WorldWideScience

Sample records for technology offers 17-to-1

  1. 17 CFR 240.14e-1 - Unlawful tender offer practices.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Unlawful tender offer... Securities Exchange Act of 1934 Regulation 14e § 240.14e-1 Unlawful tender offer practices. As a means... section 14(e) of the Act, no person who makes a tender offer shall: (a) Hold such tender offer open for...

  2. 7 CFR 3431.17 - VMLRP service agreement offer.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false VMLRP service agreement offer. 3431.17 Section 3431... Administration of the Veterinary Medicine Loan Repayment Program § 3431.17 VMLRP service agreement offer. The Secretary will make an offer to successful applicants to enter into an agreement with the Secretary to...

  3. 17 CFR 230.419 - Offerings by blank check companies.

    Science.gov (United States)

    2010-04-01

    ... derivative securities relating to securities held in the escrow or trust account may be exercised or... other derivative securities issued in the initial offering are exercisable, there is a continuous... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Offerings by blank check...

  4. 6 CFR 17.415 - Access to course offerings.

    Science.gov (United States)

    2010-01-01

    ..., home economics, music, and adult education courses. (b)(1) With respect to physical education classes... THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 17.415 Access to course...

  5. 17 CFR 240.14e-5 - Prohibiting purchases outside of a tender offer.

    Science.gov (United States)

    2010-04-01

    ...(s); (iv) The intention of the offeror to make purchases pursuant to the foreign tender offer(s) is... consideration paid outside of the tender offer that is greater than the tender offer price; and (G) Purchases or... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Prohibiting purchases outside...

  6. Strategic analysis of companies offering technology services to farmers for mobile applications media

    Directory of Open Access Journals (Sweden)

    Rodrigo da Silva Riquena

    2016-03-01

    Full Text Available The use of smart-phones and tablets is increasing the farming community before these fact companies that offer products and services to this sector are mobilizing to be active in this new reality. However, companies that operate in the rural market, not only have the aim of helping farmers in providing services through mobile technology applications, it was necessary to identify the strategic performance of these companies as a market opportunity in selling their products in the agricultural sector. Therefore, this article aimed to identify the strategic planning of technology companies to provide services through applications to farmers. The methodological approach used is a qualitative approach with the exploratory and descriptive aim of the use of content analysis of the websites of those companies studied. This study concluded that companies by offering technology services to farmers, use these services strategically to your advantage without the knowledge of the real needs of farmers.

  7. 17 CFR 230.253 - Offering circular.

    Science.gov (United States)

    2010-04-01

    .... Repetition of information should be avoided; cross-referencing of information within the document is... COMPLETENESS OF ANY OFFERING CIRCULAR OR OTHER SELLING LITERATURE. THESE SECURITIES ARE OFFERED PURSUANT TO AN...

  8. 17 CFR 230.701 - Exemption for offers and sales of securities pursuant to certain compensatory benefit plans and...

    Science.gov (United States)

    2010-04-01

    ... irrevocable election to defer is made. (iii) Derivative securities. In calculating outstanding securities for..., must be delivered. (6) If the sale involves a stock option or other derivative security, the issuer... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Exemption for offers and sales...

  9. Three-dimensional imaging technology offers promise in medicine.

    Science.gov (United States)

    Karako, Kenji; Wu, Qiong; Gao, Jianjun

    2014-04-01

    Medical imaging plays an increasingly important role in the diagnosis and treatment of disease. Currently, medical equipment mainly has two-dimensional (2D) imaging systems. Although this conventional imaging largely satisfies clinical requirements, it cannot depict pathologic changes in 3 dimensions. The development of three-dimensional (3D) imaging technology has encouraged advances in medical imaging. Three-dimensional imaging technology offers doctors much more information on a pathology than 2D imaging, thus significantly improving diagnostic capability and the quality of treatment. Moreover, the combination of 3D imaging with augmented reality significantly improves surgical navigation process. The advantages of 3D imaging technology have made it an important component of technological progress in the field of medical imaging.

  10. 17 CFR 240.14e-2 - Position of subject company with respect to a tender offer.

    Science.gov (United States)

    2010-04-01

    ... disclosing that the subject company: (1) Recommends acceptance or rejection of the bidder's tender offer; (2... accordance with such laws, regulations and policies. (d) Exemption for cross-border tender offers. The... with respect to a tender offer. 240.14e-2 Section 240.14e-2 Commodity and Securities Exchanges...

  11. Report of the 17th international workshop on nuclear safety and simulation technology (IWNSST17)

    International Nuclear Information System (INIS)

    Yoshikawa, Hidekazu

    2014-01-01

    The 17th International Workshop on Nuclear Safety and Simulation Technology (IWNSST17) was held in January 21, 2014 at Kyoto University, in Kyoto, Japan. This one-day workshop was motivated to exploit advanced safety researches for nuclear power plant (NPP) , by a unique synergetic collaboration of basically two different disciplines: material science and systems sciences. There were ten invited presentations at the ISSNP2013, and the subject of the presentations ranges from (1) material corrosion issue of NPP components, (2) application of augmented reality technology for NPP decommission, (3) functional modeling method for plant control system, (4) intrinsic understanding of Fukushima Daiichi accident phenomena based on simple physical model, (5) system reliability evaluation method for PWR safety system, (6) automatic control system design for small modular reactor, and (7) validation of computerized human-machine interface and digital I and C for PWR plant. This article provides the overview of the IWNSST17 with giving condensed summaries of all invited presentations given by international experts. (author)

  12. 17 CFR 230.155 - Integration of abandoned offerings.

    Science.gov (United States)

    2010-04-01

    ... offering disclose information about the abandoned private offering, including: (i) The size and nature of... were (or who the issuer reasonably believes were): (i) Accredited investors (as that term is defined in... document used in the private offering discloses any changes in the issuer's business or financial condition...

  13. User embracement and maternal characteristics associated with liquid offer to infants.

    Science.gov (United States)

    Niquini, Roberta Pereira; Bittencourt, Sonia Azevedo; Lacerda, Elisa Maria de Aquino; Couto de Oliveira, Maria Inês; Leal, Maria do Carmo

    2010-08-01

    To identify the maternal characteristics and welcoming actions towards mothers of infants aged less than six months associated with early liquid offer. Cross-sectional study performed in 2007, with a representative sample of mothers of infants aged less than six months (n=1,057), users of Primary Health Care (PHC) Units, in the city of Rio de Janeiro, Southeastern Brazil. A multivariate logistic regression model was used to estimate the association between explanatory variables and liquid offer, with weighing and design effect and controlled for infant age. Of all mothers, 32% did not receive the welcoming card in the maternity hospital, 47% did not receive guidance on breastfeeding at their first visit to the PHC unit after childbirth and 55% reported they had offered liquids to their infants. Women without at least six months of previous breastfeeding experience were more likely to offer liquids than those with such experience (OR=1.57; 95% CI: 1.16;2.13). Mothers who had not received guidance on breastfeeding at their first visit to the UBS after childbirth were 58% more likely to offer liquids than those who had received it. Liquid offer was positively associated with adolescence among women with a partner (OR=2.17; 95% CI: 1.10;4.30) and negatively associated with adolescence among those without a partner (OR=0.31; 95% CI: 0.11;0.85). Among women with less than eight years of education, those who had not received guidance on breastfeeding after childbirth were 1.8 times more likely to offer liquids than others who had received it. Age, marital status and previous breastfeeding experience are maternal characteristics associated with liquid offer to infants aged less than six months. Receiving early guidance on breastfeeding could reduce liquid offer to infants.

  14. Offers

    CERN Multimedia

    Association du personnel

    2010-01-01

    THEATRE FORUM DE MEYRIN 1, place des Cinq-Continents 1217 Meyrin    Special offer for members of the Staff Association: Reduced ticket prices for the play Love is my sin (in English) from 15 to 17 March at 8.30pm http://www.forum-meyrin.ch/main.php?page=119&s=12   First category: 37 CHF instead of 46 CHF Second category (seats towards the sides): 30 CHF instead of 38 CHF Please present your CERN card and your Staff Association membership card at the ticket office. Ticket reservation: tel. 022 989 34 34 (from Monday to Friday 2pm to 6pm) or e-mail : billetterie@forum-meyrin.ch  

  15. IL-17/Th17 Pathway Is Activated in Acne Lesions

    Science.gov (United States)

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  16. 17 CFR 200.26a - Office of Information Technology.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Office of Information Technology. 200.26a Section 200.26a Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Organization § 200.26a Office of Information Technology. The Office of Information Technology is responsible...

  17. 17 CFR 240.15c1-8 - Sales at the market.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Sales at the market. 240.15c1... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-8 Sales at the market... securities exchange that such security is being offered to such customer “at the market” or at a price...

  18. Prevalence of Salmonella in 11 Spices Offered for Sale from Retail Establishments and in Imported Shipments Offered for Entry to the United States.

    Science.gov (United States)

    Zhang, Guodong; Hu, Lijun; Pouillot, Régis; Tatavarthy, Aparna; Doren, Jane M Van; Kleinmeier, Daria; Ziobro, George C; Melka, David; Wang, Hua; Brown, Eric W; Strain, Errol; Bunning, Vincent K; Musser, Steven M; Hammack, Thomas S

    2017-10-04

    The U.S. Food and Drug Administration conducted a survey to evaluate Salmonella prevalence and aerobic plate counts in packaged (dried) spices offered for sale at retail establishments in the United States. The study included 7,250 retail samples of 11 spice types that were collected during November 2013 to September 2014 and October 2014 to March 2015. No Salmonella-positive samples (based on analysis of 125 g) were found among retail samples of cumin seed (whole or ground), sesame seed (whole, not roasted or toasted, and not black), and white pepper (ground or cracked), for prevalence estimates of 0.00% with 95% Clopper and Pearson's confidence intervals of 0.00 to 0.67%, 0.00 to 0.70%, and 0.00 to 0.63%, respectively. Salmonella prevalence estimates (confidence intervals) for the other eight spice types were 0.19% (0.0048 to 1.1%) for basil leaf (whole, ground, crushed, or flakes), 0.24% (0.049 to 0.69%) for black pepper (whole, ground, or cracked), 0.56% (0.11 to 1.6%) for coriander seed (ground), 0.19% (0.0049 to 1.1%) for curry powder (ground mixture of spices), 0.49% (0.10 to 1.4%) for dehydrated garlic (powder, granules, or flakes), 0.15% (0.0038 to 0.83%) for oregano leaf (whole, ground, crushed, or flakes), 0.25% (0.03 to 0.88%) for paprika (ground or cracked), and 0.64% (0.17 to 1.6%) for red pepper (hot red pepper, e.g., chili, cayenne; ground, cracked, crushed, or flakes). Salmonella isolates were serotyped, and genomes were sequenced. Samples of these same 11 spice types were also examined from shipments of imported spices offered for entry to the United States from 1 October 2011 to 30 September 2015. Salmonella prevalence estimates (based on analysis of two 375-g composite samples) for shipments of imported spices were 1.7 to 18%. The Salmonella prevalence estimates for spices offered for sale at retail establishments for all of the spice types except dehydrated garlic and basil were significantly lower than estimates for shipments of imported spice

  19. Receipt of a pediatric liver offer as the first offer reduces waitlist mortality for adult women.

    Science.gov (United States)

    Ge, Jin; Gilroy, Richard; Lai, Jennifer C

    2018-03-31

    In liver transplantation, adults with small stature have a greater susceptibility to waitlist mortality. This may explain the persistent waitlist mortality disparity that exists for women. We hypothesized that women who receive early offers of pediatric donor livers have improved waitlist survival, and that preferentially offering these organs to women mitigates this sex-based disparity. We analyzed donor liver offers from 2010 to 2014. Adult candidates who received a first offer that ranked within the first three match run positions from the donors' perspective were classified based on gender and whether they received a pediatric versus adult offer. We used competing risks regression to associate first offer type and waitlist mortality. 8,101 waitlist candidates received a first offer that was ranked within the first three match run positions: 5.6% (293/5,202) men and 6.2% (179/2,899) women received a pediatric donor liver as their first offer. In multivariable analyses, compared to adult-first men, adult-first women (sHR1.33, 95%CI 1.17-1.51, p offer had a lower risk of waitlist mortality compared to those who receive adult offers. Our data provides a simple approach to mitigating the increased waitlist mortality experienced by women by incorporating donor and recipient size, as variables, into organ allocation. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  20. 17 CFR 230.504 - Exemption for limited offerings and sales of securities not exceeding $1,000,000.

    Science.gov (United States)

    2010-04-01

    ... require the public filing and delivery to investors of a substantive disclosure document before sale, and... only to “accredited investors” as defined in § 230.501(a). (2) The aggregate offering price for an... § 230.504 fails to meet the limitation on the aggregate offering price, it does not affect the...

  1. 17 CFR 230.802 - Exemption for offerings in connection with an exchange offer or business combination for the...

    Science.gov (United States)

    2010-04-01

    ... connection with an exchange offer or business combination for the securities of foreign private issuers. 230... Offers and Business Combinations § 230.802 Exemption for offerings in connection with an exchange offer or business combination for the securities of foreign private issuers. Offers and sales in any...

  2. Conditions of the potential for commercialization of the patent: the implementation of a technology public offering system technology at CNEN

    International Nuclear Information System (INIS)

    Archila, Daniela Lima Cerqueira

    2015-01-01

    This dissertation identifies the main factors which represent the conditions for the potential commercialization of patents aiming at the implementation of a system for technology public offering at CNEN as a strategy for creating licensing opportunities to the industrial sector. The method applied refers to an exploratory case study of a patented technology selected from a sample of CNEN's patent portfolio in the biopharmaceutical sector. The case study comprehends a field research of interviews conducted with two specialists in technology and innovation management, one researcher from CNEN and a biopharmaceutical company. The results show that among the nineteen main factors - related to technology, market, business and Science and Technology Organization (STO) - the market dynamics, the potential applications of the technology and an abstract of its main benefits compared to existing technologies are the major relevant information for each technology to be included in the public offering system. Other results indicate that the evaluation of such factors may be conducted by competent professionals to bring less uncertainty and risk to the early-stage of the innovation process, as well as enhance the potential interest of a company in the technology. On the other hand, the latter requires innovation capabilities to move the technology forward – additional R&D, scale-up, manufacturing and marketing - whilst the STO needs a entrepreneurial culture that mitigates its obstacles, creates more positive solutions for its routines and processes and gives sustainability to its Technology Transfer Office (TTO) through valuing its personnel in the long term. Finally, emphasis on technological partnerships with companies can be a motivating feature for directing the STO's patent strategy to the creation of proprietary technological platforms that reflect problems experienced by the commercial environment, as well as the development of this strategic patent

  3. Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature.

    Science.gov (United States)

    Jones, Gabriela E; Mousa, Hatem A; Rowley, Helen; Houtman, Peter; Vasudevan, Pradeep C

    2015-12-01

    The objective of this study is to report the prenatal ultrasound scan findings in four fetuses from two families postnatally diagnosed with 17q12 microdeletion syndrome on microarray CGH and review the literature. We report two families presenting with prenatally detected hyperechogenic kidneys. In family 1, the mother had three pregnancies complicated by anhydramnios with bilateral hyperechogenic kidneys, hyperechogenic enlarged cystic kidneys, and bilateral hyperechogenic kidneys with polyhydramnios respectively. In family 2, prenatal ultrasound scans detected hyperechogenic kidneys. A pubmed search for all reported cases of 17q12 deletion between 2005 and 2015 was performed. All publications were reviewed, and findings summarised. Fourteen publications were deemed suitable for literature review; there was a diagnosis of 17q12 deletion with documented prenatal findings in 25 cases. Prenatal renal anomalies were reported in 88% of these cases. Anomalies were documented from 15 weeks, and most common presentation was hyperechogenic, muticystic, or enlarged kidneys. Both oligohydramnios and polyhydramnios were seen. Postnatal renal ultrasound scan findings were of muticystic or multicystic dysplastic kidney. There did not appear to be correlation of prenatal presentation and severity of renal disease. Prenatal testing should be offered to all cases of hyperechogenic kidneys, with unknown cause. © 2015 John Wiley & Sons, Ltd.

  4. 17 CFR 230.254 - Solicitation of interest document for use prior to an offering statement.

    Science.gov (United States)

    2010-04-01

    ... subject to the antifraud provisions of the federal securities laws. No solicitation or acceptance of money... document for use prior to an offering statement. 230.254 Section 230.254 Commodity and Securities Exchanges...-Conditional Small Issues Exemption § 230.254 Solicitation of interest document for use prior to an offering...

  5. French scientists offered time to set up companies

    CERN Document Server

    Butler, D

    1999-01-01

    The French minister of national education, research and technology announced that French researchers working for public research institutes and universities are to be offered up to six years sabbatical leave to set up their own companies (11 para)

  6. 17 CFR 240.15c3-1d - Satisfactory Subordination Agreements (Appendix D to 17 CFR 240.15c3-1).

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Satisfactory Subordination...-Counter Markets § 240.15c3-1d Satisfactory Subordination Agreements (Appendix D to 17 CFR 240.15c3-1). (a) Introduction. (1) This Appendix sets forth minimum and non-exclusive requirements for satisfactory...

  7. Supporting a 1:1 Program with a Student Technology Team

    Science.gov (United States)

    Peterson, Lana; Scharber, Cassandra

    2017-01-01

    Purpose: The purpose of this paper is to describe the practice of using student technology teams (STTs) offered at a high school within a 1:1 district. Design/methodology/approach: This qualitative case study (Merriam, 1998, 2009) documents how an STT program functioned in 2015-2016 academic year. Findings: Findings show the STT provided a rich…

  8. 17 CFR 230.606 - Offering not in excess of $100,000.

    Science.gov (United States)

    2010-04-01

    ... Business Investment Companies § 230.606 Offering not in excess of $100,000. No offering circular need be... forth in an offering circular. (b) No advertisement, article or other communication published in any... general type of business of the issuer; and (4) By whom orders will be filled or from whom further...

  9. 17 CFR 230.801 - Exemption in connection with a rights offering.

    Science.gov (United States)

    2010-04-01

    ... thereto, in English, to the Commission on Form CB (§ 239.800 of this chapter) by the first business day..., Exchange Offers and Business Combinations § 230.801 Exemption in connection with a rights offering. A... document to U.S. holders, including any amendments thereto, in English, on a comparable basis to that...

  10. 17 CFR 10.108 - Settlements.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Settlements. 10.108 Section 10... to the Commission; Settlements § 10.108 Settlements. (a) When offers may be made. Parties may at any time during the course of the proceeding propose offers of settlement. All offers of settlement shall...

  11. Postgraduates courses offered to nursing

    Directory of Open Access Journals (Sweden)

    Pedro Jorge Araujo

    2011-07-01

    Full Text Available Aim: To know the official masters that the Spanish Universities have offered during the academic course 2010/2011.Material and methods: Descriptive observational and transversal court study, in which it has analysed 170 university official masters and in which it has used a questionnaire with a total of 15 questions elaborated for this work.Results: 52 Spanish Universities of the 75 that there is have offered during the academic course 2010/2011 official masters that can realise for graduated in infirmary. By areas, the official masters more offered have been the ones of nutrition and alimentary security. 76,33% of the official masters have a length of 1 academic year. Almost the half of the official masters have an orientation researcher-professional and almost 40% researcher. 62,65% of the masters give of face-to-face way. In 52,1% of the official masters do not realise external practices and 86,2% has continuity with the doctorate.Conclusions: It has seen that it is necessary that expand the number of masters including other fields of study that contribute to a main specialisation of the professionals of the infirmary. An important percentage of official masters give in face-to-face modality, and there is very few offered on-line or to distance.

  12. Process for Biotransformation of Androsta-4-ene-3, 17-Dione (4-AD) to Androsta-1,4-Diene-3,17-Dione (ADD).

    Science.gov (United States)

    Prakash, Surya; Bajaj, Abhay

    2017-01-01

    Androsta-1,4-diene-3,17-dione (androstadienedione, ADD) is key intermediate for the organic synthesis of a variety of female sex hormones such as estrone, estradiol, estriol and other related derivatives. De novo synthesis of this molecule is not yet reported in any form of living system, i.e., microbial, plant, and animal. The structural complexities due to presence of several chiral carbon centers create significant hurdles in chemical synthesis of such molecules. Microbe-mediated biotransformation offer a highly reliable, cost-effective, and relatively non hazardous way for commercial manufacturing of steroidal key intermediates. Currently microbial biotransformations are extensively being exploited for large-scale production of basic intermediates such as androstenedione (AD), ADD, and several types of hydroxylated derivatives of androstane compounds. In this chapter several aspects of microbial biotransformation process of AD to ADD are discussed.

  13. Botswana Journal of Technology - Vol 17, No 2 (2008)

    African Journals Online (AJOL)

    Vacuum sewerage system: an appropriate and economical sanitation technology for flat and shallow groundwater areas · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. P.T Odirile, L Späth, R Mc Lagan. http://dx.doi.org/10.4314/bjt.v17i2.52201 ...

  14. 33 CFR 17.05-1 - Gifts.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Gifts. 17.05-1 Section 17.05-1 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL UNITED STATES COAST GUARD GENERAL GIFT FUND Administration § 17.05-1 Gifts. The gifts or bequests may be in money or...

  15. 5 CFR 339.302 - Authority to offer examinations.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Authority to offer examinations. 339.302... QUALIFICATION DETERMINATIONS Medical Examinations § 339.302 Authority to offer examinations. An agency may, at its option, offer a medical examination (including a psychiatric evaluation) in any situation where...

  16. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    proposes the following offer: 15% discount for the Staff Association members who enroll their children in summer FUTUREKIDS activities. Extracurricular Activities For Your Children The FUTUREKIDS Geneva Learning Center is open 6 days a week and offers a selection of after-school extracurricular activities for children and teenagers (ages 5 to 16). In addition to teaching in its Learning Centers, Futurekids collaborates with many private schools in Suisse Romande (Florimont, Moser, Champittet, Ecole Nouvelle, etc.) and with the Département de l'Instruction Publique (DIP) Genève. Courses and camps are usually in French but English groups can be set up on demand. FUTUREKIDS Computer Camps (during school holidays) FUTUREKIDS Computer Camps are a way of having a great time during vacations while learning something useful, possibly discovering a new hobby or even, why not, a future profession. Our computer camps are at the forefront of technology. Themes are diverse and suit all ...

  17. 21 CFR 17.1 - Scope.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Scope. 17.1 Section 17.1 Food and Drugs FOOD AND... Food, Drug, and Cosmetic Act (the act) authorizing civil money penalties for certain violations of the... trial data bank and section 303(f)(4) of the act authorizing civil money penalties for certain...

  18. 17 CFR 404.1 - Application of part to registered brokers and dealers.

    Science.gov (United States)

    2010-04-01

    ... registered brokers and dealers. 404.1 Section 404.1 Commodity and Securities Exchanges DEPARTMENT OF THE... PRESERVATION OF RECORDS § 404.1 Application of part to registered brokers and dealers. Compliance by a registered broker or dealer with § 240.17a-3 of this title (pertaining to records to be made), § 240.17a-4 of...

  19. Angiotensin-(1-7): A Novel Peptide to Treat Hypertension and Nephropathy in Diabetes?

    Science.gov (United States)

    Padda, Ranjit Singh; Shi, Yixuan; Lo, Chao-Sheng; Zhang, Shao-Ling; Chan, John S D

    2015-10-14

    The renin-angiotensin system (RAS) plays a pivotal role in mammalian homeostasis physiology. The RAS can be delineated into a classical RAS (the pressor arm) including angiotensinogen (Agt), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R), and a counterbalancing novel RAS (the depressor arm) including Agt, renin, angiotensin-converting enzyme-2 (ACE-2), angiotensin-(1-7) (Ang 1-7) and Ang 1-7 receptor (or Mas receptor (MasR)). Hyperglycemia (diabetes) induces severe tissue oxidative stress, which stimulates the pressor arm of the renal RAS axis and leads to an increase in ACE/ACE-2 ratio, with excessive formation of Ang II. There is a growing body of evidence for beneficial effects of the depressor arm of RAS (ACE-2/Ang 1-7/MasR) axis in diabetes, hypertension and several other diseased conditions. Evidence from in vitro, in vivo and clinical studies reflects anti-oxidant, anti-fibrotic, and anti-inflammatory properties of Ang 1-7. Most of the currently available therapies only target suppression of the pressor arm of RAS with angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEi). However, it is time to consider simultaneous activation of the depressor arm for more effective outcomes. This review summarizes the recent updates on the protective role of Ang 1-7 in hypertension and kidney injury in diabetes, as well as the possible underlying mechanism(s) of Ang 1-7 action, suggesting that the ACE-2/Ang 1-7/MasR axis can be developed as a therapeutic target for the treatment of diabetes-induced hypertension and renal damage.

  20. 17 CFR 270.3c-3 - Definition of certain terms used in section 3(c)(1) of the Act with respect to certain debt...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of certain terms used in section 3(c)(1) of the Act with respect to certain debt securities offered by small business... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3c-3 Definition of certain...

  1. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.

    Science.gov (United States)

    Gaspar, Nathalie; Sharp, Swee Y; Pacey, Simon; Jones, Chris; Walton, Michael; Vassal, Gilles; Eccles, Suzanne; Pearson, Andrew; Workman, Paul

    2009-03-01

    Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant GB cell lines were generated. High-resistance levels with resistance indices (RI = resistant line IC(50)/parental line IC(50)) of 20 to 137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilized. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021, and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NAD(P)H/quinone oxidoreductase 1 (NQO1) expression/activity and 17-AAG IC(50) was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors.

  2. New 17x17 assembly takes the heat

    International Nuclear Information System (INIS)

    Reparaz, A.; Brown, C.A. Sr.

    1992-01-01

    Advanced Nuclear Fuels' (ANF's) new 17 x 17 fuel assembly described in this article offers advanced features which provide increased thermal margins, higher burnup, responsiveness to electrical grid demands, improved seismic performance and superior corrosion resistance. (Author)

  3. 48 CFR 17.206 - Evaluation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Evaluation. 17.206 Section... CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 17.206 Evaluation. (a) In awarding the basic contract... officer need not evaluate offers for any option quantities when it is determined that evaluation would not...

  4. Technology Use for Diabetes Problem Solving in Adolescents with Type 1 Diabetes: Relationship to Glycemic Control.

    Science.gov (United States)

    Kumah-Crystal, Yaa A; Hood, Korey K; Ho, Yu-Xian; Lybarger, Cindy K; O'Connor, Brendan H; Rothman, Russell L; Mulvaney, Shelagh A

    2015-07-01

    This study examines technology use for problem solving in diabetes and its relationship to hemoglobin A1C (A1C). A sample of 112 adolescents with type 1 diabetes completed measures assessing use of technologies for diabetes problem solving, including mobile applications, social technologies, and glucose software. Hierarchical regression was performed to identify the contribution of a new nine-item Technology Use for Problem Solving in Type 1 Diabetes (TUPS) scale to A1C, considering known clinical contributors to A1C. Mean age for the sample was 14.5 (SD 1.7) years, mean A1C was 8.9% (SD 1.8%), 50% were female, and diabetes duration was 5.5 (SD 3.5) years. Cronbach's α reliability for TUPS was 0.78. In regression analyses, variables significantly associated with A1C were the socioeconomic status (β = -0.26, P Problem Solving Questionnaire (β = -0.26, P = 0.01), and TUPS (β = 0.26, P = 0.01). Aside from the Diabetes Self-Care Inventory--Revised, each block added significantly to the model R(2). The final model R(2) was 0.22 for modeling A1C (P problem solving and higher A1C. Adolescents with poorer glycemic control may use technology in a reactive, as opposed to preventive, manner. Better understanding of the nature of technology use for self-management over time is needed to guide the development of technology-mediated problem solving tools for youth with type 1 diabetes.

  5. 17 CFR 240.13e-4 - Tender offers by issuers.

    Science.gov (United States)

    2010-04-01

    ... begins the running of such time period shall be included except that if such event occurs on other than a business day such period shall begin to run on and shall include the first business day thereafter. (4) The... offer. (6) The term security holders means holders of record and beneficial owners of securities of the...

  6. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  7. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

    Science.gov (United States)

    Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

    2012-01-01

    The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

  8. Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.

    Science.gov (United States)

    Mork, Maureen E; Rodriguez, Andrea; Taggart, Melissa W; Rodriguez-Bigas, Miguel A; Lynch, Patrick M; Bannon, Sarah A; You, Y Nancy; Vilar, Eduardo

    2017-07-01

    Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

  9. 21 CFR 1.283 - What happens to food that is imported or offered for import without adequate prior notice?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What happens to food that is imported or offered for import without adequate prior notice? 1.283 Section 1.283 Food and Drugs FOOD AND DRUG... Imported Food Consequences § 1.283 What happens to food that is imported or offered for import without...

  10. T-cell clones from Th1, Th17 or Th1/17 lineages and their signature cytokines have different capacity to activate endothelial cells or synoviocytes.

    Science.gov (United States)

    Lavocat, Fabien; Maggi, Laura; Annunziato, Francesco; Miossec, Pierre

    2016-12-01

    To compare the direct effect of cytokines on synoviocytes and endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones and the direct cell-cell interactions with the same clones. Th17 and Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes were cultured in the presence of either isolated pro-inflammatory cytokines (IL-17 and/or TNF-α) or supernatants from the T-cell clones or co-cultured with T-cell clones themselves. IL-6 and IL-8 expression and production were analyzed. IL-17 and TNF-α induced IL-6 and IL-8 expression, although IL-17 alone had a limited effect on endothelial cells compared to synoviocytes. Supernatants from activated T-helper clones also induced IL-6 and IL-8 expression but with discrepancies between endothelial cells and synoviocytes. Endothelial cells were mostly activated by Th1 clone supernatants whereas synoviocytes were activated by all T-cell subtypes. Finally, cell-cell contact experiments showed a great heterogeneity among cell clones, even from the same lineage. IL-6 expression was mostly induced by contact with Th1 clones both in endothelial and mesenchymal cells whereas IL-8 expression was induced by all T-cell clones whatever their phenotype. We showed that endothelial cells were much more sensitive to Th1 activation whereas synoviocytes were activated by all T-helper lineages. This work highlights the heterogeneity of interactions between T-cells and stromal cells through soluble factors or direct cell contact. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Preparation and provisional certification of NBL Spectrographic Impurity Standards, CRM 123 (1-7) and 124 (1-7)

    International Nuclear Information System (INIS)

    Santoliquido, P.M.

    1983-09-01

    This report describes the design, production, and provisional certification of two new certified reference materials (CRMs): CRM No. 123 (1-7), U 3 O 8 containing 18 trace elements, and CRM No. 124 (1-7), U 3 O 8 containing 24 trace elements. The elements to be included and concentrations to be used were decided on the basis of information gathered from users of a previous CRM of this type, CRM No. 98 (1-7). The new CRMs were prepared by the addition of trace elements to high purity U 3 O 8 . Provisional certification was accomplished by an interlaboratory program in which four different laboratories analyzed the materials by carrier distillation dc arc emission spectrography

  12. Angiotensin-(1-7) augments endothelium-dependent relaxations of porcine coronary arteries to bradykinin by inhibiting angiotensin-converting enzyme 1.

    Science.gov (United States)

    Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

    2014-05-01

    Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin-(1-7) that activates Mas receptors, inhibits ACE1, and modulates bradykinin receptor sensitivity. This in vitro study compared the direct and indirect effects of angiotensin-(1-7), the ACE1 inhibitor captopril, and diminazene aceturate (DIZE) an alleged ACE2 activator in rings of porcine coronary arteries, by measuring changes of isometric tension. Angiotensin-(1-7), captopril, and DIZE did not cause significant changes in tension before or after desensitization of bradykinin receptors in preparations contracted with U46619. Bradykinin caused concentration-dependent and endothelium-dependent relaxations that were not affected by DIZE but were potentiated to a similar extent by angiotensin-(1-7) and captopril, given alone or in combination. Bradykinin responses potentiated by angiotensin-(1-7) and captopril were not affected by the BK1 antagonist SSR240612 and remained augmented in the presence of either N-nitro-L-arginine methyl ester hydrochloride plus indomethacin or TRAM-34 plus UCL-1684. ACE2 was identified in the coronary endothelium by immunofluorescence, but its basal activity was not influenced by DIZE. These results suggest that in coronary arteries, angiotensin-(1-7) and captopril both improves NO bioavailability and enhances endothelium-dependent hyperpolarization to bradykinin solely by ACE1 inhibition. Endothelial ACE2 activity cannot be increased by DIZE to produce local adequate amounts of angiotensin-(1-7) to influence vascular tone.

  13. Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.

    Science.gov (United States)

    Uchiyama, Ryosuke; Yonehara, Shin; Taniguchi, Shun'ichiro; Ishido, Satoshi; Ishii, Ken J; Tsutsui, Hiroko

    2017-08-01

    CD4 + Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4 + Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard -/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas -/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas -/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. Copyright © 2017 by The American Association of Immunologists

  14. Chemoselective synthesis of sialic acid 1,7-lactones.

    Science.gov (United States)

    Allevi, Pietro; Rota, Paola; Scaringi, Raffaella; Colombo, Raffaele; Anastasia, Mario

    2010-08-20

    The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.

  15. 17 CFR 39.1 - Scope.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Scope. 39.1 Section 39.1 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.1 Scope. The provisions of this part apply to any derivatives clearing organization as defined...

  16. The 17th Annual Magnet Technology Conference Hosted By CERN Is Proving That Opposites Attract...

    CERN Multimedia

    2001-01-01

    Hundreds were drawn together by the 17th Magnet Technology Conference, the largest conference devoted to magnets in the world. Thirty-six years ago about 50 physicists and engineers came together at SLAC, Stanford, to have a symposium on magnet technology. Simple as it seemed at the moment, it was the first time that anyone seriously considered building superconducting magnets and was the birth of the Magnet Technology (MT) conference. The conference has occurred every two years since that time and had its most recent incarnation, MT-17, hosted by CERN just last week at the International Conference Centre here in Geneva. With so much innovative work being done with magnets in the LHC and its experiments (ATLAS, CMS, Alice and LHCb), having an MT conference hosted by CERN in Geneva was expected. However, what was not expected was the level of interest with which MT-17 was met. 'We are victims of our own success', says Romeo Perin who was one of the 50 physicists/engineers who attended the Stanford symposium a...

  17. A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1

    Science.gov (United States)

    Deyle, Kaycie M.; Farrow, Blake; Qiao Hee, Ying; Work, Jeremy; Wong, Michelle; Lai, Bert; Umeda, Aiko; Millward, Steven W.; Nag, Arundhati; Das, Samir; Heath, James R.

    2015-05-01

    Ligands that can bind selectively to proteins with single amino-acid point mutations offer the potential to detect or treat an abnormal protein in the presence of the wild type (WT). However, it is difficult to develop a selective ligand if the point mutation is not associated with an addressable location, such as a binding pocket. Here we report an all-chemical synthetic epitope-targeting strategy that we used to discover a 5-mer peptide with selectivity for the E17K-transforming point mutation in the pleckstrin homology domain of the Akt1 oncoprotein. A fragment of Akt1 that contained the E17K mutation and an I19[propargylglycine] substitution was synthesized to form an addressable synthetic epitope. Azide-presenting peptides that clicked covalently onto this alkyne-presenting epitope were selected from a library using in situ screening. One peptide exhibits a 10:1 in vitro selectivity for the oncoprotein relative to the WT, with a similar selectivity in cells. This 5-mer peptide was expanded into a larger ligand that selectively blocks the E17K Akt1 interaction with its PIP3 (phosphatidylinositol (3,4,5)-trisphosphate) substrate.

  18. 17 CFR 240.15c1-7 - Discretionary accounts.

    Science.gov (United States)

    2010-04-01

    ... transactions or purchase or sale which are excessive in size or frequency in view of the financial resources... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-7 Discretionary...

  19. 17th Business Report Meeting of New Energy Industrial Technology Development Organization (NEDO). Outline of business; Dai 17 kai NEDO jigyo hokokukai. Gyomu gaiyo

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-25

    This is a report on the 17th Business Report Meeting of NEDO held in September, 1997. In Chapter 1, NEDO's business activities were outlined in terms of new energy, industrial technology, coal policy, compensation for coal mine pollution, alcohol production, etc. In Chapter 2, described were NEDO's budget and account settlement. In Chapter 3, reported were the FY 1996 results of the development of new energy, that is, the development of solar energy utilization technology, geothermal resource development, development of geothermal energy utilization technology, development of coal energy utilization technology, development of coal resource, development of fuel/storage technology, development of hydrogen/alcohol/biomass technology, development of other petroleum substituting energy technology, project for promotion of new energy introduction, project on international energy policy, project on development/introduction survey, and project on information service by NEDO Information Center. In Chapter 4, as the FY 1996 results of the R and D of industrial technology, etc., described were R and D projects, medical/welfare equipment related project, R and D projects on environmental technology, and international industry technology related projects. In Chapters 5 and 6, stated was the coal related project. In Chapter 7, mentioned was the alcohol production project. (NEDO)

  20. 17th Business Report Meeting of New Energy Industrial Technology Development Organization (NEDO). Outline of business; Dai 17 kai NEDO jigyo hokokukai. Gyomu gaiyo

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-25

    This is a report on the 17th Business Report Meeting of NEDO held in September, 1997. In Chapter 1, NEDO's business activities were outlined in terms of new energy, industrial technology, coal policy, compensation for coal mine pollution, alcohol production, etc. In Chapter 2, described were NEDO's budget and account settlement. In Chapter 3, reported were the FY 1996 results of the development of new energy, that is, the development of solar energy utilization technology, geothermal resource development, development of geothermal energy utilization technology, development of coal energy utilization technology, development of coal resource, development of fuel/storage technology, development of hydrogen/alcohol/biomass technology, development of other petroleum substituting energy technology, project for promotion of new energy introduction, project on international energy policy, project on development/introduction survey, and project on information service by NEDO Information Center. In Chapter 4, as the FY 1996 results of the R and D of industrial technology, etc., described were R and D projects, medical/welfare equipment related project, R and D projects on environmental technology, and international industry technology related projects. In Chapters 5 and 6, stated was the coal related project. In Chapter 7, mentioned was the alcohol production project. (NEDO)

  1. Enhanced expression of Ang-(1-7 during pregnancy

    Directory of Open Access Journals (Sweden)

    Brosnihan K.B.

    2004-01-01

    Full Text Available Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS. The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7 [Ang-(1-7], and of a newly cloned angiotensin converting enzyme (ACE homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7. The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7 increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7 was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7 were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7. These findings provide a basis for the physiological role of Ang-(1-7 and ACE2 during pregnancy.

  2. 17th International Conference on Textures of Materials (ICOTOM 17)

    International Nuclear Information System (INIS)

    Skrotzki, Werner; Oertel, Carl-Georg

    2015-01-01

    . Texture related research on microstructures 9. Texture-induced anisotropy 10. Insight through new experimental methods 11. Technological applications of texture studies 12. Other new developments and future trends related to the field While there was large interest in the topics 2, 3 and 8, contributions to topic 7 were much less than expected. ICOTOM 17 attracted 266 scientists from 34 countries with about one third of the participants being students. This is a very good ratio showing that we could attract the young generation. There have been 216 oral and 76 poster presentations, three of which received a poster award. It is our pleasure to thank the members of the International ICOTOM Committee for their valuable help, especially for proposing and choosing the 15 plenary speakers as well as the distinguished scientist of the texture community for the 'Bunge Award'. 130 papers were submitted for publication in the proceedings, 116 were accepted after reviewing. We would like to express our thanks to all referees for their efficient and prompt efforts. We acknowledge particularly support from the German Research Society (DFG) and the City of Dresden. We are also grateful for industrial support from Bruker Nano GmbH, Oxford Instruments GmbH, Ametek GmbH / EDAX, Labosoft S.C., PANalytical GmbH and IOP Publishing. Finally we thank all members of the National Organizing Committee, Intercom Dresden and Conwerk / Laboratory Ten for the excellent organization of ICOTOM 17 and the very pleasant collaboration. On the first day of the conference three tutorials have been offered. Each of them has been attended by about 30 participants. 1. Texture-aided residual stress identification system (TARSIuS) (organized by Prof. Dr. J. Bonarski and Mr. B. Kania) 2. MTEX - MATLAB toolbox for quantitative texture analysis (organized by Dr. R. Hielscher and Mr. F. Bachmann) 3. Grain boundary engineering (organized by Prof. N. Bozzolo and Prof. Dr. A.D. Rollett) A highlight of ICOTOM

  3. Two distinct populations of bovine IL-17⁺ T-cells can be induced and WC1⁺IL-17⁺γδ T-cells are effective killers of protozoan parasites.

    Science.gov (United States)

    Peckham, R K; Brill, R; Foster, D S; Bowen, A L; Leigh, J A; Coffey, T J; Flynn, R J

    2014-06-25

    IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4(+) and WC1(+) γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17(+) T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses.

  4. Nikkaji Dictionary: 17-エピメタンジエノン [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term 17-エピメタンジエノン 名詞 一般 * * * * 17-エピメタン...ジエノン ... Nikkaji J393.536A 200906049223014890 C CA06 UNKNOWN_2 1 7 - エピメタンジエノン

  5. Reasons Low-Income Parents Offer Snacks to Children: How Feeding Rationale Influences Snack Frequency and Adherence to Dietary Recommendations

    Directory of Open Access Journals (Sweden)

    Rachel E. Blaine

    2015-07-01

    Full Text Available Although American children snack more than ever before, the parental role in promoting snacking is not well understood. In 2012–2013 at baseline in an intervention study to prevent childhood obesity in low-income Massachusetts communities, n = 271 parents of children aged 2–12 years completed surveys regarding nutritive and non-nutritive reasons they offered children snacks, demographics, and dietary factors. An analysis of variance demonstrated that parents reported offering snacks (mean/week; standard deviation (SD for nutritive reasons like promoting growth (x̄ = 2.5; SD 2.2 or satisfying hunger (x̄ = 2.4; SD 2.1 almost twice as often as non-nutritive reasons like keeping a child quiet (x̄ = 0.7; SD 1.5 or celebrating events/holidays (x̄ = 0.8; SD 1.1. Parents reported giving young children (2–5 years more snacks to reward behavior (1.9 vs. 1.1, p < 0.001, keep quiet (1.0 vs. 0.5, p < 0.001, and celebrate achievements (1.7 vs. 1.0, p < 0.001 than parents of older children (6–12 years. Multivariable logistic regression models were used to obtain adjusted odds ratios, which indicated reduced child adherence to dietary recommendations when parents offered snacks to reward behavior (Odds Ratio (OR = 0.83; 95% Confidence Interval (CI 0.70–0.99, celebrate events/holidays (OR = 0.72; 95% CI 0.52–0.99, or achievements (OR = 0.82; 95% CI 0.68–0.98. Parental intentions around child snacking are likely important targets for obesity prevention efforts.

