WorldWideScience

Sample records for act opportunity knocks

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

    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. Opportunity Knocks: HIV Prevention in Primary Care.

    Thrun, Mark W

    2014-06-01

    Expansions in health care coverage, a comprehensive framework for HIV prevention and care, electronic medical records, and novel HIV prevention modalities create a current opportunity to change the trajectory of the HIV epidemic in the United States. HIV is increasingly disproportionately found in populations historically at higher risk, including gay men and other men who have sex with men, transgender women, injection drug users, and persons of color. This underscores the need for providers to identify persons at higher risk for HIV and assure the provision of screening and prevention services. In turn, universal screening for HIV-testing every adolescent and adult at least once in their lifetime-will increasingly be necessary to find the infrequent cases of HIV in lower risk populations. In both these domains, primary care providers will play a unique role in complementing traditional providers of HIV prevention and care services by increasing the proportion of their patients who have been screened for HIV, opening dialogues around sexual health, including asking about sexual orientation and gender identity, and prescribing antivirals as pre- and postexposure prophylaxis for their non-HIV-infected patients. Primary care providers must understand and embrace their importance along the HIV prevention and care continuum. PMID:26789615

  3. Knock knock

    Tullett, Barrie; ,

    2015-01-01

    Knock Knock is a book of concrete poetry knock knock jokes. With a couple of sight gags, a joke with an east London twang, and a low-brow cultural reference thrown in for good measure. There are two versions; a saddle stitched book with 12 jokes and a perfect bound extended cut with 16 jokes. The covers are Riso printed in a random mixture of red, black and green on different coloured stock.

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

    Ellen Os

    2014-01-01

    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 betwee...

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

    177Lu-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 177Lu-PSMA-targeted compounds.

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

    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.

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

    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.

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

    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'. PMID:26194324

  9. Missed Opportunities: The Vaccine Act of 1813

    Singla, Rohit K.

    1998-01-01

    This Paper simply exposes discontinuities between the theories and the history of the Vaccine Act, suggesting lines of further study. The focus throughout this Paper is on "getting the facts right," i.e., thoroughly recounting the history of the Vaccine Act. Part II of the paper provides some necessary historical background regarding the horrors of smallpox, the breakthrough of vaccination, and the difficulties encountered in implementing vaccination in early 19th century America. In particul...

  10. The Equal Credit Opportunity Act and Credit Rights in Housing.

    Board of Governors of the Federal Reserve System, Washington, DC.

    Designed for the general public and possibly suitable also for high school economics students, this pamphlet describes the provisions of the Equal Credit Opportunity Act. The act prohibits discrimination because of race, color, religion, national origin, sex, marital status, and age when applying for a mortgage or home improvement loan. The…

  11. The Higher Education Opportunity Act: Impact on Students with Disabilities

    Madaus, Joseph W.; Kowitt, Jennifer S.; Lalor, Adam R.

    2012-01-01

    The Higher Education Opportunity Act of 2008 (HEOA) contains several important provisions that make postsecondary education more accessible and affordable for young adults with disabilities. This is particularly true for students with intellectual disabilities, as the law created new comprehensive transition and postsecondary programs and provided…

  12. Codifying the corporate opportunity doctrine: The (UK Companies Act 2006

    John Lowry

    2012-04-01

    Full Text Available Part 10 of the UK Companies Act 2006 codifies the fiduciary and common law duties of directors as a means of addressing the key policy considerations which underpinned the company law reform project launched by the Labour Government in 1998. Focusing on the core fiduciary duty of loyalty and its corporate law manifestation in the form of the ‘corporate opportunity doctrine’, the article critically examines whether the statutory language adequately captures the totality of the duty as developed in the case law. It concludes that the formalistic language of the relevant provisions neither encompasses the breadth of the pre-existing jurisprudence nor addresses the policy objectives of the reform exercise.

  13. 75 FR 70342 - Privacy Act; System of Records: Equal Employment Opportunity Records

    2010-11-17

    ... 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... the name ``Equal Employment Opportunity Records.'' It is also proposed that the amended...

  14. 77 FR 50390 - Equal Credit Opportunity Act (Regulation B)

    2012-08-21

    ... from the Bureau's rulemaking authority by section 1029 of the Dodd-Frank Act). 76 FR 79442 (Dec. 21... policy of a government sponsored enterprise or by an automated valuation model, a broker price opinion... exemption from the appraisal delivery requirements in Sec. 1002.14 for credit unions. See 58 FR 65657,...

  15. Freedom of Information Act: Exceptional Opportunity for the Special Librarian.

    Cuddihy, Robert V.

    1980-01-01

    Provides an overview of the Freedom of Information Act (FOIA) of 1966 which established the rights of private citizens to obtain information from the federal government and the obligations of the government to provide it. Types of information generally made available, exemptions from disclosure, and creative uses of FOIA are noted. (Author/JEG)

  16. Statistical Engine Knock Control

    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...

  17. At the Center or the Margin: Massachusetts' Experience under the School-to-Work Opportunities Act.

    Diehl, William; Alex, Hoffinger; Weisstein, Ephraim

    2002-01-01

    Describes background for school-to-work effort in Massachusetts, the state's design and implementation of the School-to-Work Opportunities Act (STWOA) of 1994, the local impact of the state's STWOA grant, challenges to making school-to-work a top priority of state education reform strategies to improve student achievement, and state and local…

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

    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…

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

    Arthur M. Recesso

    1999-01-01

    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 Feder...

  20. Education and Marriage Decisions of Japanese Women and the Role of the Equal Employment Opportunity Act

    Linda N. Edwards; Takuya Hasebe; Tadashi Sakai

    2015-01-01

    Prompted by concordant upward trends in both the university advancement rate and the unmarried rate for Japanese women, this paper investigates whether the Equal Employment Opportunity Act (EEOA), which was passed in 1985, affected women•s marriage decisions either directly or via their decisions to pursue university education. To this end, we estimate a model that treats education and marriage decisions as jointly determined using longitudinal data for Japanese women. We find little eviden...

  1. How the Sarbanes-Oxley Act Has Knocked the “SOX” off the DOJ and SEC and Kept the FCPA on Its Feet

    Laura E. Kress

    2010-04-01

    Full Text Available Congress passed both the Foreign Corrupt Practices Act (“FCPA” or “the Act” and Sarbanes-Oxley Act (“SOX” in reaction to national corruption and bribery scandals.[1]  The reputation and integrity of American companies were under attack as these scandals unraveled and made international news.  Allegations of fraud, bribery and illegal practices plagued corporate America.  Congress needed legislation to address these problems to ensure its own country, as well as the international community, that the legislature would not tolerate corrupt business practices.  The FCPA was enacted to decrease corruption and bribery and to improve the accuracy of accounting and record-keeping of companies, and the SOX was enacted for very similar purposes, yet twenty five years later.  The FCPA requires companies to report their financial information in accordance with its provisions, while the SOX requires the Chief Executive Officers and Chief Financial Officers of public companies to guarantee that their financial reports are accurate.[2]  During the first twenty five years after the FCPA was enacted, the Department of Justice (“DOJ” and Securities and Exchange Commission (“SEC” did not conduct many investigations into companies that had potentially violated the Act’s provisions.  However, in the aftermath of the Enron[3] and WorldCom[4] scandals, which lead to the enactment of the SOX in 2002 and subsequent increased international awareness of the problems of bribery and financial fraud, there has been a significant increase in FCPA enforcement.[5] [1] The FCPA was enacted in 1977 in response to the Watergate scandal, and the SOX was enacted in 2002 in response to the Enron and WorldCom scandals. Lawrence A. Cunningham, Sharing Accounting’s Burden: Business Lawyers in Enron’s Dark Shadows, 57 Bus. Law. 1421, 1427 (2002 (commenting that the Enron scandal that led to the enactment of the SOX is “akin to the straw that broke the

  2. Bowlegs and Knock-Knees

    ... Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands ... and Knock-Knees Page Content Article Body Toddlers’ legs often have a bowed appearance. In fact, many children have bowing of the ...

  3. Broken or knocked out tooth

    Teeth - broken; Tooth - knocked out ... dentist right away. If your tooth is badly broken, your nerve endings may be exposed. You will ... emergency visit for a simple chip or a broken tooth that is not causing you discomfort. You ...

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

    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…

  5. 78 FR 16630 - Clean Air Act Grant: South Coast Air Quality Management District; Opportunity for Pubic Hearing

    2013-03-18

    ... AGENCY 40 CFR Part 35 Clean Air Act Grant: South Coast Air Quality Management District; Opportunity for... Quality Management District (SCAQMD) in support of its continuing air program under section 105 of the... expenditures in the programs of the South Coast Air Quality Management District. The shortfall stems from...

  6. The Science of Hard Knocks

    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…

  7. 10 CFR 905.23 - What are the opportunities for using the Freedom of Information Act to request plan and report data?

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false What are the opportunities for using the Freedom of Information Act to request plan and report data? 905.23 Section 905.23 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Integrated Resource Planning § 905.23 What are the opportunities for using the Freedom of Information Act to...

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

    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

  9. 78 FR 42942 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    2013-07-18

    ... corporate audit agreement pursuant to EPA's policy on Incentives for Self- Policing: Discovery, Disclosure, Correction and Prevention of Violations (Audit Policy), 65 FR 19618 (Apr. 11, 2000), regarding 88 office... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and...

  10. 75 FR 4552 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment, and Opportunity...

    2010-01-28

    ... Violations Final Policy Statement (Audit Policy), 65 FR 19618 (Apr. 11, 2000). Hydro also provided supplemental audit reports in 2006 and 2007. EPA and Hydro have signed an administrative Consent Agreement... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment, and...

  11. 78 FR 5800 - Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and Opportunity...

    2013-01-28

    ..., Correction and Prevention of Violations (Audit Policy), 65 FR 19,618 (April 11, 2000). EPA determined that AboveNet's disclosures satisfied all the conditions set forth in the Audit Policy, and therefore qualify... AGENCY Clean Water Act Class II: Proposed Administrative Settlement, Penalty Assessment and...

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

    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.

  13. The 1990 Clean Air Act Amendments and the Great Lakes economy: Challenges and opportunities

    This paper deals with the market for SO2 emission allowances over time and electric utility compliance choices. For currently high emitting plants ( > 2.5 lb SO2/MMBtu), the 1990 Clean Air Act Amendments (CAAA) provide for about twice as many SO2 allowances to be issued per year in Phase 1 (1995--1999) than in Phase 2. Also, considering the scrubber incentives in Phase 1, there is likely to be substantial emission banking for use in Phase 2. Allowance prices are expected to increase over time at a rate less than the return on alternative investments, so utilities which are risk neutral or other potential speculators in the allowance market are not expected to bank allowances. The allowances will be banked by risk averse utilities or the utilities may buy forward contracts for SO2 allowances. However, speculators may play an important role by selling forward contracts for SO2 allowances to the risk averse utilities. The Argonne Utility Simulation Model (ARGUS) is being revised to incorporate the provisions of the CAAA acid rain title and to simulate SO2 allowance prices, compliance choices, capacity expansion, system dispatch, fuel use, and emissions. The revised model (ARGUS2) incorporates unit-level performance data and can incorporate unit-specific compliance decisions when these are known. The model has been designed for convenience in analyzing alternatives scenarios (demand growth rates, technology mix, economic parameters, etc). 1 ref., 5 figs

  14. Pollution prevention opportunity assessment for the K-25 Site Toxic Substances Control Act Incinerator Operations, Level III

    A Level III pollution prevention opportunity assessment (PPOA) was performed for the Oak Ridge K-25 Site Toxic Substances Control Act (TSCA) Incinerator to evaluate pollution prevention (P2) options for various waste streams: The main objective of this study was to identify and evaluate options to reduce the quantities of each waste stream generated by the TSCA Incinerator operations to realize significant environmental and/or economic benefits from P2. For each of the waste streams, P2 options were evaluated following the US Environmental Protection Agency (EPA) hierarchy to (1) reduce the quantity of waste generated, (2) recycle the waste, and/or (3) use alternate waste treatment or segregation methods. This report provides process descriptions, identification and evaluation of P2 options, and final recommendations

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

    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. PMID:26916628

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

    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.

  17. Opportunity Design

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

    2012-01-01

    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....

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

    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.

  19. Handbook for Sponsors; Standards and Procedures for Work-Training Experience Programs under the Economic Opportunity Act of 1964, as Amended.

    Manpower Administration (DOL), Washington, DC. Bureau of Work-Training Programs.

    The standards and procedures presented establish the basic rules governing the development and operation of various programs administered by the U.S. Department of Labor, Bureau of Work Programs under the Economic Opportunity Act of 1964, as amended. Basic standards relate to qualification of sponsors, eligibility of enrollees, hours of work,…

  20. Knocking in an Internal-combustion Engine

    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.

  1. Knock out for subthreshold pion production

    The contribution of nucleon-nucleon-single collisions to subthreshold pion production in hadron-nucleus and nucleus-nucleus collisions, Esub(Lab) < 300 A MeV is investigated within a knock-out type model. This contribution might be important for energies higher than about 150 MeV/nucleon but decrease strongly with decreasing beam energy

  2. 76 FR 54773 - Notice of Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA...

    2011-09-02

    ..., for programs authorized by the public Health Services Act, for prevention, wellness and public health... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This...

  3. Frequency domain analysis of knock images

    High speed imaging-based knock analysis has mainly focused on time domain information, e.g. the spark triggered flame speed, the time when end gas auto-ignition occurs and the end gas flame speed after auto-ignition. This study presents a frequency domain analysis on the knock images recorded using a high speed camera with direct photography in a rapid compression machine (RCM). To clearly visualize the pressure wave oscillation in the combustion chamber, the images were high-pass-filtered to extract the luminosity oscillation. The luminosity spectrum was then obtained by applying fast Fourier transform (FFT) to three basic colour components (red, green and blue) of the high-pass-filtered images. Compared to the pressure spectrum, the luminosity spectra better identify the resonant modes of pressure wave oscillation. More importantly, the resonant mode shapes can be clearly visualized by reconstructing the images based on the amplitudes of luminosity spectra at the corresponding resonant frequencies, which agree well with the analytical solutions for mode shapes of gas vibration in a cylindrical cavity. (paper)

  4. The Americans With Disabilities Act: Equal Opportunity for Individuals With Disabilities, in Some Large Businesses, in Some Major Cities, Sometimes . . .

    Eric Allen Harris

    2008-04-01

    Full Text Available On July 26, 1990, the Americans with Disabilities Act (ADA was signed into law by President George H.W. Bush. Congress stated that the purpose of the ADA was “to provide a clear and comprehensive national mandate for the elimination of discrimination against individuals with disabilities.” The first subchapter (Title I of the ADA addresses accommodations for the disabled in the field of employment. President Bush attempted to quash “fears that the ADA is too vague or too costly” by stating that the Act struck a careful balance between the rights of individuals with disabilities and the legitimate interests of businesses. In particular, he noted that Title I of the ADA would become effective for employers with twenty-five or more employees on July 26, 1992, with an extension to employers with fifteen or more employees on July 26, 1994, thus permitting employers adequate time to become acquainted with the ADA. But in fact, the exclusion of employers with fewer than fifteen employees requires only a small percentage of the nation’s employers to ever become acquainted with the ADA at all.

  5. American Society of Clinical Oncology policy statement: opportunities in the patient protection and affordable care act to reduce cancer care disparities.

    Moy, Beverly; Polite, Blase N; Halpern, Michael T; Stranne, Steven K; Winer, Eric P; Wollins, Dana S; Newman, Lisa A

    2011-10-01

    Patients in specific vulnerable population groups suffer disproportionately from cancer. The elimination of cancer disparities is critically important for lessening the burden of cancer. The Patient Protection and Affordable Care Act provides both opportunities and challenges for addressing cancer care disparities and access to care. The American Society of Clinical Oncology (ASCO) advocates for policies that ensure access to cancer care for the underserved. Such policies include insurance reform and the reduction of economic barriers to quality health care. Building on ASCO's prior statement on disparities in cancer care (2009), this article summarizes elements of the health care law that are relevant to cancer disparities and provides recommendations for addressing major provisions in the law. It outlines specific strategies to address insurance reform, access to care, quality of care, prevention and wellness, research on health care disparities, and diversity in the health care workforce. ASCO is committed to leading efforts toward the improvement of cancer care among the most vulnerable patients. PMID:21810680

  6. The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

    Kei Miyamoto

    Full Text Available Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0 needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN mRNA to oocytes at the germinal vesicle (GV stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.

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

    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. PMID:20844424

  8. Knock characteristics of dual-fuel combustion in diesel engines using natural gas as primary fuel

    O M I Nwafor

    2002-06-01

    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 have the ignition stage followed by the combustion stage. There are three types of knock: diesel knock, spark knock and knock due to secondary ignition delay of the primary fuel (erratic knock). Several factors have been noted to feature in defining knock characteristics of dual-fuel engines that include ignition delay, pilot quantity, engine load and speed, turbulence and gas flow rate.

  9. William Knocke receives 2008 Virginia Outstanding Civil Engineer Award

    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.

  10. A Scholar Who Knocks at the Door to Friendship

    TangRuimin

    2004-01-01

    Senegalese scholar Adama Gaye came from far away Africa to visit China in March when there was still a chill in the early spring air. He is not an ordinary scholar, but an African friend who has come to knock at the door to friendship.

  11. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii.

    Shin, Sung-Eun; Lim, Jong-Min; Koh, Hyun Gi; Kim, Eun Kyung; Kang, Nam Kyu; Jeon, Seungjib; Kwon, Sohee; Shin, Won-Sub; Lee, Bongsoo; Hwangbo, Kwon; Kim, Jungeun; Ye, Sung Hyeok; Yun, Jae-Young; Seo, Hogyun; Oh, Hee-Mock; Kim, Kyung-Jin; Kim, Jin-Soo; Jeong, Won-Joong; Chang, Yong Keun; Jeong, Byeong-Ryool

    2016-01-01

    Genome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including "safe harboring" techniques shown in other organisms. PMID:27291619

  12. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii

    Shin, Sung-Eun; Lim, Jong-Min; Koh, Hyun Gi; Kim, Eun Kyung; Kang, Nam Kyu; Jeon, Seungjib; Kwon, Sohee; Shin, Won-Sub; Lee, Bongsoo; Hwangbo, Kwon; Kim, Jungeun; Ye, Sung Hyeok; Yun, Jae-Young; Seo, Hogyun; Oh, Hee-Mock; Kim, Kyung-Jin; Kim, Jin-Soo; Jeong, Won-Joong; Chang, Yong Keun; Jeong, Byeong-ryool

    2016-01-01

    Genome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including “safe harboring” techniques shown in other organisms. PMID:27291619

  13. Knock Detection in a Two-Stroke Engine to be Used in the Engine Management System

    Höglund, Filip

    2014-01-01

    Engine knock has long been a well recognized phenomenon in the automotive industry. Detecting engine knock opens up the possibility for an indirect feedback of the engine's internal combustion without installing a pressure transducer inside the cylinder. Knock detection has mainly been used for spark advance control, making it possible to control the engine close to its knock limit in search for the optimal ignition timing. This application has to a lesser extent been applied to lightweight t...

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

    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 to...

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

    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.

  16. Wiring knock-knee layouts: A global approach

    Sarrafzadeh, Majid; Wagner, Dorothea; Wagner, Frank; Weihe, Karsten

    1994-05-01

    We present a global approach to solve the three-layer wirability problem for knock-knee layouts. In general, the problem is NP-complete. Only for very restricted classes of layouts polynomial three-layer wiring algorithms are known up to now. In this paper, we show that for a large class of layouts a three-layer wiring can be constructed by solving a path problem in a special class of graphs or a two-satisfiability problem, and thus may be wired in time linear in the size of the layout area. Moreover, it is shown that a minimum stretching of the layout into a layout belonging to this class can be found by solving a clique cover problem in an interval graph. This problem is solvable in time linear in the size of the layout area as well. Altogether, the method also yields a good heuristic for the three-layer wirability problem for knock-knee layouts.

  17. Opportunity Knocks! Inquiry, the New National Social Studies and Science Standards, and You

    Ratzer, Mary Boyd

    2014-01-01

    To be recognized and adopted, the promise and potential of national standards must validate the instructional role of the school librarian and build formative knowledge through authentic process and products. Inquiry is a direct link to those dimensions. Standards that are rigorous and relevant optimize the developing brain's affinity for…

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

    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…

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

    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.

  20. Opportunities for computer abuse

    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...

  1. System and method for controlling engine knock using electro-hydraulic valve actuation

    Brennan, Daniel G

    2013-12-10

    A control system for an engine includes a knock control module and a valve control module. The knock control module adjusts a period that one or more of an intake valve and an exhaust valve of a cylinder are open based on engine knock corresponding to the cylinder. The valve control module, based on the adjusted period, controls the one or more of the intake valve and the exhaust valve using one or more hydraulic actuators.

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

    R. Sivabalakrishnan; Jegadheesan, C.

    2014-01-01

    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 q...

  3. 78 FR 26031 - Sunshine Act Notice

    2013-05-03

    ... From the Federal Register Online via the Government Publishing Office EQUAL EMPLOYMENT OPPORTUNITY COMMISSION Sunshine Act Notice AGENCY HOLDING THE MEETING: Equal Employment Opportunity Commission DATE AND.... Wellness Programs Under Federal Equal Employment Opportunity Laws. Note: In accordance with the...

  4. Numerical and experimental characterization of knock occurrence in a turbo-charged spark-ignition engine

    Highlights: • An index of knock intensity has been based on the cylinder pressure oscillations. • This index allows to set the knock limited spark at different engine operating points. • The influence of the transducer position on the measurement of the pressure oscillations is investigated. - Abstract: In this paper, knock intensity is deeply studied through experimental tests carried out on a turbo-charged spark-ignition engine. The experimental methodology is based on the analysis of the pressure signals detected within the engine combustion chamber. In order to evaluate knock intensity, fast Fourier transform (FFT) and bandpass filtering techniques have been used to process the cylinder pressure values acquired in five hundred consecutive cycles. Resonance frequencies have been found at about 8.0 kHz, 13.5 kHz and 18.5 kHz. The maximum amplitude of pressure oscillations (MAPO) has been calculated for every engine cycle. In order to discriminate between knocking cycles and free knock cycles, MAPO values are compared to threshold values. These values have been determined following a statistical approach described in the paper. An index of knock intensity, that takes into account both the extent of knocking events and the cycle- to-cycle variation has been introduced. Thus, at different engine operating points, the knock limited spark advance can be found. At the end, a numerical analysis of the combustion process has been carried out in order to find a relationship between the knock occurrence and the combustion chamber geometry. A 3-D computational model, based on AVL FIRE v2011 code, has been utilized. The 3-D model is able to predict the auto-ignition zones. By matching these zones and the map of mixture distribution, it is possible to predict the location of the most dangerous areas within the combustion chamber. Furthermore, comparisons of calculated and measured data provide sound information about the importance of pressure transducer position in

  5. Opportunity Design

    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 to...

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

    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

  7. HOLA: Hunt for Opportunities-Learn-Act

    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…

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

    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.

  9. 76 FR 31451 - Equal Credit Opportunity

    2011-06-01

    ... / Wednesday, June 1, 2011 / Rules and Regulations#0;#0; ] FEDERAL RESERVE SYSTEM 12 CFR Part 202 Equal Credit.... SUMMARY: The Board is publishing amendments to Regulation B (Equal Credit Opportunity Act) to update the...) 263-4869. SUPPLEMENTARY INFORMATION: The Equal Credit Opportunity Act (ECOA), 15 U.S.C....

  10. 76 FR 59237 - Equal Credit Opportunity

    2011-09-26

    ... 7100 AD 78 Equal Credit Opportunity AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule. SUMMARY: The Board is publishing a final rule amending Regulation B (Equal Credit Opportunity). Section 704B of the Equal Credit Opportunity Act (ECOA), as added by Section 1071 of the...

  11. Determination of knock characteristics in spark ignition engines: an approach based on ensemble empirical mode decomposition

    Li, Ning; Yang, Jianguo; Zhou, Rui; Liang, Caiping

    2016-04-01

    Knock is one of the major constraints to improve the performance and thermal efficiency of spark ignition (SI) engines. It can also result in severe permanent engine damage under certain operating conditions. Based on the ensemble empirical mode decomposition (EEMD), this paper proposes a new approach to determine the knock characteristics in SI engines. By adding a uniformly distributed and finite white Gaussian noise, the EEMD can preserve signal continuity in different scales and therefore alleviates the mode-mixing problem occurring in the classic empirical mode decomposition (EMD). The feasibilities of applying the EEMD to detect the knock signatures of a test SI engine via the pressure signal measured from combustion chamber and the vibration signal measured from cylinder head are investigated. Experimental results show that the EEMD-based method is able to detect the knock signatures from both the pressure signal and vibration signal, even in initial stage of knock. Finally, by comparing the application results with those obtained by short-time Fourier transform (STFT), Wigner-Ville distribution (WVD) and discrete wavelet transform (DWT), the superiority of the EEMD method in determining knock characteristics is demonstrated.

  12. Seizing Opportunity

    2006-01-01

    After the remarkable progress of the past five years, China has entered its new five-year plan period, starting from 2006, aiming to further its economic and social development. Though some are still talking about "China threat," many others consider the country's growth a huge opportunity. In an interview with People's Daily, Bill Fischer, former President of the Sino-European International Business School in Shanghai, comments on China's current development and also talks about problems the country fac...

  13. Utilization of Detection and Identification of Detonation (Knock) Using a Wavelet to Create a Chart for a Petrol Engine’s Characteristics

    Agus Sujono; R. Soekrisno; Eka Firmansyah; Oyas Wahyunggoro

    2015-01-01

    The development of internal combustion engine always facing with the knock problem., Indeed, the characteristics of a motor engine itself is determined by the knocking issue. In this study, a method of knocking detection through simple microphone sensor has been developed. It incorporates discrete wavelet transformation (DWT) analysis and the regression function of the sound wave envelope to identify the occurrance of knock. After detecting the knock, a 3D engine ignition chart (characteri...

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

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

    2016-01-01

    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. PMID:26817820

  15. Analysis of pressure waves in the cone-type combustion chamber under SI engine knock

    Highlights: • A 3D numerical model is conducted to investigate the shock waves in the engine knock. • Overpressure distribution on the top piston surface is caught while knocking. • Numerical simulation shows that shock waves converge in the combustion chamber. • The converged shock waves damage piston during severe knock. - Abstract: For the internal-combustion engine, super knock produced by the engine downsizing technology induces severe oscillations in a combustion chamber, which may damage the piston. In this work, 3D numerical simulation is used to study the propagation and reflection of pressure waves produced in the cone roof type combustion chamber. Overpressure distribution of top piston surface is caught. Numerical simulation shows that the pressure waves are amplified in a special zone because of the shape of the combustion chamber, which induces the overpressure much higher than that in other zones. The numerical results are validated by the damaged pistons. It is found that the converged pressure waves could be the reason which causes damage in the local region of the piston under super knock. The results obtained in the study provide assistance in the design of combustion chamber shape in order to avoid piston destroyed by the pressure waves

  16. Estimation of knock acoustical signal by parametric inversion method; Estimation du signal acoustique de cliquetis par inversion parametrique

    Boubal, O.; Oksman, J. [Ecole Superieure d' Electricite, 91 - Gif-sur-Yvette (France)

    1999-07-01

    Knock on spark ignition engines goes against car manufacturers efforts to reduce fuel consumption and exhaust gas emissions. This article develops a signal processing method to quantify knock. After discussing some classical techniques of knock energy estimation, an acoustical measurement technique is presented. An original signal processing method based on a parametric behavioral model for both knock and apparatus and a special inversion technique are used to get actual knock parameters. The knock related parameters are computed in a two step process. A deconvolution algorithm is used to obtain a signal made of unitary pulses, followed by an efficient inversion method. The whole process is applied to real data from a one-cylinder engine. Moreover, the results are compared to those obtained from an existing technique to suit a common industrial application. (authors)

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

    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.

  18. A model of knock-out of oxygen by charged particle irradiation of Bi-2212

    A model of knock-out of oxygen by charged particle (α and proton) irradiation of Bi2Sr2CaCu2O8+x (Bi-2212) is proposed on the basis of Monte Carlo TRIM calculations. In Bi-2212, the loosely bound excess oxygen is vulnerable to be displaced by particle irradiation. Binding energy and hence, displacement energy of this loosely bound excess oxygen is less compared to that of stoichiometric lattice bound oxygen and other atoms. The displaced or knocked out oxygen goes to pores or intergranular region and generates large pressure inside the sample. Because of porosity of the material, this displaced oxygen diffuses out and there is a net reduction of oxygen content of the sample. The irradiation induced oxygen knock-out is dominant in the bulk where nonionizing energy loss is maximum. (author). 29 refs., 1 fig., 3 tabs

  19. Chinese M&A,Opportunities & Risks

    Tang Jintao

    2009-01-01

    @@ Recently, the cases of Chinese enterprises' merger and acquisition are emerging in multitude. It is believed that M&A will provide opportunities for China enterprises to go global and act in the global economic environment.

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

    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.

  1. (p, α) reactions: knock-on(out) or pick-up

    Nothwithstanding the great lot of data collected starting from the beginning of fifties, it cannot be said that a good degree of knowledge about the (p, α) reaction mechanism has been reached. Experimental data are usually interpreted or on the basis of a pure pick-up or knock-on(out) mechanism, though many results suggest the importance of both mechanism

  2. Hematopoiesis in 5-Fluorouracil-Treated Adenosine A(3) Receptor Knock-Out Mice

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2015-01-01

    Roč. 64, č. 2 (2015), s. 255-262. ISSN 0862-8408 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor knock-out mice * Hematopoiesis * 5-fluorouracil-induced hematotoxicity Subject RIV: BO - Biophysics Impact factor: 1.293, year: 2014

  3. Generation and basic characterization of glutamate carboxypeptidase II knock-out mice

    Vorlová, Barbora; Kašpárek, Petr; Šácha, Pavel; Sedláček, Radislav; Konvalinka, Jan

    2016-01-01

    Roč. 25, č. 2 (2016), s. 267. ISSN 0962-8819. [Transgenic Technology Meeting (TT2016) /13./. 20.03.2016-23.03.2016, Praha] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : GCPII * PSMA * FolhI * knock-out mice Subject RIV: CE - Biochemistry

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

    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 frac

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

    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.

