status, pregnancy, or nursing; 9) possibilities for professional and technical education or retraining; and 10) remuneration criteria. Reserving places for one sex because of the presence of activities in which the sex of the employee is essential for performance or to comply with international labor treaties does not constitute discrimination. Nor do compensatory acts designed to promote equality of opportunities and treatment of both sexes in concrete situations. In cases where the provisions of this Act have been violated, specially designated judges will call the parties together and may adopt measures designed to end the situation complained of. If they deem it necessary, the judges may institute more formal proceedings. If the measures adopted are not carried out, the person violating the law is subject to a daily fine, as well as administrative penalties set out in Act 15.903 of 10 November 1987. Adverse decisions may be appealed. The state is also to undertake educative campaigns to create interest in and understanding of the problems affecting women workers, thus promoting awareness in such workers and their employers of their situation.

  7. Opportunities for computer abuse

    DEFF Research Database (Denmark)

    Willison, Robert Andrew; Backhouse, James

    2005-01-01

    Systems risk refers to the likelihood that an IS is inadequately guarded against certain types of damage or loss. While risks are posed by acts of God, hackers and viruses, consideration should also be given to the `insider' threat of dishonest employees, intent on undertaking some form of computer...... for the offender. To achieve this goal a model known as the `Crime Specific Opportunity Structure' is advanced. Focussing on the opportunities for computer abuse, the model addresses the nature of such opportunities with regards to the organisational context and the threats posed by rogue employees. Drawing...

  8. American Recovery and Reinvestment Act (ARRA) Federal Energy Management Program Technical Assistance Project 282 Renewable Energy Opportunities at Fort Gordon, Georgia

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, Brian K.; Gorrissen, Willy J.; Hand, James R.; Horner, Jacob A.; Orrell, Alice C.; Russo, Bryan J.; Weimar, Mark R.; Williamson, Jennifer L.; Nesse, Ronald J.

    2010-09-30

    This document provides an overview of renewable resource potential at Fort Gordon, based primarily upon analysis of secondary data sources supplemented with limited on-site evaluations. This effort focuses on grid-connected generation of electricity from renewable energy sources and also on ground source heat pumps for heating and cooling buildings. The effort was funded by the American Recovery and Reinvestment Act (ARRA) as follow-on to the 2005 Department of Defense (DoD) Renewables Assessment. The site visit to Fort Gordon took place on March 9, 2010.

  9. Network Analysis for the Identification of Differentially Expressed Hub Genes Using Myogenin Knock-down Muscle Satellite Cells.

    Directory of Open Access Journals (Sweden)

    Adeel Malik

    Full Text Available Muscle, a multinucleate syncytium formed by the fusion of mononuclear myoblasts, arises from quiescent progenitors (satellite cells via activation of muscle-specific transcription factors (MyoD, Myf5, myogenin: MYOG, and MRF4. Subsequent to a decline in Pax7, induction in the expression of MYOG is a hallmark of myoblasts that have entered the differentiation phase following cell cycle withdrawal. It is evident that MYOG function cannot be compensated by any other myogenic regulatory factors (MRFs. Despite a plethora of information available regarding MYOG, the mechanism by which MYOG regulates muscle cell differentiation has not yet been identified. Using an RNA-Seq approach, analysis of MYOG knock-down muscle satellite cells (MSCs have shown that genes associated with cell cycle and division, DNA replication, and phosphate metabolism are differentially expressed. By constructing an interaction network of differentially expressed genes (DEGs using GeneMANIA, cadherin-associated protein (CTNNA2 was identified as the main hub gene in the network with highest node degree. Four functional clusters (modules or communities were identified in the network and the functional enrichment analysis revealed that genes included in these clusters significantly contribute to skeletal muscle development. To confirm this finding, in vitro studies revealed increased expression of CTNNA2 in MSCs on day 12 compared to day 10. Expression of CTNNA2 was decreased in MYOG knock-down cells. However, knocking down CTNNA2, which leads to increased expression of extracellular matrix (ECM genes (type I collagen α1 and type I collagen α2 along with myostatin (MSTN, was not found significantly affecting the expression of MYOG in C2C12 cells. We therefore propose that MYOG exerts its regulatory effects by acting upstream of CTNNA2, which in turn regulates the differentiation of C2C12 cells via interaction with ECM genes. Taken together, these findings highlight a new

  10. Generation and initial characterization of FDD knock in mice.

    Directory of Open Access Journals (Sweden)

    Luca Giliberto

    2009-11-01

    Full Text Available Mutations in the integral membrane protein 2B, also known as BRI(2, a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia. In these conditions, accumulation of a C-terminal peptide (ABri and ADan cleaved off from the mutated precursor protein by the pro-protein convertase furin, leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer's disease has lead to the finding that BRI(2 interacts with the Amyloid Precursor Protein (APP, decreasing the efficiency of APP processing to generate Abeta. The interaction between the two precursors, APP and BRI(2, and possibly between Abeta and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate.We have generated the first BRI(2 Danish Knock-In (FDD(KI murine model of FDD, expressing the pathogenic decamer duplication in exon 6 of the BRI(2 gene. FDD(KI mice do not show any evident abnormal phenotype, with normal brain histology and no detectable amyloid deposition in blood vessel walls or parenchyma.This new murine mouse model will be important to further understand the interaction between APP and BRI(2, and to provide insights into the molecular basis of FDD.

  11. Opportunity Design

    DEFF Research Database (Denmark)

    Løwe Nielsen, Suna; Lassen, Astrid Heidemann; Nielsen, Louise Møller

    2013-01-01

    Entrepreneurship is about transforming novel ideas into future business, but it requires an entrepreneurial opportunity to be exploited via an effective strategic and organizational design. While the entrepreneurship literature says much about how to implement and organize new opportunities...... in a market setting (the back-end of entrepreneurial processes), it pays less attention to how entrepreneurs purposely design opportunities (the front-end of entrepreneurial processes). Drawing on methods and processes from the creative design literature, the paper introduces a framework of “opportunity...... design”. The framework explains how opportunities intentionally and pro-actively can be designed from methods and processes of moving-in and moving-out. An illustrative case of opportunity design within the area of sustainable energy and electric cars is presented to link the theoretical discussion...

  12. Study of Knocking Effect in Compression Ignition Engine with Hydrogen as a Secondary Fuel

    Directory of Open Access Journals (Sweden)

    R. Sivabalakrishnan

    2014-01-01

    Full Text Available The aim of this project is detecting knock during combustion of biodiesel-hydrogen fuel and also the knock is suppressed by timed injection of diethyl ether (DEE with biodiesel-hydrogen fuel for different loads. Hydrogen fuel is an effective alternate fuel in making a pollution-free environment with higher efficiency. The usage of hydrogen in compression ignition engine leads to production of knocking or detonation because of its lower ignition energy, wider flammability range, and shorter quenching distance. Knocking combustion causes major engine damage, and also reduces the efficiency. The method uses the measurement and analysis of cylinder pressure signal for various loads. The pressure signal is to be converted into frequency domain that shows the accurate knocking combustion of fuel mixtures. The variation of pressure signal is gradually increased and smoothly reduced to minimum during normal combustion. The rapid rise of pressure signal has occurred during knocking combustion. The experimental setup was mainly available for evaluating the feasibility of normal combustion by comparing with the signals from both fuel mixtures in compression ignition engine. This method provides better results in predicting the knocking feature of biodiesel-hydrogen fuel and the usage of DEE provides complete combustion of fuels with higher performance, and lower emission.

  13. Source characteristics of the underwater knocking displays of a male Pacific walrus (Odobenus rosmarus divergens)

    DEFF Research Database (Denmark)

    Hughes, William R.; Reichmuth, Colleen; Mulsow, Jason L.

    2011-01-01

    "knocks"’ punctuated by occasional metallic "bells." The source characteristics of the knocking sounds that were regularly emitted by a male walrus raised in captivity were examined. Knocks were produced as single 20 ms pulses, or as doublets and triplets, and were typically repeated at rates of 0.8/s......Walruses breed in winter at high latitudes in conditions that make direct observation extremely difficult. Males are known to produce complex underwater songs that can extend over multiple days and propagate over several kilometers. These acoustic displays are comprised of highly rhythmic sharp...

  14. Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs.

    Science.gov (United States)

    Halos, Lénaïg; Fourie, Josephus J; Fankhauser, Becky; Beugnet, Frederic

    2016-02-02

    A topical combination of fipronil + permethrin (Frontline Tri-Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. All treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of

  15. Opportunity cost.

    Science.gov (United States)

    O'Shea, Carolyn

    2011-05-01

    Opportunity cost and trade-off - similar concepts with slightly different meanings and definitions in different fields - are concepts that we were all probably first exposed to as a toddler. For most women however, opportunity cost and trade-off is a part of their daily lives as they try to balance their needs, including their health needs, with the demands of their families, careers and never-ending 'to do' lists.

  16. HOLA: Hunt for Opportunities-Learn-Act

    Science.gov (United States)

    Gutiérrez, Rochelle

    2015-01-01

    Most mathematics teachers know that students can be a great source for understanding what they need as thinkers, group members, mathematics learners, and future citizens. Thus, listening to students is an important teacher practice. But listening takes time, something that not all teachers feel that they have. And many attempts to listen to…

  17. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency.

    Science.gov (United States)

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y Eugene; Zhang, Jifeng

    2016-01-28

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.

  18. High-temperature expansion and knock-out properties of moulding sands with water glass

    Directory of Open Access Journals (Sweden)

    Major-Gabryś K.

    2007-01-01

    Full Text Available The article focuses on the topic of improving the knock-out properties of moulding sand with water glass and ester hardener. It is settled that the cause of worse knock-out properties of moulding sand can be brought by their thermal expansion in increased temperatures. There is a presentation of the influence of different additives, containing Al2O3, on moulding sands’ expansion in increased temperatures. Within the frames of research, there was an elaboration of the influence of authors own additive- Glassex, on the expansion phenomenon of moulding sands with water glass and ester hardener. It is concluded, that the new additive stops the expansion of moulding sands and as well it improves their knock-out properties.

  19. Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2015-01-01

    Full Text Available Purpose. The small nuclear ribonucleoprotein 200 kDa (SNRNP200 gene is a fundamental component for precursor message RNA (pre-mRNA splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP. This study aims to determine the consequences of knocking down Snrnp200 in zebrafish. Methods. Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization. Morpholino oligonucleotide (MO aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs components and retina-specific transcripts. Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining. Results. Snrnp200 was ubiquitously expressed in zebrafish. Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri-snRNP components, and downregulation of a panel of retina-specific transcripts. Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish. Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP. Conclusions. We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects.

  20. A NEW METHOD FOR CHARACTERIZING THE KNOCK RESISTANCE OF LNG FUELS USED IN THE TRANSPORTATION MARKET

    NARCIS (Netherlands)

    Levinsky, Howard; Gersen, Sander; van Essen, Martijn; van Dijk, Gerco

    2014-01-01

    To ensure that the engines to be used in LNG-fueled vehicles are matched with the expected variations in fuel composition, the knock resistance of the fuel must be determined unambiguously. Rather than rely on empirical methods using gas mixtures and “standard” engines traditionally employed for

  1. CRISPR/Cas9-mediated gene knock-down in post-mitotic neurons.

    Directory of Open Access Journals (Sweden)

    Christoph Straub

    Full Text Available The prokaryotic adaptive immune system CRISPR/Cas9 has recently been adapted for genome editing in eukaryotic cells. This technique allows for sequence-specific induction of double-strand breaks in genomic DNA of individual cells, effectively resulting in knock-out of targeted genes. It thus promises to be an ideal candidate for application in neuroscience where constitutive genetic modifications are frequently either lethal or ineffective due to adaptive changes of the brain. Here we use CRISPR/Cas9 to knock-out Grin1, the gene encoding the obligatory NMDA receptor subunit protein GluN1, in a sparse population of mouse pyramidal neurons. Within this genetically mosaic tissue, manipulated cells lack synaptic current mediated by NMDA-type glutamate receptors consistent with complete knock-out of the targeted gene. Our results show the first proof-of-principle demonstration of CRISPR/Cas9-mediated knock-down in neurons in vivo, where it can be a useful tool to study the function of specific proteins in neuronal circuits.

  2. Information-based methods for predicting gene function from systematic gene knock-downs

    Directory of Open Access Journals (Sweden)

    Byrne Alexandra B

    2008-10-01

    Full Text Available Abstract Background The rapid annotation of genes on a genome-wide scale is now possible for several organisms using high-throughput RNA interference assays to knock down the expression of a specific gene. To date, dozens of RNA interference phenotypes have been recorded for the nematode Caenorhabditis elegans. Although previous studies have demonstrated the merit of using knock-down phenotypes to predict gene function, it is unclear how the data can be used most effectively. An open question is how to optimally make use of phenotypic observations, possibly in combination with other functional genomics datasets, to identify genes that share a common role. Results We compared several methods for detecting gene-gene functional similarity from phenotypic knock-down profiles. We found that information-based measures, which explicitly incorporate a phenotype's genomic frequency when calculating gene-gene similarity, outperform non-information-based methods. We report the presence of newly predicted modules identified from an integrated functional network containing phenotypic congruency links derived from an information-based measure. One such module is a set of genes predicted to play a role in regulating body morphology based on their multiply-supported interactions with members of the TGF-β signaling pathway. Conclusion Information-based metrics significantly improve the comparison of phenotypic knock-down profiles, based upon their ability to enhance gene function prediction and identify novel functional modules.

  3. Information-based methods for predicting gene function from systematic gene knock-downs.

    Science.gov (United States)

    Weirauch, Matthew T; Wong, Christopher K; Byrne, Alexandra B; Stuart, Joshua M

    2008-10-29

    The rapid annotation of genes on a genome-wide scale is now possible for several organisms using high-throughput RNA interference assays to knock down the expression of a specific gene. To date, dozens of RNA interference phenotypes have been recorded for the nematode Caenorhabditis elegans. Although previous studies have demonstrated the merit of using knock-down phenotypes to predict gene function, it is unclear how the data can be used most effectively. An open question is how to optimally make use of phenotypic observations, possibly in combination with other functional genomics datasets, to identify genes that share a common role. We compared several methods for detecting gene-gene functional similarity from phenotypic knock-down profiles. We found that information-based measures, which explicitly incorporate a phenotype's genomic frequency when calculating gene-gene similarity, outperform non-information-based methods. We report the presence of newly predicted modules identified from an integrated functional network containing phenotypic congruency links derived from an information-based measure. One such module is a set of genes predicted to play a role in regulating body morphology based on their multiply-supported interactions with members of the TGF-beta signaling pathway. Information-based metrics significantly improve the comparison of phenotypic knock-down profiles, based upon their ability to enhance gene function prediction and identify novel functional modules.

  4. Physicochemical effects of varying fuel composition on knock characteristics of natural gas mixtures

    NARCIS (Netherlands)

    Gersen, Sander; van Essen, Martijn; van Dijk, Gerco; Levinsky, Howard

    2014-01-01

    The physicochemical origins of how changes in fuel composition affect autoignition of the end gas, leading to engine knock, are analyzed for a natural gas engine. Experiments in a lean-burn, high-speed medium-BMEP gas engine are performed using a reference natural gas with systematically varied

  5. Objective evaluation of the knocking sound of a diesel engine considering the temporal and frequency masking effect simultaneously

    Science.gov (United States)

    Yun, Dong-Un; Lee, Sang-Kwon

    2017-06-01

    In this paper, we present a novel method for an objective evaluation of knocking noise emitted by diesel engines based on the temporal and frequency masking theory. The knocking sound of a diesel engine is a vibro-acoustic sound correlated with the high-frequency resonances of the engine structure and a periodic impulsive sound with amplitude modulation. Its period is related to the engine speed and includes specific frequency bands related to the resonances of the engine structure. A knocking sound with the characteristics of a high-frequency impulsive wave can be masked by low-frequency sounds correlated with the harmonics of the firing frequency and broadband noise. The degree of modulation of the knocking sound signal was used for such objective evaluations in previous studies, without considering the masking effect. However, the frequency masking effect must be considered for the objective evaluation of the knocking sound. In addition to the frequency masking effect, the temporal masking effect occurs because the period of the knocking sound changes according to the engine speed. Therefore, an evaluation method considering the temporal and frequency masking effect is required to analyze the knocking sound objectively. In this study, an objective evaluation method considering the masking effect was developed based on the masking theory of sound and signal processing techniques. The method was applied successfully for the objective evaluation of the knocking sound of a diesel engine.

  6. Effect of Timing and Location of Hotspot on Super Knock during Pre-ignition

    KAUST Repository

    Jaasim, Mohammed

    2017-03-28

    Pre-ignition in SI engine is a critical issue that needs addressing as it may lead to super knock event. It is widely accepted that pre-ignition event emanates from hot spot(s) that can be anywhere inside the combustion chamber. The location and timing of hotspot is expected to influence the knock intensity from a pre-ignition event. In this study, we study the effect of location and timing of hot spot inside the combustion chamber using numerical simulations. The simulation is performed using a three-dimensional computational fluid dynamics (CFD) code, CONVERGE™. We simulate 3-D engine geometry coupled with chemistry, turbulence and moving structures (valves, piston). G-equation model for flame tracking coupled with multi-zone model is utilized to capture auto-ignition (knock) and solve gas phase kinetics. A parametric study on the effect of hot spot timing and location inside the combustion chamber is performed. The hot spot timing considered are -180 CAD, -90 CAD and -30 CAD and the locations of the hot spots are in the center and two edges of the piston surfaces. Simulation results for normal combustion cycle are validated against the experimental data. The simulation results show great sensitivity to the hot spot timing, and the influence of local temperature gradient is noted to be significant. In case of early hot spot timing of -180 CAD, the pre-ignition event did not lead to super knock. Nevertheless, at late hot spot timing, super knock was realized. On the other hand, the effect of hot spot location on pre-ignition event depends on the geometry of the combustion chamber.

  7. Pou4f2-GFP knock-in mouse line: A model for studying retinal ganglion cell development.

    Science.gov (United States)

    Zheng, Dongwang; Yang, Xiaoyan; Sheng, Donglai; Yu, Dongliang; Liang, Guoqing; Guo, Luming; Xu, Mei; Hu, Xu; He, Daqiang; Yang, Yang; Wang, Yuying

    2016-10-01

    Pou4f2 acts as a key node in the comprehensive and step-wise gene regulatory network (GRN) and regulates the development of retinal ganglion cells (RGCs). Accordingly, deletion of Pou4f2 results in RGC axon defects and apoptosis. To investigate the GRN involved in RGC regeneration, we generated a mouse line with a POU4F2-green fluorescent protein (GFP) fusion protein expressed in RGCs. Co-localization of POU4F2 and GFP in the retina and brain of Pou4f2-GFP/+ heterozygote mice was confirmed using immunofluorescence analysis. Compared with those in wild-type mice, the expression patterns of POU4F2 and POU4F1 and the co-expression patterns of ISL1 and POU4F2 were unaffected in Pou4f2-GFP/GFP homozygote mice. Moreover, the quantification of RGCs showed no significant difference between Pou4f2-GFP/GFP homozygote and wild-type mice. These results demonstrated that the development of RGCs in Pou4f2-GFP/GFP homozygote mice was the same as in wild-type mice. Thus, the present Pou4f2-GFP knock-in mouse line is a useful tool for further studies on the differentiation and regeneration of RGCs. © 2016 Wiley Periodicals, Inc.

  8. P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

    DEFF Research Database (Denmark)

    Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

    2005-01-01

    P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

  9. "Equal Employment Opportunity: Fact or Fantasy"

    Science.gov (United States)

    Woodard, Maurice C.

    1977-01-01

    Notes that the Civil Service Commission (CSC) has not utilized its resources to enforce the Equal Employment Opportunity Act, nor has the Equal Employment Opportunity Commission (EEOC) been capable of ferreting out racial discrimination in the private and public sectors. (Author/AM)

  10. Privacy Act

    Science.gov (United States)

    Learn about the Privacy Act of 1974, the Electronic Government Act of 2002, the Federal Information Security Management Act, and other information about the Environmental Protection Agency maintains its records.

  11. Evaluation of Anti-Knock Quality of Dicyclopentadiene-Gasoline Blends

    KAUST Repository

    Al-Khodaier, Mohannad

    2017-03-28

    Increasing the anti-knock quality of gasoline fuels can enable higher efficiency in spark ignition engines. In this study, the blending anti-knock quality of dicyclopentadiene (DCPD), a by-product of ethylene production from naphtha cracking, with various gasoline fuels is explored. The blends were tested in an ignition quality tester (IQT) and a modified cooperative fuel research (CFR) engine operating under homogenous charge compression ignition (HCCI) and knock limited spark advance (KLSA) conditions. Due to current fuel regulations, ethanol is widely used as a gasoline blending component in many markets. In addition, ethanol is widely used as a fuel and literature verifying its performance. Moreover, because ethanol exhibits synergistic effects, the test results of DCPD-gasoline blends were compared to those of ethanol-gasoline blends. The experiments conducted in this work enabled the screening of DCPD auto-ignition characteristics across a range of combustion modes. The synergistic blending nature of DCPD was apparent and appeared to be greater than that of ethanol. The data presented suggests that DCPD has the potential to be a high octane blending component in gasoline; one which can substitute alkylates, isomerates, reformates, and oxygenates.

  12. Generation of Venus reporter knock-in mice revealed MAGI-2 expression patterns in adult mice.

    Science.gov (United States)

    Ihara, Kan-ichiro; Nishimura, Tomoki; Fukuda, Tomokazu; Ookura, Tetsuya; Nishimori, Katsuhiko

    2012-01-01

    The membrane-associated guanylate kinase inverted 2 (MAGI-2) protein, which is known to localize at the tight junction of epithelial cells, contains multiple copies of the PDZ and WW domains in its structure. Although the expression pattern of Magi2 mRNA in representative organs has been previously published, its detailed cellular distribution at the histological level remains unknown. Such detailed information would be useful to clarify the biological function of MAGI-2. Here, we report the generation of Venus reporter knock-in mice for Magi2 in which exon 6 of the gene was substituted by the Venus-encoding sequence. We detected the expression of the Venus reporter protein in kidney podocytes from these knock-in mice. We also detected Venus reporter protein expression in spermatids within the testes and within neurons in various regions of the brain. Detection of the reporter protein from these diverse locations indicated the endogenous expression of MAGI-2 in these tissues. Our data suggested a potential function of MAGI-2 in the glomerular filtration process and sperm cell maturation. These data indicate that the Venus reporter knock-in mouse for Magi2 is a useful model for the further study of Magi2 gene function. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Terpineol as a novel octane booster for extending the knock limit of gasoline

    KAUST Repository

    Vallinayagam, R.

    2016-09-16

    Improving the octane number of gasoline offers the potential of improved engine combustion, as it permits spark timing advancement without engine knock. This study proposes the use of terpineol as an octane booster for gasoline in a spark ignited (SI) engine. Terpineol is a bio-derived oxygenated fuel obtained from pine tree resin, and has the advantage of higher calorific value than ethanol. The ignition delay time (IDT) of terpineol was first investigated in an ignition quality tester (IQT). The IQT results demonstrated a long ignition delay of 24.7 ms for terpineol and an estimated research octane number (RON) of 104, which was higher than commercial European (Euro V) gasoline. The octane boosting potential of terpineol was further investigated by blending it with a non-oxygenated gasoline (FACE F), which has a RON (94) lower than Euro V gasoline (RON = 97). The operation of a gasoline direct injection (GDI) SI engine fueled with terpineol-blended FACE F gasoline enabled spark timing advancement and improved engine combustion. The knock intensity of FACE F + 30% terpineol was lower than FACE F gasoline at both maximum brake torque (MBT) and knock limited spark advance (KLSA) operating points. Increasing proportions of terpineol in the blend caused peak heat release rate, in-cylinder pressure, CA50, and combustion duration to be closer to those of Euro V gasoline. Furthermore, FACE F + 30% terpineol displayed improved combustion characteristics when compared to Euro V gasoline. © 2016

  14. Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

    Science.gov (United States)

    Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Nakade, Shota; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

    2017-05-04

    The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer ( http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively.

  15. Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

    2012-01-01

    Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. PMID:22391119

  16. ‘ProPIG’ Challenges and opportunities for on farm pig researchers: How to collect sound scientific data on animal health, welfare, nutrition and environmental impact AND act as a facilitator to improve these aspects at the same time?

    OpenAIRE

    Rudolph, G.; Bochicchio, D.; Brandhofer, R.; Berner, Alfred; Butler, G; Dippel, Sabine; Dourmad, Jean-Yves; Edwards, Sandra; Früh, Barbara; Holinger, M.; Holmes, D; Illmann, Gudrun; Knop, D.; Meier, M.; Prunier, Armelle

    2014-01-01

    Challenges and opportunities of on farm research are discussed and it is concluded, that transdisciplinary on-farm research requires from all involved parties: Understanding and willingness to learn from each other Acceptance, that own field of research is only a part of the whole “on farm picture” Sound scientific methods as well as technical tools for support (e.g. tablet PCs) Move from being/expecting “experts” towards “facilitation"

  17. The Children's Internet Protection Act and E-Rate Policies in Louisiana: A Comparison of Policy Interpretations in Region III and Their Impact on Learning Opportunities of Secondary Students

    Science.gov (United States)

    Gautreaux, Madge L.

    2013-01-01

    In 2000, President Bill Clinton enacted the "Children's Internet Protection Act" (CIPA) which requires all K-12 schools and publicly funded libraries to use Internet filters to protect children from pornography and other obscene or potentially harmful online content as a stipulation for receiving E-Rate funding. The varying…

  18. Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Goat's milk, considered a substitute for cow's milk, has a high nutritional value. However, goat's milk contains various allergens, predominantly β-lactoglobulin (BLG. In this study, we employed the CRISPR/Cas9 system to target the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock-out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs into goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were modified in single sgRNA-guided targeting experiment. Among the kids, the genome-targeting efficiencies of single sgRNA were 12.5% (10 ng/μL sg1 and 0% (10 ng/μL sg2 and efficiencies of dual sgRNAs were 25.0% (25 ng/μL sg2+sg3 group and 28.6% (50 ng/μL sg2+sg3 group. Relative expression of BLG in BLG knock-out goat mammary glands significantly (p < 0.01 decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05. As expected, BLG protein had been abolished in the milk of the BLG knock-out goat. In addition, most of the targeted kids were chimeric (3/4, and their various body tissues were edited simultaneously. Our study thus provides a basis for optimizing the quality of goat milk, which can be applied to biomedical and agricultural research.

  19. Sound vibration signal processing for detection and identification detonation (knock) to optimize performance Otto engine

    Science.gov (United States)

    Sujono, A.; Santoso, B.; Juwana, W. E.

    2016-03-01

    Problems of detonation (knock) on Otto engine (petrol engine) is completely unresolved problem until now, especially if want to improve the performance. This research did sound vibration signal processing engine with a microphone sensor, for the detection and identification of detonation. A microphone that can be mounted is not attached to the cylinder block, that's high temperature, so that its performance will be more stable, durable and inexpensive. However, the method of analysis is not very easy, because a lot of noise (interference). Therefore the use of new methods of pattern recognition, through filtration, and the regression function normalized envelope. The result is quite good, can achieve a success rate of about 95%.

  20. Reaction of Quasielastic Knock-Out of Nucleons From Nuclei by Protons

    Directory of Open Access Journals (Sweden)

    Mirteymur MIRABUTALYBOV

    2016-11-01

    Full Text Available Abstract. On the basis of non-relativistic theory in the distorted-wave approximation in three dimensions, a theory of from nuclei by nucleons of intermediate energies has been developed. On the baizing on this theory the differential cross sections of quasielastic knock-out reactions of protons with shells 1 , 1   in the nucleus and  have been calculated, which allows to determine the orbital momentum of the nucleons in the nucleus before scattering by the angular distribution of emitted protons.Keywords: Reaction A (p, 2pB, distorted-wave approximation, and  nuclei.

  1. 29 CFR 452.79 - Opportunity to campaign.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Opportunity to campaign. 452.79 Section 452.79 Labor... DISCLOSURE ACT OF 1959 Campaign Safeguards § 452.79 Opportunity to campaign. There must be a reasonable... prior to the election so that he was denied an equal opportunity to campaign. Similarly, in a mail...

  2. ACT Test

    Science.gov (United States)

    ... Content View Sources Ask Us Also Known As ACT Activated Coagulation Time Formal Name Activated Clotting Time ... What is being tested? The activated clotting time (ACT) is a test that is used primarily to ...

  3. 29 CFR 1614.203 - Rehabilitation Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Rehabilitation Act. 1614.203 Section 1614.203 Labor... EMPLOYMENT OPPORTUNITY Provisions Applicable to Particular Complaints § 1614.203 Rehabilitation Act. (a... Rehabilitation Act of 1973, as amended (29 U.S.C. 791), has been violated in a complaint alleging nonaffirmative...

  4. Effect of KnockOut serum replacement on germ cell development of immature testis tissue culture.

    Science.gov (United States)

    Liu, Feng; Cai, Chunhong; Wu, Xin; Cheng, Yanxia; Lin, Tao; Wei, Guanghui; He, Dawei

    2016-01-15

    To compare KnockOut serum replacement (KSR) and fetal bovine serum (FBS) for the development of germ cells. Testicular tissues from Sprague-Dawley rats were cultured for 4 weeks in culture media supplemented with FBS or KSR. Tissue area was measured at the beginning and end of the culturing period. Testicular histology, development of the germ cells, and the diameter of seminiferous tubules were analyzed by hematoxylin and eosin staining. After 4 weeks in culture, apoptosis and expression of the stage-specific spermatogenesis marker genes Kit, Sycp3, and Crisp1 were assayed. Tissues cultured in KSR-supplemented media were able to sustain growth and gradually increase seminiferous tubule diameter during the culture period. In addition, spermatogonia, primary spermatocytes, secondary spermatocytes, and round spermatids were observed after 4 weeks in culture, and reverse transcription-PCR confirmed expression of the marker genes. In comparison, tissues cultured in FBS-supplemented media showed dwindling testicular organization, necrotic seminiferous tubules, and expression of Kit, but inconsistent expression of Sycp3 and Crisp1 KnockOut serum replacement outperforms FBS as a growth media supplements for culturing immature spermatogonial tissue culture. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of Pin1 loss in HdhQ111 knock-in mice

    Directory of Open Access Journals (Sweden)

    Elena eAgostoni

    2016-05-01

    Full Text Available Huntington’s disease (HD is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with HdhQ111 knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of HdhQ111 phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response. In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional HdhQ111 phenotypes: the unbalance in the synthesis/concentration of hormones, as well as the alteration of Wnt/β-catenin signaling. In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis.

  6. Effects of Pin1 Loss in HdhQ111 Knock-in Mice

    Science.gov (United States)

    Agostoni, Elena; Michelazzi, Silvia; Maurutto, Marta; Carnemolla, Alisia; Ciani, Yari; Vatta, Paolo; Roncaglia, Paola; Zucchelli, Silvia; Leanza, Giampiero; Mantovani, Fiamma; Gustincich, Stefano; Santoro, Claudio; Piazza, Silvano; Del Sal, Giannino; Persichetti, Francesca

    2016-01-01

    Huntington’s disease (HD) is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt) in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with HdhQ111 knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of HdhQ111 phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response (DDR). In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional HdhQ111 phenotypes: the unbalance in the “synthesis/concentration of hormones”, as well as the alteration of “Wnt/β-catenin signaling”. In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis. PMID:27199664

  7. Differential Bees Flux Balance Analysis with OptKnock for in silico microbial strains optimization.

    Directory of Open Access Journals (Sweden)

    Yee Wen Choon

    Full Text Available Microbial strains optimization for the overproduction of desired phenotype has been a popular topic in recent years. The strains can be optimized through several techniques in the field of genetic engineering. Gene knockout is a genetic engineering technique that can engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, the complexities of the metabolic networks have made the process to identify the effects of genetic modification on the desirable phenotypes challenging. Furthermore, a vast number of reactions in cellular metabolism often lead to the combinatorial problem in obtaining optimal gene deletion strategy. Basically, the size of a genome-scale metabolic model is usually large. As the size of the problem increases, the computation time increases exponentially. In this paper, we propose Differential Bees Flux Balance Analysis (DBFBA with OptKnock to identify optimal gene knockout strategies for maximizing the production yield of desired phenotypes while sustaining the growth rate. This proposed method functions by improving the performance of a hybrid of Bees Algorithm and Flux Balance Analysis (BAFBA by hybridizing Differential Evolution (DE algorithm into neighborhood searching strategy of BAFBA. In addition, DBFBA is integrated with OptKnock to validate the results for improving the reliability the work. Through several experiments conducted on Escherichia coli, Bacillus subtilis, and Clostridium thermocellum as the model organisms, DBFBA has shown a better performance in terms of computational time, stability, growth rate, and production yield of desired phenotypes compared to the methods used in previous works.

  8. Characterization of TG2 and TG1-TG2 double knock-out mouse epidermis.

    Science.gov (United States)

    Pitolli, Consuelo; Pietroni, Valentina; Marekov, Lyuben; Terrinoni, Alessandro; Yamanishi, Kiyofumi; Mazzanti, Cinzia; Melino, Gerry; Candi, Eleonora

    2017-03-01

    Transglutaminases (TGs) are a family of enzymes that catalyse the formation of isopeptide bonds between the γ-carboxamide groups of glutamine residues and the ε-amino groups of lysine residues leading to cross-linking reactions among proteins. Four members, TG1, TG2, TG3, and TG5, of the nine mammalian enzymes are expressed in the skin. TG1, TG3 and TG5 crosslinking properties are fundamental for cornified envelope assembly. In contrast, the role of TG2 in keratinization has never been studied at biochemical level in vivo. In this study, taking advantage of the TG2 knock-out (KO) and TG1 heterozygous mice, we generated and characterized the epidermis of TG1-TG2 double knock-out (DKO) mice. We performed morphological analysis of the epidermis and evaluation of the expression of differentiation markers. In addition, we performed analysis of the amino acid composition from isolated corneocytes. We found a significant change in amino acid composition in TG1KO cornified cell envelopes (CEs) while TG2KO amino acid composition was similar to wild-type CEs. Our results confirm a key role of TG1 in skin differentiation and CE assembly and demonstrate that TG2 is not essential for CE assembly and skin formation.

  9. MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems.

    Science.gov (United States)

    Sakuma, Tetsushi; Nakade, Shota; Sakane, Yuto; Suzuki, Ken-Ichi T; Yamamoto, Takashi

    2016-01-01

    Programmable nucleases enable engineering of the genome by utilizing endogenous DNA double-strand break (DSB) repair pathways. Although homologous recombination (HR)-mediated gene knock-in is well established, it cannot necessarily be applied in every cell type and organism because of variable HR frequencies. We recently reported an alternative method of gene knock-in, named the PITCh (Precise Integration into Target Chromosome) system, assisted by microhomology-mediated end-joining (MMEJ). MMEJ harnesses independent machinery from HR, and it requires an extremely short homologous sequence (5-25 bp) for DSB repair, resulting in precise gene knock-in with a more easily constructed donor vector. Here we describe a streamlined protocol for PITCh knock-in, including the design and construction of the PITCh vectors, and their delivery to either human cell lines by transfection or to frog embryos by microinjection. The construction of the PITCh vectors requires only a few days, and the entire process takes ∼ 1.5 months to establish knocked-in cells or ∼ 1 week from injection to early genotyping in frog embryos.

  10. Generation of an allelic series of knock-in mice using recombinase-mediated cassette exchange (RMCE).

    Science.gov (United States)

    Roebroek, Anton J M; Van Gool, Bart

    2014-01-01

    Molecular genetic strategies applying embryonic stem cell (ES cell) technologies to study the function of a gene in mice or to generate a mouse model for a human disease are continuously under development. Next to (conditional) inactivation of genes the application and importance of approaches to generate knock-in mutations are increasing. In this chapter the principle and application of recombinase-mediated cassette exchange (RMCE) are discussed as being a new emerging knock-in strategy, which enables easy generation of a series of different knock-in mutations within one gene. An RMCE protocol, which was used to generate a series of different knock-in mutations in the Lrp1 gene of ES cells, is described in detail as an example of how RMCE can be used to generate highly efficiently an allelic series of differently modified ES cell clones from a parental modified ES cell clone. Subsequently the differently modified ES cell clones can be used to generate an allelic series of mutant knock-in mice.

  11. ACTS 2014

    DEFF Research Database (Denmark)

    . For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the city, its...... various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes downtown.......Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art...

  12. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

    Directory of Open Access Journals (Sweden)

    Carolina R den Hartog

    Full Text Available Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs. In this study, we determined how expression of a mutant GluN1 subunit (F639A that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p. increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg. In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  13. Monte Carlo simulations of down-scattered neutron and knock-on deuteron spectra in deuterium-tritium capsule implosions

    Science.gov (United States)

    Zhao, Bin; Zheng, Jian

    2013-12-01

    A Monte Carlo particle tracking (MCPT) code has been developed and coupled to hydrodynamic simulations to generate and track primary and scattered neutrons in addition to scattered charged particles by post-processing. This code uses one dimensional (1-D) deuterium-tritium implosion profiles, and the computed down-scattered neutron and knock-on deuteron spectra are analyzed for different areal densities. The mixing effects on the spectra of down-scattered neutron and knock-on deuteron are also investigated. The implementation of the numerical scheme is analyzed, and the particle splitting technique is adopted, which is proven to efficiently reduce computational effort.

  14. The Effect of Piston-Head Temperature on Knock-Limited Power

    Science.gov (United States)

    Imming, Harry S.

    1944-01-01

    To determine the effect of piston-head temperature on knock-limited power. Tests were made in a supercharged CFR engine over a range of fuel-air ratios from 0.055 to 0.120, using S-3 reference fuel, AN-F-28, Amendment-2, aviation gasoline, and AN-F-28 plus 2 percent xylidines by weight. Tests were run at a compression ratio of 7.0 with inlet-air temperatures of 150 F and 250 F and at a compression ratio of 8.0 with an inlet-air temperature of 250 F. All other engine conditions were held constant. The piston-head temperature was varied by circulation of oil through passages in the crown of a liquid-cooled piston. This method of piston cooling decreased the piston-head temperature about 80 F. The data are not intended to constitute a recommendation as to the advisability of piston cooling in practice.

  15. Relevant feature set estimation with a knock-out strategy and random forests

    DEFF Research Database (Denmark)

    Ganz, Melanie; Greve, Douglas N; Fischl, Bruce

    2015-01-01

    Group analysis of neuroimaging data is a vital tool for identifying anatomical and functional variations related to diseases as well as normal biological processes. The analyses are often performed on a large number of highly correlated measurements using a relatively smaller number of samples...... unintuitive and difficult to determine. In this article, we propose a novel MVPA method for group analysis of high-dimensional data that overcomes the drawbacks of the current techniques. Our approach explicitly aims to identify all relevant variations using a "knock-out" strategy and the Random Forest...... algorithm. In evaluations with synthetic datasets the proposed method achieved substantially higher sensitivity and accuracy than the state-of-the-art MVPA methods, and outperformed the univariate approach when the effect size is low. In experiments with real datasets the proposed method identified regions...

  16. Generation of VDR Knock-Out Mice via Zygote Injection of CRISPR/Cas9 System.

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    Full Text Available CRISPR/Cas9 system has become a new versatile technology for genome engineering in various species. To achieve targeted modifications at the same site in both human and mice genomes by a CRISPR/Cas9 nuclease, we designed two target sites in conserved regions of vitamin D receptor (VDR gene, which cover more than 17 kb of chromosome region depending on the species. We first validated the efficacy of single sgRNA mediated gene specific modifications were 36% and 31% in HEK293T cells. Concurrently, targeted of the intervening genomic segments deletions were generated in chromosomes when two sgRNAs worked simultaneously. The large genomic DNA segments up to 23.4 Kb could be precisely deleted in human chromosomes. Subsequently, Cas9 mRNA and sgRNAs targeting VDRT1 and VDRT2 were co-microinjected into one-cell-stage embryos of C57BL/6 mice. Verified by T7E1 assay and DNA sequencing analysis, 12 mice showed VDR targeted disruption and 8 of which were biallelic knock-out, which demonstrated obvious phenotype of hair thinning. Furthermore, expression changes of Vitamin D metabolism genes in VDR-/-mice were detected. These results indicated that CRISPR/Cas9 mediated knock-out of VDR diminished its gene function in vivo. The off-target effects of CRISPR/Cas9 in VDR-/- founder mice were analyzed. Our results showed that CRISPR/Cas9 system could be employed to target the same sites in different species, when sgRNAs are designed within conserved regions, and therefore will be critically important and applicable for human disease model.

  17. Rewriting the Opportunity Theory

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.

    The aim of this paper is to further the discussion of opportunity theory by discussing its ontological and epistemological underpinnings, which have been neglected in previous discussions. The idea that opportunities have an objective component is critically examined drawing on insights from social...... constructionism. It is argued that opportunity theory needs to be rewritten....

  18. Opportunity Cost: A Reexamination

    Science.gov (United States)

    Parkin, Michael

    2016-01-01

    Is opportunity cost an ambiguous and arbitrary concept or a simple, straightforward, and fruitful one? This reexamination of opportunity cost addresses this question, and shows that opportunity cost is an ambiguous concept because "two" definitions are in widespread use. One of the definitions is indeed simple, fruitful, and one that…

  19. Recovery Act. Tapoco project. Cheoah upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Paul [Alcoa Inc., Alcoa Center, PA (United States)

    2013-10-02

    Under Funding Opportunity Announcement Number: DE-FOA-0000120, Recovery Act: Hydroelectric Facility Modernization, Alcoa Power Generating Inc. (APGI), a fully owned subsidiary of Alcoa Inc., implemented major upgrades at its Cheoah hydroelectric facility near Robbinsville, North Carolina.

  20. The Clean Air Act and the Economy

    Science.gov (United States)

    Since 1970, cleaner air and a growing economy have gone hand in hand. The Act has created market opportunities that have helped to inspire innovation in cleaner technologies for which the United States has become a global market leader.

  1. Knock-out transmembrane prostate androgen-induced protein gene suppressed triple-negative breast cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Bantari W.K. Wardhani

    2017-11-01

    Full Text Available Background: Triple negative breast cancer (TNBC tends to grow more rapidly and has poorer prognosis compared to others. High expression of transmembrane prostate androgen-induced protein (TMEPAI correlates with poor prognosis in TNBC patients. However, the mechanistic role of TMEPAI in tumorigenic remains unknown. This study aimed to knock-out TMEPAI in TNBC cell line to determine its function further in cells proliferation.Methods: CRISPR-Cas9 has been used previously to knock-out TMEPAI in Hs857T TNBC cell line. Hs587T TNBC parental cell line (wild-type/WT and TMEPAI knock out Hs 586T cell lines were cultured in Dulbecco’s modified eagle medium (DMEM supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin and amphotericin B. Both cell lines were seeded in 24-well plates and counted every two days, then proliferation rates were plotted. Afterwards, total RNA were isolated from the cells and Ki-67, and TGF-β mRNA expression levels as proliferation markers were determined.Results: Cell proliferation rates as displayed in growth curve plots showed that WT-TMEPAI cell line grew more rapidly than KO-TMEPAI. In accordance, mRNA expression levels of  Ki-67 and TGF-β  were significantly decreased KO-TMEPAI as compare to TMEPAI-WT.Conclusion: Knock-out of TMEPAI attenuates cell proliferation in TNBC.

  2. Characterizing Gaseous Fuels for Their Knock Resistance based on the Chemical and Physical Properties of the Fuel

    NARCIS (Netherlands)

    Levinsky, Howard; Gersen, Sander; van Essen, Martijn; van Dijk, Gerco

    2016-01-01

    A method is described to characterize the effects of changes in the composition of gaseous fuels on engine knock by computing the autoignition process during the compression and burn periods of the engine cycle. To account for the effects of fuel composition on the in-cylinder pressure and

  3. Balancing Acts

    Science.gov (United States)

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... It was like watching a movie, but every couple of frames were skipping. It was disorienting," the ...