  6. Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1.

    Science.gov (United States)

    Duluc, Dorothée; Joo, HyeMee; Ni, Ling; Yin, Wenjie; Upchurch, Katherine; Li, Dapeng; Xue, Yaming; Klucar, Peter; Zurawski, Sandra; Zurawski, Gerard; Oh, SangKon

    2014-06-15

    Recent compelling evidence indicates that Th17 confer host immunity against a variety of microbes, including extracellular and intracellular pathogens. Therefore, understanding mechanisms for the induction and activation of Ag-specific Th17 is important for the rational design of vaccines against pathogens. To study this, we employed an in vitro system in which influenza hemagglutinin (HA) 1 was delivered to dendritic cells (DCs) via Dectin-1 using anti-human Dectin-1 (hDectin-1)-HA1 recombinant fusion proteins. We found that healthy individuals maintained broad ranges of HA1-specific memory Th17 that were efficiently activated by DCs targeted with anti-hDectin-1-HA1. Nonetheless, these DCs were not able to induce a significant level of HA1-specific Th17 responses even in the presence of the Th17-promoting cytokines IL-1β and IL-6. We further found that the induction of surface IL-1R1 expression by signals via TCRs and common γ-chain receptors was essential for naive CD4(+) T cell differentiation into HA1-specific Th17. This process was dependent on MyD88, but not IL-1R-associated kinase 1/4. Thus, interruptions in STAT3 or MyD88 signaling led to substantially diminished HA1-specific Th17 induction. Taken together, the de novo generation of pathogen-specific human Th17 requires complex, but complementary, actions of multiple signals. Data from this study will help us design a new and effective vaccine strategy that can promote Th17-mediated immunity against microbial pathogens. Copyright © 2014 by The American Association of Immunologists, Inc.

  7. 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT

    Science.gov (United States)

    2016-09-01

    Award Number: W81XWH-15-1-0409 TITLE: 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-04094 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT 5c...testicular androgens, testosterone or dihydrotestosterone ( DHT ). Men diagnosed with advanced prostate cancer or failure potentially curative therapy are

  8. Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.

    Directory of Open Access Journals (Sweden)

    Rui-Yun Bi

    Full Text Available Temporomandibular disorders (TMDs have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7 plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ. Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored.Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ, the G protein coupled estrogen receptor (GPR30, and Nav1.7 in TG were examined using immunohistofluorescence.Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1.7

  9. 38 CFR 1.17 - Evaluation of studies relating to health effects of radiation exposure.

    Science.gov (United States)

    2010-07-01

    ... relating to health effects of radiation exposure. 1.17 Section 1.17 Pensions, Bonuses, and Veterans' Relief... health effects of radiation exposure. (a) From time to time, the Secretary shall publish evaluations of scientific or medical studies relating to the adverse health effects of exposure to ionizing radiation in the...

  10. PREFACE: 17th International Conference on Textures of Materials (ICOTOM 17)

    Science.gov (United States)

    Skrotzki, Werner; Oertel, Carl-Georg

    2015-04-01

    related research on microstructures 9. Texture-induced anisotropy 10. Insight through new experimental methods 11. Technological applications of texture studies 12. Other new developments and future trends related to the field While there was large interest in the topics 2, 3 and 8, contributions to topic 7 were much less than expected. ICOTOM 17 attracted 266 scientists from 34 countries with about one third of the participants being students. This is a very good ratio showing that we could attract the young generation. There have been 216 oral and 76 poster presentations, three of which received a poster award. It is our pleasure to thank the members of the International ICOTOM Committee for their valuable help, especially for proposing and choosing the 15 plenary speakers as well as the distinguished scientist of the texture community for the "Bunge Award". 130 papers were submitted for publication in the proceedings, 116 were accepted after reviewing. We would like to express our thanks to all referees for their efficient and prompt efforts. We acknowledge particularly support from the German Research Society (DFG) and the City of Dresden. We are also grateful for industrial support from Bruker Nano GmbH, Oxford Instruments GmbH, Ametek GmbH / EDAX, Labosoft S.C., PANalytical GmbH and IOP Publishing. Finally we thank all members of the National Organizing Committee, Intercom Dresden and Conwerk / Laboratory Ten for the excellent organization of ICOTOM 17 and the very pleasant collaboration. On the first day of the conference three tutorials have been offered. Each of them has been attended by about 30 participants. 1. Texture-aided residual stress identification system (TARSIuS) (organized by Prof. Dr. J. Bonarski and Mr. B. Kania) 2. MTEX - MATLAB toolbox for quantitative texture analysis (organized by Dr. R. Hielscher and Mr. F. Bachmann) 3. Grain boundary engineering (organized by Prof. N. Bozzolo and Prof. Dr. A.D. Rollett) A highlight of ICOTOM 17 was the

  11. Angiotensin-(1-7): Beyond the Cardio-Renal Actions

    DEFF Research Database (Denmark)

    Passos-Silva, Danielle G; Verano-Braga, Thiago; Santos, Robson AS

    2013-01-01

    and lipolysis while decreasing insulin resistance and dyslipidemia. Ang-(1-7) is also able to improve cerebroprotection against ischemic stroke, besides its effects on learning and memory. The reproductive system can also be affected by Ang-(1-7) treatment, with enhanced ovulation, spermatogenesis and sexual...... downstream effectors such as NO, FOXO1 and COX2. Through these mechanisms, Ang-(1-7) is able to improve pathological conditions such as fibrosis and inflammation in organs such as lungs, liver and kidney. In addition, this heptapeptide has positive effects in metabolism, increasing the glucose uptake...

  12. Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells.

    Science.gov (United States)

    Duechting, Andrea; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

    2017-09-12

    During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.

  13. Renewable energy technologies and its adaptation in an urban environment

    Energy Technology Data Exchange (ETDEWEB)

    Thampi, K. Ravindranathan, E-mail: ravindranathan.thampi@ucd.ie; Byrne, Owen, E-mail: ravindranathan.thampi@ucd.ie; Surolia, Praveen K., E-mail: ravindranathan.thampi@ucd.ie [SFI Strategic Research Cluster in Solar Energy Conversion, School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4 (Ireland)

    2014-01-28

    This general article is based on the inaugural talk delivered at the opening of OMTAT 2013 conference. It notes that the integration of renewable energy sources into living and transport sectors presents a daunting task, still. In spite of the fact that the earth and its atmosphere continually receive 1.7 × 10{sup 17} watts of radiation from the sun, in the portfolio of sustainable and environment friendly energy options, which is about 16% of the world’s energy consumption and mostly met by biomass, only a paltry 0.04% is accredited to solar. First and second generation solar cells offer mature technologies for applications. The most important difficulty with regards to integration with structures is not only the additional cost, but also the lack of sufficient knowledge in managing the available energy smartly and efficiently. The incorporation of PV as a part of building fabric greatly reduces the overall costs compared with retrofitting. BIPV (Building Integrated photovoltaic) is a critical technology for establishing aesthetically pleasing solar structures. Infusing PV and building elements is greatly simplified with some of the second generation thin film technologies now manufactured as flexible panels. The same holds true for 3{sup rd} generation technologies under development such as, and dye- and quantum dot- sensitized solar cells. Additionally, these technologies offer transparent or translucent solar cells for incorporation into windows and skylights. This review deals with the present state of solar cell technologies suitable for BIPV and the status of BIPV applications and its future prospects.

  14. Limits of Nature and Advances of Technology: What Does Biomimetics Have to Offer to Aquatic Robots?

    Directory of Open Access Journals (Sweden)

    F. E. Fish

    2006-01-01

    Full Text Available In recent years, the biomimetic approach has been utilized as a mechanism for technological advancement in the field of robotics. However, there has not been a full appreciation of the success and limitations of biomimetics. Similarities between natural and engineered systems are exhibited by convergences, which define environmental factors, which impinge upon design, and direct copying that produces innovation through integration of natural and artificial technologies. Limitations of this integration depend on the structural and mechanical differences of the two technologies and on the process by which each technology arises. The diversity of organisms that arose through evolutionary descent does not necessarily provide all possible solutions of optimal functions. However, in instances where organisms exhibit superior performance to engineered systems, features of the organism can be targeted for technology transfer. In this regard, cooperation between biologists and engineers is paramount.

  15. 106-17 Telemetry Standards Chapter 1

    Science.gov (United States)

    2017-07-01

    Telemetry Standards, RCC Standard 106-17 Chapter 1, July 2017 1-1 CHAPTER 1 Introduction The Telemetry Standards address the here-to-date...for Federal Radio Frequency Management . Copies of that manual may be obtained from: Executive Secretary, Interdepartmental Radio Advisory Committee

  16. 31 CFR 1.7 - Fees for services.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Fees for services. 1.7 Section 1.7 Money and Finance: Treasury Office of the Secretary of the Treasury DISCLOSURE OF RECORDS Freedom of... Department shall charge for search time at the salary rate(s) (basic pay plus 16 percent) of the employee(s...

  17. Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells.

    Science.gov (United States)

    Basdeo, Sharee A; Cluxton, Deborah; Sulaimani, Jamal; Moran, Barry; Canavan, Mary; Orr, Carl; Veale, Douglas J; Fearon, Ursula; Fletcher, Jean M

    2017-03-15

    Th17 cells are an important therapeutic target in autoimmunity. However, it is known that Th17 cells exhibit considerable plasticity, particularly at sites of autoimmune inflammation. Th17 cells can switch to become ex-Th17 cells that no longer produce IL-17 but produce IFN-γ. These ex-Th17 cells are also called nonclassical Th1 cells because of their ability to produce IFN-γ, similar to Th1 cells; however, it is unclear whether they resemble Th1 or Th17 cells in terms of their function and regulation, and whether they have a pathogenic role in autoimmunity. We compared the phenotypic and functional features of human Th17, Th1, and ex-Th17 cell populations. Our data showed that despite their loss of IL-17 expression, ex-Th17 cells were more polyfunctional in terms of cytokine production than either Th1 or bona fide Th17 cells, and produced increased amounts of proinflammatory cytokines. The proliferative brake on Th17 cells appeared to be lifted because ex-Th17 cells proliferated more than Th17 cells after stimulation. In contrast with Th1 and Th17 cells, ex-Th17 cells were highly resistant to suppression of proliferation and cytokines by regulatory T cells. Finally, we showed that ex-Th17 cells accumulated in the joints of rheumatoid arthritis patients. Taken together, these data indicate that human ex-Th17 cells are functionally distinct from Th1 and Th17 cells, and suggest that they may play a pathogenic role at sites of autoimmunity, such as the rheumatoid arthritis joint where they accumulate. These findings have implications for therapeutic strategies that target IL-17, because these may not inhibit pathogenic ex-Th17 cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

    Science.gov (United States)

    Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

    2017-01-01

    Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. 17 CFR 230.415 - Delayed or continuous offering and sale of securities.

    Science.gov (United States)

    2010-04-01

    ... majority-owned subsidiary; or (xi) Shares of common stock which are to be offered and sold on a delayed or... an existing trading market for outstanding shares of the same class at other than a fixed price. (5... and sale of securities. 230.415 Section 230.415 Commodity and Securities Exchanges SECURITIES AND...

  20. 26 CFR 1.381(c)(17)-1 - Deficiency dividend of personal holding company.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Deficiency dividend of personal holding company. 1.381(c)(17)-1 Section 1.381(c)(17)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.381(c)(17)-1...

  1. PRODUCT OFFERING AS PART OF THE NPD PROCESS IN TECHNOLOGY COMPANIES

    OpenAIRE

    MATTI J. HAVERILA

    2012-01-01

    We present an exploratory investigation of how managers conceptualize and perceive the product offering effort variables in successful and unsuccessful New Product Development (NPD) projects, and explore the role that product offering effort variables play in differentiating between successful and unsuccessful NPD outcomes. Our findings indicate that managers rely on two broad types of product offering factors, "product effort" and "price/cost effort", during the NPD process so that there are...

  2. 26 CFR 1.1502-17 - Methods of accounting.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Methods of accounting. 1.1502-17 Section 1.1502... (CONTINUED) INCOME TAXES Computation of Separate Taxable Income § 1.1502-17 Methods of accounting. (a) General rule. The method of accounting to be used by each member of the group shall be determined in...

  3. Idaho National Engineering Laboratory Waste Area Groups 1-7 and 10 Technology Logic Diagram

    International Nuclear Information System (INIS)

    O'Brien, M.C.; Meservey, R.H.; Little, M.; Ferguson, J.S.; Gilmore, M.C.

    1993-09-01

    The Idaho National Engineering Laboratory (INEL) Technology Logic Diagram (TLD) was developed to provide a decision support tool that relates Environmental Restoration (ER) and Waste Management (WM) problems at the INEL to potential technologies that can remediate these problems. The TLD identifies the research, development, demonstration, testing, and evaluation needed to develop these technologies to a state that allows technology transfer and application to an environmental restoration need. It is essential that follow-on engineering and system studies be conducted to build on the output of this project. These studies will begin by selecting the most promising technologies identified in this TLD and finding an optimum mix of technologies that will provide a socially acceptable balance between cost and risk to meet the site windows of opportunity. The TLD consists of three separate volumes: Volume I includes the purpose and scope of the TLD, a brief history of the INEL Waste Area Groups, and environmental problems they represent. A description of the TLD, definitions of terms, a description of the technology evaluation process, and a summary of each subelement, is presented. Volume II (this volume) describes the overall layout and development of the TLD in logic diagram format. This section addresses the environmental restoration of contaminated INEL sites. Specific INEL problem areas/contaminants are identified along with technology solutions, the status of the technologies, precise science and technology needs, and implementation requirements. Volume III provides the Technology Evaluation Data Sheets (TEDS) for Environmental Restoration and Waste Management (EM) activities that are referenced by a TEDS codenumber in Volume II. Each of these sheets represents a single logic trace across the TLD. These sheets contain more detail than provided for technologies in Volume II

  4. Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

    Science.gov (United States)

    Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

    2018-01-01

    Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

  5. 17 CFR 270.17g-1 - Bonding of officers and employees of registered management investment companies.

    Science.gov (United States)

    2010-04-01

    ... employees of registered management investment companies. 270.17g-1 Section 270.17g-1 Commodity and... ACT OF 1940 § 270.17g-1 Bonding of officers and employees of registered management investment companies. (a) Each registered management investment company shall provide and maintain a bond which shall...

  6. Electron-Spin Filters Would Offer Spin Polarization Greater than 1

    Science.gov (United States)

    Ting, David Z.

    2009-01-01

    A proposal has been made to develop devices that would generate spin-polarized electron currents characterized by polarization ratios having magnitudes in excess of 1. Heretofore, such devices (denoted, variously, as spin injectors, spin polarizers, and spin filters) have typically offered polarization ratios having magnitudes in the approximate range of 0.01 to 0.1. The proposed devices could be useful as efficient sources of spin-polarized electron currents for research on spintronics and development of practical spintronic devices.

  7. 1 CFR 17.3 - Criteria for emergency publication.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Criteria for emergency publication. 17.3..., AND PROCESSING OF DOCUMENTS FILING FOR PUBLIC INSPECTION AND PUBLICATION SCHEDULES Emergency Schedule § 17.3 Criteria for emergency publication. The emergency schedule is designed to provide the fastest...

  8. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

    NARCIS (Netherlands)

    L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng (Shih-Chin); A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

    2010-01-01

    textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the

  9. 17 January 2014 - Y. Sakurada Japanese Senior Vice Minister of Education, Culture, Sports, Science and Technology signing the Guest book with CERN Director-General R. Heuer and visiting the LHC tunnel at Point 1 with Technology Department Head J.M. Jiménez. Head of International Relations R. Voss present throughout.

    CERN Multimedia

    Pantelia, Anna

    2014-01-01

    17 January 2014 - Y. Sakurada Japanese Senior Vice Minister of Education, Culture, Sports, Science and Technology signing the Guest book with CERN Director-General R. Heuer and visiting the LHC tunnel at Point 1 with Technology Department Head J.M. Jiménez. Head of International Relations R. Voss present throughout.

  10. Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension.

    Science.gov (United States)

    Shenoy, Vinayak; Kwon, Kwang-Chul; Rathinasabapathy, Anandharajan; Lin, Shina; Jin, Guiying; Song, Chunjuan; Shil, Pollob; Nair, Anand; Qi, Yanfei; Li, Qiuhong; Francis, Joseph; Katovich, Michael J; Daniell, Henry; Raizada, Mohan K

    2014-12-01

    Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics. © 2014 American Heart Association, Inc.

  11. 17 CFR 230.165 - Offers made in connection with a business combination transaction.

    Science.gov (United States)

    2010-04-01

    ... a business combination transaction. 230.165 Section 230.165 Commodity and Securities Exchanges... Offers made in connection with a business combination transaction. Preliminary Note: This section is available only to communications relating to business combinations. The exemption does not apply to...

  12. Technologies Avancées - Vol 17 (2005)

    African Journals Online (AJOL)

    A. C. conduction behaviour in amorphous WO3/CEO2 thin film · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. B Yagoubi, C A Hogarth, A Boukorrt, 5-8. http://dx.doi.org/10.4314/ta.v17i1.18478 ...

  13. 17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

    Science.gov (United States)

    2010-04-01

    ... cooperation and coordination among self-regulatory organizations, and the development of a national market... with applicable financial responsibility rules. 240.17d-1 Section 240.17d-1 Commodity and Securities... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

  14. Novel Monoclonal Antibody LpMab-17 Developed by CasMab Technology Distinguishes Human Podoplanin from Monkey Podoplanin.

    Science.gov (United States)

    Kato, Yukinari; Ogasawara, Satoshi; Oki, Hiroharu; Honma, Ryusuke; Takagi, Michiaki; Fujii, Yuki; Nakamura, Takuro; Saidoh, Noriko; Kanno, Hazuki; Umetsu, Mitsuo; Kamata, Satoshi; Kubo, Hiroshi; Yamada, Mitsuhiro; Sawa, Yoshihiko; Morita, Kei-Ichi; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika Kato

    2016-04-01

    Podoplanin (PDPN) is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain in its N-terminus. Among the three PLAG domains, O-glycan on Thr52 of PLAG3 is critical for the binding with C-type lectin-like receptor-2 (CLEC-2) and is essential for platelet-aggregating activity of PDPN. Although many anti-PDPN monoclonal antibodies (mAbs) have been established, almost all mAbs bind to PLAG domains. We recently established CasMab technology to produce mAbs against membranous proteins. Using CasMab technology, we produced a novel anti-PDPN mAb, LpMab-17, which binds to non-PLAG domains. LpMab-17 clearly detected endogenous PDPN of cancer cells and normal cells in Western-blot, flow cytometry, and immunohistochemistry. LpMab-17 recognized glycan-deficient PDPN in flow cytometry, indicating that the interaction between LpMab-17 and PDPN is independent of its glycosylation. The minimum epitope of LpMab-17 was identified as Gly77-Asp82 of PDPN using enzyme-linked immunosorbent assay. Of interest, LpMab-17 did not bind to monkey PDPN, whereas the homology is 94% between human PDPN and monkey PDPN, indicating that the epitope of LpMab-17 is unique compared with the other anti-PDPN mAbs. The combination of different epitope-possessing mAbs could be advantageous for the PDPN-targeting diagnosis or therapy.

  15. 17 CFR 1.21 - Care of money and equities accruing to customers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Care of money and equities... COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.21 Care of money and equities accruing to customers. All money received directly or indirectly by...

  16. Marketing strategy to differentiate the offer

    OpenAIRE

    Miceski, Trajko; Pasovska, Silvana

    2013-01-01

    The marketing strategy for differentiation of the offers is important and accepted strategy especially by the bigger legal entities. The differentiation of the offers leads to bigger profit and bigger profitability in operation, through targeting of the demand towards the product of the enterprise. The vertical differentiation of the offers is directed towards the quality of the product itself which is observed as a something superior despite the competitive product which is observed as somet...

  17. Reverse plasticity: TGF-β and IL-6 induce Th1-to-Th17-cell transdifferentiation in the gut.

    Science.gov (United States)

    Geginat, Jens; Paroni, Moira; Kastirr, Ilko; Larghi, Paola; Pagani, Massimiliano; Abrignani, Sergio

    2016-10-01

    Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells. Thus, IFN-γ-producing Th1 effector cells specific for an intestinal microbial antigen were shown to acquire IL-17-producing capacities in the gut in a mouse model of colitis, and in response to TGF-β and IL-6 in vitro. TGF-β induced Runx1, and together with IL-6 was shown to render the ROR-γt and IL-17 promoters in Th1 cells accessible for Runx1 binding. In this commentary, we discuss how this unexpected plasticity of Th1 cells challenges our view on the generation of Th1/17 cells with the capacity to co-produce IL-17 and IFN-γ, and consider possible implications of this Th1-to-Th17-cell conversion for therapies of inflammatory bowel diseases and protective immune responses against intracellular pathogens. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Idaho National Engineering Laboratory Waste Area Groups 1-7 and 10 Technology Logic Diagram

    International Nuclear Information System (INIS)

    O'Brien, M.C.; Meservey, R.H.; Little, M.; Ferguson, J.S.; Gilmore, M.C.

    1993-09-01

    The Idaho National Engineering Laboratory (INEL) Technology Logic Diagram (TLD) was developed to provide a decision support tool that relates Environmental Restoration (ER) and Waste Management (WM) problems at the INEL to potential technologies that can remediate these problems. The TLD identifies the research, development, demonstration, testing, and evaluation needed to develop these technologies to a state that allows technology transfer and application to an environmental restoration need. It is essential that follow-on engineering and system studies be conducted to build on the output of this project. These studies will begin by selecting the most promising technologies identified in this TLD and finding an optimum mix of technologies that will provide a socially acceptable balance between cost and risk to meet the site windows of opportunity. The TLD consists of three separate volumes: Volume I includes the purpose and scope of the TLD, a brief history of the INEL Waste Area Groups, and environmental problems they represent. A description of the TLD, definitions of terms, a description of the technology evaluation process, and a summary of each subelement, is presented. Volume II describes the overall layout and development of the TLD in logic diagram format. This section addresses the environmental restoration of contaminated INEL sites. Volume III (this volume) provides the Technology Evaluation Data Sheets (TEDS) for Environmental Restoration and Waste Management (EM) activities that are reference by a TEDS code number in Volume II. Each of these sheets represents a single logic trace across the TLD. These sheets contain more detail than provided for technologies in Volume II. Data sheets are arranged alphanumerically by the TEDS code number in the upper right corner of each sheet

  19. Mechanistic Scrutiny Identifies a Kinetic Role for Cytochrome b5 Regulation of Human Cytochrome P450c17 (CYP17A1, P450 17A1.

    Directory of Open Access Journals (Sweden)

    Alexandr N Simonov

    Full Text Available Cytochrome P450c17 (P450 17A1, CYP17A1 is a critical enzyme in the synthesis of androgens and is now a target enzyme for the treatment of prostate cancer. Cytochrome P450c17 can exhibit either one or two physiological enzymatic activities differentially regulated by cytochrome b5. How this is achieved remains unknown. Here, comprehensive in silico, in vivo and in vitro analyses were undertaken. Fluorescence Resonance Energy Transfer analysis showed close interactions within living cells between cytochrome P450c17 and cytochrome b5. In silico modeling identified the sites of interaction and confirmed that E48 and E49 residues in cytochrome b5 are essential for activity. Quartz crystal microbalance studies identified specific protein-protein interactions in a lipid membrane. Voltammetric analysis revealed that the wild type cytochrome b5, but not a mutated, E48G/E49G cyt b5, altered the kinetics of electron transfer between the electrode and the P450c17. We conclude that cytochrome b5 can influence the electronic conductivity of cytochrome P450c17 via allosteric, protein-protein interactions.

  20. A kidney offer acceptance decision tool to inform the decision to accept an offer or wait for a better kidney.

    Science.gov (United States)

    Wey, Andrew; Salkowski, Nicholas; Kremers, Walter K; Schaffhausen, Cory R; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-01

    We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. We randomly selected 5000 declined offers and estimated these probabilities 3 years post-offer had the offers been accepted or declined. Predicted outcomes for declined offers were well calibrated (offers been accepted, the probabilities of graft survival and patient survival were typically higher. However, these advantages attenuated or disappeared with higher KDPI, candidate priority, and local donor supply. Donor pool restrictions were associated with worse 3-year outcomes, especially for candidates with high allocation priority. The kidney offer acceptance decision tool could inform offer acceptance by characterizing the potential risk-benefit trade-off associated with accepting or declining an offer. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. High-precision half-life measurements of the T=1/2 mirror beta decays F-17 and Cl-33

    OpenAIRE

    Grinyer, J; Grinyer, G. F; Babo, Mathieu; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J. C; Traykov, E

    2015-01-01

    Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, 17F and 33Cl, in order to eliminate the half-life as th...

  2. High-precision half-life measurements of the T=1/2 mirror β decays F17 and Cl33

    OpenAIRE

    Grinyer, J; Grinyer, G F; Babo, M; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J C; Traykov, E

    2015-01-01

    Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, F17 and Cl33, in order to eliminate the half-life as the le...

  3. [Congenital adrenal hyperplasia due to lack of 17α-hydroxylase: a report of a new mutation in the gene CYP17A1].

    Science.gov (United States)

    Perales Martínez, J I; Pina Marqués, B; de Arriba Muñoz, A; Mayayo Dehesa, E; Labarta Aizpún, J I; Loidi Fernández, L

    2015-01-01

    P450c17 enzyme catalyses two different reactions: the 17α-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17α-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2016-02-01

    Full Text Available Voltage-gated sodium channels (VGSCs are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9, Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR membrane potential (FMP blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  5. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin.

    Science.gov (United States)

    Zhao, Fang; Li, Xichun; Jin, Liang; Zhang, Fan; Inoue, Masayuki; Yu, Boyang; Cao, Zhengyu

    2016-02-16

    Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  6. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.

    Directory of Open Access Journals (Sweden)

    Paméla Gasse

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+ γδ T cells and to a lesser extent by CD4αβ(+ T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

  7. Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

    Directory of Open Access Journals (Sweden)

    Sudipta Tripathi

    2015-02-01

    Full Text Available Tolerance of the fetus by the maternal immune system is regulated through various mechanisms involving the different immune cells, both in the periphery and locally at the feto-maternal interface. The maternal T lymphocytes are aware of the paternal fetal antigens and a state of dynamic T cell homeostasis is maintained in the uterus during gestation, which involves increase in antigen-specific regulatory T cell (Treg proliferation, increase in apoptosis of antigen-specific effector T cells, and inhibition of excessive inflammation post successful implantation to ensure tolerance to the fetus. The Tregs play an important role in the maintenance of tolerance during gestation. Recently, the inflammatory T helper type 17 (Th17 cells are reported to have a role in loss of tolerance to the fetus. The interaction between costimulatory molecule programmed death 1 (PD1 and its ligand PDL1 is known to play a role in regulating both the Tregs and Th17 cells. Here we discuss how the PD1/PDL1 pathway affects these two T cell populations and its role in feto-maternal tolerance.

  8. Minimally invasive surgical approaches offer earlier time to adjuvant chemotherapy but not improved survival in resected pancreatic cancer.

    Science.gov (United States)

    Mirkin, Katelin A; Greenleaf, Erin K; Hollenbeak, Christopher S; Wong, Joyce

    2018-05-01

    Pancreatic surgery encompasses complex operations with significant potential morbidity. Greater experience in minimally invasive surgery (MIS) has allowed resections to be performed laparoscopically and robotically. This study evaluates the impact of surgical approach in resected pancreatic cancer. The National Cancer Data Base (2010-2012) was reviewed for patients with stages 1-3 resected pancreatic carcinoma. Open approaches were compared to MIS. A sub-analysis was then performed comparing robotic and laparoscopic approaches. Of the 9047 patients evaluated, surgical approach was open in 7511 (83%), laparoscopic in 992 (11%), and robotic in 131 (1%). The laparoscopic and robotic conversion rate to open was 28% (n = 387) and 17% (n = 26), respectively. Compared to open, MIS was associated with more distal resections (13.5, 24.3%, respectively, p offered significantly shorter LOS in all types. Multivariate analysis demonstrated no survival benefit for any MIS approach relative to open (all, p > 0.05). When adjusted for patient, disease, and treatment characteristics, TTC was not an independent prognostic factor (HR 1.09, p = 0.084). MIS appears to offer comparable surgical oncologic benefit with improved LOS and shorter TTC. This effect, however, was not associated with improved survival.

  9. 17 CFR 140.1 - Headquarters office.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Headquarters office. 140.1..., FUNCTIONS, AND PROCEDURES OF THE COMMISSION Organization § 140.1 Headquarters office. (a) General. The headquarters office of the Commission is located at Three Lafayette Centre, 1155 21st Street, NW., Washington...

  10. Nuclear and radiation technologies in Ukraine: opportunities, status and problems of implementation

    International Nuclear Information System (INIS)

    Gorbulyin, V.P.

    2011-01-01

    The collection contains research materials and information presented at the Scientific Conference 'Nuclear and radiation technologies in Ukraine' (September 17, 2009, Kyiv). The articles offered specific ways to address a number of issues relevant to nuclear energy, science, technology, medicine and related to the radiation and environmental safety, the use of radiation technologies in medicine, development of uranium and uranium processing industry, safety on factories of NFC, nuclear physical instrumentation, behaviour with radioactive wastes.

  11. Spin reorientation and magnetic anisotropy in Y2Co17-xCr x (x 1.17-3.0) compounds

    International Nuclear Information System (INIS)

    Fuquan, B.; Tegus, O.; Dagula, W.; Brueck, E.; Boer, F.R. de; Buschow, K.H.J.

    2005-01-01

    Spin reorientation transitions and magnetic anisotropy in Y 2 Co 17-x Cr x (x = 1.17-3.0) compounds have been investigated by means of X-ray diffraction and magnetization measurements. The powder X-ray diffraction patterns show that most samples crystallize as a single phase with the rhombohedral Th 2 Zn 17 -type structure. However, in the compound Y 2 Co 14 Cr 3 the Th 2 Zn 17 phase coexist with the hexagonal Th 2 Ni 17 -type phase. The lattice parameters a and c hardly change and the unit cell volume V increases slightly with increasing Cr content. The X-ray diffraction patterns of the aligned powder of the samples have confirmed that at room temperature the compound with x = 1.17 has planar anisotropy, but the compounds with x = 1.76, 2.34 and 3.00 have uniaxial anisotropy. Spin reorientation phenomena occur in all of the compounds. With increasing Cr content, the Curie temperature, the spin reorientation temperature, the spontaneous magnetization, and the anisotropy constant K 2 of the Y 2 Co 17-x Cr x (x = 1.17-3.0) compounds decrease strongly while the anisotropy constant K 1 increases in the range of x from 1.17 to 2.34 and then decreases in the range of x from 2.34 to 3.00

  12. Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

    Science.gov (United States)

    Saberi, Shadan; Dehghani, Aghdas; Nematbakhsh, Mehdi

    2016-01-01

    The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 μg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

  13. The Necessity and Applicability Levels of the Courses that are Offered in the Departments of Computer Education and Instructional Technologies (CEIT)

    Science.gov (United States)

    Acat, M. Bahaddin; Kilic, Abdurrahman; Girmen, Pinar; Anagun, Senegul S.

    2007-01-01

    The main purpose of this study is to identify the levels of the necessity and applicability of the courses offered in the Departments of Computer Education and Instructional Technologies based on the views of the fourth grade and graduated students. In the study descriptive research model was used. The population of the study were final-year and…

  14. 17 CFR 37.1 - Scope and definition.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Scope and definition. 37.1 Section 37.1 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES... any board of trade operating as or applying to become registered as a derivatives transaction...

  15. 28 CFR 54.415 - Access to course offerings.

    Science.gov (United States)

    2010-07-01

    ..., music, and adult education courses. (b)(1) With respect to classes and activities in physical education... SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 54.415 Access to course offerings. (a) A...

  16. 44 CFR 19.415 - Access to course offerings.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Access to course offerings. 19.415 Section 19.415 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... in wrestling, boxing, rugby, ice hockey, football, basketball, and other sports the purpose or major...

  17. 17 CFR 1.60 - Pending legal proceedings.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Pending legal proceedings. 1... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Miscellaneous § 1.60 Pending legal proceedings. (a) Every... section to be submitted to the Commission as to matters pending on the effective date of the section (May...

  18. NAD(P)H:Quinone Oxidoreductase-1 Expression Sensitizes Malignant Melanoma Cells to the HSP90 Inhibitor 17-AAG.

    Science.gov (United States)

    Kasai, Shuya; Arakawa, Nobuyuki; Okubo, Ayaka; Shigeeda, Wataru; Yasuhira, Shinji; Masuda, Tomoyuki; Akasaka, Toshihide; Shibazaki, Masahiko; Maesawa, Chihaya

    2016-01-01

    The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional induction of genes associated with antioxidant synthesis and detoxification in response to oxidative stress. Previously, we reported that KEAP1 mutation elicits constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine (DTIC) in human melanomas. The present study was conducted to clarify whether an HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma and non-small cell lung carcinoma cell lines with or without KEAP1 mutations, NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines despite the presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2 activation. Because either CDDP or DTIC produces reactive oxygen species that activate NRF2, we determined whether these agents would sensitize NQO1-low melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP combination was detected in four out of five NQO1-low cell lines, but not in the cell line with KEAP1 mutation. These data indicate that 17-AAG could be a potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1 expression.

  19. 17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis.

    Science.gov (United States)

    Siegelin, Markus David; Habel, Antje; Gaiser, Timo

    2009-02-01

    17-AAG is a selective HSP90-inhibitor that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, LN229 and U251) were treated with 17-AAG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of 17-AAG in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. 17-AAG treatment down-regulated survivin through proteasomal degradation. In addition, over-expression of survivin attenuated cytotoxicity induced by the combination of 17-AAG and TRAIL. In summary, survivin is a key regulator of TRAIL-17-AAG mediated cell death in malignant glioma.

  20. 17 CFR 256.426.1 - Donations.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Donations. 256.426.1 Section... COMPANY ACT OF 1935 Income and Expense Accounts § 256.426.1 Donations. This account shall include all payments or donations for charitable, social or community welfare purposes. ...

  1. 15 CFR Supplement No. 1 to Part 744 - Military End-Use Examples for § 744.17

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Military End-Use Examples for § 744.17 No. Supplement No. 1 to Part 744 Commerce and Foreign Trade Regulations Relating to Commerce and... End-Use Examples for § 744.17 (a) Examples of military end-uses (as described in § 744.17 (d) of this...

  2. β1 subunit stabilises sodium channel Nav1.7 against mechanical stress.

    Science.gov (United States)

    Körner, Jannis; Meents, Jannis; Machtens, Jan-Philipp; Lampert, Angelika

    2018-06-01

    The voltage-gated sodium channel Nav1.7 is a key player in neuronal excitability and pain signalling. In addition to voltage sensing, the channel is also modulated by mechanical stress. Using whole-cell patch-clamp experiments, we discovered that the sodium channel subunit β1 is able to prevent the impact of mechanical stress on Nav1.7. An intramolecular disulfide bond of β1 was identified to be essential for stabilisation of inactivation, but not activation, against mechanical stress using molecular dynamics simulations, homology modelling and site-directed mutagenesis. Our results highlight the role of segment 6 of domain IV in fast inactivation. We present a candidate mechanism for sodium channel stabilisation against mechanical stress, ensuring reliable channel functionality in living systems. Voltage-gated sodium channels are key players in neuronal excitability and pain signalling. Precise gating of these channels is crucial as even small functional alterations can lead to pathological phenotypes such as pain or heart failure. Mechanical stress has been shown to affect sodium channel activation and inactivation. This suggests that stabilising components are necessary to ensure precise channel gating in living organisms. Here, we show that mechanical shear stress affects voltage dependence of activation and fast inactivation of the Nav1.7 channel. Co-expression of the β1 subunit, however, protects both gating modes of Nav1.7 against mechanical shear stress. Using molecular dynamics simulation, homology modelling and site-directed mutagenesis, we identify an intramolecular disulfide bond of β1 (Cys21-Cys43) which is partially involved in this process: the β1-C43A mutant prevents mechanical modulation of voltage dependence of activation, but not of fast inactivation. Our data emphasise the unique role of segment 6 of domain IV for sodium channel fast inactivation and confirm previous reports that the intracellular process of fast inactivation can be

  3. IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

    Science.gov (United States)

    Stephen-Victor, Emmanuel; Sharma, Varun Kumar; Das, Mrinmoy; Karnam, Anupama; Saha, Chaitrali; Lecerf, Maxime; Galeotti, Caroline; Kaveri, Srinivas V.; Bayry, Jagadeesh

    2016-01-01

    The programed death-1 (PD-1)–programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β, but not members of the programed death pathway, is critical for human Th17 response to M. tuberculosis. PMID:27867382

  4. IL-1β but not programmed death-1 and programmed death-ligand pathway is critical for the human Th17 response to M. tuberculosis

    Directory of Open Access Journals (Sweden)

    Emmanuel Stephen-Victor

    2016-11-01

    Full Text Available The programmed death-1 (PD-1- programmed death ligand-1 (PD-L1 and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells (Tregs and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte and dendritic cell (DC-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β but not members of the programmed death pathway is critical for human Th17 response to M. tuberculosis

  5. Role of Mas receptor in renal blood flow response to angiotensin (1-7) in male and female rats.

    Science.gov (United States)

    Nematbakhsh, Mehdi; Safari, Tahereh

    2014-01-01

    Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdoserenal diseases.

  6. TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression.

    Science.gov (United States)

    Liu, Hou-Pu; Cao, Anthony T; Feng, Ting; Li, Qingjie; Zhang, Wenbo; Yao, Suxia; Dann, Sara M; Elson, Charles O; Cong, Yingzi

    2015-04-01

    Differentiated CD4(+) T cells preserve plasticity under various conditions. However, the stability of Th1 cells is unclear, as is whether Th1 cells can convert into Th17 cells and thereby contribute to the generation of IFN-γ(+) IL-17(+) CD4(+) T cells, the number of which correlates with severity of colitis. We investigated whether IFN-γ(+) Th1 cells can convert into Th17 cells under intestinal inflammation and the mechanisms involved. IFN-γ(Thy1.1+) Th1 cells were generated by culturing naïve CD4(+) T cells from IFN-γ(Thy1.1) CBir1 TCR-Tg reporter mice, whose TCR is specific for an immunodominant microbiota antigen, CBir1 flagellin, under Th1 polarizing conditions. IFN-γ(Thy1.1+) Th1 cells induced colitis in Rag(-/-) mice after adoptive transfer and converted into IL-17(+) Th17, but not Foxp3(+) Treg cells in the inflamed intestines. TGF-β and IL-6, but not IL-1β and IL-23, regulated Th1 conversion into Th17 cells. TGF-β induction of transcriptional factor Runx1 is crucial for the conversion, since silencing Runx1 by siRNA inhibited Th1 conversion into Th17 cells. Furthermore, TGF-β enhanced histone H3K9 acetylation but inhibited H3K9 trimethylation of Runx1- and ROR-γt-binding sites on il-17 or rorc gene in Th1 cells. We conclude that Th1 cells convert into Th17 cells under inflammatory conditions in intestines, which is possibly mediated by TGF-β induction of Runx1. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 17 CFR 230.236 - Exemption of shares offered in connection with certain transactions.

    Science.gov (United States)

    2010-04-01

    ... Exemptions § 230.236 Exemption of shares offered in connection with certain transactions. Shares of stock or... securities in lieu of issuing fractional shares, script certificates or order forms, in connection with a stock dividend, stock split, reverse stock split, conversion, merger or similar transaction, shall be...

  8. Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG

    International Nuclear Information System (INIS)

    Hadley, Katie E; Hendricks, Denver T

    2014-01-01

    Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status. We used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP. Expression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels. Since NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages

  9. Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG.

    Science.gov (United States)

    Hadley, Katie E; Hendricks, Denver T

    2014-05-15

    Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status. We used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP. Expression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels. Since NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages.

  10. The effect of angiotensin 1-7 on tyrosine kinases activity in rat anterior pituitary

    International Nuclear Information System (INIS)

    Rebas, Elzbieta; Zabczynska, Joanna; Lachowicz, Agnieszka

    2006-01-01

    Angiotensin 1-7 (Ang 1-7) is a peptide originated from Ang II. It is known that in vessels Ang 1-7 shows opposite effects to Ang II. Ang 1-7 can modify processes of proliferation. However, Ang 1-7 action in pituitary gland cells was never studied. Moreover, the specific binding sites for Ang 1-7 are still unknown. The aim of this study was to examine the effects of Ang 1-7 on tyrosine kinases (PTKs) activity in the anterior pituitary. The reaction of phosphorylation was carrying out in presence of different concentration of Ang 1-7 and losartan (antagonist of AT1 receptor) and PD123319 (antagonist of AT2). Our results show that Ang 1-7 inhibited activity of PTK to 60% of basic activity. Losartan did not change the Ang 1-7-induced changes in PTKs activity. The presence of PD123319 together with Ang 1-7 caused stronger inhibition PTKs activity than Ang 1-7 alone. These observations suggest that Ang 1-7 binds to the novel, unknown, specific for this peptide receptor

  11. The Effect of Technological Parameters on the Microstructure and Mechanical Properties of AlSi17Cu4 Alloy

    Directory of Open Access Journals (Sweden)

    Jaroslaw PIĄTKOWSKI

    2016-09-01

    Full Text Available The mechanical properties (HB, HV, R0.2, Rm and plastic properties (A5, Z of AlSi17Cu4 alloy when exposed to chosen technological processes, such as modification, overheating and rapid cooling, are presented in this paper. The best combination of properties was noticed in alloy overheated for 40 minutes at 920 oC and casted into a metallic mould submerged in liquid nitrogen. Moreover, the technological stability and homogeneity of alloys were evaluated based on spread of results, expressed by standard deviation. It was proven, based on microstructure analysis, that the best effect of refinement was achieved by intensive cooling of alloy preceded by its overheating. The XRD analysis indicated that the intermetallic phases, mainly θ(Al2Cu and γ1(Al4Cu9 caused hardening of the solution, improvement in mechanical properties and technological stability.DOI: http://dx.doi.org/10.5755/j01.ms.22.3.8490

  12. 21 CFR 1.285 - What happens to food that is imported or offered for import from unregistered facilities that are...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What happens to food that is imported or offered....285 Section 1.285 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Prior Notice of Imported Food Consequences § 1.285 What happens to...