  6. Study of knock in a high compression ratio SI methanol engine using LES with detailed chemical kinetics

    Highlights: • Knock in a high compression ratio spark ignition methanol engine was simulated. • We used LES coupled with detailed chemical kinetics to simulate knock. • OH radical was the predominant species during knocking combustion. • Weak species such as H2O2, CH2O, HO2 and HCO were also detected during knocking. • The stronger the reaction rate, the higher the knock intensity. - Abstract: Methanol as an alternative fuel is considered to be one of the most favorable fuels for internal combustion engines. In this paper, knock in a high compression ratio SI (Spark Ignition) methanol engine was studied by using LES (Large Eddy Simulation) coupled with detailed chemical kinetics. A 21-species, 84-reaction methanol reaction mechanism was adopted to simulate the auto-ignition and combustion process of the methanol/air mixture. The results showed that the end-gas auto-ignition first occurred in the place near the chamber wall because of the higher temperature and pressure. The evolution of OH radicals was essentially the same with the evolution of in-cylinder temperature. OH radicals could be a good temperature indicator. The concentration of HCO radicals was almost negligible during knocking combustion. There existed two effects for CH2O, OH, and H2O2, which were generation and consumption. The reaction intensities of CO, CH2O, H2O2, and OH species were higher than other species during knocking combustion

  7. 76 FR 70131 - Sunshine Act Notice

    2011-11-10

    ... From the Federal Register Online via the Government Publishing Office EQUAL EMPLOYMENT OPPORTUNITY COMMISSSION Sunshine Act Notice AGENCY HOLDING THE MEETING: Equal Employment Opportunity Commission. DATE AND... Discrimination in Employment Act, and 3. Overcoming Barriers to the Employment of Veterans with...

  8. Simulation research on the effect of cooled EGR, supercharging and compression ratio on downsized SI engine knock

    Shu, Gequn; Pan, Jiaying; Wei, Haiqiao; Shi, Ning

    2013-03-01

    Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three-dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.

  9. In-vitro Knock Down of VEGFR2 Expression Using Specific siRNA in the Culture Medium

    Moslem Jafarisani

    2015-09-01

    Full Text Available Introduction:The use of siRNAforsilencinggene expressionis expandingtoday. Knock down ofvascular endothelial growth factor is one of theobjectives ofthistechnology. In this study we aimed to inhibit the expression of receptor type II of VEGF (VEGFR-2 using specific siRNA in the culture medium.Methods: First, according to the target gene sequences, sequence of the specific siRNA were designed; blasted and built. Using RT-PCR, cDNA of HUVEC was synthesized and PCR with specific primers was reproduced. PEFGP-N1 expression vector was cloned with target gene and confirmed. Then Hela cells which has not any expression of the target genes were transfected whit cloned pEGFP-N1 vector using lipofectamin. GFP expression rate in the Hela cellsContaining initial vector and cloned vector in presence and absence of specific siRNA was assessed. Through evaluation of gene inhibition, decreasing of green fluorescence from GFP, RT-PCR was investigated.Results: The results of the two used siRNA, indicate reduced gene expression 56% and 63% in comparison with the control group (P<0.05.Conclusion: Transfection of specific VEGFR-2 siRNA using lipofectamin significantly inhibits expression of receptor. In fact,it cancut thesignal transduction pathwayand preventsthe creation ofnewblood vessels. Therefore, probably it can act as a new treatment factor for prevention or reduction of neovascularization.

  10. Numerical analysis of knock during HCCI in a high compression ratio methanol engine based on LES with detailed chemical kinetics

    Highlights: • Knock during HCCI in a high compression ratio methanol engine was modeled. • A detailed methanol mechanism was used to simulate the knocking combustion. • Compared with the SI engines, the HCCI knocking combustion burnt faster. • The reaction rate of HCO had two obvious peaks, one was positive, and another was negative. • Compared with the SI engines, the values of the reaction rates of CH2O, H2O2, and HO2 were higher, and it had negative peaks. - Abstract: In this study, knock during HCCI (homogeneous charge compression ignition) was studied based on LES (large eddy simulation) with methanol chemical kinetics (84-reaction, 21-species) in a high compression ratio methanol engine. The non-knocking and knocking combustion of SI (spark ignition) and HCCI engines were compared. The results showed that the auto-ignition spots were initially occurred near the combustion chamber wall. The knocking combustion burnt faster during HCCI than SI methanol engine. The HCO reaction rate was different from SI engine, it had two obvious peaks, one was positive peak, and another was negative peak. Compared with the SI methanol engine, in addition to the concentration of HCO, the concentrations of the other intermediate products and species such as CO, OH, CH2O, H2O2, HO2 were increased significantly; the reaction rates of CH2O, H2O2, and HO2 had negative peaks, and whose values were several times higher than SI methanol engine

  11. ACT Test

    ... ACT. It is important to evaluate how the person is responding to this ACT lower limit and to the amount of heparin ... to determine someone's heparin anticoagulant requirements, stabilize the person, and then change the monitoring tool. The ACT may be influenced by a person's platelet count ...

  12. Orthogonal gene knock out and activation with a catalytically active Cas9 nuclease

    Dahlman, James E.; Abudayyeh, Omar O.; Joung, Julia; Gootenberg, Jonathan S.; Zhang, Feng; Konermann, Silvana

    2015-01-01

    We have developed a CRISPR-based method that uses catalytically active Cas9 and distinct sgRNA constructs to knock out and activate different genes in the same cell. These sgRNAs, with 14 15 bp target sequences and MS2 binding loops, can activate gene expression using an active Cas9 nuclease, without inducing DSBs. We use these ‘dead RNAs’ to perform orthogonal gene knockout and transcriptional activation in human cells.

  13. Behavioural and molecular responses to amphetamine in the neurokinin-1 receptor knock-out mouse

    Slone-Murphy, J.

    2011-01-01

    The neurokinin-1 receptor knock-out (NK1R-/-) mouse is hyperactive and shows deficits in attentional processing, and has recently been put forward as a model of attention deficit hyperactivity disorder (ADHD). Acute amphetamine, a first-line treatment for ADHD and a drug of abuse, paradoxically reduces the hyperactivity of NK1R-/- mice, and the characteristic amphetamine-stimulated increase in striatal dopamine efflux seen in wild-type animals is attenuated in NK1R-/- mice. The...

  14. CRISPR/Cas9-Mediated Gene Knock-Down in Post-Mitotic Neurons

    Christoph Straub; Granger, Adam J.; Saulnier, Jessica L.; Sabatini, Bernardo L.

    2014-01-01

    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 CRI...

  15. Proton Beam Fast Ignition Fusion: Nonlinear Generation of Bθ-Fields by Knock-on Electrons

    Stefan, V. Alexander

    2011-10-01

    The knock-on electrons, generated by the fast proton beam in interaction with the free and bound electrons in a precompressed DT fusion pellet, outrun the proton beam, generating the Bθ-fields ahead of the beam, which may lead to the defocusing of the beam, if Bθ Tabak et al, Phys. Plasmas 1 (5), 1626 (1994); H. L. Buchanan, F. W. Chambers, E. P. Lee, S. S. Yu, R. J. Briggs, and M. N. Rosenbluth, LLNL, UCRL Report 82586, 1979.

  16. Combustion Analysis and Knock Detection in Single Cylinder DI-Diesel Engine Using Vibration Signature Analysis

    Y.V.V.SatyanarayanaMurthy

    2011-01-01

    The purpose of this paper is to detect the “knock” in Diesel engines which deteriorate the engine performance adversely. The methodology introduced in the present work suggests a newly developed approach towards analyzing the vibration analysis of diesel engines. The method is based on fundamental relationship between the engine vibration pattern and the relative characteristics of the combustion process in each or different cylinders. Knock in diesel engine is detected by measuring the vibra...

  17. Effect of Tbxl knock-down on cardiac performance in zebrafish

    ZHANG Li-feng; GUI Yong-hao; WANG Yue-xiang; JIANG Qiu; SONG Hou-yan

    2010-01-01

    Background Tbxl is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbxl-/- animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbxl knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbxl morpholino injected zebrafish embryos. Methods To elucidate these issues, Tbxl specific morpholino was used to reduce the function of Tbxl in zebrafish. The differentiation of the myocardial cells was observed using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf). The cardiac performance was analyzed by measuring ventricular shortening fraction and atrial shortening fraction.Results Tbxl morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbxl knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbxl morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbxl morpholino injected embryos.Conclusions Tbxl might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbxl knock down in zebrafish.

  18. ACTS 2014

    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....... 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...

  19. School-to-Work Opportunities. Fair Labor Standards Act and the North Carolina Wage and Hour Act. A Guide to Work-Based Learning, Federal and State Child Labor Laws, Minimum Wage Provisions, and the Provisions of Comparable North Carolina Laws. 3rd Edition.

    North Carolina State Dept. of Labor, Raleigh.

    This guide for work-based learning, the Fair Labor Standards Act (FLSA), and the North Carolina Wage and Hours Act is designed to serve employers, educators, agency placement staff, labor organizations, and all those involved in school-to-work initiatives by helping them to understand a variety of issues related to students in the workplace. Based…

  20. 76 FR 36885 - Regulation B; Equal Credit Opportunity

    2011-06-23

    ...; ] FEDERAL RESERVE SYSTEM 12 CFR Part 202 RIN No. 7100-AD-78 Regulation B; Equal Credit Opportunity AGENCY.... SUMMARY: The Board is publishing for public comment a proposed rule amending Regulation B (Equal Credit Opportunity). Section 704B of the Equal Credit Opportunity Act (ECOA), as added by Section 1071 of the...

  1. Utilization of Detection and Identification of Detonation (Knock Using a Wavelet to Create a Chart for a Petrol Engine’s Characteristics

    Agus Sujono

    2015-04-01

    Full Text Available The development of internal combustion engine always facing with the knock problem., Indeed, the characteristics of a motor engine itself is determined by the knocking issue. In this study, a method of knocking detection through simple microphone sensor has been developed. It incorporates discrete wavelet transformation (DWT analysis and the regression function of the sound wave envelope to identify the occurrance of knock. After detecting the knock, a 3D engine ignition chart (characteristic can be created as demonstrated in this paper.

  2. Programació dinàmica de port knocking per a dispositius mòbils

    ALBUJER RICO, PEDRO

    2015-01-01

    [ES] Desarrollar una aplicación móvil, e implementarla bajo IOS y Android, con el objeto de acceder a un port knocking en la parte servidora, que reprograme temporalmente el cortafuegos. Albujer Rico, P. (2015). Programació dinàmica de port knocking per a dispositius mòbils. http://hdl.handle.net/10251/56572. TFGM

  3. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R; Subramaniam, Meena; Gate, Rachel E; Haliburton, Genevieve E; Ye, Chun J; Bluestone, Jeffrey A; Doudna, Jennifer A; Marson, Alexander

    2015-08-18

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells. PMID:26216948

  4. An Improved Method to Knock Out the asd Gene of Salmonella enterica Serovar Pullorum

    Shi-Zhong Geng

    2009-01-01

    Full Text Available An asd-deleted (Δasd mutant of Salmonella enterica serovar Pullorum (SP was constructed using an improved method of gene knockout by combining the π-suicide plasmid system with the Red Disruption system. The asd gene was efficiently knocked out by the recombinant suicide vector, which replaced the asd gene with the CmR gene. Based on the balanced lethal host-vector system, the phenotype of the Δasd mutant was further defined. The improved method was simpler and more effective than previously reported conventional methods.

  5. Elektrophysiologische Hörmessung bei Megalin-knock-out-Mäusen

    König, O; Rüttiger, L; Knipper, M.; Bohlender, J; Willnow, T.; Gross, M.

    2005-01-01

    Einleitung: Megalin ist ein zur LDL-Rezeptorgruppe gehörendes Membranrezeptorprotein. Untersuchungen am Innenohrepithel der embryonalen Maus zeigen, dass der Megalinrezeptor dort exprimiert wird . An erstmals zur Verfügung stehenden Megalin-Knock-out-Mäusen soll das Hörvermögen bei Fehlen des Megalinrezeptors untersucht werden.Material und Methode: Die perinatale Überlebensrate der KO-Mäuse beträgt - bedingt durch eine hohe Missbildungsrate - lediglich 2-5%, so dass nur wenige Mäuse zur Verfü...

  6. MADD Knock-Down Enhances Doxorubicin and TRAIL Induced Apoptosis in Breast Cancer Cells

    Andrea Turner; Liang-Cheng Li; Tania Pilli; Lixia Qian; Elizabeth Louise Wiley; Suman Setty; Konstantin Christov; Lakshmy Ganesh; Maker, Ajay V; Peifeng Li; Prasad Kanteti; Tapas K Das Gupta; Prabhakar, Bellur S.

    2013-01-01

    The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in duct...

  7. Lack of Self-Administration of Cocaine in Dopamine D1 Receptor Knock-Out Mice

    Caine, S. Barak; Thomsen, Morgane; Gabriel, Kara I.; Berkowitz, Jill S.; Gold, Lisa H.; Koob, George F; Tonegawa, Susumu; Zhang, Jianhua; Xu, Ming

    2007-01-01

    Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, “knock-out” of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied...

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

    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%.

  9. The mechanism of the (p,α) reaction: pick-up or knock-out

    Several early studies of the (p,α) reaction to discrete states of the final nucleus indicated that it proceeds mainly by the pick-up mechanism, whereas more recent experiments provide qualitative arguments in favour of the knock-out mechanism. This paper reports calculations showing that the angular distributions and analysing powers of the sup(90,92)Zr(p,α)sup(87,89)Y and 118Sn(p,α)115In reactions can be equally well fitted by distorted wave calculations using either mechanism. (author)

  10. Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing

    Besaratinia, Ahmad; Pfeifer, Gerd P

    2010-01-01

    Tumor-driving mutations in the TP53 gene occur frequently in human cancers. These inactivating mutations arise predominantly from a single-point mutation in the DNA-binding domain of this tumor suppressor gene (i.e., exons 4–9). The human p53 knock-in (Hupki) mouse model was constructed using gene-targeting technology to create a mouse strain that harbors human wild-type TP53 DNA sequences in both copies of the mouse TP53 gene. Replacement of exons 4–9 of the endogenous mouse TP53 alleles in ...

  11. RECOVERY ACT: TAPOCO PROJECT: CHEOAH UPGRADE

    Tran, Paul

    2013-02-28

    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.

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

    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.

  13. Rosa26-targeted sheep gene knock-in via CRISPR-Cas9 system

    Wu, Mingming; Wei, Caihong; Lian, Zhengxing; Liu, Ruizao; Zhu, Caiye; Wang, Huihua; Cao, Jiaxue; Shen, Yuelei; Zhao, Fuping; Zhang, Li; Mu, Zhu; Wang, Yayu; Wang, Xiaogang; Du, Lixin; Wang, Chuduan

    2016-01-01

    Recent advances in our ability to design DNA binding factors with specificity for desired sequences have resulted in a revolution in genetic engineering, enabling directed changes to the genome to be made relatively easily. Technologies that facilitate specific and precise genome editing, such as knock-in, are critical for determining the functions of genes and for understanding fundamental biological processes. The CRISPR/Cas9 system has recently emerged as a powerful tool for functional genomic studies in mammals. Rosa26 gene can encode a non-essential nuclear RNA in almost all organizations, and become a hot point of exogenous gene insertion. Here, we describe efficient, precise CRISPR/Cas9-mediated Integration using a donor vector with tGFP sequence targeted in the sheep genomic Rosa26 locus. We succeeded in integrating with high efficiency an exogenous tGFP (turboGFP) gene into targeted genes in frame. Due to its simplicity, design flexibility, and high efficiency, we propose that CRISPR/Cas9-mediated knock-in will become a standard method for the generation transgenic sheep. PMID:27063570

  14. A new alpha particle diagnostic using knock-on ion tails

    We propose a new method of measuring the fast confined ct-particle distribution in a reacting plasma. The presence of ct-particles in a D-T plasma will create a high energy tail on the deuterium and tritium ion energy distributions. A 3.5 MeV alpha can transfer 3.4 MeV to a tritium ion in a single elastic scattering interaction. Calculations of the size of these knock-on tails in tokamaks such as TFTR, JET, and ITER show that it may be possible to measure these tails and provide information on the fast confined alphas. The knock-on tail ions will produce D-T neutrons with energies up to 20.7 MeV, so that D-T neutron spectroscopy can be used to monitor the alpha population. Neutron spectroscopy looks especially attractive for ITER. A collimated array of threshold neutron activation detectors could be used to deduce the confined alpha density profile. Tests of this diagnostic can also be done on TFTR and JET. Existing high energy neutral particle analyzers may allow observation of the ion tails directly via passive and/or active charge exchange

  15. Measurement of ν-values for TARN by the RF knock-out method

    The number of betatron oscillations per revolution (ν-value) can be measured experimentally by an RF knock-out method. The principle of the method is formulated. The RF knock-out system for TARN was desgned and constructed. Its design and specifications are described in detail. The experimental results with H2+ and He2+ beams with the kinetic energy of 7 MeV/u are compared with the calculation with the computer program SYNCH. The νsub(x) and νsub(z) were measured to be 2.29 and 2.12, respectively, for the excitation currents of the quadrupole magnets; I sub(D) = 121 A (G sub(D) = 0.212 kG/cm) and I sub(F) = 74.5 A (G sub(F) = 0.131 kG/cm). The calculation indicates that the corresponding values are 2.21 and 2.19, respectively, which are in fairly good agreement with the experimental ones. (author)

  16. Detection of knock occurrence in a gas SI engine from a heat transfer analysis

    This paper focuses on the transient thermal signal around an engine cylinder in order to propose a new and non-intrusive method of knock detection. Numerical simulations of unsteady heat transfer through the cylinder and inside the coolant flow are performed. The amplification of wall heat transfer due to knock is taken into account by a self-developed program. It enables one to fix the instantaneous heat flux on the internal side of the cylinder. The transient component of the thermal signal is then calculated and analysed. The effect of a machining, consisting of a transverse groove, which reduces the cylinder liner thermal resistance, is investigated. This groove disturbs the turbulent coolant flow, and its shape mainly influences the heat transfer from the wall to the fluid. The numerical results show that the use of a square groove would multiply by three the amplitude of the transient thermal signal recorded within the water compared to a smooth wall case. Moreover, the amplitude can be enhanced by using a nanofluid as coolant because of its higher thermal diffusivity

  17. Oxygen knock-out and other studies in α-irradiated polycrystalline Bi-2212 superconductor

    Bulk polycrystalline samples of Bi2Sr2CaCu2O8+σ (Bi-2212) have been irradiated with 40 MeV α-particles. Tc increases up to a certain dose. The increase in Tc is correlated with the knock-out of oxygen, which has been verified by the determination of the oxygen contents of the irradiated samples by iodometry. A model of the knock-out of oxygen is proposed on the basis of Monte-Carlo TRIM calculations. Resistivity versus temperature of the irradiated samples shows fairly metallic behaviour up to a certain dose. Excess conductivity analysis shows a cross-over from 2D to 3D behaviour in conductivity for the unirradiated sample. However, for irradiated samples, the critical fluctuation regime sets in. The interlayer coupling strengths decrease with the increase in the irradiation dose. The sample with the highest dose shows a nonmetallic behaviour in resistivity. A detailed analysis shows a conductivity behaviour in the nonmetallic region characteristic of three-dimensional variable range hopping of charge carriers. (orig.)

  18. Oxygen knock-out and other studies in {alpha}-irradiated polycrystalline Bi-2212 superconductor

    Bandyopadhyay, S.K. [Variable Energy Cyclotron Centre, Calcutta (India); Ghosh, A.K. [Jadavpur Univ., Calcutta (India). Dept. of Physics; Barat, P. [Variable Energy Cyclotron Centre, Calcutta (India); Sen Pintu [Variable Energy Cyclotron Centre, Calcutta (India); Basu, A.N. [Jadavpur Univ., Calcutta (India). Dept. of Physics; Ghosh, B. [Saha Inst. of Nuclear Physics, Calcutta (India)

    1997-08-16

    Bulk polycrystalline samples of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{sigma}} (Bi-2212) have been irradiated with 40 MeV {alpha}-particles. T{sub c} increases up to a certain dose. The increase in T{sub c} is correlated with the knock-out of oxygen, which has been verified by the determination of the oxygen contents of the irradiated samples by iodometry. A model of the knock-out of oxygen is proposed on the basis of Monte-Carlo TRIM calculations. Resistivity versus temperature of the irradiated samples shows fairly metallic behaviour up to a certain dose. Excess conductivity analysis shows a cross-over from 2D to 3D behaviour in conductivity for the unirradiated sample. However, for irradiated samples, the critical fluctuation regime sets in. The interlayer coupling strengths decrease with the increase in the irradiation dose. The sample with the highest dose shows a nonmetallic behaviour in resistivity. A detailed analysis shows a conductivity behaviour in the nonmetallic region characteristic of three-dimensional variable range hopping of charge carriers. (orig.)

  19. Rewriting the Opportunity Theory

    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....

  20. Opportunity Cost: A Reexamination

    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…

  1. A High-Speed Motion-Picture Study of Normal Combustion, Knock and Preignition in a Spark-Ignition Engines

    Rothrock, A M; Spencer, R C; Miller, Cearcy D

    1941-01-01

    Combustion in a spark-ignition engine was investigated by means of the NACA high-speed motion-picture cameras. This camera is operated at a speed of 40,000 photographs a second and therefore makes possible the study of changes that take place in the intervals as short as 0.000025 second. When the motion pictures are projected at the normal speed of 16 frames a second, any rate of movement shown is slowed down 2500 times. Photographs are presented of normal combustion, of combustion from preignitions, and of knock both with and without preignition. The photographs of combustion show that knock may be preceded by a period of exothermic reaction in the end zone that persists for a time interval of as much as 0.0006 second. The knock takes place in 0.00005 second or less.

  2. Book Act

    Kivland, Sharon

    2014-01-01

    Book Act was a new project by AMBruno, initiated by Sophie Loss, in which artist book-makers performed and embodied the concept or essence of their books through the medium of film or performance. The exhibition at The Tetley, Leeds, comprised the originating books and corresponding video work, with live performances on Sunday 9 March 2014. Book Act took place during the 17th International Contemporary Artists' Book Fair (7th to 9th March) and the exhibition continued until 26th March 2014.

  3. Combustion Analysis and Knock Detection in Single Cylinder DI-Diesel Engine Using Vibration Signature Analysis

    Y.V.V.SatyanarayanaMurthy

    2011-01-01

    Full Text Available The purpose of this paper is to detect the “knock” in Diesel engines which deteriorate the engine performance adversely. The methodology introduced in the present work suggests a newly developed approach towards analyzing the vibration analysis of diesel engines. The method is based on fundamental relationship between the engine vibration pattern and the relative characteristics of the combustion process in each or different cylinders. Knock in diesel engine is detected by measuring the vibration generated by the engine using The DC-11 FFT analyzer with accelerometer. Knock in diesel engine is mainly due to the engine miss .A diesel engine miss results from one or more cylinders when the fuel is not burning properly. Improper fuel burning is caused by Injection system problems which include, Faulty injectors, clogged fuel filters, incorrect Injection timing, Low engine compression, injection system leaks, Air leaks, faulty injection pump etc. Engine miss causes rapid combustion with very high pressures generating a rumble or dull clattering sound. Abnormally loud sound with violent vibration is called “knocking or detonation”. Engine cylinder vibration in FFT form is monitored at each load the cylinder excitation frequencies are compared with the base line frequencies using diesel oil. Time wave forms on the cylinder head are also recorded to analyze the combustion. Since the very combustion in the cylinder is the basic exciter, the vibration study of the engine cylinder through the measured FFT and time waveforms are the representatives of combustion propensity. Vibration accelerometer is mounted on the cylinder head, preferably on the bolt connecting the head and the cylinder to record the engine vibrations using DC-11 data logger which directly gives the spectral data in the form of FFT, the overall vibration levels. This FFT data recorded is collected by On-Time window based software designed by e-predict Inc., Argentina. The Time

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

    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.

  5. Potent Dystrophin knock-Down in Vitro and in Vivo Using RNAi Technonlogy and Expression Signature of Myotubes with Dystrophin knocked Down: Attempts at Unravelling the Mystery

    MM Ghahramani Seno

    2005-10-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is one of a group of genetically heterogeneous muscular dystrophies that are characterized by progressive weakness and wasting of skeletal muscle. Loss of myofibres occurs in response to a deficiency of dystrophin, a protein which is believed to be responsible for myofibre maintenance and integrity. Dystrophin forms a link between the cytoskeleton and the membrane-spanning dystrophin-associated glycoprotein complex (DAPC, indicative of a structural role for dystrophin. The application of gene therapy protocols for DMD still presents many daunting challenges due partly to intrinsic features of the dystrophin gene. Hence, improvement in the understanding of the underlying primary molecular events leading to a dystrophic pathology might pave the way for the discovery of new starting points. Here we present a strategy to use RNAi technology to study the events occurring in muscle cell development due to dystrophin deficiency. RNAi has been proven to be a powerful technology to study molecular effects due to knockdown of single genes. We have used a series of siRNAs to target and knock down the expression of dystrophin in primary cultures of mouse muscle, and subsequently used transcriptomic array analysis to identify genes whose expression were affected in response to dystrophin deficiency. The data obtained from this experiment, which include some very interesting potential new targets, are currently being analysed. We have also developed a recombinant adeno-associated virus (rAAV vector expressing an shRNA targeting dystrophin. The use of such rAAV-shDNA vectors enables us to target dystrophin in vivo to obtain a better and potentially curative insight into the pathophysiology of DMD.

  6. 29 CFR 1620.27 - Relationship to the Equal Pay Act of title VII of the Civil Rights Act.

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship to the Equal Pay Act of title VII of the Civil... OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.27 Relationship to the Equal Pay Act of title VII of the Civil Rights Act. (a) In situations where the jurisdictional prerequisites of both the EPA and title VII of...

  7. 29 CFR 1614.203 - Rehabilitation Act.

    2010-07-01

    ... Commission's ADA regulations at 29 CFR part 1630. ... 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....

  8. RNAi-mediated knocking- down of rlpk2 gene retarded soybean leaf senescence

    LI Xiaoping; MA Yuanyuan; LI Pengli; ZHANG Liwen; WANG Yong; ZHANG Ren; WANG Ningning

    2005-01-01

    Leaf senescence that occurs in the last stage of leaf development is a genetically programmed process. It is very significant to elucidate the molecular mechanisms that control the initiation and progression of leaf senescence and the way the senescence signal is transduced. In a previous study on artificially induced soybean leaf senescence, we cloned a novel gene designated rlpk2 (Genbank Accession No. AY687391) that encodes a leucine-rich repeat (LRR) receptor like protein kinase. The expression level of rlpk2 gene was shown to be strongly up-regulated during both the natural leaf senescence process in this report and the artificially induced primary-leaf-senescence process in our previous work. The RNA interference (RNAi)-mediated knocking-down of rlpk2 dramatically retarded both the natural and nutrient deficiency-induced leaf senescence in transgenic soybean. The transgenic leaves showed more cell-aggregated surface structure and higher content of chlorophyll.

  9. Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes.

    Plucińska, Kaja; Crouch, Barry; Koss, David; Robinson, Lianne; Siebrecht, Michael; Riedel, Gernot; Platt, Bettina

    2014-08-01

    Key neuropathological hallmarks of Alzheimer's disease (AD) are elevated levels of amyloid β-peptide (Aβ) species generated via amyloid precursor protein (APP) endoproteolysis and cleavage by the rate-limiting β-site enzyme 1 (BACE1). Because rodents do not develop amyloid pathologies, we here investigated whether AD-like endophenotypes can be created in mice by expression of human bace1. To avoid pitfalls of existing models, we introduced hbace1 via knock-in under the control of the CaMKII α promoter into the safe HPRT locus. We report amyloidogenic processing of murine APP in the hBACE1 mice (termed PLB4), resulting in the formation of toxic APP metabolites that accumulate intra- and extraneuronally in hippocampus and cortex. Pronounced accumulation of Aβ*56 and Aβ hexamers in the absence of plaque deposition was detected in brain tissue from symptomatic PLB4 mice. Heightened levels of inflammation (gliosis) also appeared in several AD-related brain regions (dentate gyrus, hippocampal area CA1, piriform and parietal cortices) at 6 and 12 months of age. Behaviorally, deficits in habituation to a novel environment and semantic-like memory (social transmission of food preference) were detected from 3 to 4 months of age. Impairments in spatial learning strategies in long-term reference (water maze) and working memory (Y-maze) tasks presented at 6 months, and were distinct from reductions in locomotor activity and anxiety. Overall, our data indicate for the first time that targeted, subtle forebrain-specific expression through single gene knock-in of hBACE1 is sufficient to generate AD-relevant cognitive impairments amid corresponding histopathologies, confirming human BACE as the key parameter in amyloid pathogenesis. PMID:25100603

  10. Comprehensive Opportunity and Lost Opportunity Control Model and Enterprise Risk Management

    Akira Nishimura

    2015-01-01

    The purpose of this paper is to build a comprehensive opportunity and lost opportunity control model throughwhich contemporary management accounting can act in alignment with enterprise risk management, as well as toexamine its managerial and socio-economic functions in relation to risk management in the context ofuncertainty in a global finance–oriented society. For this purpose, the paper demonstrates the structure andcharacteristics of this model specifically in contrast with traditional a...

  11. Measuring growth opportunities

    Danbolt, J.; Hirst, I.; Jones, E

    2002-01-01

    Although the impact of growth opportunities on company value has been recognized since Miller and Modigliani (1961), relatively little empirical work has been undertaken to value growth opportunities. In this study the validity of the KBM model (Kester (1984) and Brealey and Myers (1981)) is tested on a sample of 278 large UK companies for 1987-1995. Applying standard assumptions, the value of growth opportunities is found to account for a larger proportion of market values than assets-in-pla...