  4. 20 CFR 664.420 - What are leadership development opportunities?

    Science.gov (United States)

    2010-04-01

    ... LABOR YOUTH ACTIVITIES UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Youth Program Design, Elements, and... opportunities that encourage responsibility, employability, and other positive social behaviors such as: (a...

  5. Reconstructing gene-regulatory networks from time series, knock-out data, and prior knowledge

    Directory of Open Access Journals (Sweden)

    Timmer Jens

    2007-02-01

    Full Text Available Abstract Background Cellular processes are controlled by gene-regulatory networks. Several computational methods are currently used to learn the structure of gene-regulatory networks from data. This study focusses on time series gene expression and gene knock-out data in order to identify the underlying network structure. We compare the performance of different network reconstruction methods using synthetic data generated from an ensemble of reference networks. Data requirements as well as optimal experiments for the reconstruction of gene-regulatory networks are investigated. Additionally, the impact of prior knowledge on network reconstruction as well as the effect of unobserved cellular processes is studied. Results We identify linear Gaussian dynamic Bayesian networks and variable selection based on F-statistics as suitable methods for the reconstruction of gene-regulatory networks from time series data. Commonly used discrete dynamic Bayesian networks perform inferior and this result can be attributed to the inevitable information loss by discretization of expression data. It is shown that short time series generated under transcription factor knock-out are optimal experiments in order to reveal the structure of gene regulatory networks. Relative to the level of observational noise, we give estimates for the required amount of gene expression data in order to accurately reconstruct gene-regulatory networks. The benefit of using of prior knowledge within a Bayesian learning framework is found to be limited to conditions of small gene expression data size. Unobserved processes, like protein-protein interactions, induce dependencies between gene expression levels similar to direct transcriptional regulation. We show that these dependencies cannot be distinguished from transcription factor mediated gene regulation on the basis of gene expression data alone. Conclusion Currently available data size and data quality make the reconstruction of

  6. Hunting the Opportunity

    DEFF Research Database (Denmark)

    Løwe Nielsen, Suna; Rind Christensen, Poul; Lassen, Astrid Heidemann

    2017-01-01

    This paper bring together the two research fields of design and entrepreneurship in order to stimulate new knowledge on opportunity creation. A shared theoretical framework on new opportunity creation that illustrates that design and entrepreneurship can advantageously complement each other in th...... in the opportunity design process. Practical insights into the robustness of the framework are provided by a short illustrative case on electric cars....

  7. Fluorescent knock-in mice to decipher the physiopathological role of G protein-coupled receptors.

    Directory of Open Access Journals (Sweden)

    Dominique eMassotte

    2015-01-01

    Full Text Available G protein-coupled receptors (GPCRs modulate most physiological functions but are also critically involved in numerous pathological states. Approximately a third of marketed drugs target GPCRs, which places this family of receptors in the main arena of pharmacological pre-clinical and clinical research. The complexity of GPCR function demands comprehensive appraisal in native environment to collect in-depth knowledge of receptor physiopathological roles and assess the potential of therapeutic molecules. Identifying neurons expressing endogenous GPCRs is therefore essential to locate them within functional circuits whereas GPCR visualization with subcellular resolution is required to get insight into agonist-induced trafficking. Both remain frequently poorly investigated because direct visualization of endogenous receptors is often hampered by the lack of appropriate tools. Also, monitoring intracellular trafficking requires real-time visualization to gather in-depth knowledge. In this context, knock-in mice expressing a fluorescent protein or a fluorescent version of a GPCR under the control of the endogenous promoter not only help to decipher neuroanatomical circuits but also enable real-time monitoring with subcellular resolution thus providing invaluable information on their trafficking in response to a physiological or a pharmacological challenge. This review will present the animal models and discuss their contribution to the understanding of the physiopathological role of GPCRs. We will also address the drawbacks associated with this methodological approach and browse future directions.

  8. Multiple cranial organ defects after conditionally knocking out Fgf10 in the neural crest

    Directory of Open Access Journals (Sweden)

    Tathyane H.N. Teshima

    2016-10-01

    Full Text Available Fgf10 is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out Fgf10 specifically in the neural crest driven by Wnt1cre. The Wnt1creFgf10fl/fl mouse phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands and ocular glands, highlighting the neural crest origin of the Fgf10 expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where Fgf10 is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where Fgf10 is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and Fgf10 null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of Fgf10 for this tissue is mesodermal, which was confirmed using Wnt1cre-dtTom to lineage trace the boundary of the neural crest in this region. The thyroid, thymus and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighbouring source of mesodermal Fgf10 might be able to partially compensate for loss of neural crest derived Fgf10.

  9. Disruption of Rab11 activity in a knock-in mouse model of Huntington's Disease

    Science.gov (United States)

    Li, Xueyi; Sapp, Ellen; Chase, Kathryn; Comer-Tierney, Laryssa A.; Masso, Nicholas; Alexander, Jonathan; Reeves, Patrick; Kegel, Kimberly B.; Valencia, Antonio; Esteves, Miguel; Aronin, Neil; DiFiglia, Marian

    2009-01-01

    Summary The Huntington's disease (HD) mutation causes polyglutamine expansion in huntingtin (Htt) and neurodegeneration. Htt interacts with a complex containing Rab11GDP and is involved in activation of Rab11, which functions in endosomal recycling and neurite growth and long-term potentiation. Like other Rab proteins, Rab11GDP undergoes nucleotide exchange to Rab11GTP for its activation. Here we show that striatal membranes of HD140Q/140Q knock-in mice are impaired in supporting conversion of Rab11GDP to Rab11GTP. Dominant negative Rab11 expressed in the striatum and cortex of normal mice caused neuropathology and motor dysfunction, suggesting that a deficiency in Rab11 activity is pathogenic in vivo. Primary cortical neurons from HD140Q/140Q mice were delayed in recycling transferrin receptors back to the plasma membrane. Partial rescue from glutamate induced cell death occurred in HD neurons expressing dominant active Rab11. We propose a novel mechanism of HD pathogenesis arising from diminished Rab11 activity at recycling endosomes. PMID:19699304

  10. Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model

    Directory of Open Access Journals (Sweden)

    Tomoaki Nakazono

    2017-06-01

    Full Text Available The entorhinal cortex (EC has bidirectional connections with the hippocampus and plays a critical role in memory formation and retrieval. EC is one of the most vulnerable regions in the brain in early stages of Alzheimer’s disease (AD, a neurodegenerative disease with progressive memory impairments. Accumulating evidence from healthy behaving animals indicates gamma oscillations (30–100 Hz as critical for mediating interactions in the circuit between EC and hippocampus. However, it is still unclear whether gamma oscillations have causal relationship with memory impairment in AD. Here we provide the first evidence that in vivo gamma oscillations in the EC are impaired in an AD mouse model. Cross-frequency coupling of gamma (30–100 Hz oscillations to theta oscillations was reduced in the medial EC of anesthetized amyloid precursor protein knock-in (APP-KI mice. Phase locking of spiking activity of layer II/III pyramidal cells to the gamma oscillations was significantly impaired. These data indicate that the neural circuit activities organized by gamma oscillations were disrupted in the medial EC of AD mouse model, and point to gamma oscillations as one of possible mechanisms for cognitive dysfunction in AD patients.

  11. Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity.

    Directory of Open Access Journals (Sweden)

    Dmitry Akhmedov

    Full Text Available The cAMP response element binding protein (CREB is induced during fasting in the liver, where it stimulates transcription of rate-limiting gluconeogenic genes to maintain metabolic homeostasis. Adenoviral and transgenic CREB reporters have been used to monitor hepatic CREB activity non-invasively using bioluminescence reporter imaging. However, adenoviral vectors and randomly inserted transgenes have several limitations. To overcome disadvantages of the currently used strategies, we created a ROSA26 knock-in CREB reporter mouse line (ROSA26-CRE-luc. cAMP-inducing ligands stimulate the reporter in primary hepatocytes and myocytes from ROSA26-CRE-luc animals. In vivo, these animals exhibit little hepatic CREB activity in the ad libitum fed state but robust induction after fasting. Strikingly, CREB was markedly stimulated in liver, but not in skeletal muscle, after overnight voluntary wheel-running exercise, uncovering differential regulation of CREB in these tissues under catabolic states. The ROSA26-CRE-luc mouse line is a useful resource to study dynamics of CREB activity longitudinally in vivo and can be used as a source of primary cells for analysis of CREB regulatory pathways ex vivo.

  12. Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs.

    Science.gov (United States)

    Kwon, Deug-Nam; Lee, Kiho; Kang, Man-Jong; Choi, Yun-Jung; Park, Chankyu; Whyte, Jeffrey J; Brown, Alana N; Kim, Jae-Hwan; Samuel, Melissa; Mao, Jiude; Park, Kwang-Wook; Murphy, Clifton N; Prather, Randall S; Kim, Jin-Hoi

    2013-01-01

    After the knock-out (KO) of α1,3 galactosyltransfease (Gal-T), the Hanganutziu-Deicher antigen became a major antigen of the "non-Gal antigen" that is implicated in subsequent xenograft rejection. For deletion of non-Gal antigen, we successfully produced zinc finger nuclease (ZFN)-mediated monoallelic/biallelic male and female CMP-N-acetylneuraminic acid hydroxylase (CMAH) KO miniature pigs: the efficiency of the gene targeting (41.7%) was higher when donor DNA was used with the ZFN than those of ZFN alone (9.1%). Monoallelic KO pigs had no integration of exogenous DNA into their genome, indicating that this technique would provide a new avenue to reduce the risk of antibiotics resistance when organs from genetically modified pigs are transplanted into patients. Until now, both monoallelic and biallelic CMAH KO pigs are healthy and show no sign of abnormality and off-target mutations. Therefore, these CMAH null pigs on the Gal-T KO background could serve as an important model for the xenotransplantation.

  13. Analysis of DC Functions Using CD205-DTR Knock-In Mice.

    Science.gov (United States)

    Fukaya, Tomohiro; Takagi, Hideaki; Uto, Tomofumi; Arimura, Keiichi; Sato, Katsuaki

    2016-01-01

    Dendritic cells (DCs) are essential antigen-presenting cells (APCs) that consist of heterogeneous subsets, mainly classified as conventional DCs (cDCs) and plasmacytoid DCs (pDCs). CD205, an endocytic type I C-type lectin-like molecule that belongs to the mannose receptor family, is mainly expressed on CD8α(+) cDCs. However, it is unclear how CD205(+) cDCs control immune responses in vivo. To evaluate the contribution of CD205(+) cDCs to the immune system, we engineered knock-in (KI) mice that express the diphtheria toxin receptor (DTR) under the control of the Cd205 gene, which allows the selective conditional ablation of CD205(+) cDCs in vivo. Conditional ablation of CD205(+) cDCs impaired the antigen-specific priming of CD8(+) T cells to generate cytotoxic T lymphocytes (CTLs) mediated through cross presentation of soluble antigen. Upon microbial infection, CD205(+) cDCs contributed to the cross priming of CD8(+) T cells for generating antibacterial CTLs to efficiently eliminate pathogens. Here, we provide a protocol for the generation of bone marrow WT/CD205-DT chimeric mice, depletion of CD205(+) DCs and assessment of depletion efficiency, and protocols for in vivo cross presentation assay, CTL generation assay, and antibacterial immunity assay.

  14. Phospholipase D δ knock-out mutants are tolerant to severe drought stress.

    Science.gov (United States)

    Distéfano, Ayelen M; Valiñas, Matías A; Scuffi, Denise; Lamattina, Lorenzo; Ten Have, Arjen; García-Mata, Carlos; Laxalt, Ana M

    2015-01-01

    Phospholipase D (PLD) is involved in different plant processes, ranging from responses to abiotic and biotic stress to plant development. Phospholipase Dδ (PLDδ) is activated in dehydration and salt stress, producing the lipid second messenger phosphatidic acid. In this work we show that pldδ Arabidopsis mutants were more tolerant to severe drought than wild-type plants. PLDδ has been shown to be required for ABA regulation of stomatal closure of isolated epidermal peels. However, there was no significant difference in stomatal conductance at the whole plant level between wild-type and pldδ mutants. Since PLD hydrolyses structural phospholipids, then we looked at membrane integrity. Ion leakage measurements showed that during dehydration of leaf discs pldδ mutant has less membrane degradation compared to the wild-type. We further analyzed the mutants and showed that pldδ have higher mRNA levels of RAB18 and RD29A compared to wild-type plants under normal growth conditions. Transient expression of AtPLDδ in Nicotiana benthamiana plants induced a wilting phenotype. These findings suggest that, in wt plants PLDδ disrupt membranes in severe drought stress and, in the absence of the protein (PLDδ knock-out) might drought-prime the plants, making them more tolerant to severe drought stress. The results are discussed in relation to PLDδ role in guard cell signaling and drought tolerance.

  15. Thioredoxin reductase-1 knock down does not result in thioredoxin-1 oxidation.

    Science.gov (United States)

    Watson, Walter H; Heilman, Jacqueline M; Hughes, Laura L; Spielberger, Jeanine C

    2008-04-11

    The active site of thioredoxin-1 (Trx1) is oxidized in cells with increased reactive oxygen species (ROS) and is reduced by thioredoxin reductase-1 (TrxR1). The purpose of the present study was to determine the extent to which the redox state of Trx1 is sensitive to changes in these opposing reactions. Trx1 redox state and ROS generation were measured in cells exposed to the TrxR1 inhibitors aurothioglucose (ATG) and monomethylarsonous acid (MMA(III)) and in cells depleted of TrxR1 activity by siRNA knock down. The results showed that all three treatments inhibited TrxR1 activity to similar extents (90% inhibition), but that only MMA(III) exposure resulted in oxidation of Trx1. Similarly, ROS levels were elevated in response to MMA(III), but not in response to ATG or TrxR1 siRNA. Therefore, TrxR1 inhibition alone was not sufficient to oxidize Trx1, suggesting that Trx1-independent pathways should be considered when evaluating pharmacological and toxicological mechanisms involving TrxR1 inhibition.

  16. Histopathological characteristics of a novel knock-in mouse prostate cancer model

    Directory of Open Access Journals (Sweden)

    G. Wu

    2006-06-01

    Full Text Available Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50% and showed a significant correlation with age (P = 0.001. Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid, analogous to the human situation. The similarities of the KIMAP mouse model with tumors of the human prostate suggest the use of this experimental model to complement studies of human prostate cancer.

  17. Who's that Knocking at My Door? Neural Bases of Sound Source Identification.

    Science.gov (United States)

    Lemaitre, Guillaume; Pyles, John A; Halpern, Andrea R; Navolio, Nicole; Lehet, Matthew; Heller, Laurie M

    2017-01-03

    When hearing knocking on a door, a listener typically identifies both the action (forceful and repeated impacts) and the object (a thick wooden board) causing the sound. The current work studied the neural bases of sound source identification by switching listeners' attention toward these different aspects of a set of simple sounds during functional magnetic resonance imaging scanning: participants either discriminated the action or the material that caused the sounds, or they simply discriminated meaningless scrambled versions of them. Overall, discriminating action and material elicited neural activity in a left-lateralized frontoparietal network found in other studies of sound identification, wherein the inferior frontal sulcus and the ventral premotor cortex were under the control of selective attention and sensitive to task demand. More strikingly, discriminating materials elicited increased activity in cortical regions connecting auditory inputs to semantic, motor, and even visual representations, whereas discriminating actions did not increase activity in any regions. These results indicate that discriminating and identifying material requires deeper processing of the stimuli than discriminating actions. These results are consistent with previous studies suggesting that auditory perception is better suited to comprehend the actions than the objects producing sounds in the listeners' environment. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Hyperactivation of Alk induces neonatal lethality in knock-in AlkF1178L mice

    Science.gov (United States)

    Lopez-Delisle, Lucille; Pierre-Eugène, Cécile; Bloch-Gallego, Evelyne; Birling, Marie-Christine; Duband, Jean-Loup; Durand, Estelle; Bourgeois, Thomas; Matrot, Boris; Sorg, Tania; Huerre, Michel; Meziane, Hamid; Roux, Michel J.; Champy, Marie-France; Gallego, Jorge; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2014-01-01

    The ALK (Anaplastic Lymphoma Kinase) gene encodes a tyrosine kinase receptor preferentially expressed in the central and peripheral nervous systems. A syndromic presentation associating congenital neuroblastoma with severe encephalopathy and an abnormal shape of the brainstem has been described in patients harbouring de novo germline F1174V and F1245V ALK mutations. Here, we investigated the phenotype of knock-in (KI) mice bearing the AlkF1178L mutation (F1174L in human). Although heterozygous KI mice did not reproduce the severe breathing and feeding difficulties observed in human patients, behavioral tests documented a reduced activity during dark phases and an increased anxiety of mutated mice. Matings of heterozygotes yielded the expected proportions of wild-type, heterozygotes and homozygotes at birth but a high neonatal lethality was noticed for homozygotes. We documented Alk expression in several motor nuclei of the brainstem involved in the control of sucking and swallowing. Evaluation of basic physiological functions 12 hours after birth revealed slightly more apneas but a dramatic reduced milk intake for homozygotes compared to control littermates. Overall, our data demonstrate that Alk activation above a critical threshold is not compatible with survival in mice, in agreement with the extremely severe phenotype of patients carrying aggressive de novo ALK germline mutations. PMID:24811761

  19. [Annual "Door Knock" Fundraising Campaign Jubilee--for the patients and against the disease].

    Science.gov (United States)

    Robinson, Eliezer; Ziv, Miri

    2011-10-01

    Marking the annual "Door Knock" Fundraising Campaign Jubilee, this article provides an overview of the Israel Cancer Association (ICA) activity for patients and against the disease, that comply with the principles of the World Cancer Declaration (WCD) of the UICC (Union for International Cancer Control). To elucidate, as a voluntary organization, all of ICA's resources are derived exclusively from public contributions--with no funding from the government budget. This independence enables ICA to operate according to strictly professional criteria, while maintaining a global and national point of view and vision. ICA activity will be presented with respect to the international treaty, from monitoring the disease at the national level, to activity to promote research, prevention methods, early detection, enhancing treatment modalities and rehabilitation, and maintaining quality of life for patients and survivors. This presentation will also provide an overview of how ICA's initiative, in close collaboration with the Ministry of Health, and the HMO's, white relying on the volunteer activity of members of the ICA professional committees, and that of many other volunteers, leads Israel to significant accomplishments in each one of the treaty sections. These activities have resulted in concrete achievements at the national level, positioning Israel high on the global scale.

  20. LMNA knock-down affects differentiation and progression of human neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Giovanna Maresca

    Full Text Available BACKGROUND: Neuroblastoma (NB is one of the most aggressive tumors that occur in childhood. Although genes, such as MYCN, have been shown to be involved in the aggressiveness of the disease, the identification of new biological markers is still desirable. The induction of differentiation is one of the strategies used in the treatment of neuroblastoma. A-type lamins are components of the nuclear lamina and are involved in differentiation. We studied the role of Lamin A/C in the differentiation and progression of neuroblastoma. METHODOLOGY/PRINCIPAL FINDINGS: Knock-down of Lamin A/C (LMNA-KD in neuroblastoma cells blocked retinoic acid-induced differentiation, preventing neurites outgrowth and the expression of neural markers. The genome-wide gene-expression profile and the proteomic analysis of LMNA-KD cells confirmed the inhibition of differentiation and demonstrated an increase of aggressiveness-related genes and molecules resulting in augmented migration/invasion, and increasing the drug resistance of the cells. The more aggressive phenotype acquired by LMNA-KD cells was also maintained in vivo after injection into nude mice. A preliminary immunohistochemistry analysis of Lamin A/C expression in nine primary stages human NB indicated that this protein is poorly expressed in most of these cases. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first time in neuroblastoma cells that Lamin A/C plays a central role in the differentiation, and that the loss of this protein gave rise to a more aggressive tumor phenotype.

  1. Mosquito knock-down and adulticidal activities of essential oils by vaporizer, impregnated filter paper and aerosol methods

    Directory of Open Access Journals (Sweden)

    M. Ramar

    2014-09-01

    Full Text Available Essential oils from 12 medicinal plants were evaluated by three different bioassay methods (Vaporizer, Filter paper and Aerosol for Knock-down and adulticidal efficacy on the filarial vector mosquito, Culex quinquefasciatus. Based on screening results the effective plants were selected for investigating Knock-down and adulticidal potential against adult female of the laboratory-reared mosquito species, Cx. quinquefasciatus. In vaporizer bioassay method four different doses (1.25, 2.5, 5 and 10% were used. Four different doses (0.625, 1.25, 2.5 and 10% were used both filter paper (cm2 and aerosol (cm3 bioassay methods. Five essential oils (calamus, camphor, citronella, clove and eucalyptus were identified as potential treatments in vaporizer bioassay. The result showed that the knock down time decreased with increased concentration in clove oil treatment; the Knock-down time (KT 50 = 46.1 ± 0.1, 38.5 ± 0.1, 30.7 ± 0.2, and 20.1 ± 0.1 minutes was recorded at 1.25, 2.5, 5 and 10% /cm3 respectively. In filter paper method nine essential oils were identified as potential treatments. After 1 hr exposure period clove oil recorded the lowest median Knock-down time (KT50 which was calculated as 9.15 ± 0.1min/cm2. Followed by citronella (KT50 =11.4 ± 0.1 min and eucalyptus (KT50 =11.4 ±0.1min oils since they recorded lower median Knock-down time. All the twelve essential oils were identified as potential treatments in aerosol activity. The lethal time decreased when the concentration increased. At 5 % concentration the median lethal time (LT50 for clove oil was calculated as (LT50=3.80 ± 0.1minutes. The Cinnamon oil was effective which recorded (LT50 = 1.99 mins as median lethal time. Camphor (LT50 =19.6± 0.1 min oil were found to be less toxic by aerosol method. These results suggest that clove oil and cinnamon oil have the potential to be used as a eco-friendly approach for the control of the major important filaria vector Cx. quinquefasciatus

  2. Still Not Equal: Expanding Educational Opportunity in Society

    Science.gov (United States)

    Brown, M. Christopher, II, Ed.

    2007-01-01

    "Still Not Equal: Expanding Educational Opportunity in Society" addresses the successes and failures of "Brown v. Board of Education" and the Civil Rights Act of 1964, as well as the continuing challenge of expanding educational opportunity in the United States and across the Black diaspora. The educational, political, and social influence…

  3. Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Zhang, Hua; Wu, Lili; Pchitskaya, Ekaterina; Zakharova, Olga; Saito, Takashi; Saido, Takaomi; Bezprozvanny, Ilya

    2015-09-30

    Alzheimer's disease (AD) is the most common reason for elderly dementia in the world. We proposed that memory loss in AD is related to destabilization of mushroom postsynaptic spines involved in long-term memory storage. We demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key role in stability of mushroom spines by maintaining activity of synaptic Ca(2+)/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously that the STIM2-nSOC-CaMKII pathway is downregulated in presenilin 1 M146V knock-in (PS1-M146V KI) mouse model of AD, leading to loss of hippocampal mushroom spines in this model. In the present study, we demonstrate that hippocampal mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in (APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as a result of accumulation of extracellular β-amyloid 42 in APPKI culture media. Our results indicate that extracellular Aβ42 acts by overactivating mGluR5 receptor in APPKI neurons, leading to elevated Ca(2+) levels in endoplasmic reticulum, compensatory downregulation of STIM2 expression, impaired synaptic nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss in APPKI hippocampal neurons. Our results indicate that downregulation of synaptic STIM2-nSOC-CaMKII pathway causes loss of mushroom synaptic spines in both presenilin and APPKI mouse models of AD. We propose that modulators/activators of this pathway may have a potential therapeutic value for treatment of memory loss in AD. Significance statement: A direct connection between amyloid-induced synaptic mushroom spine loss and neuronal store-operated calcium entry pathway is shown. These results provide strong support for the calcium hypothesis of neurodegeneration and further validate the synaptic

  4. Altmetric opportunities for Libraries

    NARCIS (Netherlands)

    Gerritsma, W.

    2015-01-01

    Just over five years ago the concept of altmetrics was minted. For libraries and librarians this has brought a new plethora of opportunities. In the first place there is the traditional extension role. Outreach opportunities on the subject of altmetrics are manyfold, and librarians could seize the

  5. Equal Opportunity in Housing.

    Science.gov (United States)

    Commission on Civil Rights, Washington, DC.

    This overview of developments in housing opportunities for minorities and women includes an historical review of housing discrimination, its nature, and its effects. Federal legislation and Federal actions which were taken to assure equal housing opportunities for women and minorities are described. Other topic areas addressed include minority…

  6. Opportunity identification competence

    NARCIS (Netherlands)

    Baggen, Yvette

    2017-01-01

    Opportunities and their identification are of significant importance for competitiveness in today’s complex and turbulent business environment because they serve as a key influencing factor for new value-creation. Opportunity identification (OI) is interesting not only from the perspective of

  7. Equal opportunities in diversity

    CERN Multimedia

    Laëtitia Pedroso

    2010-01-01

    Promoting equal opportunities at CERN and advising the Director-General on all related matters is the task of the Equal Opportunities Officer, Doris Chromek-Burckhart, and Tim Smith, chair of the Equal Opportunities Advisory Panel. Changes are being introduced: in future, the focus of their work will be broadened to cover all aspects of diversity promotion.   The term "equal opportunities" has always been broader in scope than the equal treatment of men and women but this is what it has traditionally been confined to in practice. "We wanted to change how people see our mission", explains Doris Chromek-Burckhart. The word "diversity" has much wider connotations than "equal opportunities" and makes it clearer that we are also dealing with differences in nationality, religion, age, culture and physical ability”. Getting away from the old clichés is vital to ensuring equal treatment for everyone. The diversit...

  8. The end distance effect of knock-down furniture fasteners on bending moment resistance of corner joints

    Directory of Open Access Journals (Sweden)

    Milan Šimek

    2008-01-01

    Full Text Available The goal of this paper is to investigate the effect of the end distance of cam lock fasteners on the bending moment resistance of knock-down corner joints. The preliminary study of knock-down furniture assembly plans was done in order to discover the manufacturers’ fastener typical usage in case construction. Laminated particleboard, cam fasteners and wooden dowels were used for specimen construction. L-shaped joint specimens 760 mm in length were tested by pressing the joint members together – also called a compression test in the angle plane. The study results showed that cam fasteners with end distance of 60 mm from the member edges perform the best.

  9. New test procedure to determine fuel's knock resistance; Neues Kraftstoffpruefverfahren zur Bestimmung der Klopffestigkeit

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Karl [Hochschule Ingolstadt (Germany). Thermodynamik und Verbrennungsmotoren; Hauber, Johann; Raba, Andreas [Hochschule Ingolstadt (Germany). Inst. fuer Angewandte Forschung; Nell, Robert [Rofa Laboratory and Process Analyzers, Kritzendorf (Austria). Bereich Produktentwicklung

    2013-07-15

    Knock resistance is one of the most important quality features of gasoline that is determined by standardised motor test procedures. These procedures were developed more than 80 years ago and have been used nearly unchanged since then. During a four-year research project at Ingolstadt University of Applied Sciences, the procedures for determination of octane numbers were analysed in order to develop a new engine-based test method. (orig.)

  10. The Effect of Humidity on the Knock Behavior in a Medium BMEP Lean-Burn High-Speed Gas Engine

    NARCIS (Netherlands)

    van Essen, Vincent Martijn; Gersen, Sander; van Dijk, Gerco; Mundt, Torsten; Levinsky, Howard

    2016-01-01

    The effects of air humidity on the knock characteristics of fuels are investigated in a lean-burn, high-speed medium BMEP engine fueled with a CH4 + 4.7 mole% C3H8 gas mixture. Experiments are carried out with humidity ratios ranging from 4.3 to 11 g H2O/kg dry air. The measured pressure profiles at

  11. Constraints to the Embrace of the African Growth and Opportunity ...

    African Journals Online (AJOL)

    The African Growth and Opportunity Act (AGOA) aims at liberalising trade between Africa and the United States of America (US). Since 1 October 2000 when the Act became effective, the US has annually chronicled the performance of AGOA in a way that gives it a success rating. The assessment is based on an increased ...

  12. Numerical and Experimental Investigation of Combustion and Knock in a Dual Fuel Gas/Diesel Compression Ignition Engine

    Directory of Open Access Journals (Sweden)

    A. Gharehghani

    2012-01-01

    Full Text Available Conventional compression ignition engines can easily be converted to a dual fuel mode of operation using natural gas as main fuel and diesel oil injection as pilot to initiate the combustion. At the same time, it is possible to increase the output power by increasing the diesel oil percentage. A detailed performance and combustion characteristic analysis of a heavy duty diesel engine has been studied in dual fuel mode of operation where natural gas is used as the main fuel and diesel oil as pilot. The influence of intake pressure and temperature on knock occurrence and the effects of initial swirl ratio on heat release rate, temperature-pressure and emission levels have been investigated in this study. It is shown that an increase in the initial swirl ratio lengthens the delay period for auto-ignition and extends the combustion period while it reduces NOx. There is an optimum value of the initial swirl ratio for a certain mixture intake temperature and pressure conditions that can achieve high thermal efficiency and low NOx emissions while decreases the tendency to knock. Simultaneous increase of intake pressure and initial swirl ratio could be the solution to power loss and knock in dual fuel engine.

  13. PARP1 gene knock-out increases resistance to retinal degeneration without affecting retinal function.

    Directory of Open Access Journals (Sweden)

    Ayse Sahaboglu

    2010-11-01

    Full Text Available Retinitis pigmentosa (RP is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt. Likewise, retinal function as assessed by electroretinography (ERG was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6, we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.

  14. Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1.

    Science.gov (United States)

    Li, Li; Zhang, Quanjun; Yang, Huaqiang; Zou, Qingjian; Lai, Chengdan; Jiang, Fei; Zhao, Ping; Luo, Zhiwei; Yang, Jiayin; Chen, Qian; Wang, Yan; Newsome, Philip N; Frampton, Jon; Maxwell, Patrick H; Li, Wenjuan; Chen, Shuhan; Wang, Dongye; Siu, Tak-Shing; Tam, Sidney; Tse, Hung-Fat; Qin, Baoming; Bao, Xichen; Esteban, Miguel A; Lai, Liangxue

    2017-03-17

    Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH-/- rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH-/- rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH-/- rabbits are an attractive alternative for modeling the consequences of HT1. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1*

    Science.gov (United States)

    Li, Li; Zhang, Quanjun; Yang, Huaqiang; Zou, Qingjian; Lai, Chengdan; Jiang, Fei; Zhao, Ping; Luo, Zhiwei; Yang, Jiayin; Chen, Qian; Wang, Yan; Newsome, Philip N.; Frampton, Jon; Maxwell, Patrick H.; Li, Wenjuan; Chen, Shuhan; Wang, Dongye; Siu, Tak-Shing; Tam, Sidney; Tse, Hung-Fat; Qin, Baoming; Bao, Xichen; Esteban, Miguel A.; Lai, Liangxue

    2017-01-01

    Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH−/− rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH−/− rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH−/− rabbits are an attractive alternative for modeling the consequences of HT1. PMID:28053091

  16. Knock down Os1bglu1 β-glucosidase in rice by Agrobacterium-mediated transformation

    Directory of Open Access Journals (Sweden)

    Mariena Ketudat-Cairns

    2011-02-01

    Full Text Available This research attempted to study the function of Os1bglu1 by RNAi technique. The suppression of Os1bglu1genewas done using the 3’UTR region. The target gene fragment was cloned into the pHELLSGATE8 vector. The high percentagesof effective callus induction of 93% were obtained when the seeds were cultured on N6D medium for 4-6 weeks at 28°C. Thesuitable transformation conditions were to incubate the calli with Agrobacterium (OD 600 = 0.02 and blot dry to remove excessbacteria cells, then transferred to co-cultivation medium (pH 5.2 with 200 M acetosyringone and incubate for three days at25°C. The 20% transformation efficiency was obtained from the transformed calli with control plasmid, while transformationefficiency of only 15% was obtained from pHELLSGATE8 Os1bglu1 constructs. The transformed calli with control constructshowed higher growth rate than the transformed calli with pHELLSGATE8 Os1bglu1construct. The expression of Os1bglu1mRNA was not found in the transformed calli and siRNAs were found in the transformed calli. However no siRNAs weredetected in the control transformed calli. The regeneration efficiencies of 6% were obtained from only the calli transformedwith the control construct. The calli transformed with the knock down Os1bglu1 constructs were not able to regenerate. This may indicated that Os1bglu1 is involved in regeneration of rice from callus tissue.

  17. Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia.

    Science.gov (United States)

    Avraam, Joanne; Cohen, Gary; Drago, John; Frappell, Peter B

    2015-03-01

    Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Equal Opportunities Questionnaire

    CERN Multimedia

    2007-01-01

    The initiative to promote Equal Opportunities at CERN started in 1993. The first Equal Opportunities Officer was appointed in 1996 followed by the creation of the Equal Opportunities Advisory Panel in 1998. Initially the concern was mainly the fair treatment of women in the work-place. Today the emphasis has evolved to ensuring that diversity is used to increase creativity and productivity in the work-place. In order to ensure that all aspects of Equal Opportunities and Diversity are covered, CERN’s Equal Opportunities team has prepared a survey to obtain your input. Your answers are confidential and will only be used for generating statistics. The questionnaire is on-line and can be accessed via: https://espace.cern.ch/EOQ. We hope that you will take a few minutes of your time to give your input and would be grateful if you could reply before 15/10/07. For further information about Equal Opportunities at CERN see: http://cern.ch/equal-opportunities The Equal Opportuni...

  19. Equal Opportunities Questionnaire

    CERN Multimedia

    2007-01-01

    The initiative to promote Equal Opportunities at CERN started in 1993. The first Equal Opportunities Officer was appointed in 1996, which was followed by the creation of the Equal Opportunities Advisory Panel in 1998. Initially the concern was mainly the fair treatment of women in the work-place. Today the emphasis has evolved to ensuring that diversity is used to increase creativity and productivity in the work-place. In order to ensure that all aspects of Equal Opportunities and Diversity are covered, CERN’s Equal Opportunities team has prepared a survey to obtain your input. Your answers are confidential and will only be used for generating statistics. The questionnaire is on-line and can be accessed via: https://espace.cern.ch/EOQ. We hope that you will take a few minutes of your time to give your input and would be grateful if you could reply before 15/10/07. For further information about Equal Opportunities at CERN see: http://cern.ch/equal-opportunities The Equa...

  20. 77 FR 50390 - Equal Credit Opportunity Act (Regulation B)

    Science.gov (United States)

    2012-08-21

    ... management companies, automated valuation models, and providing copies of appraisals and valuations.\\8\\ Many... policy of a government sponsored enterprise or by an automated valuation model, a broker price opinion... would require creditors to provide free copies of all written appraisals and valuations developed in...

  1. Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175.

    Directory of Open Access Journals (Sweden)

    Liliana B Menalled

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric manifestations. Since the mutation responsible for the disease was identified as an unstable expansion of CAG repeats in the gene encoding the huntingtin protein in 1993, numerous mouse models of HD have been generated to study disease pathogenesis and evaluate potential therapeutic approaches. Of these, knock-in models best mimic the human condition from a genetic perspective since they express the mutation in the appropriate genetic and protein context. Behaviorally, however, while some abnormal phenotypes have been detected in knock-in mouse models, a model with an earlier and more robust phenotype than the existing models is required. We describe here for the first time a new mouse line, the zQ175 knock-in mouse, derived from a spontaneous expansion of the CAG copy number in our CAG 140 knock-in colony [1]. Given the inverse relationship typically observed between age of HD onset and length of CAG repeat, since this new mouse line carries a significantly higher CAG repeat length it was expected to be more significantly impaired than the parent line. Using a battery of behavioral tests we evaluated both heterozygous and homozygous zQ175 mice. Homozygous mice showed motor and grip strength abnormalities with an early onset (8 and 4 weeks of age, respectively, which were followed by deficits in rotarod and climbing activity at 30 weeks of age and by cognitive deficits at around 1 year of age. Of particular interest for translational work, we also found clear behavioral deficits in heterozygous mice from around 4.5 months of age, especially in the dark phase of the diurnal cycle. Decreased body weight was observed in both heterozygotes and homozygotes, along with significantly reduced survival in the homozygotes. In addition, we detected an early and significant decrease of striatal gene markers from 12 weeks of age

  2. Culture time of vitrified/warmed zygotes before microinjection affects the production efficiency of CRISPR-Cas9-mediated knock-in mice

    Directory of Open Access Journals (Sweden)

    Yoshiko Nakagawa

    2017-05-01

    Full Text Available Robust reproductive engineering techniques are required for the efficient and rapid production of genetically modified mice. We have reported the efficient production of genome-edited mice using reproductive engineering techniques, such as ultra-superovulation, in vitro fertilization (IVF and vitrification/warming of zygotes. We usually use vitrified/warmed fertilized oocytes created by IVF for microinjection because of work efficiency and flexible scheduling. Here, we investigated whether the culture time of zygotes before microinjection influences the efficiency of producing knock-in mice. Knock-in mice were generated using clustered regularly interspaced short palindromic repeats (CRISPR-CRISPR-associated protein 9 (Cas9 system and single-stranded oligodeoxynucleotide (ssODN or PITCh (Precise Integration into Target Chromosome system, a method of integrating a donor vector assisted by microhomology-mediated end-joining. The cryopreserved fertilized oocytes were warmed, cultured for several hours and microinjected at different timings. Microinjection was performed with Cas9 protein, guide RNA(s, and an ssODN or PITCh donor plasmid for the ssODN knock-in and the PITCh knock-in, respectively. Different production efficiencies of knock-in mice were observed by changing the timing of microinjection. Our study provides useful information for the CRISPR-Cas9-based generation of knock-in mice.

  3. Knock-in mouse model of alternating hemiplegia of childhood: behavioral and electrophysiologic characterization.

    Science.gov (United States)

    Hunanyan, Arsen S; Fainberg, Nina A; Linabarger, Molly; Arehart, Eric; Leonard, A Soren; Adil, Syed M; Helseth, Ashley R; Swearingen, Amanda K; Forbes, Stacy L; Rodriguiz, Ramona M; Rhodes, Theodore; Yao, Xiaodi; Kibbi, Nadine; Hochman, Daryl W; Wetsel, William C; Hochgeschwender, Ute; Mikati, Mohamad A

    2015-01-01

    Mutations in the ATP1α3 subunit of the neuronal Na+/K+-ATPase are thought to be responsible for seizures, hemiplegias, and other symptoms of alternating hemiplegia of childhood (AHC). However, the mechanisms through which ATP1A3 mutations mediate their pathophysiologic consequences are not yet understood. The following hypotheses were investigated: (1) Our novel knock-in mouse carrying the most common heterozygous mutation causing AHC (D801N) will exhibit the manifestations of the human condition and display predisposition to seizures; and (2) the underlying pathophysiology in this mouse model involves increased excitability in response to electrical stimulation of Schaffer collaterals and abnormal predisposition to spreading depression (SD). We generated the D801N mutant mouse (Mashlool, Mashl+/-) and compared mutant and wild-type (WT) littermates. Behavioral tests, amygdala kindling, flurothyl-induced seizure threshold, spontaneous recurrent seizures (SRS), and other paroxysmal activities were compared between groups. In vitro electrophysiologic slice experiments on hippocampus were performed to assess predisposition to hyperexcitability and SD. Mutant mice manifested a distinctive phenotype similar to that of humans with AHC. They had abnormal impulsivity, memory, gait, motor coordination, tremor, motor control, endogenous nociceptive response, paroxysmal hemiplegias, diplegias, dystonias, and SRS, as well as predisposition to kindling, to flurothyl-induced seizures, and to sudden unexpected death. Hippocampal slices of mutants, in contrast to WT animals, showed hyperexcitable responses to 1 Hz pulse-trains of electrical stimuli delivered to the Schaffer collaterals and had significantly longer duration of K+-induced SD responses. Our model reproduces the major characteristics of human AHC, and indicates that ATP1α3 dysfunction results in abnormal short-term plasticity with increased excitability (potential mechanism for seizures) and a predisposition to more

  4. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig, E-mail: blackstc@ninds.nih.gov

    2016-11-15

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also

  5. AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Chang Sik Park

    Full Text Available Histidine-rich calcium binding protein (HRC is located in the lumen of sarcoplasmic reticulum (SR that binds to both triadin (TRN and SERCA affecting Ca(2+ cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+ homeostasis is implicated in pathogenesis of cardiac hypertrophy. Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy. In the present study, we characterized the functions of HRC related to Ca(2+ cycling and pathogenesis of cardiac hypertrophy using the in vitro siRNA- and the in vivo adeno-associated virus (AAV-mediated HRC knock-down (KD systems, respectively.AAV-mediated HRC-KD system was used with or without C57BL/6 mouse model of transverse aortic constriction-induced failing heart (TAC-FH to examine whether HRC-KD could enhance cardiac function in failing heart (FH. Initially we expected that HRC-KD could elicit cardiac functional recovery in failing heart (FH, since predesigned siRNA-mediated HRC-KD enhanced Ca(2+ cycling and increased activities of RyR2 and SERCA2 without change in SR Ca(2+ load in neonatal rat ventricular cells (NRVCs and HL-1 cells. However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control. We found that phospho-RyR2, phospho-CaMKII, phospho-p38 MAPK, and phospho-PLB were significantly upregulated by HRC-KD in TAC-FH. A significantly increased level of cleaved caspase-3, a cardiac cell death marker was also found, consistent with the result of TUNEL assay.Increased Ca(2+ leak and cytosolic Ca(2+ concentration due to a partial KD of HRC could enhance activity of CaMKII and phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in TAC-FH. Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through

  6. Links and opportunities

    Science.gov (United States)

    1999-09-01

    At the end of June a new website was launched to enable young people to get involved with the UK's national Foresight programme and to help shape the future. `School of the Future - Young people with Foresight' will provide young people with the means to contribute to the national programme which develops scenarios of the future, looking at possible needs, opportunities or threats and deciding what should be done now to make sure these challenges can be met. The site can be found at www.asset.org.uk and it will be run by the Association for Schools' Science, Engineering and Technology (ASSET). The latest round of Foresight began in April and panels are taking a look at the aging population, crime prevention, built environment and transport, aerospace and systems, energy and the natural environment, information, communications and media, materials and sustainable development, amongst other topics. Information about Foresight activities and events can be obtained from the Office of Science and Technology or the Foresight Knowledge pool at www.foresight.gov.uk. The pool will act as a unique and freely accessible electronic library of views and information about the future that young people will be able to draw on for assistance and reference material. Futher assistance for students will also be on offer from museums and art galleries from now on, thanks to additional funding which has been made available over the next three years. Forty museums and galleries will share up to #2.5m for projects intended to improve students' literacy, numeracy and science skills as well as their understanding of history and art. Examples of the imaginative projects which have been put forward include use of the large collection of steam engines at the Museum of Science and Industry in Manchester to assist boys' science and literacy skills. The Museum of London will be working with over 2000 schools in the South East to provide materials for the schools' own mini-museums on the Romans

  7. 12 CFR 268.202 - Equal Pay Act.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Equal Pay Act. 268.202 Section 268.202 Banks... REGARDING EQUAL OPPORTUNITY Provisions Applicable to Particular Complaints § 268.202 Equal Pay Act. Complaints alleging violations of the Equal Pay Act shall be processed under this part. ...