  13. 17th National Conference on Sensors and Microsystems

    CERN Document Server

    Ferrari, Vittorio; Ponzoni, Andrea; Sberveglieri, Giorgio; Ferrari, Marco

    2014-01-01

    This book contains a selection of papers presented at the 17th AISEM (“Associazione Italiana Sensori e Microsistemi”) National Conference on Sensors and Microsystems, held in Brescia, 5-7 February, 2013. The conference highlighted state-of-the-art results from both theoretical and applied research in the field of sensors and related technologies. This book presents material in an interdisciplinary approach, covering many aspects of the disciplines related to sensors, including physics, chemistry, materials science, biology and applications.  ·         Provides a selection of the best papers from the 17th National Conference on Sensors and Microsystems; ·         Covers a broad range of topics relating to sensors and microsystems, including physics, chemistry, materials science, biology and applications; ·         Offers interdisciplinary coverage, aimed at defining a common ground for sensors beyond the specific differences among the different particular implementation of senso...

  14. Nav1.7 expression is increased in painful human dental pulp

    Directory of Open Access Journals (Sweden)

    Levinson S Rock

    2008-04-01

    Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

  15. 19 CFR 172.32 - Authority to accept offers.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Authority to accept offers. 172.32 Section 172.32 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE....32 Authority to accept offers. The authority to accept offers in compromise, subject to the...

  16. Advanced Earth-to-orbit propulsion technology information, dissemination and research

    Science.gov (United States)

    Wu, S. T.

    1995-01-01

    In this period of performance a conference (The 1994 Conference on Advanced Earth-to-Orbit Propulsion Technology) was organized and implemented by the University of Alabama in Huntsville and held May 15-17 to assemble and disseminate the current information on Advanced Earth-to-Orbit Propulsion Technology. The results were assembled for publication as NASA-CP-3282, Volume 1 and 2 and NASA-CP-3287.

  17. High-precision half-life measurements of the T =1 /2 mirror β decays 17F and 33Cl

    Science.gov (United States)

    Grinyer, J.; Grinyer, G. F.; Babo, M.; Bouzomita, H.; Chauveau, P.; Delahaye, P.; Dubois, M.; Frigot, R.; Jardin, P.; Leboucher, C.; Maunoury, L.; Seiffert, C.; Thomas, J. C.; Traykov, E.

    2015-10-01

    Background: Measurements of the f t values for T =1 /2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the f t values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T =1 /2 β+ emitters, 17F and 33Cl, in order to eliminate the half-life as the leading source of uncertainty in their f t values. Method: Half-lives of 17F and 33Cl were determined using β counting of implanted radioactive ion beam samples on a moving tape transport system at the Système de Production d'Ions Radioactifs Accélérés en Ligne low-energy identification station at the Grand Accélérateur National d'Ions Lourds. Results: The 17F half-life result, 64.347 (35) s, precise to ±0.05 % , is a factor of 5 times more precise than the previous world average. The half-life of 33Cl was determined to be 2.5038 (22) s. The current precision of ±0.09 % is nearly 2 times more precise compared to the previous world average. Conclusions: The precision achieved during the present measurements implies that the half-life no longer dominates the uncertainty of the f t values for both T =1 /2 mirror decays 17F and 33Cl.

  18. 49 CFR 17.1 - What is the purpose of these regulations?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What is the purpose of these regulations? 17.1 Section 17.1 Transportation Office of the Secretary of Transportation INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF TRANSPORTATION PROGRAMS AND ACTIVITIES § 17.1 What is the purpose of these regulations? (a) The...

  19. 48 CFR 570.303-3 - Late offers, modifications of offers, and withdrawals of offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Late offers, modifications of offers, and withdrawals of offers. 570.303-3 Section 570.303-3 Federal Acquisition Regulations... PROPERTY Contracting Procedures for Leasehold Interests in Real Property 570.303-3 Late offers...

  20. Idaho National Engineering Laboratory Waste Area Groups 1-7 and 10 Technology Logic Diagram. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, M.C.; Meservey, R.H.; Little, M.; Ferguson, J.S.; Gilmore, M.C.

    1993-09-01

    The Idaho National Engineering Laboratory (INEL) Technology Logic Diagram (TLD) was developed to provide a decision support tool that relates Environmental Restoration (ER) and Waste Management (WM) problems at the INEL to potential technologies that can remediate these problems. The TLD identifies the research, development, demonstration, testing, and evaluation needed to develop these technologies to a state that allows technology transfer and application to an environmental restoration need. It is essential that follow-on engineering and system studies be conducted to build on the output of this project. These studies will begin by selecting the most promising technologies identified in this TLD and finding an optimum mix of technologies that will provide a socially acceptable balance between cost and risk to meet the site windows of opportunity. The TLD consists of three separate volumes: Volume I includes the purpose and scope of the TLD, a brief history of the INEL Waste Area Groups, and environmental problems they represent. A description of the TLD, definitions of terms, a description of the technology evaluation process, and a summary of each subelement, is presented. Volume II (this volume) describes the overall layout and development of the TLD in logic diagram format. This section addresses the environmental restoration of contaminated INEL sites. Specific INEL problem areas/contaminants are identified along with technology solutions, the status of the technologies, precise science and technology needs, and implementation requirements. Volume III provides the Technology Evaluation Data Sheets (TEDS) for Environmental Restoration and Waste Management (EM) activities that are referenced by a TEDS codenumber in Volume II. Each of these sheets represents a single logic trace across the TLD. These sheets contain more detail than provided for technologies in Volume II.

  1. 17 CFR 1.27 - Record of investments.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Record of investments. 1.27... UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.27 Record of investments... record showing the following: (1) The date on which such investments were made; (2) The name of the...

  2. Nuclear-related training and education offered by nonacademic organizations (preliminary)

    International Nuclear Information System (INIS)

    Howard, L.

    1981-11-01

    The results of a survey of nuclear-related training and education provided by nonacademic training organizations are presented in this report. The survey instrument was distributed by the Institute of Nuclear Power Operations to 136 training organizations. The scope of the survey was not intended to be comprehensive, but rather to include the primary sources of nonacademic nuclear-related training and education offered to utility personnel. The survey universe was compiled from training organizations listed in the 1981 Nuclear News Buyer's Guide. Forty-three percent of the survey population (59 organizations) responded to the questionnaire of which 31 percent (42) reported they offered nuclear-related training programs and 12 percent (17) reported they did not offer any nuclear-related training

  3. 17 CFR 270.11a-3 - Offers of exchange by open-end investment companies other than separate accounts.

    Science.gov (United States)

    2010-04-01

    ... advertising that mentions the existence of the exchange offer also discloses (i) The existence of any... than two years old, at all times the offer has been outstanding) that the terms of the offer were...

  4. Turnkey offering a claimed sector 'first'.

    Science.gov (United States)

    Law, Oliver

    2011-01-01

    Manufacturer and supplier of LED theatre lights, HD camera systems, video integration technologies, and ceiling support units, Trumpf Medical Systems UK, and "logistical services" company Canute International Medical Services (CIMS), one of whose specialities is providing mobile medical units for diagnostic imaging, have entered into a partnership that will see the two companies offer fully fitted out modular operating theatres and other medical/clinical buildings incorporating the latest technology and equipment, on a fully project-managed, "turnkey" basis. Oliver Law, Trumpf Medical Systems UK managing director, explains the background, and the new service's anticipated customer benefits.

  5. Steer wrestling : Hemisphere GPS hopes to bring its auto-steering technology to the oilsands

    Energy Technology Data Exchange (ETDEWEB)

    Bentein, J.

    2009-01-15

    Hemisphere GPS has developed a technology to guide giant dump trucks used in oilsand mining operations. The technology offers the possibility to haul oilsands from northern Alberta mines using driverless, remotely-guided trucks. The GPS system would ensure more accuracy than a human operator. The technology has the potential to be commercialized within the next year, and may be adapted for the mining industry. The unmanned technology would help oilsands mine operators lower their labour costs. Hemisphere GPS gained access to the steer-by-wire technology when it purchased the Australian software company Beeline Technologies Pty Ltd. Hemisphere GPS has also developed prototype unmanned drilling rig technology which has considerable potential in the energy industry. The company has won numerous awards in recognition of its commercial achievements in science and technology. 1 fig.

  6. Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency

    Directory of Open Access Journals (Sweden)

    Mónica Fernández-Cancio

    2018-04-01

    Full Text Available The CYP17A1 gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA was impaired, explaining the patient’s steroid profile. Abiraterone could not bind and inhibit the 17α-hydroxylase activity of the CYP17A1-V366M mutant. Molecular dynamics (MD simulations showed that V366M creates a “one-way valve” and suggests a mechanism for dual activities of human CYP17A1 where, after the conversion of pregnenolone to 17OH-pregnenolone, the product exits the active site and re-enters for conversion to dehydroepiandrosterone. The V366M mutant also explained the effectiveness of the anti-prostate cancer drug abiraterone as a potent inhibitor of CYP17A1 by binding tightly at the active site in the WT enzyme. The V366M is the first human mutation to be described at the active site of CYP17A1 that causes isolated 17,20 lyase deficiency. Knowledge about the specificity of CYP17A1 activities is of importance for the development of treatments for polycystic ovary syndrome and inhibitors for prostate cancer therapy.

  7. Technology in L1

    DEFF Research Database (Denmark)

    Elf, Nikolaj Frydensbjerg; Hanghøj, Thorkild; Skaar, Håvard

    2015-01-01

    In recent decades, several Scandinavian research projects have had an explicit focus on how technology intervenes in L1 (or so-called Mother Tongue Education) practices in Swedish, Norwegian and Danish educational contexts, and how this may impact on understanding of the subject. There is currently......-of-school literacy practices. A final finding is the emphasis on teacher uncertainty regarding how and why to integrate technology within existing paradigms of the subject. This calls for further research on how technology may be justified in L1 practice, including various forms of teacher education....... no systematic overview of the documented possibilities and challenges related to the use of technology in L1. At the same time, there is terminological confusion in use of ‘technology’ and related concepts in L1. Finally, there is a general lack of critical reflection on the relation between technological...

  8. Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients.

    Science.gov (United States)

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Andreotti, Mauro; Selvaggi, Carla; Giustini, Noemi; Serafino, Sara; Schietroma, Ivan; Nunnari, Giuseppe; Antonelli, Guido; Vullo, Vincenzo; Scagnolari, Carolina

    2015-01-01

    The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression) into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory) in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

  9. Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients

    Directory of Open Access Journals (Sweden)

    Gabriella d’Ettorre

    2015-01-01

    Full Text Available The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

  10. Offer as a creative foundation of direct marketing

    Directory of Open Access Journals (Sweden)

    Kocić Milan

    2010-01-01

    Full Text Available Investments into communications mix are specific because besides significant financial resources it also involves creative marketing ideas that are a result of imagination and experience. However, the application of direct marketing communication mix is like 'a cave on iceberg'. The visible aspect presented through promotional content is only a small part of the whole process including experts from different fields. The process of creation a new communication mix of direct marketing must fully use all the challenges posed by sophisticated technology. Direct marketing depicted by new technology (cable television, telemarketing and the Internet can substantially increase the competitive advantage of enterprises in attracting their customer's attention and creating their loyalty as well. The companies use the mentioned media more frequently in order to create such offers that will lead towards strengthening loyalty of the existing customers, while simultaneously attracting those customers who were previously making purchases with our direct competitors. Hence, an offer as a creatively designed marketing vehicle proposes a number of potential benefits to a client. However, the client will be able to claim those benefits only in the case when a customer takes action as suggested by a communicated message. Basically, those are 'the rules of the game' that regulate relationship between company and client in direct marketing. Creating offers which guide the process of direct marketing is in the domain of customer relations management. Without an attractive offer, consumers will not create any type of measurable response to a company and therefore relations with clients would never emerge. On the other hand, if a company fails to continuously follow client's needs and wants, those engaged in direct sales will not be able to create adequate offers that would satisfy clients and motivate them to repeat purchases. .

  11. Evaluating alternative offering strategies for wind producers in a pool

    International Nuclear Information System (INIS)

    Rahimiyan, Morteza; Morales, Juan M.; Conejo, Antonio J.

    2011-01-01

    Highlights: → Out-of-sample analysis allows comparing diverse offers using real-world data. → Offering the best production forecast is not optimal for a wind producer. → Stochastic programming offers lead to maximum expected profit. → Offering the best production forecast is not generally optimal for risk control. → Stochastic programming offers lead to the best tradeoff profit versus risk. -- Abstract: As wind power technology matures and reaches break-even cost, wind producers find it increasingly attractive to participate in pool markets instead of being paid feed-in tariffs. The key issue is then how a wind producer should offer in the pool markets to achieve maximum profit while controlling the variability of such profit. This paper compares two families of offering strategies based, respectively, on a naive use of wind production forecasts and on stochastic programming models. These strategies are compared through a comprehensive out-of-sample chronological analysis based on real-world data. A number of relevant conclusions are then duly drawn.

  12. Taking a Technological Path to Poetry Prewriting.

    Science.gov (United States)

    Roberts, Sherron Killingsworth

    2002-01-01

    Offers a strong rationale for the idea that the journey of writing good poetry begins on a path that infuses technology into the first stage of the writing process. Presents several ideas of ways to incorporate technology into the prewriting poetry experience. Concludes that by making technology an ingredient, the true potential for synergy…

  13. 41 CFR 101-4.415 - Access to course offerings.

    Science.gov (United States)

    2010-07-01

    ..., music, and adult education courses. (b)(1) With respect to classes and activities in physical education... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 101-4.415 Access to course offerings. (a) A...

  14. 17 CFR 1.1 - Fraud in or in connection with transactions in foreign currency subject to the Commodity Exchange...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Fraud in or in connection with... Securities Exchanges COMMODITY FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Definitions § 1.1 Fraud in or in connection with transactions in foreign currency subject to the...

  15. Hospitalized Patients' Responses to Offers of Prayer.

    Science.gov (United States)

    McMillan, Kathy; Taylor, Elizabeth Johnston

    2018-02-01

    Most Americans pray; many pray about their health. When they are hospitalized, however, do patients want an offer of prayer from a healthcare provider? This project allowed for the measurement of hospitalized patient's responses to massage therapists' offers of a colloquial prayer after a massage. After the intervention, 78 patients completed questionnaires that elicited quantitative data that were analyzed using uni- and bivariate statistical analyses. In this sample, 88% accepted the offer of prayer, 85% found it helpful, and 51% wanted prayer daily. Patients may welcome prayer, as long as the clinician shows "genuine kindness and respect."

  16. 48 CFR 12.205 - Offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Offers. 12.205 Section 12... ACQUISITION OF COMMERCIAL ITEMS Special Requirements for the Acquisition of Commercial Items 12.205 Offers. (a) Where technical information is necessary for evaluation of offers, agencies should, as part of market...

  17. Neuroprotective Mechanisms of the ACE2-Angiotensin-(1-7)-Mas Axis in Stroke

    DEFF Research Database (Denmark)

    Bennion, Douglas M; Haltigan, Emily; Regenhardt, Robert W

    2015-01-01

    The discovery of beneficial neuroprotective effects of the angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and hemorrhagic stroke has spurred interest in a more complete characterization of its mechanisms of action. Here, we summarize findings that desc......The discovery of beneficial neuroprotective effects of the angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and hemorrhagic stroke has spurred interest in a more complete characterization of its mechanisms of action. Here, we summarize findings...... that describe the protective role of the ACE2-Ang-(1-7)-Mas axis in stroke, along with a focused discussion on the potential mechanisms of neuroprotective effects of Ang-(1-7) in stroke. The latter incorporates evidence describing the actions of Ang-(1-7) to counter the deleterious effects of angiotensin II...... complete understanding of the mechanisms of action of Ang-(1-7) to elicit neuroprotection will serve as an essential step toward research into potential targeted therapeutics in the clinical setting....

  18. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the Sephora shop (sells perfume, beauty products etc.) in Val Thoiry all year round. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * next “vente privée” from 21st November to 1st December 2012 Please contact the Staff Association Secretariat to get the discount voucher.

  19. Key technologies for expeditions to Mars.

    Science.gov (United States)

    French, J. R., Jr.

    A round-trip manned Mars landing mission, while difficult, is within the realm of today's technology. However, better understood and more practical advanced technologies offer promising improvements in mass performance, and some also enhance certain aspects of self-reliance for manned missions.

  20. 17 CFR 249.501a - Form BDW, notice of withdrawal from registration as broker-dealer pursuant to § 240.15b6-1, § 240...

    Science.gov (United States)

    2010-04-01

    ... withdrawal, except for social security account numbers, disclosure of which is voluntary. The information... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form BDW, notice of withdrawal... Offers § 249.501a Form BDW, notice of withdrawal from registration as broker-dealer pursuant to § 240...

  1. The role of Th1 and Th17 cells in glomerulonephritis.

    Science.gov (United States)

    Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2015-04-01

    T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.

  2. 17th Symposium of NEDO projects. Industrial technology subcommittee; Sangyo gijutsu bunkakai. Dai 17 kai jigyo hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Described herein are the reports presented to the industrial technology subcommittee, 17th symposium of NEDO projects. For development of high-efficiency industrial furnaces by high-temperature air combustion (including regenerative combustion), high-temperature air above 1000 degrees C is used, where carbon dioxide and NOX are possibly abated by 30% or more and 50%, respectively. The worldwide development is also described. For production of high-function ceramic materials at low temperature, the soft solution process is proposed for the in-situ production of these ceramic materials from the aqueous solution without using high temperature or high energy. For example, the high-functional ceramic material can be produced in-situ on a substrate by reacting the highly active aqueous solution with the substrate by a combination of, e.g., the hydrothermal and electrochemical reactions, without needing post-treatment under heating. For the marine biological technologies, deposition of living organisms is described. A geodome is developed for utilizing very deep (50m or deeper) underground spaces. It is a dome-shaped space supported by no strut, having dimensions of 50m in diameter and 30m high not to affect the surrounding environments, e.g., underground water. The techniques for creating advanced functional materials are developed by combining, e.g., laser, plasma, ion and magnetic field in diversified manners. (NEDO)

  3. 37 CFR 1.17 - Patent application and reexamination processing fees.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Patent application and reexamination processing fees. 1.17 Section 1.17 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES General Provisions Fees...

  4. Immersion francaise precoce: Arts plastiques 1-7 (Early French Immersion: Plastic Arts for Grades 1-7).

    Science.gov (United States)

    Burt, Andy; And Others

    This curriculum guide in art education is intended for use in grades 1-7 in the early French immersion program. An introductory chapter describes the educational objectives of the art program, the role of art education in child development, general and terminal objectives, methodology, the steps in graphic evolution, and an outline of the program.…

  5. 20 CFR 655.17 - Advertising requirements.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Advertising requirements. 655.17 Section 655... States (H-2B Workers) § 655.17 Advertising requirements. All advertising conducted to satisfy the... employment which are not less favorable than those to be offered to the H-2B workers. All advertising must...

  6. 48 CFR 225.7703-3 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Evaluating offers. 225... Iraq or Afghanistan 225.7703-3 Evaluating offers. (a) Evaluate offers submitted in response to... Afghanistan, as follows: (1) If the low offer is an offer of a product or service from Iraq or Afghanistan...

  7. Somatic Embryogenesis in Coffee: The Evolution of Biotechnology and the Integration of Omics Technologies Offer Great Opportunities.

    Science.gov (United States)

    Campos, Nádia A; Panis, Bart; Carpentier, Sebastien C

    2017-01-01

    One of the most important crops cultivated around the world is coffee. There are two main cultivated species, Coffea arabica and C. canephora. Both species are difficult to improve through conventional breeding, taking at least 20 years to produce a new cultivar. Biotechnological tools such as genetic transformation, micropropagation and somatic embryogenesis (SE) have been extensively studied in order to provide practical results for coffee improvement. While genetic transformation got many attention in the past and is booming with the CRISPR technology, micropropagation and SE are still the major bottle neck and urgently need more attention. The methodologies to induce SE and the further development of the embryos are genotype-dependent, what leads to an almost empirical development of specific protocols for each cultivar or clone. This is a serious limitation and excludes a general comprehensive understanding of the process as a whole. The aim of this review is to provide an overview of which achievements and molecular insights have been gained in (coffee) somatic embryogenesis and encourage researchers to invest further in the in vitro technology and combine it with the latest omics techniques (genomics, transcriptomics, proteomics, metabolomics, and phenomics). We conclude that the evolution of biotechnology and the integration of omics technologies offer great opportunities to (i) optimize the production process of SE and the subsequent conversion into rooted plantlets and (ii) to screen for possible somaclonal variation. However, currently the usage of the latest biotechnology did not pass the stage beyond proof of potential and needs to further improve.

  8. Idaho National Engineering Laboratory Waste Area Groups 1-7 and 10 Technology Logic Diagram. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, M.C.; Meservey, R.H.; Little, M.; Ferguson, J.S.; Gilmore, M.C.

    1993-09-01

    The Idaho National Engineering Laboratory (INEL) Technology Logic Diagram (TLD) was developed to provide a decision support tool that relates Environmental Restoration (ER) and Waste Management (WM) problems at the INEL to potential technologies that can remediate these problems. The TLD identifies the research, development, demonstration, testing, and evaluation needed to develop these technologies to a state that allows technology transfer and application to an environmental restoration need. It is essential that follow-on engineering and system studies be conducted to build on the output of this project. These studies will begin by selecting the most promising technologies identified in this TLD and finding an optimum mix of technologies that will provide a socially acceptable balance between cost and risk to meet the site windows of opportunity. The TLD consists of three separate volumes: Volume I includes the purpose and scope of the TLD, a brief history of the INEL Waste Area Groups, and environmental problems they represent. A description of the TLD, definitions of terms, a description of the technology evaluation process, and a summary of each subelement, is presented. Volume II describes the overall layout and development of the TLD in logic diagram format. This section addresses the environmental restoration of contaminated INEL sites. Volume III (this volume) provides the Technology Evaluation Data Sheets (TEDS) for Environmental Restoration and Waste Management (EM) activities that are reference by a TEDS code number in Volume II. Each of these sheets represents a single logic trace across the TLD. These sheets contain more detail than provided for technologies in Volume II. Data sheets are arranged alphanumerically by the TEDS code number in the upper right corner of each sheet.

  9. Merging Technology and Emotions: Introduction to Affective Computing.

    Science.gov (United States)

    Brigham, Tara J

    2017-01-01

    Affective computing technologies are designed to sense and respond based on human emotions. This technology allows a computer system to process the information gathered from various sensors to assess the emotional state of an individual. The system then offers a distinct response based on what it "felt." While this is completely unlike how most people interact with electronics today, this technology is likely to trickle into future everyday life. This column will explain what affective computing is, some of its benefits, and concerns with its adoption. It will also provide an overview of its implication in the library setting and offer selected examples of how and where it is currently being used.

  10. Microdeletion in distal 17p13.1

    DEFF Research Database (Denmark)

    Zeesman, Susan; Kjaergaard, Susanne; Hove, Hanne Buciek

    2012-01-01

    Array comparative genomic hybridization has led to the identification of new syndromes by identifying genomic imbalances not detectable by standard karyotyping methods and by allowing correlations with physical findings. Deletions in the 17p13.1 region have been reported in patients with dysmorphic...

  11. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-08-01

    cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Th1-Th17 Ratio as a New Insight in Rheumatoid Arthritis Disease.

    Science.gov (United States)

    Bazzazi, Hadi; Aghaei, Mehrdad; Memarian, Ali; Asgarian-Omran, Hossein; Behnampour, Nasser; Yazdani, Yaghoub

    2018-02-01

    The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (pTh1 cells in RA patients were less than healthy group (pTh17/Th1 cell only in new cases of RA were more than healthy control groups (pTh1/Th17 ratio in RA patients is statistically different with healthy control group (pTh1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease.

  13. C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

    Directory of Open Access Journals (Sweden)

    Ning Ma

    Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

  14. All the Missiles Work: Technological Dislocations and Military Innovation: A Case Study in US Air Force Air-to-Air Armament, Post-World War II through Operation Rolling Thunder

    Science.gov (United States)

    2015-01-01

    to materialize. However, the failure did not diminish the American military’s obsession with technology. Eight years later, the world was offered a...exhaust plume of the MiG-17 which is about a 12-foot miss and that and, you know, five cents will get you a bad cup of coffee . Secondly, its launch...feasibility and practicality.5 For example, Edgerton noted that Hitler’s obsession with developing the technologically advanced V-2 rocket drained valuable

  15. Down-regulation of the Th1, Th17, and Th22 pathways due to anti-TNF-α treatment in psoriasis.

    Science.gov (United States)

    Luan, Li; Han, Shixin; Wang, Hua; Liu, Xiaoming

    2015-12-01

    Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis. To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response. This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α). At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines. The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 17 CFR Appendix D to Part 30 - Information That a Foreign Board of Trade Should Submit When Seeking No-Action Relief To Offer...

    Science.gov (United States)

    2010-04-01

    ... primary and secondary markets for the component equities, the liquidity of the component stocks, the... applicable, by price in the index as well as the combined weighting of the five highest-weighted stocks in... in evaluating requests by foreign boards of trade to allow the offer and sale within the United...

  17. Multiscalar approach to archaeological site formation at GaJj17, East Turkana, Kenya

    Science.gov (United States)

    Murray, B. M.; Ranhorn, K. L.; Colarossi, D.; Mavuso, S. S.; Dogandžić, T.; Ziegler, M. J.; Warren, S. L.; Braun, D. R.; Harris, J. W. K.

    2017-12-01

    Kenya's East Turkana region hosts a rich Plio­Pleistocene record of fossils, archaeological artifacts, and sedimentary features whose chronostratigraphic histories are often obscured by landscape changes from erosional events and tectonic activity. The Middle Stone Age (MSA) record of the Koobi Fora Formation (KF Fm.) has particularly been subjected to this complex depositional history, making it a sparse unit and, consequently, widely understudied. Stratigraphically located in between the maximum capping unconformity of the KF Fm.'s Chari tuff ( 1.39 Ma) and that of the Galana Boi Fm. ( 10 ka), the unit provides a unique window into understanding the Late Pleistocene of the region. The MSA surface scatters at archaeological site GaJj17 prompted further study into the site's age and depositional chronology. The GaJj17 ridge is locally distinguished by its cap of Late Pleistocene sands overlying strata containing tuffs likely of the Upper Burgi (2.0­-1.87 Ma) or KBS (1.87­-1.56 Ma) members. To investigate whether GaJj17's preservation is due to tectonic deformation, a broader scale examination of the structural geology was conducted through surveys and aerial imagery. Regions of deformation were identified and mapped to establish the geological history of the locality. Resultant observations and elevation data offer insight into regional faults at the root of prolonged structural alterations which have facilitated the unique preservation of MSA materials. Through a multiscalar approach it is possible to understand both the formation of GaJj17 and the underlying processes behind preservation and destruction in the changing landscape of the Turkana basin, enabling future identification of archaeological sites through proxies of elevation, regional stratigraphy, and fault mapping. This research was supported by IRES grants 1358178 and 1358200 from the U.S. National Science Foundation.

  18. Immersion francaise precoce: Sciences de la nature 1-7 (Early French Immersion: Natural Sciences for Grades 1-7).

    Science.gov (United States)

    Burt, Andy; And Others

    This curriculum guide for the natural sciences is intended for use in grades 1-7 in the early French immersion program. The guide presents the following topics: (1) a list of general objectives; (2) a list of simple skills for children aged 5-8 and for children aged 8-12; (3) activities dealing with matter and its properties, space-time, and human…

  19. 47 CFR 17.17 - Existing structures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Existing structures. 17.17 Section 17.17... STRUCTURES Federal Aviation Administration Notification Criteria § 17.17 Existing structures. (a) The requirements found in § 17.23 relating to painting and lighting of antenna structures shall not apply to those...

  20. 33 CFR 5.37 - Offer of facilities.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Offer of facilities. 5.37 Section... GUARD AUXILIARY § 5.37 Offer of facilities. Any member of the Auxiliary desiring to place a vessel... in such communication which facility is offered. Except in emergencies, an offer to the Coast Guard...

  1. 47 CFR 17.1 - Basis and purpose.

    Science.gov (United States)

    2010-10-01

    ... antenna structure owners. The standards are referenced from two Federal Aviation Administration (FAA... STRUCTURES General Information § 17.1 Basis and purpose. (a) The rules in this part are issued pursuant to the authority contained in Title III of the Communications Act of 1934, as amended, which vest...

  2. Angiotensin-(1-7) attenuates hyposmolarity-induced ANP secretion via the Na+-K+ pump.

    Science.gov (United States)

    Shah, Amin; Oh, Young-Bin; Shan, Gao; Song, Chang Ho; Park, Byung-Hyun; Kim, Suhn Hee

    2010-09-01

    The alteration in osmolarity challenges cell volume regulation, a vital element for cell survival. Hyposmolarity causes an increase in cell volume. Recently, it has been reported that the renin-angiotensin system (RAS) plays a role in cell volume regulation. We investigated the effect of angiotensin-(1-7) [Ang-(1-7)] on hyposmolarity-induced atrial natriuretic peptide (ANP) secretion in normal and diabetic (DM) rat atria and modulation of the effect of Ang-(1-7) by the Na(+)-K(+) pump. Using isolated control rat atria, we observed that perfusion of hyposmotic solution into the atria increased ANP secretion. When Ang-(1-7) [0.1 microM or 1 microM] was perfused in a hyposmolar solution, it decreased the hyposmolarity-induced ANP secretion in a dose-dependent manner. This effect of Ang-(1-7) could be mediated by the Na(+)-K(+) pump, since ouabain, an Na(+)-K(+) pump inhibitor, significantly decreased the effect of Ang-(1-7) on hyposmolarity-induced ANP secretion. In contrast, N(omega) Nitro-l-arginine methyl ester hydrochloride (l-NAME) did not modify the effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion. Interestingly, the ANP secretion was increased robustly by the perfusion of the hyposmolar solution in the DM atria, as compared to the control atria. However, the inhibitory effect of Ang-(1-7) on the hyposmolarity-induced ANP secretion was not observed in the DM atria. In the DM atria, atrial contractility was significantly increased. Taken together, we concluded that Ang-(1-7) attenuated hyposmolarity-induced ANP secretion via the Na(+)-K(+) pump and a lack of Ang-(1-7) response in DM atria may partly relate to change in Na(+)-K(+) pump activity. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Design of a MCoTI-Based Cyclotide with Angiotensin (1-7-Like Activity

    Directory of Open Access Journals (Sweden)

    Teshome Aboye

    2016-01-01

    Full Text Available We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7 (AT1-7, the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.

  4. 48 CFR 25.503 - Group offers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Group offers. 25.503... PROGRAMS FOREIGN ACQUISITION Evaluating Foreign Offers-Supply Contracts 25.503 Group offers. (a) If the solicitation or an offer specifies that award can be made only on a group of line items or on all line items...

  5. Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and Indirect Reductive Activity.

    Science.gov (United States)

    Granato, Daniela C; E Costa, Rute A P; Kawahara, Rebeca; Yokoo, Sami; Aragão, Annelize Z; Domingues, Romênia R; Pauletti, Bianca A; Honorato, Rodrigo V; Fattori, Juliana; Figueira, Ana Carolina M; Oliveira, Paulo S L; Consonni, Silvio R; Fernandes, Denise; Laurindo, Francisco; Hansen, Hinrich P; Paes Leme, Adriana F

    2018-02-27

    A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1 K72A and catalytic site mutant Trx-1 C32/35S rescued ADAM17 activity, although the interaction with Trx-1 C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1 C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1 K72A mutant showed similar oxidant levels to Trx-1 C32/35S , even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. This unexpected Trx-1 K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass

  6. Financial Technology: Blockchain - Down to Earth

    OpenAIRE

    Demary, Markus; Demary, Vera

    2017-01-01

    The blockchain technology offers the promise to be cheaper, faster, less error-prone and safer compared to traditional financial services. Whether a market for blockchain services will emerge, depends, however, on several criteria.

  7. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offers for our members       Go Sport in Val Thoiry is offering 15% discount on all purchases made in the shop upon presentation of the Staff Association membership card (excluding promotions, sale items and bargain corner, and excluding purchases using Go Sport  and Kadéos gift cards. Only one discount can be applied to each purchase).  

  8. Glosario de Tecnologia Educativa. Monografia No. 1 (Glossary of Educational Technology. Monograph No. 1).

    Science.gov (United States)

    Chadwick, Clifton; Rojas, Alicia Mabel

    This glossary offers definitions of almost 600 terms normally associated with the field of educational technology in brief and easy-to-understand form, all in Spanish (a Portugese version exists). The terms are organized into six major areas: learning, communications, instructional design, evaluation, media production, and systems theory. (Author)

  9. 17 bit 4.35 mW 1 kHz Delta Sigma ADC and 256-to-1 multiplexer for remote handling instrumentation equipment

    Energy Technology Data Exchange (ETDEWEB)

    Verbeeck, Jens, E-mail: jens.verbeeck@esat.kuleuven.be [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); KH Kempen University College, IBW-RELIC, Kleinhoefstraat 4, 2440 Geel (Belgium); Van Uffelen, Marco [Fusion for Energy, c/Josep, n° 2, Torres Diagonal Litoral, Ed. B3, 08019 Barcelona (Spain); Steyaert, Michiel [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); Leroux, Paul [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); KH Kempen University College, IBW-RELIC, Kleinhoefstraat 4, 2440 Geel (Belgium)

    2013-10-15

    Highlights: ► We present a radiation hard 17 bit-1 kHz 4.35 mW Delta Sigma ADC. ► A radiation tolerant 256-to-1 multiplexer is shown. ► We propose a generic radiation tolerant ASIC for use in an instrumentation link. ► The ASIC can interface more than hundred pressure or resistive sensors. ► All building blocks have a simulated radiation tolerance of more than 1 MGy. -- Abstract: A radiation tolerant Delta-Sigma Analog-to-Digital Converter (ADC) and multiplexer is presented. The design features a 1.5 V, 17 bit ADC consuming 4.35 mW at a sample frequency of 1 MHz. The ADC features a bandwidth of 1 kHz and utilizes a Correlated Double Sampling technique (CDS) to remove offset and 1/f noise. The circuit maintains its 17 bit resolution upon a simulated radiation dose exceeding 1 MGy and varying temperatures between 0 °C and 85 °C. Next a multiplexer is presented. It can multiplex 256 channels at a clock frequency of 128 MHz or has a data throughput of 256 MSample/s. In addition the bit period of the multiplexer varies less then 1.5% due to the influence of temperature or radiation, which proves the temperature and radiation tolerance.

  10. Enhanced activity of an angiotensin-(1-7) neuropeptidase in glucocorticoid-induced fetal programming.

    Science.gov (United States)

    Marshall, Allyson C; Shaltout, Hossam A; Pirro, Nancy T; Rose, James C; Diz, Debra I; Chappell, Mark C

    2014-02-01

    We previously identified angiotensin converting enzyme (ACE) and an endopeptidase activity that degraded angiotensin-(1-7) [Ang-(1-7)] to Ang-(1-5) and Ang-(1-4), respectively, in the cerebrospinal fluid (CSF) of 6-month old male sheep. The present study undertook a more comprehensive analysis of the CSF peptidase that converts Ang-(1-7) to Ang-(1-4) in control and in utero betamethasone-exposed sheep (BMX). Characterization of the Ang-(1-7) peptidase revealed that the thiol agents 4-aminophenylmercuric acetate (APMA) and p-chloromercuribenzoic acid (PCMB), as well as the metallo-chelators o-phenanthroline and EDTA essentially abolished the enzyme activity. Additional inhibitors for serine, aspartyl, and cysteine proteases, as well as selective inhibitors against the endopeptidases neprilysin, neurolysin, prolyl and thimet oligopeptidases did not attenuate enzymatic activity. Competition studies against the peptidase revealed similar IC50s for Ang-(1-7) (5μM) and Ang II (3μM), but lower values for Ala(1)-Ang-(1-7) and Ang-(2-7) of 1.8 and 2.0μM, respectively. In contrast, bradykinin exhibited a 6-fold higher IC50 (32μM) than Ang-(1-7) while neurotensin was a poor competitor. Mean arterial pressure (78±1 vs. 94±2mmHg, N=4-5, Pfetal programming. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.

    LENUS (Irish Health Repository)

    White, Mary

    2012-02-01

    INTRODUCTION: The occurrence of severe sepsis may be associated with deficient pro-inflammatory cytokine production. Transforming growth factor beta-1 (TGFbeta-1) predominantly inhibits inflammation and may simultaneously promote IL-17 production. Interleukin-17 (IL-17) is a recently described pro-inflammatory cytokine, which may be important in auto-immunity and infection. We investigated the hypothesis that the onset of sepsis is related to differential TGFbeta-1 and IL-17 gene expression. METHODS: A prospective observational study in a mixed intensive care unit (ICU) and hospital wards in a university hospital. Patients (59) with severe sepsis; 15 patients with gram-negative bacteraemia but without critical illness and 10 healthy controls were assayed for TGFbeta-1, IL-17a, IL-17f, IL-6 and IL-1beta mRNA in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR and serum protein levels by ELISA. RESULTS: TGFbeta-1 mRNA levels are reduced in patients with bacteraemia and sepsis compared with controls (p=0.02). IL-6 mRNA levels were reduced in bacteraemic patients compared with septic patients and controls (p=0.008). IL-1beta mRNA levels were similar in all groups, IL-17a and IL-17f mRNA levels are not detectable in peripheral blood mononuclear cells. IL-6 protein levels were greater in patients with sepsis than bacteraemic and control patients (p<0.0001). Activated TGFbeta-1 and IL-17 protein levels were similar in all groups. IL-1beta protein was not detectable in the majority of patients. CONCLUSIONS: Down regulation of TGFbeta-1 gene transcription was related to the occurrence of infection but not the onset of sepsis. Interleukin-17 production in PBMC may not be significant in the human host response to infection.

  12. Deformation mechanism in LiF single crystals at 1.7 to 330 K

    International Nuclear Information System (INIS)

    Niaz, S.; Butt, M.Z.

    1999-01-01

    The experimental data appertaining to the influence of temperature on the critical resolved shear stress (CRSS) of LiF ionic single crystals containing 10/sup -3/ wt% of divalent metal impurities in the range 1.7 to 330 K have been analyzed within the framework of the kink-pair nucleation (KPN) model of plastic flow in crystalline materials. The CRSS-T data when plotted in log-linear coordinates exhibit three distinct regions represented by straight lines of different slopes. In the temperature range 1.7 to 90 K, the CRSS 6 determined primarily by the stress-assisted thermally-activated escape of screw dislocations trapped in the Peierls troughs. At temperatures between 90 and 260 K, the rate process of plastic deformation is unpinning of edge-dislocation segments from short was rows of randomly dispersed point defects, e.g. residual metal impurities atoms, divalent metal ion-vacancy dipoles, induced defects formed during the pre-yield stage etc. 4. However, at higher temperatures up to 330 K, the CRSS decreases rapidly with rise in temperature, probably due to the mobility of the point defects referred to, and the KPN model becomes inapplicable. (author)

  13. Technologies Assessing Limb Bradykinesia in Parkinson's Disease.

    Science.gov (United States)

    Hasan, Hasan; Athauda, Dilan S; Foltynie, Thomas; Noyce, Alastair J

    2017-01-01

    The MDS-UPDRS (Movement Disorders Society - Unified Parkinson's Disease Rating Scale) is the most widely used scale for rating impairment in PD. Subscores measuring bradykinesia have low reliability that can be subject to rater variability. Novel technological tools can be used to overcome such issues. To systematically explore and describe the available technologies for measuring limb bradykinesia in PD that were published between 2006 and 2016. A systematic literature search using PubMed (MEDLINE), IEEE Xplore, Web of Science, Scopus and Engineering Village (Compendex and Inspec) databases was performed to identify relevant technologies published until 18 October 2016. 47 technologies assessing bradykinesia in PD were identified, 17 of which offered home and clinic-based assessment whilst 30 provided clinic-based assessment only. Of the eligible studies, 7 were validated in a PD patient population only, whilst 40 were tested in both PD and healthy control groups. 19 of the 47 technologies assessed bradykinesia only, whereas 28 assessed other parkinsonian features as well. 33 technologies have been described in additional PD-related studies, whereas 14 are not known to have been tested beyond the pilot phase. Technology based tools offer advantages including objective motor assessment and home monitoring of symptoms, and can be used to assess response to intervention in clinical trials or routine care. This review provides an up-to-date repository and synthesis of the current literature regarding technology used for assessing limb bradykinesia in PD. The review also discusses the current trends with regards to technology and discusses future directions in development.

  14. Wind offering in energy and reserve markets

    DEFF Research Database (Denmark)

    Soares, Tiago; Pinson, Pierre; Morais, Hugo

    2016-01-01

    The increasing penetration of wind generation in power systems to fulfil the ambitious European targets will make wind power producers to play an even more important role in the future power system. Wind power producers are being incentivized to participate in reserve markets to increase...... their revenue, since currently wind turbine/farm technologies allow them to provide ancillary services. Thus, wind power producers are to develop offering strategies for participation in both energy and reserve markets, accounting for market rules, while ensuring optimal revenue. We consider a proportional...... offering strategy to optimally decide upon participation in both markets by maximizing expected revenue from day-ahead decisions while accounting for estimated regulation costs for failing to provide the services. An evaluation of considering the same proportional splitting of energy and reserve in both...

  15. Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

    Science.gov (United States)

    Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

    2015-02-05

    Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 17 CFR 240.16c-1 - Brokers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Brokers. 240.16c-1 Section 240... Act of 1934 Exemption of Certain Transactions from Section 16(c) § 240.16c-1 Brokers. Any transaction... a broker of an order for an account in which the broker has no direct or indirect interest. ...

  17. 27 CFR 17.131 - Formulas on TTB Form 5154.1.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formulas on TTB Form 5154.1. 17.131 Section 17.131 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... preparations, food products, flavors, flavoring extracts, or perfume which are unfit for beverage purposes and...