  12. True-breeding targeted gene knock-out in barley using designer TALE-nuclease in haploid cells.

    Maia Gurushidze

    Full Text Available Transcription activator-like effector nucleases (TALENs are customizable fusion proteins able to cleave virtually any genomic DNA sequence of choice, and thereby to generate site-directed genetic modifications in a wide range of cells and organisms. In the present study, we expressed TALENs in pollen-derived, regenerable cells to establish the generation of instantly true-breeding mutant plants. A gfp-specific TALEN pair was expressed via Agrobacterium-mediated transformation in embryogenic pollen of transgenic barley harboring a functional copy of gfp. Thanks to the haploid nature of the target cells, knock-out mutations were readily detected, and homozygous primary mutant plants obtained following genome duplication. In all, 22% of the TALEN transgenics proved knocked out with respect to gfp, and the loss of function could be ascribed to the deletions of between four and 36 nucleotides in length. The altered gfp alleles were transmitted normally through meiosis, and the knock-out phenotype was consistently shown by the offspring of two independent mutants. Thus, here we describe the efficient production of TALEN-mediated gene knock-outs in barley that are instantaneously homozygous and non-chimeric in regard to the site-directed mutations induced. This TALEN approach has broad applicability for both elucidating gene function and tailoring the phenotype of barley and other crop species.

  13. 7 CFR 33.14 - Opportunity for hearing.

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Opportunity for hearing. 33.14 Section 33.14... REGULATIONS REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Withholding Certificates § 33.14 Opportunity for hearing. The person accused shall be entitled to a hearing, provided he or she makes...

  14. 78 FR 9431 - Notice of Opportunity To File Amicus Briefs

    2013-02-08

    ... BOARD Notice of Opportunity To File Amicus Briefs AGENCY: Merit Systems Protection Board. ACTION: Notice. SUMMARY: The Merit Systems Protection Board (MSPB or Board) announces the opportunity to file amicus... Enhancement Act of 2012 (WPEA), 112 Public Law 199, may be applied retroactively to pending cases...

  15. 78 FR 17233 - Notice of Opportunity To File Amicus Briefs

    2013-03-20

    ... BOARD Notice of Opportunity To File Amicus Briefs AGENCY: Merit Systems Protection Board. ACTION: Notice. SUMMARY: The Merit Systems Protection Board (MSPB or Board) announces the opportunity to file amicus... Enhancement Act of 2012 (WPEA), 112 Public Law 199, with regard to damages may be applied retroactively...

  16. Equal opportunities in diversity

    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...

  17. Sarbanes - Oxley Act- Threat or Opportunity for Auditors?

    Ionel BOSTAN

    2010-01-01

    Full Text Available Recent events of financial publication revealed aneed for introduction of an effective reform process of thetraditional control methods and processes of decision-makingentities. The crisis of corporate governance systems, the need tointroduce new codes and self-binding and legislative rules, havepushed the legislature to the U.S. issued Sarbanes –Oxley Actmodel.Accountants and financial specialists describe the benefits ofimplementation of the SOX model, saying that the quality of thearea contributed only marginally in the creation of suchbenefits. If there would be no coercion of attitude towardsimplementing the ISO 14001 or ISO, including requirements forintegration of best practice financial, SOX would have hadreason to exist.

  18. Equal Opportunities Questionnaire

    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...

  19. Equal Opportunities Questionnaire

    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...

  20. 76 FR 40874 - Information Collection; Equal Opportunity Compliance Review Record

    2011-07-12

    ... Age Discrimination Act of 1975, as amended. Section 504 of the Rehabilitation Act of 1973, as amended... recipients' employees understand their customer service role. Collection will occur during face-to-face... Forest Service Information Collection; Equal Opportunity Compliance Review Record AGENCY: Forest...

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

    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.

  2. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  3. The Mosaic Mutants of Cucumber: A Method to Produce Knock-Downs of Mitochondrial Transcripts.

    Del Valle-Echevarria, Angel R; Kiełkowska, Agnieszka; Bartoszewski, Grzegorz; Havey, Michael J

    2015-06-01

    Cytoplasmic effects on plant performance are well-documented and result from the intimate interaction between organellar and nuclear gene products. In plants, deletions, mutations, or chimerism of mitochondrial genes are often associated with deleterious phenotypes, as well as economically important traits such as cytoplasmic male sterility used to produce hybrid seed. Presently, genetic analyses of mitochondrial function and nuclear interactions are limited because there is no method to efficiently produce mitochondrial mutants. Cucumber (Cucumis sativus L.) possesses unique attributes useful for organellar genetics, including differential transmission of the three plant genomes (maternal for plastid, paternal for mitochondrial, and bi-parental for nuclear), a relatively large mitochondrial DNA in which recombination among repetitive motifs produces rearrangements, and the existence of strongly mosaic (MSC) paternally transmitted phenotypes that appear after passage of wild-type plants through cell cultures and possess unique rearrangements in the mitochondrial DNA. We sequenced the mitochondrial DNA from three independently produced MSC lines and revealed under-represented regions and reduced transcription of mitochondrial genes carried in these regions relative to the wild-type parental line. Mass spectrometry and Western blots did not corroborate transcriptional differences in the mitochondrial proteome of the MSC mutant lines, indicating that post-transcriptional events, such as protein longevity, may compensate for reduced transcription in MSC mitochondria. Our results support cucumber as a model system to produce transcriptional "knock-downs" of mitochondrial genes useful to study mitochondrial responses and nuclear interactions important for plant performance. PMID:25873637

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

    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.

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

    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

  6. Opportunities for First Nations

    Moura, Rodrigo [Anaia Global (Canada)

    2011-07-01

    The recent development of wind energy project creates opportunities for First Nations. Although they are interested by such projects, First Nations nevertheless have questions such about how they can be a part of the wind industry, what are their rights, what investment would they need to make, and how to judge if they are getting a favourable deal. This presentation aimed at answering those questions an maintained that wind energy would bring social and economic development to First Nations communities as well as diversifying their sources of revenue. Several companies offer their services to First Nations and Anaia Global is a company which helps aboriginal people identify to promote their investment opportunities in renewable energy projects and benefit from the technology transferred to them. This presentation showed that there are significant opportunities for First Nations in the wind energy sector and that Anaia Global is focusing on helping them seize these opportunities.

  7. Creating housing opportunities

    Josephine McNeil

    2007-01-01

    Helping families of low and moderate means find opportunities in high-cost areas requires special tactics. Citizens for Affordable Housing in Newton Development Organization (CAN-DO) shows it can be done.

  8. User Frustrations as Opportunities

    Michael Weiss

    2012-01-01

    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 u...

  9. Tissue-Specific Regulation of Oncogene Expression Using Cre-Inducible ROSA26 Knock-In Transgenic Mice.

    Carofino, Brandi L; Justice, Monica J

    2015-01-01

    Cre-inducible mouse models are often utilized for the spatial and temporal expression of oncogenes. With the wide number of Cre recombinase lines available, inducible transgenesis represents a tractable approach to achieve discrete oncogene expression. Here, we describe a protocol for targeting Cre-inducible genes to the ubiquitously expressed ROSA26 locus. Gene targeting provides several advantages over standard transgenic techniques, including a known site of integration and previously characterized pattern of expression. Historically, an inherent instability of ROSA26 targeting vectors has hampered the efficiency of developing ROSA26 knock-in lines. In this protocol, we provide individual steps for utilizing Gateway recombination for cloning as well as detailed instructions for screening targeted ES cell clones. By following this protocol, one can achieve germline transmission of a ROSA26 knock-in line within several months. PMID:26069083

  10. Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference

    Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas. In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry. We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors. Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer

  11. Experimental investigation of the knock and combustion characteristics of CH4, H2, CO, and some of their mixtures

    Li, H. [National Research Council Canada, Ottawa, Ontario (Canada); Karim, G. [University of Calgary, Alberta (Canada). Department of Mechanical and Manufacturing Engineering

    2006-07-01

    Experimental data obtained in single-cylinder, variable compression ratio, spark ignition (SI), cooperative fuel research (CFR) engine when operating on CH4, H2, CO, simulated reforming product gas (2H2 + CO), and some of their mixtures are presented. The dependence of the value of some key operational and combustion variables, including the knock and lean operational limits, combustion duration, and exhaust emission on fuel composition, is investigated. The significant effect of the presence of H-bearing species such as CH4, H2, or H2O on the combustion and knock characteristics of dry CO is also highlighted. Guidelines as to the suitability of these fuels for SI engine applications are provided. (author)

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

    Walker Edward D; Black William C; Randle Nadine P; McCall P J; Ranson Hilary; Lynd Amy; Donnelly Martin J

    2005-01-01

    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. Th...

  13. Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.

    Lattante, Serena; de Calbiac, Hortense; Le Ber, Isabelle; Brice, Alexis; Ciura, Sorana; Kabashi, Edor

    2015-03-15

    Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported in 1-3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive for SQSTM1/p62 have been detected in patients with neurodegenerative disorders, including ALS/FTLD. In order to investigate the pathogenic mechanisms induced by SQSTM1 mutations in ALS/FTLD, we developed a zebrafish model. Knock-down of the sqstm1 zebrafish ortholog, as well as impairment of its splicing, led to a specific phenotype, consisting of behavioral and axonal anomalies. Here, we report swimming deficits associated with shorter motor neuronal axons that could be rescued by the overexpression of wild-type human SQSTM1. Interestingly, no rescue of the loss-of-function phenotype was observed when overexpressing human SQSTM1 constructs carrying ALS/FTLD-related mutations. Consistent with its role in autophagy regulation, we found increased mTOR levels upon knock-down of sqstm1. Furthermore, treatment of zebrafish embryos with rapamycin, a known inhibitor of the mTOR pathway, yielded an amelioration of the locomotor phenotype in the sqstm1 knock-down model. Our results suggest that loss-of-function of SQSTM1 causes phenotypic features characterized by locomotor deficits and motor neuron axonal defects that are associated with a misregulation of autophagic processes. PMID:25410659

  14. Eléments d'analyse du cliquetis et de ses effets Elements for Analyzing Knocking and Its Effects

    Douaud A.

    2006-11-01

    Full Text Available On présente dans cet article une synthèse des travaux théoriques et expérimentaux relatifs à la génération du cliquetis et à ses effets sur le fonctionnement du moteur. L'apparition du cliquetis est décrite par un mécanisme global de délai d'auto-inflammation. Des exemples d'application portant sur l'identification du délai de carburants quelconques et sur l'optimisation de l'ensemble moteurs-carburants documentent cette approche. Le cliquetis a pour conséquence un accroissement de sollicitations mécaniques et thermiques des parois de la chambre de combustion. Des méthodes et résultats d'investigation de ces phénomènes sont présentés. A synthesis is presented of theoretical and experimental research concerning the generating of knocking and its effects on engine running. The appearance of knocking is described by an overall mechanism of autoignition delay. This approach is documented by applied examples concerning the identification of the delay involved with any type of fuel and the optimizing of engine-fuel systems. Knocking causes an increase in mechanical and thermal stresses on combustion-chamber walls. Investigational methods and results concerning these phenomena are described.

  15. Links and opportunities

    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

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

    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. Autism spectrum disorder traits in Slc9a9 knock-out mice.

    Yang, Lina; Faraone, Stephen V; Zhang-James, Yanli

    2016-04-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders which begin in childhood and persist into adulthood. They cause lifelong impairments and are associated with substantial burdens to patients, families, and society. Genetic studies have implicated the sodium/proton exchanger (NHE) nine gene, Slc9a9, to ASDs and attention-deficit/hyperactivity disorder(ADHD). Slc9a9 encodes, NHE9, a membrane protein of the late recycling endosomes. The recycling endosome plays an important role in synapse development and plasticity by regulating the trafficking of membrane neurotransmitter receptors and transporters. Here we tested the hypothesis that Slc9a9 knock-out (KO) mice would show ADHD-like and ASD-like traits. Ultrasonic vocalization (USV) recording showed that Slc9a9 KO mice emitted fewer calls and had shorter call durations, which suggest communication impairment. Slc9a9 KO mice lacked a preference for social novelty, but did not show deficits in social approach; Slc9a9 KO mice spent more time self-grooming, an indicator for restricted and repetitive behavior. We did not observe hyperactivity or other behavior impairments which are commonly comorbid with ASDs in human, such as anxiety-like behavior. Our study is the first animal behavior study that links Slc9a9 to ASDs. By eliminatingNHE9 activity, it provides strong evidence that lack of Slc9a9leads to ASD-like behaviors in mice and provides the field with a new mouse model of ASDs. PMID:26755066

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

    Ayse Sahaboglu

    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.

  19. Industrial opportunities - offshore

    Industrial opportunities available in the Canadian offshore petroleum industry are discussed. Oil has been produced offshore from Nova Scotia since 1992, and offshore from Newfoundland since 1997. Special needs that must be addressed in offshore operations in eastern Canada such as the cold North Atlantic environment, isolation, logistics, safety, and quality assurance, are examined. The most obvious opportunities lie with the designing, building and installing the facilities needed to extract oil and gas from beneath the sea floor and transport it to market. However, there are also opportunities in designing and fabricating clothing, customized food containers and other equipment for offshore needs. Short term opportunities also exist in the decommissioning of depleted production fields and their facilities. One of the greatest obstacles facing new entrants into the offshore oil and gas industry is the lack of a track record. To meet this challenge, the ability to seek out partners to pursue local and international opportunities through joint ventures, strategic alliances and technology sharing partnering arrangements is of great importance. It may be the difference between success and failure. 6 figs

  20. International oil opportunities

    Some of the key issues to be addressed when selecting international opportunities, were discussed. The ideal opportunity should have the following characteristics: (1) large, low risk (2) high percentage of rent available to the investor, (3) low cost and low technical requirements, (4) low country risk, (5) low competition, (6) easy to access, and (7) favorable environment in which to work. Entering an international opportunity can be achieved by competitive bidding, direct negotiation, partnership, corporate and/or asset acquisition, and long-term relationships. Key success factors were identified as (1) applying technical financial and commercial skills in the international environment, (2) speedy response, (3) excellent relationships in the foreign country, (4) understanding the local culture, and (5) keeping a good track record. 6 figs

  1. Opportunity Knocks: Closing the Gaps between Leaders and the Public on Math, Science, & Technology Education--A Qualitative Research Report on the Kansas City Region

    Kadlec, Alison; Friedman, Will

    2010-01-01

    The Kansas City region is in many ways representative of the larger national economy. As with many cities of its size, the largest area of employment, other than in government, is in the healthcare sector. While biomedical research is a major growth area across the nation, Kansas City is also the national leader in the animal healthcare industry,…

  2. Investment Insight Opportunities Ahead

    2006-01-01

    Over the next five years, China will be shitting its focus to more balanced development and what it sees as quality growth. Its two main strategies are promoting innovation-with the government-backed industrial upgrading-and strengthening the rural economy. This shift will lead to massive investment and fresh, wealth-making opportunities. In the stock

  3. Opportunity Cost: A Reply

    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…

  4. Land of Expat Opportunity

    2009-01-01

    The international work force continues to grow as employment opportunities entice foreigners to live in China Forty-four-year-old Daniell Goodin has spent almost two decades working abroad, calling Indonesia, Hong Kong and the United States "home" for different periods of time. In May, the Australian native arrived in China, working

  5. Creating Work Opportunities.

    Michelle K. Derr; LaDonna Pavetti

    2008-01-01

    This brief profiles three programs that use difference approaches—unpaid work experience, subsidized employment, and unsubsidized transitional employment—to create work opportunities for TANF recipients who are living with a disability and have not been successful in finding competitive employment.

  6. Generating innovation opportunities:

    Kallio, Anne; Bergenholtz, Carsten

    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 in...

  7. Opportunities in microstructured photonics

    Herzig, Hans Peter; Sfez, Tristan; Scharf, Toralf

    2010-01-01

    The progress in novel light sources, detectors, materials and technology enable new opportunities and challenges for diffractive optics and nanoscale photonics. Important are also analysis tools, such as near-field imaging (SNOM). Only structures that can be characterized can be fabricated

  8. Opportunity at 'Cook Islands'

    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.

  9. Opportunity's 'Olympia' Panorama

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Opportunity's 'Olympia' Panorama (QTVR) This view from the panoramic camera on NASA's Mars Exploration Rover Opportunity shows an outcrop called 'Olympia' along the northwestern margin of 'Erebus' crater. The view spans about 120 degrees from side to side, generally looking southward. The outcrop exposes a broad expanse of sulfate-rich sedimentary rocks. The rocks were formed predominantly from windblown sediments, but some also formed in environmental conditions from damp to under shallow surface water. After taking the images that were combined into this view, Opportunity drove along along a path between sand dunes to the upper left side of the image, where a cliff in the background can be seen. This is a cliff is known as the 'Mogollon Rim.' Researchers expect it to expose more than 1 meter (3 feet) of new strata. These strata may represent the highest level observed yet by Opportunity. The image is an approximately true-color rendering generated using the panoramic camera's 750-nanometer, 530-nanometer and 430-nanometer filters.

  10. Opportunities for Taiwan's industry

    Jen-Lien Lin; Guang-Way Jang

    2004-01-01

    The Industrial Technology Research Institute (ITRI) in Taiwan recently introduced nanotechnology to local traditional industries. Nanotechnologies provide a great opportunity for these companies to meet outside challenges and join the blooming electronic and optoelectronic industries. The Nanotechnology Community (NTC) was established in 2003, with the goal of finding commercial applications. This year, the Taiwan Nanotechnology Industrialization Promotion Association (TANIPA) was established...

  11. Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology.

    Koss, David J; Robinson, Lianne; Drever, Benjamin D; Plucińska, Kaja; Stoppelkamp, Sandra; Veselcic, Peter; Riedel, Gernot; Platt, Bettina

    2016-07-01

    Models of Tau pathology related to frontotemporal dementia (FTD) are essential to determine underlying neurodegenerative pathologies and resulting tauopathy relevant behavioural changes. However, existing models are often limited in their translational value due to Tau overexpression, and the frequent occurrence of motor deficits which prevent comprehensive behavioural assessments. In order to address these limitations, a forebrain-specific (CaMKIIα promoter), human mutated Tau (hTauP301L+R406W) knock-in mouse was generated out of the previously characterised PLB1Triple mouse, and named PLB2Tau. After confirmation of an additional hTau species (~60kDa) in forebrain samples, we identified age-dependent progressive Tau phosphorylation which coincided with the emergence of FTD relevant behavioural traits. In line with the non-cognitive symptomatology of FTD, PLB2Tau mice demonstrated early emerging (~6months) phenotypes of heightened anxiety in the elevated plus maze, depressive/apathetic behaviour in a sucrose preference test and generally reduced exploratory activity in the absence of motor impairments. Investigations of cognitive performance indicated prominent dysfunctions in semantic memory, as assessed by social transmission of food preference, and in behavioural flexibility during spatial reversal learning in a home cage corner-learning task. Spatial learning was only mildly affected and task-specific, with impairments at 12months of age in the corner learning but not in the water maze task. Electroencephalographic (EEG) investigations indicated a vigilance-stage specific loss of alpha power during wakefulness at both parietal and prefrontal recording sites, and site-specific EEG changes during non-rapid eye movement sleep (prefrontal) and rapid eye movement sleep (parietal). Further investigation of hippocampal electrophysiology conducted in slice preparations indicated a modest reduction in efficacy of synaptic transmission in the absence of altered synaptic

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

    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

  13. A new knock-in mouse model of l-DOPA-responsive dystonia.

    Rose, Samuel J; Yu, Xin Y; Heinzer, Ann K; Harrast, Porter; Fan, Xueliang; Raike, Robert S; Thompson, Valerie B; Pare, Jean-Francois; Weinshenker, David; Smith, Yoland; Jinnah, Hyder A; Hess, Ellen J

    2015-10-01

    Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF

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

    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.

  15. e-Society and Children's Participation: Risks, Opportunities and Barriers

    O'Neill, Brian

    2013-01-01

    Children are important subjects of information society policy, particularly in the context of digital learning opportunities and e-inclusion. However, their participation is also a cause of concern and anxiety for policy makers. With ever-earlier adoption of new internet technologies and services by children, concerns arise as to how to ensure adequate protection whilst seeking to encourage and foster online opportunities. A delicate balancing act is required to manage risks while promoting b...

  16. [BLG gene knockout and hLF gene knock-in at BLG locus in goat by TALENs].

    Song, Shaozheng; Zhu, Mengmin; Yuan, Yuguo; Rong, Yao; Xu, Sheng; Chen, Si; Mei, Junyan; Cheng, Yong

    2016-03-01

    To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin. DNA cleavage activities of cells were verified by PCR amplification and DNA production sequencing. Then, targeting vector BLC14-TK and plasmids TALEN-3-L/R were co-transfected into goat fetal fibroblasts, both 700 μg/mL G418 and 2 μg/mL GCV were simultaneously used to screen G418-resistant cells. Detections of integration and recombination were implemented to obtain cells with hLF gene site-specific integration. We chose targeting cells as donor cells for somatic cell nuclear transfer. The mutagenicity of TALEN-3-L/R was between 25% and 30%. A total of 335 reconstructed embryos with 6 BLG-/hLF+ targeting cell lines were transferred into 16 recipient goats. There were 9 pregnancies confirmed by ultrasound on day 30 to 35 (pregnancy rate of 39.1%), and one of 50-day-old fetus with BLG-/hLF+ was achieved. These results provide the basis for hLF gene knock-in at BLG locus of goat and cultivating transgenic goat of low allergens and rich hLF in the milk. PMID:27349115

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

    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.

  18. Atomic Energy Commission Act, 2000 (Act 588)

    Act 588 of the Republic of Ghana entitled, Atomic Energy Commission Act, 2000, amends and consolidates the Atomic Energy Commission Act, 204 of 1963 relating to the establishment of the Atomic Energy Commission. Act 588 makes provision for the Ghana Atomic Energy Commission to establish more institutes for the purpose of research in furtherance of its functions and also promote the commercialization of its research and development results. (E.A.A.)

  19. Hot business - cool opportunities

    A new role for the deregulated electric utilities in the energy services market or performance contracting markets was discussed. It was argued that in view of the long tradition of close customer contact, distribution utilities are in a good position to leverage their relationship with their customers to expand the range of products and services that the ''utility'' provides to them. Real time pricing, energy services, HVAC maintenance and operation are just some of the areas where the distribution utility''s linkage to customers could be used to good advantage. Some case histories, and a list of potential product and service opportunities in the commercial/industrial and residential sectors were provided. Some of the potential pitfalls were also identified for utilities that wish to pursue these opportunities. These pitfalls included legal, marketing, risk management and funding issues

  20. User Frustrations as Opportunities

    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.

  1. Propane: North American opportunities

    Opportunities for expanding the propane market in North America are discussed. The goal of change should be to enhance client satisfaction and loyalty. The current customer base is largely comprised of pick-up trucks, vans and buses in commercial fleet service, police and similar fleet service and privately owned vehicles. Opportunities for the expansion of propane exist due to: vehicles being kept and lasting longer, allowing a longer pay-back time; exhaust emission standards becoming more stringent; the possible introduction of emission standards for substances currently not controlled; and properly combusted CO2 emissions that are at least 12% lower than gasoline. The continuing development of engine fuel management systems, application of extensive road/highway experience, matching supply and refuelling infrastructure to consumer demands, application in air quality non-attainment areas, and original equipment manufacturer, government and industry cooperation are discussed. 8 figs

  2. Project X: Physics Opportunities

    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.

  3. Opportunities for innovation

    Actual results have shown that the Construction Industry Institute (CII) offers significant opportunities for improvement in cost, schedule, and quality on most projects, and in particular, on large projects. This paper reviews the state of the construction industry, discusses how its problems are being addressed by CII, and addresses potential opportunities through the application of CII research products. CII is meeting the challenge of the industry. Just like the challenge of Department of Energy's Super Conducting Super Collider. With $1.2 billion worth of construction to be constructed during the 90s, the opportunities for innovation appear to be great. Every effort should be made while the projects are still on the high part of cost influence curve to use modern management methods and approaches to executing its work. Proper attention to all the inputs to project design is absolutely essential. Scope definition and control techniques have been developed by CII which can be used. Work packaging for the most efficient execution of engineering and construction are available as well. Approaches, incentives, and contracting strategies have also been researched by CII. Constructability programs virtually always guarantee a savings of at least 10 percent. Partnership arrangements can reduce the size of overhead for all participants in the process and eliminate the typical adversarial climates which tend to predominate on a construction project. SSC Laboratories and the PB-MK team have the opportunity to take the initiative now to make the 21st Century SSC a construction project which is executed in the 21st Century manner

  4. Equal Opportunities Advisory Panel

    HR Department

    2006-01-01

    At its meeting on 7 December 2006, the Standing Concertation Committee took note of the appointment of four new members of the Panel: Wisla Carena, Pierre Charrue, Sue Foffano and Markus Nordberg. The present composition of the Panel (appointed ad personam) is as follows: Tiziano Camporesi (Chairperson), Wisla Carena, Pierre Charrue, Sue Foffano, Josi Schinzel (Equal Opportunities Officer), Markus Nordberg, Christine Petit-Jean-Genaz et Elena Wildner. Human Resources Department Tel. 74480

  5. Exclusion, employment and opportunity

    Atkinson, Tony; Hills, John

    1998-01-01

    The relationships between employment, education, opportunity, social exclusion and poverty are central to current policy debates. Atkinson argues that the concepts of poverty, unemployment and social exclusion are closely related, but are not the same. People may be poor without being socially excluded, and vice versa. Unemployment may cause poverty, but this can be prevented. Equally, marginal jobs do not ensure social inclusion. Britton argues that convential economic analysis misses a key ...

  6. Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

    Bergner, A; Kellner, J.; da Silva, A. K.; Gamarra, F.; Huber, R M

    2006-01-01

    Background: Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards T(H)2-lymphocytes and display a b...

  7. REGION-SPECIFIC NEURON AND SYNAPSE LOSS IN THE HIPPOCAMPUS OF APPSL/PS1 KNOCK-IN MICE

    Brasnjevic, Ivona; Lardenoije, Roy; Schmitz, Christoph; van der Kolk, Nicolien; Dickstein, Dara L; Takahashi, Hisaaki; Patrick R Hof; STEINBUSCH, Harry W.M.; Rutten, Bart P.F.

    2013-01-01

    Transgenic mouse models with knock-in (KI) expression of human mutant amyloid precursor protein (APP) and/or human presenilin 1 (PS1) may be helpful to elucidate the cellular consequences of APP and PS1 misprocessing in the aging brain. Age-related alterations in total numbers of neurons and in numbers of synaptophysin-immunoreactive presynaptic boutons (SIPB), as well as the amyloid plaque load were analyzed in the hippocampal dentate gyrus (DG), CA3, and CA1–2 of 2- and 10-month-old APPSL/P...

  8. Sleep-Waking Discharge of Ventral Tuberomammillary Neurons in Wild-Type and Histidine Decarboxylase Knock-Out Mice

    Sakai, Kazuya; Takahashi, Kazumi; Anaclet, Christelle; Lin, Jian-Sheng

    2010-01-01

    Using extracellular single-unit recordings, we have determined the characteristics of neurons in the ventral tuberomammillary nucleus (VTM) of wild-type (WT) and histidine decarboxylase knock-out (HDC-KO) mice during the sleep-waking cycle. The VTM neurons of HDC-KO mice showed no histamine immunoreactivity, but were immunoreactive for the histaminergic (HA) neuron markers adenosine deaminase and glutamic acid decarboxylase 67. In the VTM of WT mice, we found waking (W)-specific, non-W-specif...

  9. Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated siRNA Delivery

    Xinyue Huang; Helen Townley

    2016-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma that is found in children and has a poor outcome for those with metastatic disease. Two histological groups have been distinguished - embryonal (ERMS) and alveolar (ARMS) forms. The ARMS subtype has higher rates of metastasis, as well as higher levels of ELMO1, which is thought to be involved in cell migration. Therefore, the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent the metastatic behaviour of ARMS...

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

    Venit, Tomáš; Dzijak, Rastislav; Rohožková, Jana; Kalendová, Alžběta; Hozák, Pavel

    Debrecen : University of Debrecen, 2013. s. 45-45. [Wilhelm Bernard Workshop on the cell nucleus /23./. 19.08.2013-24.08.2013, Debrecen] R&D Projects: GA ČR(CZ) GD204/09/H084; GA ČR GAP305/11/2232; GA TA ČR TE01020118; GA MŠk LH12143 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : atomic force microscopy * cell membrane * myosin 1C * NM1 * nuclear myosin I * myosin knock-out Subject RIV: EB - Genetics ; Molecular Biology

  11. Pou4f2 knock-in Cre mouse: A multifaceted genetic tool for vision researchers

    Simmons, Aaron B.; Bloomsburg, Samuel J.; Billingslea, Samuel A.; Merrill, Morgan M.; Li, Shuai; Thomas, Marshall W.

    2016-01-01

    nucleus, and superior colliculus. Conclusions: Pou4f2Cre provides multiple uses for the vision researcher’s genetic toolkit. First, Pou4f2Cre is a knock-in allele that can be used to eliminate Pou4f2, resulting in depletion of RGCs. Second, expression of Cre in male germ cells makes this strain an efficient germline activator of recombination, for example, to target LoxP-flanked sequences in the whole mouse. Third, Pou4f2Cre efficiently targets RGCs, amacrine cells, bipolar cells, horizontal cells, and a small number of photoreceptors within the retina, as well as the visual centers in the brain. Unlike other Cre recombinase lines that target retinal neurons, no recombination was observed in Müller or other retinal glia. These properties make this Cre recombinase line a useful tool for vision researchers. PMID:27390513

  12. 78 FR 76851 - Agency Information Collection Activities: Haitian Hemispheric Opportunity Through Partnership...

    2013-12-19

    ...As part of its continuing effort to reduce paperwork and respondent burden, CBP invites the general public and other Federal agencies to comment on an information collection requirement concerning the Haitian Hemispheric Opportunity through Partnership Encouragement Act of 2006 (``Haiti HOPE Act''). This request for comment is being made pursuant to the Paperwork Reduction Act of 1995 (Pub. L.......

  13. Picture windows of opportunity

    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.