  8. 29 CFR 1614.202 - Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Equal Pay Act. 1614.202 Section 1614.202 Labor Regulations... OPPORTUNITY Provisions Applicable to Particular Complaints § 1614.202 Equal Pay Act. (a) In its enforcement of the Equal Pay Act, the Commission has the authority to investigate an agency's employment practices on...

  9. A Leadership Journey: Personal Reflections from the School of Hard Knocks

    Directory of Open Access Journals (Sweden)

    R. Scott Pochron

    2009-12-01

    Full Text Available The following paper chronicles the evolution of the author’s thinking onleadership through the course of his work experience. Leadership is viewed as adynamical process involving both formal and informal roles. The process is initiated asan individual identifies opportunities and feels pulled to respond to emerging patterns andinitiate action to enable positive change. The dynamics between formal and informalleadership structures and leadership as a state of mind are discussed.

  10. A Leadership Journey: Personal Reflections from the School of Hard Knocks

    Directory of Open Access Journals (Sweden)

    R. Scott Pochron

    2009-12-01

    Full Text Available The following paper chronicles the evolution of the author’s thinking on leadership through the course of his work experience. Leadership is viewed as a dynamical process involving both formal and informal roles. The process is initiated as an individual identifies opportunities and feels pulled to respond to emerging patterns and initiate action to enable positive change. The dynamics between formal and informal leadership structures and leadership as a state of mind are discussed.

  11. The French Opportunity

    DEFF Research Database (Denmark)

    Andersen, Steen

    2015-01-01

    defined by administrative control, the implementation of institutions and a variety of military exploitation strategies. Plundering, looting and requisitions were frequent aggressive acts, but beyond these interventions by force, specific institutions were created to gain control over the occupied...

  12. Molecular mechanisms of irbesartan suppressing atherosclerosis in high cholesterol-diet apolipoprotein E knock-out mice.

    Science.gov (United States)

    Yao, Rui; Cheng, Xiang; Chen, Yong; Xie, Jiang-Jiao; Yu, Xian; Liao, Meng-Yang; Ding, Ying-Jun; Tang, Ting-Ting; Liao, Yu-Hua

    2010-03-04

    Atherosclerosis is a chronic inflammatory disease in which the renin-angiotensin-aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of an angiotensin type 1 receptor blocker irbesartan on atherogenesis in high cholesterol-diet apolipoprotein E knock-out mice. Adult male apolipoprotein E knock-out mice were given normal diet or high cholesterol-diet and randomized to receive no treatment or irbesartan 10 mg kg(-1) d(-1) for 12 weeks. The apolipoprotein E knock-out mice with high cholesterol-diet were associated with a marked increase in atherosclerotic lesion area, plasma lipid and angiotensin II levels, as well as the expressions of angiotensin type 1 receptor in the aorta. High cholesterol-diet feeding increases the activity of NADPH oxidase subunits (p47(phox) and Rac), extracellular signal-regulated kinase 1/2, janus kinase 2, signal transducer and activator of transcription 3, nuclear factor-kappaB and the expression of tumor necrosis factor-alpha, interleukin 6, monocyte chemoattactant protein-1 and vascular cell adhesion molecule-1 in the aortas. These changes were suppressed in mice that were treated with irbesartan 10 mg kg(-1) d(-1), with no significant change in systolic blood pressure and plasma lipid levels. The results suggest that irbesartan can attenuate atherosclerosis, and this effect is partly related to the inhibition of oxidative stress and inflammatory signal transduction pathways which eventually leads to the decrease in the expression of inflammatory cytokines. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

  13. A method for stable gene knock-down by RNA interference in larvae of the salmon louse (Lepeophtheirus salmonis).

    Science.gov (United States)

    Eichner, Christiane; Nilsen, Frank; Grotmol, Sindre; Dalvin, Sussie

    2014-05-01

    The salmon louse (Lepeophtheirus salmonis), an ectoparasitic copepod of salmonid fish, is a major threat to aquaculture in Norway, Ireland, Scotland and Canada. Due to rise in resistance against existing pesticides, development of novel drugs or vaccines is necessary. Posttranscriptional gene silencing by RNA interference (RNAi), when established in a high throughput system is a potential method for evaluation of molecular targets for new medical compounds or vaccine antigens. Successful use of RNAi has been reported in several stages of salmon lice. However, when we employed a previously described protocol for planktonic stages, no reproducible down-regulation of target genes was gained. In the present study, we describe a robust method for RNAi, where nauplius larvae are soaked in seawater added double stranded RNA (dsRNA). In order to test for when dsRNA may be introduced, and for the efficacy and duration of RNAi, we performed a series of experiments on accurately age determined larvae, ranging from the hatching egg to the copepodid with a salmon louse coatomer and a putative prostaglandin E synthase gene. Presumptive knock-down was monitored by real time PCR. Significant gene silencing was obtained only when nauplius I larvae were exposed to dsRNA during the period in which they molted to nauplius II. A knock down effect could be detected 2days after soaking, and it remained stable until the last measurement, on day 12. Soaking nauplius I larvae, knock-down was verified for six additional genes with a putative role in molting. For one chitinase, a loss-of-function phenotype with abnormal swimming was obtained. Hence, RNAi, induced in the nauplius, may facilitate studies of the molecular biology of the louse, such as the function of specific genes in developmental processes and physiology, host recognition, host-parasite interaction, and, in extension, the engineering of novel medicines. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Spark ignition engine performance and emissions in a high compression engine using biogas and methane mixtures without knock occurrence

    Directory of Open Access Journals (Sweden)

    Gómez Montoya Juan Pablo

    2015-01-01

    Full Text Available With the purpose to use biogas in an internal combustion engine with high compression ratio and in order to get a high output thermal efficiency, this investigation used a diesel engine with a maximum output power 8.5 kW, which was converted to spark ignition mode to use it with gaseous fuels. Three fuels were used: Simulated biogas, biogas enriched with 25% and 50% methane by volume. After conversion, the output power of the engine decreased by 17.64% when using only biogas, where 7 kW was the new maximum output power of the engine. The compression ratio was kept at 15.5:1, and knocking did not occur during engine operation. Output thermal efficiency operating the engine in SI mode with biogas enriched with 50% methane was almost the same compared with the engine running in diesel-biogas dual mode at full load and was greater at part loads. The dependence of the diesel pilot was eliminated when biogas was used in the engine converted in SI mode. The optimum condition of experiment for the engine without knocking was using biogas enriched with 50% methane, with 12 degrees of spark timing advance and equivalence ratio of 0.95, larger output powers and higher values of methane concentration lead the engine to knock operation. The presence of CO2 allows operating engines at high compression ratios with normal combustion conditions. Emissions of nitrogen oxides, carbon monoxide and unburnt methane all in g/kWh decreased when the biogas was enriched with 50% methane.

  15. Gene silencing in Phlebotomine sand flies: xanthine dehydrogenase knock down by dsRNA micro-injections

    Science.gov (United States)

    Sant’ Anna, Mauricio R V; Alexander, Bruce; Bates, Paul A; Dillon, Rod J

    2009-01-01

    Lutzomyia longipalpis are vectors of medically important visceral leishmaniasis in South America. Bloodfed adult females digest large amounts of protein, and xanthine dehydrogenase is thought to be a key enzyme involved in protein catabolism through the production of urate. Large amounts of heme are also released during digestion with potentially damaging consequences, as heme can generate oxygen radicals that damage to lipids, proteins and nucleic acids. However, urate is an anti-oxidant that may prevent such oxidative damage produced by heme. We investigated xanthine dehydrogenase by developing the RNAi technique for sand flies and used this technique to knock down the Lu. longipalpis xanthine dehydrogenase gene to evaluate its role in survival of adult females after blood feeding. The gene sequence of Lu. longipalpis xanthine dehydrogenase is described together with expression in different life cycle stages and RNAi knock down. Semi quantitative RT-PCR of xanthine dehydrogenase expression showed a significant increase in expression after bloodmeal ingestion. Micro-injection of dsRNA via the thorax of 1 day old adult female sand flies resulted in approximately 40% reduction of xanthine dehydrogenase gene expression in comparison to flies injected with a control dsRNA. A significant reduction of urate in the whole body and excretions of Lu. longipalpis was observed after dsRNA xanthine dehydrogenase microinjection and feeding 96h later on rabbit blood. Sand flies injected with XDH dsRNA also exhibit significantly reduced life span in comparison with the mock-injected group when fed on sucrose or when rabbit blood fed, showing that urate could be indeed an important free radical scavenger in Lu. Longipalpis. The demonstration of xanthine dehydrogenase knock down by dsRNA microinjection, low mortality of micro-injected insects and the successful bloodfeeding of injected insects demonstrated the utility of RNAi as a tool for functional analysis of genes in

  16. Generation of two H1 hESC sublines carrying a heterozygous and homozygous knock-out of RB1

    Directory of Open Access Journals (Sweden)

    Laura Steenpass

    2017-12-01

    Full Text Available Retinoblastoma is a childhood cancer of the retina caused by biallelic inactivation of the tumor suppressor gene RB1. In heritable retinoblastoma, one allele is inherited in mutant form via one of the parental germ cells. To study molecular mechanisms in retinoblastoma, two sublines of H1 hESCs were generated, carrying a knock-out allele of RB1 in the heterozygous or homozygous state. Exon 3 of RB1 was targeted and modified by nucleotide deletions using the CRISPR/Cas9 nuclease system. Based on a nearby single nucleotide polymorphism, the modification could be assigned to one allele.

  17. Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.

    Directory of Open Access Journals (Sweden)

    Nikita Zabinyakov

    Full Text Available Pyridoxine dependent epilepsy (PDE is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1 and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA, piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites. There is no animal model for high throughput drug screening. For this reason, we developed and characterized the first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9 mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by high resolution melt analysis, direct sequencing and QIAxcel system. Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry. Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp mutation in ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion and a rapid circling swim behavior earliest 8-day post fertilization (dpf. Electroencephalogram revealed large amplitude spike discharges compared to wild type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6-carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type. Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale drug screening using behavioral and biochemical features and accurately recapitulates the human PDE-ALDH7A1 disease.

  18. Generating innovation opportunities:

    DEFF Research Database (Denmark)

    Kallio, Anne; Bergenholtz, Carsten

    2011-01-01

    This study examines how a company can generate innovation opportunities by exploring and absorbing customer knowledge. The exploration can be performed via an in-depth or broad search for resources beyond organisational boundaries. Salespeople are an essential channel for an in-depth search...

  19. Raiding Opportunities and Unemployment

    DEFF Research Database (Denmark)

    Tranæs, Torben

    2001-01-01

    This article studies the impact of raiding opportunities in a labor market in which worker abilities differ. Recruiting firms can either raid an elsewhere-employed worker of known ability by bidding up his wage or go through costly search to find a good worker among the unemployed. In equilibrium...

  20. Opportunity Cost: A Reply

    Science.gov (United States)

    Parkin, Michael

    2016-01-01

    The author's objective for this reply in reexamining opportunity cost was to draw attention to two conflicting definitions of the concept in current use and to argue the case for dropping one of them. The comments of Daniel Arce, Rod O'Donnell, and Daniel Stone might be read as demonstration that the author has failed on both counts. Such a…

  1. Opportunity at 'Cook Islands'

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,825th Martian day, or sol, of Opportunity's surface mission (March 12, 2009). North is at the top. The rover had driven half a meter (1.5 feet) earlier on Sol 1825 to fine-tune its location for placing its robotic arm onto an exposed patch of outcrop including a target area informally called 'Cook Islands.' On the preceding sol, Opportunity turned around to drive frontwards and then drove 4.5 meters (15 feet) toward this outcrop. The tracks from the SOl 1824 drive are visible near the center of this view at about the 11 o'clock position. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Opportunity had previously been driving backward as a strategy to redistribute lubrication in a wheel drawing more electrical current than usual. The outcrop exposure that includes 'Cook Islands' is visible just below the center of the image. The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock. This view is presented as a cylindrical projection with geometric seam correction.

  2. Knock-down of CD44 regulates endothelial cell differentiation via NFκB-mediated chemokine production.

    Directory of Open Access Journals (Sweden)

    Berit Olofsson

    Full Text Available A striking feature of microvascular endothelial cells is their capacity to fuse and differentiate into tubular structures when grown in three-dimensional (3D extracellular matrices, in collagen or Matrigel, mimicking the in vivo blood vessel formation. In this study we demonstrate that human telomerase-immortalised foreskin microvascular endothelial (TIME cells express high levels of the hyaluronan receptor CD44 and the hyaluronidase HYAL2. Knock-down of CD44 or HYAL2 resulted in an inability of TIME cells to form a tubular network, suggesting a key regulatory role of hyaluronan in controlling TIME cell tubulogenesis in 3D matrices. Knock-down of CD44 resulted in an upregulation of mRNA expression of the chemokines CXCL9 and CXCL12, as well as their receptors CXCR3 and CXCR4. This was accompanied by a defect maturation of the tubular structure network and increased phosphorylation of the inhibitor of NFκB kinase (IKK complex and thus translocation of NFκB into the nucleus and activation of chemokine targed genes. Furthermore, the interaction between CD44 and hyaluronan determines the adhesion of breast cancer cells. In summary, our observations support the notion that the interaction between CD44 and hyaluronan regulates microvascular endothelial cell tubulogenesis by affecting the expression of cytokines and their receptors, as well as breast cancer dissemination.

  3. Cytogenetic responses to ionizing radiation exposure of human fibroblasts with knocked-down expressions of various DNA damage signaling genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Wu, Honglu

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with up-regulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. Here, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yields of MN and/or CA formation were significantly increased by suppressed expression of some of the selected genes in DSB and other DNA repair pathways. Knocked-down expression of other genes showed significant impact on cell cycle progression, possibly because of severe impairment of DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  4. Generation and characterization of a collection of knock-down lines for the chloroplast Clp protease complex in tobacco.

    Science.gov (United States)

    Moreno, Juan C; Tiller, Nadine; Diez, Mercedes; Karcher, Daniel; Tillich, Michael; Schöttler, Mark A; Bock, Ralph

    2017-04-01

    Protein degradation in chloroplasts is carried out by a set of proteases that eliminate misfolded, damaged, or superfluous proteins. The ATP-dependent caseinolytic protease (Clp) is the most complex protease in plastids and has been implicated mainly in stromal protein degradation. In contrast, FtsH, a thylakoid membrane-associated metalloprotease, is believed to participate mainly in the degradation of thylakoidal proteins. To determine the role of specific Clp and FtsH subunits in plant growth and development, RNAi lines targeting at least one subunit of each Clp ring and FtsH were generated in tobacco. In addition, mutation of the translation initiation codon was employed to down-regulate expression of the plastid-encoded ClpP1 subunit. These protease lines cover a broad range of reductions at the transcript and protein levels of the targeted genes. A wide spectrum of phenotypes was obtained, including pigment deficiency, alterations in leaf development, leaf variegations, and impaired photosynthesis. When knock-down lines for the different protease subunits were compared, both common and specific phenotypes were observed, suggesting distinct functions of at least some subunits. Our work provides a well-characterized collection of knock-down lines for plastid proteases in tobacco and reveals the importance of the Clp protease in physiology and plant development. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. User Frustrations as Opportunities

    Directory of Open Access Journals (Sweden)

    Michael Weiss

    2012-04-01

    Full Text Available User frustrations are an excellent source of new product ideas. Starting with this observation, this article describes an approach that entrepreneurs can use to discover business opportunities. Opportunity discovery starts with a problem that the user has, but may not be able to articulate. User-centered design techniques can help elicit those latent needs. The entrepreneur should then try to understand how users are solving their problem today, before proposing a solution that draws on the unique skills and technical capabilities available to the entrepreneur. Finally, an in-depth understanding of the user allows the entrepreneur to hone in on the points of difference and resonance that are the foundation of a strong customer value proposition.

  6. Crisis -- A Leadership Opportunity

    Science.gov (United States)

    2005-04-01

    recognized the great value in understanding crisis theory and the leadership strategies to employ during these situations. Additionally, we discovered...ed.: 50. Mitroff, Ian I. Crisis leadership : Planning for the Unthinkable. Hoboken: Wiley, 2004. Murphy, P. (1996). "Chaos Theory as a Model...Crisis–A Leadership Opportunity COL Victor Braden, ARNG CAPT Justin Cooper II, USN COL Michael Klingele, USA Lt Col John P

  7. ESP for finding opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Puskar, J.R.

    1996-05-01

    Remember the {open_quotes}Amazing Kreskin{close_quotes} or even Johnny Carson`s {open_quotes}Carnac{close_quotes}. They claimed to have the ability to know about things with very little information. This article describes techniques that can help you be close to as effective in diagnosing compressed air, steam/condensate, and water leaks and/or opportunities without ever leaving your boilerhouse. Consider this a short course in becoming clairvoyant.

  8. Project X: Physics Opportunities

    CERN Document Server

    Kronfeld, Andreas S; Al-Binni, Usama; Altmannshofer, Wolfgang; Ankenbrandt, Charles; Babu, Kaladi; Banerjee, Sunanda; Bass, Matthew; Batell, Brian; Baxter, David V; Berezhiani, Zurab; Bergevin, Marc; Bernstein, Robert; Bhattacharya, Sudeb; Bishai, Mary; Blum, Thomas; Bogacz, S Alex; Brice, Stephen J; Brod, Joachim; Bross, Alan; Buchoff, Michael; Burgess, Thomas W; Carena, Marcela; Castellanos, Luis A; Chattopadhyay, Subhasis; Chen, Mu-Chun; Cherdack, Daniel; Christ, Norman H; Chupp, Tim; Cirigliano, Vincenzo; Coloma, Pilar; Coppola, Christopher E; Cowsik, Ramanath; Crabtree, J Allen; Delahaye, Jean-Pierre; Denisov, Dmitri; deNiverville, Patrick; de Gouvêa, André; Dharmapalan, Ranjan; Dolgov, Alexander; Dvali, Georgi; Eichten, Estia; Engelfried, Jürgen; Ferguson, Phillip D; Gabriel, Tony; Gal, Avraham; Gallmeier, Franz; Ganezer, Kenneth S; Gardner, Susan; Glenzinski, Douglas; Godfrey, Stephen; Golubeva, Elena S; Gori, Stefania; Graves, Van B; Greene, Geoffrey; Griffard, Cory L; Haisch, Ulrich; Handler, Thomas; Hartfiel, Brandon; Hawari, Ayman; Heilbronn, Lawrence; Hill, James E; Huber, Patrick; Jaffe, David E; Johnson, Christian; Kamyshkov, Yuri; Kaplan, Daniel M; Kerbikov, Boris; Kiburg, Brendan; Kirk, Harold G; Klein, Andreas; Knoepfel, Kyle; Kopeliovich, Boris; Kopeliovich, Vladimir; Kopp, Joachim; Korsch, Wolfgang; Kribs, Graham; Lipton, Ronald; Liu, Chen-Yu; Lorenzon, Wolfgang; Lu, Zheng-Tian; Makins, Naomi C R; McKeen, David; Mills, Geoffrey; Mohapatra, Rabindra; Mokhov, Nikolai V; Mocko, Michael; Muhrer, Guenter; Mumm, Pieter; Okun, Lev; Neuffer, David; Palmer, Mark A; Palmer, Robert; Pattie, Robert W; Phillips, David G; Pronsikh, Vitaly; Pitts, Kevin; Pospelov, Maxim; Quigg, Chris; Ramberg, Erik; Ray, Amlan; Reimer, Paul E; Richards, David G; Ritz, Adam; Roy, Amit; Ruggles, Arthur; Ryne, Robert; Sarkar, Utpal; Saunders, Andy; Semertzidis, Yannis K; Serebrov, Anatoly; Shimizu, Hirohiko; Shrock, Robert; Snopok, Pavel V; Snow, William M; Sikdar, Arindam K; Soha, Aria; Spanier, Stefan; Striganov, Sergei; Tang, Zhaowen; Townsend, Lawrence; Urheim, Jon; Vainshtein, Arkady; Van Kooten, Richard J; Van de Water, Richard; Van de Water, Ruth S; Wehring, Bernard; Whitehead, Lisa; Wilson, Robert J; Worcester, Elizabeth; Young, Albert R; Wester, William C; Zeller, Geralyn

    2013-01-01

    Part 2 of "Project X: Accelerator Reference Design, Physics Opportunities, Broader Impacts". In this Part, we outline the particle-physics program that can be achieved with Project X, a staged superconducting linac for intensity-frontier particle physics. Topics include neutrino physics, kaon physics, muon physics, electric dipole moments, neutron-antineutron oscillations, new light particles, hadron structure, hadron spectroscopy, and lattice-QCD calculations.

  9. Picture windows of opportunity

    Science.gov (United States)

    Mattingly, S.

    1987-01-01

    We hate to say that we need a moderate earthquake every once in a while, but experience shows that it surely helps to sell all kinds of seismic safety programs It took the 933 Long Beach earthquake to get the Field Act passed in California requiring the strengthening of our public schools.

  10. VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs.

    Science.gov (United States)

    Sidibé, Adama; Polena, Helena; Pernet-Gallay, Karin; Razanajatovo, Jeremy; Mannic, Tiphaine; Chaumontel, Nicolas; Bama, Soumalamaya; Maréchal, Irène; Huber, Philippe; Gulino-Debrac, Danielle; Bouillet, Laurence; Vilgrain, Isabelle

    2014-08-01

    Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 ± 0.3, n = 78; and VE-Y685F, 12.48 ± 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary

  11. Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Motoharu Ono

    Full Text Available We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

  12. Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

    Science.gov (United States)

    Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

    2015-02-01

    Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

  13. Frontier Aerospace Opportunities

    Science.gov (United States)

    Bushnell, Dennis M.

    2014-01-01

    Discussion and suggested applications of the many ongoing technology opportunities for aerospace products and missions, resulting in often revolutionary capabilities. The, at this point largely unexamined, plethora of possibilities going forward, a subset of which is discussed, could literally reinvent aerospace but requires triage of many possibilities. Such initial upfront homework would lengthen the Research and Development (R&D) time frame but could greatly enhance the affordability and performance of the evolved products and capabilities. Structural nanotubes and exotic energetics along with some unique systems approaches are particularly compelling.

  14. Informal Opportunity among SMEs

    DEFF Research Database (Denmark)

    Rezaei, Shahamak; Dana, Leo-Paul; Goli, Marco

    2013-01-01

    Based on interviews with (legal and illegal) immigrants to Denmark, meetings with stakeholders and with experts in the field, this article addresses issues regarding the underground economy. Our findings show that, in Denmark, the existence of an underground economy makes it possible for semi......-compliant and non-compliant immigrants to make a living. We suggest that the underground economy in Denmark will continue to provide networks of illegal residents with opportunities for informal economic activities as trust allows entrepreneurs to function below the radar, by owning enterprises registered using...

  15. Transgenic tools for analysis of the haematopoietic system: knock-in CD45 reporter and deletor mice.

    Science.gov (United States)

    Yang, Jian; Hills, David; Taylor, Erin; Pfeffer, Klaus; Ure, Jan; Medvinsky, Alexander

    2008-09-15

    We have produced and characterised reporter knock-in CD45-YFP and CD45-Cre mice that drive expression of yellow fluorescent protein (YFP) and Cre-recombinase, respectively under control of the haematopoietic CD45 locus. CD45-YFP expression was characterised in various haematopoietic cells populations. The activity of CD45-Cre mice was assessed by crossing with silent GFP reporter mice. Flow cytometry analysis indicated that both CD45-YFP and CD45-Cre were strongly expressed in the CD45(+) compartment of peripheral blood. Expression of these markers in various populations of adult bone marrow, including primitive cell populations was also determined. These mouse models will be useful for the direct visualisation of haematopoietic cells, especially at the periphery, and for gene knockout studies, in the haematopoietic system.

  16. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

    Directory of Open Access Journals (Sweden)

    Noah Saederup

    2010-10-01

    Full Text Available Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

  17. Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

    Directory of Open Access Journals (Sweden)

    Tomáš Venit

    Full Text Available BACKGROUND: Nuclear myosin I (NM1 is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c. Located on the 11(th chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. CONCLUSION/SIGNIFICANCE: We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.

  18. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis

    Directory of Open Access Journals (Sweden)

    Jérôme eDoyen

    2013-01-01

    Full Text Available The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases CAIX and CAXII constitute a robust pHi-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibroblasts cells (-/+ CAIX and LS174Tr cells (inducible knock-down for ca9/ca12 were analyzed for cell cycle phase distribution and survival after irradiation in extracellular pHo manipulations and hypoxia (1% O2 exposure. Radiotherapy was used to target ca9/ca12-silenced LS174Tr tumors grown in nude mice. We found that diminishing the pHi-regulating capacity of fibroblasts through inhibition of NHE-1 sensitize cells to radiation-induced cell death. Secondly, the pHi-regulating function of CAIX plays a key protective role in irradiated fibroblasts in an acidic environment as accompanied by a reduced number of cells in the radiosensitive phases of the cell cycle. Thirdly, we demonstrate that irradiation of LS174Tr spheroids, silenced for either ca9 or both ca9/ca12, showed a respective 50% and 75% increase in cell death as a result of a decrease in cell number in the radioresistant S phase and a disruption of CA-mediated pHi regulation. Finally, LS174Tr tumor progression was strongly decreased when ca9/ca12 silencing was combined with irradiation in vivo. These findings highlight the combinatory use of radiotherapy with targeting of the pHi-regulating carbonic anhydrases as an anti-cancer strategy.

  19. Opportunity and obligation

    CERN Multimedia

    2012-01-01

    As anyone in the press or VIP offices can tell you, CERN is in the spotlight like never before. In the first two months of 2012, we welcomed some 56 VIP visits and 144 media visits on site. Not long ago, those were the kind of numbers we’d have had in six months, and 2012 is not a one-off.   Ever since CERN turned 50 in 2004, our visitor numbers have been growing, and that includes teachers and members of the public as well as VIPs and the media. It’s a sign of the explosion of interest around the world in our science, and to me it means two things. Firstly, it means that I owe everyone at CERN a vote of thanks, since I know that visits impinge on everyone’s time. I can assure you all, however, that it is time well spent. That’s because the second thing it tells me is that growing interest in CERN brings opportunity. Our current visibility gives the particle physics community the opportunity to drive science up the popular and political agendas, and it...

  20. Access to Education and Employment Opportunities: Implications for Poverty Reduction

    Science.gov (United States)

    Adewale, T. M.

    2011-01-01

    The study examined the linkages between Education and poverty and the possibility of poverty reduction through access to education and better employment opportunities. The paper also stressed that poverty acts as both cause and effect on lack of education. In particular the paper examined whether education is contributing to poverty reduction…

  1. Healthcare.gov: Opportunity out of Disaster. Teaching Case

    Science.gov (United States)

    Cundiff, Jacob; McCallum, Taylor; Rich, Andrew; Truax, Michael; Ward, Tamara; Havelka, Douglas

    2015-01-01

    The launch of HealthCare.gov, the website of the Affordable Care Act (AKA Obamacare), was a major public relations disaster for the Obama administration. This case examines some of the factors that contributed to the failure of the launch and then details how Optum, an information technology service provider, considered the opportunity provided by…

  2. Interactive Fiction: "New Literacy" Learning Opportunities for Children

    Science.gov (United States)

    Kozdras, Deborah; Haunstetter, Denise Marie; King, James R.

    2006-01-01

    Interactive fiction has great potential for use in schools, providing engaging and empowering opportunities for learning and literacy. Experiences with interactive fiction provide two key components lacking in contemporary storytelling mediums: autonomy (the ability to act and change on its own) and interactivity (or the ability to think and react…

  3. 20 CFR 638.541 - Job Corps training opportunities.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Job Corps training opportunities. 638.541 Section 638.541 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.541 Job Corps...

  4. Creative State Pre-K Policies Offer Smart Federal Opportunities

    Science.gov (United States)

    Pew Center on the States, 2011

    2011-01-01

    Reauthorization of the Elementary and Secondary Education Act offers an opportunity to invest in programs with the greatest educational and economic benefits. Members of Congress should look to states for flexible, innovative, bipartisan strategies to gradually grow pre-k programs. This brief highlights some of the most promising state efforts to…

  5. 78 FR 18360 - Fiscal Year (FY) 2013 Funding Opportunity

    Science.gov (United States)

    2013-03-26

    ... Service Act, as amended . Justification: Eligibility for this SPF SIG award is limited to the state of... never been awarded a SPF SIG grant from SAMHSA. The SPF SIG grant has already allowed 49 states to... of Idaho will have the opportunity to use SPF SIG funds to develop a comprehensive prevention plan at...

  6. Ionospheric research opportunity

    Science.gov (United States)

    Rickel, Dwight

    1985-05-01

    Ground-based explosions have been exploited successfully in the past as a relatively controlled source for producing ionospheric disturbances. On June 25, the Defense Nuclear Agency will conduct a high explosives test on the northern section of the White Sands Missile Range. Approximately 4,800 tons of ammonium nitrate and fuel oil (ANFO) will be detonated at ground level, producing an acoustic shock wave with a surface pressure change of approximately 20 mbar at a 6 km range. This shock front will have sufficient strength to propagate into the ionosphere with at least a 10% change in the ambient pressure across the disturbance front in the lower F region. Such an ionospheric perturbation will give ionospheric researchers an excellent opportunity to investigate acoustic propagation at ionospheric heights, shock dissipation effect, the ion-neutral coupling process, acoustic-gravity wave (traveling ionospheric disturbance) generation mechanisms, and associated RF phenomena.

  7. Valles Galdera research opportunity

    Science.gov (United States)

    1984-04-01

    Potential opportunities for research will be available after the completion this summer of a 650-m, 7.6-cm-diameter scientific core taken from the southern ring-fracture zone of Valles Caldera, New Mexico. (See Figure 1.)The Valles Caldera coring effort stems from three primary objectives: to study the hydrogeochemistry of a subsurface geothermal outflow zone of the caldera near the source of convective upflow; to obtain structural and stratigraphic information from intracaldera rock formations under the southern ring-fracture zone; and to obtain continuous core (6.25 cm) samples through the youngest volcanic unit in Valles Caldera, the Banco Bonito obsidian (approximately 0.1 to 0.05 million years).

  8. A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

    2010-01-01

    The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...

  9. The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica)

    NARCIS (Netherlands)

    Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G.F.; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J.; Malnoy, Mickael

    2016-01-01

    Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO

  10. Anticoagulant Effect of Dietary Fish Oil in Hyperlipidemia A Study of Hepatic Gene Expression in APOE2 Knock-in Mice

    NARCIS (Netherlands)

    Vanschoonbeek, Kristof; Wouters, Kristiaan; van der Meijden, Paola E. J.; van Gorp, Patrick J.; Feijge, Marion A. H.; Herfs, Marjolein; Schurgers, Leon J.; Hofker, Marten H.; de Maat, Moniek P. M.; Heemskerk, Johan W. M.

    2008-01-01

    Objective-In hyperlipidemia, dietary fish oil containing n-3 polyunsaturated fatty acids (PUFA) provokes plasma triacylglycerol lowering and hypocoagulant activity. Using APOE2 knock-in mice, the relation of these fish-oil effects with altered gene expression was investigated. Methods and

  11. Anticoagulant effect of dietary fish oil in hyperlipidemia. A study of hepatic gene expression in APOE2 knock-in mice

    NARCIS (Netherlands)

    K. Vanschoonbeek (Kristof); K. Wouters (Kristiaan); P.E.J. van der Meijden (Paola); P.J. van Gorp (Patrick); M.A.H. Feijge (Marion); M. Herfs (Marjolein); L.J. Schurgers; M.A. Hofker (Marten); M.P.M. de Maat (Moniek); J.W.M. Heemskerk (Johan)

    2008-01-01

    textabstractObjective - In hyperlipidemia, dietary fish oil containing n-3 polyunsaturated fatty acids (PUFA) provokes plasma triacylglycerol lowering and hypocoagulant activity. Using APOE2 knock-in mice, the relation of these fish-oil effects with altered gene expression was investigated. Methods

  12. Fluorescent protein tagging of endogenous protein in brain neurons using CRISPR/Cas9-mediated knock-in and in utero electroporation techniques.

    Science.gov (United States)

    Uemura, Takeshi; Mori, Takuma; Kurihara, Taiga; Kawase, Shiori; Koike, Rie; Satoga, Michiru; Cao, Xueshan; Li, Xue; Yanagawa, Toru; Sakurai, Takayuki; Shindo, Takayuki; Tabuchi, Katsuhiko

    2016-10-26

    Genome editing is a powerful technique for studying gene functions. CRISPR/Cas9-mediated gene knock-in has recently been applied to various cells and organisms. Here, we successfully knocked in an EGFP coding sequence at the site immediately after the first ATG codon of the β-actin gene in neurons in the brain by the combined use of the CRISPR/Cas9 system and in utero electroporation technique, resulting in the expression of the EGFP-tagged β-actin protein in cortical layer 2/3 pyramidal neurons. We detected EGFP fluorescence signals in the soma and neurites of EGFP knock-in neurons. These signals were particularly abundant in the head of dendritic spines, corresponding to the localization of the endogenous β-actin protein. EGFP knock-in neurons showed no detectable changes in spine density and basic electrophysiological properties. In contrast, exogenously overexpressed EGFP-β-actin showed increased spine density and EPSC frequency, and changed resting membrane potential. Thus, our technique provides a potential tool to elucidate the localization of various endogenous proteins in neurons by epitope tagging without altering neuronal and synaptic functions. This technique can be also useful for introducing a specific mutation into genes to study the function of proteins and genomic elements in brain neurons.

  13. Engineered disease resistance in cotton using RNA-interference to knock down cotton leaf curl kokhran virus-Burewala and cotton leaf curl Multan betasatellite

    Science.gov (United States)

    Cotton Leaf Curl virus Disease (CLCuD) has caused enormous losses in cotton (Gossypium hirsutum) production in Pakistan. RNA interference (RNAi) is an emerging technique that could knock out CLCuD by targeting different regions of the pathogen genome that are important for replication, transcription...

  14. Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

    Science.gov (United States)

    Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

    2017-03-01

    Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  15. Comparative Analysis of KnockOut™ Serum with Fetal Bovine Serum for the In Vitro Long-Term Culture of Human Limbal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Shaokun Zhang

    2016-01-01

    Full Text Available The limbal epithelial cells can be maintained on 3T3 feeder layer with fetal bovine serum supplemented culture medium, and these cells have been used to successfully treat limbal stem cell deficiency. However, fetal bovine serum contains unknown components and displays quantitative and qualitative lot-to-lot variations. To improve the culture condition, the defined KnockOut serum replacement was investigated to replace fetal bovine serum for culturing human limbal epithelial cell. Human primary limbal epithelial cells were cultured in KnockOut serum and fetal bovine serum supplemented medium, respectively. The cell growth rate, gene expression, and maintenance of limbal epithelial stem cells were studied and compared between these two groups. Human primary limbal epithelial cells were isolated and successfully serially cultivated in this novel KnockOut serum supplemented medium; the cell proliferation and stem cell maintenance were similar to those of cells grown in fetal bovine serum supplemented medium. These data suggests that this KnockOut serum supplemented medium is an efficient replacement to traditional fetal bovine serum supplemented medium for limbal epithelial cell culture, and this medium has great potential for long term maintenance of limbal epithelial cells, limbal epithelial stem cells transplantation, and tissue regeneration.

  16. Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids

    Directory of Open Access Journals (Sweden)

    Tetsushi Sakuma

    2015-10-01

    Full Text Available Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc gene, in Chinese hamster ovary (CHO cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins.

  17. Using strategic foresight to assess conservation opportunity.

    Science.gov (United States)

    Cook, Carly N; Wintle, Bonnie C; Aldrich, Stephen C; Wintle, Brendan A

    2014-12-01

    The nature of conservation challenges can foster a reactive, rather than proactive approach to decision making. Failure to anticipate problems before they escalate results in the need for more costly and time-consuming solutions. Proactive conservation requires forward-looking approaches to decision making that consider possible futures without being overly constrained by the past. Strategic foresight provides a structured process for considering the most desirable future and for mapping the most efficient and effective approaches to promoting that future with tools that facilitate creative thinking. The process involves 6 steps: setting the scope, collecting inputs, analyzing signals, interpreting the information, determining how to act, and implementing the outcomes. Strategic foresight is ideal for seeking, recognizing, and realizing conservation opportunities because it explicitly encourages a broad-minded, forward-looking perspective on an issue. Despite its potential value, the foresight process is rarely used to address conservation issues, and previous attempts have generally failed to influence policy. We present the strategic foresight process as it can be used for proactive conservation planning, describing some of the key tools in the foresight tool kit and how they can be used to identify and exploit different types of conservation opportunities. Scanning is an important tool for collecting and organizing diverse streams of information and can be used to recognize new opportunities and those that could be created. Scenario planning explores how current trends, drivers of change, and key uncertainties might influence the future and can be used to identify barriers to opportunities. Backcasting is used to map out a path to a goal and can determine how to remove barriers to opportunities. We highlight how the foresight process was used to identify conservation opportunities during the development of a strategic plan to address climate change in New York

  18. Learning Opportunities (Editorial

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    Denise Koufogiannakis

    2009-12-01

    Full Text Available We’ve reached the end of another year of publication at EBLIP, my first at the helm as Editor‐in‐Chief, and four full years of publication since we began. This year was a busy one with several changes to the editorial team, the addition of more Editorial Advisors, and new evidence summary writers joining our team. Most importantly, the journal continues to grow and thrive, with more people than ever participating in its success. This year we added a new section called Using Evidence in Practice, and in this issue there are two articles in that section which provide practical examples of applying evidence in the workplace. Putting evidence into practice is what EBLIP is all about, so it is my hope that this new section makes the application of evidence based practice more concrete for readers. As we began working on issue 4.4, the Editorial Team decided that it would be a good idea to seek out an Editorial Intern to help with some of the tasks we never seem to get to, given that we are all volunteers. We see the internship as an opportunity to give a library and information studies student a chance to get involved with an open access journal and learn about publishing in library and information studies, which will hopefully benefit them as they begin their new career. The Editorial Intern will assist with marketing and promotion of the journal, soliciting potential manuscripts, and proofreading. They will also participate in all editorial meetings and general discussions. We anticipate that they will bring a wealth of enthusiasm and fresh ideas to our conversations so that EBLIP Editors can also continue to learn and grow by having a fresh set of eyes involved with our processes. It will certainly be a win‐win situation and a learning opportunity for all involved. We are pleased to announce that Andrea Baer has accepted the position of Editorial Intern and joined our team in mid‐November. Andrea is currently attending the University of

  19. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  20. From knock-out phenotype to three-dimensional structure of a promising antibiotic target from Streptococcus pneumoniae.

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    Con Dogovski

    Full Text Available Given the rise in drug-resistant Streptococcus pneumoniae, there is an urgent need to discover new antimicrobials targeting this pathogen and an equally urgent need to characterize new drug targets. A promising antibiotic target is dihydrodipicolinate synthase (DHDPS, which catalyzes the rate-limiting step in lysine biosynthesis. In this study, we firstly show by gene knock out studies that S. pneumoniae (sp lacking the DHDPS gene is unable to grow unless supplemented with lysine-rich media. We subsequently set out to characterize the structure, function and stability of the enzyme drug target. Our studies show that sp-DHDPS is folded and active with a k(cat = 22 s(-1, K(M(PYR = 2.55 ± 0.05 mM and K(M(ASA = 0.044 ± 0.003 mM. Thermal denaturation experiments demonstrate sp-DHDPS exhibits an apparent melting temperature (T(M(app of 72 °C, which is significantly greater than Escherichia coli DHDPS (Ec-DHDPS (T(M(app = 59 °C. Sedimentation studies show that sp-DHDPS exists in a dimer-tetramer equilibrium with a K(D(4→2 = 1.7 nM, which is considerably tighter than its E. coli ortholog (K(D(4→2 = 76 nM. To further characterize the structure of the enzyme and probe its enhanced stability, we solved the high resolution (1.9 Å crystal structure of sp-DHDPS (PDB ID 3VFL. The enzyme is tetrameric in the crystal state, consistent with biophysical measurements in solution. Although the sp-DHDPS and Ec-DHDPS active sites are almost identical, the tetramerization interface of the s. pneumoniae enzyme is significantly different in composition and has greater buried surface area (800 Å(2 compared to its E. coli counterpart (500 Å(2. This larger interface area is consistent with our solution studies demonstrating that sp-DHDPS is considerably more thermally and thermodynamically stable than Ec-DHDPS. Our study describe for the first time the knock-out phenotype, solution properties, stability and crystal structure of DHDPS from S. pneumoniae, a

  1. Etude expérimentale du cliquetis à haut régime Experimental Study of Hight-Speed Knocking

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    Guibet J. C.

    2006-11-01

    Full Text Available La première partie de cette étude a consisté à observer et à tenter d'interpréter l'action des conditions de fonctionnement et des paramètres de réglage du moteur sur la tendance au cliquetis à haut régime. On a montré ensuite que les différentes familles chimiques d'hydrocarbures qui constituent les carburants classiques présentent chacune un comportement bien distinct en fonction de la richesse, de la pression et de la température d'admission. On a également étudié l'influence de la teneur en plomb du carburant et du type d'alkyle de plomb employé. Quelques expériences ont été effectuées afin de déterminer l'incidence d'une réduction de un point de taux de compression sur l'exigence en octane à haut régime et sur l'action des caractéristiques de composition du carburant. Enfin, en déterminant le pourcentage de cycles soumis au cliquetis pour différentes avances à l'allumage, il a été possible de fournir quelques indications permettant de mieux caractériser l'intensité du phénomène. The first part of this study consists in observing and trying to interpret the effect of operating conditions and engine tuning parameters on the tendency for high-speed knocking to appear. The different chemical families of the hydrocarbons making up conventional fuels are shown to each have a quite different behavior depending on the fuel-air equivalency ratio and the admission pressure and temperature. The influence of the lead content in the fuel and of the type of lead alkyl used is also studied. Some experiments were performed to determine the influence of a one-point reduction in the compression ratio on the high-speed octane requirement and on the effect of fuel composition properties. Lastly, by determing the percentage of cycles accompanied by knocking at different spark advances, some indications were found for better characterizing the intensity of the phenomenon.

  2. The Sleep–Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit Knock-Out Mice

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    Natalia Madrid-López

    2017-10-01

    Full Text Available There is a neural matrix controlling the sleep–wake cycle (SWC embedded within high ranking integrative mechanisms in the central nervous system. Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR participate in physiological processes occurring in sensory, endocrine and immune systems. There is a relationship between the SWC architecture, body homeostasis and sensory afferents so that disruption of afferent signaling is expected to affect the temporal organization of sleep and wake states. The analysis of the SWC of 9 nAChR knock-out animals may help to reveal the contribution of alpha-9 nAChR to sleep chronobiological determinants. Here we explore the polysomnogram in chronically implanted alpha-9 nAChR knock-out (KO and wild-type (WT individuals of the hybrid CBA/Sv129 mouse strain. Records were obtained in isolation chambers under a stable 12:12 light:dark cycle (LD. To unmask the 24-h modulation of the SWC a skeleton photoperiod (SP protocol was performed. Under LD the daily quota (in % of wakefulness (W, NREM sleep and REM sleep obtained in KO and WT animals were 45, 48 and 7, and 46, 46 and 8 respectively. Both groups exhibit nocturnal phase preference of W as well as diurnal and unimodal phase preference of NREM and REM sleep. The acrophase mean angles of KO vs. WT genotypes were not different (Zeitgeber Time: 6.5 vs. 14.9 for W, 4.3 vs. 2.8 for NREM sleep and 5.3 vs. 3.4 for REM sleep, respectively. Transference to SP do not affect daily state quotas, phase preferences and acrophases among genotypes. Unmasking phenomena of the SWC such as wake increment during the rest phase under SP was evident only among WT mice suggesting the involvement of retinal structures containing alpha-9 nAChR in masking processes. Furthermore, KO animals exhibit longer NREM and REM sleep episodes that is independent of illumination conditions. Consolidated diurnal NREM sleep contributed to obtain higher values of NREM sleep delta-EEG activity

  3. Obesogenic environment - intervention opportunities.

    Science.gov (United States)

    Fisberg, Mauro; Maximino, Priscila; Kain, Juliana; Kovalskys, Irina

    2016-01-01

    To evaluate environmental obesogenic-related factors, such as physical activity in neighborhoods and schools, nutritional behavior, and intervention programs. Critical analysis of literature with personal point of view from infant obesity experts and political advisors for public intervention. Although obesity is a public health problem affecting several age groups, it is among children and adolescents that it plays a more important role, due to treatment complexity, high likelihood of persistence into adulthood, and association with other non-transmissible diseases while still in early age. Environment is a main component of the genesis and outcomes in the near future or long term. Modification of intake with high-density food, meal skipping, and high intake of saturated fat, sugar, and salt, associated to high levels of sedentarism are main causes of obesity. Intervention opportunities are related to modifications in political, environmental, and individual settings. School and physical activities in the educational environment are intertwined with nutrition intervention in continuous education. A critical review of some different scenarios in Latin American countries is presented. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. Arc of opportunity.