  18. Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

    Science.gov (United States)

    Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

    2016-04-01

    Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Jae-Hoon Chang

    Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

  20. Next generation DIRCM for 2.1-2.3 micron wavelength based on direct-diode GaSb technology

    Science.gov (United States)

    Dvinelis, Edgaras; Naujokaitė, Greta; Greibus, Mindaugas; Trinkūnas, Augustinas; Vizbaras, Kristijonas; Vizbaras, Augustinas

    2018-02-01

    Continuous advances in low-cost MANPAD heat-seeking missile technology over the past 50 years remains the number one hostile threat to airborne platforms globally responsible for over 60 % of casualties. Laser based directional countermeasure (DIRCM) technology have been deployed to counter the threat. Ideally, a laser based DIRCM system must involve a number of lasers emitting at different spectral bands mimicking the spectral signature of the airborne platform. Up to now, near and mid infrared spectral bands have been covered with semiconductor laser technology and only SWIR band remained with bulky fiber laser technology. Recent technology developments on direct-diode GaSb laser technology at Brolis Semiconductors offer a replacement for the fiber laser source leading to significant improvements by few orders of magnitude in weight, footprint, efficiency and cost. We demonstrate that with careful engineering, several multimode emitters can be combined to provide a directional laser beam with radiant intensity from 10 kW/sr to 60 kW/sr in an ultra-compact hermetic package with weight < 30 g and overall efficiency of 15 % in the 2.1- 2.3 micron spectral band offering 150 times improvement in efficiency and reduction in footprint. We will discuss present results, challenges and future developments for such next-generation integrated direct diode DIRCM modules for SWIR band.

  1. 15 CFR 1300.1 - Reporting of exports of technology to nonmarket economy countries.

    Science.gov (United States)

    2010-01-01

    ... nonmarket economy countries. 1300.1 Section 1300.1 Commerce and Foreign Trade Regulations Relating to... § 1300.1 Reporting of exports of technology to nonmarket economy countries. (a) For purposes of complying... the export of technology to a nonmarket economy country, exporters of such technology shall be deemed...

  2. 17 CFR 200.30-1 - Delegation of authority to Director of Division of Corporation Finance.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Delegation of authority to Director of Division of Corporation Finance. 200.30-1 Section 200.30-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Organization and Program Management General...

  3. Sequence analysis of 17 NRXN1 deletions

    DEFF Research Database (Denmark)

    Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés

    2014-01-01

    into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism...

  4. Technology transfer: Half-way houses. No. 17

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, R.W.

    1995-05-01

    In the fall of 1993, 1 was asked by the Center for National Security Studies (CNSS) of the Los Alamos National Laboratory (LANL) to study the ways in which technology transfer and defense conversion had been accomplished at General Atomics (GA) and Science Applications International Corporation (SAIC) by interviewing Harold Agnew, who had served as director of Los Alamos before becoming president of General Atomics in 1979, and J. Robert Beyster, who had been a staff member at Los Alamos and at General Atomics before founding SAIC in 1969. Harold Agnew readily complied with my request for an interview and also suggested that I talk to Douglas Fouquet, who is in charge of public relations at General Atomics and is their unofficial historian. Robert Beyster was not available for an interview, but, through the courtesy of John C. Hopkins, a former director of CNSS, I was able to interview SAIC`s executive vice president, Donald M. Kerr, who is also a former director at Los Alamos, and Steven Rockwood, a sector vice president at SAIC who was formerly a staff member at the Laboratory Because Agnew, Kerr, and Rockwood are all familiar with LANL, as well as with their respective companies, the interviews becam exercises In comparative analyses of technology transfer. In what follows, I have tried to summarize both the interviews and some of the research which attended them. It is the historian`s hope that by use of comparative institutional analyses, Laboratory administrators may learn something of value in directing their efforts toward the transfer of technology to private industry and other government agencies.

  5. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    L'Occitane en Provence proposes the following offer: 10 % discount on all products in all L'Occitane shops in Metropolitan France upon presentation of your Staff Association membership card and a valid ID. This offer is valid only for one person, is non-transferable and cannot be combined with other promotions.

  6. Liquid-liquid extraction to lithium isotope separation based on room-temperature ionic liquids containing 2,2'-binaphthyldiyl-17-crown-5

    International Nuclear Information System (INIS)

    Sun Xiaoli; Zhou Wen; Gu Lin; Qiu Dan; Ren Donghong; Gu Zhiguo; Li Zaijun

    2015-01-01

    A novel liquid-liquid extraction system was investigated for the selective separation of lithium isotopes using ionic liquids (ILs = C 8 mim + PF 6 - , C 8 mim + BF 4 - , and C 8 mim + NTf 2 - ) as extraction solvent and 2,2'-binaphthyldiyl-17-crown-5 (BN-17-5) as extractant. The effects of the concentration of lithium salt, counter anion of lithium salt, initial pH of aqueous phase, extraction temperature, and time on the lithium isotopes separation were discussed. Under optimized conditions, the maximum single-stage separation factor α of 6 Li/ 7 Li obtained in the present study was 1.046 ± 0.002, indicating the lighter isotope 6 Li was enriched in IL phase while the heavier isotope 7 Li was concentrated in the solution phase. The formation of 1:1 complex Li(BN-17-5) + in the IL phase was determined on the basis of slope analysis method. The large value of the free energy change (-ΔG° = 92.89 J mol -1 ) indicated the high separation capability of the Li isotopes by BN-17-5/IL system. Lithium in Li(BN-17-5) + complex was stripped by 1 mol L -1 HCl solution. The extraction system offers high efficiency, simplicity, and green application prospect to lithium isotope separation. (author)

  7. Functionalized Fullerene Targeting Human Voltage-Gated Sodium Channel, hNav1.7.

    Science.gov (United States)

    Hilder, Tamsyn A; Robinson, Anna; Chung, Shin-Ho

    2017-08-16

    Mutations of hNa v 1.7 that cause its activities to be enhanced contribute to severe neuropathic pain. Only a small number of hNa v 1.7 specific inhibitors have been identified, most of which interact with the voltage-sensing domain of the voltage-activated sodium ion channel. In our previous computational study, we demonstrated that a [Lys 6 ]-C 84 fullerene binds tightly (affinity of 46 nM) to Na v Ab, the voltage-gated sodium channel from the bacterium Arcobacter butzleri. Here, we extend this work and, using molecular dynamics simulations, demonstrate that the same [Lys 6 ]-C 84 fullerene binds strongly (2.7 nM) to the pore of a modeled human sodium ion channel hNa v 1.7. In contrast, the fullerene binds only weakly to a mutated model of hNa v 1.7 (I1399D) (14.5 mM) and a model of the skeletal muscle hNa v 1.4 (3.7 mM). Comparison of one representative sequence from each of the nine human sodium channel isoforms shows that only hNa v 1.7 possesses residues that are critical for binding the fullerene derivative and blocking the channel pore.

  8. Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

    Science.gov (United States)

    Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

    2016-04-04

    Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

  9. Shaping concepts of technology : what concepts and how to shape them?

    NARCIS (Netherlands)

    Vries, de M.J.; Tamir, A.; Vries, de M.J.; Tamir, A.

    1997-01-01

    Philosophy of technology is a discipline that has much to offer for technology education. Insights into the real nature of technology and its relationship with science and society can help technology educators to build a subject that helps pupils get a good concept of technology and to learn to

  10. Trickle Down Technology: A Distance Education Approach to Professional Development.

    Science.gov (United States)

    Parker, Angie

    The Trickle Down Technology Project offered the impetus needed to change the way both K-12 and university educators capitalize on technology in the classroom. The project had three key components: the modeling of technology in the university classroom; online technology workshops; and interactive communication among inservice and preservice…

  11. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    New offers : Discover the theater Galpon in Geneva. The Staff Association is happy to offer to its members a discount of 8.00 CHF on a full-price ticket (tickets of 15.00 CHF instead of 22.00 CHF) so do not hesitate anymore (mandatory reservation by phone + 4122 321  21 76 as tickets are quickly sold out!). For further information, please see our website: http://staff-association.web.cern.ch/fr/content/th%C3%A9%C3%A2tre-du-galpon  

  12. 17th Business Report Meeting of New Energy Industrial Technology Development Organization (NEDO). Section Meeting on Solar Technology; Dai 17 kai jigyo hokokukai. Taiyo gijutsu bunkakai

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    In this section meeting, reports were made on the following themes: 1) outline of NEDO solar technology development; 2) commercialization study of thin film polycrystal solar cell production technology; 3) development of CdTe solar cell module production technology; 4) R and D of construction material monolithic solar cell modules; 5) development of the project overseas for solar energy technology development. In 1), outlined were the development of commercialization technology of photovoltaic power system, internationally joint demonstration development of photovoltaic power system, development of production facilities of solar cell use compound semiconductors, development of commercialization technology of solar system for industrial use, etc., and a large wind power system. In 2), the results of the study 'low cost Si substrate production by continuous cast method' were reported. In 3), the results were reported of the increase in efficiency and development of low cost production technology for large area modules. In 4), 3 kinds and 6 systems of R and D for house roofs and building walls were conducted, and possibilities of commercialization were obtained in terms of performance and economical efficiency as construction material. In 5), with the use of natural conditions and social systems in Nepal, Mongol, Thailand and Malaysia, the development for commercialization of this system is being made by joint research with each country. (NEDO)

  13. Technologies Assessing Limb Bradykinesia in Parkinson’s Disease

    Science.gov (United States)

    Hasan, Hasan; Athauda, Dilan S.; Foltynie, Thomas; Noyce, Alastair J.

    2017-01-01

    Background: The MDS-UPDRS (Movement Disorders Society – Unified Parkinson’s Disease Rating Scale) is the most widely used scale for rating impairment in PD. Subscores measuring bradykinesia have low reliability that can be subject to rater variability. Novel technological tools can be used to overcome such issues. Objective: To systematically explore and describe the available technologies for measuring limb bradykinesia in PD that were published between 2006 and 2016. Methods: A systematic literature search using PubMed (MEDLINE), IEEE Xplore, Web of Science, Scopus and Engineering Village (Compendex and Inspec) databases was performed to identify relevant technologies published until 18 October 2016. Results: 47 technologies assessing bradykinesia in PD were identified, 17 of which offered home and clinic-based assessment whilst 30 provided clinic-based assessment only. Of the eligible studies, 7 were validated in a PD patient population only, whilst 40 were tested in both PD and healthy control groups. 19 of the 47 technologies assessed bradykinesia only, whereas 28 assessed other parkinsonian features as well. 33 technologies have been described in additional PD-related studies, whereas 14 are not known to have been tested beyond the pilot phase. Conclusion: Technology based tools offer advantages including objective motor assessment and home monitoring of symptoms, and can be used to assess response to intervention in clinical trials or routine care. This review provides an up-to-date repository and synthesis of the current literature regarding technology used for assessing limb bradykinesia in PD. The review also discusses the current trends with regards to technology and discusses future directions in development. PMID:28222539

  14. 43 CFR 12.715 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.715 Section 12.715... Act-Supplies § 12.715 Evaluating offers. (a) Unless the head of the grantee organization or a designee at a level no lower than the grantee's designated awarding official determines otherwise, the offered...

  15. Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Julia Terhune

    2013-11-01

    Full Text Available The success of cellular immunotherapies against cancer requires the generation of activated CD4+ and CD8+ T-cells. The type of T-cell response generated (e.g., Th1 or Th2 will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17 play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for IL-17, other studies have shown an anti-tumor function. The induction of polarized T-cell responses can be regulated by dendritic cells (DCs. DCs are key regulators of the immune system with the ability to affect both innate and adaptive immune responses. These properties have led many researchers to study the use of ex vivo manipulated DCs for the treatment of various diseases, such as cancer and autoimmune diseases. While Th1/Tc1 cells are traditionally used for their potent anti-tumor responses, mounting evidence suggests Th17/Tc17 cells should be utilized by themselves or for the induction of optimal Th1 responses. It is therefore important to understand the factors involved in the induction of both type-1 and type-17 T-cell responses by DCs.

  16. A consortium approach to commercialized Westinghouse solid oxide fuel cell technology

    Science.gov (United States)

    Casanova, Allan

    Westinghouse is developing its tubular solid oxide fuel cells (SOFCs) for a variety of applications in stationary power generation markets. By pressurizing a SOFC and integrating it with a gas turbine (GT), power systems with efficiencies as high as 70-75% can be obtained. The first such system will be tested in 1998. Because of their extraordinarily high efficiency (60-70%) even in small sizes the first SOFC products to be offered are expected to be integrated SOFC/GT power systems in the 1-7 MW range, for use in the emerging distributed generation (DG) market segment. Expansion into larger sizes will follow later. Because of their modularity, environmental friendliness and expected cost effectiveness, and because of a worldwide thrust towards utility deregulation, a ready market is forecasted for baseload distributed generation. Assuming Westinghouse can complete its technology development and reach its cost targets, the integrated SOFC/GT power system is seen as a product with tremendous potential in the emerging distributed generation market. While Westinghouse has been a leader in the development of power generation technology for over a century, it does not plan to manufacture small gas turbines. However, GTs small enough to integrate with SOFCs and address the 1-7 MW market are generally available from various manufacturers. Westinghouse will need access to a new set of customers as it brings baseload plants to the present small market mix of emergency and peaking power applications. Small cogeneration applications, already strong in some parts of the world, are also gaining ground everywhere. Small GT manufacturers already serve this market, and alliances and partnerships can enhance SOFC commercialization. Utilities also serve the DG market, especially those that have set up energy service companies and seek to grow beyond the legal and geographical confines of their current regulated business. Because fuel cells in general are a new product, because small

  17. Interleukin-17 Gene Polymorphisms Contribute to Cancer Risk

    Directory of Open Access Journals (Sweden)

    Yu-Ming Niu

    2014-01-01

    Full Text Available Epidemiological studies have suggested that interleukin-17 (IL-17 polymorphisms are associated with cancer risk. However, the results of these studies are inconsistent. Therefore, we performed a meta-analysis to obtain a precise conclusion. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the association of the IL-17A rs2275913G>A and IL-17F rs763780T>C polymorphisms with cancer risk. Publication bias and sensitivity analyses were performed to ensure the statistical power. Overall, 10 relevant case-control studies involving 4,516 cases and 5,645 controls were included. The pooled ORs with 95% CIs indicated that the IL-17A rs2275913G>A polymorphism was significantly associated with increased cancer risk (for A versus G: OR = 1.28, 95% CI: 1.16–1.41, PC polymorphism was also significantly associated with gastric cancer development. Overall, the present meta-analysis suggests that IL-17 polymorphisms increase the risk of developing cancer, particularly gastric cancer, in the Asian (and Chinese population.

  18. 5 CFR 536.104 - Reasonable offer.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Reasonable offer. 536.104 Section 536.104... Provisions § 536.104 Reasonable offer. (a) For the purpose of determining whether grade retention eligibility or entitlement must be terminated under § 536.207 or 536.208, the offer of a position is a reasonable...

  19. An Introduction to XML and Web Technologies

    DEFF Research Database (Denmark)

    Møller, Anders; Schwartzbach, Michael Ignatieff

    , building on top of the early foundations. This book offers a comprehensive introduction to the area. There are two main threads of development, corresponding to the two parts of this book. XML technologies generalize the notion of data on the Web from hypertext documents to arbitrary data, including those...... that have traditionally been the realm of databases. In this book we cover the basic XML technology and the supporting technologies of XPath, DTD, XML Schema, DSD2, RELAX NG, XSLT, XQuery, DOM, JDOM, JAXB, SAX, STX, SDuce, and XACT. Web technologies build on top of the HTTP protocol to provide richer...

  20. Parental acceptability of contraceptive methods offered to their teen during a confidential health care visit.

    Science.gov (United States)

    Hartman, Lauren B; Shafer, Mary-Ann; Pollack, Lance M; Wibbelsman, Charles; Chang, Fay; Tebb, Kathleen P

    2013-02-01

    To examine parental acceptability of contraceptive methods offered confidentially to their adolescent daughter. A random sample of 261 parents/guardians with a daughter aged 12-17 years completed a telephone survey examining the relationship between parental acceptability of seven contraceptive methods and adolescents' likelihood to have sex, parenting beliefs, parents' sexual health as teens, sexually transmitted infection knowledge, and demographic factors. Acceptability was highest for oral contraceptive pills (59%) and lowest for intrauterine device (18%). Parental acceptance of teens' autonomy was significantly associated with increased acceptability of all methods. Parental knowledge of sexually transmitted infections was poor, and 51% found it acceptable for clinicians to provide their sexually active teen with condoms. Parents were more accepting of oral contraceptive pills and condoms compared with intrauterine devices and implants. Parental recognition of their teen's autonomy was associated with greater parental acceptability of clinicians providing their adolescent with contraceptives (regardless of the specific type of method being offered). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. The Value Simulation-Based Learning Added to Machining Technology in Singapore

    Science.gov (United States)

    Fang, Linda; Tan, Hock Soon; Thwin, Mya Mya; Tan, Kim Cheng; Koh, Caroline

    2011-01-01

    This study seeks to understand the value simulation-based learning (SBL) added to the learning of Machining Technology in a 15-week core subject course offered to university students. The research questions were: (1) How did SBL enhance classroom learning? (2) How did SBL help participants in their test? (3) How did SBL prepare participants for…

  2. 2006 annual nuclear technology conference Aachen

    International Nuclear Information System (INIS)

    Anon.

    2006-01-01

    This year's ANNUAL NUCLEAR TECHNOLOGY CONFERENCE (JK) was organized in Aachen by the Deutsches Atomforum e.V. (DAtF) and the Kerntechnische Gesellschaft e.V. (KTG). The attendance by more than 1,200 participants from 17 nations underlines the role of this specialized congress as one of the leading events in the field of nuclear power use. For several years in a row, the number of participants has been increasing steadily. The first conference day offered plenary presentations traditionally dealing mainly with political and economic issues of the use of nuclear power, including a presentation by the President of the DAtF. The lead countries of JK 2006 were Belgium and Finland with contributions to the plenary day and special meetings on selected topics. The traditional proven scheme of the three-day meeting offered plenary sessions on the first day, and technical sessions, topical sessions, poster sessions, and special events on the following days. The 'Nuclear Power Campus' was run most successfully for the fourth time, presenting to high school students and university freshmen the world of nuclear power in a transparent way. The special commitment to the young generation was stressed at JK 2006 also by the 'Competence Preservation in Nuclear Technology' workshop. Nearly 2 dozen young scientists used the forum to present results of their work. The meeting was accompanied by a technical exhibition with meeting points established by vendors, suppliers, and service providers. (orig.)

  3. 17 CFR 259.0-1 - Availability of forms.

    Science.gov (United States)

    2010-04-01

    ... may inspect the forms at this address and at the Commission's regional and district offices. (See... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Availability of forms. 259.0-1 Section 259.0-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) FORMS...

  4. Conditions of the potential for commercialization of the patent: the implementation of a technology public offering system technology at CNEN; Condicionantes do potencial de exploracao comercial da patente: a implantacao de um sistema de oferta publica de tecnologia na CNEN

    Energy Technology Data Exchange (ETDEWEB)

    Archila, Daniela Lima Cerqueira

    2015-07-01

    This dissertation identifies the main factors which represent the conditions for the potential commercialization of patents aiming at the implementation of a system for technology public offering at CNEN as a strategy for creating licensing opportunities to the industrial sector. The method applied refers to an exploratory case study of a patented technology selected from a sample of CNEN's patent portfolio in the biopharmaceutical sector. The case study comprehends a field research of interviews conducted with two specialists in technology and innovation management, one researcher from CNEN and a biopharmaceutical company. The results show that among the nineteen main factors - related to technology, market, business and Science and Technology Organization (STO) - the market dynamics, the potential applications of the technology and an abstract of its main benefits compared to existing technologies are the major relevant information for each technology to be included in the public offering system. Other results indicate that the evaluation of such factors may be conducted by competent professionals to bring less uncertainty and risk to the early-stage of the innovation process, as well as enhance the potential interest of a company in the technology. On the other hand, the latter requires innovation capabilities to move the technology forward – additional R&D, scale-up, manufacturing and marketing - whilst the STO needs a entrepreneurial culture that mitigates its obstacles, creates more positive solutions for its routines and processes and gives sustainability to its Technology Transfer Office (TTO) through valuing its personnel in the long term. Finally, emphasis on technological partnerships with companies can be a motivating feature for directing the STO's patent strategy to the creation of proprietary technological platforms that reflect problems experienced by the commercial environment, as well as the development of this strategic patent

  5. New offer for our members

    CERN Document Server

    Staff Association

    2018-01-01

    Evolution 2, your specialist for Outdoor Adventures Be it for a ski lesson, a parachute jump or for a mountain bike descent, come live an unforgettable experience with our outdoor specialists. Benefit from a 10 % discount on all activities: Offer is open to SA members and their family members living in the same household, upon presentation of the membership card. Offer available for all bookings made between 1 June 2018 and 30 May 2019. Offer available on all the Evoltion2 sites. A wide range of summer and winter activities. More information on http://evolution2.com/ Contact and reservation : +33 (0)4.50.02.63.35 management@evolution2.com

  6. 48 CFR 19.804-2 - Agency offering.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Agency offering. 19.804-2....804-2 Agency offering. (a) After completing its evaluation, the agency must notify the SBA of the... statement that prior to the offering no solicitation for the specific acquisition has been issued as a small...

  7. Th17 Cells Induce Dopaminergic Neuronal Death via LFA-1/ICAM-1 Interaction in a Mouse Model of Parkinson's Disease.

    Science.gov (United States)

    Liu, Zhan; Huang, Yan; Cao, Bei-Bei; Qiu, Yi-Hua; Peng, Yu-Ping

    2017-12-01

    T helper (Th)17 cells, a subset of CD4 + T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP + )-induced PD models. Blood-brain barrier (BBB) disruption in the substantia nigra (SN) was assessed by the signal of FITC-labeled albumin that was injected into blood circulation via the ascending aorta. Live cell imaging system was used to observe a direct contact of Th17 cells with neurons by staining these cells using the two adhesion molecules, leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1, respectively. Th17 cells invaded into the SN where BBB was disrupted in MPTP-induced PD mice. Th17 cells exacerbated DAergic neuronal loss and pro-inflammatory/neurotrophic factor disorders in MPP + -treated ventral mesencephalic (VM) cell cultures. A direct contact of LFA-1-stained Th17 cells with ICAM-1-stained VM neurons was dynamically captured. Either blocking LFA-1 in Th17 cells or blocking ICAM-1 in VM neurons with neutralizing antibodies abolished Th17-induced DAergic neuronal death. These results establish that Th17 cells infiltrate into the brain parenchyma of PD mice through lesioned BBB and exert neurotoxic property by promoting glial activation and importantly by a direct damage to neurons depending on LFA-1/ICAM-1 interaction.

  8. The KYxxL motif in Rad17 protein is essential for the interaction with the 9–11 complex

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Ikeuchi, Masayoshi; Nakayama, Yuji [Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414 (Japan); Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)

    2016-09-02

    ATR-dependent DNA damage checkpoint is the major DNA damage checkpoint against UV irradiation and DNA replication stress. The Rad17–RFC and Rad9–Rad1–Hus1 (9–11) complexes interact with each other to contribute to ATR signaling, however, the precise regulatory mechanism of the interaction has not been established. Here, we identified a conserved sequence motif, KYxxL, in the AAA+ domain of Rad17 protein, and demonstrated that this motif is essential for the interaction with the 9–11 complex. We also show that UV-induced Rad17 phosphorylation is increased in the Rad17 KYxxL mutants. These data indicate that the interaction with the 9–11 complex is not required for Rad17 protein to be an efficient substrate for the UV-induced phosphorylation. Our data also raise the possibility that the 9–11 complex plays a negative regulatory role in the Rad17 phosphorylation. We also show that the nucleotide-binding activity of Rad17 is required for its nuclear localization. - Highlights: • We have identified a conserved KYxxL motif in Rad17 protein. • The KYxxL motif is crucial for the interaction with the 9–11 complex. • The KYxxL motif is dispensable or inhibitory for UV-induced Rad17 phosphorylation. • Nucleotide binding of Rad17 is required for its nuclear localization.

  9. A key role of practical training in higher education: what can traineeship offer to trainee translators?

    Directory of Open Access Journals (Sweden)

    Nataša Hirci

    2016-12-01

    Full Text Available This paper gives an outline of Traineeship at the Department of Translation, University of Ljubljana, designed as a practical, hands-on experience in translation work for students. In the re-design of the study programmes at the Department of Translation in line with the Bologna Reform, compulsory Traineeship was introduced as part of the MA course in Translation/Interpreting, offering students an insight into real-life translation situations while providing employers with an impression of their prospective employees. The main objective of Traineeship is to give an added-value to the MA course, provide job opportunities and offer students a practical experience while workingwith the state-of-the-art translation technologies. The trainees can apply their knowledge obtained at the faculty to real-life translation assignments while gaining new skills and experience which combined contribute to a more efficient integration into the translation market. The paper explores the specific approaches to the implementation of Traineeship at the Department of Translation developed over the last decade, offering a model of good practice to other traineeship organizers.

  10. Analysis of the Organ Offers Received From European Union Countries Before and After the Introduction of a Dedicated Information Technology Portal: The COORENOR/FOEDUS Portal.

    Science.gov (United States)

    Peritore, D; Rizzato, L; Di Ciaccio, P; Trapani, S; Carella, C; Oliveti, A; Rizzo, A; Nanni Costa, A

    2017-05-01

    To optimize the use of nontransplantable organs in their own territory, the European Commission, as part of a project led by Italy, has promoted the use of an information technology (IT) portal, the COORENOR portal, developed by the Czech Republic in 2012, which evolved to become FOEDUS in 2015. To evaluate the impact of the portal on our reality, we analyzed the number and type of offers received and organs imported in the previous 48 months (period A) as well as the 48 months after the introduction of the portal (period B). We also examined the origin and the offer mode. The offers received were 404 and 753, respectively, in the two periods, with 315 (41.8%) organs received through the portal. The organs transplanted were 53 and 64, respectively, in the two periods; 20 (31.2%) were sent through the portal. The most commonly offered organs are lungs (36.7% and 29.3% of offers in periods A and B, respectively). The most transplanted organ is the liver (59.4% and 45% of transplants in periods A and B, respectively). The use of the portal has gradually increased, growing from 16.4% of the offer mode in 2012 to 84.7% in 2016. The increase of offers related to the increase of donations and the attitude to the sharing of resources has determined an increase of 19.2% of total transplants, especially for certain types such as pediatric transplants. The portal, ensuring speed and simultaneity of offer, real time sharing of information and transparency of allocation, is also used for trade in the International Partnership Agreements. Therefore, transplants have been conditioned by the existing agreements with Greece, Malta, and the countries of the South Transplant Alliance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 45 CFR 81.85 - Offer of proof.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Offer of proof. 81.85 Section 81.85 Public Welfare... 80 OF THIS TITLE Hearing Procedures § 81.85 Offer of proof. An offer of proof made in connection with... identification and shall accompany the record as the offer of proof. ...

  12. Specific Destruction of HIV Proviral p17 Gene in T Lymphoid Cells Achieved by the Genome Editing Technology.

    Science.gov (United States)

    Kishida, Tsunao; Ejima, Akika; Mazda, Osam

    2016-01-01

    Recent development in genome editing technologies has enabled site-directed deprivation of a nucleotide sequence in the chromosome in mammalian cells. Human immunodeficiency (HIV) infection causes integration of proviral DNA into the chromosome, which potentially leads to re-emergence of the virus, but conventional treatment cannot delete the proviral DNA sequence from the cells infected with HIV. In the present study, the transcription activator-like effector nucleases (TALENs) specific for the HIV p17 gene were constructed, and their activities to destroy the target sequence were evaluated. SSA assay showed a high activity of a pair of p17-specific TALENs. A human T lymphoid cell line, Jurkat, was infected with a lentivirus vector followed by transfection with the TALEN-HIV by electroporation. The target sequence was destructed in approximately 10-95% of the p17 polymerase chain reaction clones, and the efficiencies depended on the Jurkat-HIV clones. Because p17 plays essential roles for assembly and budding of HIV, and this gene has relatively low nucleotide sequence diversity, genome editing procedures targeting p17 may provide a therapeutic benefit for HIV infection.

  13. 17 CFR 239.0-1 - Availability of forms.

    Science.gov (United States)

    2010-04-01

    ... F Street, NE, Washington, DC 20549. Any persons may inspect the forms at this address and at the... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Availability of forms. 239.0-1 Section 239.0-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION FORMS PRESCRIBED...

  14. 17O(n,α)14C cross section from 25 meV to approximately 1 MeV

    International Nuclear Information System (INIS)

    Koehler, P.E.; Graff, S.M.

    1991-01-01

    We have measured the 17 O(n,α) 14 C cross section from thermal energy to approximately 1 MeV. A bump in the data near 3 keV could be fitted by a state whose properties are consistent with a known subthreshold J π =1 - level at E x =8.039 MeV. The cause of the 1/v cross section near thermal energy could not be determined although the known 2 + state at 8.213 MeV was found to be too narrow to contribute much to the thermal cross section. Our data are compared to measurements made via the inverse reaction. There are many differences between the two sets of data. The astrophysical reaction rate was calculated from the measured cross section. This reaction plays a role in the nucleosynthesis of heavy elements in nonstandard big-bang models. At big-bang temperatures, the experimental rate was found to be in fair agreement with the rate estimated from the previously known properties of states of 18 O in this region. Furthermore, using the available information from experiments, it was estimated that the 17 O(n,α) 14 C rate is approximately a factor of 10 3 --10 4 times larger than the 17 O(n,γ) 18 O rate at big-bang temperatures. As a result, there may be significant cycling between 14 C and 17 O resulting in a reduction of heavy-element nucleosynthesis

  15. In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

    Science.gov (United States)

    Lei, Li; Egli, Martin

    2016-04-01

    Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

  16. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    CERN was selected and participated in the ranking "Best Employers" organized by the magazine Bilan. To thank CERN for its collaboration, the magazine offers a reduction to the subscription fee for all employed members of personnel. 25% off the annual subscription: CHF 149.25 instead of CHF 199 .— The subscription includes the magazine delivered to your home for a year, every other Wednesday, as well as special editions and access to the e-paper. To benefit from this offer, simply fill out the form provided for this purpose. To get the form, please contact the secretariat of the Staff Association (Staff.Association@cern.ch).

  17. Dialectic Antidotes to Critics of the Technology Acceptance Model: Conceptual, Methodological, and Replication Treatments for Behavioural Modelling in Technology-Mediated Environments

    Directory of Open Access Journals (Sweden)

    Weng Marc Lim

    2018-01-01

    Full Text Available The technology acceptance model (TAM is a prominent and parsimonious conceptual lens that is often applied for behavioural modelling in technology-mediated environments. However, TAM has received a great deal of criticism in recent years. This article aims to address some of the most pertinent issues confronting TAM through a rejoinder that offers dialectic antidotes—in the form of conceptual, methodological, and replication treatments—to support the continued use of TAM to understand the peculiarities of user interactions with technology in technology-mediated environments. In doing so, this article offers a useful response to a common but often inadequately answered question about how TAM can continue to be relevant for behavioural modelling in contemporary technology-mediated environments.

  18. Angiotensina-(1-7 durante o processo inicial na cascata da ovulação em bovinos Angiotensin-(1-7 during the initial process of ovulatory cascade in cattle

    Directory of Open Access Journals (Sweden)

    Joabel Tonellotto dos Santos

    2012-10-01

    Full Text Available O presente estudo teve como objetivo avaliar o efeito da Ang-(1-7 e de seu receptor (MAS na regulação da ovulação. No experimento I, utilizando um modelo in vitro de cultivo de células foliculares, foi avaliado o efeito do tratamento com Ang-(1-7 ou do bloqueio do receptor MAS através do inibidor d-Ala7-Ang-(1-7 (A-779 na expressão de RNAm para epirregulina (Ereg; um marcador inicial do processo de ovulação em células da granulosa. No experimento II, foi utilizado um modelo in vivo de injeção intrafolicular no qual vinte vacas tiveram o ciclo estral sincronizado e, quando os folículos atingiram um diâmetro mínimo de 12mm, foi realizada a injeção intrafolicular de A-779 ou solução salina 0,9%. No momento da injeção intrafolicular, foi realizada uma aplicação IM de análogo de GnRH. A suplementação com Ang-(1-7 ou o bloqueio de seu receptor MAS em sistema de cultivo de células da granulosa não alteraram o padrão de expressão de RNAm para Ereg. A aplicação intrafolicular de A-779 (10-5M não bloqueou a ovulação quando realizada antes do início do pico esperado de LH (100% das vacas ovularam nos grupos A-779 e controle, sugerindo que a Ang-(1-7 não possui papel relevante no início da cascata ovulatória em bovinos.This study aimed to evaluate the effect of Ang-(1-7 and its receptor (MAS in the regulation of the ovulatory cascade. In the experiment I, the effect of Ang-(1-7 or d-Ala7-Ang-(1-7 (A-779; Ang-(1-7 antagonist on the epirregulin (Ereg; initial marker of ovulation process mRNA expression in granulosa cells was assessed using an in vitro model of follicular cell culture. In experiment II, it was used an in vivo intrafollicular injection model, in which twenty cows had their follicular waves synchronized and the ovarian follicular size was daily monitored by ultrasound. Follicles that reached a minimum diameter of 12mm were injected with A-779 or saline 0.9%. At the time of the intrafollicular injection

  19. Buffer-gas cooling of antiprotonic helium to 1.5 to 1.7 K, and antiproton-to–electron mass ratio

    CERN Document Server

    Hori, Masaki; Sótér, Anna; Barna, Daniel; Dax, Andreas; Hayano, Ryugo; Kobayashi, Takumi; Murakami, Yohei; Todoroki, Koichi; Yamada, Hiroyuki; Horváth, Dezső; Venturelli, Luca

    2016-01-01

    Charge, parity, and time reversal (CPT) symmetry implies that a particle and its antiparticle have the same mass. The antiproton-to-electron mass ratio Embedded Image can be precisely determined from the single-photon transition frequencies of antiprotonic helium. We measured 13 such frequencies with laser spectroscopy to a fractional precision of 2.5 × 10−9 to 16 × 10−9. About 2 × 109 antiprotonic helium atoms were cooled to temperatures between 1.5 and 1.7 kelvin by using buffer-gas cooling in cryogenic low-pressure helium gas; the narrow thermal distribution led to the observation of sharp spectral lines of small thermal Doppler width. The deviation between the experimental frequencies and the results of three-body quantum electrodynamics calculations was reduced by a factor of 1.4 to 10 compared with previous single-photon experiments. From this, Embedded Image was determined as 1836.1526734(15), which agrees with a recent proton-to-electron experimental value within 8 × 10−10.

  20. 17 CFR 249.0-1 - Availability of forms.

    Science.gov (United States)

    2010-04-01

    ..., 100 F Street, NE, Washington, DC 20549. Any person may inspect the forms at this address and at the... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Availability of forms. 249.0-1 Section 249.0-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) FORMS...

  1. 17 CFR 209.0-1 - Availability of forms.

    Science.gov (United States)

    2010-04-01

    ... may inspect the forms at this address and at the Commission's regional offices. (See § 200.11 of this... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Availability of forms. 209.0-1 Section 209.0-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION FORMS PRESCRIBED...

  2. 34 CFR 101.85 - Offer of proof.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Offer of proof. 101.85 Section 101.85 Education... PRACTICE AND PROCEDURE FOR HEARINGS UNDER PART 100 OF THIS TITLE Hearing Procedures § 101.85 Offer of proof. An offer of proof made in connection with an objection taken to any ruling of the presiding officer...

  3. 7 CFR 15.122 - Offer of proof.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Offer of proof. 15.122 Section 15.122 Agriculture..., Decisions and Administrative Review Under the Civil Rights Act of 1964 Hearing Procedures § 15.122 Offer of proof. An offer of proof made in connection with an objection taken to any ruling of the hearing officer...

  4. 43 CFR 4.840 - Offer of proof.

    Science.gov (United States)

    2010-10-01

    ... the Interior-Effectuation of Title VI of the Civil Rights Act of 1964 Hearing § 4.840 Offer of proof. An offer of proof made in connection with an objection taken to any ruling of the administrative law... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Offer of proof. 4.840 Section 4.840 Public...

  5. Inactivation and Augmentation of the Primary 3-Ketosteroid-Δ1- Dehydrogenase in Mycobacterium neoaurum NwIB-01: Biotransformation of Soybean Phytosterols to 4-Androstene- 3,17-Dione or 1,4-Androstadiene-3,17-Dione▿ †

    Science.gov (United States)

    Wei, Wei; Wang, Feng-qing; Fan, Shu-yue; Wei, Dong-zhi

    2010-01-01

    3-Ketosteroid-Δ1-dehydrogenase, KsdDM, was identified by targeted gene disruption and augmentation from Mycobacterium neoaurum NwIB-01, a newly isolated strain. The difficulty of separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene-3,17-dione (ADD) is a key bottleneck to the microbial transformation of phytosterols in industry. This problem was tackled via genetic manipulation of the KsdD-encoding gene. Mutants in which KsdDM was inactivated or augmented proved to be good AD(D)-producing strains. PMID:20453136

  6. Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

    Science.gov (United States)

    Brown, Chrysothemis C.; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M.; Noelle, Randolph J.

    2015-01-01

    Summary CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. PMID:25769610

  7. Fold-Back: Using Emerging Technologies to Move from Quality Assurance to Quality Enhancement

    Science.gov (United States)

    Leonard, Simon N.; Fitzgerald, Robert N.; Bacon, Matt

    2016-01-01

    Emerging technologies offer an opportunity for the development, at the institutional level, of quality processes with greater capacity to enhance learning in higher education than available through current quality processes. These systems offer the potential to extend use of learning analytics in institutional-level quality processes in addition…

  8. Introduction to Innovative Food Processing and Technology

    OpenAIRE

    Tokusoglu, Ozlem

    2015-01-01

    Consumers, the food industry and the regulatory agencies demand the innovative technologies to provide safe and stable foods. Nonthermal processing technologies offer unprecedented opportunities and challenges for the food industry to market safe, high quality health-promoting foods. Those innovative food processing is often perceived as an alternative to thermal food processing, yet there are many nonthermal preparatory unit operations as well as food processing and preservation opportunitie...

  9. 17 CFR 240.15c3-1e - Deductions for market and credit risk for certain brokers or dealers (Appendix E to 17 CFR 240...

    Science.gov (United States)

    2010-04-01

    ... credit risk for certain brokers or dealers (Appendix E to 17 CFR 240.15c3-1). 240.15c3-1e Section 240....15c3-1(c)(2)(vi) and (c)(2)(vii) and to compute deductions for credit risk pursuant to this Appendix E... the broker or dealer will use to calculate deductions for market and credit risk on those categories...

  10. CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.

    Science.gov (United States)

    Haas, Jan D; González, Frano H Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

    2009-12-01

    Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

  11. Good things come to those who wait: late first offers facilitate creative agreements in negotiation.

    Science.gov (United States)

    Sinaceur, Marwan; Maddux, William W; Vasiljevic, Dimitri; Perez Nückel, Ricardo; Galinsky, Adam D

    2013-06-01

    Although previous research has shown that making the first offer leads to a distributive advantage in negotiations, the current research explored how the timing of first offers affects the creativity of negotiation agreements. We hypothesized that making the first offer later rather than earlier in the negotiation would facilitate the discovery of creative agreements that better meet the parties' underlying interests. Experiment 1 demonstrated that compared with early first offers, late first offers facilitated creative agreements that better met the parties' underlying interests. Experiments 2a and 2b controlled for the duration of the negotiation and conceptually replicated this effect. The last two studies also demonstrated that the beneficial effect of late first offers was mediated by greater information exchange. Thus, negotiators need to consider the timing of first offers to fully capitalize on the first offer advantage. Implications for our understanding of creativity, motivated information exchange, and timing in negotiations are discussed.

  12. The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis.

    Science.gov (United States)

    Wacleche, Vanessa Sue; Landay, Alan; Routy, Jean-Pierre; Ancuta, Petronela

    2017-10-19

    The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.

  13. IL-1β promotes the differentiation of polyfunctional human CCR6+CXCR3+ Th1/17 cells that are specific for pathogenic and commensal microbes1

    Science.gov (United States)

    Duhen, Thomas; Campbell, Daniel J

    2014-01-01

    In humans, Th1/17 cells, identified by co-expression of the chemokine receptors CCR6 and CXCR3, have been proposed to be highly pathogenic in several autoimmune disorders due in part to their expression of the pro-inflammatory cytokines IL-17, IFN-γ and GM-CSF. However, their developmental requirements, relationship with “classic” Th17 and Th1 cells and physiological role in normal immune responses are not well understood. Here, we examined CCR6+CXCR3+ Th1/17 cells from healthy individuals, and found that ex vivo those cells produced the effector cytokines IL-17, IL-22 and IFN-γ in all possible combinations, and were highly responsive to both IL-12 and IL-23. Moreover, although the antigen specificity of CCR6+CXCR3+ Th1/17 cells showed substantial overlap with that of Th1 and Th17 cells, this population was enriched in cells recognizing certain extracellular bacteria and expressing the intestinal homing receptor integrin β7. Finally, we identified IL-1β as a key cytokine that renders Th17 cells sensitive to IL-12, and both cytokines together potently induced the differentiation of cells that produce IL-17, IFN-γ and GM-CSF. Therefore, interfering with IL-1β and IL-12 signaling in Th17 cells during inflammation may be a promising therapeutic approach to reduce their differentiation into “pathogenic” CCR6+CXCR3+ Th1/17 cells in patients with autoimmune diseases. PMID:24890729

  14. Innovative gas offers

    International Nuclear Information System (INIS)

    Sala, O.; Mela, P.; Chatelain, F.

    2007-01-01

    New energy offers are progressively made available as the opening of gas market to competition becomes broader. How are organized the combined offers: gas, electricity, renewable energies and energy services? What are the marketing strategies implemented? Three participants at this round table present their offer and answer these questions. (J.S.)