  14. Funding Opportunity: Genomic Data Centers

    Funding Opportunity CCG, Funding Opportunity Center for Cancer Genomics, CCG, Center for Cancer Genomics, CCG RFA, Center for cancer genomics rfa, genomic data analysis network, genomic data analysis network centers,

  15. Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

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

    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.

  17. ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes

    Yoshimi, Kazuto; Kunihiro, Yayoi; Kaneko, Takehito; Nagahora, Hitoshi; Voigt, Birger; Mashimo, Tomoji

    2016-01-01

    The CRISPR-Cas system is a powerful tool for generating genetically modified animals; however, targeted knock-in (KI) via homologous recombination remains difficult in zygotes. Here we show efficient gene KI in rats by combining CRISPR-Cas with single-stranded oligodeoxynucleotides (ssODNs). First, a 1-kb ssODN co-injected with guide RNA (gRNA) and Cas9 messenger RNA produce GFP-KI at the rat Thy1 locus. Then, two gRNAs with two 80-bp ssODNs direct efficient integration of a 5.5-kb CAG-GFP vector into the Rosa26 locus via ssODN-mediated end joining. This protocol also achieves KI of a 200-kb BAC containing the human SIRPA locus, concomitantly knocking out the rat Sirpa gene. Finally, three gRNAs and two ssODNs replace 58-kb of the rat Cyp2d cluster with a 6.2-kb human CYP2D6 gene. These ssODN-mediated KI protocols can be applied to any target site with any donor vector without the need to construct homology arms, thus simplifying genome engineering in living organisms. PMID:26786405

  18. Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression

    Yang, Dongshan; Song, Jun; Zhang, Jifeng; Xu, Jie; Zhu, Tianqing; Wang, Zhong; Lai, Liangxue; Chen, Y. Eugene

    2016-01-01

    The laboratory rabbit has been a valuable model system for human disease studies. To make the rabbit model more amendable to targeted gene knockin and stable gene over-expression, we identified a rabbit orthologue of the mouse Rosa26 locus through genomic sequence homology analysis. Real-time PCR and 5′ RACE and 3′ RACE experiments revealed that this locus encodes two transcript variants of a long noncoding RNA (lncRNA) (rbRosaV1 and rbRosaV2). Both variants are expressed ubiquitously and stably in different tissues. We next targeted the rabbit Rosa26 (rbRosa26) locus using CRISPR/Cas9 and produced two lines of knock-in rabbits (rbRosa26-EGFP, and rbRosa26-Cre-reporter). In both lines, all the founders and their offspring appear healthy and reproduce normally. In F1 generation animals, the rbRosa26-EGFP rabbits express EGFP, and the rbRosa26-Cre-reporter rabbits express tdTomato ubiquitously in all the tissues examined. Furthermore, disruption of rbRosa26 locus does not adversely impact the animal health and reproduction. Therefore, our work establishes rbRosa26 as a safe harbor suitable for nuclease mediated gene targeting. The addition of rbRosa26 to the tool box of transgenic research is expected to allow diverse genetic manipulations, including gain-of function, conditional knock out and lineage-tracing studies in rabbits. PMID:27117226

  19. ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes.

    Yoshimi, Kazuto; Kunihiro, Yayoi; Kaneko, Takehito; Nagahora, Hitoshi; Voigt, Birger; Mashimo, Tomoji

    2016-01-01

    The CRISPR-Cas system is a powerful tool for generating genetically modified animals; however, targeted knock-in (KI) via homologous recombination remains difficult in zygotes. Here we show efficient gene KI in rats by combining CRISPR-Cas with single-stranded oligodeoxynucleotides (ssODNs). First, a 1-kb ssODN co-injected with guide RNA (gRNA) and Cas9 messenger RNA produce GFP-KI at the rat Thy1 locus. Then, two gRNAs with two 80-bp ssODNs direct efficient integration of a 5.5-kb CAG-GFP vector into the Rosa26 locus via ssODN-mediated end joining. This protocol also achieves KI of a 200-kb BAC containing the human SIRPA locus, concomitantly knocking out the rat Sirpa gene. Finally, three gRNAs and two ssODNs replace 58-kb of the rat Cyp2d cluster with a 6.2-kb human CYP2D6 gene. These ssODN-mediated KI protocols can be applied to any target site with any donor vector without the need to construct homology arms, thus simplifying genome engineering in living organisms. PMID:26786405

  20. Steel Industry Marginal Opportunity Analysis

    none,

    2005-09-01

    The Steel Industry Marginal Opportunity Analysis (PDF 347 KB) identifies opportunities for developing advanced technologies and estimates both the necessary funding and the potential payoff. This analysis determines what portion of the energy bandwidth can be captured through the adoption of state-of-the-art technology and practices. R&D opportunities for addressing the remainder of the bandwidth are characterized and plotted on a marginal opportunity curve.

  1. Frontier Aerospace Opportunities

    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.

  2. Opportunities for Taiwan's industry

    Jen-Lien Lin

    2004-12-01

    Full Text Available The Industrial Technology Research Institute (ITRI in Taiwan recently introduced nanotechnology to local traditional industries. Nanotechnologies provide a great opportunity for these companies to meet outside challenges and join the blooming electronic and optoelectronic industries. The Nanotechnology Community (NTC was established in 2003, with the goal of finding commercial applications. This year, the Taiwan Nanotechnology Industrialization Promotion Association (TANIPA was established, with the support of the Industrial Development Bureau, Ministry of Economic Affairs (MOEA, to formulate a strategy for industrial applications in Taiwan and to facilitate cooperation between industries, universities, and research institutes.

  3. On Mars Exploration Rovers - Spirit and Opportunity

    李颖; 吴文忠

    2004-01-01

    NASA's twin Mars exploration rovers, now named Spirit and Opportunity, are designed to study the history of water on Mars. These robotic geologists are equipped with a robotic arm, a drilling tool, three spectrometers, and four pairs of cameras that allow them to have a human-like, 3D view of the terrain. Each rover could travel as far as 100 meters in one day to act as Mars scientists eyes and hands, exploring an environment where humans can't yet go.

  4. Opportunities for computer abuse

    Willison, Robert; 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 abuse. Against this backdrop, a number of researchers have addressed the extent to which security managers are cognizant of the very nature of systems risk. In particular, they note how security pr...

  5. Opportunity and obligation

    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...

  6. 32 CFR 505.3 - Privacy Act systems of records.

    2010-07-01

    ... AND PUBLIC RELATIONS ARMY PRIVACY ACT PROGRAM § 505.3 Privacy Act systems of records. (a) Systems of... Register in a system of records notice, which will provide the public an opportunity to comment before DA... Register on new, amended, altered, or deleted systems of records to inform the public of the Privacy...

  7. 75 FR 54331 - Privacy Act of 1974; System of Records

    2010-09-07

    ... updates needed as a result of legislative changes to the Higher Education Act of 1965, as amended (HEA..., 2007, and by the Higher Education Opportunity Act (Pub. L. 110-315) (HEOA), enacted on August 14, 2008... SMART) Grants, and Teacher Education Assistance for College and Higher Education (TEACH) Grants,...

  8. Nuclear Regulatory Authority Act, 2015 (Act 895)

    An Act to establish a Nuclear Regulatory Authority in Ghana. This Act provides for the regulation and management of activities and practices for the peaceful use of nuclear material or energy, and to provide for the protection of persons and the environment against the harmful effects of radiation; and to ensure the effective implementation of the country’s international obligations and for related matters. This Act replaced the Radiation Protection Instrument, of 1993 (LI 1559).

  9. A verification scenario of knock-on tail formation due to nuclear plus interference scattering in 3He-containing deuterium plasmas

    A scenario to verify the knock-on tail formation in deuteron distribution function by nuclear plus interference (NI) scattering and validate the Boltzmann-Fokker-Planck (BFP) model is proposed. Deuterium plasma with 3He-beam injection is considered and on the basis of the BFP model, knock-on tail formation in deuteron distribution function by energetic protons and the resulting modification of the neutron emission spectrum are examined. A recognizable change in the energetic-neutron emission rate due to the knock-on tail formation is presented. The noise neutrons for the measurement arising from the T(d,n)4He reaction is also evaluated by continuous-energy Monte Carlo transport simulation. The influence of the noise (slowing-down) neutrons on the measurement is discussed. (author)

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

    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…

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

    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…

  12. Future Testing Opportunities to Ensure Sustainability of the Biofuels Industry

    The Energy Independence and Security Act (EISA) of 2007 increased the intensity of biofuel research and development throughout the U.S. For the Soil and Plant Analysis Community, this will undoubtedly create new opportunities to provide analytical services that will help ensure mandates such as the ...

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

    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…

  14. Opportunities within ASTERICS

    van der Meer, Rob; Cimò, Giuseppe

    2016-04-01

    ASTERICS, The Astronomy ESFRI and Research Infrastructure Cluster project, brings together astronomers and astroparticle physicists of 22 institutes in Europe to help Europe's world-leading observatories work together to find common solutions to their Big Data challenges, their interoperability and scheduling, and their data access, searching for cross-cutting solutions with mutual and wide-ranging benefit to all concerned. ASTERICS is a four year project, funded through the European Union's Horizon 2020 Framework Programme. The facilities supported by ASTERICS include SKA, CTA, KM3NeT, E-ELT. ASTERICS aims to open up multi messenger astronomy to all scientists and the public through the Virtual Observatory and the citizen science work. I will draw a picture of the landscape in which ASTERICS operates and the possible interaction with the Very Large Volume Neutrino Telescope community. Attention will be given to emerging opportunities for the Neutrino community and how these can be recognised or created.

  15. Opportunities within ASTERICS

    Meer Rob van der

    2016-01-01

    Full Text Available ASTERICS, The Astronomy ESFRI and Research Infrastructure Cluster project, brings together astronomers and astroparticle physicists of 22 institutes in Europe to help Europe's world-leading observatories work together to find common solutions to their Big Data challenges, their interoperability and scheduling, and their data access, searching for cross-cutting solutions with mutual and wide-ranging benefit to all concerned. ASTERICS is a four year project, funded through the European Union's Horizon 2020 Framework Programme. The facilities supported by ASTERICS include SKA, CTA, KM3NeT, E-ELT. ASTERICS aims to open up multi messenger astronomy to all scientists and the public through the Virtual Observatory and the citizen science work. I will draw a picture of the landscape in which ASTERICS operates and the possible interaction with the Very Large Volume Neutrino Telescope community. Attention will be given to emerging opportunities for the Neutrino community and how these can be recognised or created.

  16. Generation opportunities in Alberta

    Reid-Carlson, D. [Optimum Energy Management Inc., Calgary, AB (Canada)

    1998-07-01

    Optimum Energy Management Inc. (OEMI) specializes in: (1) energy management services and training, (2) regulatory consulting, and (3) energy economics and forecasting. As an example of the company`s special expertise, this historical account and future supply and demand forecast for electricity, and for oil and gas in Alberta was presented. The exercise included a review of the Alberta Pool price study and power generation opportunities in a deregulated market, including risks. A rise in pool prices to $25 to $30 per MWh by the year 2000, and a softening of prices beyond the turn of the century were predicted, along with continued regulatory reform and increased levels of competition. Natural gas convergence is expected to drive electricity prices in the future. 1 tab., 11 figs.

  17. An ab-initio analysis of the influence of knock-on-atom induced damage on the peak tensile strength of 3C-SiC grain boundaries

    Han, Yousung; Tomar, Vikas

    2014-01-01

    The effect of knock-on atom induced damage on the peak tensile strength of cubic silicon carbide (3C-SiC) is examined using an ab initio simulation framework based on Car Parrinello Molecular Dynamics method. The framework examines the effect of impact damage caused by a knock-on atom with velocities corresponding to four different kinetic energy levels (50 eV, 500 eV, 1 keV, and 2 keV) in three different SiC structure samples with different grain boundary (GB) configurations. Analyses show t...

  18. 20 CFR 664.600 - Are Local Boards required to offer summer employment opportunities in the local youth program?

    2010-04-01

    ... employment opportunities in the local youth program? 664.600 Section 664.600 Employees' Benefits EMPLOYMENT... INVESTMENT ACT Summer Employment Opportunities § 664.600 Are Local Boards required to offer summer employment opportunities in the local youth program? (a) Yes, Local Boards are required to offer summer youth...

  19. Using strategic foresight to assess conservation opportunity.

    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

  20. Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated siRNA Delivery

    Xinyue Huang

    2016-03-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma that is found in children and has a poor outcome for those with metastatic disease. Two histological groups have been distinguished - embryonal (ERMS and alveolar (ARMS forms. The ARMS subtype has higher rates of metastasis, as well as higher levels of ELMO1, which is thought to be involved in cell migration. Therefore, the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent the metastatic behaviour of ARMS cells. However, challenges still lie in the delivery of nucleotides to a tumour site. Herein, we have described the use of a variety of mesoporous silica nanoparticles as a delivery system for siRNA that is specific for ELMO1 and shown the effective reduction in cell invasive behaviour in these cells.

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

    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.

  2. Knock-down of miR-221 and miR-222 in the radiosensitization of breast cancer cells

    Objective: To investigate the radiosensitizing effect of knock-down of miR-221 miR-222 on MCF-7 human breast cancer cells and explore the possible mechanism. Methods: Antisense oligonucleotides of miR-221 and miR-222 (AS-miR-221 and AS-miR-222), mediated by lipofectamine, were transfected to MCF-7 cells to knock down miR-221 and miR-222, Northern blotting was conducted to detect the expression of miR-221 and miR-222 in transfected cells. The cell apoptosis was detected by flow cytometry and Caspase-3 and Caspase-7 activity assay. Clonogenic assay was used to measure the sensitizing enhancement ratio. Target genes of miR-221 and miR-222 relevant to radio-sensitivity were searched using bioinformatics analysis. The targeted protein expression was determined by Western blot analysis. Results: The expression of miR-221 and miR-222 in the AS-miR-221/222 cells determined by Northern blotting was significantly reduced. Compared with the control group, the cell apoptosis and mitotic cell death after the radiation were significantly higher in AS-miR-221/222 cells. The sensitizing enhancement ratio was 1.87. Based on bioinformatics analysis, PTEN was a target gene of miR-221 and miR-222 which could enhance the radiosensitivity of MCF-7 cells. In AS-miR-221/222 cells, the expression of PTEN was up-regulated while pAkt down-regulated. Conclusions: AS-miR-221 and AS-miR-222 may enhance the radiosensitivity of MCF-7 breast cancer cells by up-regulating the expression of PTEN. (authors)

  3. Learning Opportunities (Editorial

    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

  4. Inequality of Opportunity in Egypt

    Hassine, Nadia Belhaj

    2012-01-01

    The article evaluates the contribution of inequality of opportunity to earnings inequality in Egypt and analyzes its evolution across three time periods and different population groups. It provides parametric and nonparametric estimates of a lower bound for the degree of inequality of opportunity for wage and salary workers. On average, the contribution of opportunity-shaping circumstances to earnings inequality declined from 22 percent in 1988 to 15 percent in 2006. Levels of inequality of o...

  5. Poverty Rankings of Opportunity Profiles

    Vito Peragine; Ernesto Savaglio; Stefano Vannucci

    2008-01-01

    We address the problem of ranking distributions of opportunity sets in terms of poverty. In order to accomplish this task, we identify a suitable notion of ‘multidimensional poverty line’ and we characterize axiomatically several poverty rankings of opportunity profiles. Among them, the Head-Count and the Opportunity-Gap poverty rankings, which are the natural counterparts of the most widely used income poverty indices.

  6. Challenges and Opportunities

    A series of overhead viewgraphs accompanied this presentation. The viewgraphs presented 1998 year-end predictions of oil and gas prices. Comparisons of projected versus actual values for 1998 for natural gas consumption, production, imports and wellhead prices for the United States were also presented. A comparison of projected versus actual consumption values for 1998 in the residential, commercial, industrial and electric generation sectors was included. In many cases actual versus projected values were quite different. The importance of storage to balancing the market was illustrated. Graphs depicting gas production, workover rigs, reserve life comparisons, and GOM natural gas rig count and production for the U.S. were described. Drilling activity in the Gulf of Mexico was summarized. The total wells drilled in 1997 was 1223 compared to 1019 in 1998. The factors affecting deliverability additions on the Gulf of Mexico shelf include smaller new discoveries, diminishing completion opportunities in older fields, few productive zones in new discoveries and a rapid decline rate resulting from smaller reservoirs. 6 tabs., 13 figs

  7. Comprehensive Opportunity and Lost Opportunity Control Model and Enterprise Risk Management

    Akira Nishimura

    2015-07-01

    Full Text Available The purpose of this paper is to build a comprehensive opportunity and lost opportunity control model throughwhich contemporary management accounting can act in alignment with enterprise risk management, as well as toexamine its managerial and socio-economic functions in relation to risk management in the context ofuncertainty in a global finance–oriented society. For this purpose, the paper demonstrates the structure andcharacteristics of this model specifically in contrast with traditional and other control models that have beenpreviously addressed for controlling the changes and diversity of business environments. We can recognize fromthis demonstration that the accounting control system based on opportunity and lost opportunity control modelhas shifted its fundamental focus from feedback systems, profitability, and managerial control to feed-forward,value creation, and enterprise governance. The paper also refers to the socio-economic function that the modelfulfills in the disclosure and transparency of the risk management process. These results lead to the conclusionthat contemporary management accounting expands its short-term efficiency and company-centeredeffectiveness into long-term efficiency and social effectiveness.

  8. Assertive Community Treatment (ACT)

    ... services—including both ER visits and inpatient hospitalizations—ACT team members are also well-connected with local hospitals and have the ability to work with hospital and emergency room staff. ACT teams ...

  9. Marine Mammal Protection Act

    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...

  10. ACTS data center

    Syed, Ali; Vogel, Wolfhard J.

    1993-01-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

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

    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.

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

    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.

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

    Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

    2015-01-01

    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. PMID:26473830

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

    Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper; Klein, David C; Møller, Morten

    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...

  15. 9 CFR 335.40 - Opportunity for presentation of views before report of criminal violations.

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Opportunity for presentation of views... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE FEDERAL MEAT INSPECTION ACT Criminal Violations § 335.40 Opportunity for presentation of...

  16. Nuclear Installations Act 1965

    This Act governs all activities related to nuclear installations in the United Kingdom. It provides for the licensing procedure for nuclear installations, the duties of licensees, the competent authorities and carriers of nuclear material in respect of nuclear occurrences, as well as for the system of third party liability and compensation for nuclear damage. The Act repeals the Nuclear Installations (Licensing and Insurance) Act 1959 and the Nuclear Installations (Amendment Act) 1965 except for its Section 17(2). (NEA)

  17. Forgetting ACT UP

    Juhasz, Alexandra

    2012-01-01

    When ACT UP is remembered as the pinnacle of postmodern activism, other forms and forums of activism that were taking place during that time--practices that were linked, related, just modern, in dialogue or even opposition to ACT UP's "confrontational activism"--are forgotten. In its time, ACT UP was embedded in New York City, and a larger world,…

  18. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Ghulam Muhammad Kundi

    2008-12-01

    Full Text Available ABSTRACT 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.

  19. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    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.

  20. Opportunity-Sensitive Poverty Measurement

    Brunori, Paolo; Francisco H.G. Ferreira; Lugo, Maria Ana; Peragine, Vito

    2013-01-01

    This paper offers an axiomatic characterization of two classes of poverty measures that are sensitive to inequality of opportunity, one a strict subset of the other. The proposed indices are sensitive not only to income shortfalls from the poverty line, but also to differences in the opportunities faced by people with different predetermined characteristics, such as race or family backgrou...

  1. Investment opportunities as real options

    Rovčanin, Adnan

    2005-01-01

    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 im...

  2. 增压发动机怠速敲缸噪声研究%Research on Idle Knocking Noise of Turbocharged Engine

    冯圆; 杨瑞文; 陈红兵; 黄春生; 王勇

    2013-01-01

    通过研究某增压发动机的怠速敲缸噪声,总结了活塞总成系统的噪声分类,研究了活塞偏心量、连杆大头油孔以及活塞冷却喷嘴对怠速敲缸噪声的影响.研究结果显示,活塞偏心量和连杆大头的油孔对于改善怠速敲缸噪声有很好的效果,而活塞冷却喷嘴不仅能起到冷却活塞的作用,还对怠速敲缸噪声有决定性的影响.通过改变活塞冷却喷嘴的开启压力,在怠速时开启,可以完全消除怠速敲缸噪声.%Based on the idle knocking noise of a turbocharged engine,the noise classification of piston assembly was summarized,and the influences of piston offset,connecting rod big end hole and piston oil nozzle on the idle knocking were researched.The results showed that the piston offset and connecting rod big end hole could improve the idle knocking effectively.The piston oil nozzle had decisive effect on improving the idle knocking noise besides cooling the piston.The optimized opening pressure of piston oil nozzle could eliminate the idle knocking noise.

  3. Indirect Speech Acts

    李威

    2001-01-01

    Indirect speech acts are frequently used in verbal communication, the interpretation of them is of great importance in order to meet the demands of the development of students' communicative competence. This paper, therefore, intends to present Searle' s indirect speech acts and explore the way how indirect speech acts are interpreted in accordance with two influential theories. It consists of four parts. Part one gives a general introduction to the notion of speech acts theory. Part two makes an elaboration upon the conception of indirect speech act theory proposed by Searle and his supplement and development of illocutionary acts. Part three deals with the interpretation of indirect speech acts. Part four draws implication from the previous study and also serves as the conclusion of the dissertation.

  4. Lunar Science Opportunities for Students within Higher Education

    Bailey, B.; Daou, D.; Minafra, J.

    2011-10-01

    The NASA Lunar Science Institute (NLSI) is a virtual institute focused on lunar science, training the next generation of lunar scientists, and education and public outreach. As part of the NLSI 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. This talk will outline several opportunities for undergraduate and graduate students as well as earlycareer scientists and engineers to engage the lunar science and exploration communities through workshops, conferences, online seminars and classes, student exchange programs and internships.

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

    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

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

    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.

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

    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

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

    Highlights: ► Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. ► Up-regulation of ABCG1 improves lung function. ► Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ) and the PPARγ-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 PPARγ. 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)-PPARγ 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 PPARγ 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 analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice

  9. Promoting Prevention Through the Affordable Care Act: Workplace Wellness

    Anderko, Laura; Roffenbender, Jason S.; Goetzel, Ron Z.; Millard, Francois; Wildenhaus, Kevin; DeSantis, Charles; Novelli, William

    2012-01-01

    Public health in the United States can be improved by building workplace “cultures of health” that support healthy lifestyles. The Affordable Care Act (ACA), which includes the Prevention and Public Health Fund, will support a new focus on prevention and wellness, offering opportunities to strengthen the public’s health through workplace wellness initiatives. This article describes the opportunity the ACA provides to improve worker wellness.

  10. Biogas Opportunities Roadmap Progress Report

    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.

  11. Tax Act encourages business purchases in 2009.

    Epple, Rick

    2009-01-01

    In talking with dentists, the awareness level of the opportunity provided by the American Recovery and Reinvestment Act seems to be rather low. The Act provides tax breaks for dental practice owners to create jobs by making it attractive to invest in their practices. However, lower taxes should not be what drives the decision making process. First and foremost, the capital improvements need to make sense from a business and return-on-investment standpoint. There is not much time to complete the project(s) in 2009 and to benefit from the tax breaks afforded by the ARRA. Therefore, dentists should consult with their tax advisors as soon as possible to take full advantage of the provisions the Act provides. PMID:19757644

  12. Quantum measurement act as a "speech act"

    Schneider, J

    2005-01-01

    I show that the quantum measurement problem can be understood if the measurement is seen as a ``speech act'' in the sense of modern language theory. The reduction of the state vector is in this perspective an intersubjectice -- or better a-subjective -- symbolic process. I then give some perspectives on applications to the ``Mind-Body problem''.

  13. Histamine 1 receptor knock out mice show age-dependent susceptibility to status epilepticus and consequent neuronal damage.

    Kukko-Lukjanov, Tiina-Kaisa; Grönman, Maria; Lintunen, Minnamaija; Laurén, Hanna B; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2012-06-01

    The central histaminergic neuron system is an important regulator of activity stages such as arousal and sleep. In several epilepsy models, histamine has been shown to modulate epileptic activity and histamine 1 (H1) receptors seem to play a key role in this process. However, little is known about the H1 receptor-mediated seizure regulation during the early postnatal development, and therefore we examined differences in severity of kainic acid (KA)-induced status epilepticus (SE) and consequent neuronal damage in H1 receptor knock out (KO) and wild type (WT) mice at postnatal days 14, 21, and 60 (P14, P21, and P60). Our results show that in P14 H1 receptor KO mice, SE severity and neuronal damage were comparable to those of WT mice, whereas P21 KO mice had significantly decreased survival, more severe seizures, and enhanced neuronal damage in various brain regions, which were observed only in males. In P60 mice, SE severity did not differ between the genotypes, but in KO group, neuronal damage was significantly increased. Our results suggest that H1 receptors could contribute to regulation of seizures and neuronal damage age-dependently thus making the histaminergic system as a challenging target for novel drug design in epilepsy. PMID:22348791

  14. Vpx-Independent Lentiviral Transduction and shRNA-Mediated Protein Knock-Down in Monocyte-Derived Dendritic Cells.

    Wojciech Witkowski

    Full Text Available The function of dendritic cells (DCs in the immune system is based on their ability to sense and present foreign antigens. Powerful tools to research DC function and to apply in cell-based immunotherapy are either silencing or overexpression of genes achieved by lentiviral transduction. To date, efficient lentiviral transduction of DCs or their monocyte derived counterparts (MDDCs required high multiplicity of infection (MOI or the exposure to the HIV-2/SIV protein Vpx to degrade viral restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1. Here we present a Vpx-independent method for efficient (>95% transduction of MDDCs at lower MOI. The protocol can be used both for ectopic gene expression and knock-down. Introducing shRNA targeting viral entry receptor CD4 and restriction factor SAMHD1 into MDDCs resulted in down-regulation of targeted proteins and, consequently, expected impact on HIV infection. This protocol for MDDCs transduction is robust and free of the potential risk arising from the use of Vpx which creates a virus infection-prone environment, potentially dangerous in clinical setting.

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

    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. PMID:22983956

  16. Generation and evaluation of Myostatin knock-out rabbits and goats using CRISPR/Cas9 system.

    Guo, Rihong; Wan, Yongjie; Xu, Dan; Cui, Libin; Deng, Mingtian; Zhang, Guomin; Jia, Ruoxin; Zhou, Wenjun; Wang, Zhen; Deng, Kaiping; Huang, Mingrui; Wang, Feng; Zhang, Yanli

    2016-01-01

    Myostatin (Mstn) is a conserved negative regulator of skeletal muscle mass in mammals. However, whether precise disruption of Mstn in livestock can be achieved and safely used to improve meat productivity has not been proven. We applied CRISPR/Cas9 system to generate Mstn knock-out (KO) rabbits and goats and then analyzed the changes in their phenotypes to answer this question. We efficiently generated 24 Mstn KO rabbits out of 32 newborn infants after embryo injection with two sgRNAs targeting rabbit Mstn, and found that the Mstn KO rabbits exhibited increased birthweight and a significantly increase in the weight ratios of the quadriceps and biceps muscles to the whole body. Mstn KO also caused high probability of enlarged tongue phenomenon and severe health problems such as stillbirth and early stage death. Using the same method, one out of four goats was generated with edition at Mstn locus. The early stage growth rate of this goat outperformed the control goats. In conclusion, we efficiently generated Mstn KO rabbits and goats using CRISPR/Cas9 technology. However, Mstn KO causes severe health problems and may also have the same effects on other species. This safety issue must be studied further before applied to animal reproduction processes. PMID:27417210

  17. CHO cells knocked out for TSC2 display an improved productivity of antibodies under fed batch conditions.

    McVey, Duncan; Aronov, Michael; Rizzi, Giovanni; Cowan, Alexis; Scott, Charo; Megill, John; Russell, Reb; Tirosh, Boaz

    2016-09-01

    The kinase mTOR operates in two cellular complexes, mTORC1 and mTORC2. mTORC1 adjusts metabolic activity according to external growth conditions and nutrients availability. When conditions are prosperous, mTOR facilitates protein and lipid biosyntheses and inhibits autophagy, while under metabolic constraints, however, its attenuation induces a catabolic program, energy preservation and autophagy. CHO is a key cell line for manufacturing of biologics owing to its remarkable ability to grow to high densities and maintain protein production and secretion for extended times. While high mTOR activity has been associated with high productivity in CHO cells, its inhibition by rapamycin has also been documented to augment productivity via promotion of viability. Here using CRISPR/Cas9 editing we engineered CHO cells to enforce high mTORC1 activity by knocking-out TSC2, a major mTOR inhibitory protein, or PTEN, a phosphatase that attenuates the PI3K/AKT/mTOR pathway. Only TSC2-deleted cells exhibited a constitutive activation of mTORC1 under fed batch conditions. Cells grew larger in size, synthesized more proteins and displayed an over twofold elevation in their specific productivity. While peak viable cell density was compromised, overall titers increased to an extent dependent upon the parental clone. Our data underscore manipulation of TSC as a strategy to improve performance of CHO cell in bioreactors. Biotechnol. Bioeng. 2016;113: 1942-1952. © 2016 Wiley Periodicals, Inc. PMID:26888596

  18. Side chain modified peptide nucleic acids (PNA for knock-down of six3 in medaka embryos

    Dorn Sebastian

    2012-08-01

    Full Text Available Abstract Background Synthetic antisense molecules have an enormous potential for therapeutic applications in humans. The major aim of such strategies is to specifically interfere with gene function, thus modulating cellular pathways according to the therapeutic demands. Among the molecules which can block mRNA function in a sequence specific manner are peptide nucleic acids (PNA. They are highly stable and efficiently and selectively interact with RNA. However, some properties of non-modified aminoethyl glycine PNAs (aegPNA hamper their in vivo applications. Results We generated new backbone modifications of PNAs, which exhibit more hydrophilic properties. When we examined the activity and specificity of these novel phosphonic ester PNAs (pePNA molecules in medaka (Oryzias latipes embryos, high solubility and selective binding to mRNA was observed. In particular, mixing of the novel components with aegPNA components resulted in mixed PNAs with superior properties. Injection of mixed PNAs directed against the medaka six3 gene, which is important for eye and brain development, resulted in specific six3 phenotypes. Conclusions PNAs are well established as powerful antisense molecules. Modification of the backbone with phosphonic ester side chains further improves their properties and allows the efficient knock down of a single gene in fish embryos.