    Science.gov (United States)

    Delaney, Adam Vai

    2011-07-01

    Born in Port Moresby, Papua New Guinea, the author had a 20 year career in diplomacy, political affairs, and development policy analysis at the Pacific Islands Forum, the United Nations in New York; the Prime Minister's Department in Papua New Guinea (PNG) and in the Foreign Ministry of PNG. He has also been involved in theatre for over a decade in PNG, and participated in a three-month program at the Eugene O'Neill Theatre Center in Connecticut, USA. He is currently the Business Development Manager at the Torres Strait Regional Authority (Commonwealth) on Thursday Island. Since 1975 the Australian government's overseas development policy has supported various sectoral programs in its neighbouring countries, in particular Papua New Guinea and the Solomon Islands. The "creative" field has not been prominent in this strategy. While natural resources and the sports sectors have gained much greater attention, in terms of being viable international commercial enterprises, the arts, have remained stagnant. In this paper the need for joint programs genuinely supporting "wellbeing" and promoting social enterprise throughout the "arc of opportunity" is described to harness Melanesian creativity to compete successfully in world-markets, starting with penetration of the largest economy at its door-step: Australia.

  5. 29 CFR 1601.2 - Terms defined in title VII of the Civil Rights Act, the Americans with Disabilities Act, and the...

    Science.gov (United States)

    2010-07-01

    ... Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURAL REGULATIONS Definitions § 1601.2 Terms defined in title VII of the Civil Rights Act, the Americans with Disabilities Act, and the Genetic Information Nondiscrimination Act. The terms person, employer, employment...

  6. Influence of Compression Ratio on High Load Performance and Knock Behavior for Gasoline Port-Fuel Injection, Natural Gas Direct Injection and Blended Operation in a Spark Ignition Engine

    Energy Technology Data Exchange (ETDEWEB)

    Pamminger, Michael; Sevik, James; Scarcelli, Riccardo; Wallner, Thomas; Hall, Carrie

    2017-03-28

    Natural Gas (NG) is an alternative fuel which has attracted a lot of attention recently, in particular in the US due to shale gas availability. The higher hydrogen-to-carbon (H/C) ratio, compared to gasoline, allows for decreasing carbon dioxide emissions throughout the entire engine map. Furthermore, the high knock resistance of NG allows increasing the efficiency at high engine loads compared to fuels with lower knock resistance. NG direct injection (DI) allows for fuel to be added after intake valve closing (IVC) resulting in an increase in power density compared to an injection before IVC. Steady-state engine tests were performed on a single-cylinder research engine equipped with gasoline (E10) port-fuel injection (PFI) and NG DI to allow for in-cylinder blending of both fuels. Knock investigations were performed at two discrete compression ratios (CR), 10.5 and 12.5. Operating conditions span mid-load, wide-open-throttle and boosted conditions, depending on the knock response of the fuel blend. Blended operation was performed using E10 gasoline and NG. An additional gasoline type fuel (E85) with higher knock resistance than E10 was used as a high-octane reference fuel, since the octane rating of E10-NG fuel blends is unknown. Spark timing was varied at different loads under stoichiometric conditions in order to study the knock response as well as the effects on performance and efficiency. As anticipated, results suggest that the knock resistance can be increased significantly by increasing the NG amount. Comparing the engine operation with the least knock resistant fuel, E10 PFI, and the fuel blend with the highest knock resistance, 75% NG DI, shows an increase in indicated mean effective pressure of about 9 bar at CR 12.5. The usage of reference fuels with known knock characteristics allowed an assessment of knock characteristic of intermediate E10-NG blend levels. Mathematical correlations were developed allowing characterizing the occurrence of knocking

  7. 18 CFR 8.11 - Information respecting use and development of public recreational opportunities.

    Science.gov (United States)

    2010-04-01

    ... POWER ACT RECREATIONAL OPPORTUNITIES AND DEVELOPMENT AT LICENSED PROJECTS § 8.11 Information respecting... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Information respecting use and development of public recreational opportunities. 8.11 Section 8.11 Conservation of Power and...

  8. 9 CFR 335.40 - Opportunity for presentation of views before report of criminal violations.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Opportunity for presentation of views before report of criminal violations. 335.40 Section 335.40 Animals and Animal Products FOOD SAFETY AND... UNDER THE FEDERAL MEAT INSPECTION ACT Criminal Violations § 335.40 Opportunity for presentation of views...

  9. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-10-01

    Full Text Available IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  10. Motor and memory testing of long-lived pregnancy-associated plasma protein--a knock-out mice.

    Science.gov (United States)

    Mason, Emily J; Grell, Jacquelyn A; West, Sally A; Conover, Cheryl A

    2014-12-01

    Mice deficient in pregnancy-associated plasma protein-A (PAPP-A), an IGF binding protein protease, have been shown to be resistant to experimentally induced atherosclerosis and diabetic nephropathy, and, in the laboratory environment, live 30-40% longer than wild-type littermates in association with delayed incidence and occurrence of age-related neoplasms and degenerative diseases. PAPP-A is highly expressed in the cerebellum and hippocampus of the mouse brain. Therefore, the studies presented here were aimed at determining motor behavior, learning and retention in PAPP-A knock-out (KO) mice compared to wild-type (WT) littermates with age. Balance and coordination were assessed using an accelerating rotarod; learning and memory were assessed in a Stone T-maze. Time on the rotarod decreased with age but there was no significant difference between PAPP-A KO and WT mice at any of the testing ages. Latency to reach the goal box and number of errors committed in the Stone T-maze did not change with age and there were no significant differences between PAPP-A KO and WT mice. Lack of PAPP-A in mice did not impact central regulation of coordination, learning or memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Motor and Memory Testing of Long-lived Pregnancy-Associated Plasma Protein-A Knock-out Mice

    Science.gov (United States)

    Mason, Emily J.; Grell, Jacquelyn A.; West, Sally A.; Conover, Cheryl A.

    2014-01-01

    Mice deficient in pregnancy-associated plasma protein-A (PAPP-A), an IGF binding protein protease, have been shown to be resistant to experimentally-induced atherosclerosis and diabetic nephropathy, and, in the laboratory environment, live 30–40% longer than wild-type littermates in association with delayed incidence and occurrence of age-related neoplasms and degenerative diseases. OBJECTIVE PAPP-A is highly expressed in the cerebellum and hippocampus of the mouse brain. Therefore, the studies presented here were aimed at determining motor behavior, learning and retention in PAPP-A knock-out (KO) mice compared to wild-type (WT) littermates with age. DESIGN Balance and coordination were assessed using an accelerating rotarod; learning and memory were assessed in a Stone T-maze. RESULTS Time on the rotarod decreased with age but there was no significant difference between PAPP-A KO and WT mice at any of the testing ages. Latency to reach the goal box and number of errors committed in the Stone T-maze did not change with age and there were no significant differences between PAPP-A KO and WT mice. CONCLUSION Lack of PAPP-A in mice did not impact central regulation of coordination, learning or memory. PMID:25179152

  12. Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient.

    Science.gov (United States)

    Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd

    2015-12-01

    A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice.

    Science.gov (United States)

    Dong, Pengzhi; Pan, Lanlan; Zhang, Xiting; Zhang, Wenwen; Wang, Xue; Jiang, Meixiu; Chen, Yuanli; Duan, Yajun; Wu, Honghua; Xu, Yantong; Zhang, Peng; Zhu, Yan

    2017-02-23

    Hawthorn (Crataegus pinnatifida Bunge) leave have been used to treat cardiovascular diseases in China and Europe. Hawthorn leave flavonoids (HLF) are the main part of extraction. Whether hawthorn leave flavonoids could attenuate the development of atherosclerosis and the possible mechanism remain unknown. High-fat diet (HFD) mixed with HLF at concentrations of 5mg/kg and 20mg/kg were administered to apolipoprotein E (apoE) knock out mice. 16 weeks later, mouse serum was collected to determine the lipid profile while the mouse aorta dissected was prepared to measure the lesion area. Hepatic mRNA of genes involved in lipid metabolism were determined. Peritoneal macrophages were collected to study the impact of HLF on cholesterol efflux, formation of foam cell and the expression of ATP binding cassette transporter A1 (ABCA1). Besides, in vivo reverse cholesterol transport (RCT) was conducted. HLF attenuated the development of atherosclerosis that the mean atherosclerotic lesion area in en face aortas was reduced by 23.1% (Pflavonoids can slow down the development of atherosclerosis in apoE knockout mice via induced expression of genes involved in antioxidant activities, inhibition of the foam cell formation and promotion of RCT in vivo, which implies the potential use in the prevention of atherosclerosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Proteomics data on MAP Kinase Kinase 3 knock out bone marrow derived macrophages exposed to cigarette smoke extract

    Directory of Open Access Journals (Sweden)

    Roshni Srivastava

    2017-08-01

    Full Text Available This data article reports changes in the phosphoproteome and total proteome of cigarette smoke extract (CSE exposed WT and MAP Kinase Kinase 3 knock out (MKK3−/− bone marrow derived macrophages (BMDM. The dataset generated is helpful for understanding the mechanism of CSE induced inflammation and the role of MAP kinase signaling pathway. The cellular proteins were labeled with isobaric tags for relative and absolute quantitation (iTRAQ® reagents and analyzed by LC-MS/MS. The standard workflow module for iTRAQ® quantification within the Proteome Discoverer was utilized for the data analysis. Ingenuity Pathway Analysis (IPA software and Reactome was used to identify enriched canonical pathways and molecular networks (Mannam et al., 2016 [1]. All the associated mass spectrometry data has been deposited in the Yale Protein Expression Database (YPED with the web-link to the data: http://yped.med.yale.edu/repository/ViewSeriesMenu.do;jsessionid=6A5CB07543D8B529FAE8C3FCFE29471D?series_id=5044&series_name=MMK3+Deletion+in+MEFs

  15. G-Protein-Gated Inwardly Rectifying Potassium (GIRK) Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward

    Science.gov (United States)

    Tipps, Megan E.; Raybuck, Jonathan D.; Kozell, Laura B.; Lattal, K. Matthew; Buck, Kari J.

    2016-01-01

    Background G protein-coupled inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood. Methods We compare conditioned place preference (CPP) in GIRK3 subunit knock-out (GIRK3−/−), heterozygote (GIRK3+/−), and wild-type (WT) mice. In addition, the development of locomotor tolerance/sensitization and the effects of ethanol intoxication on associative learning (fear conditioning) are also assessed. Results Our data show significant ethanol CPP in GIRK3−/− and GIRK3+/− mice, but not in the WT littermates. In addition, we demonstrate that these effects are not due to differences in ethanol metabolism, the development of ethanol tolerance/sensitivity, or associative learning abilities. While there were no consistent genotype differences in the fear conditioning assay, our data do show a selective sensitization of the impairing effects of ethanol intoxication on contextual learning, but no effect on cued learning. Conclusions These findings suggest that GIRK3 plays a role in ethanol reward. Further, the selectivity of this effect suggests that GIRK channels could be an effective therapeutic target for the prevention and/or treatment of alcoholism. PMID:27012303

  16. ReacKnock: identifying reaction deletion strategies for microbial strain optimization based on genome-scale metabolic network.

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    Zixiang Xu

    Full Text Available Gene knockout has been used as a common strategy to improve microbial strains for producing chemicals. Several algorithms are available to predict the target reactions to be deleted. Most of them apply mixed integer bi-level linear programming (MIBLP based on metabolic networks, and use duality theory to transform bi-level optimization problem of large-scale MIBLP to single-level programming. However, the validity of the transformation was not proved. Solution of MIBLP depends on the structure of inner problem. If the inner problem is continuous, Karush-Kuhn-Tucker (KKT method can be used to reformulate the MIBLP to a single-level one. We adopt KKT technique in our algorithm ReacKnock to attack the intractable problem of the solution of MIBLP, demonstrated with the genome-scale metabolic network model of E. coli for producing various chemicals such as succinate, ethanol, threonine and etc. Compared to the previous methods, our algorithm is fast, stable and reliable to find the optimal solutions for all the chemical products tested, and able to provide all the alternative deletion strategies which lead to the same industrial objective.

  17. Knock-Down of IL-1Ra in Obese Mice Decreases Liver Inflammation and Improves Insulin Sensitivity

    Science.gov (United States)

    Franck, Niclas; Maris, Michael; Nalbandian, Sarah; Talukdar, Saswata; Schenk, Simon; Hofmann, Hans-Peter; Bullough, David; Osborn, Olivia

    2014-01-01

    Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice. PMID:25244011

  18. Knock-down of IL-1Ra in obese mice decreases liver inflammation and improves insulin sensitivity.

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    Niclas Franck

    Full Text Available Interleukin 1 Receptor antagonist (IL-1Ra is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice.

  19. CRISPR/Cas9-AAV Mediated Knock-in at NRL Locus in Human Embryonic Stem Cells

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    Xianglian Ge

    2016-01-01

    Full Text Available Clustered interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9-mediated genome engineering technologies are sparking a new revolution in biological research. This technology efficiently induces DNA double strand breaks at the targeted genomic sequence and results in indel mutations by the error-prone process of nonhomologous end joining DNA repair or homologous recombination with a DNA repair template. The efficiency of genome editing with CRISPR/Cas9 alone in human embryonic stem cells is still low. Gene targeting with adeno-associated virus (AAV vectors has been demonstrated in multiple human cell types with maximal targeting frequencies without engineered nucleases. However, whether CRISPR/Cas9-mediated double strand breaks and AAV based donor DNA mediated homologous recombination approaches could be combined to create a novel CRISPR/Cas9-AAV genetic tool for highly specific gene editing is not clear. Here we demonstrate that using CRISPR/Cas9-AAV, we could successfully knock-in a DsRed reporter gene at the basic motifleucine zipper transcription factor (NRL locus in human embryonic stem cells. For the first time, this study provides the proof of principle that these two technologies can be used together. CRISPR/Cas9-AAV, a new genome editing tool, offers a platform for the manipulation of human genome.

  20. Knocking down expression of the auxin-amidohydrolase IAR3 alters defense responses in Solanaceae family plants.

    Science.gov (United States)

    D'Ippolito, Sebastian; Vankova, Radomira; Joosten, Matthieu H A J; Casalongué, Claudia A; Fiol, Diego F

    2016-12-01

    In plants, indole-3-acetic acid (IAA) amido hydrolases (AHs) participate in auxin homeostasis by releasing free IAA from IAA-amino acid conjugates. We investigated the role of IAR3, a member of the IAA amido hydrolase family, in the response of Solanaceous plants challenged by biotrophic and hemi-biotrophic pathogens. By means of genome inspection and phylogenic analysis we firstly identified IAA-AH sequences and putative IAR3 orthologs in Nicotiana benthamiana, tomato and potato. We evaluated the involvement of IAR3 genes in defense responses by using virus-induced gene silencing. We observed that N. benthamiana and tomato plants with knocked-down expression of IAR3 genes contained lower levels of free IAA and presented altered responses to pathogen attack, including enhanced basal defenses and higher tolerance to infection in susceptible plants. We showed that IAR3 genes are consistently up-regulated in N. benthamiana and tomato upon inoculation with Phytophthora infestans and Cladosporium fulvum respectively. However, IAR3 expression decreased significantly when hypersensitive response was triggered in transgenic tomato plants coexpressing the Cf-4 resistance gene and the avirulence factor Avr4. Altogether, our results indicate that changes in IAR3 expression lead to alteration in auxin homeostasis that ultimately affects plant defense responses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

    Directory of Open Access Journals (Sweden)

    Luis Segu

    Full Text Available Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4, but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4 knock-out (KO and wild-type (WT mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT, the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

  2. CRISPR/Cas9-mediated gene modification and gene knock out in the human-infective parasite Trichomonas vaginalis.

    Science.gov (United States)

    Janssen, Brian D; Chen, Yi-Pei; Molgora, Brenda M; Wang, Shuqi E; Simoes-Barbosa, Augusto; Johnson, Patricia J

    2018-01-10

    The sexually-transmitted parasite Trichomonas vaginalis infects ~1/4 billion people worldwide. Despite its prevalence and myriad adverse outcomes of infection, the mechanisms underlying T. vaginalis pathogenesis are poorly understood. Genetic manipulation of this single-celled eukaryote has been hindered by challenges presented by its complex, repetitive genome and inefficient methods for introducing DNA (i.e. transfection) into the parasite. Here, we have developed methods to increase transfection efficiency using nucleofection, with the goal of efficiently introducing multiple DNA elements into a single T. vaginalis cell. We then created DNA constructs required to express several components essential to drive CRISPR/Cas9-mediated DNA modification: guide RNA (gRNA), the Cas9 endonuclease, short oligonucleotides and large, linearized DNA templates. Using these technical advances, we have established CRISPR/Cas9-mediated repair of mutations in genes contained on circular DNA plasmids harbored by the parasite. We also engineered CRISPR/Cas9 directed homologous recombination to delete (i.e. knock out) two non-essential genes within the T. vaginalis genome. This first report of the use of the CRISPR/Cas9 system in T. vaginalis greatly expands the ability to manipulate the genome of this pathogen and sets the stage for testing of the role of specific genes in many biological processes.

  3. Knocking Down TMPRSS2-ERG Fusion Oncogene by siRNA Could be an Alternative Treatment to Flutamide

    Directory of Open Access Journals (Sweden)

    Giorgia Urbinati

    2016-01-01

    Full Text Available Our purpose was to develop a new pharmacological approach for the treatment of prostate cancer (PCa, the most common neoplasia in men. Recently, we developed siRNA against the fusion oncogene TMPRSS2-ERG found in 50% of patients and showed an antitumoral activity in animal model. Herein, we want to compare or combine the developed siRNA to flutamide (FLU, one of the gold-standard treatment of PCa. Therefore, concomitant or subsequent association of FLU to siRNA TMPRSS2-ERG was performed in VCaP cells and in SCID mice bearing xenografted VCaP tumors. ERG, androgen receptor, cleaved-caspase-3 as well as phase 1 and 2 drug-metabolizing enzymes were investigated within tumors. We observed similar results in terms of TMPRSS2-ERG knock-down and cell viability impairment for all distinct schedules of administration. The association of siRNA TMPRSS2-ERG-squalene nanoparticles with flutamide displayed similar tumor growth inhibition as mice treated with siRNA TMPRSS2-ERG-squalene nanoparticles alone and was paralleled with modification of expression of ERG, androgen receptor, and cleaved-caspase-3. Phase 1 and 2 enzymes were essentially affected by FLU and reverted when combined with squalenoylated siRNA. In conclusion, these results confirm the therapeutic effectiveness of squalenoyl siRNA nanomedicine for PCa based on siRNA TMPRSS2-ERG.

  4. CRISPR/Cas9-AAV Mediated Knock-in at NRL Locus in Human Embryonic Stem Cells.

    Science.gov (United States)

    Ge, Xianglian; Xi, Haitao; Yang, Fayu; Zhi, Xiao; Fu, Yanghua; Chen, Ding; Xu, Ren-He; Lin, Ge; Qu, Jia; Zhao, Junzhao; Gu, Feng

    2016-11-29

    Clustered interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome engineering technologies are sparking a new revolution in biological research. This technology efficiently induces DNA double strand breaks at the targeted genomic sequence and results in indel mutations by the error-prone process of nonhomologous end joining DNA repair or homologous recombination with a DNA repair template. The efficiency of genome editing with CRISPR/Cas9 alone in human embryonic stem cells is still low. Gene targeting with adeno-associated virus (AAV) vectors has been demonstrated in multiple human cell types with maximal targeting frequencies without engineered nucleases. However, whether CRISPR/Cas9-mediated double strand breaks and AAV based donor DNA mediated homologous recombination approaches could be combined to create a novel CRISPR/Cas9-AAV genetic tool for highly specific gene editing is not clear. Here we demonstrate that using CRISPR/Cas9-AAV, we could successfully knock-in a DsRed reporter gene at the basic motifleucine zipper transcription factor (NRL) locus in human embryonic stem cells. For the first time, this study provides the proof of principle that these two technologies can be used together. CRISPR/Cas9-AAV, a new genome editing tool, offers a platform for the manipulation of human genome.

  5. Impaired phloem loading in zmsweet13a,b,c sucrose transporter triple knock-out mutants in Zea mays.

    Science.gov (United States)

    Bezrutczyk, Margaret; Hartwig, Thomas; Horshman, Marc; Char, Si Nian; Yang, Jinliang; Yang, Bing; Frommer, Wolf B; Sosso, Davide

    2018-02-16

    Crop yield depends on efficient allocation of sucrose from leaves to seeds. In Arabidopsis, phloem loading is mediated by a combination of SWEET sucrose effluxers and subsequent uptake by SUT1/SUC2 sucrose/H + symporters. ZmSUT1 is essential for carbon allocation in maize, but the relative contribution to apoplasmic phloem loading and retrieval of sucrose leaking from the translocation path is not known. Here we analysed the contribution of SWEETs to phloem loading in maize. We identified three leaf-expressed SWEET sucrose transporters as key components of apoplasmic phloem loading in Zea mays L. ZmSWEET13 paralogues (a, b, c) are among the most highly expressed genes in the leaf vasculature. Genome-edited triple knock-out mutants were severely stunted. Photosynthesis of mutants was impaired and leaves accumulated high levels of soluble sugars and starch. RNA-seq revealed profound transcriptional deregulation of genes associated with photosynthesis and carbohydrate metabolism. Genome-wide association study (GWAS) analyses may indicate that variability in ZmSWEET13s correlates with agronomical traits, especifically flowering time and leaf angle. This work provides support for cooperation of three ZmSWEET13s with ZmSUT1 in phloem loading in Z. mays. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  6. Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model.

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Morbin, Michela; Uggetti, Andrea; Moda, Fabio; D'Amato, Ilaria; Giordano, Carla; d'Amati, Giulia; Cozzi, Anna; Levi, Sonia; Hayflick, Susan; Tiranti, Valeria

    2012-12-15

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration.

  7. Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Morbin, Michela; Uggetti, Andrea; Moda, Fabio; D'Amato, Ilaria; Giordano, Carla; d'Amati, Giulia; Cozzi, Anna; Levi, Sonia; Hayflick, Susan; Tiranti, Valeria

    2012-01-01

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration. PMID:22983956

  8. The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia.

    Directory of Open Access Journals (Sweden)

    Matthieu M Vermeren

    Full Text Available Phospholipase D2 (PLD2 is an enzyme that produces phosphatidic acid (PA, a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction.

  9. Generation of a Tlx1(CreER-Venus) knock-in mouse strain for the study of spleen development.

    Science.gov (United States)

    Nakahara, Ryo; Kawai, Yasuhiro; Oda, Akihisa; Nishimura, Miyuki; Murakami, Akikazu; Azuma, Takachika; Kaifu, Tomonori; Goitsuka, Ryo

    2014-11-01

    The spleen is a lymphoid organ that serves as a unique niche for immune reactions, extramedullary hematopoiesis, and the removal of aged erythrocytes from the circulation. While much is known about the immunological functions of the spleen, the mechanisms governing the development and organization of its stromal microenvironment remain poorly understood. Here we report the generation and analysis of a Tlx1(Cre) (ER) (-Venus) knock-in mouse strain engineered to simultaneously express tamoxifen-inducible CreER(T2) and Venus fluorescent protein under the control of regulatory elements of the Tlx1 gene, which encodes a transcription factor essential for spleen development. We demonstrated that Venus as well as CreER expression recapitulates endogenous Tlx1 transcription within the spleen microenvironment. When Tlx1(Cre) (ER) (-Venus) mice were crossed with the Cre-inducible reporter strain, Tlx1-expressing cells as well as their descendants were specifically labeled following tamoxifen administration. We also showed by cell lineage tracing that asplenia caused by Tlx1 deficiency is attributable to altered contribution of mesenchymal cells in the spleen anlage to the pancreatic mesenchyme. Thus, Tlx1(Cre) (ER) (-Venus) mice represent a new tool for lineage tracing and conditional gene manipulation of spleen mesenchymal cells, essential approaches for understanding the molecular mechanisms of spleen development. © 2014 Wiley Periodicals, Inc.

  10. Adult Learning Opportunities in Nepal

    Science.gov (United States)

    Regmi, Krishna; Regmi, Sharada

    2008-01-01

    This paper presents the initial findings from a study of education system in Nepal. This paper examines the adult learning opportunities within the educational and cultural contexts by reviewing available literature relevant to Nepal. Findings show that there are wider opportunities for adult learning than those considered from education and…

  11. New Opportunities for Appalachian Women.

    Science.gov (United States)

    Farr, Sidney Saylor

    2003-01-01

    The New Opportunity School for Women in Berea, Kentucky, is a 3-week residential program for low-income women who need jobs. The program offers courses in resume writing, interview skills, computer basics, and building self-esteem. Women are placed in jobs on Berea College's campus, cultural opportunities are provided through field trips, and…

  12. Oilseeds business opportunities in Ethiopia

    NARCIS (Netherlands)

    Wijnands, J.H.M.; Biersteker, J.; Hiel, R.

    2007-01-01

    In this study the business opportunities for Dutch companies in the Ethiopian oilseeds sector are explored. Opportunities for setting up sustainable export chains should mutually benefit Dutch companies as well as the Ethiopian oilseeds sector in particular and the Ethiopian society in general.

  13. Generation of an Rx-tTA: TetOp-Cre knock-in mouse line for doxycycline regulated Cre activity in the Rx expression domain.

    Directory of Open Access Journals (Sweden)

    Timothy F Plageman

    Full Text Available Genetic deletion of mouse genes has played a crucial role in our understanding of embryonic eye development. Transgenic, tissue specific Cre recombinase expression in various eye structures has facilitated these experiments. However, an early expressing, temporally-regulated, optic vesicle-specific Cre line has not been available. In this report, we detail the generation and analysis of a knock-in, inducible Cre line designed to drive recombination specifically within the Rx expression domain. Crossing this line with a reporter line demonstrates that recombination can be mediated within the early optic vesicle and throughout retinal development. Recombination can also be mediated in the Rx-expressing, ventral diencephalon and future posterior pituitary gland. Furthermore, it was demonstrated that dietary doxycycline could effectively modulate Cre activity. This line has the potential to facilitate conditional knock-out experimentation to study early retina and/or posterior pituitary development.

  14. Effect of Water-Alcohol Injection and Maximum Economy Spark Advance on Knock-Limited Performance and Fuel Economy of a Large Air-Cooled Cylinder

    Science.gov (United States)

    Heinicke, Orville H.; Vandeman, Jack E.

    1945-01-01

    An investigation was conducted to determine the effect of a coolant solution of 25 percent ethyl alcohol, 25 percent methyl alcohol, and 50 percent water by volume and maximum-economy spark advance on knock-limited performance and fuel economy of a large air-cooled cylinder. The knock-limited performance of the cylinder at engine speeds of 2100 and 2500 rpm was determined for coolant-fuel ratios of 0.0, 0.2, and 0.4. The effect of water-alcohol injection on fuel economy was determined in constant charge-air flow tests. The tests were conducted at a spark advance of 20 deg B.T.C. and maximum-economy spark advance.

  15. Investigating of the Knocking Out Properties of Moulding Sands with New Inorganic Binders Used for Castings of Non-ferrous Metal Alloys in Comparison with the Previously Used

    Directory of Open Access Journals (Sweden)

    I. Izdebska-Szanda

    2012-12-01

    Full Text Available The article presents the results of investigations, which make a fragment of the broad-scale studies carried out as a part of the projectPOIG.01.01.02-00-015/09 “Advanced materials and technologies”.One of the objectives of the introduction of new inorganic binders is to provide a good knocking out properties of moulding sands, whilemaintaining an appropriate level of strength properties.Therefore, a logical continuation of the previous studies were carried out the tests knocking out properties of moulding sands with newinorganic binders, including making moulds, pouring them by the chosen of non-ferrous metal alloys, knoking-out, and determining theknocking out work.The results of the study were related to the research results obtained by applying the moulding sand performed by existing technology.

  16. Autism: Why Act Early?

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Past Emails Autism: Why Act Early? Language: English (US) Español (Spanish) ... helped the world make sense." Florida teenager with Autism Spectrum Disorder "Because my parents acted early, I ...

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... that affects the pancreas and other organs, and how to treat and live with this chronic disease. Role ... of your CF care team can show you how to perform many different ACTs and recommend specific ACTs ...

  18. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  20. VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease

    OpenAIRE

    Mallikarjun Badadani; Angèle Nalbandian; Watts, Giles D.; Jouni Vesa; Masashi Kitazawa; Hailing Su; Jasmin Tanaja; Eric Dec; Wallace, Douglas C.; Jogeshwar Mukherjee; Vincent Caiozzo; Matthew Warman; Kimonis, Virginia E.

    2010-01-01

    Dominant mutations in the valosin containing protein (VCP) gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumul...

  1. Equal opportunities group. His mission : accelerating equal opportunities at CERN

    CERN Multimedia

    Patrice Loïez

    2000-01-01

    L. to r.: Michel Mayoud, Christine Petit-Jean-Genaz, the Equal Opportunities Officer Sudeshna Datta-Cockerill, Elena Wildner, Anne-Sylvie Cerne, Karl-Heinz Kissler, the Chairman John Ellis and Eva-Maria Groniger-Voss

  2. The Paradox of Equal Opportunities

    Directory of Open Access Journals (Sweden)

    Mitja Sardoč

    2014-06-01

    Full Text Available The basic assumption of the idea of equal opportunities is based on the assertion that all individuals competing for an advantaged social position should have equal opportunities, i.e., that each and every one of them should have fair opportunities to achieve a particular goal. Despite the fact that equal opportunities is one of the basic mechanisms for a just distribution of advantageous social positions, the idea of fair equality of opportunity remains divided between different competing political projects, e.g., egalitarian liberalism, libertarian political theory, multiculturalism, etc. This paper examines two basic dimensions of equal opportunities to which existing conceptions fail to offer a unanimous answer, i.e., a the issue of fairness and b the issue of the currency of fairness. The concluding part of this paper presents two basic paradoxes that determine both the direction of the discussion as well as the possible solutions to the achievement of fair equal opportunities as part of any process for competing for advantageous social positions.

  3. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease.

    Directory of Open Access Journals (Sweden)

    Mallikarjun Badadani

    2010-10-01

    Full Text Available Dominant mutations in the valosin containing protein (VCP gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD. We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCP(R155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies.

  4. RNAi-mediated knock-down of arylamine N-acetyltransferase-1 expression induces E-cadherin up-regulation and cell-cell contact growth inhibition.

    Directory of Open Access Journals (Sweden)

    Jacky M Tiang

    Full Text Available Arylamine N-acetyltransferase-1 (NAT1 is an enzyme that catalyzes the biotransformation of arylamine and hydrazine substrates. It also has a role in the catabolism of the folate metabolite p-aminobenzoyl glutamate. Recent bioinformatics studies have correlated NAT1 expression with various cancer subtypes. However, a direct role for NAT1 in cell biology has not been established. In this study, we have knocked down NAT1 in the colon adenocarcinoma cell-line HT-29 and found a marked change in cell morphology that was accompanied by an increase in cell-cell contact growth inhibition and a loss of cell viability at confluence. NAT1 knock-down also led to attenuation in anchorage independent growth in soft agar. Loss of NAT1 led to the up-regulation of E-cadherin mRNA and protein levels. This change in E-cadherin was not attributed to RNAi off-target effects and was also observed in the prostate cancer cell-line 22Rv1. In vivo, NAT1 knock-down cells grew with a longer doubling time compared to cells stably transfected with a scrambled RNAi or to parental HT-29 cells. This study has shown that NAT1 affects cell growth and morphology. In addition, it suggests that NAT1 may be a novel drug target for cancer therapeutics.

  5. A combination method for simulation of secondary knock-on atoms of boron carbide induced by neutron irradiation in SPRR-300

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jian-Chun [Key Laboratory of Radiation Physics and Technology of Education Ministry of China, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, Sichuan 610064 (China); Feng, Qi-Jie; Liu, Xian-Kun [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China); Zhan, Chang-Yong [Key Laboratory of Radiation Physics and Technology of Education Ministry of China, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, Sichuan 610064 (China); Zou, Yu, E-mail: zouyu@scu.edu.cn [Key Laboratory of Radiation Physics and Technology of Education Ministry of China, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, Sichuan 610064 (China); Liu, Yao-Guang [Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China)

    2016-02-01

    A multiscale sequence of simulation should be used to predict properties of materials under irradiation. Binary collision theory and molecular dynamics (MDs) method are commonly used to characterize the displacement cascades induced by neutrons in a material. In order to reduce the clock time spent for the MD simulation of damages induced by high-energy primary knock-on atoms (PKAs), the damage zones were split into sub-cascade according to the sub-cascade formation criteria. Two well-known codes, Geant4 and TRIM, were used to simulate high-energy PKA-induced cascades in B{sub 4}C and then produce the secondary knock-on atom (SKA) energy spectrum. It has been found that both high-energy primary knock-on B and C atoms move a long range in the boron carbide. These atoms produce sub-cascades at the tip of trajectory. The energy received by most of the SKAs is <10 keV, which can be used as input to reduce the clock time spent for MD simulation.

  6. DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells

    Directory of Open Access Journals (Sweden)

    Jansen Bastiaan JH

    2011-10-01

    Full Text Available Abstract Background Dendritic cells (DCs are the highly specialized antigen presenting cells of the immune system that play a key role in regulating immune responses. DCs can efficiently initiate immune responses or induce tolerance. Due to this dual function, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. Characterization of DC-specific genes, leading to better understanding of DC immunobiology, will help to guide their use in clinical settings. We previously identified DC-STAMP, a multi-membrane spanning protein preferentially expressed by DCs. DC-STAMP resides in the endoplasmic reticulum (ER of immature DCs and translocates towards the Golgi compartment upon maturation. In this study we knocked down DC-STAMP in mouse bone marrow-derived DCs (mBMDCs to determine its function. Results We demonstrate that DC-STAMP knock-down mBMDCs secrete less IL-6, IL-12, TNF-α and IL-10 while IL-1 production is enhanced. Moreover, LPS-matured DC-STAMP knock-down mBMDCs show impaired T cell activation potential and induction of Th1 responses in an alloreaction. Conclusions We show that DC-STAMP plays an important role in cytokine production by mBMDCs following LPS exposure. Our results reveal a novel function of DC-STAMP in regulating DC-initiated immune responses.

  7. Spectrum Effect Relationship and Component Knock-Out in Angelica Dahurica Radix by High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer

    Directory of Open Access Journals (Sweden)

    Jinmei Wang

    2017-07-01

    Full Text Available Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied spectrum-effect relationship and component knock-out methods to make it clear. HPLC was used to obtain the specific chromatograms. The effects on tyrosinase activity were examined by measuring the oxidation rate of levodopa in vitro. Partial least squares method was used to examine the spectrum-effect relationships. The knocked-out samples were prepared by HPLC method, and the identification of knocked-out compounds was conducted by the high performance liquid chromatography-four stage rod-electrostatic field orbit trap high resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36, S37, S40, and S41 were positively correlated to inhibitory activity of Angelica dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively correlated. When the concentration of each sample was 1 g·mL−1, equal to the amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and isoimperatorin had inhibitory effects on tyrosinase activity whereas byakangelicin and bergapten had activating effects.

  8. Reduction in open field activity in the absence of memory deficits in the AppNL-G-F knock-in mouse model of Alzheimer's disease.

    Science.gov (United States)

    Whyte, Lauren S; Hemsley, Kim M; Lau, Adeline A; Hassiotis, Sofia; Saito, Takashi; Saido, Takaomi C; Hopwood, John J; Sargeant, Timothy J

    2018-01-15

    The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the AppNL-F and AppNL-G-F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of AppNL-G-F/NL-G-F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between AppNL-G-F/NL-G-F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between AppNL-G-F/NL-G-F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of AppNL-G-F/NL-G-F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in AppNL-G-F/NL-G-F knock-in brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Numerical Investigation of Injection Timing Influence on Fuel Slip and Influence of Compression Ratio on Knock Occurrence in Conventional Dual Fuel Engine

    Directory of Open Access Journals (Sweden)

    Mario Sremec

    2017-12-01

    Full Text Available Compressed natural gas can be used in diesel engine with great benefits, but because of its low reactivity it is usually used in a so called dual fuel combustion process. Optimal parameters for dual fuel engines are not yet investigated thoroughly which is the motivation for this work. In this work, a numerical study performed in a cycle simulation tool (AVL Boost v2013 on the influence of different injection timings on fuel slip into exhaust and influence of compression ratio on knock phenomena in port injected dual fuel engine was conducted. The introduction of natural gas into the intake port of a diesel engine usually results in some fuel slipping into the exhaust port due to valve overlap. By analysing the simulation results, the injection strategy that significantly decreases the natural gas slip is defined. The knock occurrence study showed that the highest allowed compression ratio that will result in knock free operation of the presented engine is 18 for ambient intake condition, while for charged intake conditions the compression ratio should be lowered to 16.

  10. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease.

    Science.gov (United States)

    Badadani, Mallikarjun; Nalbandian, Angèle; Watts, Giles D; Vesa, Jouni; Kitazawa, Masashi; Su, Hailing; Tanaja, Jasmin; Dec, Eric; Wallace, Douglas C; Mukherjee, Jogeshwar; Caiozzo, Vincent; Warman, Matthew; Kimonis, Virginia E

    2010-10-05

    Dominant mutations in the valosin containing protein (VCP) gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT) images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCP(R155H/+) knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies.

  11. Surfactant secretion in LRRK2 knock-out rats: changes in lamellar body morphology and rate of exocytosis.

    Directory of Open Access Journals (Sweden)

    Pika Miklavc

    Full Text Available Leucine-rich repeat kinase 2 (LRRK2 is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/- mice revealed significantly enlarged lamellar bodies (LBs in alveolar type II (ATII epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca(2+ release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca(2+-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca(2+ signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca(2

  12. Surfactant secretion in LRRK2 knock-out rats: changes in lamellar body morphology and rate of exocytosis.

    Science.gov (United States)

    Miklavc, Pika; Ehinger, Konstantin; Thompson, Kristin E; Hobi, Nina; Shimshek, Derya R; Frick, Manfred

    2014-01-01

    Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revealed significantly enlarged lamellar bodies (LBs) in alveolar type II (ATII) epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca(2+) release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca(2+)-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca(2+) signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid) release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca(2+) signaling and

  13. Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Alejandro Garanto

    Full Text Available Leber congenital amaurosis (LCA is the most severe form of retinal dystrophy with an onset in the first year of life. The most frequent genetic cause of LCA, accounting for up to 15% of all LCA cases in Europe and North-America, is a mutation (c.2991+1655AG in intron 26 of CEP290. This mutation generates a cryptic splice donor site resulting in the insertion of an aberrant exon (exon X containing a premature stop codon to CEP290 mRNA. In order to study the pathophysiology of the intronic CEP290 mutation, we generated two humanized knock-in mouse models each carrying ~6.3 kb of the human CEP290 gene, either with or without the intronic mutation. Transcriptional characterization of these mouse models revealed an unexpected splice pattern of CEP290 mRNA, especially in the retina. In both models, a new cryptic exon (coined exon Y was identified in ~5 to 12% of all Cep290 transcripts. This exon Y was expressed in all murine tissues analyzed but not detected in human retina or fibroblasts of LCA patients. In addition, exon x that is characteristic of LCA in humans, was expressed at only very low levels in the retina of the LCA mouse model. Western blot and immunohistochemical analyses did not reveal any differences between the two transgenic models and wild-type mice. Together, our results show clear differences in the recognition of splice sites between mice and humans, and emphasize that care is warranted when generating animal models for human genetic diseases caused by splice mutations.

  14. Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis.

    Science.gov (United States)

    Garanto, Alejandro; van Beersum, Sylvia E C; Peters, Theo A; Roepman, Ronald; Cremers, Frans P M; Collin, Rob W J

    2013-01-01

    Leber congenital amaurosis (LCA) is the most severe form of retinal dystrophy with an onset in the first year of life. The most frequent genetic cause of LCA, accounting for up to 15% of all LCA cases in Europe and North-America, is a mutation (c.2991+1655AG) in intron 26 of CEP290. This mutation generates a cryptic splice donor site resulting in the insertion of an aberrant exon (exon X) containing a premature stop codon to CEP290 mRNA. In order to study the pathophysiology of the intronic CEP290 mutation, we generated two humanized knock-in mouse models each carrying ~6.3 kb of the human CEP290 gene, either with or without the intronic mutation. Transcriptional characterization of these mouse models revealed an unexpected splice pattern of CEP290 mRNA, especially in the retina. In both models, a new cryptic exon (coined exon Y) was identified in ~5 to 12% of all Cep290 transcripts. This exon Y was expressed in all murine tissues analyzed but not detected in human retina or fibroblasts of LCA patients. In addition, exon x that is characteristic of LCA in humans, was expressed at only very low levels in the retina of the LCA mouse model. Western blot and immunohistochemical analyses did not reveal any differences between the two transgenic models and wild-type mice. Together, our results show clear differences in the recognition of splice sites between mice and humans, and emphasize that care is warranted when generating animal models for human genetic diseases caused by splice mutations.

  15. Metabolic activation of diesel exhaust carcinogens in primary and immortalized human TP53 knock-in (Hupki) mouse embryo fibroblasts.

    Science.gov (United States)

    Kucab, Jill E; Phillips, David H; Arlt, Volker M

    2012-04-01

    Approximately 50% of human tumors have a mutation in TP53. The pattern and spectra of TP53 mutations often differ between cancer types, perhaps due to different etiological factors. The Hupki (human TP53 knock-in) mouse embryo fibroblast (HUF) immortalization assay is useful for studying mutagenesis in the human TP53 gene by environmental carcinogens. Prior to initiating an immortalization assay, carcinogen treatment conditions must be optimized, which can require a large number of cells. As primary HUF cultures senesce within 2 weeks, restricting their use, we investigated whether immortalized HUFs retaining wild-type TP53 can be surrogates for primary HUFs in initial treatment optimization. DNA damage by eight compounds found in diesel exhaust, benzo[a]pyrene, 3-nitrobenzanthrone, 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene, 6-nitrochrysene, and 3-nitrofluorene, was assessed by (32) P-postlabeling and the alkaline comet assay in primary HUFs and in an immortal HUF cell line J201. For most compounds, higher levels of DNA adducts accumulated in J201 cells than in primary HUFs. This difference was not reflected in the comet assay or by cell viability changes. Experiments in three additional immortal HUF cell lines (AAI49, U56, and E2-143) confirmed strong differences in DNA adduct levels compared with primary HUFs. However, these did not correlate with the protein expression of Nqo1 or Nat1/2, or with gene expression of Cyp1a1 or Cyp1b1. Our results show that using immortal HUFs as surrogates for primary HUFs in genotoxicity screening has limitations and that DNA adduct formation is the best measure of genotoxicity of the nitro-polycyclic aromatic hydrocarbons tested in HUFs. Copyright © 2011 Wiley Periodicals, Inc.