  15. Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

    Science.gov (United States)

    Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

    2018-01-01

    To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

  16. Availability of websites offering to sell psilocybin spores and psilocybin.

    Science.gov (United States)

    Lott, Jason P; Marlowe, Douglas B; Forman, Robert F

    2009-09-01

    This study assesses the availability of websites offering to sell psilocybin spores and psilocybin, a powerful hallucinogen contained in Psilocybe mushrooms. Over a 25-month period beginning in March 2003, eight searches were conducted in Google using the term "psilocybin spores." In each search the first 100 nonsponsored links obtained were scored by two independent raters according to standardized criteria to determine whether they offered to sell psilocybin or psilocybin spores. No attempts were made to procure the products offered for sale in order to ascertain whether the marketed psilocybin was in fact "genuine" or "counterfeit." Of the 800 links examined, 58% led to websites offering to sell psilocybin spores. Additionally, evidence that whole Psilocybe mushrooms are offered for sale online was obtained. Psilocybin and psilocybin spores were found to be widely available for sale over the Internet. Online purchase of psilocybin may facilitate illicit use of this potent psychoactive substance. Additional studies are needed to assess whether websites offering to sell psilocybin and psilocybin spores actually deliver their products as advertised.

  17. Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production.

    Science.gov (United States)

    Hakkarainen, Janne; Jokela, Heli; Pakarinen, Pirjo; Heikelä, Hanna; Kätkänaho, Laura; Vandenput, Liesbeth; Ohlsson, Claes; Zhang, Fu-Ping; Poutanen, Matti

    2015-09-01

    Hydroxysteroid (17β)-dehydrogenase type 1 (HSD17B1) catalyzes the conversion of low active 17-ketosteroids, androstenedione (A-dione) and estrone (E1) to highly active 17-hydroxysteroids, testosterone (T) and E2, respectively. In this study, the importance of HSD17B1 in ovarian estrogen production was determined using Hsd17b1 knockout (HSD17B1KO) mice. In these mice, the ovarian HSD17B enzyme activity was markedly reduced, indicating a central role of HSD17B1 in ovarian physiology. The lack of Hsd17b activity resulted in increased ovarian E1:E2 and A-dione:T ratios, but we also observed reduced progesterone concentration in HSD17B1KO ovaries. Accordingly with the altered steroid production, altered expression of Star, Cyp11a1, Lhcgr, Hsd17b7, and especially Cyp17a1 was observed. The ovaries of HSD17B1KO mice presented with all stages of folliculogenesis, while the corpus luteum structure was less defined and number reduced. Surprisingly, bundles of large granular cells of unknown origin appeared in the stroma of the KO ovaries. The HSD17B1KO mice presented with severe subfertility and failed to initiate pseudopregnancy. However, the HSD17B1KO females presented with normal estrous cycle defined by vaginal smears and normal puberty appearance. This study indicates that HSD17B1 is a key enzyme in ovarian steroidogenesis and has a novel function in initiation and stabilization of pregnancy. © FASEB.

  18. 17 CFR 240.17a-1 - Recordkeeping rule for national securities exchanges, national securities associations...

    Science.gov (United States)

    2010-04-01

    ... national securities exchanges, national securities associations, registered clearing agencies and the... Certain Stabilizing Activities § 240.17a-1 Recordkeeping rule for national securities exchanges, national...) Every national securities exchange, national securities association, registered clearing agency and the...

  19. The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis

    Directory of Open Access Journals (Sweden)

    Vanessa Sue Wacleche

    2017-10-01

    Full Text Available The T helper 17 (Th17 cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.

  20. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

    Directory of Open Access Journals (Sweden)

    Aghdas Dehghani

    2015-01-01

    Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

  1. Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

    Science.gov (United States)

    Brown, Chrysothemis C; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; Al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M; Noelle, Randolph J

    2015-03-17

    CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

    Science.gov (United States)

    Li, Xia; Wang, Bin; Li, Yuzhu; Wang, Li; Zhao, Xiangzhong; Zhou, Xianbin; Guo, Yuqi; Jiang, Guosheng; Yao, Chengfang

    2013-01-09

    The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17

  3. Human Blood CD1c+ Dendritic Cells Promote Th1 and Th17 Effector Function in Memory CD4+ T Cells.

    Science.gov (United States)

    Leal Rojas, Ingrid M; Mok, Wai-Hong; Pearson, Frances E; Minoda, Yoshihito; Kenna, Tony J; Barnard, Ross T; Radford, Kristen J

    2017-01-01

    Dendritic cells (DC) initiate the differentiation of CD4 + helper T cells into effector cells including Th1 and Th17 responses that play an important role in inflammation and autoimmune disease pathogenesis. In mice, Th1 and Th17 responses are regulated by different conventional (c) DC subsets, with cDC1 being the main producers of IL-12p70 and inducers of Th1 responses, while cDC2 produce IL-23 to promote Th17 responses. The role that human DC subsets play in memory CD4 + T cell activation is not known. This study investigated production of Th1 promoting cytokine IL-12p70, and Th17 promoting cytokines, IL-1β, IL-6, and IL-23, by human blood monocytes, CD1c + DC, CD141 + DC, and plasmacytoid DC and examined their ability to induce Th1 and Th17 responses in memory CD4 + T cells. Human CD1c + DC produced IL-12p70, IL-1β, IL-6, and IL-23 in response to R848 combined with LPS or poly I:C. CD141 + DC were also capable of producing IL-12p70 and IL-23 but were not as proficient as CD1c + DC. Activated CD1c + DC were endowed with the capacity to promote both Th1 and Th17 effector function in memory CD4 + T cells, characterized by high production of interferon-γ, IL-17A, IL-17F, IL-21, and IL-22. These findings support a role for CD1c + DC in autoimmune inflammation where Th1/Th17 responses play an important role in disease pathogenesis.

  4. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  5. 17 CFR 201.240 - Settlement.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Settlement. 201.240 Section... of Practice Initiation of Proceedings and Prehearing Rules § 201.240 Settlement. (a) Availability... party to a proceeding already instituted, may, at any time, propose in writing an offer of settlement...

  6. Engineering Technology Showcase to feature high-tech products from 18 companies

    OpenAIRE

    Gilbert, Karen

    2007-01-01

    The Student Technology Council (STC) at Virginia Tech is sponsoring an Engineering Technology Showcase on Tuesday, March 27. In addition to providing a platform for technology companies to show off their most recent innovations, technology presentations will be offered by Virginia Tech faculty and staff on topics ranging from a virtual greenhouse to the System X supercomputer.

  7. Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

    Science.gov (United States)

    Bonomo, Silvia; Hansen, Cecilie H.; Petrunak, Elyse M.; Scott, Emily E.; Styrishave, Bjarne; Jørgensen, Flemming Steen; Olsen, Lars

    2016-07-01

    Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells.

  8. Too good to be true: rhesus monkeys react negatively to better-than-expected offers.

    Directory of Open Access Journals (Sweden)

    Emily J Knight

    Full Text Available To succeed in a dynamically changing world, animals need to predict their environments. Humans, in fact, exhibit such a strong desire for consistency that one of the most well-established findings in social psychology is the effort people make to maintain consistency among their beliefs, attitudes, and behavior. However, displeasure with unpredictability leads to a potential paradox, because a positive outcome that exceeds one's expectations often leads to increased subjective value and positive affect, not the opposite. We tested the hypothesis that two evolutionarily-conserved evaluation processes underlie goal-directed behavior: (1 consistency, concerned with prediction errors, and (2 valuation, concerned with outcome utility. Rhesus monkeys (Macaca mulatta viewed a food item and then were offered an identical, better, or worse food, which they could accept or reject. The monkeys ultimately accepted all offers, attesting to the influence of the valuation process. However, they were slower to accept the unexpected offers, and they exhibited aversive reactions, especially to the better-than-expected offers, repeatedly turning their heads and looking away before accepting the food item. Our findings (a provide evidence for two separable evaluation processes in primates, consistency and value assessment, (b reveal a direct relationship between consistency assessment and emotional processes, and (c show that our wariness with events that are much better than expected is shared with other social primates.

  9. Improving Chemistry Education by Offering Salient Technology Training to Preservice Teachers: A Graduate-Level Course on Using Software to Teach Chemistry

    Science.gov (United States)

    Tofan, Daniel C.

    2009-01-01

    This paper describes an upper-level undergraduate and graduate-level course on computers in chemical education that was developed and offered for the first time in Fall 2007. The course provides future chemistry teachers with exposure to current software tools that can improve productivity in teaching, curriculum development, and education…

  10. Annotation Method (AM): SE17_AM1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available abase search. Peaks with no hit to these databases are then selected to secondary s...earch using exactMassDB and Pep1000 databases. After the database search processes, each database hits are m...SE17_AM1 PowerGet annotation A1 In annotation process, KEGG, KNApSAcK and LipidMAPS are used for primary dat

  11. Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.

    Science.gov (United States)

    Abimannan, Thiruvaimozhi; Peroumal, Doureradjou; Parida, Jyoti R; Barik, Prakash K; Padhan, Prasanta; Devadas, Satish

    2016-10-01

    Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4 + T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet. Interestingly, in both the subsets, PB increased the expression of IL-4 by enhancing reactivation induced ERK1/2 phosphorylation. We further investigated the cytokine modulatory effect of PB on CD4 + T cells isolated from PBMCs of patients with Rheumatoid Arthritis, a well-known Th17 and or Th1 mediated disease. In human CD4 + T cells from Rheumatoid Arthritis patients, PB reduced the frequencies of IL-17A + (Th17), IFN - γ + (Th1) and IL-17A + /IFN - γ + (Th17/1) cells and also inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. N-Acetyl Cysteine (NAC) an antioxidant completely reversed PB mediated cytokine modulatory effects in both mouse and human cells indicating a direct role for ROS. Together our data suggest that oxidative microenvironment can alter cytokine response of terminally differentiated cells and thus altering intracellular ROS could be a potential way to target Th17 and Th1 cells in autoimmune disorders. Copyright © 2016. Published by Elsevier Inc.

  12. Water Technology Lecture 1: Introducing Water Technology

    OpenAIRE

    Gray, Nicholas Frederick

    2017-01-01

    This is a full set of PowerPoint lectures for a course in Water Technology currently given at Trinity College, University of Dublin by professor N.F. Gray. The lectures cover all aspects of water and wastewater treatment and are available for use to lecturers or those interested in the subject. The lecture series is to be used in conjunction with the new textbook ?Water Science and Technology? (4th edition) published by CRC Press in 2017. Lecture 1 is an introduction to the water indust...

  13. Special offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions. TPG: reduced rates on annual transport passes for active and retired staff. Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret. FNAC: 5% reduction on FNAC vouchers. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  14. Photon technology. Hard photon technology; Photon technology. Hard photon gijutsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    For the application of photon to industrial technologies, in particular, a hard photon technology was surveyed which uses photon beams of 0.1-200nm in wavelength. Its features such as selective atom reaction, dense inner shell excitation and spacial high resolution by quantum energy are expected to provide innovative techniques for various field such as fine machining, material synthesis and advanced inspection technology. This wavelength region has been hardly utilized for industrial fields because of poor development of suitable photon sources and optical devices. The developmental meaning, usable time and issue of a hard photon reduction lithography were surveyed as lithography in ultra-fine region below 0.1{mu}m. On hard photon analysis/evaluation technology, the industrial use of analysis, measurement and evaluation technologies by micro-beam was viewed, and optimum photon sources and optical systems were surveyed. Prediction of surface and surface layer modification by inner shell excitation, the future trend of this process and development of a vacuum ultraviolet light source were also surveyed. 383 refs., 153 figs., 17 tabs.

  15. Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene.

    Science.gov (United States)

    Goupil, Mathieu; Cousineau-Côté, Vincent; Aumont, Francine; Sénéchal, Serge; Gaboury, Louis; Hanna, Zaher; Jolicoeur, Paul; de Repentigny, Louis

    2014-10-26

    The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1. Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection. These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.

  16. 17 CFR 200.1 - General statement and statutory authority.

    Science.gov (United States)

    2010-04-01

    ...) Investigation of securities frauds, manipulations, and other violations, and the imposition and enforcement of... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false General statement and statutory authority. 200.1 Section 200.1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE...

  17. Pollution Reduction Technology Program, Turboprop Engines, Phase 1

    Science.gov (United States)

    Anderson, R. D.; Herman, A. S.; Tomlinson, J. G.; Vaught, J. M.; Verdouw, A. J.

    1976-01-01

    Exhaust pollutant emissions were measured from a 501-D22A turboprop engine combustor and three low emission combustor types -- reverse flow, prechamber, and staged fuel, operating over a fuel-air ratio range of .0096 to .020. The EPAP LTO cycle data were obtained for a total of nineteen configurations. Hydrocarbon emissions were reduced from 15.0 to .3 lb/1000 Hp-Hr/cycle, CO from 31.5 to 4.6 lb/1000 Hp-Hr/cycle with an increase in NOx of 17 percent, which is still 25% below the program goal. The smoke number was reduced from 59 to 17. Emissions given here are for the reverse flow Mod. IV combustor which is the best candidate for further development into eventual use with the 501-D22A turboprop engine. Even lower emissions were obtained with the advanced technology combustors.

  18. Depolarized Inactivation Overcomes Impaired Activation to Produce DRG Neuron Hyperexcitability in a Nav1.7 Mutation in a Patient with Distal Limb Pain

    NARCIS (Netherlands)

    Huang, J.; Yang, Y; Dib-Hajj, S.D.; Es, M. van; Zhao, P.; Salomon, J.; Drenth, J.P.; Waxman, S.G.

    2014-01-01

    Sodium channel Nav1.7, encoded by SCN9A, is expressed in DRG neurons and regulates their excitability. Genetic and functional studies have established a critical contribution of Nav1.7 to human pain disorders. We have now characterized a novel Nav1.7 mutation (R1279P) from a female human subject

  19. Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory.

    Science.gov (United States)

    Lazaroni, Thiago L N; Raslan, Ana Cláudia S; Fontes, Walkiria R P; de Oliveira, Marilene L; Bader, Michael; Alenina, Natalia; Moraes, Márcio F D; Dos Santos, Robson A; Pereira, Grace S

    2012-01-01

    It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. MAP17 and SGLT1 protein expression levels as prognostic markers for cervical tumor patient survival.

    Directory of Open Access Journals (Sweden)

    Marco Perez

    Full Text Available MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types.

  1. Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation.

    Science.gov (United States)

    Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

    2016-12-20

    Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner. Moreover, arctigenin was recognized to be an agonist of ERβ, which could bind to ERβ with a moderate affinity, promote dissociation of ERβ/HSP90 complex and nuclear translocation and phosphorylation of ERβ, and increase the transcription activity. Following activation of ERβ, arctigenin inhibited the activity of mTORC1 by disruption of ERβ-raptor-mTOR complex assembly. Deficiency of ERβ markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ERβ, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ERβ might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.

  2. Parametric Cost and Schedule Modeling for Early Technology Development

    Science.gov (United States)

    2018-04-02

    Research NoteNational Security Rep rt PARAMETRIC MODELING FOR EARLY TECHNOLOGY DEVELOPMENT COST AND SCHEDULE Chuck...Alexander NSR_11x17_Cover_CostModeling_v8.indd 1 11/20/17 3:15 PM PARAMETRIC COST AND SCHEDULE MODELING FOR EARLY  TECHNOLOGY DEVELOPMENT Chuck...COST AND SCHEDULE MODELING FOR EARLY  TECHNOLOGY DEVELOPMENT iii Contents Figures

  3. Idaho National Engineering Laboratory waste area groups 1--7 and 10 Technology Logic Diagram

    International Nuclear Information System (INIS)

    O'Brien, M.C.; Meservey, R.H.; Little, M.; Ferguson, J.S.; Gilmore, M.C.

    1993-09-01

    The Technology Logic Diagram was developed to provide technical alternatives for environmental restoration projects at the Idaho National Engineering Laboratory. The diagram (three volumes) documents suggested solutions to the characterization, retrieval, and treatment phases of cleanup activities at contaminated sites within 8 of the laboratory's 10 waste area groups. Contaminated sites at the laboratory's Naval Reactor Facility and Argonne National Laboratory-West are not included in this diagram

  4. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

    Science.gov (United States)

    van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

    2018-05-01

    Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

  5. 14 CFR 16.231 - Offer of proof.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Offer of proof. 16.231 Section 16.231... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.231 Offer of proof. A party whose evidence has been excluded by a ruling of the hearing officer may offer the evidence on the record...

  6. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

    Directory of Open Access Journals (Sweden)

    Yiangou Yiangos

    2010-06-01

    Full Text Available Abstract Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS, considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5 and controls (n = 12, and the other patients with BMS (n = 7 and controls (n = 10. BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS. Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS.

  7. Sodium channel Nav1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome

    Science.gov (United States)

    2010-01-01

    Background Voltage gated sodium channels Nav1.7 are involved in nociceptor nerve action potentials and are known to affect pain sensitivity in clinical genetic disorders. Aims and Objectives To study Nav1.7 levels in dental pulpitis pain, an inflammatory condition, and burning mouth syndrome (BMS), considered a neuropathic orofacial pain disorder. Methods Two groups of patients were recruited for this study. One group consisted of patients with dental pulpitis pain (n = 5) and controls (n = 12), and the other patients with BMS (n = 7) and controls (n = 10). BMS patients were diagnosed according to the International Association for the Study of Pain criteria; a pain history was collected, including the visual analogue scale (VAS). Immunohistochemistry with visual intensity and computer image analysis were used to evaluate levels of Nav1.7 in dental pulp tissue samples from the dental pulpitis group, and tongue biopsies from the BMS group. Results There was a significantly increased visual intensity score for Nav1.7 in nerve fibres in the painful dental pulp specimens, compared to controls. Image analysis showed a trend for an increase of the Nav1.7 immunoreactive % area in the painful pulp group, but this was not statistically significant. When expressed as a ratio of the neurofilament % area, there was a strong trend for an increase of Nav1.7 in the painful pulp group. Nav1.7 immunoreactive fibres were seen in abundance in the sub-mucosal layer of tongue biopsies, with no significant difference between BMS and controls. Conclusion Nav1.7 sodium channel may play a significant role in inflammatory dental pain. Clinical trials with selective Nav1.7 channel blockers should prioritise dental pulp pain rather than BMS. PMID:20529324

  8. GeoguideRome, urban geotourism offer powered by mobile application technology

    Science.gov (United States)

    Pica, Alessia; Grangier, Lucien; Reynard, Emmanuel; Kaiser, Christian; Del Monte, Maurizio

    2016-04-01

    educate the users to the links existing between geology/geomorphology and Man (History and Legends). The itinerary develops in 9 stops, represented on the city map and geolocalized; a list of the stops allows the access to the contents and the illustrations. Each stop illustrates its related themes through a set of corresponding icons. The mobile applications Geoguide (igd.unil.ch/geoguide/) have several strenghts : • Accessible online, as a website, they allow the users to add advanced contents and to organize the city visit at home or to re-experience it after the trip; •They are usable on any kind of device (smartphones, tablets, computers) and in its stand-alone mobile app version do not require any Internet connection, making them easily accessible to anyone; •They do not have any impact on the field, such as panels or signs on the sites for which autorizations can be difficult to obtain in urban environments; •They allow the tourism sector to increase the tourist offer of a city with naturalistic contents, often neglected in the context of cultural tourism. References Del Monte M., Fredi P., Pica A., Vergari F. (2013). Geosites within Rome City center (Italy): a mixture of cultural and geomorphological heritage. Geogr. Fis.Din. Quat., 36, 241-257, DOI 10.4461/GFDQ.2013.36.. Kenteris M., Gavalas D., Economous D. ( 2011). Electronic mobile guides : a survey. Pers. Ubiquit. Comput., 15(1), 97-11. Pica A., Vergari F., Fredi P., Del Monte M. (2015). The Aeterna Urbs Geomorphological Heritage (Rome, Italy). Geoheritage, DOI 10.1007/s12371-015-0150-3. Reynard E., Kaiser C., Martin S., Regolini G. (2015). An application for Geosciences communication by smartphones and tablets. In: Lollino G. et al. (ed.) Engineering Geology for Society and Territory, Volume 8. Heidelberg, Springer, 265-268, DOI 10.1007/978-3-319-09408-3_46.

  9. Technology roadmaps

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, B. [Natural Resources Canada, Ottawa, ON (Canada). CANMET Energy Technology Centre

    2003-07-01

    The purpose of a technology road map is to define the state of a current technology, relevant market issues, and future market needs; to develop a plan that industry can follow to provide these new products and services; and to map technology pathways and performance goals for bringing these products and services to market. The three stages (planning, implementation, and reviewing and updating), benefits, and status of the Clean Coal Technology Roadmap are outlined. Action Plan 2000, a $1.7 million 2000 Climate Change Technology and Innovation Program, which uses the technology roadmapping process, is described. The members of the management steering committee for the Clean Coal Technology Roadmap are listed. A flowsheet showing activities until November 2004, when the final clean coal road map is due, is included.

  10. 14 CFR 13.225 - Offer of proof.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Offer of proof. 13.225 Section 13.225... INVESTIGATIVE AND ENFORCEMENT PROCEDURES Rules of Practice in FAA Civil Penalty Actions § 13.225 Offer of proof. A party whose evidence has been excluded by a ruling of the administrative law judge may offer the...

  11. 48 CFR 17.203 - Solicitations.

    Science.gov (United States)

    2010-10-01

    ... higher than the base price only if the acceptance does not prejudice any other offeror; and (2) Limit... normally should allow option quantities to be offered without limitation as to price, and there shall be no limitation as to price if the option quantity is to be considered in the evaluation for award (see 17.206...

  12. 43 CFR 12.815 - Evaluating offers.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.815 Section 12.815 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT REQUIREMENTS AND... Act-Construction Materials § 12.815 Evaluating offers. (a) The restrictions of the Buy American Act do...

  13. 17 CFR 256.930.1 - General advertising expenses.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false General advertising expenses... UTILITY HOLDING COMPANY ACT OF 1935 2. Expense § 256.930.1 General advertising expenses. This account shall include the cost of materials used and expenses incurred in advertising and related activities...

  14. Genealogies of Modern Technology

    DEFF Research Database (Denmark)

    Riis, Søren

    2008-01-01

    Does modern technology differ from ancient technology and does it have a unique essence? This twofold question opens one of Martin Heidegger's most influential philosophical inquiries, The Question Concerning Technology. The answer Heidegger offers has inspired various critiques and appraisals from...... a vast number of contemporary scholars of technology.1 Heidegger's answer is traditionally thought to suggest a great difference between ancient and modern technology. However, by re-examining Heidegger's text, it is possible to discover previously ignored or misunderstood lines of thoughts that affirm...... a multi-stable interpretation of the origin of modern technology. In what follows, we shall see how The Question Concerning Technology in fact supports three different genealogies of modern technology...

  15. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.

    Science.gov (United States)

    Jiang, Teng; Xue, Liu-Jun; Yang, Yang; Wang, Qing-Guang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang; Zhang, Ying-Dong

    2018-04-17

    During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.

  16. Special Offers

    CERN Multimedia

    Association du personnel

    2011-01-01

    Walibi Rhône-Alpes is open until 31 October. Reduced prices for children and adults at this French attraction park in Les Avenières. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  17. Wind offering in energy and reserve markets

    Science.gov (United States)

    Soares, T.; Pinson, P.; Morais, H.

    2016-09-01

    The increasing penetration of wind generation in power systems to fulfil the ambitious European targets will make wind power producers to play an even more important role in the future power system. Wind power producers are being incentivized to participate in reserve markets to increase their revenue, since currently wind turbine/farm technologies allow them to provide ancillary services. Thus, wind power producers are to develop offering strategies for participation in both energy and reserve markets, accounting for market rules, while ensuring optimal revenue. We consider a proportional offering strategy to optimally decide upon participation in both markets by maximizing expected revenue from day-ahead decisions while accounting for estimated regulation costs for failing to provide the services. An evaluation of considering the same proportional splitting of energy and reserve in both day- ahead and balancing market is performed. A set of numerical examples illustrate the behavior of such strategy. An important conclusion is that the optimal split of the available wind power between energy and reserve strongly depends upon prices and penalties on both market trading floors.

  18. 17 CFR 240.15c1-2 - Fraud and misrepresentation.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Fraud and misrepresentation. 240.15c1-2 Section 240.15c1-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Securities Exchange Act of 1934 Rules Relating to Over-The-Counter Markets § 240.15c1-2 Fraud and...

  19. What Bulgarian Banks offer via Internet: an Overview

    OpenAIRE

    Bojidar Bojinov

    2003-01-01

    The new information technologies adoption and e-commerce emergence change the role of financial intermediaries in new E-conomy. During the last years, the bank started an expansion to the web – they offer broad range of traditional bank products and services via Internet. The remote banking become one of the main channels for bank services distribution. The Internet expansion of the Bulgarian banks is at its beginning. The showed results are based on the Internet research, which has aimed to ...

  20. CERN Technical Training 2006: Software and System Technologies Curriculum - Scheduled

    CERN Multimedia

    2006-01-01

    Course Sessions (October 2006-March 2007) The Software and System Technologies Curriculum of the CERN Technical Training Programme offers comprehensive training in C++, Java, Perl, Python, XML, OO programming, JCOP/PVSS, database design and Oracle. In the PERL, C++, OO and Java course series there are some places available on the following course sessions, currently scheduled until March 2007: Object-Oriented Analysis and Design using UML: 17-19 October 2006 (3 days) JAVA 2 Enterprise Edition - Part 1: Web Applications: 19-20 October 2006 (2 days) JAVA - Level 1: 30 October -1 November 2006 (3 days) PERL 5 - Advanced Aspects: 2 November 2006 (1 day) C++ Programming Part 1 - Introduction to Object-Oriented Design and Programming: 14-16 November 2006 (3 days) JAVA - Level 2: 4-7 December 2006 (4 days) C++ Programming Part 2 - Advanced C++ and its Traps and Pitfalls: 12-15 December 2006 (4 days) JAVA 2 Enterprise Edition - Part 2: Enterprise JavaBeans: 18-20 December 2006 (3 days) C++ for Particle Physicists:...

  1. Investor Reaction to Mandatory Offers on the Warsaw Stock Exchange

    Directory of Open Access Journals (Sweden)

    Szymon Okoń

    2012-06-01

    Full Text Available The following paper aims to assess investor reaction to mandatory offers on the Warsaw Stock Exchange, which is important because knowledge about these reactions can be used to make better investment decisions. This paper highlights the importance of procedure in making a mandatory offer and its grounds in the Polish legal system. Additionally, it presents empirical research on the reactions of investors to mandatory offers on the Warsaw Stock Exchange. It has been provided that mandatory offers have a significant impact on the price of a company’s shares listed on the Warsaw Stock Exchange. Knowledge about the reactions of investors to a mandatory offer may be used when selecting securities for an investment portfolio. The findings may provide guidance in deciding whether to begin or end investment in the company, both for individual and institutional investors. The event study methodology approach used in the paper is regarded as valuable and can be the basis for further research in other areas of the capital market research, especially in the context of information efficiency.

  2. Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn

    Directory of Open Access Journals (Sweden)

    Black Joel A

    2012-11-01

    Full Text Available Abstract Background Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn. Results Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF, exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals. Conclusions The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.

  3. Special Offers

    CERN Multimedia

    Association du personnel

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions. TPG: reduced rates on annual transport passes for active and retired staff. Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret. Walibi: reduced prices for children and adults at this French attraction park in Les Avenières. FNAC: 5% reduction on FNAC vouchers. For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  4. Genetic variation in the HSD17B1 gene and risk of prostate cancer.

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2005-11-01

    Full Text Available Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002 inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes

  5. Leveraging technology to enhance addiction treatment and recovery.

    Science.gov (United States)

    Marsch, Lisa A

    2012-01-01

    Technology such as the Internet and mobile phones offers considerable promise for affecting the assessment, prevention, and treatment of and recovery from substance use disorders. Technology may enable entirely new models of behavioral health care within and outside of formal systems of care. This article reviews the promise of technology-based therapeutic tools for affecting the quality and reach of addiction treatment and recovery support systems, as well as the empirical support to date for this approach. Potential models for implementing technology-based interventions targeting substance use disorders are described. Opportunities to optimize the effectiveness and impact of technology-based interventions targeting addiction and recovery, along with outstanding research needs, are discussed.

  6. 17 CFR 1.22 - Use of customer funds restricted.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Use of customer funds... REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.22 Use of customer funds restricted. No futures commission merchant shall use, or permit the use of, the customer funds of...

  7. Advanced technology heavy water monitors offering reduced implementation costs

    International Nuclear Information System (INIS)

    Kalechstein, W.; Hippola, K.B.

    1984-10-01

    The development of second generation heavy water monitors for use at CANDU power stations and heavy water plants has been completed and the instruments brought to the stage of commercial availability. Applications of advanced technology and reduced utilization of custom manufactured components have together resulted in instruments that are less expensive to produce than the original monitors and do not require costly station services. The design has been tested on two prototypes and fully documented, including the inspection and test procedures required for manufacture to the CSA Z299.3 quality verfication program standard. Production of the new monitors by a commercial vendor (Barringer Research Ltd.) has begun and the first instrument is scheduled for delivery to CRNL's NRU reactor in late 1984

  8. Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions

    DEFF Research Database (Denmark)

    Bonomo, Silvia; Jorgensen, Flemming Steen; Olsen, Lars

    2017-01-01

    Cytochrome P450 17A1 (CYP17A1) catalyzes C17 hydroxylation of pregnenolone and progesterone and the subsequent C17–C20 bond cleavage (lyase reaction) to form androgen precursors. Compound I (Cpd I) and peroxo anion (POA) are the heme-reactive species underlying the two reactions. We have characte...... the concept that the selectivity of the steroidogenic CYPs is ruled by direct interactions with the enzyme, in contrast to the selectivity of drug-metabolizing CYPs, where the reactivity of the substrates dominates....... characterized the reaction path for both the hydroxylase and lyase reactions using density functional theory (DFT) calculations and the enzyme–substrate interactions by molecular dynamics (MD) simulations. Activation barriers for positions subject to hydroxylase reaction have values close to each other and span...

  9. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells

    Directory of Open Access Journals (Sweden)

    Gjertsen Bjørn

    2010-07-01

    Full Text Available Abstract Background Several observations suggest that immunological events early after chemotherapy, possibly during the period of severe treatment-induced cytopenia, are important for antileukemic immune reactivity in acute myeloid leukemia (AML. We therefore investigated the frequencies of various T cell subsets (TC1, TH1, TH17 and CD25+ FoxP3+ TREG cells in AML patients with untreated disease and following intensive chemotherapy. Results Relative levels of circulating TC1 and TH1 cells were decreased in patients with severe chemotherapy-induced cytopenia, whereas TH17 levels did not differ from healthy controls. Increased levels of regulatory CD25+ FoxP3+ T cells were detected in AML patients with untreated disease, during chemotherapy-induced cytopenia and during regeneration after treatment. TH17 and TH1 levels were significantly higher in healthy males than females, but this gender difference was not detected during chemotherapy-induced cytopenia. Finally, exogenous IL17-A usually had no or only minor effects on proliferation of primary human AML cells. Conclusions We conclude that the effect of intensive AML chemotherapy differ between circulating T cell subsets, relative frequencies of TH17 cells are not affected by chemotherapy and this subset may affect AML cells indirectly through their immunoregulatory effects but probably not through direct effects of IL17-A.

  10. 31 CFR 342.0 - Offering of notes.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Offering of notes. 342.0 Section 342.0 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... or greater denomination. This offering was effective from May 1, 1967 until the close of business...

  11. Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1.

    Science.gov (United States)

    Endo, Yusuke; Asou, Hikari K; Matsugae, Nao; Hirahara, Kiyoshi; Shinoda, Kenta; Tumes, Damon J; Tokuyama, Hirotake; Yokote, Koutaro; Nakayama, Toshinori

    2015-08-11

    Chronic inflammation due to obesity contributes to the development of metabolic diseases, autoimmune diseases, and cancer. Reciprocal interactions between metabolic systems and immune cells have pivotal roles in the pathogenesis of obesity-associated diseases, although the mechanisms regulating obesity-associated inflammatory diseases are still unclear. In the present study, we performed transcriptional profiling of memory phenotype CD4 T cells in high-fat-fed mice and identified acetyl-CoA carboxylase 1 (ACC1, the gene product of Acaca) as an essential regulator of Th17 cell differentiation in vitro and of the pathogenicity of Th17 cells in vivo. ACC1 modulates the DNA binding of RORγt to target genes in differentiating Th17 cells. In addition, we found a strong correlation between IL-17A-producing CD45RO(+)CD4 T cells and the expression of ACACA in obese subjects. Thus, ACC1 confers the appropriate function of RORγt through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Th1, Th17, CXCL16 and homocysteine elevated after intracranial and cervical stent implantation.

    Science.gov (United States)

    Tang, Yanyan; Wei, Yunfei; Ye, Ziming; Qin, Chao

    2017-08-01

    The presence of Th1 and Th17 cells has been observed as major inducers in inflammation and immune responses associated stenting. However, there is rare data on the impact of Th1, Th17, CXCL16 and homocysteine after cerebral stent implantation. Here, we performed the statistical analysis to first evaluate the variation of the Th17and Th1 cells and their related cytokines, CXCL16 and homocysteine in the peripheral blood of patients with cerebral stenting. The flow cytometry was used to detect the proportion of Th1 and Th17 cells in peripheral blood mononuclear cells (PBMCs). The enzyme-linked immunosorbent assay was used to measure the serum concentrations of IFN-γ, IL-17 and CXCL16. Plasma homocysteine was examined by immunoturbidimetry. The level of Th1, CXCL16 and homocysteine showed an increase at 3 d, followed by the continuous decrease at 7 d and 3 months. The frequency of Th17 cells increased to a peak at three days, and subsequently decreased with a higher level than baseline. Our data revealed that the variation in Th1, Th17, CXCL16 and homocysteine in peripheral blood of patients with stenting may be implicated in inflammation after intracranial and cervical stent implantation. A better understanding of these factors will provide help for further drug design and clinical therapy.

  13. Advanced testing and validation centre gets electric vehicle technology to market faster

    Energy Technology Data Exchange (ETDEWEB)

    Astil, T.; Girard, F. [National Research Council of Canada, Vancouver, BC (Canada). Inst. for Fuel Cell Innovation

    2010-07-01

    The National Research Council (NRC) Institute for Fuel Cell Innovation is advancing Canada's clean energy advantage through NRC's technology cluster initiatives, which help Canadian small and medium enterprises achieve commercialization breakthroughs in key sectors. This presentation discussed the technology evaluation program (TEP) offered by the NRC Institute for Fuel Cell Innovation. The presentation discussed the TEPs mission, advanced testing and validation centre (ATVC), previous ATVC clients, environmental chamber, dynamometer, vibration table, electrochemical battery testing, and electrochemical testing laboratory. The ATVC is a specialized and safe environment for objective, reliable and accurate standardized testing applications of electric vehicle technologies. It offers independent test services to external organizations, making it easier to prove that electric vehicle technologies will perform under specific operating conditions. figs.

  14. Offer

    CERN Multimedia

    Staff Association

    2015-01-01

    RRP Communication organizes cultural events such as concerts, shows, sporting events. The members of the Staff Association profits from a reduction of 10 CHF per ticket. How to proceed: The ticket reservation is made by mail info@rrp.ch. You need to give the following information: Name of the show, and which date chosen Number of tickets, and category Name and surname Address Telephone number Mention “offer CERN”, and attach a photocopy of your Staff Association member card. After your reservation, you will be sent a copy with a payslip to the address mentioned above. Once paid, the members have the possibility to: pick up their ticket(s) from the cash register the evening of the show (opens 1 hour before the show) by showing their member card; receive the ticket(s) to the address indicated above, by registered mail, subject to an extra cost of 10CHF. Next show : More information at http://www.rrp.ch/

  15. Arctigenin functions as a selective agonist of estrogen receptor ? to restrict mTORC1 activation and consequent Th17 differentiation

    OpenAIRE

    Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

    2016-01-01

    Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ER? largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condit...

  16. Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Eto, Masumi, E-mail: masumi.eto@jefferson.edu [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Kirkbride, Jason A.; Chugh, Rishika; Karikari, Nana Kofi [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Kim, Jee In [Department of Molecular Physiology and Biophysics, and Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, PA 19107 (United States); Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu 700-422 (Korea, Republic of)

    2013-04-26

    Highlights: •Non-canonical roles of the myosin phosphatase inhibitor (CPI-17) were studied. •CPI-17 is localized in the nucleus of hyperplastic cancer and smooth muscle cells. •CPI-17 Ser12 phosphorylation may regulate the nuclear import. •CPI-17 regulates histone H3 phosphorylation and cell proliferation. •The nuclear CPI-17-PP1 axis plays a proliferative role in cells. -- Abstract: CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17 kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17 expression in proliferating cells, such as pancreatic cancer and hyperplastic SM cells. Immunofluorescence showed that CPI-17 was concentrated in nuclei of human pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected in the proliferating vascular SM cell culture and cells at neointima of rat vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI-17 at Ser12 attenuated the nuclear import. CPI-17 phosphorylated at Ser12 was not localized at nuclei, suggesting a suppressive role of Ser12 phosphorylation in the nuclear import. Activated CPI-17 bound to all three isoforms of PP1 catalytic subunit in Panc1 nuclear extracts. CPI-17 knockdown in Panc1 resulted in dephosphorylation of histone H3 at Thr3, Ser10 and Thr11, whereas it had no effects on the phosphorylation of myosin light chain and merlin, the known targets of MLCP. In parallel, CPI-17 knockdown suppressed Panc1 proliferation. We propose that CPI-17 accumulated in the nucleus through the N-terminal tail targets multiple PP1 signaling pathways regulating cell proliferation.

  17. 17 CFR 270.27d-1 - Reserve requirements for principal underwriters and depositors to carry out the obligations to...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Reserve requirements for....27d-1 Reserve requirements for principal underwriters and depositors to carry out the obligations to... reserve and as security for the purpose of assuring the refund of charges required by sections 27(d) and...

  18. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

    Directory of Open Access Journals (Sweden)

    Freddyson J Martínez-Rivera

    Full Text Available The abuse of anabolic androgenic steroids (AAS has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH. In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM. These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  19. Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties.

    Science.gov (United States)

    Prajeeth, Chittappen K; Kronisch, Julius; Khorooshi, Reza; Knier, Benjamin; Toft-Hansen, Henrik; Gudi, Viktoria; Floess, Stefan; Huehn, Jochen; Owens, Trevor; Korn, Thomas; Stangel, Martin

    2017-10-16

    Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in the central nervous system (CNS). Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammation. Previously, we have shown that only Th1 but not Th17 effectors activate microglia. However, it is not clear which cells are targets of Th17 effectors in the CNS. To understand the effects driven by Th17 cells in the CNS, we induced experimental autoimmune encephalomyelitis in wild-type mice and CD4 + T cell-specific integrin α4-deficient mice where trafficking of Th1 cells into the CNS was affected. We compared microglial and astrocyte response in the brain and spinal cord of these mice. We further treated astrocytes with supernatants from highly pure Th1 and Th17 cultures and assessed the messenger RNA expression of neurotrophic factors, cytokines and chemokines, using real-time PCR. Data obtained was analyzed using the Kruskal-Wallis test. We observed in α4-deficient mice weak microglial activation but comparable astrogliosis to that of wild-type mice in the regions of the brain populated with Th17 infiltrates, suggesting that Th17 cells target astrocytes and not microglia. In vitro, in response to supernatants from Th1 and Th17 cultures, astrocytes showed altered expression of neurotrophic factors, pro-inflammatory cytokines and chemokines. Furthermore, increased expression of chemokines in Th1- and Th17-treated astrocytes enhanced recruitment of microglia and transendothelial migration of Th17 cells in vitro. Our results demonstrate the delicate interaction between T cell subsets and glial cells and how they communicate to mediate their effects. Effectors of Th1 act on both microglia and astrocytes whereas Th17 effectors preferentially target astrocytes to promote neuroinflammation.

  20. Using Digital Technology to See Angles from Different Angles. Part 1: Corners

    Science.gov (United States)

    Host, Erin; Baynham, Emily; McMaster, Heather

    2014-01-01

    In Part 1 of their article, Erin Host, Emily Baynham and Heather McMaster use a combination of digital technology and concrete materials to explore the concept of "corners". They provide a practical, easy to follow sequence of activities that builds on students' understandings. [For "Using Digital Technology to See Angles from…

  1. 15 CFR 90.13 - Offer of hearing.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Offer of hearing. 90.13 Section 90.13 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade BUREAU OF THE CENSUS, DEPARTMENT OF COMMERCE PROCEDURE FOR CHALLENGING CERTAIN POPULATION AND INCOME ESTIMATES § 90.13 Offer of...

  2. Rethinking agency and medical adherence technology: applying Actor Network Theory to the case study of Digital Pills.

    Science.gov (United States)

    Hurtado-de-Mendoza, Alejandra; Cabling, Mark L; Sheppard, Vanessa B

    2015-12-01

    Much literature surrounding medical technology and adherence posits that technology is a mechanism for social control. This assumes that the medical establishment can take away patients' agency. Although power relationships and social control can play a key role, medical technology can also serve as an agentive tool to be utilized. We (1) offer the alternative framework of Actor Network Theory to view medical technology, (2) discuss the literature on medication adherence and technology, (3) delve into the ramifications of looking at adherence as a network and (4) use Digital Pills as a case study of dispersed agency. © 2015 John Wiley & Sons Ltd.

  3. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th November 2011 New BCGE Business partner benefits As you may remember thanks to our BCGE business partner agreement you benefit from various advantages such as free annual subscription on your Silver or Gold credit card both for yourself and your partner (joint account). Please be informed that as of October 1st  2011 the below mentioned features will be added to your annual credit card subscription : MasterCard/Visa Silver and Gold: travel cancellation as well as related services such as holiday interruption best guaranteed price Only for Ma...