  19. Spatial and temporal lineage analysis of a Pitx3-driven Cre-recombinase knock-in mouse model.

    Marten P Smidt

    Full Text Available Development and function of mesodiencephalic dopaminergic (mdDA neurons has received a lot of scientific interest since these neurons are critically involved in neurological diseases as Parkinson and psychiatric diseases as schizophrenia, depression and attention deficit hyperactivity disorder (ADHD. The understanding of the molecular processes that lead to normal development and function of mdDA neurons has provided insight in the pathology and provided critical information on new treatment paradigms. In order to be able to study specific genetic ablation in mdDA neurons a new tools was developed that drives Cre-recombinase under the control of the Pitx3 locus. The Pitx3 gene is well known for its specific expression in mdDA neurons and is present at the onset of terminal differentiation. Analysis of newly generated Pitx3-Cre knock-in mice shows that Cre expression, measured through the activation of eYfp by removal of a "Stop" signal (LoxP-Stop-LoxP-eYfp reporter mouse, is present at the onset of terminal differentiation and mimics closely the native Pitx3 expression domain. In conclusion, we present here a new Cre-driver mouse model to be used in the restricted ablation of interesting genes in mdDA neurons in order to improve our understanding of the underlying molecular programming.

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

    Noah Saederup

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

  1. Novel therapeutic targets in osteoarthritis: Narrative review on knock-out genes involved in disease development in mouse animal models.

    Veronesi, Francesca; Della Bella, Elena; Cepollaro, Simona; Brogini, Silvia; Martini, Lucia; Fini, Milena

    2016-05-01

    Osteoarthritis (OA) can affect every joint, especially the knee. Given the complexity of this pathology, OA is difficult to treat with current therapies, which only relieve pain and inflammation and are not capable of restoring tissues once OA has started. Currently, researchers focus on finding a therapeutic strategy that may help to arrest disease progression. The present narrative review gives an overview of the genes involved in the development and progression of OA, assessing in vivo studies performed in knock-out mice affected by OA, to suggest new therapeutic strategies. The article search was performed on the PubMed database and www.webofknowledge.com website with the following keywords: "knee osteoarthritis" AND "knockout mice". The included studies were in English and published from 2005 to 2015. Additional papers were found within the references of the selected articles. In the 55 analyzed in vivo studies, genes mainly affected chondrocyte homeostasis, inflammatory processes, extracellular matrix and the relationship between obesity and OA. Genes are defined as inducing, preventing and not influencing OA. This review shows that joint homeostasis depends on a variety of genetic factors, and preventing or restoring the loss of a gene encoding for protective proteins, or inhibiting the expression of proteins that induce OA, might be a potential therapeutic approach. However, conclusions cannot be drawn because of the wide variability concerning the technique used for OA induction, the role of the genes, the method for tissue evaluations and the lack of assessments of all joint tissues. PMID:27059198

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

    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.

  3. Ammonia excretion in Caenorhabditis elegans: Physiological and molecular characterization of the rhr-2 knock-out mutant.

    Adlimoghaddam, Aida; O'Donnell, Michael J; Kormish, Jay; Banh, Sheena; Treberg, Jason R; Merz, David; Weihrauch, Dirk

    2016-05-01

    Previous studies have shown the free living soil nematode Caenorhabditis elegans (N2 strain) to be ammonotelic. Ammonia excretion was suggested to take place partially via the hypodermis, involving the Na(+)/K(+)-ATPase (NKA), V-ATPase (VAT), carbonic anhydrase, NHX-3 and a functional microtubule network and at least one Rh-like ammonia transporter RHR-1. In the current study, we show that a second Rh-protein, RHR-2, is highly expressed in the hypodermis, here also in the apical membrane of that tissue. To further characterize the role of RHR-2 in ammonia excretion, a knock-out mutant rhr-2 (ok403), further referred to as ∆rhr-2, was employed. Compared to wild-type worms (N2), this mutant showed a lower rate of ammonia excretion and a lower hypodermal H(+) excretion rate. At the same time rhr-1, nka, vat, and nhx-3 showed higher mRNA expression levels when compared to N2. Also, in contrast to N2 worms, ∆rhr-2 did not show enhanced ammonia excretion rates when exposed to a low pH environment, suggesting that RHR-2 represents the apical NH3 pathway that allows ammonia trapping via the hypodermis in N2 worms. A hypothetical model for the mechanism of hypodermal ammonia excretion is proposed on the basis of data in this and previous investigations. PMID:26872996

  4. Radiological Protection Act 1970

    This Act provides for the establishment of a Radiological Protection Board to undertake research and advise on protection from radiation hazards. Its functions include provision of advice to Government departments with responsibilities in relation to protection of sectors of the community or the community as a whole against the hazards of ionizing radiation. The Act, which lays down that the Board shall replace certain departments concerned with radiation protection, repeals several Sections of the Radioactive Substances Act 1948 and the Science and Technology Act 1965. (NEA)

  5. ACT Verbal Prep Course

    Standridge, Nathan

    2012-01-01

    Comprehensive Prep for ACT Verbal. Every year, students pay 1,000 and more to test prep companies to prepare for the verbal sections of the ACT. Now you can get the same preparation in a book. The verbal sections are not easy. There is no quick fix that will allow you to "beat" the ACT, but it is very learnable. If you study hard and master the techniques in this book, your score will improve-significantly. The ACT cannot be "beaten." But it can be mastered-through hard work, analytical thought, and by training yourself to think like a test writer. Many of the exercises in this book are design

  6. US Forest Service Recreation Opportunities

    US Forest Service, Department of Agriculture — A map service on the www depicting the recreation opportunity information that the Forest Service collects through the Recreation Portal and shares with the public...

  7. Employment opportunities for the disabled

    Delsen, L.W.M.

    1996-01-01

    Policy makers in the OECD Member States have developed quite different programmes and institutional arrangements to create and promote employment opportunities for the disabled. These policy approaches include legal interventions, employment support services, financial support of open employment and

  8. Opportunity Cost of Distance Education

    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.

  9. Wind Technologies & Evolving Opportunities (Presentation)

    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.

  10. Opportunity formation in social entrepreneurship

    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...... 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 and...... alternative to the discovery view and to our understanding of the role of opportunities in the social entrepreneurship process.  Practical implications - The findings suggest that the social entrepreneur is one that actively creates external circumstances rather than responds to opportunities already present...

  11. EMU and Portfolio Diversification Opportunities

    Kpate ADJAOUTE; Danthine, Jean-Pierre

    2001-01-01

    This paper studies the impact of EMU on portfolio diversification opportunities. We find a significant increase in the correlation between stock returns, whether they are computed on the basis of market or sector indices. This is true for two definitions of the pre-convergence and convergence periods. Diversification opportunities within the Euro-area have thus been reduced. The culprit appears to be less the disappearance of currency risk than the convergence of economic structures and/or th...

  12. Greating opportunities at Luncheon Party

    2010-01-01

    @@ On January 26, more than 200 representatives from the business circles in China and Argentina joined together to find more opportunities at the Luncheon Party for China-Argentina Opportunities in Trade, Investment and Business.The Luncheon was jointly initiated by CCPIT and Argentina's Embassy in China.Mr. Yu Ping, Vice President of CCPIT, and Mr. Tayana, Minister of International Trade and Culture of Argentina attended and addressed the luncheon.

  13. Network marketing as an opportunity

    Hakun, Peter

    2010-01-01

    The objective of this thesis is to clarify network marketing and how it works and to describe its advantages, disadvantages and opportunity which it offers to producer, distributor and consumer. The first chapter gives a definition of network marketing, explains how it works and refers to its history. In the second chapter the network marketing is compared to common distribution chain from producer's as well as consumer's point of view. Opportunities which network marketing offers to a distri...

  14. Opportunity Lowers for Egress (animation)

    2004-01-01

    This animation strings together three images from the rear hazard-identification camera on the Mars Exploration Rover Opportunity. The 'movie' shows the lander before and after it successfully tilted itself forward by hyperextending its rear lander petal downward. This manuever was performed in preparation for egress, or rolling off the lander at Meridiani Planum, Mars. Opportunity will roll north off the lander, opposite this viewpoint.

  15. Inequality of opportunity in India

    Singh, Ashish

    2010-01-01

    The paper associates inequality of opportunities with outcome differences that can be accounted by pre-determined circumstances which lie beyond the control of an individual, such as parental education, parental occupation, caste, religion and place of birth. The overall opportunity share estimates (parametric) of total consumption expenditure inequality due to a set of circumstances comprising of caste, religion, geographical region, parental education and parental occupation vary from 16% t...

  16. A Human t-PA Mutant cDNA Cassette Knocked in the Murine fgfr-4 Locus Targeting for Mammary Gland Expression

    Fu-Yu LIN; Hong-Xing CHEN; Xuan CHENG; Xiao YANG; Ji-Xian DENG; Pei-Tang HUANG

    2004-01-01

    The expression of foreign gene in transgenic animals produced by pronuclear microinjection is often confounded by the position effects caused by not only the nature of chromosomal integration site but also the number and arrangement of multiple transgene copies. Gene targeting provides a new way to overcome these inhibitions by introducing single-copy transgene into a chosen site. The choice of a good chromosomal site will favor transgene expression in a predictable fashion. In this study, we tested a new site (fgfr-4) for foreign gene integration and expression. A t-PA mutant (t-PAm) expression cassette under bovine αs1-casein regulatory sequences was efficiently knocked-infgfr-4 site through homologous recombination. The t-PAm was expressed in the milk of all targeted mice. Our experiment indicates that the fgfr-4 may be a candidate site for knocking foreign gene to make transgenic animals.

  17. A comparison of single knock-on and complete bubble destruction models of the fission induced re-solution of gas atoms from bubbles

    In previous theoretical studies of the behaviour of the fission gases in nuclear fuel, the Nelson single knock-on model of the fission induced re-solution of gas atoms from fission gas bubbles has been employed. In the present investigation, predictions from this model are compared with those from a complete bubble destruction model of the re-solution process. The main conclusions of the study are that the complete bubble destruction model predicts more gas release after a particular irradiation time than the single knock-on model, for the same choice of the model parameters, and that parameter sets chosen to give the same gas release predict significantly different bubble size distribution functions. (author)

  18. 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

    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.

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

    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.

  20. Radiation emitting devices act

    This Act, entitled the Radiation Emitting Devices Act, is concerned with the sale and importation of radiation emitting devices. Laws relating to the sale, lease or import, labelling, advertising, packaging, safety standards and inspection of these devices are listed as well as penalties for any person who is convicted of breaking these laws

  1. Opportunities for learning and knowledge creation in practice

    Nilsen, Etty Ragnhild

    2010-01-01

    This study contributes to our understanding of opportunities for learning and knowledge creation at work. Through an interpretive case study the aim is to add insight to the theoretical debate on learning and knowledge creation, as well as inform managerial practice. Findings in this study show a gap between a strategic vision of "becoming a learning organization" and how this is translated and acted upon in ongoing work practices. This is underpinned by a view on knowledge and learning that ...

  2. EDUCATIONAL OPPORTUNITIES OF COLLAGE AS A DIDACTIC MEANS: INTERDISCIPLINARY APPROACH

    I. B. Ryzhkina

    2015-01-01

    The research aim is to examine the functions and educational opportunities of collage as a didactic means.The methodology and methods involve the multilateral theoretical data analysis and generalization; activity approach to pupils’ perception analysis; communicative approach to finding the interrelation between the perception and speech act; lingua-cultural approach to collage consideration as a sign, information vehicle and communication subject; and developmental teaching approach.The aut...

  3. Act local, think global

    Tip O'Neill, one of the grand old men of modem US politics, once famously remarked that all politics is local. Like most politicians who succeed on the national stage - and not just in the US - it was a truth he never lost sight of. What is true for politicians is equally true in the communications business. We may increasingly live in a global village, but successful companies - even multi-nationals - forget the importance of local and regional public relations at their peril. Think of Douglas Ivester, the CEO of Coca-Cola at the time of the 1999 Belgian contamination scandal, who allegedly reacted to first reports of the crisis by asking: 'Where the hell is Belgium?' A more appropriate question today - several years after Coke's share price toppled and the CEO was unceremoniously sacked - might be: 'Who the hell is Douglas Nester?' But - to adapt another famous phrase - the fact that communications (and marketing) professionals still need to 'act local' as much as ever before should not blind us to the growing need to 'think global'. In the nuclear industry, as in the world economy generally, increasing global integration is a reality, as are the international nature of the news media and the increasingly global nature of the anti-nuclear pressure groups. Indeed, it was the growing need for a truly global information network to counter these trends, by increasing the overall speed and accuracy of the worldwide nuclear information flow, that led the nuclear community to establish NucNet in 1991. So where exactly is the line between local and regional nuclear communications on the one hand, and global communications on the other? Is there one spin for a regional audience, and another for a global audience? This presentation proposes some guiding principles, by examining the response of nuclear communicators world-wide to the new communications agenda imposed in the wake of the September 11th suicide attacks in the US. NucNet President Doug McRoberts and Executive

  4. Cell- and region-specific miR30-based gene knock-down with temporal control in the rat brain

    Xu Haibo

    2010-12-01

    Full Text Available Abstract Background RNA interference (RNAi emerges as a powerful tool to induce loss-of-function phenotypes. In the context of the brain, gene manipulation is best targeted to specific subsets of cells in order to achieve a physiologically relevant outcome. Polymerase II-based viral expression systems can be used to cell-specifically express constructs incorporating flanking and loop sequences from endogenous microRNA (miRNA, which directs the designed hairpins into the endogenous gene silencing machinery. While many studies have documented non-cell-selective gene knock-down in the brain, it has not been tested whether different cell types or different areas of the central nervous system (CNS are equally amenable to this approach. We have evaluated this issue using a tetracycline (Tet-controllable and cell-specific miRNA 30 (miR30-based short hairpin (shRNA interference system. Results To achieve targeted expression two cell type-specific promoters were used; the enhanced compact glial fibrillary acidic protein (GfaABC1D promoter and the enhanced human synapsin-1 (SYN promoter. Powerful luciferase (Luc and the neuronal isoform of nitric oxide synthase (nNOS gene knock-down were achieved both in vitro and in vivo. Administration of doxycycline (Dox abrogated gene silencing. However, the efficacy of gene knock-down in both neurones and astrocytes in the hippocampus (HIP was lower than that in the dorsal vagal complex of the brainstem (DVC. This was not due to regional differences in the expression of the the key enzymes involved in miRNA processing. Conclusions The results from the presented experiments demonstrated that selective gene knock-down in subsets of brain cells is achievable. However, there are some presently unknown regional factors which affect either the processing of miRNA-based cassettes or their potency for gene silencing.

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

    Shaokun Zhang; Zaoxia Liu; Guanfang Su; Hong Wu

    2016-01-01

    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 prima...

  6. A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure

    Sun, Lei; Gilligan, Jeff; Staber, Cynthia; Schutte, Ryan J; Nguyen, Vivian; O'Dowd, Diane K.; Reenan, Robert

    2012-01-01

    Over 40 missense mutations in the human SCN1A sodium channel gene are linked to an epilepsy syndrome termed genetic epilepsy with febrile seizures plus (GEFS+). Inheritance of GEFS+ is dominant but the underlying cellular mechanisms remain poorly understood. Here we report knock-in of a GEFS+ SCN1A mutation (K1270T) into the Drosophila sodium channel gene, para, causes a semi-dominant temperature-induced seizure phenotype. Electrophysiological studies of GABAergic interneurons in the brains o...

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

    Tetsushi Sakuma; Mitsumasa Takenaga; Yoshinori Kawabe; Takahiro Nakamura; Masamichi Kamihira; Takashi Yamamoto

    2015-01-01

    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, includi...

  8. Comprehensive Behavioral and Molecular Characterization of a New Knock-In Mouse Model of Huntington’s Disease: zQ175

    Menalled, Liliana B.; Kudwa, Andrea E.; Miller, Sam; Fitzpatrick, Jon; Watson-Johnson, Judy; Keating, Nicole; Ruiz, Melinda; Mushlin, Richard; Alosio, William; McConnell, Kristi; Connor, David; Murphy, Carol; Oakeshott, Steve; Kwan, Mei; Beltran, Jose

    2012-01-01

    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 p...

  9. Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11β knock-down.

    Esmaeili, M; Ghaedi, K; Shoaraye Nejati, A; Nematollahi, M; Shiralyian, H; Nasr-Esfahani, M H

    2016-01-15

    Peroxisomes constitute special cellular organelles which display a variety of metabolic functions including fatty acid oxidation and free radical elimination. Abundance of these flexible organelles varies in response to different environmental stimuli. It has been demonstrated that PEX11β, a peroxisomal membrane elongation factor, is involved in the regulation of size, shape and number of peroxisomes. To investigate the role of PEX11β in neural differentiation of mouse embryonic stem cells (mESCs), we generated a stably transduced mESCs line that derives the expression of a short hairpin RNA against Pex11β gene following doxycycline (Dox) induction. Knock-down of Pex11β, during neural differentiation, significantly reduced the expression of neural progenitor cells and mature neuronal markers (p<0.05) indicating that decreased expression of PEX11β suppresses neuronal maturation. Additionally, mRNA levels of other peroxisome-related genes such as PMP70, Pex11α, Catalase, Pex19 and Pex5 were also significantly reduced by Pex11β knock-down (p<0.05). Interestingly, pretreatment of transduced mESCs with peroxisome proliferator-activated receptor γ agonist (pioglitazone (Pio)) ameliorated the inhibitory effects of Pex11β knock down on neural differentiation. Pio also significantly (p<0.05) increased the expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mESC. Results elucidated the importance of Pex11β expression in neural differentiation of mESCs, thereby highlighting the essential role of peroxisomes in mammalian neural differentiation. The observation that Pio recovered peroxisomal function and improved neural differentiation of Pex11β knocked-down mESCs, proposes a potential new pharmacological implication of Pio for neurogenesis in patients with peroxisomal defects. PMID:26562432

  10. Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

    Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

    2008-09-01

    Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients. PMID:18558633

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

    Tiang, Jacky M; Butcher, Neville J; Cullinane, Carleen; Humbert, Patrick O; Minchin, Rodney F

    2011-01-01

    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. PMID:21347396

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

    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.

  13. Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair.

    He, Xiangjun; Tan, Chunlai; Wang, Feng; Wang, Yaofeng; Zhou, Rui; Cui, Dexuan; You, Wenxing; Zhao, Hui; Ren, Jianwei; Feng, Bo

    2016-05-19

    CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires-eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. PMID:26850641

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

    Wu, Jian-Chun; Feng, Qi-Jie; Liu, Xian-Kun; Zhan, Chang-Yong; Zou, Yu; Liu, Yao-Guang

    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 B4C 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.

  15. Complete knock down (CKD) house made of wood from waste biomass and plastic for disaster struck areas

    people living for months if not years in tents provided as temporary shelter. Fibersit, has come up with the idea to build Complete Knock Down (CKD) houses of wood made from waste material as describes above. The initial project will involve building 3 houses with basic facilities with a size of 20 ft x 20 ft (400 sqft) at the current factory site in Banting, Selangor. It is proposed to get the local youths (about 5 volunteers - from the World Youth Foundation) to be trained in putting up and knocking down the houses. After, this training, a new site will be chosen for the house to be located and the youths can be the agents to put up these houses in the new locations (preferably in Rural Sarawak or Sabah). It is suggested to get the involvement of MERCY Malaysia, UNDP and UN Habitat into this project as it will be easier to promote the project to the Nation and International arena upon its success. (author)

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

    José Dijair Antonino de Souza Júnior

    Full Text Available 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.

  17. Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age.

    Amita Vaidya

    2014-07-01

    Full Text Available Accumulation of genome rearrangements is a characteristic of aged tissues. Since genome rearrangements result from faulty repair of DNA double strand breaks (DSBs, we hypothesized that DNA DSB repair becomes less efficient with age. The Non-Homologous End Joining (NHEJ pathway repairs a majority of DSBs in vertebrates. To examine age-associated changes in NHEJ, we have generated an R26NHEJ mouse model in which a GFP-based NHEJ reporter cassette is knocked-in to the ROSA26 locus. In this model, NHEJ repair of DSBs generated by the site-specific endonuclease, I-SceI, reconstitutes a functional GFP gene. In this system NHEJ efficiency can be compared across tissues of the same mouse and in mice of different age. Using R26NHEJ mice, we found that NHEJ efficiency was higher in the skin, lung, and kidney fibroblasts, and lower in the heart fibroblasts and brain astrocytes. Furthermore, we observed that NHEJ efficiency declined with age. In the 24-month old animals compared to the 5-month old animals, NHEJ efficiency declined 1.8 to 3.8-fold, depending on the tissue, with the strongest decline observed in the skin fibroblasts. The sequence analysis of 300 independent NHEJ repair events showed that, regardless of age, mice utilize microhomology sequences at a significantly higher frequency than expected by chance. Furthermore, the frequency of microhomology-mediated end joining (MMEJ events increased in the heart and lung fibroblasts of old mice, suggesting that NHEJ becomes more mutagenic with age. In summary, our study provides a versatile mouse model for the analysis of NHEJ in a wide range of tissues and demonstrates that DNA repair by NHEJ declines with age in mice, which could provide a mechanism for age-related genomic instability and increased cancer incidence with age.

  18. Epothilone B Confers Radiation Dose Enhancement in DAB2IP Gene Knock-Down Radioresistant Prostate Cancer Cells

    Purpose: In metastatic prostate cancer, DOC-2/DAB2 interactive protein (DAB2IP) is often downregulated and has been reported as a possible prognostic marker to predict the risk of aggressive prostate cancer (PCa). Our preliminary results show that DAB2IP-deficient PCa cells are radioresistant. In this study, we investigated the anticancer drug Epothilone B (EpoB) for the modulation of radiosensitivity in DAB2IP-deficient human PCa cells. Methods and Materials: We used a stable DAB2IP-knock down human PCa cell line, PC3 shDAB2IP, treated with EpoB, ionizing radiation (IR), or the combined treatment of EpoB and IR. The modulation of radiosensitivity was determined by surviving fraction, cell cycle distribution, apoptosis, and DNA double-strand break (DSB) repair. For in vivo studies, the PC3shDAB2IP xenograft model was used in athymic nude mice. Results: Treatment with EpoB at IC50 dose (33.3 nM) increased cellular radiosensitivity in the DAB2IP-deficient cell line with a dose enhancement ratio of 2.36. EpoB delayed the DSB repair kinetics after IR and augmented the induction of apoptosis in irradiated cells after G2/M arrest. Combined treatment of EpoB and radiation enhanced tumor growth delay with an enhancement factor of 1.2. Conclusions: We have demonstrated a significant radiation dose enhancement using EpoB in DAB2IP-deficient prostate cancer cells. This radiosensitization can be attributed to delayed DSB repair, prolonged G2 block, and increased apoptosis in cells entering the cell cycle after G2/M arrest.

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

    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

  20. Cystamine and cysteamine prevent 3-NP-induced mitochondrial depolarization of Huntington's disease knock-in striatal cells.

    Mao, Zhengkuan; Choo, Yeun Su; Lesort, Mathieu

    2006-04-01

    Abstract Cystamine significantly improved motor deficits and extended survival in mouse models of Huntington's disease (HD); however, the precise mechanism(s) by which cystamine and the related compound cysteamine are beneficial remain to be elucidated. Using clonal striatal cell lines from wild-type (STHdhQ7/HdhQ7) and mutant huntingtin knock-in (STHdhQ111/HdhQ111) mice, we have tested the hypothesis that cystamine and cysteamine could be beneficial by preventing the depolarization of mitochondria in cell cultures. Treatment with 3-nitroproprionic acid (3-NP), a mitochondrial complex II inhibitor, induces mitochondrial depolarization and cell death of mutant HD striatal cells but not of wild-type cells. The 3-NP-mediated decrease in the mitochondrial membrane potential was attenuated by 50 microm cystamine and completely inhibited by 250 microm cystamine. Similar results were obtained using cysteamine (50-500 microm). In addition, both cystamine and cysteamine significantly attenuated the 3-NP-induced cell death. Treatment of mutant HD striatal cells with 3-NP resulted in a robust decrease in the cellular and mitochondrial levels of glutathione (GSH) compared with cells exposed to the vehicle alone. Pre-treatment of the cells with cystamine and cysteamine completely prevented the 3-NP-mediated decrease in cellular and mitochondrial GSH levels. Incubation with L-buthionine (S,R) sulfoximine (BSO) 250 microm in combination with cystamine (250 microm) or cysteamine (250 microm) prior to being treated with 3-NP completely prevented the beneficial effects of cystamine and cysteamine on the 3-NP-mediated mitochondrial depolarization. These results demonstrate that cystamine and cysteamine prevent the 3-NP-induced mitochondrial depolarization of HD striatal cell cultures. PMID:16623826

  1. Canada's Clean Air Act

    This paper provided an outline of Canada's Clean Air Act and examined some of the regulatory changes that will occur as a result of its implementation. The Act is being introduced to strengthen the legislative basis for taking action on reducing air pollution and GHGs, and will allow the government to regulate both indoor and outdoor air pollutants and GHGs. The Act will require the Ministers of the Environment and Health to establish national air quality objectives, as well as to monitor and report on their attainment. The Canadian Environmental Protection Act will be amended to enable the government to regulate the blending of fuels and their components. The Motor Vehicle Fuel Consumption Standards Act will also be amended to enhance the government's authority to regulate vehicle fuel efficiency. The Energy Efficiency Act will also be expanded to allow the government to set energy efficiency standards and labelling requirements for a wider range of consumer and commercial products. The Act will commit to short, medium and long-term industrial air pollution targets. Regulations will be proposed for emissions from industry; on-road and off-road vehicles and engines; and consumer and commercial products. It was concluded that the Government of Canada will continue to consult with provinces, territories, industries and Canadians to set and reach targets for the reduction of both indoor and outdoor air pollutants and GHG emissions. 6 figs

  2. The Radiation Protection Act

    The new Radiation Protection Act (1988:220) entered into force in Sweden on July 1st, 1988. This book presents the Act as well as certain regulations connected to it. As previously, the main responsibility for public radiation protection will rest with one central radiation protection authority. According to the 1988 Act, the general obligations with regard to radiation protection will place a greater responsibility than in the past on persons carrying out activities involving radiation. Under the act, it is possible to adjust the licensing and supervisory procedures to the level of danger of the radiation source and the need for adequate competence, etc. The Act recognises standardised approval procedures combined with technical regulations for areas where the risks are well known. The Act contains several rules providing for more effective supervision. The supervising authority may in particular decide on the necessary regulations and prohibitions for each individual case. The possibilities of using penal provisions have been extended and a rule on the mandatory execution of orders has been introduced. The Ordinance on Radiation Protection (1988:293) designates the National Institute of Radiation Protection (SSI) as the central authority referred to in the Radiation Protection Act. The book also gives a historic review of radiation protection laws in Sweden, lists regulations issued by SSI and presents explanations of radiation effects and international norms in the area. (author)

  3. The Energy Act 1983

    Part II of This Act came into force on 1 September 1983 and is concerned with nuclear installations. Its main purpose is to amend the Nuclear Installations Act 1965 to give effect to the provisions of two Protocols amending the Paris Convention on nuclear third party liability and the Brussels Convention Supplementary to the Paris Convention respectively. The principal effect of these modifications is to increase the sums available to meet claims for nuclear damage. The United Kingdom is a Party to both Conventions and the provisions of the 1983 Act will enable it to ratify the Protocols. (NEA)

  4. The Experiment as Act

    Søndergaard, Morten

    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...

  5. Career opportunities in clinical engineering.

    Morse, W A

    1992-01-01

    The varied career opportunities open to clinical engineers are described in this paper. Many of these opportunities are within the medical device industry in research, development, manufacturing design, regulatory activities, production, operations, sales, marketing, service, and management. Additional opportunities are available in hospitals, with the Veterans Administration, or working as an entrepreneur or a consultant. Each of these careers requires specific training and skills, and they all require a fundamental scientific knowledge of physical principles and mathematics. Research and management, however, require different educational preparation. The research emphasis should be on theoretical principles and creativity; the management emphasis should be on financial and labor problems. In all clinical engineering careers, the individual is a problem solver. PMID:10120058

  6. International ROR: risk, opportunity, reward

    Norcen Energy Resources Limited's pursuit of international oil and gas opportunities since the late 1980s were outlined. By 1994 Norcen had exploration and production concessions in 12 countries stretching from Algeria, Russia, Argentina, Indonesia to offshore Australia. The company had seen its share of risks, opportunities and rewards. Since 1994 international efforts of the Company have been focused on lower risk opportunities with exploration upside in defined core areas of South America, particularly in Venezuela, a country with conventional, heavy and ultra-heavy oil resources exceeding that of Saudi Arabia. These, and other similar foreign investments in the formerly closed national oil industries of South America have been greatly facilitated by the political liberalization, economic reforms and stabilization that have taken place there over the past ten years. The story of Norcen's successful bidding on the Oritupano-Leona production block in 1993 and Delta Centro exploration block in 1996 was the subject of this presentation

  7. Opportunity's Surroundings on Sol 1687

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on the 1,687th Martian day, or sol, of its surface mission (Oct. 22, 2008). Opportunity had driven 133 meters (436 feet) that sol, crossing sand ripples up to about 10 centimeters (4 inches) tall. The tracks visible in the foreground are in the east-northeast direction. Opportunity's position on Sol 1687 was about 300 meters southwest of Victoria Crater. The rover was beginning a long trek toward a much larger crater, Endeavour, about 12 kilometers (7 miles) to the southeast. This view is presented as a cylindrical projection with geometric seam correction.