  16. Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.

    Science.gov (United States)

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2015-02-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients. Copyright © 2013. Published by Elsevier Inc.

  17. Disruption of seven hypothetical aryl alcohol dehydrogenase genes from Saccharomyces cerevisiae and construction of a multiple knock-out strain.

    Science.gov (United States)

    Delneri, D; Gardner, D C; Bruschi, C V; Oliver, S G

    1999-11-01

    By in silicio analysis, we have discovered that there are seven open reading frames (ORFs) in Saccharomyces cerevisiae whose protein products show a high degree of amino acid sequence similarity to the aryl alcohol dehydrogenase (AAD) of the lignin-degrading fungus Phanerochaete chrysosporium. Yeast cultures grown to stationary phase display a significant aryl alcohol dehydrogenase activity by degrading aromatic aldehydes to the corresponding alcohols. To study the biochemical and the biological role of each of the AAD genes, a series of mutant strains carrying deletion of one or more of the AAD-coding sequences was constructed by PCR-mediated gene replacement, using the readily selectable marker kanMX. The correct targeting of the PCR-generated disruption cassette into the genomic locus was verified by analytical PCR and by pulse-field gel electrophoresis (PFGE) followed by Southern blot analysis. Double, triple and quadruple mutant strains were obtained by classical genetic methods, while the construction of the quintuple, sextuple and septuple mutants was achieved by using the marker URA3 from Kluyveromyces lactis, HIS3 from Schizosaccharomyces pombe and TRP1 from S. cerevisiae. None of the knock-out strains revealed any mutant phenotype when tested for the degradation of aromatic aldehydes using both spectrophotometry and high performance liquid chromatography (HPLC). Specific tests for changes in the ergosterol and phospholipids profiles did not reveal any mutant phenotype and mating and sporulation efficiencies were not affected in the septuple deletant. Compared to the wild-type strain, the septuple deletant showed an increased resistance to the anisaldehyde, but there is a possibility that the nutritional markers used for gene replacement are causing this effect. Copyright 1999 John Wiley & Sons, Ltd.

  18. Knocking-down Meloidogyne incognita proteases by plant-delivered dsRNA has negative pleiotropic effect on nematode vigor.

    Science.gov (United States)

    Antonino de Souza Júnior, José Dijair; Ramos Coelho, Roberta; Tristan Lourenço, Isabela; da Rocha Fragoso, Rodrigo; Barbosa Viana, Antonio Américo; Lima Pepino de Macedo, Leonardo; Mattar da Silva, Maria Cristina; Gomes Carneiro, Regina Maria; Engler, Gilbert; de Almeida-Engler, Janice; Grossi-de-Sa, Maria Fatima

    2013-01-01

    The root-knot nematode Meloidogyne incognita causes serious damage and yield losses in numerous important crops worldwide. Analysis of the M. incognita genome revealed a vast number of proteases belonging to five different catalytic classes. Several reports indicate that M. incognita proteases could play important roles in nematode parasitism, besides their function in ordinary digestion of giant cell contents for feeding. The precise roles of these proteins during parasitism however are still unknown, making them interesting targets for gene silencing to address protein function. In this study we have knocked-down an aspartic (Mi-asp-1), a serine (Mi-ser-1) and a cysteine protease (Mi-cpl-1) by RNAi interference to get an insight into the function of these enzymes during a host/nematode interaction. Tobacco lines expressing dsRNA for Mi-ser-1 (dsSER), Mi-cpl-1 (dsCPL) and for the three genes together (dsFusion) were generated. Histological analysis of galls did not show clear differences in giant cell morphology. Interestingly, nematodes that infected plants expressing dsRNA for proteases produced a reduced number of eggs. In addition, nematode progeny matured in dsSER plants had reduced success in egg hatching, while progeny resulting from dsCPL and dsFusion plants were less successful to infect wild-type host plants. Quantitative PCR analysis confirmed a reduction in transcripts for Mi-cpl-1 and Mi-ser-1 proteases. Our results indicate that these proteases are possibly involved in different processes throughout nematode development, like nutrition, reproduction and embryogenesis. A better understanding of nematode proteases and their possible role during a plant-nematode interaction might help to develop new tools for phytonematode control.

  19. The Lrp4R1170Q Homozygous Knock-In Mouse Recapitulates the Bone Phenotype of Sclerosteosis in Humans.

    Science.gov (United States)

    Boudin, Eveline; Yorgan, Timur; Fijalkowski, Igor; Sonntag, Stephan; Steenackers, Ellen; Hendrickx, Gretl; Peeters, Silke; De Maré, Annelies; Vervaet, Benjamin; Verhulst, Anja; Mortier, Geert; D'Haese, Patrick; Schinke, Thorsten; Van Hul, Wim

    2017-08-01

    Sclerosteosis is a rare autosomal recessive bone disorder marked by hyperostosis of the skull and tubular bones. Initially, we and others reported that sclerosteosis was caused by loss-of-function mutations in SOST, encoding sclerostin. More recently, we identified disease-causing mutations in LRP4, a binding partner of sclerostin, in three sclerosteosis patients. Upon binding to sclerostin, LRP4 can inhibit the canonical WNT signaling that is known to be an important pathway in the regulation of bone formation. To further investigate the role of LRP4 in the bone formation process, we generated an Lrp4 mutated sclerosteosis mouse model by introducing the p.Arg1170Gln mutation in the mouse genome. Extensive analysis of the bone phenotype of the Lrp4R1170Q/R1170Q knock-in (KI) mouse showed the presence of increased trabecular and cortical bone mass as a consequence of increased bone formation by the osteoblasts. In addition, three-point bending analysis also showed that the increased bone mass results in increased bone strength. In contrast to the human sclerosteosis phenotype, we could not observe syndactyly in the forelimbs or hindlimbs of the Lrp4 KI animals. Finally, we could not detect any significant changes in the bone formation and resorption markers in the serum of the mutant mice. However, the serum sclerostin levels were strongly increased and the level of sclerostin in the tibia was decreased in Lrp4R1170Q/R1170Q mice, confirming the role of LRP4 as an anchor for sclerostin in bone. In conclusion, the Lrp4R1170Q/R1170Q mouse is a good model for the human sclerosteosis phenotype caused by mutations in LRP4 and can be used in the future for further investigation of the mechanism whereby LRP4 regulates bone formation. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  20. Hippocampal dysregulation of neurofibromin-dependent pathways is associated with impaired spatial learning in engrailed 2 knock-out mice.

    Science.gov (United States)

    Provenzano, Giovanni; Pangrazzi, Luca; Poli, Andrea; Pernigo, Mattia; Sgadò, Paola; Genovesi, Sacha; Zunino, Giulia; Berardi, Nicoletta; Casarosa, Simona; Bozzi, Yuri

    2014-10-01

    Genome-wide association studies indicated the homeobox-containing transcription factor Engrailed-2 (En2) as a candidate gene for autism spectrum disorders (ASD). Accordingly, En2 knock-out (En2(-/-)) mice show anatomical and behavioral "ASD-like" features, including decreased sociability and learning deficits. The molecular pathways underlying these deficits in En2(-/-) mice are not known. Deficits in signaling pathways involving neurofibromin and extracellular-regulated kinase (ERK) have been associated with impaired learning. Here we investigated the neurofibromin-ERK cascade in the hippocampus of wild-type (WT) and En2(-/-) mice before and after spatial learning testing. When compared with WT littermates, En2(-/-) mice showed impaired performance in the Morris water maze (MWM), which was accompanied by lower expression of the activity-dependent gene Arc. Quantitative RT-PCR, immunoblotting, and immunohistochemistry experiments showed a marked downregulation of neurofibromin expression in the dentate gyrus of both naive and MWM-treated En2(-/-) mice. ERK phosphorylation, known to be induced in the presence of neurofibromin deficiency, was increased in the dentate gyrus of En2(-/-) mice after MWM. Treatment of En2(-/-) mice with lovastatin, an indirect inhibitor of ERK phosphorylation, markedly reduced ERK phosphorylation in the dentate gyrus, but was unable to rescue learning deficits in MWM-trained mutant mice. Further investigation is needed to unravel the complex molecular mechanisms linking dysregulation of neurofibromin-dependent pathways to spatial learning deficits in the En2 mouse model of ASD. Copyright © 2014 the authors 0270-6474/14/3413281-08$15.00/0.

  1. Atxn2 Knockout and CAG42-Knock-in Cerebellum Shows Similarly Dysregulated Expression in Calcium Homeostasis Pathway.

    Science.gov (United States)

    Halbach, Melanie Vanessa; Gispert, Suzana; Stehning, Tanja; Damrath, Ewa; Walter, Michael; Auburger, Georg

    2017-02-01

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disorder with preferential affection of Purkinje neurons, which are known as integrators of calcium currents. The expansion of a polyglutamine (polyQ) domain in the RNA-binding protein ataxin-2 (ATXN2) is responsible for this disease, but the causal roles of deficient ATXN2 functions versus aggregation toxicity are still under debate. Here, we studied mouse mutants with Atxn2 knockout (KO) regarding their cerebellar global transcriptome by microarray and RT-qPCR, in comparison with data from Atxn2-CAG42-knock-in (KIN) mouse cerebellum. Global expression downregulations involved lipid and growth signaling pathways in good agreement with previous data. As a novel effect, downregulations of key factors in calcium homeostasis pathways (the transcription factor Rora, transporters Itpr1 and Atp2a2, as well as regulator Inpp5a) were observed in the KO cerebellum, and some of them also occurred subtly early in KIN cerebellum. The ITPR1 protein levels were depleted from soluble fractions of cerebellum in both mutants, but accumulated in its membrane-associated form only in the SCA2 model. Coimmunoprecipitation demonstrated no association of ITPR1 with Q42-expanded or with wild-type ATXN2. These findings provide evidence that the physiological functions and protein interactions of ATXN2 are relevant for calcium-mediated excitation of Purkinje cells as well as for ATXN2-triggered neurotoxicity. These insights may help to understand pathogenesis and tissue specificity in SCA2 and other polyQ ataxias like SCA1, where inositol regulation of calcium flux and RORalpha play a role.

  2. Opportunities and Internationalisation of PSFs

    DEFF Research Database (Denmark)

    Jensen, Søren Henning; Poulfelt, Flemming

    2017-01-01

    The article focuses on the relationship between internationalisation and opportunities of firms within the professional services industry. The key question explored is whether internationalisation of PSFs is a passive strategy driven by clients' internationalisation or if it is a deliberate search...... for opportunities that drives the internationalisation processes. This is being analysed by scrutinising the literature to check if this perspective can be understood and explained from an opportunity angle. The paper shows that there is no apparent pattern among the various PSF articles that relates...... to the particular take on internationalisation for the individual article and therefore shows the same variation....

  3. Biogas Opportunities Roadmap Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-12-01

    In support of the Obama Administration's Climate Action Plan, the U.S. Department of Energy, the U.S. Environmental Protection Agency, and U.S. Department of Agriculture jointly released the Biogas Opportunities Roadmap Progress Report, updating the federal government's progress to reduce methane emissions through biogas systems since the Biogas Opportunities Roadmap was completed by the three agencies in July 2014. The report highlights actions taken, outlines challenges and opportunities, and identifies next steps to the growth of a robust biogas industry.

  4. The Visitor Who Knocks.

    Science.gov (United States)

    Blythe, Chris

    1994-01-01

    The author describes his visit to an elderly Inuit and the interaction resulting from his request to buy an old harpoon that the Inuit had used in hunting. He concludes that, no matter how long he lives in the village, he will never completely understand the Inuit culture, nor will they completely accept him. (LP)

  5. Knocking out the Argonautes.

    NARCIS (Netherlands)

    Steiner, F.A.; Plasterk, R.H.A.

    2006-01-01

    Argonaute proteins are key players in gene silencing involving small RNAs. In this issue, Yigit et al. (2006) report a comprehensive study of Argonautes in the worm that places many of the 27 family members into a complex gene-silencing network.

  6. Wind Technologies & Evolving Opportunities (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Robichaud, R.

    2014-07-01

    This presentation covers opportunities for wind technology; wind energy market trends; an overview of the National Wind Technology Center near Boulder, Colorado; wind energy price and cost trends; wind turbine technology improvements; and wind resource characterization improvements.

  7. Opportunity Cost of Distance Education

    Science.gov (United States)

    Turkoglu, Recep

    2004-01-01

    In this study, opportunity cost (OC) of distance education (DE) has been examined. In addition, factors which affect OC of DE have been investigated. (Contains 1 table.) [Abstract modified to meet ERIC guidelines.

  8. New Opportunities for Targeted Immunotherapy

    Science.gov (United States)

    A team of NCI researchers has reported that several types of gastrointestinal cancer have tumor-specific mutations that can be recognized by the immune system, thereby offering a new therapeutic opportunity for patients with these tumors.

  9. Opportunity formation in social entrepreneurship

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.

    2011-01-01

    Purpose - This paper aims to explore the concept of opportunity and its role in social entrepreneurship processes. Design/methodology/approach - A single-case study of a sustainable community in Denmark. The data include interviews, documents and television programmes. Findings - The case study...... in the field of social entrepreneurship, while contributing to the development of the creation view of opportunities. Key words - Opportunity, Social entrepreneurship, Process, Sustainability, Case Study Paper type - Research paper...... finds that the opportunity takes a number of different forms in the process. These different forms are the result of a continuous mobilisation of actors. On the basis of these findings a model of social entrepreneurship processes is proposed, where the process is driven by mobilisation...

  10. Learning opportunities in 'student assistantships'.

    Science.gov (United States)

    Burford, Bryan; Ellis, Edward; Williamson, Alyson; Forrest, Ian; Forest, Ian; Vance, Gillian

    2015-04-01

    In order to gain experience of the skills required when they begin practice, all final-year medical students in the UK undertake a 'student assistantship', working alongside first-year postgraduate doctors. In this study, we examined the learning opportunities open to students in one locality during two periods of assistantship: one in medicine; one in surgery. Final-year students and their supervisors completed online questionnaires. The students' questionnaire explored general perceptions of the placement, and whether 15 potential learning opportunities (identified as 'desk-' or 'patient-oriented') had been 'taken', 'missed' or were 'not available'. The supervisors' questionnaire explored their perceptions of students' learning during the assistantship. Overall, 86 student questionnaires and 17 supervisor questionnaires were returned (response rates of 57 and 63%, respectively). Students reported more desk-based learning opportunities, of which more were taken up, than patient-oriented learning opportunities. Surgical placements were associated with more 'missed' opportunities than medical placements. Across all tasks, many students felt that some learning opportunities were not present in their assistantship. By contrast, supervisors felt students 'made the most' of assistantships. Students' overall perceptions of the assistantship were positively related to the level of experience that they had attained (r = 0.40-0.54). The assistantship fulfils its aims for many students, but individual experience gained varies considerably. Some opportunities are not being taken, with 'patient-oriented' opportunities more likely to be missed, whereas others are not available during placements. Supervisors may overestimate the educational value of the assistantship, with implications for its management and delivery. © 2015 John Wiley & Sons Ltd.

  11. Strong morphological defects in conditional Arabidopsis abp1 knock-down mutants generated in absence of functional ABP1 protein [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Jaroslav Michalko

    2016-01-01

    Full Text Available The Auxin Binding Protein 1 (ABP1 is one of the most studied proteins in plants. Since decades ago, it has been the prime receptor candidate for the plant hormone auxin with a plethora of described functions in auxin signaling and development. The developmental importance of ABP1 has recently been questioned by identification of Arabidopsis thaliana abp1 knock-out alleles that show no obvious phenotypes under normal growth conditions. In this study, we examined the contradiction between the normal growth and development of the abp1 knock-outs and the strong morphological defects observed in three different ethanol-inducible abp1 knock-down mutants (abp1-AS, SS12K, SS12S. By analyzing segregating populations of abp1 knock-out vs. abp1 knock-down crosses we show that the strong morphological defects that were believed to be the result of conditional down-regulation of ABP1 can be reproduced also in the absence of the functional ABP1 protein. This data suggests that the phenotypes in abp1 knock-down lines are due to the off-target effects and asks for further reflections on the biological function of ABP1 or alternative explanations for the missing phenotypic defects in the abp1 loss-of-function alleles.

  12. Expression of wild-type Rp1 protein in Rp1 knock-in mice rescues the retinal degeneration phenotype.

    Directory of Open Access Journals (Sweden)

    Qin Liu

    Full Text Available Mutations in the retinitis pigmentosa 1 (RP1 gene are a common cause of autosomal dominant retinitis pigmentosa (adRP, and have also been found to cause autosomal recessive RP (arRP in a few families. The 33 dominant mutations and 6 recessive RP1 mutations identified to date are all nonsense or frameshift mutations, and almost exclusively (38 out of 39 are located in the 4(th and final exon of RP1. To better understand the underlying disease mechanisms of and help develop therapeutic strategies for RP1 disease, we performed a series of human genetic and animal studies using gene targeted and transgenic mice. Here we report that a frameshift mutation in the 3(rd exon of RP1 (c.686delC; p.P229QfsX35 found in a patient with recessive RP1 disease causes RP in the homozygous state, whereas the heterozygous carriers are unaffected, confirming that haploinsufficiency is not the causative mechanism for RP1 disease. We then generated Rp1 knock-in mice with a nonsense Q662X mutation in exon 4, as well as Rp1 transgenic mice carrying a wild-type BAC Rp1 transgene. The Rp1-Q662X allele produces a truncated Rp1 protein, and homozygous Rp1-Q662X mice experience a progressive photoreceptor degeneration characterized disorganization of photoreceptor outer segments. This phenotype could be prevented by expression of a normal amount of Rp1 protein from the BAC transgene without removal of the mutant Rp1-Q662X protein. Over-expression of Rp1 protein in additional BAC Rp1 transgenic lines resulted in retinal degeneration. These findings suggest that the truncated Rp1-Q662X protein does not exert a toxic gain-of-function effect. These results also imply that in principle gene augmentation therapy could be beneficial for both recessive and dominant RP1 patients, but the levels of RP1 protein delivered for therapy will have to be carefully controlled.

  13. Identification of genes differentially expressed in myogenin knock-down bovine muscle satellite cells during differentiation through RNA sequencing analysis.

    Directory of Open Access Journals (Sweden)

    Eun Ju Lee

    Full Text Available BACKGROUND: The expression of myogenic regulatory factors (MRFs consisting of MyoD, Myf5, myogenin (MyoG and MRF4 characterizes various phases of skeletal muscle development including myoblast proliferation, cell-cycle exit, cell fusion and the maturation of myotubes to form myofibers. Although it is well known that the function of MyoG cannot be compensated for other MRFs, the molecular mechanism by which MyoG controls muscle cell differentiation is still unclear. Therefore, in this study, RNA-Seq technology was applied to profile changes in gene expression in response to MyoG knock-down (MyoGkd in primary bovine muscle satellite cells (MSCs. RESULTS: About 61-64% of the reads of over 42 million total reads were mapped to more than 13,000 genes in the reference bovine genome. RNA-Seq analysis identified 8,469 unique genes that were differentially expressed in MyoGkd. Among these genes, 230 were up-regulated and 224 were down-regulated by at least four-fold. DAVID Functional Annotation Cluster (FAC and pathway analysis of all up- and down-regulated genes identified overrepresentation for cell cycle and division, DNA replication, mitosis, organelle lumen, nucleoplasm and cytosol, phosphate metabolic process, phosphoprotein phosphatase activity, cytoskeleton and cell morphogenesis, signifying the functional implication of these processes and pathways during skeletal muscle development. The RNA-Seq data was validated by real time RT-PCR analysis for eight out of ten genes as well as five marker genes investigated. CONCLUSIONS: This study is the first RNA-Seq based gene expression analysis of MyoGkd undertaken in primary bovine MSCs. Computational analysis of the differentially expressed genes has identified the significance of genes such as SAP30-like (SAP30L, Protein lyl-1 (LYL1, various matrix metalloproteinases, and several glycogenes in myogenesis. The results of the present study widen our knowledge of the molecular basis of skeletal muscle

  14. Efficient Generation of Myostatin Knock-Out Sheep Using CRISPR/Cas9 Technology and Microinjection into Zygotes.

    Directory of Open Access Journals (Sweden)

    M Crispo

    Full Text Available While CRISPR/Cas9 technology has proven to be a valuable system to generate gene-targeted modified animals in several species, this tool has been scarcely reported in farm animals. Myostatin is encoded by MSTN gene involved in the inhibition of muscle differentiation and growth. We determined the efficiency of the CRISPR/Cas9 system to edit MSTN in sheep and generate knock-out (KO animals with the aim to promote muscle development and body growth. We generated CRISPR/Cas9 mRNAs specific for ovine MSTN and microinjected them into the cytoplasm of ovine zygotes. When embryo development of CRISPR/Cas9 microinjected zygotes (n = 216 was compared with buffer injected embryos (n = 183 and non microinjected embryos (n = 173, cleavage rate was lower for both microinjected groups (P<0.05 and neither was affected by CRISPR/Cas9 content in the injected medium. Embryo development to blastocyst was not affected by microinjection and was similar among the experimental groups. From 20 embryos analyzed by Sanger sequencing, ten were mutant (heterozygous or mosaic; 50% efficiency. To obtain live MSTN KO lambs, 53 blastocysts produced after zygote CRISPR/Cas9 microinjection were transferred to 29 recipient females resulting in 65.5% (19/29 of pregnant ewes and 41.5% (22/53 of newborns. From 22 born lambs analyzed by T7EI and Sanger sequencing, ten showed indel mutations at MSTN gene. Eight showed mutations in both alleles and five of them were homozygous for indels generating out-of frame mutations that resulted in premature stop codons. Western blot analysis of homozygous KO founders confirmed the absence of myostatin, showing heavier body weight than wild type counterparts. In conclusion, our results demonstrate that CRISPR/Cas9 system was a very efficient tool to generate gene KO sheep. This technology is quick and easy to perform and less expensive than previous techniques, and can be applied to obtain genetically modified animal models of interest for

  15. A simplified high-throughput method for pyrethroid knock-down resistance (kdr detection in Anopheles gambiae

    Directory of Open Access Journals (Sweden)

    Walker Edward D

    2005-03-01

    Full Text Available Abstract Background A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation. Methods A Hot Ligation Oligonucleotide Assay (HOLA was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique. Results and Discussion The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous. Conclusion The method is capable of detecting both the East and West African kdr alleles

  16. Distribution of knock-down resistance mutations in Anopheles gambiae molecular forms in west and west-central Africa

    Directory of Open Access Journals (Sweden)

    Caccone Adalgisa

    2008-04-01

    Full Text Available Abstract Background Knock-down resistance (kdr to DDT and pyrethroids in the major Afrotropical vector species, Anopheles gambiae sensu stricto, is associated with two alternative point mutations at amino acid position 1014 of the voltage-gated sodium channel gene, resulting in either a leucine-phenylalanine (L1014F, or a leucine-serine (L1014S substitution. In An. gambiae S-form populations, the former mutation appears to be widespread in west Africa and has been recently reported from Uganda, while the latter, originally recorded in Kenya, has been recently found in Gabon, Cameroon and Equatorial Guinea. In M-form populations surveyed to date, only the L1014F mutation has been found, although less widespread and at lower frequencies than in sympatric S-form populations. Methods Anopheles gambiae M- and S-form specimens from 19 sites from 11 west and west-central African countries were identified to molecular form and genotyped at the kdr locus either by Hot Oligonucleotide Ligation Assay (HOLA or allele-specific PCR (AS-PCR. Results The kdr genotype was determined for about 1,000 An. gambiae specimens. The L1014F allele was found at frequencies ranging from 6% to 100% in all S-form samples (N = 628, with the exception of two samples from Angola, where it was absent, and coexisted with the L1014S allele in samples from Cameroon, Gabon and north-western Angola. The L1014F allele was present in M-form samples (N = 354 from Benin, Nigeria, and Cameroon, where both M- and S-forms were sympatric. Conclusion The results represent the most comprehensive effort to analyse the overall distribution of the L1014F and L1014S mutations in An. gambiae molecular forms, and will serve as baseline data for resistance monitoring. The overall picture shows that the emergence and spread of kdr alleles in An. gambiae is a dynamic process and that there is marked intra- and inter-form heterogeneity in resistance allele frequencies. Further studies are needed to

  17. 1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice.

    Science.gov (United States)

    Kim, Il Yong; Jung, Jeeyoun; Jang, Mi; Ahn, Yun Gyong; Shin, Jae Hoon; Choi, Ji Won; Sohn, Mi Ra; Shin, Sun Mee; Kang, Dae-Gil; Lee, Ho-Sub; Bae, Yun Soo; Ryu, Do Hyun; Seong, Je Kyung; Hwang, Geum-Sook

    2010-12-17

    AHNAK is a giant protein of approximately 700 kDa identified in human neuroblastomas and skin epithelial cells. Recently, we found that AHNAK knock-out (AHNAK(-/-)) mice have a strong resistance to high-fat diet-induced obesity. In this study, we applied (1)H NMR-based metabolomics with multivariate statistical analysis to compare the altered metabolic patterns detected in urine from high-fat diet (HFD) fed wild-type and AHNAK(-/-) mice and investigate the mechanisms underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice. In global profiling, principal components analysis showed a clear separation between the chow diet and HFD groups; wild-type and AHNAK(-/-) mice were more distinctly separated in the HFD group compared to the chow diet group. Based on target profiling, the urinary metabolites of HFD-fed AHNAK(-/-) mice gave higher levels of methionine, putrescine, tartrate, urocanate, sucrose, glucose, threonine, and 3-hydroxyisovalerate. Furthermore, two-way ANOVAs indicated that diet type, genetic type, and their interaction (gene × diet) affect the metabolite changes differently. Most metabolites were affected by diet type, and putrescine, threonine, urocanate, and tartrate were also affected by genetic type. In addition, cis-aconitate, succinate, glycine, histidine, methylamine (MA), phenylacetylglycine (PAG), methionine, putrescine, uroconate, and tartrate showed interaction effects. Through the pattern changes in urinary metabolites of HFD-fed AHNAK(-/-) mice, our data suggest that the strong resistance to HFD-induced obesity in AHNAK(-/-) mice comes from perturbations of amino acids, such as methionine, putrescine, threonine, and histidine, which are related to fat metabolism. The changes in metabolites affected by microflora such as PAG and MA were also observed. In addition, resistance to obesity in HFD-fed AHNAK(-/-) mice was not related to an activated tricarboxylic acid cycle. These findings demonstrate that (1)H NMR

  18. Knock and drill technique: A simple tips for the instrumentation in complex craniovertebral junction anomalies without using fluoroscopy

    Directory of Open Access Journals (Sweden)

    Arun Srivastava

    2017-01-01

    Full Text Available Context: Existence of complex variable bony and vertebral artery (VA anomalies at craniovertebral junction (CVJ in subset of complex CVJ anomalies demands individualized instrumentation policy and placing screws in each bone requires strategic preoperative planning and intraoperative skills. Aim: To evaluate the clinical accuracy of knock and drill (K and D technique for the screw placement in complex CVJ anomalies. Settings and Design: Prospective study and operative technical note. Materials and Methods: Totally 36 consecutive patients (16 - pediatrics, 20 - adult patients of complex CVJ: Complete/partial occipitalized C1 vertebra; at least one hypoplastic (C1/C2 articular mass, rotational component, and variations in the third part of VA were included in this study. Preoperative detail computed tomography (CT CT CVJ with three-dimensional reconstruction was done for the assessment of CVJ anatomy and facet joint orientation. The accuracy of novel technique was assessed with postoperative CT to evaluate cortical breach in between 5th and 7th postoperative day in all the patients. All patients were underwent clinico-radiological evaluation at 6-month follow-up. Results: Totally 144 screws were placed using K and D technique (pediatric group - 64 screws, adult patients - 80 screws. Total of 12 screws were placed in C1 lateral mass in both age group without any bony cortical breach and complication. Sixteen C2 pedicle screws and 12 C2 pars screw in pediatrics and 18 C2 pedicle screws in adult patients were placed without any bony breach or VA injury. Out of thirty subaxial lateral mass screws in pediatric group, the bony breach was encountered with one screw (3.3%. Total of 38 C2 pars screws was placed in adult group in which bony breach along with VA injury was encounter with 1screw (2.6%. Conclusion: A simple technique of K and D for placing a screw increases the accuracy and spectrum of bony purchase and has the potential to reduce the

  19. Median knock-down time as a new method for evaluating insecticide-treated textiles for mosquito control

    Directory of Open Access Journals (Sweden)

    Pigeon Olivier

    2008-06-01

    Full Text Available Abstract Background Insecticide treated bed nets are major tools for the Roll Back Malaria campaign. There are two types of Long-Lasting Insecticide-treated Nets (LNs on the market: coated nets and insecticide-incorporated nets. Nets provided to this market need a recommendation from the World Health Organization to be purchased by donors and NGOs. During laboratory study (phase I, the first step consists in evaluating the wash resistance of a new LN product. When insecticide-incorporated nets are washed, it takes time to regenerate the insecticidal activity, i.e. insecticide must migrate to the net surface to be accessible to mosquitoes. The interval of time required for regeneration must be carefully determined to ensure the accuracy of further results. WHOPES procedures currently recommend the determination of the regeneration time by using mortality data. However, as mortality cannot exceed 100%, a LN that regenerates a surface concentration exceeding the dosage for 100% mortality, will have its regeneration time underestimated. Methods The Median Knock Down Time (MKDT was determined as function of insecticide dosage on an inert surface, glass, and on polyester nettings using an acetone solution or a simple emulsion. Dosage response was also established for mortality data. The same method was then applied to a commercially polyethylene netting, currently under WHOPES evaluation, to determine the dynamics of regeneration as function of repeated washings. The deltamethrin content of these nets was estimated by Capillary Gas Chromatography (GC-ECD. Results MKDT was a linear function of log insecticide dosage on glass as on nettings. Mortality data were either 0 or 100% for most concentrations except for a narrow range. MKDT was log linear function of total deltamethrin content in a commercial polyethylene net exposed to washings. The regeneration time of this net increased with the number of washes and MKDT became higher. A new, easy and rapid

  20. 25 CFR 700.33 - Act (The Act).

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88 Stat...

  1. Opportunity's Surroundings on Sol 1818

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends. The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view. The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock. This view is presented as a cylindrical projection with geometric seam correction.

  2. Research Handbook on Entrepreneurial Opportunities

    DEFF Research Database (Denmark)

    complemented by an outstanding Delphi panel of six leading scholars of the field: Lowell Busenitz, Dimo Dimov, James O. Fiet, Denis Grégoire, Jeff McMullen and Mike Wright. This carefully edited selection of current and topical contributions will be of immense value to students, researchers and scholars......With a wide-ranging set of contributions, this book provides a compilation of cutting-edge original research in the field of entrepreneurial opportunities. The book reopens the subject from diverse perspectives focusing on theories and approaches to entrepreneurial opportunities. The book has been...

  3. 76 FR 58241 - Opportunity for Designation in the Jamestown, ND; Lincoln, NE; Memphis, TN; and Sioux City, IA...

    Science.gov (United States)

    2011-09-20

    ... Grain Inspection, Packers and Stockyards Administration Opportunity for Designation in the Jamestown, ND... Servicing These areas AGENCY: Grain Inspection, Packers and Stockyards Administration, USDA. ACTION: Notice..., Acting Administrator, Grain Inspection, Packers, and Stockyards Administration. BILLING CODE 3410-KD-P ...

  4. 75 FR 29310 - Opportunity for Designation in the Columbus, OH; Dallas, TX; and Decatur, IN Areas; Request for...

    Science.gov (United States)

    2010-05-25

    ... Grain Inspection, Packers and Stockyards Administration Opportunity for Designation in the Columbus, OH... AGENCY: Grain Inspection, Packers and Stockyards Administration, USDA. ACTION: Notice. SUMMARY: The..., Acting Administrator, Grain Inspection, Packers and Stockyards Administration. BILLING CODE 3410-KD-P ...

  5. Pro416Arg cherubism mutation in Sh3bp2 knock-in mice affects osteoblasts and alters bone mineral and matrix properties.

    Science.gov (United States)

    Wang, Chiachien J; Chen, I-Ping; Koczon-Jaremko, Boguslawa; Boskey, Adele L; Ueki, Yasuyoshi; Kuhn, Liisa; Reichenberger, Ernst J

    2010-05-01

    Cherubism is an autosomal dominant disorder in children characterized by unwarranted symmetrical bone resorption of the jaws with fibrous tissue deposition. Mutations causing cherubism have been identified in the adaptor protein SH3BP2. Knock-in mice with a Pro416Arg mutation in Sh3bp2 exhibit a generalized osteoporotic bone phenotype. In this study, we examined the effects of this "cherubism" mutation on spectroscopic indices of "bone quality" and on osteoblast differentiation. Fourier-transform infrared imaging (FTIRI) analysis of femurs from wild-type and Sh3bp2 knock-in mice showed decreased mineral content, decreased mineral crystallinity/crystal size, and increased collagen maturity in homozygous mutants. To assess osteoblast maturation in vivo, knock-in mice were crossed with transgenic mice over-expressing GFP driven by 3.6-kb or 2.3-kb Col1a1 promoter fragments. Reduced numbers of mature osteoblasts were observed in homozygous mice. Neonatal calvarial cultures, which were enriched for osteoblasts by depletion of hematopoietic cells (negative selection for Ter119- and CD45-positive cells) were investigated for osteoblast-specific gene expression and differentiation, which demonstrated that differentiation and mineralization in homozygous osteoblast cultures was impaired. Co-cultures with calvarial osteoblasts and bone marrow macrophages showed that mutant osteoblasts appear to increase osteoclastogenesis resulting in increased bone resorption on bone chips. In summary, the Sh3bp2 mutation in cherubism mice alters bone quality, reduces osteoblast function, and may contribute to excessive bone resorption by osteoclasts. Our data, together with previous osteoclast studies, demonstrate a critical role of Sh3bp2 in bone remodeling and osteoblast differentiation. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  6. Cytotoxic Effects during Knock Out of Multiple Porcine Endogenous Retrovirus (PERV Sequences in the Pig Genome by Zinc Finger Nucleases (ZFN.

    Directory of Open Access Journals (Sweden)

    Marwan Semaan

    Full Text Available Xenotransplantation has been proposed as a solution to the shortage of suitable human donors for transplantation and pigs are currently favoured as donor animals. However, xenotransplantation may be associated with the transmission of zoonotic microorganisms. Whereas most porcine microorganisms representing a risk for the human recipient may be eliminated by designated pathogen free breeding, multiple copies of porcine endogenous retroviruses (PERVs are integrated in the genome of all pigs and cannot be eliminated this way. PERVs are released as infectious particles and infect human cells. The zinc finger nuclease (ZFN technology allows knocking out specifically cellular genes, however it was not yet used to eliminate multiple integrated proviral sequences with a strong conservation in the target sequence. To reduce the risk of horizontal PERV transmission and to knock out as many as possible proviruses, for the first time the powerful tool of the ZFN technology was used. ZFN were designed to bind specifically to sequences conserved in all known replication-competent proviruses. Expression and transport of the ZFN into the nucleus was shown by Western blot analysis, co-localisation analysis, PLA and FRET. Survival of transfected cells was analysed using fluorescent ZFN and cell counting. After transfection a strong expression of the ZFN proteins and a co-localisation of the expressed ZFN proteins were shown. However, expression of the ZFN was found to be extremely toxic for the transfected cells. The induced cytotoxicity was likely due to the specific cutting of the high copy number of the PERV proviruses, which is also commonly observed when ZFN with low specificity cleave numerous off-target sites in a genome. This is the first attempt to knock out multiple, nearly identical, genes in a cellular genome using ZFN. The attempt failed, and other strategies should be used to prevent PERV transmission.

  7. Knock Resistance and Fine Particle Emissions for Several Biomass-Derived Oxygenates in a Direct-Injection Spark-Ignition Engine

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliff, Matthew A.; Burton, Jonathan; Sindler, Petr; Christensen, Earl; Fouts, Lisa; Chupka, Gina M.; McCormick, Robert L.

    2016-04-01

    Several high octane number oxygenates that could be derived from biomass were blended with gasoline and examined for performance properties and their impact on knock resistance and fine particle emissions in a single cylinder direct-injection spark-ignition engine. The oxygenates included ethanol, isobutanol, anisole, 4-methylanisole, 2-phenylethanol, 2,5-dimethyl furan, and 2,4-xylenol. These were blended into a summertime blendstock for oxygenate blending at levels ranging from 10 to 50 percent by volume. The base gasoline, its blends with p-xylene and p-cymene, and high-octane racing gasoline were tested as controls. Relevant gasoline properties including research octane number (RON), motor octane number, distillation curve, and vapor pressure were measured. Detailed hydrocarbon analysis was used to estimate heat of vaporization and particulate matter index (PMI). Experiments were conducted to measure knock-limited spark advance and particulate matter (PM) emissions. The results show a range of knock resistances that correlate well with RON. Molecules with relatively low boiling point and high vapor pressure had little effect on PM emissions. In contrast, the aromatic oxygenates caused significant increases in PM emissions (factors of 2 to 5) relative to the base gasoline. Thus, any effect of their oxygen atom on increasing local air-fuel ratio was outweighed by their low vapor pressure and high double-bond equivalent values. For most fuels and oxygenate blend components, PMI was a good predictor of PM emissions. However, the high boiling point, low vapor pressure oxygenates 2-phenylethanol and 2,4-xylenol produced lower PM emissions than predicted by PMI. This was likely because they did not fully evaporate and combust, and instead were swept into the lube oil.

  8. The Child Justice Act

    African Journals Online (AJOL)

    Stephan

    1995-06-16

    Jun 16, 1995 ... I want to express my gratitude to them all. 1 In the past a few different categories of young offenders were specifically addressed in our law. For example, s 290 of the Criminal Procedure Act 51 of 1977 (before its repeal by the Child. Justice Act 75 of 2008) had specific provisions for "young offenders" under ...

  9. ACT and College Success

    Science.gov (United States)

    Bleyaert, Barbara

    2010-01-01

    What is the relationship between ACT scores and success in college? For decades, admissions policies in colleges and universities across the country have required applicants to submit scores from a college entrance exam, most typically the ACT (American College Testing) or SAT (Scholastic Aptitude Test). This requirement suggests that high school…

  10. Marine Mammal Protection Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Marine Mammal Protection Act (MMPA or Act) prohibits, with certain exceptions, the "take" of marine mammals in U.S. waters and by U.S. citizens on the high seas,...

  11. Transitions as Speech Acts.

    Science.gov (United States)

    Fesmire, Alice Ann

    1993-01-01

    Reviews speech act theory to explain the function of writing transitions in terms of the illocutionary and perlocutionary effect of explicit performatives. Identifies explicit performatives in samples of professional writing in technical and academic areas. Suggest ways to revise textbooks to include the findings from speech act theory. (SR)

  12. Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Hilary Moffitt

    2009-11-01

    Full Text Available Huntington's disease (HD is an inherited progressive neurodegenerative disorder caused by a CAG repeat expansion in the ubiquitously expressed HD gene resulting in an abnormally long polyglutamine repeat in the huntingtin protein. Polyglutamine inclusions are a hallmark of the neuropathology of HD. We have previously shown that inclusion pathology is also present in the peripheral tissues of the R6/2 mouse model of HD which expresses a small N-terminal fragment of mutant huntingtin. To determine whether this peripheral pathology is a consequence of the aberrant expression of this N-terminal fragment, we extend this analysis to the genetically precise knock-in mouse model of HD, HdhQ150, which expresses mutant mouse huntingtin.We have previously standardized the CAG repeat size and strain background of the R6/2 and HdhQ150 knock-in mouse models and found that they develop a comparable and widespread neuropathology. To determine whether HdhQ150 knock-in mice also develop peripheral inclusion pathology, homozygous Hdh(Q150/Q150 mice were perfusion fixed at 22 months of age, and tissues were processed for histology and immunohistochemistry with the anti-huntingtin antibody S830. The peripheral inclusion pathology was almost identical to that found in R6/2 mice at 12 weeks of age with minor differences in inclusion abundance.The highly comparable peripheral inclusion pathology that is present in both the R6/2 and HdhQ150 knock-in models of HD indicates that the presence of peripheral inclusions in R6/2 mice is not a consequence of the aberrant expression of an N-terminal huntingtin protein. It remains to be determined whether peripheral inclusions are a pathological feature of the human disease. Both mouse models carry CAG repeats that cause childhood disease in humans, and therefore, inclusion pathology may be a feature of the childhood rather than the adult forms of HD. It is important to establish the extent to which peripheral pathology causes

  13. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    Vasopressin (AVP) is both a neuroendocrine hormone located in magnocellular neurosecretory neurons of the hypothalamus of mammals but also a neurotransmitter/neuromodulator in the parvocellular suprachiasmatic nucleus (SCN). The SCN is the endogenous clock of the brain and exhibits a prominent...... circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

  14. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Directory of Open Access Journals (Sweden)

    Yukiko Ihara

    Full Text Available The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG, a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB, which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+ bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg were recorded using a video-electroencephalography (EEG monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  15. Nikola Tesla Educational Opportunity School.

    Science.gov (United States)

    Design Cost Data, 2001

    2001-01-01

    Describes the architectural design, costs, general description, and square footage data for the Nikola Tesla Educational Opportunity School in Colorado Springs, Colorado. A floor plan and photos are included along with a list of manufacturers and suppliers used for the project. (GR)

  16. Operationalizing Lawfare: Opportunity and Risk

    Science.gov (United States)

    2017-05-25

    December 2016, https://www.gpo.gov/fdsys/pkg/PLAW-104publ201/pdf/PLAW-104publ201.pdf, accessed 8 December 2016. 10 USA TODAY, "Military Snaps Up...but it is impossible to evaluate opportunity and risk without being able to make a relative comparison. The danger of lawfare is inflating the

  17. Future landscapes: opportunities and challenges

    Science.gov (United States)

    John Stanturf

    2015-01-01

    The global magnitude of degraded and deforested areas is best approached by restoring landscapes. Heightened international perception of the importance of forests and trees outside forests (e.g., woodlands, on farms) demands new approaches to future landscapes. The current need for forest restoration is two billion ha; most opportunities are mosaic restoration in the...

  18. Suborbital Research and Development Opportunities

    Science.gov (United States)

    Davis, Jeffrey R.

    2011-01-01

    This slide presentation reviews the new strategies for problem solving in the life sciences in the suborbital realm. Topics covered are: an overview of the space life sciences, the strategic initiatives that the Space Life Sciences organization engaged in, and the new business model that these initiatives were developed. Several opportunities for research are also reviewed.

  19. Analysis of Business Opportunities & Entrepreneurial

    African Journals Online (AJOL)

    ETIWISTIC

    2013-04-29

    Apr 29, 2013 ... them to enhance global opportunities in the world of business. These are the group of people we call entrepreneurs. According to Hisrich, Peters and Shepherd (2009) the basic function of an entrepreneur is to reform or revolutionize the pattern of production by exploiting an invention or, more generally, ...

  20. Latino Immigration, Education, and Opportunity

    Science.gov (United States)

    Jimenez, Rosa M.