  4. Chemoselective reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by various hydride reagents.

    Science.gov (United States)

    Kim, Eunjeong; Ma, Eunsook

    2007-04-01

    The chemoselectivity of rigid cyclic alpha,beta-unsaturated carbonyl group on the reducing agents was influenced by the ring size and steric factor. Cholesterol (cholest-5-en-3beta-ol) and dehydroepiandrosterone (DHEA) were oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione. They were reduced with NaBH(4), lithium tri-sec-butylborohydride (l-Selectride), LiAlH(4), 9-borabicyclo[3.3.1]nonane (9-BBN), lithium triethylborohydride (Super-hydride), and BH(3) x (CH(3))(2)S in various conditions, respectively. Reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by NaBH(4) (4 equiv.) produced 4,6-cholestadien-3beta-ol and 4,6-androstadiene-3beta,17beta-diol, respectively. Reduction by l-Selectride (12 equiv.) afforded 4,6-cholestadien-3alpha-ol and 4,6-androstadiene-3alpha,17beta-diol, chemoselectively. Reaction with Super-hydride (12 equiv.) produced 4,6-cholestadien-3-one and 3-oxo-4,6-androstadien-17beta-ol. Reduction of 1,4,6-cholestatrien-3-one by 9-BBN (14 equiv.) produced 1,4,6-cholestatrien-3alpha-ol, but 1,4,6-androstatriene-3,17-dione was not reacted with 9-BBN in the reaction conditions. Reaction of LiAlH(4) (6 equiv.) formed 4,6-cholestadien-3beta-ol and 3-oxo-1,4,6-androstatrien-17beta-ol. Reduction of 1,4,6-cholestatrien-3-one by BH(3) x (CH(3))(2)S (11 equiv.) gave cholestane as major compound and unlike reactivity of cholesterol, 1,4,6-androstatriene-3,17-dione by 8 equiv. of BH(3) x (CH(3))(2)S formed 3-oxo-1,4,6-androstatrien-17beta-ol. LiAlH(4) and BH(3) x (CH(3))(2)S showed relatively low chemoselectivity.

  5. Special Offers

    CERN Multimedia

    Association du personnel

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions.     TPG: reduced rates on annual transport passes for active and retired staff.     Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret.     Walibi: reduced prices for children and adults at this French attraction park in Les Avenières.       FNAC: 5% reduction on FNAC vouchers.       For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  6. Special Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions.     TPG: reduced rates on annual transport passes for all active and retired staff.     Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret.     Walibi: reduced prices for children and adults at this French attraction park in Les Avenières.       FNAC: 5% reduction on FNAC vouchers.       For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  7. Translocation 1;7 in dyshematopoiesis: possibly induced with a nonrandom geographic distribution

    International Nuclear Information System (INIS)

    Scheres, J.M.; Hustinx, T.W.; Holdrinet, R.S.; Geraedts, J.P.; Hagemeijer, A.; van der Blij-Philipsen, M.

    1984-01-01

    Eight patients with various hematologic disorders had an identical chromosomal aberration in their bone marrow or unstimulated peripheral blood, a translocation t(1;7) interpreted as t(1;7)(p11;p11). The translocation chromosome replaced one normal chromosome number7; therefore, the karyotype of the abnormal cells was trisomic for 1q and monosomic for 7q. Including four cases from the literature, a total of 12 patients (4 women, 8 men) with this translocation are known at the moment. The translocation does not seem to be associated with a specific disorder, but almost all patients had a preleukemic syndrome during some stage of their disease. It is very remarkable that 11 of the 12 patients lived in the Netherlands, and 7 patients had a history of iatrogenic exposure to alkylating agents or irradiation; one patient was a radiation worker and another one had a history of toxic exposure to chloramphenicol. It is suggested, therefore, that the t(1;7) is a possibly induced chromosomal aberration with a clearly nonrandom geographic distribution

  8. 17 CFR 270.12d1-1 - Exemptions for investments in money market funds.

    Science.gov (United States)

    2010-04-01

    ...)(3) and 270.17e-1(d)(2), the payment of a commission, fee, or other remuneration to a broker shall be...) of the Act if: (1) The commission, fee, or other remuneration is paid in connection with the sale of... directors, the company's investment adviser performs the duties of the board of directors. [71 FR 36655...

  9. Genetic linkage of hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease) to markers of chromosomes 1 and 17

    NARCIS (Netherlands)

    Defesche, J. C.; Hoogendijk, J. E.; de Visser, M.; de Visser, O.; Bolhuis, P. A.

    1990-01-01

    Hereditary motor and sensory neuropathy type 1 (HMSN I) is an autosomal dominant disorder genetically localized on chromosome 1 in a few families and on chromosome 17 in other families. We analyzed linkage between 6 markers of chromosome 1, 2 markers of chromosome 17, and the HMSN I locus using

  10. The Lab of the Future: Using Technology to Teach Foreign Language.

    Science.gov (United States)

    Underwood, John H.

    1993-01-01

    Describes the role of technology in teaching foreign languages. Offers a brief history of language lab technologies, including computer use for drill-and-practice, text reconstruction, and simulations and games. Discusses tool programs, intelligent systems, video technology, satellite television, videodisc and interactive video, hypertext and…

  11. Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Yangyang Li

    2015-01-01

    Full Text Available Type 1 diabetes (T1D is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic islet β cells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17 cells along with impaired T regulatory (Treg cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes.

  12. Contribution of 194.1 keV Resonance to 17O(p, alpha) 14N Reaction Rate using R Matrix Code

    International Nuclear Information System (INIS)

    Chafa, A.; Messili, F.Z.; Barhoumi, S.

    2009-01-01

    Knowledge of the 17 O(p, alpha ) 14 N reaction rates is required for evaluating elemental abundances in a number of hydrogen - burning stellar sites. This reaction is specifically very important for nucleosynthesis of the rare oxygen isotope 17 O. Classical novae are thought to be a major source of 17 O in the Galaxy and produce the short-live radioisotope 18 F whose + decay is followed by a gamma ray emission which could be observed with satellites such as the Integral observatory. As the 17 O(p, alpha) 14 N and 17 O(p, alpha ) 18 F reactions govern the destruction of 17 O and the formation of 1 '8F, their rates are decisive in determining the final abundances of these isotopes. Stellar temperatures of primary importance for nucleosynthesis are typically in the ranges T = 0.01-0.1 GK for red giant, AGB, and massive stars, and T 0.01-0.4 GK for classical nova explosions In recent work, we observed, for the first time, a resonance a 183.3 keV corresponding to level in 18 F at Ex 5789.8 ± 0.3 keV. A new astrophysical parameters of this resonance are found. In this work we study this reaction using numerical code based on R matrix method including the new values of level energy and parameters of 183.3 keV resonance in order to show his contribution to 17 O(p, alpha) 14 N reaction rates. We also use old parameters values of this resonance given in Keiser work for comparison. We show that this resonance predominate the reaction rates in all range of stellar temperature for classical nova explosions. This is in good agreement with our work with experimental method. We also study cross section and differential cross section 17 O(p, alpha ) 14 N reaction with R matrix method

  13. AZD5363 inhibits inflammatory synergy between interleukin-17 and insulin/insulin-like growth factor 1

    Directory of Open Access Journals (Sweden)

    Chong eChen

    2014-12-01

    Full Text Available In the United States, one third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1 and interleukin-17 (IL-17. Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-kappa B (NF-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase GSK3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1, C-C motif ligand 20 (Ccl20 and interleukin-6 (Il-6 in wild-type, GSK3α-/-, and GSK3β-/- mouse embryonic fibroblast (MEF cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17- induced expression of Cxcl1, Ccl20 and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.

  14. 2006 annual nuclear technology conference Aachen; Jahrestagung Kerntechnik 2006

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2006-07-15

    This year's ANNUAL NUCLEAR TECHNOLOGY CONFERENCE (JK) was organized in Aachen by the Deutsches Atomforum e.V. (DAtF) and the Kerntechnische Gesellschaft e.V. (KTG). The attendance by more than 1,200 participants from 17 nations underlines the role of this specialized congress as one of the leading events in the field of nuclear power use. For several years in a row, the number of participants has been increasing steadily. The first conference day offered plenary presentations traditionally dealing mainly with political and economic issues of the use of nuclear power, including a presentation by the President of the DAtF. The lead countries of JK 2006 were Belgium and Finland with contributions to the plenary day and special meetings on selected topics. The traditional proven scheme of the three-day meeting offered plenary sessions on the first day, and technical sessions, topical sessions, poster sessions, and special events on the following days. The 'Nuclear Power Campus' was run most successfully for the fourth time, presenting to high school students and university freshmen the world of nuclear power in a transparent way. The special commitment to the young generation was stressed at JK 2006 also by the 'Competence Preservation in Nuclear Technology' workshop. Nearly 2 dozen young scientists used the forum to present results of their work. The meeting was accompanied by a technical exhibition with meeting points established by vendors, suppliers, and service providers. (orig.)

  15. Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

    Science.gov (United States)

    Wester, Anita; Devocelle, Marc; Tallant, E Ann; Chappell, Mark C; Gallagher, Patricia E; Paradisi, Francesca

    2017-10-01

    Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.

  16. Identification of intracellular proteins and signaling pathways in human endothelial cells regulated by angiotensin-(1-7).

    Science.gov (United States)

    Meinert, Christian; Gembardt, Florian; Böhme, Ilka; Tetzner, Anja; Wieland, Thomas; Greenberg, Barry; Walther, Thomas

    2016-01-01

    The study aimed to identify proteins regulated by the cardiovascular protective peptide angiotensin-(1-7) and to determine potential intracellular signaling cascades. Human endothelial cells were stimulated with Ang-(1-7) for 1 h, 3 h, 6 h, and 9 h. Peptide effects on intracellular signaling were assessed via antibody microarray, containing antibodies against 725 proteins. Bioinformatics software was used to identify affected intracellular signaling pathways. Microarray data was verified exemplarily by Western blot, Real-Time RT-PCR, and immunohistochemical studies. The microarray identified 110 regulated proteins after 1 h, 119 after 3 h, 31 after 6 h, and 86 after 9 h Ang-(1-7) stimulation. Regulated proteins were associated with high significance to several metabolic pathways like “Molecular Mechanism of Cancer” and “p53 signaling” in a time dependent manner. Exemplarily, Western blots for the E3-type small ubiquitin-like modifier ligase PIAS2 confirmed the microarray data and displayed a decrease by more than 50% after Ang-(1-7) stimulation at 1 h and 3 h without affecting its mRNA. Immunohistochemical studies with PIAS2 in human endothelial cells showed a decrease in cytoplasmic PIAS2 after Ang-(1-7) treatment. The Ang-(1-7) mediated decrease of PIAS2 was reproduced in other endothelial cell types. The results suggest that angiotensin-(1-7) plays a role in metabolic pathways related to cell death and cell survival in human endothelial cells.

  17. 17 CFR 8.16 - Settlement offers.

    Science.gov (United States)

    2010-04-01

    ... Section 8.16 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION EXCHANGE PROCEDURES FOR DISCIPLINARY, SUMMARY, AND MEMBERSHIP DENIAL ACTIONS Disciplinary Procedure § 8.16 Settlement... the disciplinary committee at any time after the investigation report is completed. The disciplinary...

  18. A 'variable' stellar object in a variable blue nebula V-V 1-7

    International Nuclear Information System (INIS)

    Rao, N.K.; Gilra, D.P.

    1981-01-01

    V-V 1-7 is supposed to be one of the few planetary nebulae with Ao central stars and was included in the planetary-nebula catalogue as PK 235 + 1 0 1. The nebula was seen on the blue Palomar Observatory Sky Survey (POSS) print but not on the red print; as a result it was thought that it might be a reflection nebula. However, the symmetry of the nebula around the central star (HD 62001), and also the ultraviolet photometric variability of this central star led others to suggest that the nebula might be a nova shell. Subsequently it was found that the nebula V-V 1-7 has disappeared. It is not seen on any direct plate known to us except the POSS blue plate. In this paper the disappearance is reported (along with the nebula) of a stellar object, which appears within the 'nebular shell' of V-V 1-7 on the POSS blue plate, but not on the red plate. (author)

  19. Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis.

    Science.gov (United States)

    Conti, Heather R; Whibley, Natasha; Coleman, Bianca M; Garg, Abhishek V; Jaycox, Jillian R; Gaffen, Sarah L

    2015-01-01

    Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.

  20. Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis

    Science.gov (United States)

    Conti, Heather R.; Whibley, Natasha; Coleman, Bianca M.; Garg, Abhishek V.; Jaycox, Jillian R.; Gaffen, Sarah L.

    2015-01-01

    Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections. PMID:25849644

  1. Offers

    CERN Document Server

    Staff Association

    2015-01-01

    New offer for our members. The Staff Association CERN staff has recently concluded a framework agreement with AXA Insurance Ltd, General-Guisan-Strasse 40, 8401 Winterthur. This contract allows you to benefit from a preferential tariff and conditions for insurances: Motor vehicles for passenger cars and motorcycles of the product line STRADA: 10% discount Household insurance (personal liability and household contents) the product line BOX: 10% discount Travel insurance: 10% discount Buildings: 10% discount Legal protection: 10% discount AXA is number one on the Swiss insurance market. The product range encompasses all non-life insurance such as insurance of persons, property, civil liability, vehicles, credit and travel as well as innovative and comprehensive solutions in the field of occupational benefits insurance for individuals and businesses. Finally, the affiliate AXA-ARAG (legal expenses insurance) completes the offer. Armed with your staff association CERN card, you can always get the off...

  2. Distal technologies and type 1 diabetes management.

    Science.gov (United States)

    Duke, Danny C; Barry, Samantha; Wagner, David V; Speight, Jane; Choudhary, Pratik; Harris, Michael A

    2018-02-01

    Type 1 diabetes requires intensive self-management to avoid acute and long-term health complications. In the past two decades, substantial advances in technology have enabled more effective and convenient self-management of type 1 diabetes. Although proximal technologies (eg, insulin pumps, continuous glucose monitors, closed-loop and artificial pancreas systems) have been the subject of frequent systematic and narrative reviews, distal technologies have received scant attention. Distal technologies refer to electronic systems designed to provide a service remotely and include heterogeneous systems such as telehealth, mobile health applications, game-based support, social platforms, and patient portals. In this Review, we summarise the empirical literature to provide current information about the effectiveness of available distal technologies to improve type 1 diabetes management. We also discuss privacy, ethics, and regulatory considerations, issues of global adoption, knowledge gaps in distal technology, and recommendations for future directions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Who are the adolescents saying "No" to cannabis offers.

    Science.gov (United States)

    Burdzovic Andreas, Jasmina; Pape, Hilde; Bretteville-Jensen, Anne Line

    2016-06-01

    Adolescents who refuse direct cannabis offers and remain non-users represent a potentially very informative, yet surprisingly understudied group. We examined a range of risk and protective factors putatively associated with this poorly understood "cannabis-resilient" profile. Paper-and-pencil questionnaires assessing substance use, peer and family relations, and behavioral and personality characteristics were completed by 19,303 middle- and high-school students from 82 schools in Norway (response rate 84%) The lifetime prevalence of cannabis use was 7.6%. Another 10.4% reported no use of the drug despite having received recent cannabis offers. Results from the multinomial logistic regression revealed a set of characteristics differentiating adolescents who resisted such offers from those who: (a) neither received the offers nor used, and, more importantly, (b) used the drug. Specifically, parent-child relationship quality, negative drug-related beliefs, absence of close relationships with cannabis-users, low delinquency, no regular tobacco use, and infrequent alcohol intoxication were all associated with increased odds of being in the cannabis-resilient vs. cannabis-user group. This pattern of results was comparable across middle- and high-school cohorts, but the parent-child relationship quality and delinquency were significantly associated with cannabis-resilient vs. cannabis-use outcome only among younger and older adolescents, respectively. Among other low-risk characteristics, better relationships with parents and beliefs that drug use is problematic were associated with adolescents' refusals to accept cannabis offers. These results may have implications for novel preventive strategies targeting cannabis-exposed adolescents. Copyright © 2016. Published by Elsevier Ireland Ltd.

  4. Predominant modifier of extreme liver cancer susceptibility in C57BR/cdJ female mice localized to 6 Mb on chromosome 17

    Science.gov (United States)

    Peychal, Stephanie E.-M.; Bilger, Andrea; Pitot, Henry C.; Drinkwater, Norman R.

    2009-01-01

    Sex hormones influence the susceptibility of inbred mice to liver cancer. C57BR/cdJ (BR) females are extremely susceptible to spontaneous and chemically induced liver tumors, in part due to a lack of protection against hepatocarcinogenesis normally offered by ovarian hormones. BR males are also moderately susceptible, and the susceptibility of both sexes of BR mice to liver tumors induced with N,N-diethylnitrosamine relative to the resistant C57BL/6J (B6) strain is caused by two loci designated Hcf1 and Hcf2 (hepatocarcinogenesis in females) located on chromosomes 17 and 1, respectively. The Hcf1 locus on chromosome 17 is the predominant modifier of liver cancer in BR mice. To validate the existence of this locus and investigate its potential interaction with Hcf2, congenic mice for each region were generated. Homozygosity for the B6.BR(D17Mit164-D17Mit2) region resulted in a 4-fold increase in liver tumor multiplicity in females and a 4.5-fold increase in males compared with B6 controls. A series of 16 recombinants covering the entire congenic region was developed to further narrow the area containing Hcf1. Susceptible heterozygous recombinants demonstrated a 3- to 7-fold effect in females and a 1.5- to 2-fold effect in males compared with B6 siblings. The effect in susceptible lines completely recapitulated the susceptibility of heterozygous full-length chromosome 17 congenics and furthermore narrowed the location of the Hcf1 locus to a single region of the chromosome from 30.05 to 35.83 Mb. PMID:19255062

  5. Studiemiljø2011: Rapporterne 1-7

    DEFF Research Database (Denmark)

    Jensen, Torben K.; Herrmann, Kim Jesper; Bager, Anna Juul

    2011-01-01

    En undersøgelse af studiemiljøet på Aarhus Universitetet, foråret 2011 Rapport nr. 1: Studiemiljø2011 - Aarhus Universitet Rapport nr. 2: Studiemiljø2011 - Science and Technology Rapport nr. 3: Studiemiljø2011 - Health Rapport nr. 4: Studiemiljø2011 - Business and Social Sciences Rapport nr. 5......: Studiemiljø2011 - Arts Rapport nr. 6: Studiemiljø2011 - Teknisk rapport Rapport nr. 7: Studiemiljø2011 - Studerende med handicap...

  6. 78 FR 13885 - Notice of HUD-Held Multifamily & Healthcare Loan Sale, Second Offering (MHLS 2013-1)

    Science.gov (United States)

    2013-03-01

    ...-708-2625, extension 3927. Hearing- or speech-impaired individuals may call 202-708-4594 (TTY). These... are eligible to submit bids on the Mortgage Loans in the second offering for MHLS 2013- 1. Freedom of... the Freedom of Information Act and all regulations promulgated thereunder. Scope of Notice This notice...

  7. Employer health insurance offerings and employee enrollment decisions.

    Science.gov (United States)

    Polsky, Daniel; Stein, Rebecca; Nicholson, Sean; Bundorf, M Kate

    2005-10-01

    To determine how the characteristics of the health benefits offered by employers affect worker insurance coverage decisions. The 1996-1997 and the 1998-1999 rounds of the nationally representative Community Tracking Study Household Survey. We use multinomial logistic regression to analyze the choice between own-employer coverage, alternative source coverage, and no coverage among employees offered health insurance by their employer. The key explanatory variables are the types of health plans offered and the net premium offered. The models include controls for personal, health plan, and job characteristics. When an employer offers only a health maintenance organization married employees are more likely to decline coverage from their employer and take-up another offer (odds ratio (OR)=1.27, phealth plan coverage an employer offers affects whether its employees take-up insurance, but has a smaller effect on overall coverage rates for workers and their families because of the availability of alternative sources of coverage. Relative to offering only a non-HMO plan, employers offering only an HMO may reduce take-up among those with alternative sources of coverage, but increase take-up among those who would otherwise go uninsured. By modeling the possibility of take-up through the health insurance offers from the employer of the spouse, the decline in coverage rates from higher net premiums is less than previous estimates.

  8. Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates.

    Science.gov (United States)

    Feigelson, H S; McKean-Cowdin, R; Coetzee, G A; Stram, D O; Kolonel, L N; Henderson, B E

    2001-01-15

    We conducted a nested case-control study to evaluate whether polymorphisms in two genes involved in estrogen metabolism, CYP17 and HSD17B1, were useful in developing a breast cancer risk model that could help discriminate women who are at higher risk of breast cancer. If polymorphisms in these genes affect the level of circulating estrogens, they may directly influence breast cancer risk. The base population for this study is a multiethnic cohort study that includes African-American, Non-Latina White, Japanese, Latina, and Native Hawaiian women. For this analysis, 1508 randomly selected controls and 850 incident breast cancer cases of the first four ethnic groups who agreed to provide a blood specimen were included (76 and 80% response rates, respectively). The CYP17 A2 allele and the HSD17B1 A allele were considered "high-risk" alleles. Subjects were then classified according to number of high-risk alleles. After adjusting for age, weight, and ethnicity, we found that carrying one or more high-risk alleles increases the risk of advanced breast cancer in a dose-response fashion. The risk among women carrying four high-risk alleles was 2.21 [95% confidence interval (CI), 0.98-5.00; P for trend = 0.03] compared with those who carried none. This risk was largely limited to women who were not taking hormone replacement therapy (relative risk, 2.60; 95% CI, 0.95-7.14) and was most pronounced among those weighing 170 pounds or less (RR, 3.05; 95% CI, 1.29-7.25). These findings suggest that breast cancer risk has a strong genetic component and supports the theory that the underlying mechanism of "complex traits" can be understood using a multigenic model of candidate genes.

  9. 17 CFR 242.100 - Preliminary note; definitions.

    Science.gov (United States)

    2010-04-01

    ... with the distribution participant, issuer, or selling security holder that direct, effect, or recommend... course of its business. Distribution means an offering of securities, whether or not subject to... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Preliminary note; definitions...

  10. Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

    Science.gov (United States)

    Chen, Xuemei; Wang, Junfu; Wang, Rui; Su, Qinghong; Luan, Junwen; Huang, Haiyan; Zhou, Peng; Liu, Jinsheng; Xu, Xiaoqun

    2016-02-01

    Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included. The expression levels of Th1-, Th2- and Th17-associated cytokines in hypopharyngeal cancer tissues and pericarcinoma tissues were detected. The relationship between Th1, Th2, or Th17 infiltration and metastasis was studied. Our results showed that the mRNA and protein expressions of Th1 cytokines were lower, while the expressions of Th2 and Th17 cytokines were higher in tumor tissues, and the intensity of expression was strengthened with clinical stage increasing. Cancer tissues had higher level expressions of Th2 and Th17 cytokines than that of pericarcinoma tissues. From the above data, we speculated that high expressions of Th2- and Th17-associated cytokines in hypopharyngeal carcinoma may contribute to cancer development and metastasis.

  11. Beyond Techno-Utopia: Critical Approaches to Digital Health Technologies

    Directory of Open Access Journals (Sweden)

    Deborah Lupton

    2014-12-01

    Full Text Available This editorial presents an overview of digital health technologies, discusses previous research and introduces the contributions to the special issue “Beyond Techno-Utopia: Critical Approaches to Digital Health Technologies”. It is argued that thus far, few critical analyses of digital health technologies have been published in the social science literature, particularly in relation to the newest technologies. While the articles collected here in this special issue have gone some way in offering a critical response to digital health technologies, they represent only a beginning. Many more compelling topics remain to be investigated. The editorial ends with outlining directions for future research in this area.

  12. 17 CFR 275.206(4)-1 - Advertisements by investment advisers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Advertisements by investment advisers. 275.206(4)-1 Section 275.206(4)-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT ADVISERS ACT OF 1940 § 275.206(4)-1 Advertisements by investment advisers. (a) It shall...

  13. Getting Your Counselor to Support Technology Education

    Science.gov (United States)

    Preble, Brian C.

    2016-01-01

    Is there a disconnect between counselors and educators in technology and vocational education? What is counseling, and what is a school counselor's role in a secondary school setting? How can one work with his or her guidance staff to ensure that students better understand your course offerings? The development of relationships, knowledge, and…

  14. Technology Applied to ELT: Reviewing Practical Uses to Enhance English Teaching Programs

    Directory of Open Access Journals (Sweden)

    Javier Rojas Serrano

    2007-12-01

    Full Text Available In this paper, the author reports on some of the areas of technology currently used in the teaching and learning of languages, and reviews some of the uses of technological tools that are present in the English Adult Program and activities carried out at The Centro Colombo Americano (CCA in Bogota, Colombia. After briefly describing what is being applied worldwide in terms of what is being done at the CCA, some suggestions are offered in order to enhance the English teaching and learning processes through the use of new technologies.

  15. BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Kang, Youra; Timilshina, Maheshwor; Nam, Tae-Gyu; Jeong, Byeong-Seon; Chang, Jae-Hoon

    2017-02-28

    CD4 + T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases. In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund's adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells. BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.

  16. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    New season 2015-2016 The new season was revealed in May, and was warmly welcomed by the press, which is especially enthusiastic about the exceptional arrival of Fanny Ardand in September in the framework of Cassandre show. Discover the programme 2015-2016. The theatre La Comédie proposes different offers to our members Benefit from a reduction of 20 % on a full price ticket during all the season: from 38 CHF to 23 CHF ticket instead of 50 CHF to 30 CHF depending on the show. Buy two seasonal tickets at the price of one (offers valid upon availability, and until 30 september 2015) 2 Cards Libertà for 240 CHF instead of 480 CHF. Cruise freely through the season with 8 perfomances of your choice per season. These cards are transferrable, and can be shared with one or more accompanying persons. 2 Abo Piccolo for 120 CHF instead of 240 CHF. Let yourself be surprised a theatre performance with our discovery seasonal tickets, which includes 4 flagship perfomances for the season. ...

  17. 59 MDW/Science and Technology Poster

    Science.gov (United States)

    2017-04-28

    the Air Force, and Science and Engineering community Employ innov1tlve technologies ind lj)prOIChH to sustain health, performance ind revolutionize...Medics Through Patient.Centered Care Our Goals Provide technic1I expertise and resources, project management assistance, direction, ind...SGYU SUBJECT: Professional Presentation Approval • ’ ...... -""""’ ~ 18 APR 20 17 1. Your paper, entitled 59 MDW/ Science & Technology Poster

  18. 17 CFR 240.36a1-1 - Exemption from Section 7 for OTC derivatives dealers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from Section 7 for OTC derivatives dealers. 240.36a1-1 Section 240.36a1-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934...

  19. Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis.

    Directory of Open Access Journals (Sweden)

    Heather R Conti

    Full Text Available Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.

  20. T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

    Science.gov (United States)

    Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

    2012-11-01

    T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

  1. Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Louise M Burrell

    Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

  2. JST Thesaurus Headwords and Synonyms: 1次記憶装置 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term 1次記憶装置 名詞 サ変接続 * * * * 主メモリ シュメモリ シュメモリ Thesaurus2015 200906038702033733 C EA17 MULTI_WORD 1 次 記憶 装置

  3. Applications of induction linac technology to heavy ion fusion

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1977-07-01

    Evaluation of the application of heavy ion accelerators to ignite d-t pellets in a thermonuclear reactor is discussed. Accelerator design requirements considered include transport-limited current, beam injection conditions, and pulse bunching and focusing characteristics. The desirability of resonant and non-resonant accelerating structures is comparatively examined. The required power system switch tubes are discussed. It is concluded that heavy ion accelerators could offer a promising solution to the pellet-igniter problem. The advantages pointed out for this approach include electric efficiency greater than 10 percent, the possibility of high repetition rates (1 to 10 Hz), and a mature technological base

  4. Overview of the French offer in nuclear training: 60 years to serve development and knowledge transfer

    International Nuclear Information System (INIS)

    Fanjas, Y.; Navon-Gross, A.; Mougel, B.; Verdier, A.

    2017-01-01

    As early as the beginning of its nuclear program, France has developed a wide range of higher education programs and occupational training in nuclear sciences, nuclear technologies and nuclear engineering. INSTN (Institute for Nuclear Sciences and Nuclear Technologies) was founded in 1956 inside CEA premises at Saclay to issue the diploma of 'ingenieur en genie atomique'. This diploma is still delivered and celebrated its 60. anniversary in 2016. A large course offering has been added to the sole initial INSTN diploma. Throughout France and each year about 2000 students are awarded a diploma opening the gates of nuclear industry or research from vocational baccalaureates (130) to doctoral thesis (200) via engineer/master degrees (1270). Continuous training has also been developed, employees from the nuclear industry benefit from 16 days a year of training in average. French high education systems are open to foreign students and 9 master degrees in nuclear engineering are entirely taught in English. (A.C.)

  5. Theoretical Prediction of the Heats of Formation, Densities, and Relative Sensitivities for 1,7-dinitro-3,4,5,8-tetra N-oxide-bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro-3,5,8-tri N-oxide bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro 3,5-bis N-oxide bis([1,2,3]triazolo)[4,5-b:5’,4’ e]pyrazine, 1,7-dinitro 1,7-dihydrobis([1,2,3]triazolo)[4,5-b:4’,5’-e]pyrazine

    Science.gov (United States)

    2016-09-01

    estimation of the impact sensitivities has been calculated. This report outlines the procedures used to generate this information, as well as Cheetah...1 US ARMY ARDEC (PDF) A DISTASIO 1 US ARMY ARDEC (PDF) S NICOLICH 1 NAVAL SURF WARFARE (PDF) CNTR J MANNION 17 DIR USARL

  6. 17 CFR 240.8c-1 - Hypothecation of customers' securities.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Hypothecation of customers... Securities Exchange Act of 1934 Hypothecation of Customers' Securities § 240.8c-1 Hypothecation of customers... any customer under circumstances: (1) That will permit the commingling of securities carried for the...

  7. CSIR Technology Impact 2002

    CSIR Research Space (South Africa)

    CSIR

    2002-01-01

    Full Text Available This issue of Technology Impact offers a brief snapshot of CSIR activities during the year under review (1 March 2001 - 28 February 2002) by highlighting a number of innovative projects and initiatives in these areas....

  8. Species used for drug testing reveal different inhibition susceptibility for 17beta-hydroxysteroid dehydrogenase type 1.

    Directory of Open Access Journals (Sweden)

    Gabriele Möller

    Full Text Available Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1 for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17beta-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17beta-HSD types 1, 2, 4, 5 and 7 but also against 17beta-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17beta-HSDs analyzed were observed. Especially, the rodent 17beta-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17beta-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution.

  9. A Space-Age University without Campus or Faculty Offers Its TV Courses Nationwide via Satellite.

    Science.gov (United States)

    Fields, Cheryl M.

    1987-01-01

    The National Technological University, a consortium of engineering schools, offers programs based on satellite transmissions of live and videotaped graduate courses to industrial sites around the country. (MSE)

  10. Natural abundant (17) O NMR in a 1.5-T Halbach magnet.

    Science.gov (United States)

    Sørensen, Morten K; Bakharev, Oleg N; Jensen, Ole; Nielsen, Niels Chr

    2016-06-01

    We present mobile, low-field (17) O NMR as a means for monitoring oxygen in liquids. Whereas oxygen is one of the most important elements, oxygen NMR is limited by a poor sensitivity related to low natural abundance and gyro-magnetic ratio of the NMR active (17) O isotope. Here, we demonstrate (17) O NMR detection at a Larmor frequency of 8.74 MHz in a 1.5-T Halbach neodymium magnet with a home-built digital NMR instrument suitable for large-scale production and in-line monitoring applications. The proposed (17) O NMR sensor may be applied for direct, noninvasive measurements of water content in, for example, oil, manure, or food in automated quality or process control. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Biopower market impact: Applying advanced technologies to specific needs

    International Nuclear Information System (INIS)

    Gregoire, C.E.; Bain, R.L.; Craig, K.R.

    1994-01-01

    The impact of biopower on the electric power capacity in the United States is projected to increase 5- to 10-fold by the year 2010. A number of competing technologies will likely be available that will provide a variety of advantages for the U.S. economy, from creating jobs in rural areas to increasing the demand for component manufacturing. Biopower also offers environmental advantages over conventional fossil fuel-fired power plants, particularly global climate change benefits. Feedstock type and availability, proximity to users or transmission stations, and markets for potential byproducts will influence which biomass conversion technology is selected and the scale of operation. Cofiring biomass in aging coal-fired power plants represents a near-term alternative for reducing sulfur and CO 2 emissions. Producing biocrude from pyrolysis processes may be suitable for isolated feedstock supplies with high transportation costs or to supply fuel to a single large family in a centralized area. Integrated gasification/combined cycle (IGCC) systems offer high efficiencies and low capital costs. More advanced systems, including fuel cells, will offer additional opportunities for increasing the impact of biopower on the nation's power production

  12. 17 CFR 240.15c1-3 - Misrepresentation by brokers, dealers and municipal securities dealers as to registration.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Misrepresentation by brokers...-The-Counter Markets § 240.15c1-3 Misrepresentation by brokers, dealers and municipal securities..., as used in section 15(c)(1) of the Act, is hereby defined to include any representation by a broker...

  13. Th17 cells and IL-17 in protective immunity to vaginal candidiasis.

    Science.gov (United States)

    Pietrella, Donatella; Rachini, Anna; Pines, Mark; Pandey, Neelam; Mosci, Paolo; Bistoni, Francesco; d'Enfert, Cristophe; Vecchiarelli, Anna

    2011-01-01

    Th17 cells play a major role in coordinating the host defence in oropharyngeal candidiasis. In this study we investigated the involvement of the Th17 response in an animal model of vulvovaginal candidiasis (VVC). To monitor the course of infection we exploited a new in vivo imaging technique. i) The progression of VVC leads to a strong influx of neutrophils in the vagina soon after the challenge which persisted despite the resolution of infection; ii) IL-17, produced by vaginal cells, particularly CD4 T cells, was detected in the vaginal wash during the infection, reaching a maximum 14 days after the challenge; iii) The amount and kinetics of IL-23 in vaginal fluids were comparable to those in vaginal cells; iv) The inhibition of Th17 differentiation led to significant inhibition of IL-17 production with consequent exacerbation of infection; v) An increased production of βdefensin 2 was manifested in cells of infected mice. This production was strongly reduced when Th17 differentiation was inhibited and was increased by rIL-17 treatment. These results imply that IL-17 and Th17, along with innate antimicrobial factors, have a role in the immune response to vaginal candidiasis.

  14. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: Children from 5 to 15 years old: 30 CHF instead of 39 CHF Adults from 16 years old: 36 CHF instead of 49 CHF Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  15. Offers

    CERN Multimedia

    Association du personnel

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: – Children from 5 to 15 years old: 30 CHF instead of 39 CHF – Adults from 16 years old: 36 CHF instead of 49 CHF – Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  16. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Single tariff Adulte/Enfant Tickets “Zone terrestre” 20 euros instead of 25 euros. Access to Aqualibi: 5 euros instead of 8 euros on presentation of your ticket SA member. Free for children under 3, with limited access to the attractions. More information on our website : http://association.web.cern.ch/association/en/OtherActivities/Walibi.html

  17. 1H diffusion-weighted, 13C and 17O NMR spectroscopy: methodological developments to study brain structure and function in vivo

    International Nuclear Information System (INIS)

    Najac, Chloe

    2014-01-01

    Magnetic Resonance Spectroscopy is a unique tool that allows acquiring brain biochemical profiles and quantifying many cellular parameters in vivo. During this thesis, three different techniques have been developed: (i) 1 H diffusion-weighted, (ii) carbon-13 ( 13 C) and (iii) oxygen-17 ( 17 O) NMR spectroscopy to study brain structure and function in vivo. Brain metabolites are cell-specific endogenous tracers of the intracellular space whose translational diffusion depends on many cellular properties (e.g.: cytosol viscosity and intracellular restriction). Studying the variation of the diffusion coefficient (ADC) as a function of diffusion time (td) allows untangling and quantifying those parameters. In particular, measuring metabolites ADC at long diffusion times gives information about the metabolites compartmentation in cells. In a first study, we measured neuronal and astrocytic metabolites ADC over a large time window (from 80 ms to 1 s) in a large voxel in the macaque brain. No dependence of all metabolites ADC on td was observed suggesting that metabolites primarily diffuse in neuronal (dendrites and axons) and astrocytic processes and are not confined inside the cell body and organelles (nucleus, mitochondria). The large size of the voxel, due to low detection sensitivity, did not allow us to study metabolites compartmentation in pure white (WM) and grey matters (GM). Therefore, we performed a new study in the human brain. Results showed that in both WM and GM metabolites diffuse in fiber-like cell structure. Finally, using an even larger time window (up to 2 s) in the macaque brain and analytical models mimicking the cell structure, we estimated the length of neuronal (∼110 μm) and astrocytic (∼70 μm) processes. ATP (adenosine triphosphate), the main source of energy in the organism, is produced thanks to glucose oxidation inside the mitochondria. 13 C NMR spectroscopy is a well-known technique to study brain energy metabolism and can be used to

  18. Angiotensin-(1-7 Promotes Resolution of Neutrophilic Inflammation in a Model of Antigen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Lívia C. Barroso

    2017-11-01

    Full Text Available Defective resolution of inflammation may be crucial for the initiation and development of chronic inflammatory diseases, such as arthritis. Therefore, it has been suggested that therapeutic strategies based on molecules that facilitate inflammation resolution present great potential for the treatment of chronic inflammatory diseases. In this study, we investigated the effects and role of angiotensin-(1-7 [Ang-(1-7] in driving resolution of neutrophilic inflammation in a model of arthritis. For this purpose, male C57BL/6 mice were subjected to antigen-induced arthritis and treated with Ang-(1-7 at the peak of the inflammatory process. Analysis of the number of inflammatory cells, apoptosis, and immunofluorescence for NF-κB was performed in the exudate collected from the knee cavity. Neutrophil accumulation in periarticular tissue was measured by assaying myeloperoxidase activity. Apoptosis of human neutrophil after treatment with Ang-(1-7 was evaluated morphologically and by flow cytometry, and NF-κB phosphorylation by immunofluorescence. Efferocytosis was evaluated in vivo. Therapeutic treatment with Ang-(1-7 at the peak of inflammation promoted resolution, an effect associated with caspase-dependent neutrophils apoptosis and NF-κB inhibition. Importantly, Ang-(1-7 was also able to induce apoptosis of human neutrophils, an effect associated with NF-κB inhibition. The pro-resolving effects of Ang-(1-7 were inhibited by the Mas receptor antagonist A779. Finally, we showed that Ang-(1-7 increased the efferocytic ability of murine macrophages. Our results clearly demonstrate that Ang-(1-7 resolves neutrophilic inflammation in vivo acting in two key step of resolution: apoptosis of neutrophils and their removal by efferocytosis. Ang-(1-7 is a novel mediator of resolution of inflammation.

  19. Structure and magnetic properties of Gd2Co17-xCr x (1.17 ≤ x ≤ 3.0) compounds

    International Nuclear Information System (INIS)

    Fuquan, B.; Tegus, O.; Dagula, W.; Brueck, E.; Klaasse, J.C.P.; Buschow, K.H.J.

    2007-01-01

    The structure and magnetic properties of Gd 2 Co 17-x Cr x (1.17 ≤ x ≤ 3.0) compounds have been investigated by means of X-ray diffraction (XRD) and magnetization measurements. The powder X-ray diffraction patterns show that all samples crystallize as a single phase with the rhombohedral Th 2 Zn 17 -type structure. The lattice parameters a and the unit cell volume V increases slightly with increasing Cr content, but the c parameter varies in a less simple way with increasing Cr content. The X-ray diffraction patterns of the magnetically aligned samples show that all compounds investigated have uniaxial anisotropy. Spin reorientation phenomena occur in all of the compounds. The Curie temperature T C , the spin reorientation temperature T sr , the spontaneous magnetization M 0 and the saturation magnetization M s decrease with the increasing Cr content. The anisotropy constant K 1 and the anisotropy field B a of the compounds at room temperature reach a maximum for x = 1.76. The M 0 and M s increase with increasing temperature from 5 K to 300 K. The easy-axis anisotropy of all compounds changes to easy-plane anisotropy at low temperatures and the spin reorientation phenomena are more pronounced for low Cr concentration

  20. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation

    Science.gov (United States)

    Estacion, M.; Vohra, B. P. S; Liu, S.; Hoeijmakers, J.; Faber, C. G.; Merkies, I. S. J.; Lauria, G.; Black, J. A.

    2015-01-01

    Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na+ concentration ([Na+]) and intracellular [Ca2+] following stimulation with high [K+] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca2+] transients evoked by high [K+] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K+] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K+] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca2+ or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K+] and 2-DG. These results point to [Na+] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca2+ toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID:26156380

  1. What makes Chinese firms to choose international external technology sources? An inquiry on internationalization, innovation and institutions

    DEFF Research Database (Denmark)

    Li-Ying, Jason; Wang, Yuandi

    2013-01-01

    . However, we have also witnessed an emerging trend of external acquisition of technology by EMFs firms in both international and domestic markets. Why some EMFs are active in sourcing both domestic and international technologies instead of being significantly in favour of foreign technologies from...... framework. Based on a unique sample of 389 Chinese firms on their inward technology licensing activities through an observation period from 2000 to 2005, it is found that (1) firms’ international market orientation; (2) firm’s technological capability; (3) regional innovation capability; and (4......External technology sourcing from developed countries has been one of the most important vehicles by which emerging market firms (EMFs) sustain competiveness. Foreign advanced technologies offer EMFs opportunities to gain access to state-of-the-art technologies and upgrade their competitiveness...

  2. Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice.

    Science.gov (United States)

    Jonsson, A; Fransson, R; Haramaki, Y; Skogh, A; Brolin, E; Watanabe, H; Nordvall, G; Hallberg, M; Sandström, A; Nyberg, F

    2015-07-09

    Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Comparison of the Isothermal Oxidation Behavior of As-Cast Cu-17%Cr and Cu-17%Cr-5%Al. Part 1; Oxidation Kinetics

    Science.gov (United States)

    Raj. Sai V.

    2008-01-01

    The isothermal oxidation kinetics of as-cast Cu-17%Cr and Cu-17%Cr-5%Al in air were studied between 773 and 1173 K under atmospheric pressure. These observations reveal that Cu- 17%Cr-5%Al oxidizes at significantly slower rates than Cu-17%Cr. The rate constants for the alloys were determined from generalized analyses of the data without an a priori assumption of the nature of the oxidation kinetics. Detailed analyses of the isothermal thermogravimetric weight change data revealed that Cu-17%Cr exhibited parabolic oxidation kinetics with an activation energy of 165.9 9.5 kJ mol-1. In contrast, the oxidation kinetics for the Cu-17%Cr- 5%Al alloy exhibited a parabolic oxidation kinetics during the initial stages followed by a quartic relationship in the later stages of oxidation. Alternatively, the oxidation behavior of Cu-17%CR- 5%Al could be better represented by a logarithmic relationship. The parabolic rate constants and activation energy data for the two alloys are compared with literature data to gain insights on the nature of the oxidation mechanisms dominant in these alloys.