  8. TEACHER TALK AND LEARNER OPPORTUNITY

    LanWeidong

    2004-01-01

    Adopting the position that maximizing learner involvement is conducive to second language acquisition, this paper aims to explore the relationship between teacher talk and learner opportunities in language classrooms in senior schools through classroom observation techniques. Four excellent high school teachers from Zhejiang province in China are involved in this research. The results reveal that such features as minimal teacher talking time, referential questions, extended wait time,discoursal feedback can increase potential of learning opportunities through classroom interaction in language classrooms in high schools.

  9. Opportunity's Surroundings on Sol 1818

    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.

  10. Marine Pollution Prevention Act

    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)...

  11. Acts of Research

    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...... 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...... knowledge production and norms. It is argued that knowledge production is not a stable concept, but may indicate a series of acts of research that allow each art practice to participate in a collective constitution of both the term and its practice....

  12. Clean Water Act

    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...

  13. National Environmental Policy Act

    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. Abandoned Shipwreck Act

    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...

  15. Affordable Care Act (ACA)

    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...

  16. Endangered Species Act

    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...

  17. Energy Policy Act

    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)...

  18. Acting Antarctica: science on stage

    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.

  19. 78 FR 12423 - Privacy Act of 1974; System of Records

    2013-02-22

    ... the contract or agreement. 15. For Data Breach Response and Remedial Efforts--VA may, on its own... required by 5 U.S.C. 552a(r) (Privacy Act) and guidelines issued by OMB (65 FR 77677), December 12, 2000... as may be authorized by law. 8. For the Equal Employment Opportunity Commission--To...

  20. 76 FR 2113 - Sunshine Act; Notice of Meeting

    2011-01-12

    ... From the Federal Register Online via the Government Publishing Office EQUAL EMPLOYMENT OPPORTUNITY COMMISSION Sunshine Act; Notice of Meeting DATE AND TIME: Wednesday, January 19, 2011, 9:30 a.m. Eastern Time... 1. Announcement of Notation Votes, and 2. Human Trafficking and Forced Labor--Invited Panelists...

  1. 76 FR 12395 - Small Business Jobs Act Implementation

    2011-03-07

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Small Business Jobs Act Implementation AGENCY: U.S. Small Business Administration. ACTION: Notice... exporting. See Notice of Grant Opportunities to States: STEP Grant Program, 76 FR 10082 (Feb. 23,...

  2. 75 FR 76758 - Sunshine Act; OPIC Annual Public Hearing

    2010-12-09

    ... CORPORATION Sunshine Act; OPIC Annual Public Hearing Time and Date: 3:30 p.m., Thursday, January 20, 2011.... Status: Hearing OPEN to the Public at 3:30 p.m. Purpose: Annual Public Hearing to afford an opportunity...: OIC is a U.S. Government agency that provides, on a commercial basis, political risk insurance...

  3. 78 FR 5516 - Sunshine Act: OPIC Annual Public Hearing

    2013-01-25

    ... CORPORATION Sunshine Act: OPIC Annual Public Hearing TIME AND DATE: 2 p.m., Wednesday, March 13, 2013. PLACE...: Hearing open to the public at 2 p.m. PURPOSE: Annual Public Hearing to afford an opportunity for any... INFORMATION: OPIC is a U.S. Government agency that provides, on a commercial basis, political risk...

  4. 3 CFR - Ensuring Responsible Spending of Recovery Act Funds

    2010-01-01

    ... middle class. The Recovery Act is designed to stimulate the economy through measures that, among other...-quality educational opportunities, preserve and improve access to affordable health care, provide middle-class tax relief, and protect those in greatest need. It is not intended to fund projects for...

  5. Decomposing equality of opportunity by income sources

    Giuseppe Pignataro

    2009-01-01

    An opportunity egalitarian view focus not only on equality of outcomes but essentially on the means or opportunities to realize such outcomes. In this paper we propose a methodology to decompose an opportunity egalitarian Atkinson index by income sources seeking for a measure of overall equality into an opportunity and a responsibility component.

  6. Opportunities in independent gas storage

    The range of business opportunities currently available for the midstream oil and gas business were discussed with particular focus on storage opportunities. Alberta Energy Co. (AEC) Ltd.'s two midstream business units include AEC Pipelines and Gas Processing, and AEC Storage and Hub Services. These two businesses provide the company with good investment returns, stable cash flow, and some significant strategic synergies with their exploration and production businesses. In 1988, the AECO C Hub in southeastern Alberta was created as an outgrowth of AEC's gas production operations on the Suffield block, where they had depleted gas reservoirs with high rock quality suitable for high deliverability storage. With the AECO C Hub, AEC was able to offer firm storage contracts of from 1 to 20 years, and to introduce short term interruptible parking and lending services, title exchange, a spot price index for greater price discovery, and an electronic nomination system. AEC is currently completing construction of their second commercial storage facility, the Wild Goose project, in northern California. Debottlenecking' the Western Canada supply basin should provide additional opportunities for further expansion not only for AEC but also for other midstream service providers. Opportunities are especially available in the areas of new storage facilities to serve location-specific needs, replacement of declining storage capacity, replacement of retiring facilities, technological optimization of existing facilities, more flexible, higher deliverability facilities and commercial optimization of existing facilities. A map of the hubs and market centres of North America are included. 5 figs

  7. Nikola Tesla Educational Opportunity School.

    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)

  8. Opportunity Cost of Distance Education

    Recep TURKOĞLU

    2004-01-01

    Full Text Available In this study; opportunity cost (OC of distance education (DE has been examined. In addition, Factors, which affect OC of DE, have been investigated according to institute, which develops DE and puts it into practice, student/parent whose target of DE program is and teacher who works for DE program.

  9. Closing the Windows on Opportunity.

    Coombs, Norman

    1995-01-01

    The rapid adoption of graphic user interface (GUI), as indicated by Microsoft's Windows95 and the Internet's increased use of graphics, is threatening information technology opportunities for people with disabilities. Recent legislation requires that schools provide access to computers and information technology, and producers of Mosaic are…

  10. Opportunity for a New Millennium.

    New Jersey State Commission on Higher Education.

    The New Jersey Educational Opportunity Fund (EOF) aims to provide access to higher education for disadvantaged students in order to increase diversity in New Jersey's institutions of higher education. This report is issued in accordance with the EOF Board of Directors' responsibility to inform the Commission on Higher Education, the Governor, and…

  11. Music education - changes and opportunities

    Nasev, Lence

    2015-01-01

    Scientific and technological revolution directly or indirectly affects at improvements to education. The purpose of this article is to highlight the need of changes and opportunities to improve the work of the class teachers. Key Words: modern teacher, teaching plan and program, textbooks, students

  12. Opportunity at 'Cook Islands' (Vertical)

    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 vertical 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.

  13. Opportunity at 'Cook Islands' (Polar)

    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.

  14. Investment opportunities with YPFB capitalization

    Investment opportunities with Yacimientos Petroliferos Fiscales Bolivianos (LPFB) in La Paz, Bolivia, were discussed, especially as they may be affected by the new Hydrocarbon Law No. 1689, whose main objective is to encourage investments in Bolivia and to increase production capacity through investors' incorporation. Some of the areas of potential importance examined included reserve development, transportation, upstream consulting, and hydrocarbon development

  15. Educational Homogamy: Preferences or Opportunities?

    Nielsen, Helena Skyt; Svarer, Michael

    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...

  16. Dismantling College Opportunity in California

    The Civil Rights Project/ Proyecto Derechos Civiles

    2011-01-01

    These studies released today call attention to the fact that cuts to higher education impact students, their families, CSU faculty, and staff well beyond the classroom. Reduction in access, retention, and increase in cost are disproportionately impacting traditionally underrepresented students, and are being felt within their personal lives. Related Documents Dismantling College Opportunity in California These three reports constitute Part Four of The ...

  17. 12 CFR 268.406 - Civil action: Title VII, Age Discrimination in Employment Act and Rehabilitation Act.

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Civil action: Title VII, Age Discrimination in... Equal Employment Opportunity Commission § 268.406 Civil action: Title VII, Age Discrimination in... complaint is authorized under title VII, the ADEA and the Rehabilitation Act to file a civil action in...

  18. The CEO's second act.

    Nadler, David A

    2007-01-01

    When a CEO leaves because of performance problems, the company typically recruits someone thought to be better equipped to fix what the departing executive couldn't--or wouldn't. The board places its confidence in the new person because of the present dilemma's similarity to some previous challenge that he or she dealt with successfully. But familiar problems are inevitably succeeded by less familiar ones, for which the specially selected CEO is not quite so qualified. More often than not, the experiences, skills, and temperament that yielded triumph in Act I turn out to be unequal to Act II's difficulties. In fact, the approaches that worked so brilliantly in Act I may be the very opposite of what is needed in Act II. The CEO has four choices: refuse to change, in which case he or she will be replaced; realize that the next act requires new skills and learn them; downsize or circumscribe his or her role to compensate for deficiencies; or line up a successor who is qualified to fill a role to which the incumbent's skills and interests are no longer suited. Hewlett-Packard's Carly Fiorina exemplifies the first alternative; Merrill Lynch's Stanley O'Neal the second; Google's Sergey Brin and Larry Page the third; and Quest Diagnostics' Ken Freeman the fourth. All but the first option are reasonable responses to the challenges presented in the second acts of most CEOs' tenures. And all but the first require a power of observation, a propensity for introspection, and a strain of humility that are rare in the ranks of the very people who need those qualities most. There are four essential steps executives can take to discern that they have entered new territory and to respond accordingly: recognition that their leadership style and approach are no longer working; acceptance of others' advice on why performance is faltering; analysis and understanding of the nature of the Act II shift; and, finally, decision and action. PMID:17286076

  19. Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

    Gamarra Fernando

    2006-02-01

    Full Text Available Abstract Background Airway smooth muscle cells (ASMC play a key role in bronchial hyperresponsiveness (BHR. A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO mice show key features of allergic asthma such as a shift towards TH2-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca2+-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma. Methods Lung slices of 100 to 200 μm thickness were obtained from T-bet KO- and wild-type mice. Airway contraction in response to acetylcholine (ACH was measured by video-microscopy and Ca2+-signaling in single ASMC of lung slices was assessed using two-photon-microscopy. Results Airways from T-bet KO-mice showed increased baseline airway tone (BAT and BHR compared to wild-type mice. This could be mimicked by incubation of lung slices from wild-type mice with IL-13. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca2+-concentrations, whereas BHR correlated with higher ACH-induced Ca2+-transients and an increased proportion of ASMC showing Ca2+-oscillations. Emptying intracellular Ca2+-stores using caffeine or cyclopiazonic acid induced higher Ca2+-elevations in ASMC from T-bet KO- compared to wild-type mice. Conclusion Altered Ca2+-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO-mice as a murine asthma model. We propose that a higher Ca2+-content of the intracellular Ca2+-stores is involved in the pathophysiology of these changes.

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

    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

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

    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

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

    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

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

    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

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

    Crispo, M.; Mulet, A. P.; Tesson, L.; Barrera, N.; Cuadro, F.; dos Santos-Neto, P. C.; Nguyen, T. H.; Crénéguy, A.; Brusselle, L.; Anegón, I.; Menchaca, A.

    2015-01-01

    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 biomedicine and

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

    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.

  6. 29 CFR 1608.12 - Equal employment opportunity plans adopted pursuant to section 717 of title VII.

    2010-07-01

    ... section 717 of title VII. 1608.12 Section 1608.12 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION AFFIRMATIVE ACTION APPROPRIATE UNDER TITLE VII OF THE CIVIL RIGHTS ACT OF... VII. If adherence to an Equal Employment Opportunity Plan, adopted pursuant to section 717 of...

  7. No 592 - Radiation Act

    This Act will enter into force on 1 January 1992. The scope of the Act is extensive as, in addition to ionizing radiation, it will also apply to activities involving exposure to natural radiation and non-ionizing radiation. Its purpose is to prevent and restrict harmful effects to health resulting from radiation. The basic principles of the Act are that the practice involving radiation should be justified; radiation protection should be optimized; and radiation doses should be as low as reasonably achievable. Licensed organisations using radiation will be responsible for the safety of the activity involving exposure to radiation and for having available the appropriate expertise to this effect. The required so-called safety licence provides the regulatory control to ensure that radiation is used sensibly, that the equipment and shields are technically acceptable and the operating personnel is competent, and that the radioactive waste is dealt with appropriately. The Radiation Act will also apply to nuclear activities within the scope of the 1987 Nuclear Energy Act

  8. The Clean Air Act

    The Clean Air Act amendments alter the complex laws affecting atmospheric pollution and at the same time have broad implications for energy. Specifically, the Clean Air Act amendments for the first time deal with the environmental problem of acid deposition in a way that minimizes energy and economic impacts. By relying upon a market-based system of emission trading, a least cost solution will be used to reduce sulfur dioxide (SO2) emissions by almost 40 percent. The emission trading system is the centerpiece of the Clean Air Act (CAA) amendments effort to resolve energy and environmental interactions in a manner that will maximize environmental solutions while minimizing energy impacts. This paper will explore how the present CAA amendments deal with the emission trading system and the likely impact of the emission trading system and the CAA amendments upon the electric power industry

  9. THE RIGHT TO EDUCATION ACT: AN OVERVIEW

    SONIA

    2012-12-01

    Full Text Available A man without education is no more than an animal. The growth and development of a state is primarily dependent upon the quality of education given to the people. In India Right to Education Act (RTE was passed on 4th August 2009 which provides for free and compulsory education for children between the age of 6 and 14 years. The Act came into force on 1 April 2010. The problems on the path of education of children includes child labour, misery of girl child in India and poor quality of education. Article 51A of constitution also makes its obligatory for parent or guardian as the case may be to provide opportunities for education to his child or ward between the age of six and fourteen years. Although RTE Act is a major landmark in the history of India but there are certain limitations of the Act which if removed then education will reach every child in India which is their right. “There is only one purpose in the whole of Life –Education”.“Otherwise what is the use of me and women, land and wealth”. – Swami Vivekananda“Education is the most powerful weapon which you can use to change the world”.– Nelson Mandela

  10. ST–ACTS

    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, using...... 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...

  11. Atomic Energy Act 1989

    This Act, which entered into force on 1 september 1989, contains a series of provisions dealing with different subjects: increase of public financing for British Nuclear Fuels plc, amendment of the Nuclear Installations Act 1965 regarding the powers of the Health and Safety Executive to recover expenses directly from nuclear operators and obligation of the UKAEA to take out insurance or other financial security to cover its liability and finally, measures to enable the UK to ratify the IAEA Convention on Assistance in Case of a Nuclear Accident or Radiological Emergency

  12. Opportunities in Reform: Bioethics and Mental Health Ethics.

    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. PMID:26424211

  13. Eand P opportunities in Brazil

    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.

  14. Opportunity Captures 'Lion King' Panorama

    2004-01-01

    [figure removed for brevity, see original site] Click on the image for Opportunity Captures 'Lion King' Panorama (QTVR) This approximate true-color panorama, dubbed 'Lion King,' shows 'Eagle Crater' and the surrounding plains of Meridiani Planum. It was obtained by the Mars Exploration Rover Opportunity's panoramic camera on sols 58 and 60 using infrared (750-nanometer), green (530-nanometer) and blue (430-nanometer) filters. This is the largest panorama obtained yet by either rover. It was taken in eight segments using six filters per segment, for a total of 558 images and more than 75 megabytes of data. Additional lower elevation tiers were added to ensure that the entire crater was covered in the mosaic. This panorama depicts a story of exploration including the rover's lander, a thorough examination of the outcrop, a study of the soils at the near-side of the lander, a successful exit from Eagle Crater and finally the rover's next desination, the large crater dubbed 'Endurance'.

  15. Investment opportunities as real options

    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.

  16. Opportunity's Surroundings on Sol 1798

    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.

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

    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.

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

    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.

  19. Decadal opportunities for space architects

    Sherwood, Brent

    2012-12-01

    A significant challenge for the new field of space architecture is the dearth of project opportunities. Yet every year more young professionals express interest to enter the field. This paper derives projections that bound the number, type, and range of global development opportunities that may be reasonably expected over the next few decades for human space flight (HSF) systems so those interested in the field can benchmark their goals. Four categories of HSF activity are described: human Exploration of solar system bodies; human Servicing of space-based assets; large-scale development of space Resources; and Breakout of self-sustaining human societies into the solar system. A progressive sequence of capabilities for each category starts with its earliest feasible missions and leads toward its full expression. The four sequences are compared in scale, distance from Earth, and readiness. Scenarios hybridize the most synergistic features from the four sequences for comparison to status quo, government-funded HSF program plans. Finally qualitative, decadal, order-of-magnitude estimates are derived for system development needs, and hence opportunities for space architects. Government investment towards human planetary exploration is the weakest generator of space architecture work. Conversely, the strongest generator is a combination of three market drivers: (1) commercial passenger travel in low Earth orbit; (2) in parallel, government extension of HSF capability to GEO; both followed by (3) scale-up demonstration of end-to-end solar power satellites in GEO. The rich end of this scale affords space architecture opportunities which are more diverse, complex, large-scale, and sociologically challenging than traditional exploration vehicle cabins and habitats.

  20. Employment opportunities for the disabled

    Delsen, L.W.M.

    1996-01-01

    Policy makers in the OECD Member States have developed quite different programmes and institutional arrangements to create and promote employment opportunities for the disabled. These policy approaches include legal interventions, employment support services, financial support of open employment and sheltered employment. This chapter describes the various instruments supporting employment of disabled people applied in the EU Member States and the USA. Their effectiveness is assessed, based on...

  1. Office of Equal Opportunity Programs

    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

  2. Financial Consolidation: Dangers and Opportunities

    Frederic S. Mishkin

    1999-01-01

    This paper argues that although financial consolidation creates some dangers because it is leading to larger institutions who might expose the U.S. financial system to increased systemic risk, these dangers can be handled by vigilant supervision and a government safety net with an appropriate amount of constructive ambiguity. Financial consolidation also opens up opportunities to dramatically reduce the scope of deposit insurance and limit it to narrow bank accounts, thus substantially reduci...

  3. The Economics of Strategic Opportunity

    Denrell, Jerker; Fang, Christina; Winter, Sidney G.

    2003-01-01

    As emphasized by Barney (1986), any explanation of superior profitability must account for why the resources supporting such profitability could have been acquired for a price below their rent generating capacity. Building upon the literature in economics on coordination failures and incomplete markets, we suggest a framework for analyzing such strategic factor market inefficiencies. Our point of departure is that a strategic opportunity exists whenever prices fail to reflect the value of a r...

  4. Online Learning: Increasing Learning Opportunities

    Hajhashemi, Karim; Anderson, Neil; Jackson, Cliff; Caltabiano, Nerina

    2014-01-01

    Internet and networked technologies have expanded delivery mode opportunities in education. In recent years, many universities have offered either predominantly online courses or online learning platforms embedded within traditional modes of on-campus and face-to-face learning. Online learning has thus developed into a priority within modern educational facilities and has grown significantly both in Australia and other countries. To consider the connection between student learning and effecti...

  5. Immigrant Capital and Entrepreneurial Opportunities

    Malavika Sundararajan; Binod Sundararajan

    2016-01-01

    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 successf...

  6. Opportunity at 'Cook Islands' (Stereo)

    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.

  7. Reminder - Equal Opportunities Advisory Panel

    HR Department

    2007-01-01

    At its meeting on 7 December 2006, the Standing Concertation Committee also took note of the nomination of a fourth new member of the Panel: Wisla Carena. The present composition of the Panel (appointed ad personam) is now as follows: Tiziano Camporesi (Chairperson), Wisla Carena, Pierre Charrue, Sue Foffano, Josi Schinzel (Equal Opportunities Officer), Markus Nordberg, Christine Petit-Jean-Genaz and Elena Wildner. Human Resources Department Tel. 74480

  8. Immigrant Capital and Entrepreneurial Opportunities

    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.

  9. Engineering ethics challenges and opportunities

    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...

  10. Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

    Gamarra Fernando; Kemp da Silva Anita; Kellner Julia; Bergner Albrecht; Huber Rudolf M

    2006-01-01

    Abstract Background Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards TH2-lymphocytes and displ...

  11. The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice

    Vidal, Ruben; Sammeta, Neeraja; Garringer, Holly J.; Sambamurti, Kumar; Miravalle, Leticia; Lamb, Bruce T.; Ghetti, Bernardino

    2012-01-01

    Genetically engineered mice have been generated to model cerebral β-amyloidosis, one of the hallmarks of Alzheimer disease (AD) pathology, based on the overexpression of a mutated cDNA of the amyloid-β precursor protein (AβPP) or by knock-in of the murine Aβpp gene alone or with presenilin1 mutations. Here we describe the generation and initial characterization of a new mouse line based on the presence of 2 copies of the human genomic region encoding the wild-type AβPP and the L166P presenili...

  12. Disruption of the developmentally-regulated Col2a1 pre-mRNA alternative splicing switch in a transgenic knock-in mouse model

    Lewis, Renate; Ravindran, Soumya; Wirthlin, Louisa; Traeger, Geoffrey; Fernandes, Russell J.; McAlinden, Audrey

    2012-01-01

    The present study describes the generation of a knock-in mouse model to address the role of type II procollagen (Col2a1) alternative splicing in skeletal development and maintenance. Alternative splicing of Col2a1 precursor mRNA is a developmentally-regulated event that only occurs in chondrogenic tissue. Normally, chondroprogenitor cells synthesize predominantly exon 2-containing mRNA isoforms (type IIA and IID) while Col2a1 mRNA devoid of exon 2 (type IIB) is the major isoform produced by d...

  13. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia;

    characteristics of human psoriasis skin. Blockade of TNF- function with specific inhibitors at the protein level has resulted in a rapid clinical improvement in psoriasis patients, demonstrating that TNF- inhibition offers a promising therapy of psoriasis. Whether TNF- -encoding RNA is a valid therapeutic target...... control samples treated with irrelevant shRNAs, were selected and cloned into lentiviral vectors. The lentiviral vectors expressing TNF- shRNAs were used to transduce HEK-293 cells and verify vector-derived knock-down of stable TNF- expression in vitro. The most efficient TNF- -directed shRNA, which in...... valid therapeutic target in psoriasis treatment....

  14. RNAi-Mediated Knock-Down of Arylamine N-acetyltransferase-1 Expression Induces E-cadherin Up-Regulation and Cell-Cell Contact Growth Inhibition

    Tiang, Jacky M; Butcher, Neville J.; Cullinane, Carleen; Humbert, Patrick O.; Minchin, Rodney F

    2011-01-01

    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 c...

  15. Large genomic fragment deletion and functional gene cassette knock-in via Cas9 protein mediated genome editing in one-cell rodent embryos

    Liren Wang; Yanjiao Shao; Yuting Guan; Liang Li; Lijuan Wu; Fangrui Chen; Meizhen Liu; Huaqing Chen; Yanlin Ma; Xueyun Ma; Mingyao Liu; Dali Li

    2015-01-01

    The CRISPR-Cas RNA-guided system has versatile uses in many organisms and allows modification of multiple target sites simultaneously. Generating novel genetically modified mouse and rat models is one valuable application of this system. Through the injection of Cas9 protein instead of mRNA into embryos, we observed fewer off-target effects of Cas9 and increased point mutation knock-in efficiency. Large genomic DNA fragment (up to 95 kb) deletion mice were generated for in vivo study of lncRN...

  16. Restoration of Cocaine Stimulation and Reward by Reintroducing Wild Type Dopamine Transporter in Adult Knock-in Mice with a Cocaine-Insensitive Dopamine Transporter

    Wu, Haiyin; O’Neill, Brian; Han, Dawn D; Thirtamara-Rajamani, Keerthi; Wang, Yanlin; Gu, Howard H.

    2014-01-01

    In previous studies, we generated knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) and found cocaine does not stimulate locomotion or produce reward in these mice, indicating DAT inhibition is necessary for cocaine stimulation and reward. However, DAT uptake is reduced in DAT-CI mice and thus the lack of cocaine responses could be due to adaptive changes. To test this, we used adeno-associated virus (AAV) to reintroduce the cocaine-sensitive wild type DAT (AAV-DATwt...

  17. 某型柴油机发生捣缸原因分析及预防措施%Reasons Aanlysis of Cylinder Knock and Its Preventive Measures

    龚伦超; 彭敦

    2012-01-01

    针对MTU16V396TE94型船用柴油机连杆断裂发生敲击捣缸故障,进行了原因分析,提出了有效的解决方法。%Based on marine engine MTU16V396TE94, the failure of the connecting-rod is illustrated briefly. Upon analysis, the main reason for the knocking of the connecting-rod is that the crack in the airframe, the paper puts forward an effective solution.

  18. The USA PATRIOT Act.

    Minow, Mary; Coyle, Karen; Kaufman, Paula

    2002-01-01

    Explains the USA PATRIOT (Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism) Act, passed after the September 11 terrorist attacks, and its implications for libraries and patron records. Considers past dealings with the FBI; court orders; search warrants; wiretaps; and subpoenas. Includes:…

  19. An Act of Colonization

    Rasmussen, Anders Bo

    , Denmark and the United States signed an act on July 19, 1862, wherein the U.S. Navy agreed to unload “all negroes, mulattoes, or persons of color, delivered from on board vessels seized in the prosecution of the slave trade.” Yet, despite the two countries’ mutual interests in employing “laborers of...

  20. Ocean Dumping Control Act

    This Act provides for the control of dumping of wastes and other substances in the ocean in accordance with the London Convention of 1972 on Prevention of Marine Pollution by the Dumping of Wastes and other Matter to which Canada is a Party. Radioactive wastes are included in the prohibited and restricted substances. (NEA)

  1. Atomic Energy Control Act

    This act provides for the establishment of the Atomic Energy Control Board. The board is responsible for the control and supervision of the development, application and use of atomic energy. The board is also considered necessary to enable Canada to participate effectively in measures of international control of atomic energy

  2. Compelling Research Opportunities using Isotopes

    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) medicine

  3. Compelling Research Opportunities using Isotopes

    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

  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.

    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. PMID:26197710

  5. 76 FR 76475 - Tregaron Opportunity Fund I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

    2011-12-07

    ...). Tregaron Opportunity Fund I, L.P. proposes to provide debt financing to PIU Management, LLC, 1860 West University Drive, Suite 108, Tempe, AZ 85281. The financing is brought within the purview of Sec. 107.730(a... Investment Act of 1958, as amended (``the Act''), in connection with the financing of a small concern,...

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

    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

  7. On Retractable S-Acts

    R.KHOSRAVI

    2012-01-01

    In this paper we introduce a class of right S-acts called retractable S-acts which are right S-acts with homomorphisms into their all subacts.We also give some classifications of monoids by comparing such acts with flatness properties.

  8. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  9. Knock-down of protein L-isoaspartyl O-methyltransferase increases β-amyloid production by decreasing ADAM10 and ADAM17 levels

    Narkhyun BAE; Se Eun BYEON; Jihyuk SONG; Sang-Jin LEE; Moosik KWON; Inhee MOOK-JUNG; Jae Youl CHO; Sungyoul HONG

    2011-01-01

    Aim: To examine the role of protein L-isoaspartyl O-methyltransferase (PIMT; EC 2.1.1.77) on the secretion of Aβ peptides.Methods: HEK293 APPsw cells were treated with PIMT siRNA or adenosine dialdehyde (AdOX), a broad-spectrum methyltransferase inhibitor. Under the conditions, the level of Aβ secretion and regulatory mechanism by PIMT were examined.Results: Knock-down of PIMT and treatment with AdOX significantly increased Aβ40 secretion. Reductions in levels of PIMT decreased the secretion of soluble amyloid precursor protein alpha (sAPPα) without altering the total expression of APP or its membrane-bound C83 fragment. However, the levels of the C99 fragment generated by β-secretase were enhanced. Moreover, the decreased secretion of sAPPα resulting from PIMT knock-down seemed to be linked with the suppression of the expression of α-secretase gene products,α-disintegrin and metalloprotease 10 (ADAM10) and ADAM17, as indicated by Western blot analysis. In contrast, ADAM10 was not down-regulated in response to treatment with the protein arginine methyltransferase (PRMT) inhibitor, AMI-1.Conclusion: This study demonstrates a novel role for PIMT, but not PRMT, as a negative regulator of Aβ peptide formation and a potential protective factor in the pathogenesis of AD.

  10. High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder.

    Manoj Kumar

    Full Text Available Autism spectrum disorders (ASD comprise an etiologically heterogeneous set of neurodevelopmental disorders. Neuroligin-3 (NL-3 is a cell adhesion protein that mediates synapse development and has been implicated in ASD. We performed ex-vivo high resolution magnetic resonance imaging (MRI, including diffusion tensor imaging (DTI and behavioral (social approach and zero maze tests at 3 different time points (30, 50 and 70 days-of-age on NL-3 and wild-type littermates to assess developmental brain abnormalities in NL-3 mice. MRI data were segmented in 39 different gray and white matter regions. Volumetric measurements, along with DTI indices from these segmented regions were also performed. After controlling for age and gender, the NL-3 knock-in animals demonstrated significantly reduced sociability and lower anxiety-related behavior in comparison to their wild type littermates. Significantly reduced volume of several white and gray matter regions in the NL-3 knock-in mice were also observed after considering age, gender and time point as covariates. These findings suggest that structural changes in the brain of NL-3 mice are induced by the mutation in the NL-3 gene. No significant differences in DTI indices were observed, which suggests that the NL-3 mutation may not have a profound effect on water diffusion as detected by DTI. The volumetric and DTI studies aid in understanding the biology of disrupting function on an ASD risk model and may assist in the development of imaging biomarkers for ASD.

  11. Knock-down of HEXA and HEXB genes correlate with the absence of the immunostimulatory function of HSC-derived dendritic cells.