    2012-01-01

    Immigration is often framed as a problem, yet it is also a time of remarkable opportunity. While immigrants come to the United States from all over the world, the author focuses on the unique and urgent issues related to Latino immigration. Immigrant Latinos have changed the face of America and U.S. schools. Approximately one in five K-12 students…

  1. Opportunity at 'Cook Islands' (Polar)

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,825th Martian day, or sol, of Opportunity's surface mission (March 12, 2009). North is at the top. This view is presented as a polar projection with geometric seam correction. The rover had driven half a meter (1.5 feet) earlier on Sol 1825 to fine-tune its location for placing its robotic arm onto an exposed patch of outcrop including a target area informally called 'Cook Islands.' On the preceding sol, Opportunity turned around to drive frontwards and then drove 4.5 meters (15 feet) toward this outcrop. The tracks from the SOl 1824 drive are visible near the center of this view at about the 11 o'clock position. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Opportunity had previously been driving backward as a strategy to redistribute lubrication in a wheel drawing more electrical current than usual. The outcrop exposure that includes 'Cook Islands' is visible just below the center of the image. The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

  2. Obesogenic environment – intervention opportunities

    Directory of Open Access Journals (Sweden)

    Mauro Fisberg

    2016-05-01

    Conclusion: Intervention opportunities are related to modifications in political, environmental, and individual settings. School and physical activities in the educational environment are intertwined with nutrition intervention in continuous education. A critical review of some different scenarios in Latin American countries is presented.

  3. Acts of kindness and acts of novelty affect life satisfaction.

    Science.gov (United States)

    Buchanan, Kathryn E; Bardi, Anat

    2010-01-01

    The present experiment was designed to establish the effects of acts of kindness and acts of novelty on life satisfaction. Participants aged 18-60 took part on a voluntary basis. They were randomly assigned to perform either acts of kindness, acts of novelty, or no acts on a daily basis for 10 days. Their life satisfaction was measured before and after the 10-day experiment. As expected, performing acts of kindness or acts of novelty resulted in an increase in life satisfaction.

  4. Knock-in fibroblasts and transgenic blastocysts for expression of human FGF2 in the bovine β-casein gene locus using CRISPR/Cas9 nuclease-mediated homologous recombination.

    Science.gov (United States)

    Jeong, Young-Hee; Kim, Yeong Ji; Kim, Eun Young; Kim, Se Eun; Kim, Jiwoo; Park, Min Jee; Lee, Hong-Gu; Park, Se Pill; Kang, Man-Jong

    2016-06-01

    Many transgenic domestic animals have been developed to produce therapeutic proteins in the mammary gland, and this approach is one of the most important methods for agricultural and biomedical applications. However, expression and secretion of a protein varies because transgenes are integrated at random sites in the genome. In addition, distal enhancers are very important for transcriptional gene regulation and tissue-specific gene expression. Development of a vector system regulated accurately in the genome is needed to improve production of therapeutic proteins. The objective of this study was to develop a knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the bovine β-casein gene locus. The F2A sequence was fused to the human FGF2 gene and inserted into exon 3 of the β-casein gene. We detected expression of human FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2 protein in the culture media using western blot analysis when the knock-in vector was introduced. We transfected the knock-in vector into bovine ear fibroblasts and produced knock-in fibroblasts using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was more efficient than conventional methods. In addition, we produced knock-in blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our knock-in fibroblasts may help to create cloned embryos for development of transgenic dairy cattle expressing human FGF2 protein in the mammary gland via the expression system of the bovine β-casein gene.

  5. Opportunity for selection in human health.

    Science.gov (United States)

    Govindaraju, Diddahally R

    2014-01-01

    Natural selection defined by differential survival and reproduction of individuals in populations is influenced by genetic, developmental, and environmental factors operating at every age and stage in human life history: generation of gametes, conception, birth, maturation, reproduction, senescence, and death. Biological systems are built upon a hierarchical organization nesting subcellular organelles, cells, tissues, and organs within individuals, individuals within families, and families within populations, and the latter among other populations. Natural selection often acts simultaneously at more than one level of biological organization and on specific traits, which we define as multilevel selection. Under this model, the individual is a fundamental unit of biological organization and also of selection, imbedded in a larger evolutionary context, just as it is a unit of medical intervention imbedded in larger biological, cultural, and environmental contexts. Here, we view human health and life span as necessary consequences of natural selection, operating at all levels and phases of biological hierarchy in human life history as well as in sociological and environmental milieu. An understanding of the spectrum of opportunities for natural selection will help us develop novel approaches to improving healthy life span through specific and global interventions that simultaneously focus on multiple levels of biological organization. Indeed, many opportunities exist to apply multilevel selection models employed in evolutionary biology and biodemography to improving human health at all hierarchical levels. Multilevel selection perspective provides a rational theoretical foundation for a synthesis of medicine and evolution that could lead to discovering effective predictive, preventive, palliative, potentially curative, and individualized approaches in medicine and in global health programs. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Draconian dress act repealed.

    Science.gov (United States)

    Mhone, C

    1994-01-01

    The Dress Act was put into place in Malawi by the government of President Kamuzu Banda after the long period of direct colonialism. The act made it illegal for women in Malawi to be seen publicly wearing dresses which did not completely cover their knees or wearing pants; men had to wear their hair short. Police officers even scrutinized women's attire at private house parties and in homes. The autocratic political structure established by Banda, however, was voted out in a referendum June 14, 1993. Pressure by opposition forces such as the United Democratic Front forced a repeal of the act on November 16 of the same year. The repeal was vigorously attacked by female Parliament members as a move which would result in moral degradation and an increase in the level of sexual harassment against women. Other citizens and tourists have generally detested the act. The act has most certainly kept many potential visitors from vacationing in Malawi. Some expert observers think that repeals of the Dress Act, the Forfeiture Act, and legislation which allowed the government to detain opposition figures without trial were done to garner support from the Paris Club for the resumption of balance of payments support suspended due to the country's poor human rights record.

  7. Sarbanes Oxley Act

    OpenAIRE

    Těšínský, Josef

    2011-01-01

    The diploma thesis is focused on corporate fraud problematic, on The Sarbanes-Oxley Act of 2002 and on problematics of internal control systems and corporate governance, which relate closely with the Sarbanes-Oxley act. The goal of my diploma thesis is to highlight the significance of corporate fraud problematic and create an integrated summary of requirements placed on companies, which either have to or want to comply with the Sarbanes-Oxley act. The opening part of the diploma thesis is foc...

  8. The Experiment as Act

    DEFF Research Database (Denmark)

    Søndergaard, Morten

    to identify and locate the experiments of POEX65 as acts; and to ask the questions: what constitutes those acts as experiments? and how do we possibly archive them? My purpose, then, is to define the methodologies to obtain the contours of a post-phenomenology of experimental artistic production in order...... to be able to analyse the phenomena found at POEX65. Here I will use the notion of the ‘ontological theatre’ (Pickering), which, according to Pickering, is acted out in experimental art productions. The experiment could thus be seen as an ‘agency-realism’ – as an ‘act’ of relations across the aesthetics...

  9. 75 FR 63703 - Privacy Act of 1974; Privacy Act Regulation

    Science.gov (United States)

    2010-10-18

    ... CFR Part 261a Privacy Act of 1974; Privacy Act Regulation AGENCY: Board of Governors of the Federal...) is issuing a final rule to amend its regulation implementing the Privacy Act of 1974 (Privacy Act..., and applicants for Board employment, for access to their records under the Privacy Act; the amendment...

  10. Reducing the Levels of Akt Activation by PDK1 Knock-in Mutation Protects Neuronal Cultures against Synthetic Amyloid-Beta Peptides

    Directory of Open Access Journals (Sweden)

    Shaobin Yang

    2018-01-01

    Full Text Available The Akt kinase has been widely assumed for years as a key downstream effector of the PI3K signaling pathway in promoting neuronal survival. This notion was however challenged by the finding that neuronal survival responses were still preserved in mice with reduced Akt activity. Moreover, here we show that the Akt signaling is elevated in the aged brain of two different mice models of Alzheimer Disease. We manipulate the rate of Akt stimulation by employing knock-in mice expressing a mutant form of PDK1 (phosphoinositide-dependent protein kinase 1 with reduced, but not abolished, ability to activate Akt. We found increased membrane localization and activity of the TACE/ADAM17 α-secretase in the brain of the PDK1 mutant mice with concomitant TNFR1 processing, which provided neurons with resistance against TNFα-induced neurotoxicity. Opposite to the Alzheimer Disease transgenic mice, the PDK1 knock-in mice exhibited an age-dependent attenuation of the unfolding protein response, which protected the mutant neurons against endoplasmic reticulum stressors. Moreover, these two mechanisms cooperatively provide the mutant neurons with resistance against amyloid-beta oligomers, and might singularly also contribute to protect these mice against amyloid-beta pathology.

  11. Exacerbation of spontaneous autoimmune nephritis following regulatory T cell depletion in B cell lymphoma 2-interacting mediator knock-out mice.

    Science.gov (United States)

    Wang, Y M; Zhang, G Y; Wang, Y; Hu, M; Zhou, J J; Sawyer, A; Cao, Q; Wang, Y; Zheng, G; Lee, V W S; Harris, D C H; Alexander, S I

    2017-05-01

    Regulatory T cells (Tregs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of Tregs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of Tregs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of Tregs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting Tregs . Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim-/- ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that Treg depletion in Bim-/- mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after Treg depletion in Bim-/- mice. This study demonstrates that transient depletion of Tregs leads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice. © 2017 British Society for Immunology.

  12. Designing and Cloning Molecular Constructs to Knock Out N-Acetylglucosamine Phosphatidylinositol De-N-Acetylase (GPI12 Gene in Leishmania major (MRHO/IR/75/ER

    Directory of Open Access Journals (Sweden)

    Pooya GHASEMI NEJAD ALMANI

    2016-12-01

    Full Text Available Background: Leishmaniasis represents a major public health concern in tropical and sub-tropical countries. At present, there is no efficacious vaccine against the disease and new control methods are needed. One way to access this important goal is to knock out genes of specific macromolecules to evaluate the effect of deletion on the growth, multiplication, pathogenesis and immunity of the parasite. The aim of this study was to design and clone molecular constructs to knock out N-acetylglucosamine phosphatidylinositol de-N-acetylase (GPI12 gene in Leishmania major.Methods: For designing and making molecular constructs, we used pLEXSY-neo2 and pLEXSY-hyg2 vectors. The molecular constructs were cloned in E. coli strain Top10. The molecular constructs were transfected by electroporation into L. major in two stages.Results: The molecular constructs were confirmed by Colony PCR and sequencing. The recombinant strains were isolated by selective antibiotics, after which they were confirmed by PCR, Southern and Western blots.Conclusion: Recombinant parasites were created and examined for subsequent study. With the use of molecular constructs, it was possible to remove and study gene GPI12 and to achieve a live recombinant Leishmania parasite that maintained the original form of the antigenic parasites. This achievement can be used as an experimental model for vaccine development studies. Further investigations are essential to check this model in a suitable host.

  13. Designing and Cloning Molecular Constructs to Knock Out N-Acetylglucosamine Phosphatidylinositol De-N-Acetylase (GPI12) Gene in Leishmania major (MRHO/IR/75/ER).

    Science.gov (United States)

    Ghasemi Nejad Almani, Pooya; Sharifi, Iraj; Kazemi, Bahram; Babaei, Zahra; Bandehpour, Mojgan; Salari, Samira; Saedi Dezaki, Ebrahim

    2016-01-01

    Leishmaniasis represents a major public health concern in tropical and sub-tropical countries. At present, there is no efficacious vaccine against the disease and new control methods are needed. One way to access this important goal is to knock out genes of specific macromolecules to evaluate the effect of deletion on the growth, multiplication, pathogenesis and immunity of the parasite. The aim of this study was to design and clone molecular constructs to knock out N-acetylglucosamine phosphatidylinositol de-N-acetylase (GPI12) gene in Leishmania major. For designing and making molecular constructs, we used pLEXSY-neo2 and pLEXSY-hyg2 vectors. The molecular constructs were cloned in E. coli strain Top10. The molecular constructs were transfected by electroporation into L. major in two stages. The molecular constructs were confirmed by Colony PCR and sequencing. The recombinant strains were isolated by selective antibiotics, after which they were confirmed by PCR, Southern and Western blots. Recombinant parasites were created and examined for subsequent study. With the use of molecular constructs, it was possible to remove and study gene GPI12 and to achieve a live recombinant Leishmania parasite that maintained the original form of the antigenic parasites. This achievement can be used as an experimental model for vaccine development studies. Further investigations are essential to check this model in a suitable host.

  14. Energy Policy Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Energy Policy Act (EPA) addresses energy production in the United States, including: (1) energy efficiency; (2) renewable energy; (3) oil and gas; (4) coal; (5)...

  15. Clean Water Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Clean Water Act (CWA) establishes the basic structure for regulating discharges of pollutants into U.S. waters and regulating quality standards for surface...

  16. Affordable Care Act (ACA)

    Data.gov (United States)

    Social Security Administration — The Affordable Care Act (ACA) is a federal statute enacted with a goal of increasing the quality and affordability of health insurance. Through a web service, CMS...

  17. Endangered Species Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The purpose of the Endangered Species Act (ESA) is to protect and recover imperiled species and the ecosystems upon which they depend. The U.S. Fish and Wildlife...

  18. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CYSTIC FIBROSIS Learn about cystic fibrosis, a genetic lung disorder that affects the pancreas and other organs, ... Clearance Techniques (ACTs) Autogenic Drainage (AD) Basics of Lung Care Chest Physical Therapy Coughing and Huffing High- ...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... resources you need to continuously build upon this work. Awards and Grants Career Development Awards Research Awards ... The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory ...

  20. Abandoned Shipwreck Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Abandoned Shipwreck Act of 1987 (ASA) affirms the authority of state governments to claim ownership to, protect, and manage abandoned shipwrecks on state...

  1. Act250 Permits

    Data.gov (United States)

    Vermont Center for Geographic Information — The dataset includes the geographic location for Act 250 permits issued since the inception of the law in 1970. Base permit numbers only are included; permit...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ...

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  4. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

  5. DREAM Act, Part II

    National Research Council Canada - National Science Library

    Miranda, María Eugenia

    2011-01-01

    .... For nearly a decade Congress has failed to pass a bill - the Development Relief and Education for Alien Minors Act - that would grant AJulema legal residence and free her from a life in the shadows...

  6. Clean Water Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data represent geographic terms used within the Clean Water Act (CWA). The CWA establishes the basic structure for regulating the addition of pollutants...

  7. ACT250 Districts

    Data.gov (United States)

    Vermont Center for Geographic Information — The ACT 250 Districts layer is part of a larger dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes...

  8. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... What to Consider Regarding a Lung Transplant Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular ... that help thin and move the mucus, and antibiotics. Bronchodilators should be inhaled before you start ACTs. ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... an eCard Submit Your Artwork Honor a Loved One Create a Tribute Page Find a Tribute Page ... to try. However, the best ACT is the one that you are most likely to perform as ...

  10. Acts of Research

    DEFF Research Database (Denmark)

    Nelund, Sidsel

    described as knowledge producers and exhibitions and art works as instances of knowledge production. Acts of Research: Knowledge Production in Contemporary Arts between Knowledge Economy and Critical Practices analyses this development. The academic discussion of knowledge production in the arts has taken...... place mostly in seminars and articles, in which knowledge is often discussed as an intrinsic quality of the artwork. Acts of Research, however, is devoted to studying the rise of knowledge production in contemporary art from the perspective of artistic, curatorial and educational research...... with an awareness of larger political, economic, geographical and art-related aspects. The concept of ‘acts of research’ is suggested as a way to understand knowledge production as a creative act in which research carried out in relation to a specific material challenges and resists the protocols of conventional...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... NACFC Carolyn and C. Richard Mattingly Leadership in Mental Health Care Award Mary M. Kontos Award NACFC ... you clear the thick, sticky mucus from your lungs. ACTs are often used with other treatments, including ...

  12. Marine Pollution Prevention Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Marine Pollution Prevention Act of 2008 implements the International Convention for the Prevention of Pollution from Ships, including related Protocols (MARPOL)...

  13. National Environmental Policy Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The National Environmental Policy Act (NEPA) was the first major environmental law in the United States and established national environmental policies for the...

  14. Eand P opportunities in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Castilho, Marcelo [National Petroleum Agency of Brasil (Brazil)

    2011-07-01

    Brazil is one of the world's largest economies and the country also has significant heavy oil reserves. This report from the National Petroleum Agency of Brazil aims at presenting the situation of the oil and gas sector in Brazil in terms of resources, production, regulatory framework and opportunities for the future. Brazil has numerous sedimentary basins at its disposal, most of them being prospected by both national and foreign companies from all over the world. Brazil has over 14 billion barrels of proven reserves, its production is 2,1 MMBbl/d and heavy oil represents almost 40% of that production. The National Petroleum Agency of Brazil is responsible for the implementation of oil sector policy with the aims of maintaining self-sufficiency, implementing good practices in terms of health and safety, and increasing local content. This paper pointed out that Brazil has an important opportunity to enhance its energy sector through the development of heavy oil.

  15. Opportunity's Surroundings on Sol 1798

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top. The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock. This view is presented as a cylindrical projection with geometric seam correction.

  16. Opportunity structures for selective exposure

    DEFF Research Database (Denmark)

    Skovsgaard, Morten; Shehata, Adam; Strömbäck, Jesper

    2016-01-01

    is to investigate the two types of selective exposure in a country—Sweden—where the opportunity structures for selective exposure differ from the American context. This study investigates both types of selective exposure in relation to televised party-leader interviews. Based on panel survey data, the findings show...... interest. Evidence for both has been found primarily in an American context, while there is less research on European countries. This is problematic, as the opportunity structures for different forms of selectivity vary across media environments. Against this background, the purpose of this study...... that selective exposure based on political interest is substantially more important than selective exposure based on ideological preferences in explaining exposure to party-leader interviews. To substantiate this finding, the results are replicated with partisan learning as the dependent variable....

  17. Investment opportunities as real options

    Directory of Open Access Journals (Sweden)

    Adnan Rovčanin

    2005-06-01

    Full Text Available Opportunity (optional approach to capital investment appraisal represents, completely new theoretical and methodological framework for investment analysis. Compared to traditional, discount cash flow (DCF model of analysis, the optional approach provides opportunity for valuation and managing flexibility, i.e. possibility of approaching (amending the previous decisions in compliance with market changes. Risk and uncertainty are inevitably following the capital investment. Therefore, the importance of optional approach to investments is also that it provides possible better “treatment” of risks in the investment analysis, and also more rational allocation of resources, accordingly. This approach should be of more interest to the Countries in transition, considering the limited financial sources as well as risk and uncertainty are emphasized.

  18. UTBB FDSOI: Evolution and opportunities

    Science.gov (United States)

    Monfray, Stephane; Skotnicki, Thomas

    2016-11-01

    As today's 28 nm FDSOI (Fully Depleted Silicon On Insulator) technology is at the industrialization level, this paper aims to summarize the key advantages allowed by the thin BOX (Buried Oxide) of the FDSOI, through the technology evolution but also new opportunities, among logic applications and extending the possibilities offered by the platform. We will summarize how the advantages provided by the thin BOX have been first explored and developed, and how the back biasing techniques are the key to the outstanding performances provided by the FDSOI at low voltage. Then, as the FDSOI technology is also a solution to develop innovative platforms and applications, we will detail some opportunities. In particular, we will present monolithic 3D integration, ultra-low power devices for IoT (Internet of Things) and ultra-sensitive sensors.

  19. Acting Antarctica: science on stage

    Science.gov (United States)

    Ciceri, Piera; Tizzoni, Paola; Pierro, Luigia

    2016-04-01

    Key-words: Polar science, Earth science, Theatre, Hands on activities The legendary Antarctic Expedition of sir E. Shackleton and his crew of 27 aboard the Endurance (1914/16) trapped in the Antarctic ice has become the starting point to learn about Polar Science and Climate Change. While the students were involved into this incredible adventure by the astonishing images of the Australian photographer Frank Hurley (who joined the crew), they discovered the world in which this story happened. Students were then involved in hands-on activities and role plays and have become the writers of the play "Uomini a scienza ai confini del mondo". They act the story of Shackelton's expedition and they tell at the same time to the audience about ice pack, ice cores and their role in understanding the past of the climate, physical and geographical characteristic of polar regions, thermal phenomena related to adaptations of polar animals, solar radiation at different latitude, day/night duration. The theater was the place to "stage" some scientific experiments and to explain the current research carried out in polar regions and their importance in climate change studies and to stress some similarities between Antarctica and space. The project was carried out from teachers of science, letters and geography and was born in collaboration with the "Piccolo Teatro di Milano" and the association "Science Under 18" with the support of a professional actor and director and was played for other schools at "EXPO 2015" in Milano (Italy). In our opinion drama activities improve reading comprehension, and both verbal and non-verbal communication skills. To be able to write and to act, students need a deep understanding of contents. Arts, including theatre, are a good key to involve emotionally students. To have an audience different from their own teachers and classmates offers a real task and the opportunity to play and let grow real skills.

  20. A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Shuqiu

    2012-08-01

    Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

  1. Immigrant Capital and Entrepreneurial Opportunities

    Directory of Open Access Journals (Sweden)

    Malavika Sundararajan

    2016-01-01

    Full Text Available Objective: The main objective of this study is to define and operationalize the concept of immigrant capital, a key factor that differentiates immigrant from host country entrepreneurs in how they recognize and start new ventures. Research Design & Methods: A detailed analysis of contemporary immigrant entrepreneurship and opportunity recognition literature was carried out. Using grounded theory, we synthesized the outcomes from the analysis of eight Canadian and U.S. case studies of successful immigrant entrepreneurs with the key findings from the literature to define and develop a model of immigrant capital. Findings: Based on our grounded theory development process we show that the concept of immigrant capital as a distillate of human, cultural, economic and social capital that goes beyond expected opportunity recognition (OR drivers like prior knowledge and prior experience to differentiate and enhance the immigrant entrepreneur’s ability to recognize business opportunities compared to host country entrepreneurs. We found immigrant capital to be a consequence of being boundary spanners in host and home country networks. Implications & Recommendations: Understanding a unique resource like immigrant capital, will help immigrant as well as host country entrepreneurs further develop their opportunity recognition ability by bridging gaps and fulfilling the needs for both, immigrant and host country consumers. Contribution & Value Added: The main contribution is the theoretical development, identification and definition of the immigrant capital model and propositions that will articulate the factors that lead to the conceptualization and operationalization of immigrant capital. Furthermore, the immigrant capital model can serve host country entrepreneurs to develop cross-cultural networks and jump-start entrepreneurial activities in their home countries as well as learn how to expand their operations into global markets.

  2. IICT Skills and Employment Opportunities

    OpenAIRE

    Hilal Atasoy

    2011-01-01

    This study analyzes information communication technology (ICT) use and skills of workers, and their effects on employment opportunities. I employ a confidential data set provided by Statistical Institute of Turkey that includes detailed surveys on ICT use by households and individuals. The data contains information on ICT skills: starting from the most basic ones such as using an excel spreadsheet and uploading or transferring files, to more advanced skills such as knowing a programming langu...

  3. Brexit: potential opportunities, potential risks.

    Science.gov (United States)

    2017-01-21

    ▪ Identifying opportunities and risks that might arise from the UK's exit from the European Union▪ Managing mental health issues and building resilient teams▪ Supporting efforts to eliminate rabiesThese were among matters discussed by the BVA Council at its meeting on December 7, 2016. The BVA President, Gudrun Ravetz, chaired the meeting, which was held at the BVA's headquarters in Mansfield Street, London. British Veterinary Association.

  4. A ‘Smart’ Opportunity

    DEFF Research Database (Denmark)

    Breitenbauch, Henrik Ø.; Giegerich, Bastian

    2012-01-01

    cooperation, however, leads industry to think about cooperation mostly in terms of delays and market-distorting principles. With this backward-looking mindset, industry risks missing a crucial growth potential, a market that will only exist because of Smart Defense. Across the Atlantic, industry should seize...... this opportunity as eagerly as it would any good business development prospect. Simply put, the Smart Defense framework will offer a way to sell products that would not otherwise be sold....

  5. Opportunity at 'Cook Islands' (Stereo)

    Science.gov (United States)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11854 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11854 NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,825th Martian day, or sol, of Opportunity's surface mission (March 12, 2009). North is at the top. This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left. The rover had driven half a meter (1.5 feet) earlier on Sol 1825 to fine-tune its location for placing its robotic arm onto an exposed patch of outcrop including a target area informally called 'Cook Islands.' On the preceding sol, Opportunity turned around to drive frontwards and then drove 4.5 meters (15 feet) toward this outcrop. The tracks from the SOl 1824 drive are visible near the center of this view at about the 11 o'clock position. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Opportunity had previously been driving backward as a strategy to redistribute lubrication in a wheel drawing more electrical current than usual. The outcrop exposure that includes 'Cook Islands' is visible just below the center of the image. The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock. This view is presented as a cylindrical-perspective projection with geometric seam correction.

  6. Rural Entrepreneurship: Challenges and Opportunities

    OpenAIRE

    Imedashvili, Sopiko; Kekua, Ani; Ivchenko, Polina

    2013-01-01

    According to World Bank Report published in 2012, the rural population in Sweden is 15.3 %. Rural population is calculated as difference between total populations minus urban population. 15.3 % clearly shows how important rural areas are for Sweden’s future development. Entrepreneurship plays the integral role in rural area development. However, earlier research has shown only economic perspective of rural development. On the other hand, the new ways to discover the challenges and opportuniti...

  7. Office of Equal Opportunity Programs

    Science.gov (United States)

    Chin, Jennifer L.

    2004-01-01

    The NASA Glenn Office of Equal Opportunity Programs works to provide quality service for all programs and/or to assist the Center in becoming a model workplace. During the summer of 2004, I worked with Deborah Cotleur along with other staff members to create and modify customer satisfaction surveys. This office aims to assist in developing a model workplace by providing functions as a change agent to the center by serving as an advisor to management to ensure equity throughout the Center. In addition, the office serves as a mediator for the Center in addressing issues and concerns. Lastly, the office provides assistance to employees to enable attainment of personal and organizational goals. The Office of Equal Opportunities is a staff office which reports and provides advice to the Center Director and Executive Leadership, implements laws, regulations, and presidential executive orders, and provides center wide leadership and assistance to NASA GRC employees. Some of the major responsibilities of the office include working with the discrimination complaints program, special emphasis programs (advisory groups), management support, monitoring and evaluation, contract compliance, and community outreach. During my internship in this office, my main objective was to create four customer satisfaction surveys based on EO retreats, EO observances, EO advisory boards, and EO mediation/counseling. I created these surveys after conducting research on past events and surveys as well as similar survey research created and conducted by other NASA centers, program for EO Advisory group members, leadership training sessions for supervisors, preventing sexual harassment training sessions, and observance events. I also conducted research on the style and format from feedback surveys from the Marshall Equal Opportunity website, the Goddard website, and the main NASA website. Using the material from the Office of Equal Opportunity Programs at Glenn Research Center along with my

  8. Engineering ethics challenges and opportunities

    CERN Document Server

    Bowen, W Richard

    2014-01-01

    Engineering Ethics: Challenges and Opportunities aims to set a new agenda for the engineering profession by developing a key challenge: can the great technical innovation of engineering be matched by a corresponding innovation in the acceptance and expression of ethical responsibility?  Central features of this stimulating text include:   ·         An analysis of engineering as a technical and ethical practice providing great opportunities for promoting the wellbeing and agency of individuals and communities. ·         Elucidation of the ethical opportunities of engineering in three key areas:             - Engineering for Peace, emphasising practical amelioration of the root causes of    conflict rather than military solutions.             - Engineering for Health, focusing on close collaboration with healthcare professionals      for both the promotion and restoration of health.             - Engineering for Development, providing effective solution...

  9. 29 CFR 1626.2 - Terms defined in the Age Discrimination in Employment Act of 1967, as amended.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Terms defined in the Age Discrimination in Employment Act... EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.2 Terms defined in the Age Discrimination in Employment Act of 1967, as amended. The terms person, employer, employment...

  10. THE PRESENCE OF EQUAL OPPORTUNITIES IN HR MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Eva Farkas

    2014-07-01

    Full Text Available Ensuring equal opportunities is a priority for CEO-s and decision makers, however, it is often not put into practice. Changes in recent years along with the priorities of the EU and the efforts made to banish discrimination becoming more prominent brought with themselves a pressure on firms to provide equal opportunities for the different under-privileged social groups. In Hungary the Act CXXV of 2003 on discrimination and equal opportunities lists the groups in need of protection. The law requires employers with more than fifty employees to have an equal opportunities program. In spite of this, these programs are often general and do not implement the changes and goals identified after the assessment. Still, strategies and plans are only worth how much of them are realized. Our article is about the conscious principles of the Hungarian business sector about equality and whether there are regional differences. We compare answers given by both employers and employees on the subject of the extent to which the above mentioned principles are realized by the management and whether the employees experience these changes. Our theory is that the prioritisation of equal opportunities in firms is more the result of access to project funds than that of inner initiative from the firm's management. We analyse our research questions using a quantitative method on a regionally representative national sample. We examined 992 firms with special attention on those and their employees who had some sort of written guidelines on equal opportunities and plans on implementing these. In our paper we give a short review on the importance of equal opportunities, it's manifestation in HR management and it's written declaration, the so called Equal Opportunities Plan (EOP. The efforts of the EU and access to financial resources for the EU projects as a condition our hypotheses are that (1 at least 30% of the firms studied have written guidelines or declaration on equal

  11. Compelling Research Opportunities using Isotopes

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-04-23

    Isotopes are vital to the science and technology base of the US economy. Isotopes, both stable and radioactive, are essential tools in the growing science, technology, engineering, and health enterprises of the 21st century. The scientific discoveries and associated advances made as a result of the availability of isotopes today span widely from medicine to biology, physics, chemistry, and a broad range of applications in environmental and material sciences. Isotope issues have become crucial aspects of homeland security. Isotopes are utilized in new resource development, in energy from bio-fuels, petrochemical and nuclear fuels, in drug discovery, health care therapies and diagnostics, in nutrition, in agriculture, and in many other areas. The development and production of isotope products unavailable or difficult to get commercially have been most recently the responsibility of the Department of Energy's Nuclear Energy program. The President's FY09 Budget request proposed the transfer of the Isotope Production program to the Department of Energy's Office of Science in Nuclear Physics and to rename it the National Isotope Production and Application program (NIPA). The transfer has now taken place with the signing of the 2009 appropriations bill. In preparation for this, the Nuclear Science Advisory Committee (NSAC) was requested to establish a standing subcommittee, the NSAC Isotope Subcommittee (NSACI), to advise the DOE Office of Nuclear Physics. The request came in the form of two charges: one, on setting research priorities in the short term for the most compelling opportunities from the vast array of disciplines that develop and use isotopes and two, on making a long term strategic plan for the NIPA program. This is the final report to address charge 1. NSACI membership is comprised of experts from the diverse research communities, industry, production, and homeland security. NSACI discussed research opportunities divided into three areas: (1

  12. The theory act

    DEFF Research Database (Denmark)

    Wæver, Ole

    2015-01-01

    such as social equality or solidarity and equal opportunities for genders, all of which would not be conceivable in a ‘state of nature’ ethology. To acknowledge in theory and investigate such power is at the same time to foster it and defend it against the risk of regression into forms of social life based...

  13. Acting Like Rain

    Science.gov (United States)

    Baldwin, Kathryn; Wilson, Allison

    2017-01-01

    Having high-quality early childhood education programs that prepare children for success in school and later years continues to be an ever increasing national priority. While the "Next Generation Science Standards" ("NGSS") do not provide standards for preschool, there are ample opportunities to use the Standards as a guide to…

  14. Overcoming Obstacles: Opportunities of academically talented women in Iran

    Directory of Open Access Journals (Sweden)

    Shahla Alborzi, Ph.D

    2008-03-01

    Full Text Available The aim of the present research was to study the lifetime obstacles and opportunities of academically successful women working at Iran universities. Successful female academics in Iran are concerned about the social and personal barriers to pursuing successful careers in academia. These women continually work to overcome these barriers in an ongoing process called overcoming obstacles. This basic social process has five stages: perceiving inequality, conflicting, dissolving, empowering and acting purposefully. Throughout the process, these women have first become aware of gender inequities and then worked towards overcoming them using self-motivation properties and support from external sources such as family, mentors and colleagues. This substantive theory, though rooted in a specific country with a strong male dominated social structure, is applicable to all societies as they continue to work towards equitable access to high-level career opportunities.

  15. A unique funding opportunity for public health in Texas.

    Science.gov (United States)

    Schlenker, Thomas; Huber, Carol A

    2015-01-01

    In addition to the Affordable Care Act, states are more frequently turning to Medicaid waivers to achieve the "Triple Aim" goals of improving the experience of care, improving population health, and reducing per capita costs. These demonstration waivers provide opportunities to test innovative ways to finance and deliver care. Texas is currently implementing a waiver known as the Transformation and Quality Improvement Program. Its inclusion of public health agencies is a unique approach to a system typically limited to traditional providers. San Antonio Metropolitan Health District is one public health agency taking advantage of this new funding opportunity to implement 6 new or expanded programs targeting health issues of highest priority in this south Texas region. This article discusses the use of Medicaid waivers and the advantages and challenges of public health agency participation.

  16. Clinical leadership development and education for nurses: prospects and opportunities

    Directory of Open Access Journals (Sweden)

    Joseph ML

    2015-07-01

    Full Text Available M Lindell Joseph, Diane L Huber College of Nursing, The University of Iowa, Iowa City, IA, USA Abstract: With the implementation of the Affordable Care Act, elevated roles for nurses of care coordinator, clinical nurse leader, and advanced practice registered nurse have come to the forefront. Because change occurs so fast, matching development and education to job requirements is a challenging forecasting endeavor. The purpose of this article is to envision clinical leadership development and education opportunities for three emerging roles. The adoption of a common framework for intentional leadership development is proposed for clinical leadership development across the continuum of care. Solutions of innovation and interdependency are framed as core concepts that serve as an opportunity to better inform clinical leadership development and education. Additionally, strategies are proposed to advance knowledge, skills, and abilities for crucial implementation of improvements and new solutions at the point of care. Keywords: clinical leadership, nursing leadership, CNL, care coordination, innovation, interdependency

  17. Infants' unprovoked acts of force toward others.

    Science.gov (United States)

    Dahl, Audun

    2016-11-01

    Infants harm others at higher rates than older children and adults. A common explanation is that infants fail to regulate their frustration, becoming aggressive when they do not get what they want. The present research investigated whether infants also use force against others without provocation, for instance because they seek to explore the consequences of hitting or try to pet someone using too much force. Two studies with infants aged 11 to 24 months investigated infants' use of force against others in everyday life using maternal report (Study 1) and direct observation (Study 2). In both studies, a large proportion of infants' acts of force were unprovoked and occurred without signs of infant distress. Unlike provoked acts, unprovoked acts showed a decrease late in the second year and were positively associated with reports of infant pleasure-proneness. The presence of unprovoked acts of harm may reflect that infants' actions are not reliably guided by an aversion for harming others and may provide unique opportunities for early moral development. © 2015 John Wiley & Sons Ltd.

  18. Ubiquitin ligase RNF123 mediates degradation of heterochromatin protein 1α and β in lamin A/C knock-down cells.

    Directory of Open Access Journals (Sweden)

    Pankaj Chaturvedi

    Full Text Available The nuclear lamina is a key determinant of nuclear architecture, integrity and functionality in metazoan nuclei. Mutations in the human lamin A gene lead to highly debilitating genetic diseases termed as laminopathies. Expression of lamin A mutations or reduction in levels of endogenous A-type lamins leads to nuclear defects such as abnormal nuclear morphology and disorganization of heterochromatin. This is accompanied by increased proteasomal degradation of certain nuclear proteins such as emerin, nesprin-1α, retinoblastoma protein and heterochromatin protein 1 (HP1. However, the pathways of proteasomal degradation have not been well characterized.To investigate the mechanisms underlying the degradation of HP1 proteins upon lamin misexpression, we analyzed the effects of shRNA-mediated knock-down of lamins A and C in HeLa cells. Cells with reduced levels of expression of lamins A and C exhibited proteasomal degradation of HP1α and HP1β but not HP1γ. Since specific ubiquitin ligases are upregulated in lamin A/C knock-down cells, further studies were carried out with one of these ligases, RNF123, which has a putative HP1-binding motif. Ectopic expression of GFP-tagged RNF123 directly resulted in degradation of HP1α and HP1β. Mutational analysis showed that the canonical HP1-binding pentapeptide motif PXVXL in the N-terminus of RNF123 was required for binding to HP1 proteins and targeting them for degradation. The role of endogenous RNF123 in the degradation of HP1 isoforms was confirmed by RNF123 RNAi experiments. Furthermore, FRAP analysis suggested that HP1β was displaced from chromatin in laminopathic cells.Our data support a role for RNF123 ubiquitin ligase in the degradation of HP1α and HP1β upon lamin A/C knock-down. Hence lamin misexpression can cause degradation of mislocalized proteins involved in key nuclear processes by induction of specific components of the ubiquitin-proteasome system.

  19. Ethical Perspectives of Equal Opportunities

    Directory of Open Access Journals (Sweden)

    Traian PALADE

    2016-07-01

    Full Text Available This paper focuses on the analysis of the fair equality of the concept of opportunity from the perspective of the moral and reasonable justifications brought to support positive discrimination. Although contemporary democratic societies guarantee the absence of discrimination by securing the formal equality of opportunity, this seems to be insufficient to balance opportunities. The Rawlsian model has gained ground, by advancing a redistribution of the resources to support the disadvantaged ones, which is implemented through special measures. The compulsory quotas for admission to higher education or public institutions, addressed to some disadvantaged groups, are one of the effective means of implementing fairness. As this system has shattered the principle of reward judging by one‟s merits, and ending up as a form of inverse discrimination of the majority groups, it is necessary that we analyse the arguments and the boomerang effects of the special measures. The undertaking proposed by the present paper is structured around highlighting the ethical aspects, as well as the consequences resulting from the arguments in favour of positive discrimination. Do we have the moral obligation to make up for the past inequalities suffered by some groups? Does preferential treatment really ensure the genuine integration of such groups? Do special measures contribute in creating social justice? Without the claim of having responded definitively and exhaustively to these questions, this paper attempts to emphasise the ethical dilemma that raises when special measures favour one group or another, when a group is protected judging by only one criterion, or when only an implementation area is selected.

  20. Energy Development Opportunities for Wyoming

    Energy Technology Data Exchange (ETDEWEB)

    Larry Demick

    2012-11-01

    The Wyoming Business Council, representing the state’s interests, is participating in a collaborative evaluation of energy development opportunities with the NGNP Industry Alliance (an industry consortium), the University of Wyoming, and the US Department of Energy’s Idaho National Laboratory. Three important energy-related goals are being pursued by the State of Wyoming: Ensuring continued reliable and affordable sources of energy for Wyoming’s industries and people Restructuring the coal economy in Wyoming Restructuring the natural gas economy in Wyoming

  1. Educational Homogamy: Preferences or Opportunities?

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Svarer, Michael

    of the systematic sortingon education is due to low search frictions in marriage markets of the educationalinstitutions. The other half is attributed to complementarities in household pro-duction, since income properties of the joint income process show no influence on partner selection.......Individuals match on length and type of education. We investigate whether thesystematic relationship between educations of partners is explained by opportuni-ties (e.g. low search frictions) or preferences (e.g. complementarities in householdproduction or portfolio optimization). We find that half...

  2. Neuroepigenomics: resources, obstacles, and opportunities

    Directory of Open Access Journals (Sweden)

    John S. Satterlee

    2015-01-01

    Full Text Available Long-lived postmitotic cells, such as most human neurons, must respond effectively to ongoing changes in neuronal stimulation or microenvironmental cues through transcriptional and epigenomic regulation of gene expression. The role of epigenomic regulation in neuronal function is of fundamental interest to the neuroscience community, as these types of studies have transformed our understanding of gene regulation in postmitotic cells. This perspective article highlights many of the resources available to researchers interested in neuroepigenomic investigations and discusses some of the current obstacles and opportunities in neuroepigenomics.

  3. Challenges and opportunities for REDD+

    DEFF Research Database (Denmark)

    Pasgaard, Maya; Sun, Zhanli; Müller, Daniel

    2016-01-01

    Reducing Emissions from Deforestation and forest Degradation (REDD+) is a promising mechanism of payments for ecosystem services with the aim to effectively reduce emissions in an efficient and equitable manner. REDD+ is part of the Paris-agreement reached at the UNFCCC COP21 in December 2015...... the opportunities and challenges of REDD+ for achieving effective, efficient and equitable outcomes and co-benefits (3E+). We substantiate our survey results with a literature review. Results suggest that the challenges in achieving the 3E+ relate to the disproportionality between deforestation drivers...

  4. Salutogenic Window of Opportunity in Nutrition Promotion

    NARCIS (Netherlands)

    Bouwman, L.I.; Swan, E.C.

    2013-01-01

    Their workshop will discuss Antonovsky’s Salutogenic Framework and how it offers a window of opportunity for enabling healthy lifestyle practices and nutrition promotion. During the interactive workshop, participants will have the opportunity to practice Salutogenic thinking through discussion,

  5. Modular manufacturing processes : Status, challenges, and opportunities

    NARCIS (Netherlands)

    Baldea, Michael; Edgar, Thomas F.; Stanley, Bill L.; Kiss, Anton A.

    2017-01-01

    Chemical companies are constantly seeking new, high-margin growth opportunities, the majority of which lie in high-grade, specialty chemicals, rather than in the bulk sector. To realize these opportunities, manufacturers are increasingly considering decentralized, flexible production facilities:

  6. Examining equity of opportunities for learning mathematics through positioning theory

    Science.gov (United States)

    Tait-McCutcheon, Sandi L.; Loveridge, Judith

    2016-06-01

    This exploratory study examined how two teachers from two New Zealand primary schools introduced and taught the same mathematics lesson to their lowest ability group of year 2 and 3 students. Emphasis was given to analysing the positioning of the teacher and students and the developing storylines and social acts from that positioning. Different positionings by teachers of themselves and their students led to inequitable opportunities for active and collaborative participation in the mathematics. The differences in pedagogy revealed through the use of positioning theory suggest that the way teachers positioned themselves and their students was more influential than the resources they were teaching with.

  7. Equalization of opportunity: Definitions and implementable conditions

    OpenAIRE

    Francesco Andreoli; Arnaud Lefranc

    2013-01-01

    This paper develops a criterion of opportunity equalization, that is consistent with theoretical views of equality of opportunity. Our analysis rests on the characterization of inequality of opportunity as a situation where some groups in society enjoy an illegitimate advantage. In this context, equalization of opportunity requires that the extent of the illegitimate advantage enjoyed by the privileged groups falls. Robustness requires that this judgement be supported by the broadest class of...

  8. Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice

    DEFF Research Database (Denmark)

    Nansen, A; Christensen, Jan Pravsgaard; Röpke, C

    1998-01-01

    Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN-gamma is r......Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN......, a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may...

  9. Multiphysics simulations: challenges and opportunities.

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, D.; McInnes, L. C.; Woodward, C.; Gropp, W.; Myra, E.; Pernice, M. (Mathematics and Computer Science); (KAUST and Columbia Univ.); (Lawrence Livermore National Laboratory); (Univ. of Illinois at Urbana-Champaign); (Univ. of Mich.); (Idaho National Lab.)

    2012-11-29

    This report is an outcome of the workshop Multiphysics Simulations: Challenges and Opportunities, sponsored by the Institute of Computing in Science (ICiS). Additional information about the workshop, including relevant reading and presentations on multiphysics issues in applications, algorithms, and software, is available via https://sites.google.com/site/icismultiphysics2011/. We consider multiphysics applications from algorithmic and architectural perspectives, where 'algorithmic' includes both mathematical analysis and computational complexity and 'architectural' includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. We also initiate a modest suite of test problems encompassing features present in many applications.