  4. The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

    Science.gov (United States)

    Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

    2017-07-15

    The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT 1 ) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The directory of United States coal & technology export resources. Profiles of domestic US corporations, associations and public entities, nationwide, which offer products or services suitable for export, relating to coal and its utilization

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    The purpose of this directory is to provide a listing of available U.S. coal and coal related resources to potential purchasers of those resources abroad. The directory lists business entities within the US which offer coal related resources, products and services for sale on the international market. Each listing is intended to describe the particular business niche or range of product and/or services offered by a particular company. The listing provides addresses, telephones, and telex/fax for key staff in each company committed to the facilitation of international trade. The content of each listing has been formulated especially for this directory and reflects data current as of the date of this edition. The directory listings are divided into four primary classifications: coal resources; technology resources; support services; and financing and resource packaging. The first three of which are subdivided as follows: Coal Resources -- coal derivatives, coal exporters, and coal mining; Technology Resources -- advanced utilization, architects and engineers, boiler equipment, emissions control and waste disposal systems, facility construction, mining equipment, power generation systems, technical publications, and transport equipment; Support Services -- coal transport, facility operations, freight forwarders, sampling services and equipment, and technical consultants. Listings for the directory were solicited on the basis of this industry breakdown. Each of the four sections of this directory begins with a matrix illustrating which companies fall within the particular subclassifications specific to that main classification. A general alphabetical index of companies and an index by product/service classification are provided following the last section of the directory.

  6. Offering self-administered oral HIV testing to truck drivers in Kenya to increase testing: a randomized controlled trial.

    Science.gov (United States)

    Kelvin, Elizabeth A; George, Gavin; Mwai, Eva; Nyaga, Eston; Mantell, Joanne E; Romo, Matthew L; Odhiambo, Jacob O; Starbuck, Lila; Govender, Kaymarlin

    2018-01-01

    We conducted a randomized controlled trial among 305 truck drivers from two North Star Alliance roadside wellness clinics in Kenya to see if offering HIV testing choices would increase HIV testing uptake. Participants were randomized to be offered (1) a provider-administered rapid blood (finger-prick) HIV test (i.e., standard of care [SOC]) or (2) a Choice between SOC or a self-administered oral rapid HIV test with provider supervision in the clinic. Participants in the Choice arm who refused HIV testing in the clinic were offered a test kit for home use with phone-based posttest counseling. We compared HIV test uptake using the Mantel Haenszel odds ratio (OR) adjusting for clinic. Those in the Choice arm had higher odds of HIV test uptake than those in the SOC arm (OR = 1.5), but the difference was not statistically significant (p = 0.189). When adding the option to take an HIV test kit for home use, the Choice arm had significantly greater odds of testing uptake (OR = 2.8, p = 0.002). Of those in the Choice arm who tested, 26.9% selected the SOC test, 64.6% chose supervised self-testing in the clinic, and 8.5% took a test kit for home use. Participants varied in the HIV test they selected when given choices. Importantly, when participants who refused HIV testing in the clinic were offered a test kit for home use, an additional 8.5% tested. Offering truck drivers a variety of HIV testing choices may increase HIV testing uptake in this key population.

  7. Lessons from patents. Using patents to measure technological change in environmental models

    International Nuclear Information System (INIS)

    Popp, David

    2005-01-01

    When studying solutions to long-term environmental problems such as climate change, it is important to consider the role that technological change may play. Nonetheless, to date few economic models of environmental policy explicitly model the link between policy and technological change. There is a growing body of evidence that the incentives offered by prices and environmental regulations have a strong influence on both the creation and adoption of new technologies. In several recent papers, I have used patent data to examine the links between environmental policy and technological change. In addition, I have used the results of this research to calibrate the ENTICE model (for ENdogenous Technological change) of climate change, which links energy-related R and D to changes in the price of carbon. Drawing on my experiences from empirical studies on innovation and from modeling the climate change problem, in this paper I review some of the key lessons from recent empirical work using patents to study environmental innovation and diffusion, and discuss its implications for modeling climate change policy. I conclude by offering suggestions for future research

  8. Technology transfer in CANDU marketing

    International Nuclear Information System (INIS)

    Pon, G.A.

    1982-06-01

    The author discusses how the CANDU system lends itself to technology transfer, the scope of CANDU technology transfer, and the benefits and problems associated with technology transfer. The establishment of joint ventures between supplier and client nations offers benefits to both parties. Canada can offer varying technology transfer packages, each tailored to a client nation's needs and capabilities. Such a package could include all the hardware and software necessary to develop a self-sufficient nuclear infrastructure in the client nation

  9. Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review.

    Science.gov (United States)

    Asadi-Samani, Majid; Bagheri, Nader; Rafieian-Kopaei, Mahmoud; Shirzad, Hedayatollah

    2017-08-01

    Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. CSIR Technology Impact 2003

    CSIR Research Space (South Africa)

    CSIR

    2003-01-01

    Full Text Available This issue of Technology Impact offers a brief snapshot of CSIR activities during the year under review (1 March 2002 - 28 February 2003) by highlighting a number of innovative projects and initiatives in various CSIR business units....

  11. The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

  12. Using Avatars to Model Weight Loss Behaviors: Participant Attitudes and Technology Development

    Science.gov (United States)

    Napolitano, Melissa A.; Hayes, Sharon; Russo, Giuseppe; Muresu, Debora; Giordano, Antonio; Foster, Gary D.

    2013-01-01

    Background: Virtual reality and other avatar-based technologies are potential methods for demonstrating and modeling weight loss behaviors. This study examined avatar-based technology as a tool for modeling weight loss behaviors. Methods: This study consisted of two phases: (1) an online survey to obtain feedback about using avatars for modeling weight loss behaviors and (2) technology development and usability testing to create an avatar-based technology program for modeling weight loss behaviors. Results: Results of phase 1 (n = 128) revealed that interest was high, with 88.3% stating that they would participate in a program that used an avatar to help practice weight loss skills in a virtual environment. In phase 2, avatars and modules to model weight loss skills were developed. Eight women were recruited to participate in a 4-week usability test, with 100% reporting they would recommend the program and that it influenced their diet/exercise behavior. Most women (87.5%) indicated that the virtual models were helpful. After 4 weeks, average weight loss was 1.6 kg (standard deviation = 1.7). Conclusion: This investigation revealed a high level of interest in an avatar-based program, with formative work indicating promise. Given the high costs associated with in vivo exposure and practice, this study demonstrates the potential use of avatar-based technology as a tool for modeling weight loss behaviors. PMID:23911189

  13. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    The “La Comédie” theatre unveiled its programme for the season 2016–2017 in late May, and it was met with great enthusiasm by the press. Leading names of the European and Swiss theatre scenes, such as director Joël Pommerat who recently won four Molière awards, will make an appearance! We are delighted to share this brand new, rich and varied programme with you. The “La Comédie” theatre has various discounts for our members Buy 2 subscriptions for the price of 1 : 2 cards “Libertà” for CHF 240.- instead of CHF 480.- Cruise freely through the season with an 8-entry card valid for the shows of your choice. These cards are transferable and can be shared with one or more accompanying persons. 2 cards “Piccolo” for CHF 120 instead of CHF 240.- This card lets you discover 4 shows which are suitable for all audiences (offers valid while stock lasts and until October 31, 20...

  14. 19 CFR 115.17 - Appeal to Commissioner of Customs.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

  15. Residential home heating: The potential for air source heat pump technologies as an alternative to solid and liquid fuels

    International Nuclear Information System (INIS)

    Kelly, J. Andrew; Fu, Miao; Clinch, J. Peter

    2016-01-01

    International commitments on greenhouse gases, renewables and air quality warrant consideration of alternative residential heating technologies. The residential sector in Ireland accounts for approximately 25% of primary energy demand with roughly half of primary home heating fuelled by oil and 11% by solid fuels. Displacing oil and solid fuel usage with air source heat pump (ASHP) technology could offer household cost savings, reductions in emissions, and reduced health impacts. An economic analysis estimates that 60% of homes using oil, have the potential to deliver savings in the region of €600 per annum when considering both running and annualised capital costs. Scenario analysis estimates that a grant of €2400 could increase the potential market uptake of oil users by up to 17% points, whilst a higher oil price, similar to 2013, could further increase uptake from heating oil users by 24% points. Under a combined oil-price and grant scenario, CO_2 emissions reduce by over 4 million tonnes per annum and residential PM_2_._5 and NO_X emissions from oil and peat reduce close to zero. Corresponding health and environmental benefits are estimated in the region of €100m per annum. Sensitivity analyses are presented assessing the impact of alternate discount rates and technology performance. This research confirms the potential for ASHP technology and identifies and informs policy design considerations with regard to oil price trends, access to capital, targeting of grants, and addressing transactions costs. - Highlights: • Air Source Heat Pumps can offer substantial savings over oil fired central heating. • Significant residential air and climate emission reductions are possible. • Associated health and environmental benefits are estimated up to €100m per annum. • Results can inform policy interventions in the residential market to support change.

  16. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Science.gov (United States)

    Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  17. Introduction to the papers of TWG16: Learning Mathematics with Technology and Other Resources

    NARCIS (Netherlands)

    Drijvers, P.H.M.; Faggiano, Eleonora; Geraniou, Eirini; Weigand, Hans-Georg

    2017-01-01

    The use of technology and other resources for mathematical learning is a current issue in the field of mathematics education and lags behind the rapid advances in Information and Communication Technology. Technological developments offer opportunities, which are not straightforward to exploit in

  18. Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.

    Science.gov (United States)

    Su, Yixin; Bi, Jianli; Pulgar, Victor M; Chappell, Mark C; Rose, James C

    2017-06-01

    We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na + ) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to angiotensin-(1-7) [Ang-(1-7)]. The present study determined the Na + uptake and nitric oxide (NO) response to low-dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as percentage of basal uptake or area under the curve for Na + or percentage of control for NO. Male Beta RPTC exhibited greater Na + uptake than male vehicle cells (433 ± 28 vs. 330 ± 26%; P 0.05). Ang-(1-7) significantly inhibited Na + uptake in RPTC from vehicle male (214 ± 11%) and from both vehicle (190 ± 14%) and Beta (209 ± 11%) females but failed to attenuate Na + uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1-7) in male but not female RPTC. Both the Na + and NO responses to Ang-(1-7) were blocked by Mas receptor antagonist d-Ala 7 -Ang-(1-7). We conclude that the tubular Ang-(1-7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na + handling by the renal tubules. Copyright © 2017 the American Physiological Society.

  19. Creation of a European network dedicated to technology transfer

    CERN Multimedia

    2008-01-01

    The CERN Council recently approved the creation of a technology transfer network, whose aim will be to improve European industry’s access to the technologies developed by the particle physics community in the Member States. The gas detectors for the TOTEM experiment (GEM) offer potential for fruitful collaboration within the framework of the TT network. Many other technologies are going down the same road.The desire to set up a technology transfer network follows on from the European Strategy for Particle Physics, approved by the CERN Council on 14 July 2006 in Lisbon. In this context, special emphasis was laid on European industry’s participation in the implementation of particle physics programmes and, in particular, its access to the new technologies developed by the scientific community. It was recognised that effort needs to be put into improving the efficiency of technology transfer...

  20. 17 CFR 240.11a-1 - Regulation of floor trading.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Regulation of floor trading... Securities Exchange Act of 1934 Adoption of Floor Trading Regulation (rule 11a-1) § 240.11a-1 Regulation of floor trading. (a) No member of a national securities exchange, while on the floor of such exchange...

  1. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    Science.gov (United States)

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-11-14

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  2. Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics.

    Science.gov (United States)

    Xiao, Fei; Yang, Maohua; Xu, Youjun; Vongsangnak, Wanwipa

    2015-01-01

    Cytochrome P450 17A1 (CYP17A1) is associated in the steroid hormone biosynthesis in human. As cell proliferation of prostate cancer in response to androgen steroid, an inhibition of CYP17A1 becomes an alternative approach to inhibit biosynthesis of androgen and support treatment of prostate cancer. However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD) simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy.

  3. Could 3D bioprinted tissues offer future hope for microtia treatment?

    Science.gov (United States)

    Thomas, Daniel J

    2016-08-01

    Microtia is a congenital deformity where the pinna is underdeveloped. Contraindications to rib surgery for microtia reconstruction include high-risk surgical status and chest-wall deformities [1-2]. However does stem-cell-based 3D Bioprinting offer revolutionary therapeutic options for patients with such tissue abnormalities. As a technology, 3D-bioprinting is being developed to generate homogeneous tissues by depositing a low viscosity printable cellular-active gel which matures into a tissue [3]. Currently on-going research is developing the process towards producing cartilage tissues for use in reconstructive surgery. This process focuses on using the natural self-organising properties of cells in order to produce a functional tissue which has measurable: mechanical, metabolic and functional properties. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Developing an integrated technology roadmapping process to meet regional technology planning needs: the e-bike pilot study

    NARCIS (Netherlands)

    Cowan, Kelly R.; Daim, Tugrul U.; Walsh, Steven Thomas; Kocaoglu, Dundar F.; Anderson, Timothy R.; Daim, Tugrul U.; Kozanoglu, Dilek Cetindamar; Niwa, Kiyoshi; Perman, Gary

    2014-01-01

    Smart grid is a promising class of new technologies offering many potential benefits for electric utility systems, including possibilities for smart appliances which can communicate with power systems and help to better match supply and demand. Additional services include the ability to better

  5. Fourteen-year trends in sodium content of menu offerings at eight leading fast-food restaurants in the USA.

    Science.gov (United States)

    Rudelt, Amanda; French, Simone; Harnack, Lisa

    2014-08-01

    To examine changes in the Na content of lunch/dinner menu offerings at eight of the leading fast-food restaurants in the USA between 1997/1998 and 2009/2010. Menu offerings and nutrient composition information for the menu items were obtained from archival versions of the University of Minnesota Nutrition Coordinating Center (NCC) Food and Nutrient Database. Nutrient composition information for lunch/dinner menu items sold by the fast-food restaurants included in the present study was updated in the database biannually. Menus were analysed for changes in mean Na content of all menu offerings (except beverages) and specific categories of menu items among all restaurants and for each individual restaurant. Lunch/dinner food menu of eight leading US fast-food restaurants. Between 1997/1998 and 2009/2010 the mean Na content of menu offerings across the eight restaurants increased by 23·4 %. Examining specific food categories, mean Na content of entrées by increased 17·2 % and that of condiments increased by 26·1 %. Only side dishes showed a decrease of 6·6 %. None of the restaurants examined had a decrease in Na across the lunch/dinner menu offerings over the 14 years examined. Results suggest that over the time period studied there has been no meaningful reduction in the Na content of lunch/dinner menu offerings at the leading fast-food restaurants examined in the present study.

  6. Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.

    Science.gov (United States)

    Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex

    2008-07-24

    17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.

  7. A prototype to study cognitive and aesthetic aspects of mixed reality technologies

    OpenAIRE

    Gunia, Artur; Indurkhya, Bipin

    2017-01-01

    Mixed reality systems integrate virtual reality with real-world perception and cognition to offer enhanced interaction possibilities with the environment. Our aim is to demonstrate that mixed reality technologies strongly affect our aesthetic sense and mental models. So, in designing such technologies, we need to incorporate perspectives from different disciplines. We present different approaches and implementations of cognitive enhancement and cognitive technologies, consider some practical ...

  8. Comparing the New York State Smokers' Quitline Reach, Services Offered, and Quit Outcomes to 44 Other State Quitlines, 2010 to 2015.

    Science.gov (United States)

    Mann, Nathan; Nonnemaker, James; Chapman, LeTonya; Shaikh, Asma; Thompson, Jesse; Juster, Harlan

    2018-06-01

    To summarize the reach, services offered, and cessation outcomes of the New York Quitline and compare with other state quitlines. Descriptive study. Forty-five US states. State-sponsored tobacco cessation quitlines in 45 US states that provided complete data to the Centers for Disease Control and Prevention's National Quitline Data Warehouse (NQDW) for 24 quarters over 6 years (2010-Q1 through 2015-Q4). Telephone quitlines that offer tobacco use cessation services, including counseling, self-help materials, and nicotine replacement therapy (NRT), to smokers at no cost to them. Percentage of adult tobacco users in the state who received counseling and/or free NRT from state quitlines (reach), services offered by state quitlines, and cessation outcomes among quitline clients 7 months after using quitline services. Reach, services offered, and cessation outcomes for the New York Quitline were compared with similar measures for the other 44 state quitlines with complete NQDW data for all quarters from 2010 through 2015. New York's average annual quitline reach from 2010 through 2015 was 3.0% per year compared to 1.1% per year for the other 44 states examined. Although the New York Quitline was open fewer hours per week and offered fewer counseling sessions and a smaller amount of free NRT than most of the other 44 state quitlines, the New York Quitline had similar quit rates to most of those state quitlines.

  9. Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

    Science.gov (United States)

    Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto

    2016-01-01

    Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Offer

    CERN Multimedia

    CARLSON WAGONLIT TRAVEL

    2011-01-01

    Special offer   From 14th to 28th February 2011: no CWT service fee! For any new reservation of a holiday package (flight + hotel/apartment) from a catalog “summer 2011” For any additional information our staff is at your disposal from Monday – Friday, from 8h30 to 16h30. Phone number 72763 or 72797 Carlson Wagonlit Tavel, Agence du CERN  

  11. CSIR Technology Impact 2001

    CSIR Research Space (South Africa)

    CSIR

    2001-01-01

    Full Text Available This issue of Technology Impact offers a brief snapshot of CSIR activities during the year under review (1 March 2000 - 28 February 2001) by highlighting a number of innovative projects and initiatives in these areas. It present a rich canvas...

  12. Tools to Use in an Information Technology Class--and Best of All They Are FREE!

    Science.gov (United States)

    Swanson, Dewey; Gusev, Dmitri A.

    2016-01-01

    Purdue Polytechnic has several locations in the state of Indiana offering students a chance to get a Purdue degree. The Computer and Information Technology (CIT) department offers the CIT degree at three sites in Indiana: Anderson, Columbus and Kokomo. CIT offers several potential majors including Cybersecurity, Network Engineering, Systems…

  13. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2012 Half-day ticket: 5 hours, same price weekends, public holidays and weekdays. Children from 5 to 15 years old: 26 CHF instead of 35 CHF Adults from 16 years old: 32 CHF instead of 43 CHF Bonus! Free for children under 5. Aquaparc Les Caraïbes sur Léman 1807 Le Bouveret (VS)

  14. The genetics of dementias. Part 1: Molecular basis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-06-01

    Full Text Available Frontotemporal dementia (FTD, characterized by neurodegeneration mainly in the frontal and temporal lobes, accounts for ca. 10–15�0of all dementias. In 1892 the Czech-German neuropsychiatrist Arnold Pick reported the first case of FTD in a 71-year-old patient suffering from progressive dementia, memory disturbances, and aphasia associated with frontal and temporal lobe atrophy and the presence of neuronal inclusions. Later the inclusions were named Pick bodies. The neuropathological hallmark of FTD is very differentiated. In contrast to Alzheimer’s disease (AD, there are neither senile plaques nor neurofibrillary tangles in the brains of FTD patients. Frontotemporal dementias are tauopathies, a group of disorders caused by aberrant metabolism of tau protein, a family of proteins associated with microtubules (MAPT: macrotubule-associated tau protein. In the nervous system the protein stabilizes microtubules in neuronal axons and is thus responsible for crucial processes in neuron metabolism, such as signal transduction, plasticity, and intracellular transport. In the human brain, six isoforms are produced from the MAPT gene (chromosome 17 q21.2 by alternative mRNA splicing. The isoforms differ in the number of amino acids in the protein chain, the presence of three (3R tau type or four (4R tau type domains responsible for binding to microtubules, and one or two inserts containing from 29 to 58 amino acids. The isoforms are modified posttranslationally by hyperphosphorylation, glycation, or oxidation, which can change the protein’s properties and disturb its normal function. Altered metabolism of tau protein changes its interactions with tubulin, leading to destabilization of the microtubule structure and initiating the generation of toxic tau aggregates. The first mutations in the MAPT gene responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17 were found in 1998. So far over 40 mutations in the MAPT

  15. 33 CFR 17.01-10 - Authority to receive gifts.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Authority to receive gifts. 17.01... GENERAL UNITED STATES COAST GUARD GENERAL GIFT FUND General Provisions § 17.01-10 Authority to receive gifts. (a) The Commandant, United States Coast Guard, may accept, receive, hold, or administer gifts...

  16. A randomised controlled trial to assess the effectiveness of offering study results as an incentive to increase response rates to postal questionnaires [ISRCTN26118436

    Directory of Open Access Journals (Sweden)

    Torgerson David J

    2005-10-01

    Full Text Available Abstract Background Postal questionnaires are widely used to collect outcome data on participants. However, a poor response to questionnaires will reduce the statistical power of the study and may introduce bias. A meta analysis of ten trials offering study results, largely in the fields of education and marketing, was shown to be ineffective, with the odds ratio for response with offering research findings is 0.92 (95% CI 0.75 to 1.11. However uncertainty still exists as it is uncertain whether results from such trials can be extrapolated to that of a health care setting. The aim of this study was to assess whether offering participants study results increases the response rates to postal questionnaires. Methods 1038 women aged over 70 years were remotely randomised by computer in a 3:1 ratio. 250 participants did not receive the offer of knowing the results of the trial and 788 participants were offered the results of the trial in a postal questionnaire. The main outcome measure was response rate. Chi square test was used to evaluate the overall differences in response rate between the two groups. An adjusted analysis, adjusting for whether the participant was taking calcium and age was also undertaken. Results The response rates were not significantly different Odds Ratio 0.88 (95% confidence intervals 0.48 to 1.63 p = 0.69. Conclusion Offering study results to women living in the community aged over 70 does not increase response rates to postal questionnaires. Although researchers have an ethical obligation to offer participants study results, since 10% of women did not wish to receive the results, investigators should give participants the option to opt out of receiving the study's results.

  17. The renal urate transporter SLC17A1 locus: confirmation of association with gout.

    Science.gov (United States)

    Hollis-Moffatt, Jade E; Phipps-Green, Amanda J; Chapman, Brett; Jones, Gregory T; van Rij, Andre; Gow, Peter J; Harrison, Andrew A; Highton, John; Jones, Peter B; Montgomery, Grant W; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2012-04-27

    Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

  18. Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney.

    Science.gov (United States)

    Nastase, Madalina-Viviana; Zeng-Brouwers, Jinyang; Beckmann, Janet; Tredup, Claudia; Christen, Urs; Radeke, Heinfried H; Wygrecka, Malgorzata; Schaefer, Liliana

    2017-12-15

    Th1 and Th17 cells, T helper (Th) subtypes, are key inducers of renal fibrosis. The molecular mechanisms of their recruitment into the kidney, however, are not well understood. Here, we show that biglycan, a proteoglycan of the extracellular matrix, acting in its soluble form as a danger signal, stimulates autonomously the production of Th1 and Th17 chemoattractants CXCL10 and CCL20 in macrophages. In the presence of IFNγ, biglycan synergistically stimulates CXCL9. In macrophages deficient for TLR2, TLR4, and their adaptor molecules MyD88 or TRIF, we identified highly selective mechanisms of biglycan-dependent Th1/17 chemoattraction. Thus, the expression of CXCL9 and CXCL10, common chemoattractants for CXCR3-positive Th1 and Th17 cells, is triggered in a biglycan-TLR4/TRIF-dependent manner. By contrast, biglycan induces CCL20 chemokine production, responsible for CCR6-positive Th17 cell recruitment, in a TLR2/4/MyD88-dependent manner. Importantly, at the onset of diabetes mellitus and lupus nephritis we provide evidence for biglycan-dependent recruitment of Th1 and Th17 cells, IFNγ and IL-17 production, and development of albuminuria in mice lacking or overexpressing soluble biglycan. Furthermore, by genetic ablation of Cxcl10 we showed in vivo involvement of this chemokine in biglycan-dependent recruitment of Th1 and Th17 cells into the kidney. Finally, a positive correlation of biglycan and CXCL10/CXCL9 levels was detected in plasma from patients with diabetic nephropathy and lupus nephritis. Taken together, we identified biglycan as a novel trigger of Th1 and Th17 cell recruitment into the kidney and we postulate that interfering with biglycan/TLR/TRIF/MyD88-signaling might provide novel therapeutic avenues for renal fibrosis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  19. REASONS FOR STUDENT DISCONTINUATION IN ENGINEERING DEGREE COURSES OFFERED AT A DISTANCE

    Directory of Open Access Journals (Sweden)

    S. Anbahan ARIADURAI

    2009-01-01

    Full Text Available Faculty of Engineering Technology of the Open University of Sri Lanka has been offering engineering programmes at a distance for the last two decades or so. However, completion rates in Faculty of Engineering Technology are lower compared to the other faculties of the University. This paper investigates the reasons for low completion rates in the faculty and suggests ways and means to overcome this problem. The study concludes that increasing student numbers will not necessarily increase percentage of students completing the programme though the number of students completing is increased. It is found that students offering courses for the first time in the system of distance education in their academic career perform poorer because they are not conversant with distance education techniques. It is recommended that the Faculty must offer an orientation programme on distance education to all the students enrolling for the first time, before they commence their regular programmes. Further, it has been found that considerable percentage of students who obtain eligibility to sit the final examination by completing the continuous assessments do not sit the final examination. This has been found to contribute towards non-completion of programmes as students sitting the final examination in the subsequent years perform poorly in their exams. To overcome this problem, it is recommended that current practise of allowing the student to carry forward their eligibility to unlimited period of time must be disbanded.

  20. The Future of Classification in Wheelchair Sports; Can Data Science and Technological Advancement Offer an Alternative Point of View?

    Science.gov (United States)

    van der Slikke, Rienk M A; Bregman, Daan J J; Berger, Monique A M; de Witte, Annemarie M H; Veeger, Dirk-Jan H E J

    2017-11-01

    Classification is a defining factor for competition in wheelchair sports, but it is a delicate and time-consuming process with often questionable validity. 1 New inertial sensor based measurement methods applied in match play and field tests, allow for more precise and objective estimates of the impairment effect on wheelchair mobility performance. It was evaluated if these measures could offer an alternative point of view for classification. Six standard wheelchair mobility performance outcomes of different classification groups were measured in match play (n=29), as well as best possible performance in a field test (n=47). In match-results a clear relationship between classification and performance level is shown, with increased performance outcomes in each adjacent higher classification group. Three outcomes differed significantly between the low and mid-class groups, and one between the mid and high-class groups. In best performance (field test), a split between the low and mid-class groups shows (5 out of 6 outcomes differed significantly) but hardly any difference between the mid and high-class groups. This observed split was confirmed by cluster analysis, revealing the existence of only two performance based clusters. The use of inertial sensor technology to get objective measures of wheelchair mobility performance, combined with a standardized field-test, brought alternative views for evidence based classification. The results of this approach provided arguments for a reduced number of classes in wheelchair basketball. Future use of inertial sensors in match play and in field testing could enhance evaluation of classification guidelines as well as individual athlete performance.

  1. Offers INTERSOCCER

    CERN Multimedia

    Staff Association

    2014-01-01

      Summer Football camps   New offer to the members of the Staff Association – INTERSOCCER: 12% discount on summer football camps and courses for children (bilingual) so do not hesitate anymore!    

  2. Offer patterns of nationally placed livers by donation service area.

    Science.gov (United States)

    Lai, Jennifer C; Feng, Sandy; Vittinghoff, Eric; Roberts, John P

    2013-04-01

    We previously reported that national liver distribution is highly concentrated in 6 US centers, and this raises the possibility of expedited placement. Therefore, we evaluated all national offers of nationally placed livers (n=1625) to adult wait-list candidates from February 2005 to January 2010. We developed a model to predict national utilization pathways; pathways exceeding the best-fit linear unbiased predictions by ≥3 standard errors were defined as preferred. All 51 donation service areas (DSAs) placed 1 or more livers nationally, but the percentage per DSA ranged from 1% to 36%. Of 2830 possible national DSA-center pathways, 87% were used. Five hundred eighty livers (36%) were accepted on the first national offer. Four DSAs accounted for 47% of first-national-offer livers, and 44% of these were accepted by a single center. In comparison with first-offer livers using nonpreferred pathways, first offers along a preferred pathway were offered to fewer status 1 candidates (19% versus 61%) and had lower median model for end-stage liver disease (MELD) scores (22 versus 36, Poffer to non-status 1 candidates with MELD scores less than their local transplant MELD scores. Although this practice may facilitate liver placement, it raises the possibility of expedience trumping patient need. Here we propose changes to the national liver distribution system that will help to balance equity, efficiency, and transparency. Copyright © 2013 American Association for the Study of Liver Diseases.

  3. [Undergraduate education of medical technologists to promote scientific and technological literacy].

    Science.gov (United States)

    Yamaguchi, Hiroyuki; Akizawa, Hirotsugu

    2010-07-01

    It is becoming increasingly important for today's medical technologists to receive proper training on the safety of medical treatment and healthcare in order to accommodate the rapid changes and advancement in medical technology. In particular, because of the increase of hospital-acquired infections, the role of medical technologists involved in infection control has become much more important. In addition, particularly in Japan, the career options available to students graduating with a degree in medical technology have become much more diverse, ranging from research laboratories to clinical services; however, undergraduate education for medical technologists is limited. It is therefore deemed necessary for undergraduate students to be provided with adequate training from their universities by offering a wider selection of classes in this subject area. In this paper, we summarize our preliminary findings on the trial lessons that are offered to medical technology students in their microbiology class. These lessons are designed to enhance students' academic potential and to engage their interest.

  4. 14 CFR 151.29 - Procedures: Offer, amendment, and acceptance.

    Science.gov (United States)

    2010-01-01

    ... resolution or ordinance must, as appropriate under the local law— (1) Set forth the terms of the offer at... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Procedures: Offer, amendment, and... § 151.29 Procedures: Offer, amendment, and acceptance. (a) Upon approving a project, the Administrator...

  5. The need to know caregiver perspectives toward using smart home technology.

    Science.gov (United States)

    Giger, Jarod T; Markward, Martha

    2011-01-01

    This article reviews the literature on adults with serious mental illness, their caregivers, and smart home technology. The article provides compelling evidence for social workers to undertake research aimed at investigating caregivers' perceptions toward using smart home technology for care of adult family members or friends with a serious mental illness. Empirical support for using smart home technologies with adults with serious mental illness is provided, and recommendations for future social work research are offered.

  6. 17 CFR 12.17 - Satisfaction of complaint.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Satisfaction of complaint. 12... RELATING TO REPARATIONS General Information and Preliminary Consideration of Pleadings § 12.17 Satisfaction... as the complainant will accept in satisfaction of his claim; and (b) by submitting to the Commission...

  7. 17 CFR 240.3a44-1 - Proprietary government securities transactions incidental to the futures-related business of a...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Proprietary government securities transactions incidental to the futures-related business of a CFTC-regulated person. 240.3a44-1 Section 240.3a44-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED...

  8. Application of virtual reality technology to activities for offering information to the general public in the Mizunami Underground Research Laboratory Project

    International Nuclear Information System (INIS)

    Saito, Hiroshi; Kawase, Keiichi; Sugihara, Kozo; Yamamoto, Junta

    2000-01-01

    The Tono Geoscience Center is carrying out the Mizunami Underground Research Laboratory Project (MIU Project), as part of its scientific research program, in Mizunami City, Gifu Prefecture. We believe that the public and especially the local residents should have a precise understanding of the MIU project. Therefore, to provide information we have used virtual reality (VR) technology in the project since 1996. Software to introduce both the MIU Project and the geology of the Tono district has been completed. The Tono district is characterized by uranium ore deposits, and by clay deposits which are used by the pottery industry. Software with some amusement value, such as hot spring drilling, has also been completed. We plan further software development of VR technology to increase the feeling of realism. (author)

  9. 17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells.

    Science.gov (United States)

    Adeosun, Samuel O; Albert, Paul R; Austin, Mark C; Iyo, Abiye H

    2012-05-01

    Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT(1A) receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE(2)) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE(2)-induced downregulation of the 5-HT(1A) receptor in the neuroblastoma cell line SH SY5Y. Cells were treated with 10 nM of 17βE(2) for 3 or 48 h, followed by a 24-h withdrawal period. Proteins were isolated and analyzed by western blotting. 17βE(2) treatment increased NUDR immunoreactivity while Freud-1 and the 5-HT(1A) receptor showed significant decreases. Upon withdrawal of 17βE(2), protein expression returned to control levels, except for NUDR, which remained significantly elevated in the 3-h treatment. Taken together, these data support a non-genomic downregulation of 5-HT(1A) receptor protein by 17βE(2), which does not involve NUDR and Freud-1. Rather, changes in both transcription factors seem to be compensatory/homeostatic responses to changes in 5-HT(1A) receptor induced by 17βE(2). These observations further highlight the importance of NUDR and Freud-1 in regulating 5-HT(1A) receptor expression.

  10. 24 CFR 17.9 - Referral to Department of Justice.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Referral to Department of Justice... Procedures § 17.9 Referral to Department of Justice. When Department of Justice approval or consultation is required under § 17.8, the referral or request shall be transmitted to the Department of Justice by the...

  11. Reasons Low-Income Parents Offer Snacks to Children: How Feeding Rationale Influences Snack Frequency and Adherence to Dietary Recommendations

    Science.gov (United States)

    Blaine, Rachel E.; Fisher, Jennifer Orlet; Taveras, Elsie M.; Geller, Alan C.; Rimm, Eric B.; Land, Thomas; Perkins, Meghan; Davison, Kirsten K.

    2015-01-01

    Although American children snack more than ever before, the parental role in promoting snacking is not well understood. In 2012–2013 at baseline in an intervention study to prevent childhood obesity in low-income Massachusetts communities, n = 271 parents of children aged 2–12 years completed surveys regarding nutritive and non-nutritive reasons they offered children snacks, demographics, and dietary factors. An analysis of variance demonstrated that parents reported offering snacks (mean/week; standard deviation (SD)) for nutritive reasons like promoting growth (x̄ = 2.5; SD 2.2) or satisfying hunger (x̄ = 2.4; SD 2.1) almost twice as often as non-nutritive reasons like keeping a child quiet (x̄ = 0.7; SD 1.5) or celebrating events/holidays (x̄ = 0.8; SD 1.1). Parents reported giving young children (2–5 years) more snacks to reward behavior (1.9 vs. 1.1, p parents of older children (6–12 years). Multivariable logistic regression models were used to obtain adjusted odds ratios, which indicated reduced child adherence to dietary recommendations when parents offered snacks to reward behavior (Odds Ratio (OR) = 0.83; 95% Confidence Interval (CI) 0.70–0.99), celebrate events/holidays (OR = 0.72; 95% CI 0.52–0.99), or achievements (OR = 0.82; 95% CI 0.68–0.98). Parental intentions around child snacking are likely important targets for obesity prevention efforts. PMID:26197335

  12. Association of plasma angiotensin-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Pan-Pan Hao

    Full Text Available We recently found that overexpression of angiotensin (Ang-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7 and Ang-I to Ang-(1-9, may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1-7 level and left ventricular function in patients with type 2 diabetes mellitus.We measured the left ventricular ejection fraction (EF, ratio of early to late left ventricular filling velocity (E/A and ratio of early diastolic mitral inflow to annular velocity (E/Ea by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7 level in patients with a poor EF (15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1-7 level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1-7, hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1-7 level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1-7 and hemoglobin A1c levels predicted E/Ea.Plasma Ang-(1-7 level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients.

  13. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a.

    Science.gov (United States)

    Deuis, Jennifer R; Dekan, Zoltan; Wingerd, Joshua S; Smith, Jennifer J; Munasinghe, Nehan R; Bhola, Rebecca F; Imlach, Wendy L; Herzig, Volker; Armstrong, David A; Rosengren, K Johan; Bosmans, Frank; Waxman, Stephen G; Dib-Hajj, Sulayman D; Escoubas, Pierre; Minett, Michael S; Christie, Macdonald J; King, Glenn F; Alewood, Paul F; Lewis, Richard J; Wood, John N; Vetter, Irina

    2017-01-20

    Human genetic studies have implicated the voltage-gated sodium channel Na V 1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na V 1.7 (IC 50 0.9 nM) with at least 40-1000-fold selectivity over all other Na V subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na V 1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na V 1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na V 1.7 inhibitors produced profound analgesia. Our results suggest that in these inflammatory models, acute administration of peripherally restricted Na V 1.7 inhibitors can only produce analgesia when administered in combination with an opioid.

  14. The (x, T) magnetic phase diagram of Y2Co17-xCrx (1.17-bar x-bar 3) compounds by neutron diffraction

    International Nuclear Information System (INIS)

    Schobinger-Papamantellos, P.; Buschow, K.H.J.; Fuquan, B.; Tegus, O.; Brueck, E.; Boer, F.R. de; Ritter, C.

    2006-01-01

    We present the (x, T) phase diagram of the ferromagnetic Y 2 Co 17-x Cr x (x=1.17, 1.76, 2.34, 3) compounds with rhombohedral structure (space group R3-bar m, Th 2 Zn 17 -type), determined for the entire magnetically ordered regime from high-resolution neutron-diffraction data. Substitution of small amounts of Cr for Co was found to have drastic effects on the magnetic properties such as a decrease of the Curie (T C ) and spin reorientation (T SR ) temperatures as well as a decrease of the ordered-moment values. These effects could be brought into connection to the fact that Cr was found to have a preference for the four Co sites in the following order 6c>18f>9d>18h. The number of Cr atoms found occupying the latter two sites, however, is within experimental error negligible. The magnetic phase diagram comprises three distinct regions of magnetic order in addition to the paramagnetic state: (a) the HT range (easy axis) (b) the LT (easy plane) for 0 C and T SR . It also leads to the formation of varying portions of the hexagonal Th 2 Ni 17 -modification (with similar magnetic properties) in samples with x>=1.76. The crystal and magnetic structure of both modifications were refined simultaneously

  15. Association of provider recommendation and offer and influenza vaccination among adults aged ≥18 years - United States.

    Science.gov (United States)

    Lu, Peng-Jun; Srivastav, Anup; Amaya, Ashley; Dever, Jill A; Roycroft, Jessica; Kurtz, Marshica Stanley; O'Halloran, Alissa; Williams, Walter W

    2018-02-01

    Influenza vaccination has been recommended for all persons aged ≥6 months since 2010. Data from the 2016 National Internet Flu Survey were analyzed to assess provider vaccination recommendations and early influenza vaccination during the 2016-17 season among adults aged ≥18 years. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with early vaccine uptake by provider vaccination recommendation status. Overall, 24.0% visited a provider who both recommended and offered influenza vaccination, 9.0% visited a provider who only recommended but did not offer, 25.1% visited a provider who neither recommended nor offered, and 41.9% did not visit a doctor from July 1 through date of interview. Adults who reported that a provider both recommended and offered vaccine had significantly higher vaccination coverage (66.6%) compared with those who reported that a provider only recommended but did not offer (48.4%), those who neither received recommendation nor offer (32.0%), and those who did not visit a doctor during the vaccination period (28.8%). Results of multivariable logistic regression indicated that having received a provider recommendation, with or without an offer for vaccination, was significantly associated with higher vaccination coverage after controlling for demographic and access-to-care factors. Provider recommendation was significantly associated with influenza vaccination. However, overall, 67.0% of adults did not visit a doctor during the vaccination period or did visit a doctor but did not receive a provider recommendation. Evidence-based strategies such as client reminder/recall, standing orders, provider reminders, or health systems interventions in combination should be undertaken to improve provider recommendation and influenza vaccination coverage. Other factors significantly associated with a higher level of influenza vaccination included age ≥50 years, being Hispanic

  16. Fear and guilt in proposers : Using emotions to explain offers in ultimatum bargaining

    NARCIS (Netherlands)

    Nelissen, R.M.A.; Leliveld, M.C.; van Dijk, E; Zeelenberg, M.

    We argue that offers in bargaining are guided by the emotions that proposers anticipate when contemplating their offers. In particular, we reason that positive offers may be driven by fear and guilt, where fear is more related to the perceived consequences of having one's offer rejected, and guilt

  17. The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation.

    Science.gov (United States)

    Xiao, Yucheng; Blumenthal, Kenneth; Jackson, James O; Liang, Songping; Cummins, Theodore R

    2010-12-01

    The voltage-gated sodium channel Na(v)1.7 plays a crucial role in pain, and drugs that inhibit hNa(v)1.7 may have tremendous therapeutic potential. ProTx-II and huwentoxin-IV (HWTX-IV), cystine knot peptides from tarantula venoms, preferentially block hNa(v)1.7. Understanding the interactions of these toxins with sodium channels could aid the development of novel pain therapeutics. Whereas both ProTx-II and HWTX-IV have been proposed to preferentially block hNa(v)1.7 activation by trapping the domain II voltage-sensor in the resting configuration, we show that specific residues in the voltage-sensor paddle of domain II play substantially different roles in determining the affinities of these toxins to hNa(v)1.7. The mutation E818C increases ProTx-II's and HWTX-IV's IC(50) for block of hNa(v)1.7 currents by 4- and 400-fold, respectively. In contrast, the mutation F813G decreases ProTx-II affinity by 9-fold but has no effect on HWTX-IV affinity. It is noteworthy that we also show that ProTx-II, but not HWTX-IV, preferentially interacts with hNa(v)1.7 to impede fast inactivation by trapping the domain IV voltage-sensor in the resting configuration. Mutations E1589Q and T1590K in domain IV each decreased ProTx-II's IC(50) for impairment of fast inactivation by ~6-fold. In contrast mutations D1586A and F1592A in domain-IV increased ProTx-II's IC(50) for impairment of fast inactivation by ~4-fold. Our results show that whereas ProTx-II and HWTX-IV binding determinants on domain-II may overlap, domain II plays a much more crucial role for HWTX-IV, and contrary to what has been proposed to be a guiding principle of sodium channel pharmacology, molecules do not have to exclusively target the domain IV voltage-sensor to influence sodium channel inactivation.

  18. Determination of S17(0) from transfer reactions

    International Nuclear Information System (INIS)

    Tribble, R.E.; Azhari, A.; Clark, H.L.; Gagliardi, C.A.; Lui, Y.; Mukhamedzhanov, A.M.; Sattarov, A.; Trache, L.; Burjan, V.; Cejpek, J.; Kroha, V.; Piskor, S.; Vincour, J.