    Tiribuzi, Roberto; D'Angelo, Francesco; Berardi, Anna C; Martino, Sabata; Orlacchio, Aldo

    2012-01-01

    In an attempt to investigate whether the genetic defect in the HEXA and HEXB genes (which causes the absence of the lysosomal β-N-acetyl-hexosaminidase), are related to the wide inflammation in GM2 gangliosidoses (Tay-Sachs and Sandhoff disease), we have chosen the dendritic cells (DCs) as a study model. Using the RNA interference approach, we generated an in vitro model of HEXs knock-down immunogenic DCs (i-DCs) from CD34(+)-haemopoietic stem cells (CD34(+)-HSCs), thus mimicking the Tay-Sachs (HEXA-/-) and Sandhoff (HEXB-/-) cells. We showed that the absence of β-N-acetyl-hexosaminidase activity does not alter the differentiation of i-DCs from HSCs, but it is critical for the activation of CD4(+)T cells because knock-down of HEXA or HEXB gene causes a loss of function of i-DCs. Notably, the silencing of the HEXA gene had a stronger immune inhibitory effect, thereby indicating a major involvement of β-N-acetyl-hexosaminidase A isoenzyme within this mechanism. PMID:21997228

  12. The Act of Walking

    Vestergaard, Maria Quvang Harck; Olesen, Mette; Helmer, Pernille Falborg

    2014-01-01

    ’ of mobility (Jensen 2013:111) such as the urban environment, and the infrastructures. Walking has indeed also a ‘software dimension’ as an embodied performance that trigger the human senses (Jensen 2013) and which is closely related to the habitus and identity of the individual (Halprin 1963). The...... individual 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 the individuals evaluate, interpret and act (Bourdieu 1984), and how this affects their choice to walk. Therefore it could be questioned if whether an assessment of the physical environment is sufficient to identify all the factors that influence the individual perception of ‘walkability’, or...

  13. On the Concept of Equity in Opportunity

    Hyun H. Son

    2011-01-01

    Measuring the equity of opportunity in a given society is an essential ingredient in the formulation of policies and programs that promote inclusive growth. In this paper, equity of opportunity is defined and measured through the theoretical framework of the social opportunity function, a concept similar to the social welfare function. The functional and graphical distribution of opportunity is discussed through the generalized Lorenz curve and the Bonferroni curve, while complete ranking of ...

  14. Regional development - rural employment opportunities

    Tamas Forgacs

    2010-06-01

    Full Text Available The way of employment is changing. The primary and secondary sector offers less and less workplaces, shifting employment into the tertiary sector. Nevertheless, we are facing increasing rural unemployment, as the tertiary sector is based mostly around the high populated towns, but the primary and secondary sector generates unemployment in the rural areas. This trend projects a vision of a very centralized Europe, which is opposite with the efforts of regionalization. In this study we evaluate these trends, and build a generic model which can be used to create employment opportunities in the rural areas, based on the specificities of the tertiary sector.

  15. IAEA safeguards: Challenges and opportunities

    The history of the IAEA safeguards regime is described. New challenges and opportunities are discussed in connection with the discovery in Iraq of a clandestine nuclear weapons development programme, the difficulties experienced in the implementation of the safeguards agreement with the Democratic People's Republic of Korea, the conclusion of a comprehensive safeguards agreement with Argentina, Brazil and the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials, recent developments in South Africa, the emergence of newly independent States that made up the former USSR. 2 figs

  16. Energy Development Opportunities for Wyoming

    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

  17. Atomic Energy Act 1946

    This Act provides for the development of atomic energy in the United Kingdom and for its control. It details the duties and powers of the competent Minister, in particular his powers to obtain information on and to inspect materials, plant and processes, to control production and use of atomic energy and publication of information thereon. Also specified is the power to search for and work minerals and to acquire property. (NEA)

  18. Toxic Substances Control Act

    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).

  19. On Speech Act Theory

    邓仁毅

    2009-01-01

    Speech act has developed from the work of linguistic philosophers and originates in Austin's observation and study. It was the particular search for the eonstative, utterances which describe something outside the text and can therefore be judged true or false that prompted John L. Austin to direct his attention to the distinction with so -called performa-tires. The two representative linguists are Aus-tin and Searle.

  20. Acting for Opera Singers

    Hamilton, Jennifer

    2015-01-01

    As the majority of professional classical singers earn a significant part of their living in opera, it is vital that conservatoires and studios are able to provide fit-for-purpose education for these trainee artists. As opera productions today are increasingly influenced by the trends in cinema and live-streamed media, this study sought to identify and clarify the range and detail of acting and performance skills required of opera singers in this evolving professional environment. A significa...

  1. Radiological protection act, 1991

    This Act provides for the establishment of the Radiological Protection Institute of Ireland and dissolves An Bord Fuinnimh Nuicleigh (the Board), transferring its assets and liabilities to the Institute. It sets out a range of radiation protection measures to be taken by various Ministers in the event of a radiological emergency and gives effect at national level to the Assistance Convention, the Early Notification Convention and the Physical Protection Convention. The Institute is the competent Irish authority for the three Conventions. (NEA)

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

    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.

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

    Tait-McCutcheon, Sandi L.; Loveridge, Judith

    2016-03-01

    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.

  4. Educational opportunities from the SSC

    High energy physics and education are very closely interwoven. Most physics laboratories are located at universities or are operated by consortiums of universities. Fermilab and the SSC are operated by the Universities Research Association, URA, a consortium of 69 major research universities and 3 associate members. Another example of this laboratory and universities relationship is the Continuous Electron Beam Accelerator Facility, CEBAF, which is operated by the Southeastern Universities Research Association, SURA, another consortium of 39 major universities. The education potential inherent in the planning, construction and operation of the SSC is immense. The SSC, as the world's largest scientific instrument and, as the most power accelerator, will have a natural attraction as the preeminent institution in the scientific community. In addition to the primary objective of probing the fundamental composition of matter, the SSC will appear to a broad segment of the population and will create the opportunity for both passive and active educational experiences on the part of staff, students and visitors. On the esoteric level, the SSC will be a magnet for the scientific community and will attract from around the world the finest minds in the field of high energy physics. On the human level, the laboratory will become an integral part of the community and will be an object of great interest to local residents and visitors. The SSC planners should recognize the opportunity to be a contributing institution to both the local and the world community

  5. Procurement and participation opportunities onshore

    Maritimes and Northeast Pipelines Company is constructing a 1048 km underground gas transmission pipeline that will transport Sable natural gas to markets in Nova Scotia, New Brunswick and New England. The Sable Offshore Energy Project brings opportunities for new industries to Atlantic Canada, including the potential for future Sable gas exploration, development and production which will provide thousands of jobs and benefits for local businesses during the construction phase. Maritimes and Northeast Pipelines plan to maximize local content for the construction of the 565 km Canadian portion of the pipeline. The construction phase alone should create about 1,500 jobs during peak times. Seventy per cent of the labour will be sourced locally. Clean-up, landscaping, fencing and tile repair, monitoring services and pipeline inspection are some of the other opportunities that will be contracted to local businesses. Major long-term benefits of the project are expected to be in the construction of lateral or feeder pipelines and in the construction of gas distribution utilities

  6. Multiphysics simulations: challenges and opportunities.

    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.

  7. Realising the organisational learning opportunities

    An aspect of proactive safety management is learning lessons from unforeseen events. As BNFL has expanded and extended its nuclear services to many more sites, the potential for organisational learning has grown, but sharing through informal networking has become progressively harder. This potential problem has been solved by implementing formalised company-wide arrangements to turn incidents and accidents into organisational learning opportunities through a system called 'Learning from Experience' (LFE). LFE enables event causes and corrective actions to be identified and shared across all BNFL's sites, initially in the UK but ultimately throughout the world. The result is prevention of events having similar causes, and development of a learning culture which breaks down the barriers to adopting best practice'. Key aspects of the system are: Applying root cause analysis to all significant events; Logging all events, their causes and corrective actions onto a Company-wide database; Screening the database regularly by locally appointed Feedback Co-ordinators trained in identifying learning opportunities and knowledgeable of their own business area, and; Placing and tracking actions to prevent similar events at local Event Review Meetings. The paper describes the implementation and initial experience in operation of the LFE system, which is seen as a significant step towards becoming an expanding and learning company with no accidents or incidents. (author)

  8. Export opportunities in developing countries

    Developing countries will offer major opportunities to US exporters of energy and related environmental equipment in the next ten years. These opportunities arise because the markets in developing countries will be growing much faster than those in the developed countries during this period, and because these countries will not in most cases have strong domestic manufacturers to compete against. US technologies will help these countries solve their energy, environmental, and economic development problems, and help the US solve its serious trade balance problems. This market will represent over $200 billion between now and 2000. There are, however, many potential problems. These include a lack of focus and coordination among US government trade assistance organizations, a lack of interest on the part of US firms in exporting and an unwillingness to make the needed investments, barriers put up by the governments of potential foreign customers, and strong international competition. This paper describes how the United States Agency for International Development's (A.I.D.) Office of Energy and other US agencies are helping US firms resolve these problems with a comprehensive program of information, trade promotion assistance, and co-funding of feasibility studies. In addition, there are monies available to match unfair concessionary financing offered by our major competitors

  9. Imaging Opportunities in Radiation Oncology

    Interdisciplinary efforts may significantly affect the way that clinical knowledge and scientific research related to imaging impact the field of Radiation Oncology. This report summarizes the findings of an intersociety workshop held in October 2008, with the express purpose of exploring 'Imaging Opportunities in Radiation Oncology.' Participants from the American Society for Radiation Oncology (ASTRO), National Institutes of Health (NIH), Radiological Society of North America (RSNA), American Association of physicists in Medicine (AAPM), American Board of Radiology (ABR), Radiation Therapy Oncology Group (RTOG), European Society for Therapeutic Radiology and Oncology (ESTRO), and Society of Nuclear Medicine (SNM) discussed areas of education, clinical practice, and research that bridge disciplines and potentially would lead to improved clinical practice. Findings from this workshop include recommendations for cross-training opportunities within the allowed structured of Radiology and Radiation Oncology residency programs, expanded representation of ASTRO in imaging related multidisciplinary groups (and reciprocal representation within ASTRO committees), increased attention to imaging validation and credentialing for clinical trials (e.g., through the American College of Radiology Imaging Network (ACRIN)), and building ties through collaborative research as well as smaller joint workshops and symposia.

  10. The Clean Air Act Amendments of 1990

    The natural gas liquids industry and specifically the gas processing business has not been rosy the last several years. processors have been faced with low NGL prices, high inventories and more regulations which have forced product margins to all time lows and have resulted in plant closings, mergers and a determined search for those processors that are left for ways to make ends meet until times get better. Whether a barometer for the future or merely a fluke in the economy, things got better in 1990. Last year represented a change for the positive in all the indicators characterizing the gas processing business. An early winter in 1989, propane distribution problems, overall increases in petrochemical demand for NGLs and the fear brought on by events in Kuwait all contributed to changes in the marketplace. For the gas processor, these events combined with relatively low natural gas prices to produce wider processing margins and a degree of prosperity. The biggest regulatory event in 1990 however was without a doubt the Clean Air Act Amendments. These sweeping changes to the 1970 Clean Air Act promise to affect the economy and public health well into the next century. The purpose of this paper is to examine first the major provisions of the Clean Air Act Amendments of 1990 and then relate those anticipated changes to the gas processing industry. As will be examined later, the Amendments will create both threats and opportunities for gas processors

  11. Opportunities for green growth; Vihreaen kasvun mahdollisuudet

    Antikainen, R.; Mickwitz, P.; Seppaelae, J. [and others

    2013-03-15

    The report seeks an answer to the question as to the kind of policy decisions (steps) by which preconditions for green growth may be created in Finland. The proposed steps are based on a review of earlier research and studies relating to Finland's key consumption and production systems (food, housing, transport and energy) and to certain path finding countries in terms of the green economy (the Netherlands, Germany, Sweden, Brazil). In addition, the report examines various models by which systemic change towards a green economy may be supported. The report also highlights successful examples of green business activity and measures to promote green growth. Green Growth is defined as low-carbon, resource-efficient economic growth based on safeguarding the functional capacity of ecosystems while promoting wellbeing and social justice. Green growth is considered to have significant worldwide potential, which is currently evident particularly in the rapid growth of cleantech demand. Successful future actors will be more material- and energy-efficient than their competitors, and they will be able to provide services and products flexibly for a low-carbon society. There are opportunities for green growth in all sectors of society. Green growth may consist of an entirely new kind of business activity and create new companies, but there are also opportunities in our traditional energy- and resource-intensive industries. Companies have a key role in growth, but realising green growth also requires changes in consumption. Central, regional and local government will act as facilitators in creating the preconditions for green growth. The report presents a number of policy measures and processes by which Finland can support green growth. Proposals for steps towards green growth include: (A.) Creating preconditions for green growth through a joint vision and political commitment. (B.) Stimulating companies' green growth potential and boosting green demand. (C

  12. Williamson Act - The California Land Conservation Act of 1965

    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...

  13. A Study on the Korea Database Industry Promotion Act Legislation

    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.

  14. Job Patterns for Minorities & Women in Private Industry, 1981. Equal Employment Opportunity Report. Volume 2.

    Equal Employment Opportunity Commission, Washington, DC.

    As part of its mandate under Title VII of the Civil Rights Act of 1964, the Equal Employment Opportunity Commission requires periodic reports from public and private employees, unions, and labor organizations, indicating the makeup of their workforce by sex and by race-ethnic categories. This volume contains two tables summarizing data obtained as…

  15. Job Patterns for Minorities & Women in Private Industry, 1981. Equal Employment Opportunity Report. Volume 1.

    Equal Employment Opportunity Commission, Washington, DC.

    As part of its mandate under Title VII of the Civil Rights Act of 1964, the Equal Employment Opportunity Commission requires periodic reports from public and private employers, unions, and labor organizations, indicating the makeup of their workforce by sex and by race/ethnic categories. This volume contains two tables summarizing data obtained as…

  16. Teaching English Language Learners in Mainstream Science Classrooms: Teacher Practice and Educational Opportunity

    Schroeder, Carlotta Dorothy

    2011-01-01

    Equal educational opportunity for English language learners (ELLs) has been a goal of the public educational system in the United States. Language policy reforms have increased accountability in order for schools to improve student achievement and measure the progress of ELLs. The No Child Left Behind Act (NCLB) requires assessment and…

  17. Puerto Rican Participation in Job Opportunities and Basic Skills (JOBS) Programs. A Preliminary Assessment.

    Cruz, Jose E.

    This report presents the findings of a preliminary assessment of the strengths and weaknesses of the Job Opportunities and Basic Skills (JOBS) programs, the welfare-to-work centerpiece of the Family Support Act, for moving Puerto Rican welfare recipients closer to self-sufficiency. Programs in Newark (New Jersey), New York City, and Philadelphia…

  18. Biotechnological opportunities in biosurfactant production.

    Geys, Robin; Soetaert, Wim; Van Bogaert, Inge

    2014-12-01

    In the recent years, biosurfactants proved to be an interesting alternative to petrochemically derived surfactants. Two classes of biosurfactants, namely glycolipids and lipopeptides, have attracted significant commercial interest. Despite their environmental advantages and equal performance, commercialization of these molecules remains a challenge due to missing acquaintance of the applicants, higher price and lack of structural variation. The latter two issues can partially be tackled by screening for novel and better wild-type producers and optimizing the fermentation process. Yet, these traditional approaches cannot overcome all hurdles. In this review, an overview is given on how biotechnology offers opportunities for increased biosurfactant production and the creation of new types of molecules, in this way enhancing their commercial potential. PMID:24995572

  19. Angiogenesis and Its Therapeutic Opportunities

    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.

  20. Multiphysics simulations: Challenges and opportunities

    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.

  1. CORIDORS: DEVELOPMENT OPPORTUNITY OF SERBIA

    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.

  2. Biomass Business Opportunities Viet Nam

    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)

  3. Photovoltaic research opportunities. Final report

    Macaleer, B.; Bowers, J.; Hurlburt, B.

    1985-11-19

    The purpose of this study is to identify opportunities for photovoltaic (PV) research projects to capitalize on related but non-PV research. The study is performed under the assumption that a considerable body of ongoing semiconductor research in non-PV areas could be of value to its PV Program and the PV community in general. Research related to III-V compounds, thin films, and crystalline silicon materials is included. Research that is known to be PV-related or sponsored by DOE was excluded from consideration. The study resulted in 11 recommendations (research areas) and a subset of 58 specific research projects. In addition, over 75 non-PV research managers in the semiconductor field are identified as potential sources of ideas which could benefit photovoltaics.

  4. Multiphysics Simulations: Challenges and Opportunities

    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.

  5. Physics opportunities with meson beams

    Briscoe, William J.; Doering, Michael; Haberzettl, Helmut; Strakovsky, Igor I. [The George Washington University, Washington, DC (United States); Manley, D.M. [Kent State University, Kent, OH (United States); Naruki, Megumi [Kyoto University, Kyoto (Japan); Swanson, Eric S. [University of Pittsburgh, Pittsburgh, PA (United States)

    2015-10-15

    Over the past two decades, meson photo- and electroproduction data of unprecedented quality and quantity have been measured at electromagnetic facilities worldwide. By contrast, the meson-beam data for the same hadronic final states are mostly outdated and largely of poor quality, or even non-existent, and thus provide inadequate input to help interpret, analyze, and exploit the full potential of the new electromagnetic data. To reap the full benefit of the high-precision electromagnetic data, new high-statistics data from measurements with meson beams, with good angle and energy coverage for a wide range of reactions, are critically needed to advance our knowledge in baryon and meson spectroscopy and other related areas of hadron physics. To address this situation, a state-of-the-art meson-beam facility needs to be constructed. The present paper summarizes unresolved issues in hadron physics and outlines the vast opportunities and advances that only become possible with such a facility. (orig.)

  6. Realize a world of opportunity

    The Export Development Corporation (EDC) is a federal government-owned financial institution established to support Canadian firms of all sizes in the pursuit of international trade and investment opportunities. EDC is doing business in over 200 countries, worth over $40 billion. Over 5,000 Canadian companies were using EDC products and services in 1999. EDC offers accounts receivable insurance, contract insurance, political risk insurance and various financial products such as direct buyer loans, lines of credit, guarantees for bonds, access to surety services, and limited recourse structured finance. In evaluating a prospective transaction, EDC looks for assurances of the Canadian exporter's capability to deliver as promised, a credit-worthy counter-party, the viability of the project including, when deemed necessary, an environmental review, and benefits to Canada. CDM projects and environmental projects in general are within the mandate of EDC, provided they meet EDC's normal due diligence and analysis requirements

  7. Physics Opportunities with Meson Beams

    Briscoe, William J; Haberzettl, Helmut; Manley, D Mark; Naruki, Megumi; Strakovsky, Igor I; Swanson, Eric S

    2015-01-01

    Over the past two decades, meson photo- and electro-production data of unprecedented quality and quantity have been measured at electromagnetic facilities worldwide. By contrast, the meson-beam data for the same hadronic final states are mostly outdated and largely of poor quality, or even nonexistent, and thus provide inadequate input to help interpret, analyze, and exploit the full potential of the new electromagnetic data. To reap the full benefit of the high-precision electromagnetic data, new high-statistics data from measurements with meson beams, with good angle and energy coverage for a wide range of reactions, are critically needed to advance our knowledge in baryon and meson spectroscopy and other related areas of hadron physics. To address this situation, a state of-the-art meson-beam facility needs to be constructed. The present paper summarizes unresolved issues in hadron physics and outlines the vast opportunities and advances that only become possible with such a facility.

  8. Business Opportunities for Small Reactors

    This report assesses the market potential and identifies a number of potential paths for developing the small nuclear reactor business. There are several potential opportunities identified and evaluated. Selecting a specific approach for the business development requires additional information related to a specific market and sources of capital to support the investment. If and how a market for small nuclear plants may develop is difficult to predict because of the complexity of the economic and institutional factors that will influence such development. Key factors are; economics, safety, proliferation resistance and investment risk. The economic and political interest of any of the identified markets is also dependent on successful demonstration of the safety and reliability of small nuclear reactor. Obtaining a US-NRC Standard Design approval would be an important development step toward establishing a market for small reactors. (authors)

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

    Pankaj Chaturvedi

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  10. Plastics recycling: challenges and opportunities.

    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

  11. ITER safety challenges and opportunities

    Results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ''ITER is capable of meeting anticipated regulatory dose limits,'' but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. We need much research and development (R ampersand D) and design analysis to establish that ITER meets regulatory requirements. We have a further opportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, we need to overcome three programmatic challenges and three technical challenges. The first programmatic challenge is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of the three key technical challenges is plasma engineering -- burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost. Some design requirements are now too strict; some are too lax. Fuel cycle design requirements are presently too strict, mandating inappropriate T separation from H and D. Heat sink requirements are presently too lax; they should be strengthened to ensure that maximum loss of coolant accident temperatures drop

  12. CRISPR/Cas9 allows efficient and complete knock-in of a destabilization domain-tagged essential protein in a human cell line, allowing rapid knockdown of protein function.

    Arnold Park

    Full Text Available Although modulation of protein levels is an important tool for study of protein function, it is difficult or impossible to knockdown or knockout genes that are critical for cell growth or viability. For such genes, a conditional knockdown approach would be valuable. The FKBP protein-based destabilization domain (DD-tagging approach, which confers instability to the tagged protein in the absence of the compound Shield-1, has been shown to provide rapid control of protein levels determined by Shield-1 concentration. Although a strategy to knock-in DD-tagged protein at the endogenous loci has been employed in certain parasite studies, partly due to the relative ease of knock-in as a result of their mostly haploid lifecycles, this strategy has not been demonstrated in diploid or hyperploid mammalian cells due to the relative difficulty of achieving complete knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease-mediated targeted genome cleavage has been shown to allow highly efficient homologous recombination at the targeted locus. We therefore assessed the feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1 in human 293T cells. Using a double antibiotic selection strategy to select clones with at least two knock-in alleles, we obtained numerous complete knock-in clones within three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells was Shield-1 concentration-dependent, and removal of Shield-1 resulted in destabilization of DD-TCOF1 over the course of hours. We further confirmed that the tagged TCOF1 retained the nucleolar localization of the wild-type untagged protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth, as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated homologous recombination to completely knock-in a DD tag likely represents a generalizable and

  13. Affordable Care Act and Women

    ... Privacy Policy FOIA Plain Writing Act No Fear Act Disclaimers Viewers & Players Assistant Secretary for Planning and Evaluation, Room 415F U.S. Department of Health and Human Services 200 Independence Avenue, SW Washington, D.C. ...

  14. ACT/SAT College Survey.

    Stafford, John E.

    1998-01-01

    Reports on findings of a survey designed to discover whether higher education institutions' admission standards accept SAT I or ACT and if there is preference for either, and whether ACT could be submitted in lieu of SAT II subject tests. Eighty-six percent of the reporting schools indicated no preference; 28 schools indicated that the ACT was an…

  15. Atomic Energy Authority Act 1954

    This Act provides for the setting up of an Atomic Energy Authority for the United Kingdom. It also makes provision for the Authority's composition, powers, duties, rights and liabilities, and may amend, as a consequence of the establishment of the Authority and in connection therewith, the Atomic Energy Act, 1946, the Radioactive Substances Act 1948 and other relevant enactments. (NEA)

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

    Nansen, A; Christensen, Jan Pravsgaard; Röpke, C; Marker, O; Scheynius, A; Thomsen, Allan Randrup

    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...... inflammatory exudate disclosed that leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production of tumor necrosis-alpha and NO) was significantly impaired. Notably, 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...

  17. The 1990 Clean Air Act amendments

    The impacts of the 1990 Clean Air Act Amendments on utilities are substantial, presenting a host of new technical challenges, introducing new business risks, changing costs of electric generation, creating new winners and losers, and calling for new organizational responses capable of dealing with the complexity and short time for decisions. The magnitude of costs and unknowns puts clean air compliance into a new league of energy issues, in which the decisions utilities must make are not simply technological or engineering economic choices, but rather are very complex business decisions with numerous stakeholders, pitfalls, and opportunities. This paper summarizes the key regulatory requirements of the CAAA, outlines compliance options and questions facing the utility industry, and addresses how utility strategic business decisions could be affected

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

    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.

  19. Characterization of the MPS I-H knock-in mouse reveals increased femoral biomechanical integrity with compromised material strength and altered bone geometry

    Arin K. Oestreich

    2015-12-01

    Full Text Available Mucopolysaccharidosis type I (MPS I, is an autosomal recessive lysosomal storage disorder caused by a deficiency in the α-L-iduronidase enzyme, resulting in decreased enzymatic activity and accumulation of glycosaminoglycans. The disorder phenotypically manifests with increased urine glycosaminoglycan excretion, facial dysmorphology, neuropathology, cardiac manifestations, and bone deformities. While the development of new treatment strategies have shown promise in attenuating many symptoms associated with the disorder, the bone phenotype remains unresponsive. The aim of this study was to investigate and further characterize the skeletal manifestations of the Idua-W392X knock-in mouse model, which carries a nonsense mutation corresponding to the IDUA-W402X mutation found in Hurler syndrome (MPS I-H patients. μCT analysis of the microarchitecture demonstrated increased cortical thickness, trabecular number, and trabecular connectivity along with decreased trabecular separation in the tibiae of female homozygous Idua-W392X knock-in (IDUA−/− mice, and increased cortical thickness in male IDUA−/− tibiae. Cortical density, as determined by μCT, and bone mineral density distribution, as determined by quantitative backscattered microscopy, were equivalent in IDUA−/− and wildtype (Wt bone. However, tibial porosity was increased in IDUA−/− cortical bone. Raman spectroscopy results indicated that tibiae from female IDUA−/− had decreased phosphate to matrix ratios and increased carbonate to phosphate ratios compared to Wt female tibiae, whereas these ratios remained equivalent in male IDUA−/− and Wt tibiae. Femora demonstrated altered geometry and upon torsional loading to failure analysis, female IDUA−/− mouse femora exhibited increased torsional ultimate strength, with a decrease in material strength relative to Wt littermates. Taken together, these findings suggest that the IDUA−/− mutation results in increased bone

  20. Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).

    Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio

    2015-11-01

    Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a

  1. Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down.

    Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

    2016-09-01

    Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting the gene phosphatase and tensin homolog (PTEN) in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the "wrong" side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical adeno-associated virus (AAV)-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral biotinylated dextran amine (BDA) injections in PTEN-deleted mice with spinal cord injury and in noninjured PTEN-floxed mice that had not received AAV-Cre. In noninjured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in gray matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side; in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using short hairpin (sh)RNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the noninjured CST, highlighting one aspect of how the resultant circuitry from regenerating axons may differ from that of the uninjured CST. J. Comp. Neurol. 524:2654-2676, 2016. © 2016 Wiley Periodicals, Inc. PMID:26878190

  2. A Balancing Act?

    Gerstlberger, Wolfgang; Knudsen, Mette Præst; Stampe, Ian

    efficiency moderates the effect of market attention on new product development. The paper therefore concludes that product innovation and energy efficiency is a balancing act, focusing on one will have detrimental effects on the other! These findings point to the conclusion that researchers and practitioners......With an undifferentiated catchword ‘eco-innovation’ is a largely understudied area, but of high relevance to the society and companies given the strong focus especially by governments on grand challenges like climate change, green technologies and environmental challenges. The paper utilizes the...... 2009 European Manufacturing Survey for the Danish sub-sample including 335 manufacturing firms. Through factor analysis, the paper confirms three main focus areas of new product development in relation to production facilities: efficiency considerations, market attention and greening of innovation...

  3. Triple acting radial seal

    Ebert, Todd A; Carella, John A

    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.

  4. A Balancing Act?

    Gerstlberger, Wolfgang; Stampe, Ian; Knudsen, Mette Præst

    efficiency moderates the effect of market attention on new product development. The paper therefore concludes that product innovation and energy efficiency is a balancing act, focusing on one will have detrimental effects on the other! These findings point to the conclusion that researchers and practitioners....... Logistic regression analysis demonstrates that while market attention is important for new product development, green aspects of innovation and efficiency considerations for innovation are important for the energy efficiency of the production companies. Combining these models highlights that energy...... in innovation management have to take the specificities and interactions of different types of eco-innovation more carefully in consideration than so far and to formulate new managerial practices combining energy efficiency and product innovation....

  5. 24 CFR 180.415 - Notice of proposed adverse action regarding Federal financial assistance in non-Fair Housing Act...

    2010-04-01

    ... CFR parts 1, 6, 8, or 146, the General Counsel shall file a notice of proposed adverse action with the... FOR EQUAL OPPORTUNITY, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT EMPLOYMENT AND BUSINESS OPPORTUNITY... govern the proceeding. (c) Consolidation. The ALJ may provide for non-Fair Housing Act proceedings at...

  6. Opportunities of Continuing Adult Education

    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

  7. CRISIS LEADERSHIP - AN ORGANIZATIONAL OPPORTUNITY

    James E. Prewitt

    2011-09-01

    Full Text Available Reactive leadership and crisis management have been synonymous for years. This flows from the belief that crisis is unpredictable and unexpected, which is simply not true. Crisis has its genesis in the values, beliefs, culture, or behavior of an organization which become incongruent with the milieu in which the organization operates. A leader, who is able to read the signals of looming crisis and understands how to harness the exigency brought on by the situation, can diminish the potential dangers and take full advantage of the resulting opportunities. This paper presents a generic crisis lifecycle as a representation of overall crisis. Since a crisis can be broken down into three unique phases, crisis lifecycles can be understood and utilized for the benefit of the organization. In the first phase of the lifecycle, the organization finds itself mired in a static phase which equates to a comfort zone. In this first phase leaders struggle when they attempt to introduce change or learning due to the organizations preference to avoid conflict and maintain stasis. When a crisis engulfs an organization then the stasis that envelops the organization evaporates and gives rise to the second phase or the disaster phase. The disaster phase often threatens the very existence of the organization. When the organization successfully eliminates the immediate organizational threat, the organization is able to enter the adjustive phase of the crisis lifecycle. In this third phase, the leader has the undivided attention of the organization and the underlying urgency to solve the issues that led to the crisis in the first place. Regrettably, many leaders don’t take advantage of this golden opportunity and push the organization back toward the status-quo which ensures that the crisis will return in force. The study of crisis leadership has become more important since the dawn of the new millennium because leaders in all areas face differing degrees of crisis in

  8. A multidisciplinary conceptualization of conservation opportunity.

    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

  9. Salutogenic Window of Opportunity in Nutrition Promotion

    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, group exercises, and case studies. The conference will be a great opportunity to share expertise and network as it provides reports from top scientists and practitioners on what we know about strategie...