  10. The Growth Opportunity Channel of Debt Structure

    NARCIS (Netherlands)

    Giambona, E.; Golec, J.

    2012-01-01

    This paper studies the importance of growth opportunities for debt structure decisions. High growth firms use more unsecured debt to preserve financial flexibility (in the form of untapped secured debt capacity) in connection with future growth opportunities: the growth opportunity channel of debt

  11. The Growth Opportunity Channel of Debt Structure

    NARCIS (Netherlands)

    Giambona, E.; Golec, J.

    2013-01-01

    This paper studies the importance of growth opportunities for debt structure decisions. High growth firms use more unsecured debt to preserve financial flexibility (in the form of untapped secured debt capacity) in connection with future growth opportunities: the growth opportunity channel of debt

  12. Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Lara Moumné

    Full Text Available Huntington's disease (HD is an autosomal dominant progressive neurodegenerative disorder caused by an expansion of a CAG/polyglutamine repeat for which there are no disease modifying treatments. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression and has been recapitulated across multiple HD models. Altered histone acetylation has been proposed to underlie this transcriptional dysregulation and histone deacetylase (HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA, have been shown to improve polyglutamine-dependent phenotypes in numerous HD models. However potent pan-HDAC inhibitors such as SAHA display toxic side-effects. To better understand the mechanism underlying this potential therapeutic benefit and to dissociate the beneficial and toxic effects of SAHA, we set out to identify the specific HDAC(s involved in this process. For this purpose, we are exploring the effect of the genetic reduction of specific HDACs on HD-related phenotypes in the R6/2 mouse model of HD. The study presented here focuses on HDAC3, which, as a class I HDAC, is one of the preferred targets of SAHA and is directly involved in histone deacetylation. To evaluate a potential benefit of Hdac3 genetic reduction in R6/2, we generated a mouse carrying a critical deletion in the Hdac3 gene. We confirmed that the complete knock-out of Hdac3 is embryonic lethal. To test the effects of HDAC3 inhibition, we used Hdac3(+/- heterozygotes to reduce nuclear HDAC3 levels in R6/2 mice. We found that Hdac3 knock-down does not ameliorate physiological or behavioural phenotypes and has no effect on molecular changes including dysregulated transcripts. We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD.

  13. Impaired Cytogenetic Damage Repair and Cell Cycle Regulation in Response to Ionizing Radiation in Human Fibroblast Cells with Individual Knock-down of 25 Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish; Jeevarajan, Antony; Pierson, Duane; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  14. Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology.

    Directory of Open Access Journals (Sweden)

    Ying-Chang Lu

    Full Text Available Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4(tm1Dontuh/tm1Dontuh mice homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4(tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4(tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4(tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4(tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4(-/- mice and Slc26a4(loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains.

  15. Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology.

    Science.gov (United States)

    Lu, Ying-Chang; Wu, Chen-Chi; Shen, Wen-Sheng; Yang, Ting-Hua; Yeh, Te-Huei; Chen, Pei-Jer; Yu, I-Shing; Lin, Shu-Wha; Wong, Jau-Min; Chang, Qing; Lin, Xi; Hsu, Chuan-Jen

    2011-01-01

    Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4(tm1Dontuh/tm1Dontuh) mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4(tm1Dontuh/tm1Dontuh) mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4(tm1Dontuh/tm1Dontuh) mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4(-/-) mice and Slc26a4(loop/loop) mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains.

  16. RNAi knock-down of LHCBM1, 2 and 3 increases photosynthetic H2 production efficiency of the green alga Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Melanie Oey

    Full Text Available Single cell green algae (microalgae are rapidly emerging as a platform for the production of sustainable fuels. Solar-driven H2 production from H2O theoretically provides the highest-efficiency route to fuel production in microalgae. This is because the H2-producing hydrogenase (HYDA is directly coupled to the photosynthetic electron transport chain, thereby eliminating downstream energetic losses associated with the synthesis of carbohydrate and oils (feedstocks for methane, ethanol and oil-based fuels. Here we report the simultaneous knock-down of three light-harvesting complex proteins (LHCMB1, 2 and 3 in the high H2-producing Chlamydomonas reinhardtii mutant Stm6Glc4 using an RNAi triple knock-down strategy. The resultant Stm6Glc4L01 mutant exhibited a light green phenotype, reduced expression of LHCBM1 (20.6% ±0.27%, LHCBM2 (81.2% ±0.037% and LHCBM3 (41.4% ±0.05% compared to 100% control levels, and improved light to H2 (180% and biomass (165% conversion efficiencies. The improved H2 production efficiency was achieved at increased solar flux densities (450 instead of ∼100 µE m(-2 s(-1 and high cell densities which are best suited for microalgae production as light is ideally the limiting factor. Our data suggests that the overall improved photon-to-H2 conversion efficiency is due to: 1 reduced loss of absorbed energy by non-photochemical quenching (fluorescence and heat losses near the photobioreactor surface; 2 improved light distribution in the reactor; 3 reduced photoinhibition; 4 early onset of HYDA expression and 5 reduction of O2-induced inhibition of HYDA. The Stm6Glc4L01 phenotype therefore provides important insights for the development of high-efficiency photobiological H2 production systems.

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... ACTIONS Health Care Reform Priorities for the CF Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy ... We recognize the value of tapping into the ...

  18. Special Appropriation Act Projects

    Science.gov (United States)

    EPA is sometimes directed to provide funding to a specific entity for study, purpose, or activity.This information will be of interest to a community or other entity that has been identified in one of EPA's appropriations acts to receive such funding.

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they can do on their ... (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  20. [Schema therapy - ACT - mindfulness].

    Science.gov (United States)

    Cousineau, Pierre; Ngô, Thanh-Lan

    2013-01-01

    For schema therapy, significant weight is given to early experiences of social life. They lead to the creation of memories, largely implicit. These memories are reactivated in specific contexts and are often managed through dysfunctional strategies. Schema therapy seeks to modify these memories categorized as patterns. Acceptance and Commitment Therapy (ACT), meanwhile, aims to transform our reactions linked to our learning history and to develop a greater flexibility taking into account what occurs in the present moment. Several techniques originate from the mindfulness tradition and seek to transform the individual into a witness of his own experience, rather than someone acting out patterns based on his learning history. Despite their different paradigms, it is possible to combine these approaches. As schemas manifest through somatic reactions, thoughts, affects, action tendencies, it becomes possible to try to change the relationship between the individual and these private experiences through the use of mindfulness, philosophical concepts and techniques derived from ACT. This is the aim of this article. Essay presenting the use of a schema mindfulness flash card to help patients tolerate intense affects generated by the activation of schemas and to attain greater adaptive flexibility (Healthy Adult mode). It is possible to integrate ACT techniques and concept to schema therapy in order to facilitate adaptive flexibility.

  1. Environmental Threats to Security, Stability, and U.S. Interests in Southern Africa: Opportunity Knocks - Time for a Comprehensive Region Defense Environmental International Cooperation and Environmental Security Assistance Strategy

    Science.gov (United States)

    2009-01-01

    environmental efforts. Such as strategy should be centered upon three pillars: 1. Geography (anchor state and ink spot approach) 2. Environmental...Furthermore, human induced soil erosion and degradation - driven by tree cutting for firewood and charcoal production, commercial afforestation and...of stream flow), and fishing.59 Much of this is due to illegal logging for charcoal production (for domestic and transborder markets) enabled by

  2. Exploration Science Opportunities for Students within Higher Education

    Science.gov (United States)

    Bailey, Brad; Minafra, Joseph; Schmidt, Gregory

    2016-10-01

    The NASA Solar System Exploration Research Virtual Institute (SSERVI) is a virtual institute focused on exploration science related to near-term human exploration targets, training the next generation of lunar scientists, and education and public outreach. As part of the SSERVI mission, we act as a hub for opportunities that engage the public through education and outreach efforts in addition to forming new interdisciplinary, scientific collaborations.SSERVI provides opportunities for students to bridge the scientific and generational gap currently existing in the planetary exploration field. This bridge is essential to the continued international success of scientific, as well as human and robotic, exploration.The decline in funding opportunities after the termination of the Apollo missions to the Moon in the early 1970's produced a large gap in both the scientific knowledge and experience of the original lunar Apollo researchers and the resurgent group of young lunar/NEA researchers that have emerged within the last 15 years. One of SSERVI's many goals is to bridge this gap through the many networking and scientific connections made between young researchers and established planetary principle investigators. To this end, SSERVI has supported the establishment of NextGen Lunar Scientists and Engineers group (NGLSE), a group of students and early-career professionals designed to build experience and provide networking opportunities to its members. SSERVI has also created the LunarGradCon, a scientific conference dedicated solely to graduate and undergraduate students working in the lunar field. Additionally, SSERVI produces monthly seminars and bi-yearly virtual workshops that introduce students to the wide variety of exploration science being performed in today's research labs. SSERVI also brokers opportunities for domestic and international student exchange between collaborating laboratories as well as internships at our member institutions. SSERVI provides a

  3. Ethanol production from woody biomass: Silvicultural opportunities for suppressed western conifers

    Science.gov (United States)

    Andrew Youngblood; Junyong Zhu; C. Tim. Scott

    2010-01-01

    The 2007 Energy Security and Independence Act (ESIA) requires 16 billion gallons of ethanol to be produced from lignocellulose biomass by 2022 in the United States. Forests can be a key source of renewable lignocellulose for ethanol production if cost and conversion efficiency barriers can be overcome. We explored opportunities for using woody biomass from thinning...

  4. ESSA: New Law, New Opportunity. A Brief Guide to Excellence for State Leaders

    Science.gov (United States)

    Dean, Stephanie; Hassel, Bryan C.; Hassel, Emily Ayscue; Steiner, Lucy

    2016-01-01

    State and district leaders have a chance under ESSA (the 2016 Every Student Succeeds Act) to use their new funding flexibility to take a new approach that focuses on excellence for teachers, and students. This brief explains four opportunities to go beyond the requirements of ESSA to achieve a culture of excellence, one that attracts even more…

  5. Introduction: Reauthorization: An Opportunity for Substantive Change in How Students Pay for College

    Science.gov (United States)

    Gross, Jacob P.

    2015-01-01

    Originally signed into law on November 8, 1965, by President Lyndon B. Johnson, the most current version of the law, the Higher Education Opportunity Act (HEOA; PL 110-315), contains eight titles: teacher quality enhancement, strengthening institutions, student assistance, developing institutions, international education programs, graduate and…

  6. Opportunities for visual resource management in the Southern Appalachian Coal Basin

    Science.gov (United States)

    John W. Simpson

    1979-01-01

    This paper outlines the opportunities for visual resource management (VRM) in the southern Appalachian coal basin resulting from the Surface Mining Control and Reclamation Act. It focuses upon VRM as a regulatory activity that works to insure the proper enforcement of the law and effective development of its implementation programs. VRM for Appalachian surface mining...

  7. Multiphysics simulations: Challenges and opportunities

    KAUST Repository

    Keyes, David E.

    2013-02-01

    We consider multiphysics applications from algorithmic and architectural perspectives, where "algorithmic" includes both mathematical analysis and computational complexity, and "architectural" includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities. © The Author(s) 2012.

  8. Angiogenesis and Its Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  9. CORIDORS: DEVELOPMENT OPPORTUNITY OF SERBIA

    Directory of Open Access Journals (Sweden)

    Laketa Marko

    2011-12-01

    Full Text Available Long-term vision of the Republic of Serbia is for it to be: territorially determined and regionally balanced, of sustainable economic growth and competitive, socially coherent and stable, infrastructurally equipped and accessible in terms of transportation, of preserved and protected natural and cultural heritage, high-quality living environment and functionally integrated into environment. High-quality transportation infrastructure is one of the main conditions of linking and integration into a broader environment. The aim of this paper is to show, based on the identification of the effects expected (internal and external, that Corridors 7 and 10, as logistics resources, are a development opportunity of Serbia and that its realization will multiply contribute to the achievement of long-term development goals of Serbia.

  10. Biomass Business Opportunities Viet Nam

    Energy Technology Data Exchange (ETDEWEB)

    Zwebe, D. [SNV Netherlands Development Organisation, Ha Noi (Viet Nam)

    2012-03-15

    The goal of this survey is to provide a more specific and integral perspective in which niches, relevant policy development by the Vietnamese government, legislation and sustainability criteria are clearly addressed to benefit both the Dutch Private sector as well as to stimulate Dutch-Vietnamese cooperation and support the Vietnamese government in its search for tangible options to develop the desired enabling environment for a sustainable biomass/biofuel market. The following activities are defined to be executed to reach the goal of the project: Biomass availability in Vietnam (Chapter 2); Government of Vietnam and Energy (Chapter 3); The opportunities and barriers to enter the market in Vietnam (Chapter 4 and 5); Stakeholder analysis of the bio-energy sector (Chapter 6); and Recommendations (Chapter 7)

  11. Multiphysics Simulations: Challenges and Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, David; McInnes, Lois C.; Woodward, Carol; Gropp, William; Myra, Eric; Pernice, Michael; Bell, John; Brown, Jed; Clo, Alain; Connors, Jeffrey; Constantinescu, Emil; Estep, Don; Evans, Kate; Farhat, Charbel; Hakim, Ammar; Hammond, Glenn E.; Hansen, Glen; Hill, Judith; Isaac, Tobin; Jiao, Xiangmin; Jordan, Kirk; Kaushik, Dinesh; Kaxiras, Efthimios; Koniges, Alice; Lee, Ki Hwan; Lott, Aaron; Lu, Qiming; Magerlein, John; Maxwell, Reed M.; McCourt, Michael; Mehl, Miriam; Pawlowski, Roger; Randles, Amanda; Reynolds, Daniel; Riviere, Beatrice; Rude, Ulrich; Scheibe, Timothy D.; Shadid, John; Sheehan, Brendan; Shephard, Mark; Siegel, Andrew; Smith, Barry; Tang, Xianzhu; Wilson, Cian; Wohlmuth, Barbara

    2013-02-12

    We consider multiphysics applications from algorithmic and architectural perspectives, where ‘‘algorithmic’’ includes both mathematical analysis and computational complexity, and ‘‘architectural’’ includes both software and hardware environments. Many diverse multiphysics applications can be reduced, en route to their computational simulation, to a common algebraic coupling paradigm. Mathematical analysis of multiphysics coupling in this form is not always practical for realistic applications, but model problems representative of applications discussed herein can provide insight. A variety of software frameworks for multiphysics applications have been constructed and refined within disciplinary communities and executed on leading-edge computer systems. We examine several of these, expose some commonalities among them, and attempt to extrapolate best practices to future systems. From our study, we summarize challenges and forecast opportunities.

  12. Polymer Informatics: Opportunities and Challenges.

    Science.gov (United States)

    Audus, Debra J; de Pablo, Juan J

    2017-10-01

    We are entering an era where large volumes of scientific data, coupled with algorithmic and computational advances, can reduce both the time and cost of developing new materials. This emerging field known as materials informatics has gained acceptance for a number of classes of materials, including metals and oxides. In the particular case of polymer science, however, there are important challenges that must be addressed before one can start to deploy advanced machine learning approaches for designing new materials. These challenges are primarily related to the manner in which polymeric systems and their properties are reported. In this viewpoint, we discuss the opportunities and challenges for making materials informatics as applied to polymers, or equivalently polymer informatics, a reality.

  13. Challenges and opportunities in presbycusis.

    Science.gov (United States)

    Parham, Kourosh; McKinnon, Brian J; Eibling, David; Gates, George A

    2011-04-01

    The population aged 65 years and older is increasing at a faster rate than the total population, with predictions that by 2030, 20% of the population will be 65 years or older. In 2006, between 35% and 50% of those aged 65 years or older reportedly had presbycusis, a sensory impairment that contributes to social isolation and loss of autonomy and is associated with anxiety, depression, and cognitive decline. To address these concerns, the Geriatric Committee of the American Academy of Otolaryngology, in conjunction with the Hearing Committee, focused on 3 challenges and opportunities in the management of presbycusis: (1) the financial burden of caring for patients with presbycusis in the face of increasing costs and declining reimbursements; (2) future treatment options arising from improved understanding of the molecular mechanisms underlying presbycusis, and (3) recognition of central presbycusis as a condition commonly superimposed on peripheral age-related hearing loss whose diagnosis and management can improve outcomes.

  14. Strengths, weaknesses, opportunities and threats

    DEFF Research Database (Denmark)

    Bull, Joseph William; Jobstvogt, N.; Böhnke-Henrichs, A.

    2016-01-01

    The ecosystem services concept (ES) is becoming a cornerstone of contemporary sustainability thought. Challenges with this concept and its applications are well documented, but have not yet been systematically assessed alongside strengths and external factors that influence uptake. Such an assess......The ecosystem services concept (ES) is becoming a cornerstone of contemporary sustainability thought. Challenges with this concept and its applications are well documented, but have not yet been systematically assessed alongside strengths and external factors that influence uptake....... Such an assessment could form the basis for improving ES thinking, further embedding it into environmental decisions and management.The Young Ecosystem Services Specialists (YESS) completed a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis of ES through YESS member surveys. Strengths include the approach...

  15. Opportunities From the Digital Revolution

    Directory of Open Access Journals (Sweden)

    Louise Corti

    2016-11-01

    Full Text Available In the 1990s, the term “online” research emerged as a new and vibrant suite of methods, focused on exploitation of sources not collected by traditional social science methods. Today, at least one part of the research life cycle is likely to be carried out “online,” from data collection through to publishing. In this article, we seek to understand emergent modes of doing and reporting qualitative research “online.” With a greater freedom now to term oneself a “researcher,” what opportunities and problems do working with online data sources bring? We explore implications of emerging requirements to submit supporting data for social science journal articles and question whether these demands might disrupt the very nature of and identity of qualitative research. Finally, we examine more recent forms of publishing and communicating research that support outputs where data play an integral role in elucidating context and enhancing the reading experience.

  16. Energy efficiency opportunities in Hotels

    Directory of Open Access Journals (Sweden)

    Dina Said

    2017-03-01

    Full Text Available According to the statistics in Egypt (2013, the number of hotels is 1193, about 407 of them have contracted power greater than 500 kW.Air conditioning, lighting, water heating and refrigeration represent the main activities demanding electrical energy in hotel business.The energy consumption per night spend changes a lot, depending on various factors; facilities provided, category of hotel, occupancy , geographical situation, weather conditions, nationality of clients, design and control of the installations.Energy benchmarking is an internal management tool designed to provide ongoing, reliable and verifiable tracking on the hotels performance. The most useful performance indicator (or Energy Efficiency Benchmarking of hotels are: Lighting Power Density (LPD in W (for lighting/m2, and energy intensity (kWh/m2/ y.There are multiple benefits for improving energy in hotel business; reduces the hotel's operating cost, reduces climate change risks and promotes green tourism.Energy efficiency opportunities are low-cost measures and cost- effective investments.   There are many energy saving opportunities for lighting in hotel's guest rooms as well as the more obvious savings in lobbies and exterior lighting areas. Behavior campaigns can yield substantial energy savings, both through the guests and housekeeper behavior. Encouraging housekeepers to use natural light during room cleaning is a simple first step to implement energy saving program.This paper presents the energy efficiency guidelines and energy benchmarking for hotels. Also a case study showing how the energy efficiency program implemented is presented. 

  17. Plastics recycling: challenges and opportunities.

    Science.gov (United States)

    Hopewell, Jefferson; Dvorak, Robert; Kosior, Edward

    2009-07-27

    Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3-4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it

  18. Plastics recycling: challenges and opportunities

    Science.gov (United States)

    Hopewell, Jefferson; Dvorak, Robert; Kosior, Edward

    2009-01-01

    Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3–4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it

  19. Application of systems thinking in health: opportunities for translating theory into practice

    Science.gov (United States)

    Malik, Asmat Ullah

    2015-01-01

    Systems thinking is not a new concept to health system strengthening; however, one question remains unanswered: How policy-makers, system designers and consultants with a system thinking philosophy should act (have acted) as potential change agents in actually gaining opportunities to introduce systems thinking? Development of Comprehensive Multi-Year Plans (cMYPs) for Immunization System is one such opportunity because almost all Low- and Middle-Income Countries (LMICs) develop and implement cMYPs every five years. Without building upon examples and showing practical application, the discussions and deliberations on systems thinking may fade away with passage of time. There are opportunities that exist around us in our existing health systems that we can benefit from starting with an incremental approach and generating evidence for longer lasting system-wide changes. PMID:26340394

  20. Dreams and acting out.

    Science.gov (United States)

    Grinberg, L

    1987-01-01

    Dreams can be used as containers that free patients from increased tension. This may be the principal function of certain types of dreams, called "evacuative dreams." They are dreams used for getting rid of unbearable affects and unconscious fantasies, or as a safety valve for partial discharge of instinctual drives. These dreams are observed primarily in borderline and psychotic patients, but can also be seen in the regressive states of neurotic patients during weekends and other periods of separation. Such dreams have to be differentiated from "elaborative dreams," which have a working-through function and stand in an inverse relationship to acting out: the greater the production of elaborative dreams, the less the tendency to act out, and vice versa.

  1. ST–ACTS

    DEFF Research Database (Denmark)

    Gidofalvi, Gyozo; Pedersen, Torben Bach

    2006-01-01

    hot issue in the area of spatio–temporal databases [7]. While existing Moving Object Simulators (MOSs) address different physical aspects of mobility, they neglect the important social and geo–demographical aspects of it. This paper presents ST–ACTS, a Spatio–Temporal ACTivity Simulator that, usi......–temporal distributions of activities, which make it essential for the development of adequate spatiotemporal data management and data mining techniques....... various geo–statistical data sources and intuitive principles, models the so far neglected aspects. ST–ACTS considers that (1) objects (representing mobile users) move from one spatio–temporal location to another with the objective of performing a certain activity at the latter location; (2) not all users...

  2. RECOGNISING SPEECH ACTS

    Directory of Open Access Journals (Sweden)

    Phyllis Kaburise

    2012-09-01

    Full Text Available Speech Act Theory (SAT, a theory in pragmatics, is an attempt to describe what happens during linguistic interactions. Inherent within SAT is the idea that language forms and intentions are relatively formulaic and that there is a direct correspondence between sentence forms (for example, in terms of structure and lexicon and the function or meaning of an utterance. The contention offered in this paper is that when such a correspondence does not exist, as in indirect speech utterances, this creates challenges for English second language speakers and may result in miscommunication. This arises because indirect speech acts allow speakers to employ various pragmatic devices such as inference, implicature, presuppositions and context clues to transmit their messages. Such devices, operating within the non-literal level of language competence, may pose challenges for ESL learners.

  3. Emerging Issues and Opportunities in Health Information Technology.

    Science.gov (United States)

    Nardi, Elizabeth A; Lentz, Lisa Korin; Winckworth-Prejsnar, Katherine; Abernethy, Amy P; Carlson, Robert W

    2016-10-01

    When used effectively, health information technology (HIT) can transform clinical care and contribute to new research discoveries. Despite advances in HIT and increased electronic health record adoption, many challenges to optimal use, interoperability, and data sharing exist. Data standardization across systems is limited, and scanned medical note documents result in unstructured data that make reporting on quality measures for reimbursement burdensome. Different policies and initiatives, including the Health Information Technology for Economic and Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the National Cancer Moonshot initiative, among others, all recognize the impact that HIT can have on cancer care. Given the growing role HIT plays in health care, it is vital to have effective and efficient HIT systems that can exchange information, collect credible data that is analyzable at the point of care, and improves the patient-provider relationship. In June 2016, NCCN hosted the Emerging Issues and Opportunities in Health Information Technology Policy Summit. The summit addressed challenges, issues, and opportunities in HIT as they relate to cancer care. Keynote presentations and panelists discussed moving beyond Meaningful Use, HIT readiness to support and report on quality care, the role of HIT in precision medicine, the role of HIT in the National Cancer Moonshot initiative, and leveraging HIT to improve quality of clinical care. Copyright © 2016 by the National Comprehensive Cancer Network.

  4. A Vanishing Act

    DEFF Research Database (Denmark)

    la Cour, Anders; Hecht, Janus; Stilling, Maria Kirstine

    2016-01-01

    The use of information and communication technology (ICT) has played an important role in the reforms that have taken place in Western welfare societies over the past two decades. ICT is regarded as a way to provide transparency and information exchange among providers, users and politicians. Thi...... internal contradictions in the organization of elderly home care services so that key processes have become outright invisible. This trick, the paper argues, is essentially an act of what Bourdieu calls social magic....

  5. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  6. Energy efficiency opportunities in the Canadian brewing industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    This guide is one of several that will be issued over time as part of the Canadian Industry Program for Energy Conservation (CIPEC). The objective in this instance is to describe data related to industrial energy use in the Canadian brewing industry and the opportunities for energy efficiency within the industry. The various industry task forces within CIPEC act as the focal point for identifying energy efficiency potential and improvement opportunities, establish energy efficiency targets for their respective sectors, reviewing and addressing barriers, and developing and implementing strategies for the achievement of targets. This guide, compiled on behalf of the brewing industry task force of CIPEC, is designed to demonstrate practical support for federal government objectives to reduce greenhouse gas emissions, help in the development of the industry`s energy efficiency targets and draw up an action plan to realize this target. Accordingly, the guide provides brief descriptions of energy efficiency opportunities, and describes proven and tested energy and money-saving methods. These methods include procedural changes, employee involvement, common-sense good housekeeping tips, energy audits, improvements in maintenance practices, changes in the operational and control functions, capital investments, and improvements through monitoring and targeting. Integrating energy efficiency improvement efforts with an environmental management system is also described as part of demonstrating good corporate citizenship. Various energy efficiency case histories taken from brewing industry experiences are described as examples of the kind of energy efficiency measures that breweries could profitably undertake. refs., tabs., figs.

  7. Opportunities of Continuing Adult Education

    Directory of Open Access Journals (Sweden)

    Lidija Ušeckienė

    2011-04-01

    Full Text Available After becoming the member state of the European Union, Lithuania undertook all the obligations of a member state. One of them is the implementation of The Lisbon Strategy aiming at the worlds most dynamic and competitive knowledge– based economy by 2010. Under the strategy, a stronger economy will drive job creation, sustainable development, and social inclusion. These changes demand the modernisation of education systems in the E U states, Lithuania among them. To achieve this objective, political forces came to an agreement on the future of Lithuanian education. In 2003 The Seimas of the Republic of Lithuania approved of National Education Strategy 2003–2012. This strategy is special not only because it is based on the experiences of the reform, addresses current and future world’s challenges and opportunities, maintains links with other strategic national reforms, but also emphasises efforts to ensure quality lifelong education for Lithuanian population and striving to become a partner in modern knowledge-based economy. Therefore, an extensive discussion on lifelong education strategies on individual and institution levels in all spheres of social and personal life has started in the E U and Lithuania. Nowadays lifelong learning is not just one aspect of education and training; it gradually is becoming the most important principle in the continuum of complex learning contexts. Such vision must be implemented this decade. The object of the research: the preconditions for the development of continuing adult education. The aim of the research: to examine the peculiarities of the preconditions for the development of continuing adult education in Pakruojis region. The methods of the research: analysis of references and documents on education; an anonymous survey in written form (a questionnaire; statistical analysis of data. The sample. The research was conducted in Pakruojis region in January-April, 2006. 300 respondents of different age

  8. A Study on the Korea Database Industry Promotion Act Legislation

    Directory of Open Access Journals (Sweden)

    Bae, Seoung-Hun

    2013-09-01

    Full Text Available The Database Industry Promotion Act was proposed at the National Assembly plenary session on July 26, 2012 and since then it has been in the process of enactment in consultation with all the governmental departments concerned. The recent trend of economic globalization and smart device innovation suggests a new opportunity and challenges for all industries. The database industry is also facing a new phase in an era of smart innovation. Korea is in a moment of opportunity to take an innovative approach to promoting the database industry. Korea should set up a national policy to promote the database industry for citizens, government, and research institutions, as well as enterprises. Above all, the Database Industry Promotion Act could play a great role in promoting the social infrastructure to enhance the capacity of small and medium-sized enterprises. This article discusses the background of the development of the Database Industry Promotion Act and its legislative processes in order to clarify its legal characteristics, including the meaning of the act. In addition, this article explains individual items related to the overall structure of the Database Industry Promotion Act. Finally, this article reviews the economic effects of the database industry for now and the future.

  9. Opportunities in Reform: Bioethics and Mental Health Ethics.

    Science.gov (United States)

    Williams, Arthur Robin

    2016-05-01

    Last year marks the first year of implementation for both the Patient Protection and Affordable Care Act and the Mental Health Parity and Addiction Equity Act in the United States. As a result, healthcare reform is moving in the direction of integrating care for physical and mental illness, nudging clinicians to consider medical and psychiatric comorbidity as the expectation rather than the exception. Understanding the intersections of physical and mental illness with autonomy and self-determination in a system realigning its values so fundamentally therefore becomes a top priority for clinicians. Yet Bioethics has missed opportunities to help guide clinicians through one of medicine's most ethically rich and challenging fields. Bioethics' distancing from mental illness is perhaps best explained by two overarching themes: 1) An intrinsic opposition between approaches to personhood rooted in Bioethics' early efforts to protect the competent individual from abuses in the research setting; and 2) Structural forces, such as deinstitutionalization, the Patient Rights Movement, and managed care. These two themes help explain Bioethics' relationship to mental health ethics and may also guide opportunities for rapprochement. The potential role for Bioethics may have the greatest implications for international human rights if bioethicists can re-energize an understanding of autonomy as not only free from abusive intrusions but also with rights to treatment and other fundamental necessities for restoring freedom of choice and self-determination. Bioethics thus has a great opportunity amid healthcare reform to strengthen the important role of the virtuous and humanistic care provider. © 2015 John Wiley & Sons Ltd.

  10. National Corn Growers Association Clean Water Act and TMDL Program: An Introduction and Basic Desk Reference for Corn Growers

    Science.gov (United States)

    The primer from the National Corn Growers Association includes information on the Clean Water Act, TMDLs, a hypothetical TMDL case study and opportunities for the agricultural community's involvement in development and implementation of TMDLs.

  11. Williamson Act - The California Land Conservation Act of 1965

    Data.gov (United States)

    California Department of Resources — The California Land Conservation Act of 1965 - commonly referred to as the Williamson Act - is the State's primary program for the conservation of private land in...

  12. Equality of Opportunity for Well-Being

    DEFF Research Database (Denmark)

    Mahler, Daniel Gerszon; Ramos, Xavier

    2017-01-01

    A growing literature has tried to measure the extent to which individuals have equal opportunities to acquire income. At the same time, policy makers have doubled down on efforts to go beyond income when measuring well- being. We attempt to bridge these two areas by measuring the extent to which...... individuals have equal opportunities to achieve a high level of well-being. We use the German Socio-Economic Panel to measure well-being in four different ways including incomes. This makes it possible to determine if the way well-being is measured matters for identifying who the opportunity......-deprived are and for tracking inequality of opportunity over time. We find that, regardless of how well-being is measured, the same people are opportunity-deprived and equality of opportunity has improved over the past 20 years. This suggests that going beyond income has little relevance if the objective is to provide equal...

  13. Foreword: Follow-on Biologics: Implementation Challenges and Opportunities.

    Science.gov (United States)

    Paradise, Jordan

    2011-01-01

    This Book of the Seton Hall Law Review presents the contributions to Follow-On Biologics: Implementation Challenges and Opportunities, a one-day roundtable event hosted by Seton Hall University School of Law in the fall of 2010. The roundtable fostered an international dialogue regarding the future of follow-on biologics in the United States resulting from the Patient Protection and Affordable Care Act of March 2010. THE BIOLOGIC PRICE COMPETITION AND INNOVATION ACT OF 2010. The March 23, 2010, enactment of the Patient Protection and Affordable Care Act (PPACA) and the companion Health Care and Education Affordability Reconciliation Act of 2010 ushered in landmark reform of the American health care system. Along with sweeping overhauls of the health care system generally, PPACA also provides a new regulatory challenge for the Food and Drug Administration (FDA). A subtitle within PPACA, the Biologics Price Competition and Innovation Act (BPCIA), bestows upon FDA broad authority to implement an abbreviated approval route to market for biological products (also known as biologics) that are "biosimilar" to an existing marketed product. The brief introduction will provide a basic comparison of biologics and conventional pharmaceutical drugs that will prove central to the FDA's development of this follow-on biologic pathway as well as specifically examine the content and scope of the BPCIA provisions and identify future challenges for the FDA. It will conclude by highlighting details of presentations during the roundtable held at the Seton Hall University School of Law and introduce the two resulting articles contained with this Book of the Seton Hall Law Review.

  14. Market opportunity in computational proteomics.

    Science.gov (United States)

    Razvi, Enal

    2002-03-01

    The current exuberance on the potential of proteomics as a means to deploy the wealth of the human genome is expected to last into the coming years. Unlike the genome, a finite entity with a fixed number of base pairs of the genetic material, the proteome is "plastic", changing throughout growth and development and environmental stresses, as well as in pathological situations. Our proteomes change over time, and therefore there is no one proteome; the proteome is for practical purposes an infinite entity. It is therefore crucial to build systems that are capable of manipulating the information content that is the proteome, thence the need for computational proteomics as a discipline. In this Market View article, we present the industry landscape that is emerging in the computational proteomics space. This space is still in its infancy and for the most part undefined; therefore we seek to present the market opportunity in informatics in the drug discovery space and then extend that to an examination of industry trends in proteomics. Thus, the gestalt is a set of predictions as to the evolution of the landscape in computational proteomics over the coming years.

  15. Clinical Bioinformatics: challenges and opportunities.

    Science.gov (United States)

    Bellazzi, Riccardo; Masseroli, Marco; Murphy, Shawn; Shabo, Amnon; Romano, Paolo

    2012-01-01

    Network Tools and Applications in Biology (NETTAB) Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics. The NETTAB 2011 workshop, held in Pavia, Italy, in October 2011 was aimed at presenting some of the most relevant methods, tools and infrastructures that are nowadays available for Clinical Bioinformatics (CBI), the research field that deals with clinical applications of bioinformatics. In this editorial, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions. Some of the most important design features of a CBI-ICT infrastructure are presented, including data warehousing, modularity and flexibility, open-source development, semantic interoperability, integrated search and retrieval of -omics information. Clinical Bioinformatics goals are ambitious. Many factors, including the availability of high-throughput "-omics" technologies and equipment, the widespread availability of clinical data warehouses and the noteworthy increase in data storage and computational power of the most recent ICT systems, justify research and efforts in this domain, which promises to be a crucial leveraging factor for biomedical research.

  16. OPPORTUNITIES TO PRODUCE HEALTHIER BEEF

    Directory of Open Access Journals (Sweden)

    G. HOLLÓ

    2008-10-01

    Full Text Available In this study the opportunities for enhancing the beneficial fatty acid in beef was examined. The effect of diet (extensive vs. intensive diet, forage to concentrate ratio, feeding concentrates rich in n-3 fatty acids and the breed (old: Hungarian Grey, dual purpose: Hungarian Simmental, dairy: Hungarian Holstein-Friesian was investigated on the fatty acid composition of beef. Findings reveal that the extensive diet with linseed supplemented concentrate influenced the n-6/n-3 ratio and the CLA content of longissimus muscle more advantageous concerning human nutrition. The meat from Hungarian Grey (HG contained more CLA and less n-6 fatty acids than that of Holstein-Friesian bulls. The different forage to concentrate ratio with/without linseed supplementation did not significantly affect the performance and slaughter traits in Hungarian Simmental (HS young bulls. The wider forage to linseed concentrate ratio caused slightly higher dressing percentage, meat and fat proportion and lower bone in carcass. The effect of muscle type on chemical composition of muscles is more significant than that of the diet. SFA and MUFA were affected by muscle type, n-3 fatty acids and n-6/n-3 fatty acid ratio of the diet. The level of cis-9 trans-11 CLA (mg/100 g was influenced by muscle type, but not by diet.

  17. Tuberculosis diagnostics: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Vijay Nema

    2012-01-01

    Full Text Available Tuberculosis (TB has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field.

  18. Obesogenic environment – intervention opportunities

    Directory of Open Access Journals (Sweden)

    Mauro Fisberg

    2016-06-01

    Full Text Available ABSTRACT Objectives: To evaluate environmental obesogenic-related factors, such as physical activity in neighborhoods and schools, nutritional behavior, and intervention programs. Sources: Critical analysis of literature with personal point of view from infant obesity experts and political advisors for public intervention. Data synthesis: Although obesity is a public health problem affecting several age groups, it is among children and adolescents that it plays a more important role, due to treatment complexity, high likelihood of persistence into adulthood, and association with other non- transmissible diseases while still in early age. Environment is a main component of the genesis and outcomes in the near future or long term. Modification of intake with high-density food, meal skipping, and high intake of saturated fat, sugar, and salt, associated to high levels of sedentarism are main causes of obesity. Conclusion: Intervention opportunities are related to modifications in political, environmental, and individual settings. School and physical activities in the educational environment are intertwined with nutrition intervention in continuous education. A critical review of some different scenarios in Latin American countries is presented.

  19. Green ergonomics: challenges and opportunities.

    Science.gov (United States)

    Hanson, Margaret A

    2013-01-01

    Addressing the causes and consequences of environmental degradation presents significant challenges for humankind. This paper considers what ergonomics/human factors (E/HF) professionals can contribute to understanding and tackling some of the issues that arise through the movement towards a more environmentally sustainable economy. These issues are considered in relation to work in green industries (specifically, sustainable energy production, recycling and organic food production), and there is a need to ensure that these jobs are safe and healthy; the design of products and systems that are 'environmentally friendly' to facilitate their acceptability and use and how E/HF professionals can contribute to understanding and promoting behavioural change relating to environmental choices. The activities of some international organisations in this area are identified and the potential for E/HF involvement is considered. The implications for the E/HF profession are discussed. This paper considers how ergonomics/human factors professionals can contribute to the movement towards more sustainable and 'environmentally friendly' design and work. Potential challenges and opportunities are discussed in relation to jobs in green industries, products and systems and behaviour change.

  20. Opportunities at Geoscience in Veracruz

    Science.gov (United States)

    Welsh-Rodríguez, C.

    2006-12-01

    The State of Veracruz is located in the central part of the Gulf of Mexico. It has enormous natural, economic and cultural wealth, is the third most populous state in Mexico, with nearly 33 % of the nation's water resources. It has an enormous quantity of natural resources, including oil, and is strategically located in Mexico. On one hand, mountains to the east are a natural border on the other lies the Gulf of Mexico. Between these two barriers are located tropical forests, mountain forests, jungles, wetlands, reefs, etc., and the land is one of the richest in biodiversity within the Americas. Veracruz, because of its geographical characteristics, presents an opportunity for research and collaboration in the geosciences. The region has experienced frequent episodes of torrential rainfalls, which have caused floods resulting in large amounts of property damage to agriculture, housing, infrastructure and, in extreme situations, loss of human life. In 2004 Veracruz University initiated a bachelor degree in Geography, which will prepare professionals to use their knowledge of geosciences to understand and promote integrated assessment of the prevailing problems in the State. Along with the geography program, the Earth Science Center offers other research programs in seismology, vulcanology, climatology, sustainable development and global change. Because of these characteristics, Veracruz is an optimal environment for active research in the geosciences, as well as for sharing the results of this research with educators, students, and all learners. We look forward to facilitating these efforts in the coming years.

  1. Opportunities for women in physics

    Energy Technology Data Exchange (ETDEWEB)

    Max, C.E.

    1978-10-25

    The most effective way to maximize opportunities for women in physics is to create more women physicists. With the current ratio of only 1 women per 30 practicing physicists, women cannot be expected to make many outstanding or visible contributions to the field. To encourage more high-school and college women to enter physics and other sciences, a ''Network of Women Scientists'' is developing a wide variety of educational programs in the San Francisco Bay Area. These programs are described and form a model that could be emulated in other metropolitan areas. At the graduate and postgraduate levels, women tend toward career patterns that can make it more difficult to realize their full potential. The majority of married women physicists have husbands in the same or allied fields. Women avoid the growing areas of industrial and applied research, instead favoring teaching, where job openings are more limited. Data showing the influence of such career patterns on women's productivity are discussed. 7 figures.

  2. The Opportunity Cost of Capital

    Directory of Open Access Journals (Sweden)

    Ayman Chit PhD

    2015-04-01

    Full Text Available The opportunity cost of the capital invested in pharmaceutical research and development (R&D to bring a new drug to market makes up as much as half the total cost. However, the literature on the cost of pharmaceutical R&D is mixed on how, exactly, one should calculate this “hidden” cost. Some authors attempt to adopt models from the field of finance, whereas other prominent authors dismiss this practice as biased, arguing that it artificially inflates the R&D cost to justify higher prices for pharmaceuticals. In this article, we examine the arguments made by both sides of the debate and then explain the cost of capital concept and describe in detail how this value is calculated. Given the significant contribution of the cost of capital to the overall cost of new drug R&D, a clear understanding of the concept is critical for policy makers, investors, and those involved directly in the R&D.

  3. Developer disappointed by lost opportunity

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2004-05-01

    A proposal by Sea Breeze Power Corporation for a 150 to 300 MW Knob Hill Wind Farm on the northern tip of Vancouver Island failed to make it past the qualification stage, ending an opportunity to investigate some of the issues that would have helped to clarify how wind technology might fit into BC Hydro's supply mix. Without commenting on the Sea Breeze proposal, a recent draft report by BC Hydro touches on the issue of capacity value of wind power by considering it as 'not proven commercially' and making the assumption in its calculations that wind power has a 'dependable capacity value' of zero, unless at least three years of site-specific data is available. Sea Breeze spokesmen disagree with BC Hydro's assessment of wind power's capacity value, and cite PJM Interconnection, a respected regional transmission organization covering all or part of eight states in the eastern US, giving wind turbines a capacity value equal to 20 per cent of their nameplate rating. Sea Breeze's Knob Hill project is currently undergoing environmental assessment. The company intends to press ahead with the project and continue to seek markets for its power. It intends to bid on BC Hydro's forthcoming general call for energy in the fall; it also responded to a recent request for renewable energy proposals by the Oregon-based utility, PacifiCorp.

  4. A multidisciplinary conceptualization of conservation opportunity.

    Science.gov (United States)

    Moon, Katie; Adams, Vanessa M; Januchowski-Hartley, Stephanie R; Polyakov, Maksym; Mills, Morena; Biggs, Duan; Knight, Andrew T; Game, Edward T; Raymond, Christopher M

    2014-12-01

    An opportunity represents an advantageous combination of circumstances that allows goals to be achieved. We reviewed the nature of opportunity and how it manifests in different subsystems (e.g., biophysical, social, political, economic) as conceptualized in other bodies of literature, including behavior, adoption, entrepreneur, public policy, and resilience literature. We then developed a multidisciplinary conceptualization of conservation opportunity. We identified 3 types of conservation opportunity: potential, actors remove barriers to problem solving by identifying the capabilities within the system that can be manipulated to create support for conservation action; traction, actors identify windows of opportunity that arise from exogenous shocks, events, or changes that remove barriers to solving problems; and existing, everything is in place for conservation action (i.e., no barriers exist) and an actor takes advantage of the existing circumstances to solve problems. Different leverage points characterize each type of opportunity. Thus, unique stages of opportunity identification or creation and exploitation exist: characterizing the system and defining problems; identifying potential solutions; assessing the feasibility of solutions; identifying or creating opportunities; and taking advantage of opportunities. These stages can be undertaken independently or as part of a situational analysis and typically comprise the first stage, but they can also be conducted iteratively throughout a conservation planning process. Four types of entrepreneur can be identified (business, policy, social, and conservation), each possessing attributes that enable them to identify or create opportunities and take advantage of them. We examined how different types of conservation opportunity manifest in a social-ecological system (the Great Barrier Reef) and how they can be taken advantage of. Our multidisciplinary conceptualization of conservation opportunity strengthens and

  5. Neighborhood Crime and Young Males' Job Opportunity

    OpenAIRE

    Keith R. Ihlanfeldt

    2006-01-01

    A puzzling aspect of America's crime problem is the concentration of crime in poor, inner-city neighborhoods. The economic model of crime suggests that this concentration may be caused by a dearth of legitimate earnings opportunities for young males living in these neighborhoods. While studies on spatial mismatch in the low-skilled labor market have documented the relatively poor job opportunity possessed by youth in these neighborhoods, there exists no evidence on the role job opportunity pl...