  10. Career Opportunities for Physicists: Panel Discussion

    2016-03-01

    We live in a world full of opportunity for physics graduates. Join us for a unique opportunity to learn about some of these opportunities from our diverse panel of working physicists from industrial, national lab, and academic sectors. Topics of discussion will include panelists' daily experiences, how physics serves them in their career, and advice to students interested in following a similar path. Light refreshments will be served.

  11. Employees’ Entrepreneurial Attitudes and Opportunity Recognition

    Rintamäki, Timo; Vassil, Afzali

    2012-01-01

    Background: Organizations’ ability to recognize opportunities can provide competitive advantage for organizations in changing environment. In innovation-driven countries many en-trepreneurial people are working as employees in established companies and pursuing opportunities as corporate entrepreneurs. This is a group which researchers have dis-criminated by focusing only on CEO’s and entrepreneur’s opportunity identification capability. We would like to research the topic of employees’ oppor...

  12. Neighborhood Crime and Young Males' Job Opportunity

    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...

  13. Evaluating Program Effectiveness: A Case Study of the School-to-Work Opportunities Act in California

    Neumark, David

    2006-01-01

    Evaluations of the effectiveness of government programs may serve both to improve program implementation and to convey to policymakers information on the effectiveness of these programs. However, the evidence generated from programs and their providers--perhaps especially when these programs are decentralized and implemented and run locally--may…

  14. 76 FR 41434 - Removal of Certain Requirements Related to the Prescription Drug Marketing Act; Opportunity for...

    2011-07-14

    ... proposed rule to require that the pedigree only go back to the last authorized distributor of record (64 FR... with the manufacturer, and that the identifying statement (also known as the ``pedigree'') must include... respect to the statutory pedigree requirements of the PDMA, as long as the pedigree identifies the...

  15. OPPORTUNITIES TO PRODUCE HEALTHIER BEEF

    G. HOLLÓ

    2013-12-01

    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.

  16. Tuberculosis diagnostics: Challenges and opportunities

    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.

  17. ITER safety challenges and opportunities

    This paper reports on results of the Conceptual Design Activity (CDA) for the International Thermonuclear Experimental Reactor (ITER) suggest challenges and opportunities. ITER is capable of meeting anticipated regulatory dose limits, but proof is difficult because of large radioactive inventories needing stringent radioactivity confinement. Much research and development (R ampersand D) and design analysis is needed to establish that ITER meets regulatory requirements. There is a further oportunity to do more to prove more of fusion's potential safety and environmental advantages and maximize the amount of ITER technology on the path toward fusion power plants. To fulfill these tasks, three programmatic challenges and three technical challenges must be overcome. The first step is to fund a comprehensive safety and environmental ITER R ampersand D plan. Second is to strengthen safety and environment work and personnel in the international team. Third is to establish an external consultant group to advise the ITER Joint Team on designing ITER to meet safety requirements for siting by any of the Parties. The first of three key technical challenges is plasma engineering - burn control, plasma shutdown, disruptions, tritium burn fraction, and steady state operation. The second is the divertor, including tritium inventory, activation hazards, chemical reactions, and coolant disturbances. The third technical challenge is optimization of design requirements considering safety risk, technical risk, and cost

  18. Marine geomorphometry: Overview and opportunities.

    Micallef, Aaron; Lecours, Vincent; Dolan, Margaret; Lucieer, Vanessa

    2016-04-01

    Multibeam echosounder data comprise the primary source for digital terrain models of the seafloor. Recent advances in seafloor surveying technologies have resulted in a dramatic increase in the quantity and resolution of multibeam echosounder data, prompting a renewed interest in employing geomorphometric techniques to investigate the seafloor. Marine geomorphometric techniques are not as varied and as extensively applied as in terrestrial environments. This is due to the difficultly with capturing terrain variability underwater, since changes in topography are more subdued in comparison to terrestrial landscapes. Issues related to scale are also relevant in submarine settings, but they manifest themselves differently due to the differences in input data. In the last decade, a suite of marine geomorphometric techniques have been developed - terrain attributes, feature-based quantitative representation, automated classification - and employed to investigate a wide range of phenomena - seafloor landforms and geomorphic processes, geohazards, hydrodynamics, habitats. This contribution provides an overview of progress made in marine geomorphometry in the last decade as well as highlights the opportunities and challenges faced by this thriving field of research in the near future.

  19. New design opportunities with OVI

    Bleikolm, Anton F.

    1998-04-01

    Optically Variable Ink (OVITM) chosen for its unique colour shifting properties is applied to the currencies of more than 50 countries. An significant colour difference at viewing angles of 90 degrees and 30 degrees respectively makes colour copying impossible. New manufacturing techniques for the interference pigment (OVP) provide ever better cost/performance ratios. Screen printing presses newly available on the market guarantee production speeds of 8000 sheets/hour or 130 meters/minute in the case of web printing, perfectly in line with the traditional equipment for manufacturing of currency. Specifically developed ink formulations allow UV-curing at high speed or oxidative drying to create highly mechanically and chemically resistant colour shifting prints. The unique colour shifting characteristics together with overprinting in intaglio give design opportunities providing the best protection against colour copying or commercial reprint. Specific designs of OVP together with high security ingredients allow the formulation of machine readable optically variable inks useful for the authentication and sorting of documents.

  20. Research opportunities in photochemical sciences

    NONE

    1996-07-01

    The workshop entitled {open_quotes}Research Opportunities in Photochemical Sciences{close_quotes} was initiated by the U.S. Department of Energy (DOE), Office of Energy Research (ER), Office of Basic Energy Sciences (BES), Division of Chemical Sciences. The National Renewable Energy Laboratory (NREL) in Golden, Colorado was requested by ER to host the workshop. It was held February 5-8, 1996 at the Estes Park Conference Center, Estes Park, CO, and attended by about 115 leading scientists and engineers from the U.S., Japan, and Europe; program managers for the DOE ER and Energy Efficiency and Renewable Energy (EERE) programs also attended. The purpose of the workshop was to bridge the communication gap between the practioneers and supporters of basic research in photochemical science and the practioneers and supporters of applied research and development in technologies related to photochemical science. For the purposes of the workshop the definition of the term {open_quotes}photochemical science{close_quotes} was broadened to include homogeneous photochemistry, heterogeneous photochemistry, photoelectrochemistry, photocatalysis, photobiology (for example, the light-driven processes of biological photosynthesis and proton pumping), artificial photosynthesis, solid state photochemistry, and solar photochemistry. The technologies under development through DOE support that are most closely related to photochemical science, as defined above, are the renewable energy technologies of photovoltaics, biofuels, hydrogen energy, carbon dioxide reduction and utilization, and photocatalysis for environmental cleanup of water and air. Individual papers were processed separately for the United states Department of Energy databases.

  1. CANDU co-generation opportunities

    Modern technology makes use of natural energy 'wealth' (uranium) to produce useful energy 'currency' (electricity) that can be used to society's benefit. This energy currency can be further applied to help solve a difficult problem faced by mankind. Within the next few years we must reduce our use of the same fuels which have made many countries wealthy - fossil fuels. Fortunately, electricity can be called upon to produce another currency, namely hydrogen, which has some distinct advantages. Unlike electricity, hydrogen can be stored and can be recovered for later use as fuel. It also is extremely useful in chemical processes and refining. To achieve the objective of reducing greenhouse gas emissions hydrogen must, of course, be produced using a method which does not emit such gases. This paper summarizes four larger studies carried out in Canada in the past few years. From these results we conclude that there are several significant opportunities to use nuclear fission for various co-generation technologies that can lead to more appropriate use of energy resources and to reduced emissions. (author)

  2. Forecast of Contracting and Subcontracting Opportunities, Fiscal year 1995

    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.

  3. GWAS 2011: Opportunities and challenges

    Jian-Jun Liu; Xue-Jun Zhang

    2011-01-01

    The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent samples,linkage disequilibrium (LD) -based systematic genome-wide interrogation,and vigorous statistical standard for declaring genetic association,GWAS has greatly advanced the genetic studies of human disease by successfully identifying over 4 thousands of genetic susceptibility SNPs or loci for 210 diseases/traits in human.Besides its unrivaled scientific achievements,GWAS has also transformed the communities of human genetics by stimulating unprecedented broad and large-scale collaboration and data sharing across different groups and countries,which has enabled some mega genetic studies where dozens or hundreds of thousands of samples were investigated through mete-analysis,providing enormous statistical power for discovering genetic variants,even the ones with very moderate effect on disease phenotype or physiological trait.While the success of GWAS has been widely recognized,there are many concerns on GWAS that are being passionately debated.In particular,there ate heated discussions on why only a limited proportion,quiet often a small proportion,of genetic heritability can be explained by the GWAS findings,and whether and how the GWAS findings have really advanced the biological investigation and understanding of disease mechanisms.Concerning these shortcomings of GWAS,many have genuinely questioned the perspective of translating the GWAS findings into clinical practice.To provide a platform to discuss the progresses and shortcomings of GWAS,a nature conference,titled “GWAS 2011:Opportunities and Challenges”,was organized through the collaboration between the Nature Genetics and Anhui Medical University,which was held in Hefei,China on May 19-21,2011.

  4. Genetic Information Nondiscrimination Act. Final rule.

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act of 2008 as they relate to employer-sponsored wellness programs. This rule addresses the extent to which an employer may offer an inducement to an employee for the employee's spouse to provide information about the spouse's manifestation of disease or disorder as part of a health risk assessment (HRA) administered in connection with an employer-sponsored wellness program. Several technical changes to the existing regulations are included. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) that addresses the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. PMID:27192741

  5. Salutogenic Window of Opportunity in Nutrition Promotion

    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, grou

  6. Putting Opportunism in the Back Seat

    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...

  7. Marketing Opportunities in the Digital World.

    Kiani, G. Reza

    1998-01-01

    Addresses the opportunities offered by the Web to marketers. Considers the Web as a two-way communication model in which four different communication states can take place. Suggests the necessity of new concepts and models for marketers to manage their Web sites, and presents opportunities supporting the marketers' objectives in the new…

  8. Challenges and Opportunities for Libraries in Pakistan

    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...

  9. 76 FR 41590 - Equal Credit Opportunity

    2011-07-15

    ... Credit Transactions Act of 2003 (FACT Act), which amended the FCRA (January 2010 Final Rule). 75 FR 2724... set the designated transfer date as July 21, 2011. 75 FR 57252 (Sept. 20, 2010). On March 15, 2011... of the Dodd-Frank Act. 76 FR 13896. The comment period closed on April 14, 2011.\\2\\ The...

  10. The becoming of an entrepreneurial opportunity

    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...... 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...

  11. Social problems as sources of opportunity – antecedents of social entrepreneurship opportunities

    Agnieszka Żur

    2016-02-01

    Full Text Available Objective: Based on extensive literature review, this paper aims to establish if, why and how, in given environmental and market contexts, social entrepreneurship (SE opportunities are discovered and exploited. It positions social problems as sources of entrepreneurial opportunity. The article presents an integrated process-based view of SE opportunity antecedents and concludes with a dynamic model of SE opportunity. Research Design & Methods: To fulfil its goal, the paper establishes opportunity as unit of research and explores the dynamics of opportunity recognition. To identify the components of SE opportunity through a process-based view, the study follows the steps of critical literature review method. The literature review follows with logical reasoning and inference, which results in the formulation of a model proposition of social entrepreneurship opportunity. Findings: The paper presents a holistic perspective on opportunity antecedents in SE context and introduces social problems, information, social awareness and entrepreneurial mindset  as fundamental components of social entrepreneurship opportunity equation. Implications & Recommendations: It is necessary to remember for policy makers, investors and partners involved within the social sector, that social problems can be the source of entrepreneurial opportunity. Training, assisting and engaging socially aware entrepreneurs is a promising line of development for all communities. Contribution & Value Added: The major contribution of this study lies in extending the existing body of social entrepreneurship research by providing a new perspective, placing social problem as opportunity in the centre of the discussion.

  12. JK '98: Acting responsibly

    For the first time, a paper delivered at the Annual Nuclear Conference was presented by two authors, the CEO of Bayernwerk AG, Dr. Otto Majewski, and the CEO of the Power Generation Division (KWU) of Siemens AG, Adolf Huettl, reflecting the operators' and the vendors' points of view about the present situation of nuclear power use in Germany and the need to maintain its share in the energy mix. The events associated with shipments of casks for radioactive waste have rekindled the debate about the responsibility of the peaceful use of nuclear power in the nuclear opposition camp. That debate needs to be put back on a factual basis. If no consensus could be achieved now about the use of nuclear power as a whole, at least consensus had to be reached about the future approach to spent fuel and waste management. From the outset, the nuclear industry has shown a high degree of responsibility, developing concepts of using uranium as an energy source in an economically viable and responsible way. It is showing responsibility also in making provision for the future. The safe and economically successful operation of today's nuclear power plants is an important reason for developing new reactor concepts. That development of new rector lines depends critically on the preservation and advancement of specialized knowledge. Know-how needs to be preserved and developed further not only for future nuclear power plants but also for the plants existing now, which still have service lives of several decades. Sustainable energy supply requires all sources of energy to be exploited, especially those which do not generate carbon dioxide. All the options currently known must be kept open and preserved, respectively, for coming generations. Acting responsibly means adding to the choices available. (orig.)

  13. [Euthanasia and medical act].

    2011-05-01

    Right to life -as the prohibition of intentionally and arbitrarily taking life, even with authorization of the concerned one- is an internationally recognized right. In many countries, debate regarding euthanasia is more centered in its convenience, social acceptability and how it is regulated, than in its substantial legitimacy. Some argue that euthanasia should be included as part of clinical practice of health professionals, grounded on individual's autonomy claims-everyone having the liberty to choose how to live and how to die. Against this, others sustain that life has a higher value than autonomy, exercising autonomy without respecting the right to life would become a serious moral and social problem. Likewise, euthanasia supporters some-times claim a 'right to live with dignity', which must be understood as a personal obligation, referred more to the ethical than to the strictly legal sphere. In countries where it is already legalized, euthanasia practice has extended to cases where it is not the patient who requests this but the family or some healthcare professional, or even the legal system-when they think that the patient is living in a condition which is not worthy to live. Generalization of euthanasia possibly will end in affecting those who need more care, such as elder, chronically ill or dying people, damaging severely personal basic rights. Nature, purpose and tradition of medicine rule out the practice of euthanasia, which ought not be considered a medical act or legitimately compulsory for physicians. Today's medicine counts with effective treatments for pain and suffering, such as palliative care, including sedative therapy, which best preserves persons dignity and keeps safe the ethos of the medical profession. PMID:22051717

  14. The Price-Anderson Act

    The Price-Anderson Act establishes nuclear liability law in the United States. First passed in 1957, it has influenced other nuclear liability legislation around the world. The insurer response the nuclear accident at Three Mile Island in 1979 demonstrates the application of the Act in a real life situation. The Price-Anderson Act is scheduled to be renewed in 2002, and the future use of commercial nuclear power in tge United States will be influenced by this renewal. (author)

  15. Atomic Energy Authority Act 1971

    This Act provides for the transfer of property, rights, liabilities and obligations of parts of the undertaking of the United Kingdom Atomic Energy Autority, to two new Compagnies set up for this purpose: the Bristish Nuclear Fuels Limited, and the Radiochemical Centre Limited. Patents licences and registered designs owned by the Autority at the time of the transfer are not included therein. The Act also includes amendments to the Nuclear Installations Act 1965, notably as regards permits to operate granted to a body corporate. Finally, the Schedule to this Act lays down a certain number of provisions relating to security and the preservation of secrets. (NEA)

  16. Opportunities for Funding at NSF

    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

  17. Offsets - An opportunity of Financing

    Nuclear Research Reactors sometimes need to implement projects to upgrade, revamp or convert their reactor, acquire new fuel elements, etc. However, as their activities are mainly of noncommercial nature, they sometimes lack of financial resources to implement these projects by themselves. Several solutions exist: loans, governmental budget, subsidies from international organizations (IAEA). Offsets are another source of financing. They also are free of charge for the reactor. The objective of offsets is to Identify, implement and finance projects that: directly create or sustain a local economic activity of high-added value, would not have happened without the Obligor's intervention, and are of crucial importance given the country's political background (favor employment, technology transfers, training and education, research and development, etc.). Companies worldwide are willing to finance local projects to fulfill their Offset Obligation. Local organizations or institutions are willing to invest to increase their activities but lack of financial resources. Offset regulations are an opportunity on both sides and are free for the local organization. The monetary value of an Offset obligation is calculated as a percentage of the main contract price (or as a percentage of the imported part value). That percentage depends on the Country's legislation and on the nature of the main contract (defense or civilian). This value has to be compensated by an equivalent economic value (a Project's cost is different from its value). There is two ways of assessing a value: - Political aspects: The Project is of political importance for the country (development of an export capability, technology and/or know-how transfers) and the project in line with the country's political priorities (employment, research, international presence, etc.). - Economic benefits: the project directly sustains or creates additional activities, turnover, R and D, employment, etc. It benefits directly

  18. 75 FR 29 - Privacy Act, Government in the Sunshine Act, Freedom of Information Act (“FOIA”), and Federal...

    2010-01-04

    ... of Information Act of 1966, as amended, 5 U.S.C. 552, and the Federal Election Campaign Act (``FECA... the Sunshine Act, Freedom of Information Act (``FOIA''), and Federal Election Campaign Act (``FECA... word ``meeting.'' Corrections to Freedom of Information Act Rules in Part 4 of Title 11 of the Code...

  19. Nuclear Material (Offences) Act 1983

    The main purpose of this Act is to enable the United Kingdom to ratify the Convention on the Physical Protection of Nuclear Material which opened for signature at Vienne and New York on 3 March 1980. The Act extends throughout the United Kingdom. (NEA)

  20. Online Challenge versus Offline ACT

    Peckham, Irvin

    2010-01-01

    This article compares essays written in response to the ACT Essay prompt and a locally developed prompt used for placement. The two writing situations differ by time and genre: the ACT Essay is timed and argumentative; the locally developed is untimed and explanatory. The article analyzes the differences in student performance and predictive…

  1. Implementing the Amended FOI Act.

    McClain, Wallis

    The Freedom of Information Act amendments, which became effective in February 1975, have so far yielded mixed results. This report provides an account of how different federal agencies are implementing this amended statute. Among the topics discussed are modifications of the original 1966 Freedom of Information Act, which were made in the attempt…

  2. 76 FR 59073 - Privacy Act

    2011-09-23

    ... From the Federal Register Online via the Government Publishing Office CENTRAL INTELLIGENCE AGENCY 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...

  3. Atomic Energy Commission Act, 1963

    Promulgated in 1963, the Atomic Energy Commission Act (204) established and vested in the Ghana Atomic Energy Commission the sole responsibility for all matters relating to the peaceful uses of atomic energy in the country. Embodied in the Act are provisions relating to the powers, duties, rights and liabilities of the Commission. (EAA)

  4. Maintenance of State Effort for Higher Education: "Barriers to Equal Educational Opportunity in Addressing the Rising Costs of a College Education"

    Alexander, F. King

    2011-01-01

    A Maintenance of Effort (MOE) provision for higher education was first adopted in the Higher Education Opportunity Act of 2008 and was included as a requirement for states to participate in the American Recovery and Reinvestment Act of 2009 (ARRA). The information in this article was presented before the U.S. House of Representatives Committee on…

  5. Generating Innovation Opportunities - Exploring Unexpressed Customer Knowledge

    Kallio, Anne; Bergenholtz, Carsten

    2009-01-01

    generate innovation opportunities by exploring unexpressed customer knowledge? Based on an action research project in an organisation, the study presents an empirical example of how innovation opportunities can be generated by having salespeople apply an anthropological perspective when interacting with......This study focuses on how a company can generate innovation opportunities by exploring unexpressed customer knowledge. In an open innovation paradigm, exploration can be performed via an in-depth or broad search of resources beyond organisational boundaries. Salespeople are an essential channel to...

  6. The child opportunity index: improving collaboration between community development and public health.

    Acevedo-Garcia, Dolores; McArdle, Nancy; Hardy, Erin F; Crisan, Unda Ioana; Romano, Bethany; Norris, David; Baek, Mikyung; Reece, Jason

    2014-11-01

    Improving neighborhood environments for children through community development and other interventions may help improve children's health and reduce inequities in health. A first step is to develop a population-level surveillance system of children's neighborhood environments. This article presents the newly developed Child Opportunity Index for the 100 largest US metropolitan areas. The index examines the extent of racial/ethnic inequity in the distribution of children across levels of neighborhood opportunity. We found that high concentrations of black and Hispanic children in the lowest-opportunity neighborhoods are pervasive across US metropolitan areas. We also found that 40 percent of black and 32 percent of Hispanic children live in very low-opportunity neighborhoods within their metropolitan area, compared to 9 percent of white children. This inequity is greater in some metropolitan areas, especially those with high levels of residential segregation. The Child Opportunity Index provides perspectives on child opportunity at the neighborhood and regional levels and can inform place-based community development interventions and non-place-based interventions that address inequities across a region. The index can also be used to meet new community data reporting requirements under the Affordable Care Act. PMID:25367989

  7. Vietnam: opportunities in a developing oil and gas market

    The aim of this report is to act as an introduction to Vietnam and its oil industry opportunities for manufacturing, contracting, service and supplies companies which are seeking entry into other markets. The chapters of the report present an overview of the country, its recent history and formative events; in addition, the country's economy, industries and rebuilding process are reviewed. Detailed attention is given to trade, investment and finance, as these factors directly influence all business ventures in Vietnam, and are essential considerations in the assessment of the overall business environment. The appendices contain an extensive list of organisational contacts in Vietnam, the U.K. and elsewhere, and other useful information to support these activities. (author)

  8. Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment.

    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.

  9. Conditional Expression of E2A-HLF Induces B-Cell Precursor Death and Myeloproliferative-Like Disease in Knock-In Mice.

    Jesús Duque-Afonso

    Full Text Available Chromosomal translocations are driver mutations of human cancers, particularly leukemias. They define disease subtypes and are used as prognostic markers, for minimal residual disease monitoring and therapeutic targets. Due to their low incidence, several translocations and their biological consequences remain poorly characterized. To address this, we engineered mouse strains that conditionally express E2A-HLF, a fusion oncogene from the translocation t(17;19 associated with 1% of pediatric B-cell precursor ALL. Conditional oncogene activation and expression were directed to the B-cell compartment by the Cre driver promoters CD19 or Mb1 (Igα, CD79a, or to the hematopoietic stem cell compartment by the Mx1 promoter. E2A-HLF expression in B-cell progenitors induced hyposplenia and lymphopenia, whereas expression in hematopoietic stem/progenitor cells was embryonic lethal. Increased cell death was detected in E2A-HLF expressing cells, suggesting the need for cooperating genetic events that suppress cell death for B-cell oncogenic transformation. E2A-HLF/Mb1.Cre aged mice developed a fatal myeloproliferative-like disorder with low frequency characterized by leukocytosis, anemia, hepatosplenomegaly and organ-infiltration by mature myelocytes. In conclusion, we have developed conditional E2A-HLF knock-in mice, which provide an experimental platform to study cooperating genetic events and further elucidate translational biology in cross-species comparative studies.

  10. Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload.

    Elena Montes-Cobos

    Full Text Available Mineralocorticoid receptor (MR inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox. Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.

  11. Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload

    Montes-Cobos, Elena; Li, Xiao; Fischer, Henrike J.; Sasse, André; Kügler, Sebastian; Didié, Michael; Toischer, Karl; Fassnacht, Martin; Dressel, Ralf; Reichardt, Holger M.

    2015-01-01

    Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes. PMID:26605921

  12. Large genomic fragment deletion and functional gene cassette knock-in via Cas9 protein mediated genome editing in one-cell rodent embryos.

    Wang, Liren; Shao, Yanjiao; Guan, Yuting; Li, Liang; Wu, Lijuan; Chen, Fangrui; Liu, Meizhen; Chen, Huaqing; Ma, Yanlin; Ma, Xueyun; Liu, Mingyao; Li, Dali

    2015-01-01

    The CRISPR-Cas RNA-guided system has versatile uses in many organisms and allows modification of multiple target sites simultaneously. Generating novel genetically modified mouse and rat models is one valuable application of this system. Through the injection of Cas9 protein instead of mRNA into embryos, we observed fewer off-target effects of Cas9 and increased point mutation knock-in efficiency. Large genomic DNA fragment (up to 95 kb) deletion mice were generated for in vivo study of lncRNAs and gene clusters. Site-specific insertion of a 2.7 kb CreERT2 cassette into the mouse Nfatc1 locus allowed labeling and tracing of hair follicle stem cells. In addition, we combined the Cre-Loxp system with a gene-trap strategy to insert a GFP reporter in the reverse orientation into the rat Lgr5 locus, which was later inverted by Cre-mediated recombination, yielding a conditional knockout/reporter strategy suitable for mosaic mutation analysis. PMID:26620761

  13. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

    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.

  14. Comparison of immune response in Pacific white shrimp, Litopenaeus vannamei, after knock down of Toll and IMD gene in vivo.

    Liu, Yongjie; Song, Lei; Sun, Yuhang; Liu, Tao; Hou, Fujun; Liu, Xiaolin

    2016-07-01

    The Toll and immune deficiency (IMD) pathways are essential for inducing immune related genes during invasion of pathogens. In the present study, transcripts of eight pathway-related genes in Litopenaeus vannamei, including Toll, IMD, Pelle, IAP1, TRAF6, ALF, Crustin and Penaeidin3 were analyzed to further understand the potential relationship between Toll and IMD pathway. The high transcription levels of TRAF6, Pelle, Toll, IMD and IAP1 in selected tissues indicates their functional roles in Toll and IMD pathways. The increased mRNA expression of Toll and IMD detected in the early stage might suggest the inducible role of Toll and IMD upon bacterial infection. Moreover, the continuous increase of IMD and the high level of Pelle and TRAF6 in Vibrio anguillarum challenged group indicated that Gram-negative bacterium can activate both the Toll and IMD signaling pathway. Silencing of Toll by a dsRNA-mediated RNAi strongly increased the transcripts of IMD, Pelle, TRAF6, IAP1 and Akirin, knocking down of IMD also markedly increased the transcripts of Toll, Pelle, IAP1 and Akirin. Furthermore, ALF expression was significantly increased in response to V. anguillarum and Micrococcus lysodeikticus challenge, while the transcripts of Crustin and Pen3 in hemocytes were significantly reduced in V. anguillarum group, but rose significantly following M. lysodeikticus infection. In summary, we speculate that Toll and IMD pathway are not independent in shrimp, but linked to defense against bacterial infection. PMID:26855014

  15. Establishment of Immortalized BMP2/4 Double Knock-Out Osteoblastic Cells Is Essential for Study of Osteoblast Growth, Differentiation, and Osteogenesis.

    Wu, Li-An; Wang, Feng; Donly, Kevin J; Baker, Andrew; Wan, Chunyan; Luo, Daoshu; MacDougall, Mary; Chen, Shuo

    2016-06-01

    Bone morphogenetic proteins 2 and 4 (BMP2/4) are essential for osteoblast differentiation and osteogenesis. Generation of a BMP2/4 dual knock-out ((ko/ko) ) osteoblastic cell line is a valuable asset for studying effects of BMP2/4 on skeletal development. In this study, our goal was to create immortalized mouse deleted BMP2/4 osteoblasts by infecting adenoviruses with Cre recombinase and green fluorescent protein genes into immortalized murine floxed BMP2/4 osteoblasts. Transduced BMP2/4(ko/ko) cells were verified by green immunofluorescence and PCR. BMP2/4(ko/ko) osteoblasts exhibited small size, slow cell proliferation rate and cell growth was arrested in G1 and G2 phases. Expression of bone-relate genes was reduced in the BMP2/4(ko/ko) cells, resulting in delay of cell differentiation and mineralization. Importantly, extracellular matrix remodeling was impaired in the BMP2/4(ko/ko) osteoblasts as reflected by decreased Mmp-2 and Mmp-9 expressions. Cell differentiation and mineralization were rescued by exogenous BMP2 and/or BMP4. Therefore, we for the first time described establishment of an immortalized deleted BMP2/4 osteoblast line useful for study of mechanisms in regulating osteoblast lineages. J. Cell. Physiol. 231: 1189-1198, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26595646

  16. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells

    Sun, Jenny J.

    2016-01-01

    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. PMID:27441631

  17. Investigation on the partial resistance of Cpkk2 knock out strain of Cryphonectria parasitica to Cryphonectria hypovirus 1 infection in presence of Geneticin and Geneticin resistance gene.

    Turina, Massimo; Rossi, Marika; Moretti, Marino

    2016-07-01

    We have recently characterized the central components of the three MAP kinase cascades present in Cryphonectria parasitica : the MEK genes cpkk1, cpkk2 and cpkk3. When we attempted to infect through anastomosis the three knock out strains with Cryphonectria hypovirus 1 (CHV1), only the deletion strain of Cpkk2, the yeast Ste7 homologue, involved in mating and filamentous growth, could not be infected. We then proceeded to attempt virus infection through transformation of Δcpkk2 protoplasts using an infectious cDNA clone able to establish virus infection through transformation. In this case, a very limited number of strains could be recovered as stable transformants compared to the efficiency of control transformations with plasmid carrying only the antibiotic marker. Furthermore, transformants carrying actively replicating virus could be isolated only if the selection marker Geneticin was used during the very initial selection process, and not maintained throughout the growth of the colonies. Moreover, Δcpkk2 isolates that maintained the virus lost Geneticin resistance. We therefore unveiled a specific negative interaction among virus infection, presence of Geneticin in the growth media, and lack of Cpkk2 MEK in the fungal host. PMID:26643512

  18. Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

    Sun, Jenny J; Ray, Russell

    2016-01-01

    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. PMID:27441631

  19. Opportunities for investment. National privatization plans

    The following topics were dealt with: Introduction to EBRD; Investment opportunities; Requirements for successful privatization; Challenges; How EBRD can help. 30 EBRD offices in 27 countries of operations (former Soviet and Socialist countries) are presented. (R.P.)

  20. USAJOBS Job Opportunity Announcements (JOA) REST API

    Office of Personnel Management — This REST-based API is designed to support lightweight Federal Job Opportunity Announcement (JOA) content consumption by consumers. It is anticipated that this API...