  6. Putting Opportunism in the Back Seat

    DEFF Research Database (Denmark)

    Foss, Nicolai; Weber, Libby

    2013-01-01

    TCE and its applications in management research put more emphasis on opportunism than on bounded rationality. By augmenting the bounded rationality assumption to include interpretive limitations, we show that there are sources of costly conflict that are not rooted in opportunism. Moreover, we sh...... that bounded rationality may drive opportunism. All hierarchal forms are inherently subject to specific bounded-rationality-based conflicts, thus have different capacities to mitigate bounded-rationality-based transaction costs....

  7. Challenges Persist Under Americans With Disabilities Act Amendments Act: How Can Oncology Providers Help?

    Science.gov (United States)

    Feuerstein, Michael; Gehrke, Amanda K; McMahon, Brian T; McMahon, Megan C

    2017-06-01

    To determine whether the Amendments to the hallmark Americans with Disabilities Act (ADA; effective January 2009), which provide increased access to the antidiscrimination laws for many with chronic illness, are related to changes in workplace discrimination allegations in individuals with a history of cancer. Information collected by the Equal Employment Opportunities Commission was used to compare allegations of discrimination and their merit before (2001 to 2008) and after (2009 to 2011) implementation of the Amendments Act. Allegations related to terms of employment (eg, promotions, wages) were more likely to be filed (odds ratio [OR], 1.34; 95% CI, 1.11 to 1.61) and determined to have merit (OR, 1.35; 95% CI, 1.03 to 1.77) after implementation of the Amendments Act. Allegations related to workplace relations (eg, harassment, discipline, discharge) were also more likely to be filed post Amendments Act (OR, 1.48; 95% CI, 1.23 to 1.78), although the merit of this complaint remained stable. Filing of all other allegations of discrimination (ie, hiring, reasonable accommodation, and termination) and their merit remained unchanged post Amendments Act. Despite the implementation of the Amendments Act, discrimination allegations in those with a history of cancer persisted or in certain areas increased. Although prevention of workplace discrimination rests primarily with employers, the oncology care team is uniquely qualified to provide information related to residual symptoms and function that can facilitate more personalized solutions to workplace discrimination, such as successful workplace accommodations. Information is provided that can assist the oncology team in their efforts to improve work outcomes.

  8. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  9. Quantitative Electroencephalographic Analysis Provides an Early-Stage Indicator of Disease Onset and Progression in the zQ175 Knock-In Mouse Model of Huntington's Disease

    Science.gov (United States)

    Fisher, Simon P.; Schwartz, Michael D.; Wurts-Black, Sarah; Thomas, Alexia M.; Chen, Tsui-Ming; Miller, Michael A.; Palmerston, Jeremiah B.; Kilduff, Thomas S.; Morairty, Stephen R.

    2016-01-01

    Study Objectives: Patients with Huntington's disease (HD) show a high prevalence of sleep disorders that typically occur prior to the onset of motoric symptoms and neurodegeneration. Our understanding of the pathophysiological alterations in premanifest HD is limited, hindering the ability to measure disease modification in response to treatment. We used a full-length knock-in HD model to determine early changes in the electroencephalogram (EEG) and sleep that may predict the onset and progression of the disease. Methods: A 10-month longitudinal study was designed to determine the effect of the HD mutation on the EEG and sleep/wake changes in heterozygous (HET) and homozygous (HOM) zQ175 mice and wild-type (WT) littermates from 8 to 48 w of age. Mice were instrumented with tethered headmounts to record EEG/electromyography signals. Telemeters were implanted to continuously measure locomotor activity (LMA) and body temperature (Tb). Sleep deprivation (SDep) was performed at 8, 12, 16, 24, 32, and 48 w of age. Results: The HD mutation disrupted the EEG field potential from 8–12 w in an age- and mutant huntington dose-dependent manner, prior to changes in sleep/wake states, LMA, and Tb. Prominent effects of the HD mutation on the EEG included a progressive reduction in low frequency power, a slowing of rapid eye movement peak theta frequency, and the emergence of state-dependent beta/gamma oscillations. There was no effect of genotype on the relative increase in nonrapid eye movement delta power or sleep time in response to SDep. Conclusions: The expression of the Huntington's disease (HD) mutation results in complex EEG alterations that occur prior to deficits in behavioral measures and are one of the earliest phenotypes uncovered in this mouse model. Despite these EEG changes, homeostatic responses to sleep loss were preserved in HET and HOM zQ175 mice. Greater insight into the localization and response of these EEG alterations to novel therapies may enable early

  10. Striatal Synaptosomes from Hdh140Q/140Q Knock-in Mice have Altered Protein Levels, Novel Sites of Methionine Oxidation, and Excess Glutamate Release after Stimulation

    Science.gov (United States)

    Valencia, Antonio; Sapp, Ellen; Kimm, Jeffrey S.; McClory, Hollis; Ansong, Kwadwo A.; Yohrling, George; Kwak, Seung; Kegel, Kimberly B.; Green, Karin M.; Shaffer, Scott A.; Aronin, Neil; DiFiglia, Marian

    2014-01-01

    Background: Synaptic connections are disrupted in patients with Huntington’s disease (HD). Synaptosomes from postmortem brain are ideal for synaptic function studies because they are enriched in pre- and post-synaptic proteins important in vesicle fusion, vesicle release, and neurotransmitter receptor activation. Objective: To examine striatal synaptosomes from 3, 6 and 12 month old WT and Hdh140Q/140Q knock-in mice for levels of synaptic proteins, methionine oxidation, and glutamate release. Methods: We used Western blot analysis, glutamate release assays, and liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Striatal synaptosomes of 6 month old Hdh140Q/140Q mice had less DARPP32, syntaxin 1 and calmodulin compared to WT. Striatal synaptosomes of 12 month old Hdh140Q/140Q mice had lower levels of DARPP32, alpha actinin, HAP40, Na+/K+-ATPase, PSD95, SNAP-25, TrkA and VAMP1, VGlut1 and VGlut2, increased levels of VAMP2, and modifications in actin and calmodulin compared to WT. More glutamate released from vesicles of depolarized striatal synaptosomes of 6 month old Hdh140Q/140Q than from age matched WT mice but there was no difference in glutamate release in synaptosomes of 3 and 12 month old WT and Hdh140Q/140Q mice. LC-MS/MS of 6 month old Hdh140Q/140Q mice striatal synaptosomes revealed that about 4% of total proteins detected (>600 detected) had novel sites of methionine oxidation including proteins involved with vesicle fusion, trafficking, and neurotransmitter function (synaptophysin, synapsin 2, syntaxin 1, calmodulin, cytoplasmic actin 2, neurofilament, and tubulin). Altered protein levels and novel methionine oxidations were also seen in cortical synaptosomes of 12 month old Hdh140Q/140Q mice. Conclusions: Findings provide support for early synaptic dysfunction in Hdh140Q/140Q knock-in mice arising from altered protein levels, oxidative damage, and impaired glutamate neurotransmission and suggest that study of synaptosomes could be of

  11. Contribution of 5-HT2 receptor subtypes to sleep-wakefulness and respiratory control, and functional adaptations in knock-out mice lacking 5-HT2A receptors.

    Science.gov (United States)

    Popa, Daniela; Léna, Clément; Fabre, Véronique; Prenat, Caroline; Gingrich, Jay; Escourrou, Pierre; Hamon, Michel; Adrien, Joëlle

    2005-12-07

    Serotonin (5-hydroxytryptamine; 5-HT) plays key roles in sleep-wakefulness regulation. Evidence indicates that 5-HT2 receptors are involved mainly in non-rapid eye movement sleep (NREMS) regulation and respiratory control. Here, we investigated the relative contribution of 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptor subtypes to NREMS and breathing during sleep, using 5-HT2 subtype-selective ligands in wild-type (5-HT(2A)+/+) and knock-out (5-HT(2A)-/-) mice that do not express 5-HT(2A) receptors. Acute blockade of 5-HT(2A) receptors induced an increase in NREMS in 5-HT(2A)+/+ mice, but not 5-HT(2A)-/- mutants, which spontaneously expressed less NREMS than wild-type animals. In 5-HT(2A)+/+ mice, 5-HT(2B) receptor blockade produced a reduction of NREMS, whereas receptor activation induced an increase in this sleep stage. These effects were less pronounced in 5-HT(2A)-/- mice, indicating a lower sensitivity of 5-HT(2B) receptors in mutants, with no change in 5-HT(2B) mRNA. Blockade of 5-HT(2C) receptors had no effect on NREMS in both strains. In addition, an increase in EEG power density after sleep deprivation was observed in 5-HT(2A)+/+ mice but not in 5-HT(2A)-/- mice. Whole-body plethysmographic recordings indicated that 5-HT(2A) receptor blockade in 5-HT(2A)+/+ mice reduced NREMS apneas and bradypneas that occurred after sighs. In contrast, in 5-HT(2A)-/- mutants, NREMS apneas were not modified, and bradypnea after sighs were more pronounced. Our results demonstrate that 5-HT exerts a 5-HT(2B)-mediated facilitation of NREMS, and an influence respectively inhibitory on NREMS and facilitatory on sleep apnea generation, via 5-HT(2A) receptors. Moreover, 5-HT(2A) gene knock-out leads to functional compensations yielding adaptive changes opposite to those caused by pharmacological blockade of 5-HT(2A) receptors in 5-HT(2A)+/+ mice.

  12. Knocking-down of CREPT prohibits the progression of oral squamous cell carcinoma and suppresses cyclin D1 and c-Myc expression.

    Directory of Open Access Journals (Sweden)

    Juntao Ma

    Full Text Available As a regulator essential for many cell cycle-related proteins, the robust expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT implicates a poor diagnosis of endoderm and mesoderm-derived tumors. Whether CREPT plays the same role in the tumorigenesis derived from ectodermal tissues remains elusive.To explore the role of CREPT in ectoderm-derived tumors, cells from 7oral squamous cell carcinoma (OSCC lines and 84clinical OSCC samples were exploited in this study. Quantitative PCR, Western blot assay and immunohistochemistry were applied in the evaluation of CREPT, cyclin D1 and c-Myc expression. Knocking-down of CREPT was performed by lentivirus delivering specific shRNA of CREPT. The effects of CREPT on OSCC were examined by cell proliferation, colony formation, apoptosis, cell migration and xenograft implantation experiments.Compared with human normal oral keratinocytes, OSCC cell lines showed a significantly elevated expression of CREPT in both mRNA and protein levels. Consistently, samples from OSCC patients also exhibited a noticeably stronger CREPT expression than the noncancerous samples. In contrast, knocking down of CREPT in OSCC cell lines significantly reduced proliferation, colony formation and migration as well as the expression of cyclin D1 and c-Myc, but promoted apoptosis. Statistical analysis also suggested that CREPT expression was significantly correlated with the T and N classification of OSCC. Furthermore, CAL27 mouse xenograft model confirmed that down-regulation of CREPT prohibited cyclin D1 and c-Myc expression, through which decreased the in vivo tumor growth, but increased the survival ratio of hosts.In OSCC cell lines, up-regulated CREPT expression enhanced cell proliferation, migration and cell cycle as well as promoted cyclin D1 and c-Myc expression as it did in endoderm and mesoderm-origin tumors. Our study strongly suggests that CREPT could be used as a marker for the OSCC prognosis and

  13. Safer GM-Crops: Opportunities for Innovations

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Safer GM-Crops: Opportunities for Innovations. Rakesh Tuli. National Agri-Food Biotechnology Institute, Mohali. National Botanical Research Institute, Lucknow.

  14. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    costs of opportunism are determined as a product of four factors. The four factors are: likelihood of discovering supplier opportunism, buyer’s internalized quantity as reaction to supplier opportunism, asset specificity of external supplier’s investments, and multiplicator effects. Each......When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expected...... of these factors are explained and discussed in the paper. The paper ends by offering a number of theoretical and managerial implications....

  15. Market imperfections, opportunity and sustainable entrepreneurship

    National Research Council Canada - National Science Library

    Cohen, Boyd; Winn, Monika I

    2007-01-01

    .... We show that these opportunities establish the foundations for an emerging model of sustainable entrepreneurship, one which enables founders to obtain entrepreneurial rents while simultaneously...

  16. Teaching Speech Acts

    Directory of Open Access Journals (Sweden)

    Teaching Speech Acts

    2007-01-01

    Full Text Available In this paper I argue that pragmatic ability must become part of what we teach in the classroom if we are to realize the goals of communicative competence for our students. I review the research on pragmatics, especially those articles that point to the effectiveness of teaching pragmatics in an explicit manner, and those that posit methods for teaching. I also note two areas of scholarship that address classroom needs—the use of authentic data and appropriate assessment tools. The essay concludes with a summary of my own experience teaching speech acts in an advanced-level Portuguese class.

  17. The Act of Walking

    DEFF Research Database (Denmark)

    Vestergaard, Maria Quvang Harck; Olesen, Mette; Helmer, Pernille Falborg

    2014-01-01

    perception of ‘walkability’ is based upon a subjective judgement of different physical factors, such as sidewalk width, traffic volumes and building height (Ewing and Handy 2009:67). And iIn order to understand the act of walking it is therefore necessary to create a vocabulary to understand how and why...... internalize the common norms and values of pedestrian culture and are influenced by their physical environment when walking. In conclusion the chapter questions and discusses how this knowledge could be used in future planning practices....

  18. Forecast of Contracting and Subcontracting Opportunities, Fiscal year 1995

    Energy Technology Data Exchange (ETDEWEB)

    1995-02-01

    Welcome to the US Department of Energy`s Forecast of Contracting and Subcontracting Opportunities. This forecast, which is published pursuant to Public Low 100--656, ``Business Opportunity Development Reform Act of 1988,`` is intended to inform small business concerns, including those owned and controlled by socially and economically disadvantaged individuals, and women-owned small business concerns, of the anticipated fiscal year 1995 contracting and subcontracting opportunities with the Department of Energy and its management and operating contractors and environmental restoration and waste management contractors. This document will provide the small business contractor with advance notice of the Department`s procurement plans as they pertain to small, small disadvantaged and women-owned small business concerns.Opportunities contained in the forecast support the mission of the Department, to serve as advocate for the notion`s energy production, regulation, demonstration, conservation, reserve maintenance, nuclear weapons and defense research, development and testing, when it is a national priority. The Department`s responsibilities include long-term, high-risk research and development of energy technology, the marketing of Federal power, and maintenance of a central energy data collection and analysis program. A key mission for the Department is to identify and reduce risks, as well as manage waste at more than 100 sites in 34 states and territories, where nuclear energy or weapons research and production resulted in radioactive, hazardous, and mixed waste contamination. Each fiscal year, the Department establishes contracting goals to increase contracts to small business concerns and meet our mission objectives.

  19. Missed opportunities in child healthcare

    Directory of Open Access Journals (Sweden)

    Linda Jonker

    2014-01-01

    Full Text Available Background: Various policies in health, such as Integrated Management of Childhood Illnesses, were introduced to enhance integrated service delivery in child healthcare. During clinical practice the researcher observed that integrated services may not be rendered.Objectives: This article describes the experiences of mothers that utilised comprehensive child health services in the Cape Metropolitan area of South Africa. Services included treatment for diseases; preventative interventions such as immunisation; and promotive interventions, such as improvement in nutrition and promotion of breastfeeding.Method: A qualitative, descriptive phenomenological approach was applied to explore the experiences and perceptions of mothers and/or carers utilising child healthcare services. Thirty percent of the clinics were selected purposively from the total population. A convenience purposive non-probability sampling method was applied to select 17 mothers who met the criteria and gave written consent. Interviews were conducted and recorded digitally using an interview guide. The data analysis was done using Tesch’s eight step model.Results: Findings of the study indicated varied experiences. Not all mothers received information about the Road to Health book or card. According to the mothers, integrated child healthcare services were not practised. The consequences were missed opportunities in immunisation, provision of vitamin A, absence of growth monitoring, feeding assessment and provision of nutritional advice.Conclusion: There is a need for simple interventions such as oral rehydration, early recognition and treatment of diseases, immunisation, growth monitoring and appropriate nutrition advice. These services were not offered diligently. Such interventions could contribute to reducing the incidence of child morbidity and mortality.

  20. Cooperative Projects - Challenges and Opportunities

    Science.gov (United States)

    Schubotz, Wiebke; Brücher, Tim; Vamborg, Freja

    2017-04-01

    Today's research in Germany is often organized in large projects and collaborations, so-called cooperative projects ("Verbundprojekte" in German). These projects are defined by a large number of members (more than 50) and participating institutes, e.g. institutes of research organizations such as the Max-Planck society and the Leibniz association, Helmholtz centres, and universities. For coordination purposes these projects usually have a general project manager or project coordinator close to the speaker of the project. Despite this overarching position, it is often challenging for the project manager to really overview the entire project as he is, for example, not involved in the individual institute's recruitment processes or research connections to other institutes via other projects. Additionally, there is neither a formal obligation for the principal investigators and project scientists to report changes within their sub-projects, nor any formal dependency between these sub-projects and the coordination office to ensure a contemporary update of changes and progress in their specific tasks of the project. Therefore, the idea of a coordinating position to oversee the entire cooperative project is sometimes difficult to reach. Furthermore, project managers usually have no formal connection to other project managers. This means that recurrent tasks, for which cooperation between project managers would be helpful, need to be reinvented for each project anew. Due to the lack of this more formalized cooperation between project managers, acquired expertise is often lost. We will illustrate the challenges of this kind of project management based on projects at the Max Planck Institute for Meteorology (Hamburg) and the Helmholtz Centre for Ocean Research (GEOMAR, Kiel), but also point out opportunities that arise within a large collaboration of partners. Moreover, we present an approach to coordinate management processes in order to overcome some of the aforementioned

  1. 76 FR 59073 - Privacy Act

    Science.gov (United States)

    2011-09-23

    ... 32 CFR Part 1901 Privacy Act AGENCY: Central Intelligence Agency. ACTION: Proposed rule. SUMMARY: Consistent with the Privacy Act (PA), the Central Intelligence Agency (CIA) has undertaken and completed a... Act (PA), the CIA has undertaken and completed a review of its public PA regulations. As a result of...

  2. 78 FR 73466 - Privacy Act

    Science.gov (United States)

    2013-12-06

    ... CORPORATION 22 CFR Part 707 Privacy Act AGENCY: Overseas Private Investment Corporation. ACTION: Notice of... (``OPIC'') Privacy Act (``PA'') regulations by making substantive and administrative changes. These... confidential or inappropriate for public disclosure. Regulatory Flexibility Act (5 U.S.C. 601 et seq.) Pursuant...

  3. Speech Acts and Rhetorical Action.

    Science.gov (United States)

    Steinmann, Martin, Jr.

    Some authorities wish to persuasively define rhetoric as formal or public speeches, while others hold to a more traditional and broader definition pointing to the relevance of speech-act theory to support them. Central to speech-act theory is the illocutionary act (uttering at least one sentence of some language under certain conditions). Two…

  4. Speech Acts and Conversational Interaction.

    Science.gov (United States)

    Geis, Michael L.

    This book unites speech act theory and conversation analysis to advance a theory of conversational competence, called the Dynamic Speech Act Theory (DSAT). In contrast to traditional speech act theory that focuses almost exclusively on intuitive assessments of isolated, constructed examples, this theory is predicated on the assumption that speech…

  5. Report: Measuring the Impact of the Food Quality Protection Act: Challenges and Opportunities

    Science.gov (United States)

    Report #2006-P-00028, August 1, 2006. The EPA OIG found that OPP has primarily measured its success and the impact of FQPA by adherence to its reregistration schedule rather than by reductions in risk to children’s health.

  6. 78 FR 5800 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-01-28

    ... (202) 566-1927. FOR FURTHER INFORMATION CONTACT: Sanda Howland, Special Litigation and Projects...; telephone: (202) 564- 5022; fax: (202) 564-9001; email: howland[email protected] . I. Background This...

  7. 78 FR 49512 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-08-14

    ... included operating facilities, corporate offices, warehouses, and other storage locations. On October 2... Agreement in accordance with the Consolidated Rules of Practice, 40 CFR part 22, specifically 40 CFR 22.13(b...

  8. 78 FR 36749 - Determination Under the African Growth and Opportunity Act

    Science.gov (United States)

    2013-06-19

    ... determined that certain textile and apparel goods from Benin shall be treated as ``folklore articles'' and..., including handloomed, handmade, or folklore articles of a beneficiary country that are certified as such by..., folklore articles, or ethnic printed fabrics. See 66 FR 7271, 7271-72 (January 22, 2001) and 70 FR 37959...

  9. 75 FR 40774 - Determination Under the African Growth and Opportunity Act

    Science.gov (United States)

    2010-07-14

    ... determined that certain textile and apparel goods from Burkina Faso shall be treated as ``folklore articles... sub-Saharan African countries, including handloomed, handmade, or folklore articles of a beneficiary... treated as being handloomed, handmade, folklore articles, or ethnic printed fabrics. See 66 FR 7271, 7271...

  10. 76 FR 22095 - Clean Air Act: Opportunity To Comment, Activities Required by Federal Facilities Compliance...

    Science.gov (United States)

    2011-04-20

    ... Cumberland Fossil Plant, located in Stewart County, Cumberland City, Tennessee; the John Sevier Fossil Plant... Sevier plant, six units at the Widows Creek plant, and all ten units at the Johnsonville plant. Further...

  11. 78 FR 42942 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    Science.gov (United States)

    2013-07-18

    ... be free of any defects or viruses. For additional information about EPA's public docket, visit the... on information provided by MetroPCS and use of the Economic Benefit (BEN) computer model. Of this...

  12. Sqstm1-GFP knock-in mice reveal dynamic actions of Sqstm1 during autophagy and under stress conditions in living cells.

    Science.gov (United States)

    Eino, Atsushi; Kageyama, Shun; Uemura, Takefumi; Annoh, Hiromichi; Saito, Tetsuya; Narita, Ichiei; Waguri, Satoshi; Komatsu, Masaaki

    2015-12-01

    Sqstm1 serves as a signaling hub and receptor for selective autophagy. Consequently, dysregulation of Sqstm1 causes imbalances in signaling pathways and disrupts proteostasis, thereby contributing to the development of human diseases. Environmental stresses influence the level of Sqstm1 by altering its expression and/or autophagic degradation, and also changes the localization of Sqstm1, making it difficult to elucidate the actions and roles of this protein. In this study, we developed knock-in mice expressing Sqstm1 fused to GFP (Sqstm1-GFP(KI/+)). Using these Sqstm1-GFP(KI/+) mice, we revealed for the first time the dynamics of endogenous Sqstm1 in living cells. Sqstm1-GFP was translocated to a restricted area of LC3-positive structures, which primarily correspond to the inside of autophagosomes, and then degraded. Moreover, exposure to arsenite induced expression of Sqstm1-GFP, followed by accumulation of the fusion protein in large aggregates that were degraded by autophagy. Furthermore, suppression of autophagy in Sqstm1-GFP(KI/+) mouse livers caused accumulation of Sqstm1-GFP and formation of GFP-positive aggregate structures, leading to severe hepatic failure. These results indicate that Sqstm1-GFP(KI/+) mice are a useful tool for analyzing Sqstm1 in living cells and intact animals. © 2015. Published by The Company of Biologists Ltd.

  13. [Biological characteristics of an Hog1 MAPK homologous gene FoHog1 knock-out mutant of Fusarium oxysporum f. sp. cubense].

    Science.gov (United States)

    Mao, Chao; Chen, Pingya; Dai, Qingdong; Yang, Laying; Huang, Junsheng

    2014-11-04

    This study was aimed to obtain a mitogen-activated protein kinase (MAPK) gene namely FoHog1 from Fusarium oxysporum f. sp. cubense and to verify its function. We amplified FoHog1 gene by PCR and RT-PCR methods and analyzed it through bioinformatics method. PEG-mediated protoplast transformation was used to create the deletion mutants of FoHog1 gene. We analyzed different biological characteristics between knock-out strain and wild-type strain. FoHog1 gene encoding a putative protein of 357 amino acids and its genetic relationship with different Fusarium' s protein. Compared with the wild-type strain, FoHog1 deletion mutants have loose hyphae colony, less spores production, lower dry weight of hyphae and more sensitive to temperature, pH and osmotic stress. FoHog1 deletion mutants also have reduced colonization ability compared with the wild-type strain. FoHog1 gene participated in mycelial growth, sporulation, catabolism of sodium acetate and ammonium chloride, osmotic stress response and pathogenic process with Fusarium oxysporum f. sp. cubense Race 4.

  14. Micro RNA-214 contributes to proteasome independent downregulation of beta catenin in Huntington's disease knock-in striatal cell model STHdhQ111/Q111.

    Science.gov (United States)

    Ghatak, Supratim; Raha, Sanghamitra

    2015-04-10

    Role of beta catenin in Huntington's disease (HD) is not clear. Previous studies on HD reported varied levels of beta catenin. In the present study we showed that beta catenin is post transcriptionally down-regulated in mutant huntingtin knock-in cell model STHdhQ111/Q111. This in turn leads to decreased level of wnt/beta catenin responsive genes. We observed that Gsk3beta or Gsk3beta (phospho Ser 9) is unaltered in HD and this down-regulation of beta catenin is independent of proteasomal degradation. Finally, we showed that the overexpression of miR-214 leads to the down-regulation of beta catenin at protein level only and reduces its transcriptional activity. We concluded that, miR-214 contributes to the processes that result in proteasome independent post transcriptional down-regulation of beta catenin in STHdhQ111/Q111, probably through inhibition of protein synthesis from beta catenin mRNA. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jenny J Sun

    Full Text Available CRISPR/Cas9 mediated DNA double strand cutting is emerging as a powerful approach to increase rates of homologous recombination of large targeting vectors, but the optimization of parameters, equipment and expertise required remain barriers to successful mouse generation by single-step zygote injection. Here, we sought to apply CRISPR/Cas9 methods to traditional embryonic stem (ES cell targeting followed by blastocyst injection to overcome the common issues of difficult vector construction and low targeting efficiency. To facilitate the study of noradrenergic function, which is implicated in myriad behavioral and physiological processes, we generated two different mouse lines that express FLPo recombinase under control of the noradrenergic-specific Dopamine-Beta-Hydroxylase (DBH gene. We found that by co-electroporating a circular vector expressing Cas9 and a locus-specific sgRNA, we could target FLPo to the DBH locus in ES cells with shortened 1 kb homology arms. Two different sites in the DBH gene were targeted; the translational start codon with 6-8% targeting efficiency, and the translational stop codon with 75% targeting efficiency. Using this approach, we established two mouse lines with DBH-specific expression of FLPo in brainstem catecholaminergic populations that are publically available on MMRRC (MMRRC_041575-UCD and MMRRC_041577-UCD. Altogether, this study supports simplified, high-efficiency Cas9/CRISPR-mediated targeting in embryonic stem cells for production of knock-in mouse lines in a wider variety of contexts than zygote injection alone.

  16. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

    Science.gov (United States)

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

    2014-07-16

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. Copyright © 2014 the authors 0270-6474/14/349506-10$15.00/0.

  17. The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

    Directory of Open Access Journals (Sweden)

    Jingsheng Liang

    2015-01-01

    Full Text Available We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine mutation in human cardiac troponin I (cTnI on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV and right (RV ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

  18. Knock-in of nuclear localised beta-galactosidase reveals that the tyrosine phosphatase Ptprv is specifically expressed in cells of the bone collar.

    Science.gov (United States)

    Dacquin, R; Mee, P J; Kawaguchi, J; Olmsted-Davis, E A; Gallagher, J A; Nichols, J; Lee, K; Karsenty, G; Smith, A

    2004-04-01

    Ptprv is a member of the transmembrane tyrosine phosphatase gene family reported to be expressed in osteoblasts and gonads. To better define the developmental and tissue specificity of Ptprv expression, we generated knock-in mice expressing a nuclear localised beta-galactosidase reporter under the control of resident Ptprv regulatory elements. Histochemical staining of Ptprv-nLacZ mice revealed that Ptprv expression is readily detectable in the foetal gonadal ridge of both sexes and in adult gonads where it is localised to Sertoli cells of the testis and celomic epithelial cells of the ovaries. During early limb development, Ptprv expression is prominent in the apical ectodermal ridge of the limb bud. At latter stages of development, Ptprv is predominantly expressed in the perichondrial and periosteal region of long bones, known as the bone collar. In contrast to previous indications from in vitro studies, there is little if any expression in mature osteoblasts in vivo. Analysis of Ptprv mRNA localisation by in situ hybridization in parallel with molecular markers of chondrocytes and osteoblasts confirmed the specific expression of Ptprv in immature bone collar cells. The specificity of Ptprv expression in these cells may be a useful tool to elucidate their role in the transition of skeletal elements from cartilage template to bone. Copyright 2004 Wiley-Liss, Inc.

  19. Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

    Science.gov (United States)

    Schmouth, J-F; Banks, K G; Mathelier, A; Gregory-Evans, C Y; Castellarin, M; Holt, R A; Gregory-Evans, K; Wasserman, W W; Simpson, E M

    2012-04-01

    Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

  20. Accelerated Systemic Autoimmunity in the Absence of Somatic Hypermutation in 564Igi: A Mouse Model of Systemic Lupus with Knocked-In Heavy and Light Chain Genes

    Directory of Open Access Journals (Sweden)

    Gabrielle McDonald

    2017-09-01

    Full Text Available 564Igi mice have knocked-in immunoglobulin (Ig heavy (H and light (L chain genes that encode an autoantibody recognizing RNA. Previously, we showed that these mice produce pathogenic IgG autoantibodies when activation-induced deaminase (AID is expressed in pre-B and immature B cells but not when it is expressed only in mature B cells. AID has two functions; it is necessary for somatic hypermutation (SHM and class switch recombination (CSR. To determine the role of each of these functions in the generation of pathogenic autoantibodies, we generated 564Igi mice that carry a mutant AID-encoding gene, Aicda (AicdaG23S, which is capable of promoting CSR but not SHM. We found that 564Igi AicdaG23S mice secreted class-switched antibodies (Abs at levels approximately equal to 564Igi mice. However, compared to 564Igi mice, 564Igi AicdaG23S mice had increased pathogenic IgG Abs and severe systemic lupus erythematosus-like disease, including, glomerulonephritis, and early death. We suggest that in 564Igi mice SHM by AID changes Ig receptors away from self reactivity, thereby mitigating the production of autoantibody, providing a novel mechanism of tolerance.

  1. Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment.

    Directory of Open Access Journals (Sweden)

    Munkyung Kim

    Full Text Available Alport syndrome is a genetic disease of collagen IV (α3, 4, 5 resulting in renal failure. This study was designed to investigate sex-phenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using Col4a3 knock out (Col4a3KO mice, an established genetic model of autosomal recessive Alport syndrome. No sex differences in the evolution of body mass loss, renal pathology, biomarkers of tubular damage KIM-1 and NGAL, or deterioration of kidney function were observed during the life span of Col4a3KO mice. These findings confirm that, similar to human autosomal recessive Alport syndrome, female and male Col4a3KO mice develop renal failure at the same age and with similar severity. The specific contribution of macrophage infiltration to Alport disease, one of the prominent features of the disease in human and Col4a3KO mice, remains unknown. This study shows that depletion of kidney macrophages in Col4a3KO male mice by administration of clodronate liposomes, prior to clinical onset of disease and throughout the study period, does not protect the mice from renal failure and interstitial fibrosis, nor delay disease progression. These results suggest that therapy targeting macrophage recruitment to kidney is unlikely to be effective as treatment of Alport syndrome.

  2. Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice.

    Science.gov (United States)

    Scoumanne, Ariane; Molina-Ortiz, Patricia; Monteyne, Daniel; Perez-Morga, David; Erneux, Christophe; Schurmans, Stéphane

    2016-09-01

    Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression and function of the two other family members ITPKA and ITPKB are rather well characterized, similar information is lacking for ITPKC. Here, we first defined the expression of Itpkc mRNA and protein in mouse tissues and cells using in situ hybridization and new antibodies. Surprisingly, we found that cells positive for ITPKC in the studied tissues express either a multicilium (tracheal and bronchial epithelia, brain ependymal cells), microvilli forming a brush border (small and large intestine, and kidney proximal tubule cells) or a flagellum (spermatozoa), suggesting a role for ITPKC either in the development or the function of these specialized cellular structures. Given this surprising expression, we then analyzed ITPKC function in multiciliated tracheal epithelial cells and sperm cells using our Itpkc knock-out mouse model. Unfortunately, no significant difference was observed between control and mutant mice for any of the parameters tested, leaving the exact in vivo function of this third Ins(1,4,5)P3 3-kinase still open. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Opportunities and Risks in Semiconductor Metrology

    Science.gov (United States)

    Borden, Peter

    2005-09-01

    New metrology opportunities are constantly emerging as the semiconductor industry attempts to meet scaling requirements. The paper summarizes some of the key FEOL and BEOL needs. These must be weighed against a number of considerations to ensure that they are good opportunities for the metrology equipment supplier. The paper discusses some of these considerations.

  4. Mapping Community-based Natural Learning Opportunities.

    Science.gov (United States)

    Dunst, Carl J.; Herter, Serena; Shields, Holly; Bennis, Leslie

    2001-01-01

    This article explains the use of a community mapping methodology to identify natural learning environments and inclusion opportunities for young children with disabilities. Four steps are discussed: (1) selecting kinds of learning opportunities for mapping; (2) gathering information about community learning sources; (3) developing an informational…

  5. UAV imagery analysis: challenges and opportunities

    Science.gov (United States)

    Grant, Barbara G.

    2017-05-01

    As UAV imaging continues to expand, so too do the opportunities for improvements in data analysis. These opportunities, in turn, present their own challenges including the need for real time radiometric and spectral calibration; the continued development of quality metrics facilitating exploitation of strategic and tactical imagery; and the need to correct for sensor and platform-induced artifacts in image data.

  6. The distribution of Schumpeterian and Kirznerian opportunities

    NARCIS (Netherlands)

    de Jong, J.P.J.|info:eu-repo/dai/nl/168220849; Marsili, O.

    2015-01-01

    Despite their presence in modern entrepreneurship theories, empirical investigations of opportunity types are scarce. We develop a 5-dimensional bipolar scale to measure the extent in which opportunities are Schumpeterian or Kirznerian. Drawing on this measure, we examine the shape of the

  7. Political opportunity structures, democracy, and civil war

    NARCIS (Netherlands)

    Gleditsch, K.S.; Ruggeri, A.

    2010-01-01

    Theories of mobilization suggest that groups are more likely to resort to violence in the presence of political opportunity structures that afford greater prospects for extracting concessions from the government or better opportunities to topple ruling governments. However, existing efforts to

  8. Index of Economic Freedom: Unrealized Pedagogical Opportunities

    Science.gov (United States)

    Maier, Mark; Miller, John A.

    2017-01-01

    Although the Index of Economic Freedom appears in many economic textbooks, their coverage of the index misses opportunities to teach statistical and policy-related concepts important for the principles course. The standard textbook presentation passes up an opportunity to examine the statistical issues of weighting in composite index numbers and…

  9. Determinants Of Missed Opportunities For Immunization Among ...

    African Journals Online (AJOL)

    Missed opportunities in immunization had been a global public health obstacle to the attainment of the Millennium Development Goal of reducing child mortality by two-thirds by 2015. Studies have also shown that missed opportunities in both routine and supplementary immunization contribute significantly to the low ...

  10. Preventive maintenance at opportunities of restricted duration

    NARCIS (Netherlands)

    R. Dekker (Rommert); E. Smeitink

    1994-01-01

    textabstractThis article deals with the problem of setting priorities for the execution of maintenance packages at randomly occurring opportunities. These opportunities are of restricted duration, implying that only a limited number of packages can be executed. The main idea proposed is to set up a

  11. On Risks and Opportunities in Financial Markets

    NARCIS (Netherlands)

    S.D. Lansdorp (Simon)

    2012-01-01

    textabstractInvesting in financial securities inevitably involves risks on the one hand and opportunities on the other hand. This thesis bundles four different studies on risks and/or opportunities in financial markets. In one study, we examine the cross-sectional explanatory power of different

  12. Luquillo Experimental Forest: Research History and Opportunities

    Science.gov (United States)

    Nancy L. Harris; Ariel E. Lugo; Sandra Brown; Tamara Heartsill-Scalley

    2012-01-01

    The goals of this Luquillo Experimental Forest: Research History and Opportunities are to synthesize the new research that has emerged from the LEF since the publication of Brown et al. (1983) into a concise summary of key research findings and to highlight opportunities for future research that will contribute to a greater understanding of the structure and function...

  13. Challenges and Opportunities for Libraries in Pakistan

    OpenAIRE

    Shafiq Ur, Rehman; Pervaiz, Ahmad

    2007-01-01

    Abstract: This paper, based on review of literature, observation, and informal conversations, discusses various challenges regarding finance, collection development, ICTs, human resources, library education, library association and research & development faced by library profession in Pakistan. The opportunities to meet these challenges have also been explored. Keywords: Library challenges and opportunities (Pakistan); Librarianship (Pakistan); Library issues; Library profession in Pa...

  14. Opportunists and opportunities: the 2010 SHEA Lecture.

    Science.gov (United States)

    Henderson, David K

    2010-11-01

    My experience as a hospital epidemiologist at the National Institutes of Health Clinical Center has underscored the importance of aggressively managing infection with opportunistic pathogens and of taking advantage of opportunities as they arise (most often as crises). I review selected aspects of my career and use these as examples of the opportunists and opportunities now facing healthcare epidemiology.

  15. Identifying Business Opportunities | Ovadje | LBS Management ...

    African Journals Online (AJOL)

    ... to distinguish between a nice idea and a real opportunity. Important sources of business opportunities are identified: unsatisfied needs due to the difficult economic environment, and new avenues opened by changes in government regulations, demography and technology. LBS Management Review Vol.6(2) 2001: 82-88 ...

  16. Quantum Information: Opportunities and Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bennink, Ryan S [ORNL

    2008-01-01

    Modern society is shaped by the ability to transmit, manipulate, and store large amounts of information. Although we tend to think of information as abstract, information is physical, and computing is a physical process. How then should we understand information in a quantum world, in which physical systems may exist in multiple states at once and are altered by the very act of observation? This question has evolved into an exciting new field of research called Quantum Information (QI). QI challenges many accepted rules and practices in computer science. For example, a quantum computer would turn certain hard problems into soft problems, and would render common computationally-secure encryption methods (such as RSA) insecure. At the same time, quantum communication would provide an unprecedented kind of intrinsic information security at the level of the smallest physical objects used to store or transmit the information. This talk provides a general introduction to the subject of quantum information and its relevance to cyber security. In the first part, two of the stranger aspects of quantum physics namely, superposition and uncertainty are explained, along with their relation to the concept of information. These ideas are illustrated with a few examples: quantum ID cards, quantum key distribution, and Grover s quantum search algorithm. The state-of-the-art in quantum computing and communication hardware is then discussed, along with the daunting technological challenges that must be overcome. Relevant experimental and theoretical efforts at ORNL are highlighted. The talk concludes with speculations on the short- and long-term impact of quantum information on cyber security.

  17. Opportunities for Funding at NSF

    Science.gov (United States)

    Kafafi, Zakya H.

    2009-03-01

    Materials science, inter- and multi-disciplinary in nature, provides the bridge to many areas of fundamental and applied sciences such as biology, chemistry, physics, mathematics, computer sciences, and engineering. Strong links that may exist between materials science and other disciplines, such as biology or chemistry or physics, very often lead to novel applications and enable technologies of great benefit to our society. The Division of Materials Research (DMR) invested 274.0 M in FY 2008 and is estimated to invest 324.6 M in FY 2009 funding research and education as well as enabling tools & instrumentation for individual investigators, groups, centers, and national facilities. DMR programs cover a wide spectrum of materials research and education ranging from condensed matter and materials physics, solid-state and materials chemistry, multifunctional, hybrid, electronic, photonic, metallic, ceramic, polymeric, bio-materials, composites and nanostructures to list a few. New modes of funding, research opportunities and directions, such as the recent SOLAR solicitation, will be described. This Solar Energy Initiative launched jointly by three divisions, namely Chemistry, Materials Research and Mathematical Science is aimed at supporting truly interdisciplinary efforts that address the scientific challenges of highly efficient harvesting, conversion, and storage of solar energy. The goal of this new program is to create a new modality of linking the mathematical with the chemical and materials sciences to develop transformative paradigms based on the integrated expertise and synergy from three disciplinary communities. DMR is also seeking new ways to transform materials science and education, and make it more attractive as a career for bright, young women & men. A description will be given of several workshops held this year and planned for next year with this purpose in mind. Outreach programs that emphasize how the innovations resulting from materials research

  18. The becoming of an entrepreneurial opportunity

    DEFF Research Database (Denmark)

    Herholdt-Lomholdt, Sine Maria

    forms of constructivist and social-constructivist approaches, by Alvarez and Barney (Alvarez & Barney 2007; Alvarez & Barney 2010) named creation theory. Within these approaches the entrepreneurial opportunity is growing from different forms of action and co-creation either among professions or between...... a phenomenological and aesthetic approach to innovation and entrepreneurship. In this paper I pay specific attention to the ontology of opportunities from such approach and how it differs from a social-constructivist approach to opportunities as something co-created. Through this paper I show three distinct...... differences between creation theory and a phenomenological-aesthetic approach to entrepreneurial opportunities. At first opportunities within creation theory starts out in disharmonies, whereas a phenomenological-aesthetic approach would prefer to start with a sense of harmony. Second creation theory is based...

  19. Conversation, speech acts, and memory.

    Science.gov (United States)

    Holtgraves, Thomas

    2008-03-01

    Speakers frequently have specific intentions that they want others to recognize (Grice, 1957). These specific intentions can be viewed as speech acts (Searle, 1969), and I argue that they play a role in long-term memory for conversation utterances. Five experiments were conducted to examine this idea. Participants in all experiments read scenarios ending with either a target utterance that performed a specific speech act (brag, beg, etc.) or a carefully matched control. Participants were more likely to falsely recall and recognize speech act verbs after having read the speech act version than after having read the control version, and the speech act verbs served as better recall cues for the speech act utterances than for the controls. Experiment 5 documented individual differences in the encoding of speech act verbs. The results suggest that people recognize and retain the actions that people perform with their utterances and that this is one of the organizing principles of conversation memory.

  20. Triple acting radial seal

    Science.gov (United States)

    Ebert, Todd A [West Palm Beach, FL; Carella, John A [Jupiter, FL

    2012-03-13

    A triple acting radial seal used as an interstage seal assembly in a gas turbine engine, where the seal assembly includes an interstage seal support extending from a stationary inner shroud of a vane ring, the interstage seal support includes a larger annular radial inward facing groove in which an outer annular floating seal assembly is secured for radial displacement, and the outer annular floating seal assembly includes a smaller annular radial inward facing groove in which an inner annular floating seal assembly is secured also for radial displacement. A compliant seal is secured to the inner annular floating seal assembly. The outer annular floating seal assembly encapsulates the inner annular floating seal assembly which is made from a very low alpha material in order to reduce thermal stress.