    1998-01-01

    The S-factor for the direct capture reaction 7 Be(p,γ) 8 B can be found at astrophysical energies from the asymptotic normalization coefficients which provide the normalization of the tails of the overlap functions for 8 B→ 7 Be+p. Peripheral transfer reactions offer a technique to determine these asymptotic normalization coefficients. As a test of the technique, the 16 O( 3 He,d) 17 F reaction has been used to determine asymptotic normalization coefficients for transitions to the ground and first excited states of 17 F. The S-factors for 16 O(p,γ) 17 F calculated from these 17 F→ 16 O+p asymptotic normalization coefficients are found to be in very good agreement with recent measurements. Following the same technique, the 10 B( 7 Be, 8 B) 9 Be reaction has been used to measure the asymptotic normalization coefficient for 7 Be(p,γ) 8 B. This result provides an indirect determination of S 17 (0). copyright 1998 American Institute of Physics

  19. 17 CFR 240.13b2-1 - Falsification of accounting records.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Falsification of accounting records. 240.13b2-1 Section 240.13b2-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Required Reports § 240.13b2-1 Falsification of accounting records. No person shall directly or indirectly...

  20. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certain prima facie investment companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment...

  1. Oak Ridge National Laboratory Technology Logic Diagram. Volume 1, Technology Evaluation: Part B, Remedial Action

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    The Oak Ridge National Laboratory Technology Logic Diagram (TLD) was developed to provide a decision-support tool that relates environmental restoration (ER) and waste management (WM) problems at Oak Ridge National Laboratory (ORNL) to potential technologies that can remediate these problems. The TLD identifies the research, development, demonstration, testing, and evaluation needed to develop these technologies to a state that allows technology transfer and application to decontamination and decommissioning (D&D), remedial action (RA), and WM activities. The TLD consists of three fundamentally separate volumes: Vol. 1 (Technology Evaluation), Vol. 2 (Technology Logic Diagram), and Vol. 3 (Technology Evaluation Data Sheets). Part A of Vols. 1 and 2 focuses on D&D. Part B of Vols. 1 and 2 focuses on RA of contaminated facilities. Part C of Vols. 1 and 2 focuses on WM. Each part of Vol. 1 contains an overview of the TLD, an explanation of the program-specific responsibilities, a review of identified technologies, and the ranking os remedial technologies. Volume 2 (Pts. A, B, and C) contains the logic linkages among EM goals, environmental problems, and the various technologies that have the potential to solve these problems. Volume 3 (Pts. A, B, and C) contains the TLD data sheets. The focus of Vol. 1, Pt. B, is RA, and it has been divided into six chapters. The first chapter is an introduction, which defines problems specific to the ER Program for ORNL. Chapter 2 provides a general overview of the TLD. Chapters 3 through 5 are organized into necessary subelement categories: RA, characterization, and robotics and automation. The final chapter contains regulatory compliance information concerning RA.

  2. 17β-estradiol induces stearoyl-CoA desaturase-1 expression in estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Belkaid, Anissa; Duguay, Sabrina R.; Ouellette, Rodney J.; Surette, Marc E.

    2015-01-01

    To sustain cell growth, cancer cells exhibit an altered metabolism characterized by increased lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the production of monounsaturated fatty acids that are essential for membrane biogenesis, and is required for cell proliferation in many cancer cell types. Although estrogen is required for the proliferation of many estrogen-sensitive breast carcinoma cells, it is also a repressor of SCD-1 expression in liver and adipose. The current study addresses this apparent paradox by investigating the impact of estrogen on SCD-1 expression in estrogen receptor-α-positive breast carcinoma cell lines. MCF-7 and T47D mammary carcinomas cells and immortalized MCF-10A mammary epithelial cells were hormone-starved then treated or not with 17β-estradiol. SCD-1 activity was assessed by measuring cellular monounsaturated/saturated fatty acid (MUFA/SFA) ratios, and SCD-1 expression was measured by qPCR, immunoblot, and immunofluorescence analyses. The role of SCD-1 in cell proliferation was measured following treatment with the SCD-1 inhibitor A959372 and following SCD-1 silencing using siRNA. The involvement of IGF-1R on SCD-1 expression was measured using the IGF-1R antagonist AG1024. The expression of SREBP-1c, a transcription factor that regulates SCD-1, was measured by qPCR, and by immunoblot analyses. 17β-estradiol significantly induced cell proliferation and SCD-1 activity in MCF-7 and T47D cells but not MCF-10A cells. Accordingly, 17β-estradiol significantly increased SCD-1 mRNA and protein expression in MCF-7 and T47D cells compared to untreated cells. Treatment of MCF-7 cells with 4-OH tamoxifen or siRNA silencing of estrogen receptor-α largely prevented 17β-estradiol-induced SCD-1 expression. 17β-estradiol increased SREBP-1c expression and induced the mature active 60 kDa form of SREBP-1. The selective SCD-1 inhibitor or siRNA silencing of SCD-1 blocked the 17β-estradiol-induced cell proliferation and increase in

  3. Decision support for organ offers in liver transplantation.

    Science.gov (United States)

    Volk, Michael L; Goodrich, Nathan; Lai, Jennifer C; Sonnenday, Christopher; Shedden, Kerby

    2015-06-01

    Organ offers in liver transplantation are high-risk medical decisions with a low certainty of whether a better liver offer will come along before death. We hypothesized that decision support could improve the decision to accept or decline. With data from the Scientific Registry of Transplant Recipients, survival models were constructed for 42,857 waiting-list patients and 28,653 posttransplant patients from 2002 to 2008. Daily covariate-adjusted survival probabilities from these 2 models were combined into a 5-year area under the curve to create an individualized prediction of whether an organ offer should be accepted for a given patient. Among 650,832 organ offers from 2008 to 2013, patient survival was compared by whether the clinical decision was concordant or discordant with model predictions. The acceptance benefit (AB)--the predicted gain or loss of life by accepting a given organ versus waiting for the next organ--ranged from 3 to -22 years (harm) and varied geographically; for example, the average benefit of accepting a donation after cardiac death organ ranged from 0.47 to -0.71 years by donation service area. Among organ offers, even when AB was >1 year, the offer was only accepted 10% of the time. Patient survival from the time of the organ offer was better if the model recommendations and the clinical decision were concordant: for offers with AB > 0, the 3-year survival was 80% if the offer was accepted and 66% if it was declined (P decision support may improve patient survival in liver transplantation. © 2015 American Association for the Study of Liver Diseases.

  4. Conference Offers Girls Opportunity to Expand Career Horizons

    Science.gov (United States)

    Offers Girls Opportunity to Expand Career Horizons For more information contact: e:mail: Public Affairs Golden, Colo., Feb. 11, 1997 -- Expanding Your Horizons, a conference for girls grades 6 - 9 and Employed Women, Girls Incorporated of Metro Denver, King Soopers, McDonalds, the TCI Adult Program and the

  5. Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung infection.

    Science.gov (United States)

    Li, Jing; Dong, Xiaojing; Zhao, Lei; Wang, Xiao; Wang, Yan; Yang, Xi; Wang, Hong; Zhao, Weiming

    2016-07-01

    Natural killer (NK) cell is an important component in innate immunity, playing a critical role in bridging innate and adaptive immunity by modulating the function of other immune cells including T cells. In this study, we focused on the role of NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung infection. We found that NK cell-depleted mice showed decreased Th1 and Th17 cells, which was correlated with reduced interferon-γ, interleukin (IL)-12, IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor gamma t expression compared with mice treated with the isotype control antibody. In contrast, NK cell depletion significantly increased Treg in cell number and related transcription factor (Foxp3) expression. The opposite trends of changes of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg ratios. The data implicate that NK cells play an important role in host defence against chlamydial lung infection, mainly through maintaining Th1/Treg and Th17/Treg balance. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. What Bulgarian Banks offer via Internet: an Overview (v2)

    OpenAIRE

    Bojidar Bojinov

    2003-01-01

    The new information technologies adoption and e-commerce emergence change the role of financial intermediaries in new E-conomy. During the last years, the bank started an expansion to the web – they offer broad range of traditional bank products and services via Internet. The remote banking become one of the main channels for bank services distribution. The Internet expansion of the Bulgarian banks is at its beginning. The showed results are based on the Internet research, which has aimed to ...

  7. Emotional Expression in Simple Line Drawings of a Robot's Face Leads to Higher Offers in the Ultimatum Game.

    Science.gov (United States)

    Terada, Kazunori; Takeuchi, Chikara

    2017-01-01

    In the present study, we investigated whether expressing emotional states using a simple line drawing to represent a robot's face can serve to elicit altruistic behavior from humans. An experimental investigation was conducted in which human participants interacted with a humanoid robot whose facial expression was shown on an LCD monitor that was mounted as its head (Study 1). Participants were asked to play the ultimatum game, which is usually used to measure human altruistic behavior. All participants were assigned to be the proposer and were instructed to decide their offer within 1 min by controlling a slider bar. The corners of the robot's mouth, as indicated by the line drawing, simply moved upward, or downward depending on the position of the slider bar. The results suggest that the change in the facial expression depicted by a simple line drawing of a face significantly affected the participant's final offer in the ultimatum game. The offers were increased by 13% when subjects were shown contingent changes of facial expression. The results were compared with an experiment in a teleoperation setting in which participants interacted with another person through a computer display showing the same line drawings used in Study 1 (Study 2). The results showed that offers were 15% higher if participants were shown a contingent facial expression change. Together, Studies 1 and 2 indicate that emotional expression in simple line drawings of a robot's face elicits the same higher offer from humans as a human telepresence does.

  8. Road Materials and Pavement Design Volume 17(1)

    CSIR Research Space (South Africa)

    De Beer, Morris

    2016-03-01

    Full Text Available Materials and Pavement Design Volume 17, 2016 - Issue 1 Editorial Board Page ebi | Published online: 03 Oct 2016  http://dx.doi.org/10.1080/14680629.2016.1244475 Editors-in-Chief Hervé DI BENEDETTO - University of Lyon/ENTPE, Vaulx-en-Velin, France... Andrew Charles COLLOP - De Montfort University, Leicester, UK William G. BUTTLAR - University of Missouri, Urbana-Champaign, USA Editor-in-Chief at Large Jorge B. Sousa - Consulpav, Oeiras, Portugal Associate Editors Morris de Beer - CSIR Built...

  9. 17 CFR 249.507 - Form 7-M, consent to service of process by an individual nonresident broker-dealer.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form 7-M, consent to service of process by an individual nonresident broker-dealer. 249.507 Section 249.507 Commodity and... Forms for Statements Made in Connection With Exempt Tender Offers § 249.507 Form 7-M, consent to service...

  10. 17 CFR 249.509 - Form 9-M, consent to service of process by a partnership nonresident broker-dealer.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form 9-M, consent to service of process by a partnership nonresident broker-dealer. 249.509 Section 249.509 Commodity and... Forms for Statements Made in Connection With Exempt Tender Offers § 249.509 Form 9-M, consent to service...

  11. Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes.

    Science.gov (United States)

    Arellano, Gabriel; Acuña, Eric; Reyes, Lilian I; Ottum, Payton A; De Sarno, Patrizia; Villarroel, Luis; Ciampi, Ethel; Uribe-San Martín, Reinaldo; Cárcamo, Claudia; Naves, Rodrigo

    2017-01-01

    Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) ( n  = 21), different clinical forms of MS ( n  = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) ( n  = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.

  12. Offer

    CERN Multimedia

    Staff Association

    2010-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 22th to 29th November 2010

  13. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 25th to 27th March 2011  

  14. Invitation to the IAEA FR17 Conference on Fast Reactors, Russia, 2017

    International Nuclear Information System (INIS)

    Rachkov, V.

    2013-01-01

    Russian Federation has a large successful experience of peaceful application of nuclear power and it is a leader in development of fast reactors that permit to create sustainable and safe base for future world nuclear power. Russian Government approved in 2010 a Federal Target Program “Nuclear power technologies of a new generation for period of 2010-2015 and with outlook to 2020” aimed at creation of new technological platform for future nuclear power based on fast reactors. State Atomic Energy Corporation “Rosatom” supports activities of the IAEA on strengthening international collaboration on fast reactors and invites IAEA to host next FR17 Conference on FRs in Russia in 2017

  15. Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-β estradiol and nonylphenol

    International Nuclear Information System (INIS)

    Soverchia, L.; Ruggeri, B.; Palermo, F.; Mosconi, G.; Cardinaletti, G.; Scortichini, G.; Gatti, G.; Polzonetti-Magni, A.M.

    2005-01-01

    Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17β and different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP) on the expression of liver ERβ-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17β) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP), or 10 -7 M of estradiol-17β. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17β and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17β plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERβ-1 mRNA in the liver, demonstrating that both estradiol-17β and 4-NP modulate the vitellogenin rate through interaction with the ERβ-1 subtype. The

  16. Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

    Science.gov (United States)

    Domingo-Gonzalez, Racquel; Das, Shibali; Griffiths, Kristin L; Ahmed, Mushtaq; Bambouskova, Monika; Gopal, Radha; Gondi, Suhas; Muñoz-Torrico, Marcela; Salazar-Lezama, Miguel A; Cruz-Lagunas, Alfredo; Jiménez-Álvarez, Luis; Ramirez-Martinez, Gustavo; Espinosa-Soto, Ramón; Sultana, Tamanna; Lyons-Weiler, James; Reinhart, Todd A; Arcos, Jesus; de la Luz Garcia-Hernandez, Maria; Mastrangelo, Michael A; Al-Hammadi, Noor; Townsend, Reid; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B; Kaplan, Gilla; Horne, William; Kolls, Jay K; Artyomov, Maxim N; Rangel-Moreno, Javier; Zúñiga, Joaquín; Khader, Shabaana A

    2017-10-05

    Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.

  17. Evidence that cytochrome b5 acts as a redox donor in CYP17A1 mediated androgen synthesis

    International Nuclear Information System (INIS)

    Duggal, Ruchia; Liu, Yilin; Gregory, Michael C.; Denisov, Ilia G.; Kincaid, James R.; Sligar, Stephen G.

    2016-01-01

    Cytochrome P450 17A1 (CYP17A1) is an important drug target for castration resistant prostate cancer. It is a bi-functional enzyme, catalyzing production of glucocorticoid precursors by hydroxylation of pregnene-nucleus, and androgen biosynthesis by a second C−C lyase step, at the expense of glucocorticoid production. Cytochrome b 5 (cyt b 5 ) is known to be a key regulator of the androgen synthesis reaction in vivo, by a mechanism that is not well understood. Two hypotheses have been proposed for the mechanism by which cyt b 5 increases androgen biosynthesis. Cyt b 5 could act as an allosteric effector, binding to CYP17A1 and either changing its selective substrate affinity or altering the conformation of the P450 to increase the catalytic rate or decrease unproductive uncoupling channels. Alternatively, cyt b 5 could act as a redox donor for supply of the second electron in the P450 cycle, reducing the oxyferrous complex to form the reactive peroxo-intermediate. To understand the mechanism of lyase enhancement by cyt b 5 , we generated a redox-inactive form of cyt b 5 , in which the heme is replaced with a Manganese-protoporphyrin IX (Mn-b 5 ), and investigated enhancement of androgen producing lyase reaction by CYP17A1. Given the critical significance of a stable membrane anchor for all of the proteins involved and the need for controlled stoichiometric ratios, we employed the Nanodisc system for this study. The redox inactive form was observed to have no effect on the lyase reaction, while reactions with the normal heme-iron containing cyt b 5 were enhanced ∼5 fold as compared to reactions in the absence of cyt b 5 . We also performed resonance Raman measurements on ferric CYP17A1 bound to Mn-b 5 . Upon addition of Mn-b 5 to Nanodisc reconstituted CYP17A1, we observed clear evidence for the formation of a b 5 -CYP17A1 complex, as noted by changes in the porphyrin modes and alteration in the proximal Fe−S vibrational frequency. Thus, although Mn-b 5 binds

  18. Fitting Handled Objects into Apertures by 17- to 36-Month-Old Children: The Dynamics of Spatial Coordination

    Science.gov (United States)

    Jung, Wendy P.; Kahrs, Björn A.; Lockman, Jeffrey J.

    2018-01-01

    Handled artifacts are ubiquitous in human technology, but how young children engage in spatially coordinated behaviors with these artifacts is not well understood. To address this issue, children (N = 30) from 17-36 months were studied with motion tracking technology as they fit the distal segment of a handled artifact into a slot. The handle was…

  19. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kristi Alnek

    Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  20. TECHNOLOGY-ENHANCED TEACHING: A REVOLUTIONARY APPROACH TO TEACHING ENGLISH AS A FOREIGN LANGUAGE

    Directory of Open Access Journals (Sweden)

    Alberth Alberth

    2013-01-01

    Full Text Available The online course offerings have grown exponentially globally since the turn of the 21st century - be they as a primary mode of instruction or as a supplement to traditional face-to-face classroom instruction, and this phenomenon is most noticeable in higher education. More recently, the new technology has also been integrated into the English as a Foreign Language,henceforth called EFL, classrooms. This article argues that the notion of technology-enhanced language learning is not just an intriguing idea – it is a necessity, for it has a great potential to offer in facilitating the development of English language proficiency of EFL learners through computer-mediated communication. Additionally, it contends that the new technology can potentially address most, if not all, of the shortcomings inherent to the EFL classroom including, but not limited to, lack of exposure to the target language, lack of practice, and lack of learning resources. Theoretical implications of technology-enhanced language teaching and learning will also be explored.

  1. High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Paola Adele Lonati

    Full Text Available BACKGROUND: High interleukin (IL-17A levels are characteristically found in the skin of systemic sclerosis (SSc individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237 and decreased frequency of IL-17F+ (p = 0.0127 and IL-17C+ cells (p = 0.0008 when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186 in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109 and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low and IL-17E (high

  2. Immune response to Bifidobacterium bifidum strains support Treg/Th17 plasticity.

    Directory of Open Access Journals (Sweden)

    Patricia López

    Full Text Available In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th or regulatory (Treg responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs. Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC to further determine their capability to induce the differentiation of naïve CD4(+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed.

  3. Offering memorable patient experience through creative, dynamic marketing strategy

    Science.gov (United States)

    Raţiu, M; Purcărea, T

    2008-01-01

    Creative, dynamic strategies are the ones that identify new and better ways of uniquely offering the target customers what they want or need. A business can achieve competitive advantage if it chooses a marketing strategy that sets the business apart from anyone else. Healthcare services companies have to understand that the customer should be placed in the centre of all specific marketing operations. The brand message should reflect the focus on the patient. Healthcare products and services offered must represent exactly the solutions that customers expect. The touchpoints with the patients must be well mastered in order to convince them to accept the proposed solutions. Healthcare service providers must be capable to look beyond customer's behaviour or product and healthcare service aquisition. This will demand proactive and far–reaching changes, including focusing specifically on customer preference, quality, and technological interfaces; rewiring strategy to find new value from existing and unfamiliar sources; disintegrating and radically reassembling operational processes; and restructuring the organization to accommodate new typess of work and skill. PMID:20108466

  4. Offering memorable patient experience through creative, dynamic marketing strategy.

    Science.gov (United States)

    Purcărea, Victor Lorín; Raţíu, Monica; Purcărea, Theodor; Davila, Carol

    2008-01-01

    Creative, dynamic strategies are the ones that identify new and better ways of uniquely offering the target customers what they want or need. A business can achieve competitive advantage if it chooses a marketing strategy that sets the business apart from anyone else. Healthcare services companies have to understand that the customer should be placed in the centre of all specific marketing operations. The brand message should reflect the focus on the patient. Healthcare products and services offered must represent exactly the solutions that customers expect. The touchpoints with the patients must be well mastered in order to convince them to accept the proposed solutions. Healthcare service providers must be capable to look beyond customer's behaviour or product and healthcare service aquisition. This will demand proactive and far-reaching changes, including focusing specifically on customer preference, quality, and technological interfaces; rewiring strategy to find new value from existing and unfamiliar sources: disintegrating and radically reassembling operational processes: and restructuring the organization to accommodate new types of work and skill.

  5. IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

    Science.gov (United States)

    Chahbi, Mayssa; Haouami, Youssra; Sfar, Imen; Abdelmoula, Leila; Ben Abdallah, Taieb; Gorgi, Yousr

    2018-01-01

    Background Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. PMID:29584788

  6. Issues Related to Experience & Automated Agent Technology in Synthetic Task Performance

    National Research Council Canada - National Science Library

    Coovert, Michael D; Riddle, Dawn L; Gordon, Thomas; Miles, Donald; Hoffman, Kimberly; King, Thomas; Elliott, Linda; Dalrymple, Mathieu; Schiflett, Samual; Chaiken, Scott

    2001-01-01

    .... Elliott, Stoyen and Chaiken (2000) note the limits of human cognitive processing relative to this demand and suggest agent technology has the potential to offer effective information and decision support the human operator...

  7. Use of a D17Z1 oligonucleotide probe for human DNA quantitation prior to PCR analysis of polymorphic DNA markers

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, S.; Alavaren, M.; Varlaro, J. [Roche Molecular Systems, Alameda, CA (United States)] [and others

    1994-09-01

    The alpha-satellite DNA locus D17Z1 contains primate-specific sequences which are repeated several hundred times per chromosome 17. A probe that was designed to hybridize to a subset of the D17Z1 sequence can be used for very sensitive and specific quantitation of human DNA. Sample human genomic DNA is immobilized on nylon membrane using a slot blot apparatus, and then hybridized with a biotinylated D17Z1 oligonucleotide probe. The subsequent binding of streptavidin-horseradish peroxidase to the bound probe allows for either calorimetric (TMB) or chemiluminescent (ECL) detection. Signals obtained for sample DNAs are then compared to the signals obtained for a series of human DNA standards. For either detection method, forty samples can be quantitated in less than two hours, with a sensitivity of 150 pg. As little as 20 pg of DNA can be quantitated when using chemiluminescent detection with longer film exposures. PCR analysis of several VNTR and STR markers has indicated that optimal typing results are generally obtained within a relatively narrow range of input DNA quantities. Too much input DNA can lead to PCR artifacts such as preferential amplification of smaller alleles, non-specific amplification products, and exaggeration of the DNA synthesis slippage products that are seen with STR markers. Careful quantitation of human genomic DNA prior to PCR can avoid or minimize these problems and ultimately give cleaner, more unambiguous PCR results.

  8. Attending to others: how digital technologies direct young people's nightlife

    Directory of Open Access Journals (Sweden)

    J. Truong

    2018-05-01

    Full Text Available It is a growing phenomenon that young people use mobile information and communication technologies during their nightlife. This article offers an empirical examination of how young people's nightlife is shaped by engagement with the mobile phone application WhatsApp. Drawing on Sara Ahmed's phenomenological concept of orientation, I examine how WhatsApp extends young people's nightlife and how young people become orientated therein. On the one hand, I show that nightlife acquires new boundaries and fixities that encourage young people to direct their attention towards missing social relations and absent nightlife places. On the other hand, I find that young people create new perceptions of how to inhabit and spend leisure time and space. I argue that digital technologies reorientate young people, which I suggest offers novel means of addressing young people's contemporary nightlife practices, places, spaces, and social relations.

  9. Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties

    DEFF Research Database (Denmark)

    Prajeeth, Chittappen K; Kronisch, Julius; Khorooshi, Reza M. H.

    2017-01-01

    Background: Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in the central nervous system (CNS). Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammation. Previously we have shown that only Th1...... mice where trafficking of Th1 cells into the CNS was affected. We compared microglia and astrocyte response in the brain and spinal cord of these mice. We further treated astrocytes with supernatants from highly pure Th1 and Th17 cultures and assessed the mRNA expression of neurotrophic factors......, cytokines and chemokines using real-time PCR. Data obtained was analysed using Kruskal- Wallis test. Results: We observed in α4-deficient mice weak microglial activation but comparable astrogliosis to that of wild-type mice in the regions of the brain populated with Th17 infiltrates suggesting that Th17...

  10. Offers

    CERN Document Server

    Staff Association

    2011-01-01

    Banque cantonale de Genève (BCGE) The BCGE Business partner programme devised for members of the CERN Staff Association offers personalized banking solutions with preferential conditions. The advantages are linked to salary accounts (free account keeping, internet banking, free Maestro and credit cards, etc.), mortgage lending, retirement planning, investment, credit, etc. The details of the programme and the preferential conditions are available on our website: http://association.web.cern.ch/association/en/OtherActivities/BCGE.html.  

  11. Do you want some spiritual support? Different rates of positive response to chaplains' versus nurses' offer.

    Science.gov (United States)

    Martinuz, Marco; Dürst, Anne-Véronique; Faouzi, Mohamed; Pétremand, Daniel; Reichel, Virginie; Ortega, Barbara; Waeber, Gérard; Vollenweider, Peter

    2013-01-01

    Access to spiritual support appears to be important in the hospital setting. The offer of spiritual support can be done by different providers such as doctors, nurses or chaplains. Who should initiate or coordinate this spiritual care. This study addresses the following questions: 1) How many patients accept spiritual proposition? 2) What is the better mode of proposition? The study's objectives are the assessment and comparison of the rates of acceptance to an offer of spiritual support made by nurses and chaplains. Two hundred twenty-three consecutive hospitalized patients hospitalized received a proposal of spiritual support and were randomly assigned to one of two conditions. Results revealed that 85.8% of patients accepted the offer in the chaplains' group and 38.5% in the nurses' group. Acceptance of the offer of spiritual support was positively associated with the proposal being made by the chaplains by the frequency of meditation and age, and negatively related to physical well-being.

  12. Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    2015-01-01

    However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy.

  13. 17 CFR 270.3c-1 - Definition of beneficial ownership for certain 3(c)(1) funds.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of beneficial... AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3c-1 Definition of beneficial ownership for certain 3(c)(1) funds. (a) As used in this section: (1) The term...

  14. Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues.

    Science.gov (United States)

    Fransson, Rebecca; Nordvall, Gunnar; Bylund, Johan; Carlsson-Jonsson, Anna; Kratz, Jadel M; Svensson, Richard; Artursson, Per; Hallberg, Mathias; Sandström, Anja

    2014-12-11

    The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.

  15. Percutaneous closure of patent ductus arteriosus in small infants with significant lung disease may offer faster recovery of respiratory function when compared to surgical ligation.

    Science.gov (United States)

    Abu Hazeem, Anas A; Gillespie, Matthew J; Thun, Haley; Munson, David; Schwartz, Matthew C; Dori, Yoav; Rome, Jonathan J; Glatz, Andrew C

    2013-10-01

    To describe our experience with percutaneous closure of patent ductus arteriosus (PDA) in small infants and compare outcomes to matched surgical patients. Ligation via thoracotomy has been used to close PDAs in small infants, but has been associated with respiratory and hemodynamic compromise. We hypothesized that percutaneous closure would offer faster recovery of respiratory function. Patients closure between January 2000 and April 2012 were reviewed and matched to contemporary surgical patients on gestational age (GA), birth weight (BW), procedure weight (WT), and ventilation mode. Patients returned to baseline respiratory status when the product of mean airway pressure and FiO2 returned to pre-procedural levels. Eight matched pairs were included. Median BW, GA, and WT were 1.43 kg (0.52-2.97), 29.8 weeks (24-39), and 2.8 kg (2.2-3.9) for catheter patients and 1.55 kg (0.48-3.04), 29 weeks (23-37), and 2.75 kg (2.3-4.2) for surgical patients. Complete PDA closure occurred in all. The median time to return to baseline respiratory status was significantly shorter in the percutaneous group (17 hr (range 0-113) vs. 53 hr (range 13-219), P closure of PDA in small infants on respiratory support is equivalent in safety and efficacy and may offer shorter recovery time than surgical ligation. Copyright © 2013 Wiley Periodicals, Inc.

  16. 17 CFR 8.13 - Answer to charges.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Answer to charges. 8.13 Section 8.13 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION EXCHANGE PROCEDURES FOR DISCIPLINARY, SUMMARY, AND MEMBERSHIP DENIAL ACTIONS Disciplinary Procedure § 8.13 Answer to...

  17. The Unknown Oldowan: ~1.7-Million-Year-Old Standardized Obsidian Small Tools from Garba IV, Melka Kunture, Ethiopia.

    Directory of Open Access Journals (Sweden)

    Rosalia Gallotti

    Full Text Available The Oldowan Industrial Complex has long been thought to have been static, with limited internal variability, embracing techno-complexes essentially focused on small-to-medium flake production. The flakes were rarely modified by retouch to produce small tools, which do not show any standardized pattern. Usually, the manufacture of small standardized tools has been interpreted as a more complex behavior emerging with the Acheulean technology. Here we report on the ~1.7 Ma Oldowan assemblages from Garba IVE-F at Melka Kunture in the Ethiopian highland. This industry is structured by technical criteria shared by the other East African Oldowan assemblages. However, there is also evidence of a specific technical process never recorded before, i.e. the systematic production of standardized small pointed tools strictly linked to the obsidian exploitation. Standardization and raw material selection in the manufacture of small tools disappear at Melka Kunture during the Lower Pleistocene Acheulean. This proves that 1 the emergence of a certain degree of standardization in tool-kits does not reflect in itself a major step in cultural evolution; and that 2 the Oldowan knappers, when driven by functional needs and supported by a highly suitable raw material, were occasionally able to develop specific technical solutions. The small tool production at ~1.7 Ma, at a time when the Acheulean was already emerging elsewhere in East Africa, adds to the growing amount of evidence of Oldowan techno-economic variability and flexibility, further challenging the view that early stone knapping was static over hundreds of thousands of years.

  18. The Unknown Oldowan: ~1.7-Million-Year-Old Standardized Obsidian Small Tools from Garba IV, Melka Kunture, Ethiopia.

    Science.gov (United States)

    Gallotti, Rosalia; Mussi, Margherita

    2015-01-01

    The Oldowan Industrial Complex has long been thought to have been static, with limited internal variability, embracing techno-complexes essentially focused on small-to-medium flake production. The flakes were rarely modified by retouch to produce small tools, which do not show any standardized pattern. Usually, the manufacture of small standardized tools has been interpreted as a more complex behavior emerging with the Acheulean technology. Here we report on the ~1.7 Ma Oldowan assemblages from Garba IVE-F at Melka Kunture in the Ethiopian highland. This industry is structured by technical criteria shared by the other East African Oldowan assemblages. However, there is also evidence of a specific technical process never recorded before, i.e. the systematic production of standardized small pointed tools strictly linked to the obsidian exploitation. Standardization and raw material selection in the manufacture of small tools disappear at Melka Kunture during the Lower Pleistocene Acheulean. This proves that 1) the emergence of a certain degree of standardization in tool-kits does not reflect in itself a major step in cultural evolution; and that 2) the Oldowan knappers, when driven by functional needs and supported by a highly suitable raw material, were occasionally able to develop specific technical solutions. The small tool production at ~1.7 Ma, at a time when the Acheulean was already emerging elsewhere in East Africa, adds to the growing amount of evidence of Oldowan techno-economic variability and flexibility, further challenging the view that early stone knapping was static over hundreds of thousands of years.

  19. 17 CFR 31.3 - Fraud in connection with certain transactions in silver or gold bullion or bulk coins, or other...

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Fraud in connection with... Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION LEVERAGE TRANSACTIONS § 31.3 Fraud... fraud or deceit upon any person, in, or in connection with (1) an offer to make or the making of, any...

  20. Emotional Expression in Simple Line Drawings of a Robot's Face Leads to Higher Offers in the Ultimatum Game

    Directory of Open Access Journals (Sweden)

    Kazunori Terada

    2017-05-01

    Full Text Available In the present study, we investigated whether expressing emotional states using a simple line drawing to represent a robot's face can serve to elicit altruistic behavior from humans. An experimental investigation was conducted in which human participants interacted with a humanoid robot whose facial expression was shown on an LCD monitor that was mounted as its head (Study 1. Participants were asked to play the ultimatum game, which is usually used to measure human altruistic behavior. All participants were assigned to be the proposer and were instructed to decide their offer within 1 min by controlling a slider bar. The corners of the robot's mouth, as indicated by the line drawing, simply moved upward, or downward depending on the position of the slider bar. The results suggest that the change in the facial expression depicted by a simple line drawing of a face significantly affected the participant's final offer in the ultimatum game. The offers were increased by 13% when subjects were shown contingent changes of facial expression. The results were compared with an experiment in a teleoperation setting in which participants interacted with another person through a computer display showing the same line drawings used in Study 1 (Study 2. The results showed that offers were 15% higher if participants were shown a contingent facial expression change. Together, Studies 1 and 2 indicate that emotional expression in simple line drawings of a robot's face elicits the same higher offer from humans as a human telepresence does.

  1. Simulated structure and imaging of NTCDI on Si(1 1 1)-7 × 7 : a combined STM, NC-AFM and DFT study

    Science.gov (United States)

    Jarvis, S. P.; Sweetman, A. M.; Lekkas, I.; Champness, N. R.; Kantorovich, L.; Moriarty, P.

    2015-02-01

    The adsorption of naphthalene tetracarboxylic diimide (NTCDI) on Si(111)-7 × 7 is investigated through a combination of scanning tunnelling microscopy (STM), noncontact atomic force microscopy (NC-AFM) and density functional theory (DFT) calculations. We show that NTCDI adopts multiple planar adsorption geometries on the Si(111)-7 × 7 surface which can be imaged with intramolecular bond resolution using NC-AFM. DFT calculations reveal adsorption is dominated by covalent bond formation between the molecular oxygen atoms and the surface silicon adatoms. The chemisorption of the molecule is found to induce subtle distortions to the molecular structure, which are observed in NC-AFM images.

  2. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 11th to 23rd November 2013 Please contact the Staff Association Secretariat to get the discount voucher.  

  3. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Simply present your Staff Association membership card when you make your purchase. Plus 20 % reduction during their “vente privée”* three or four times a year. * Next “vente privée” from 24th September to 6th November 2014 Please contact the Staff Association Secretariat to get the discount voucher.  

  4. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th May 2012 Please contact the Staff Association Secretariat to get the discount voucher  

  5. Model Based Business and IT Cloud Alignment as a Cloud Offering

    OpenAIRE

    Robert Woitsch; Wilfrid Utz

    2015-01-01

    Cloud computing proved to offer flexible IT solutions. Although large enterprises may benefit from this technology by educating their IT departments, SMEs are dramatically falling behind in cloud usage and hence lose the ability to efficiently adapt their IT to their business needs. This paper introduces the project idea of the H2020 project CloudSocket, by elaborating the idea of Business Processes as a Service, where concept models and semantics are applied to align business pro...

  6. A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma.

    Science.gov (United States)

    Pacey, Simon; Gore, Martin; Chao, David; Banerji, Udai; Larkin, James; Sarker, Sarah; Owen, Karen; Asad, Yasmin; Raynaud, Florence; Walton, Mike; Judson, Ian; Workman, Paul; Eisen, Tim

    2012-02-01

    A Phase II study to screen for anti-melanoma activity of the heat shock protein 90 (HSP90) inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin) was performed. The primary endpoint was the rate of disease stabilisation in patients with progressive, metastatic melanoma treated with 17-AAG. Secondary endpoints were to determine: the toxicity of 17-AAG, the duration of response(s), median survival and further study the pharmacokinetics and pharmacodynamics of 17-AAG. Patients with metastatic melanoma (progressive disease documented ≤6 months of entering study) were treated with weekly, intravenous 17-AAG. A Simon one sample two stage minimax design was used. A stable disease rate of ≥25% at 6 months was considered compatible with 17-AAG having activity. Fourteen patients (8 male: 6 female) were entered, eleven received 17-AAG (performance status 0 or 1). Median age was 60 (range 29-81) years. The majority (93%) received prior chemotherapy and had stage M1c disease (71%). Toxicity was rarely ≥ Grade 2 in severity and commonly included fatigue, headache and gastrointestinal disturbances. One of eleven patients treated with 17-AAG had stable disease for 6 months and median survival for all patients was 173 days. The study was closed prematurely prior to completion of the first stage of recruitment and limited planned pharmacokinetic and pharmacodynamic analyses. Some evidence of 17-AAG activity was observed although early study termination meant study endpoints were not reached. Stable disease rates can be incorporated into trials screening for anti-melanoma activity and further study of HSP90 inhibitors in melanoma should be considered.

  7. 12 CFR 563g.21 - Filing of copies of offering circulars in certain exempt offerings.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Filing of copies of offering circulars in certain exempt offerings. 563g.21 Section 563g.21 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.21 Filing of copies of offering circulars in certain...

  8. Strategic Motives Drive Proposers to Offer Fairly in Ultimatum Games: An fMRI Study.

    Science.gov (United States)

    Chen, Yin-Hua; Chen, Ying-Chun; Kuo, Wen-Jui; Kan, Kamhon; Yang, C C; Yen, Nai-Shing

    2017-04-03

    The hypothesis of strategic motives postulates that offering fairly in the Ultimatum Game (UG) is to avoid rejection and receive money. In this fMRI study, we used a modified UG to elucidate how proposers reached decisions of offering fairly and to what extent they considered offering selfishly with different stakes. We had proposers choose between a fair and a selfish offer with different degrees of selfishness and stake sizes. Proposers were less likely and spent more time choosing the fair offer over a slightly-selfish offer than a very selfish offer independent of stakes. Such choices evoked greater activation in the dorsal anterior cingulate cortices that typically involve in allocation of cognitive control for cost/benefit decision making. Choosing a fair offer in higher stakes evoked greater activation in the anterior cingulate gyrus (ACCg) and the areas that previously have been implicated in reward and theory of mind. Furthermore, choosing a slightly selfish offer over a fair offer evoked greater activation in the anterior cingulate sulcus, ACCg, ventral tegmental area (or substantia nigra) and anterior insular cortex signalling the higher gain and implying higher rejection risk. In conclusion, our findings favoured the hypothesis that proposers offer fairly based on the strategic motives.

  9. The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.

    Directory of Open Access Journals (Sweden)

    Christiane Desel

    Full Text Available Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB, the synthetic analog of the mycobacterial cord factor trehalose-6,6-dimycolate (TDM, is a potent adjuvant inducing strong Th1 and Th17 immune responses. We previously identified the C-type lectin Mincle as receptor for these glycolipids that triggers the FcRγ-Syk-Card9 pathway for APC activation and adjuvanticity. Interestingly, in vivo data revealed that the adjuvant effect was not solely Mincle-dependent but also required MyD88. Therefore, we dissected which MyD88-dependent pathways are essential for successful immunization with a tuberculosis subunit vaccine. We show here that antigen-specific Th1/Th17 immune responses required IL-1 receptor-mediated signals independent of IL-18 and IL-33-signaling. ASC-deficient mice had impaired IL-17 but intact IFNγ responses, indicating partial independence of TDB adjuvanticity from inflammasome activation. Our data suggest that the glycolipid adjuvant TDB triggers Mincle-dependent IL-1 production to induce MyD88-dependent Th1/Th17 responses in vivo.

  10. Service Offering at Electrical Equipment Manufacturers

    Directory of Open Access Journals (Sweden)

    Lucie Kaňovská

    2015-09-01

    Full Text Available Purpose of the article: The aim of the paper is to uncover ways of managing service offering provided by electrical equipment manufactures in the Czech Republic. The segment is extremely important for Czech industry nowadays, especially because of many companies being subcontractors for the car industry and mechanical engineering. The producers of electric equipment comply with the Czech industry classification CZ-NACE 27. Methodology/methods: The questionnaire in the form of the Likert scale was prepared to gather information about customer services. The respondents were usually directors or managers, e.g. employees with high competencies of knowing customer services in this particular market. The total of 22 companies were included in the survey. Research was focused on the following industries classifications belonging to CZ-NACE 27: CZ-NACE 27, CZ-NACE 271 and CZ-NACE 273. According to Czech Statistical Office the total number of companies belonging to these 3 segments is 136. It means 16,2% companies belonging to CZ-NACE 27 participated in our research. Basic statistical methods were used to analyse the complete database. Scientific aim: The paper deals with the problem of service offering provided by today’s manufacturers. Global understanding of services that manufacturers really develop, sell, deliver and manage is still limited. Findings: Managing service offering provided by today‘s manufacturers shows that 1 Manufacturers not offer only tangible products, but also wide range of services and even information and support. 2 New products are not designed only according to company technicians, but also according to their customers. Their products and services are developed, tested and improved according to their needs. 3 Services provide complex customer care from time product selection to its end. Conclusions: Manufacturers of tangible products need to enlarge their product offering to be able to satisfy customers. Therefore

  11. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development.

    Science.gov (United States)

    Franco, David; Li, Wenjing; Qing, Fang; Stoyanov, Cristina T; Moran, Thomas; Rice, Charles M; Ho, David D

    2010-08-09

    The failure to develop an effective vaccine against HIV-1 infection has led the research community to seek new ways of raising qualitatively different antibody and cellular immune responses. Towards this goal, we investigated the yellow fever 17D vaccine strain (YF17D), one of the most effective vaccines ever made, as a platform for HIV-1 vaccine development. A test antigen, HIV-1 p24 (clade B consensus), was inserted near the 5' end of YF17D, in frame and upstream of the polyprotein (YF-5'/p24), or between the envelope and the first non-structural protein (YF-E/p24/NS1). In vitro characterization of these recombinants indicated that the gene insert was more stable in the context of YF-E/p24/NS1. This was confirmed in immunogenicity studies in mice. CD8(+) IFN-gamma T-cell responses against p24 were elicited by the YF17D recombinants, as were specific CD4(+) T cells expressing IFN-gamma and IL-2. A balanced CD4(+) and CD8(+) T-cell response was notable, as was the polyfunctionality of the responding cells. Finally, the protective efficacy of the YF17D recombinants, particularly YF-E/p24/NS1, in mice challenged with a vaccinia expressing HIV-1 Gag was demonstrated. These results suggest that YF17D warrants serious consideration as a live-attenuated vector for HIV-1 vaccine development. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Seniors-on-line: introducing older people to technology.

    Science.gov (United States)

    Irizarry, C; Downing, A; Elford, C

    1997-03-01

    Retired Engineers are playing an important role in ensuring that older people are not excluded from the benefits of technological advances. Technology is playing an increasingly important role in the lives of older people as it is incorporated into assistive devices, home security, access to health care, banking, communication and many other areas. However, if older people are unfamiliar with new technologies and find them daunting, they may not benefit fully from these advances. In order to minimize difficulties arising from unfamiliarity with technology, an introductory computer course was offered to people aged 55 and over. Teaching methods appropriate to the needs of older people were used: small classes, students and instructors from same age cohort, slow pace of presentation and ample opportunity to ask questions. Retired Engineers make up the majority of instructors. Three hundred and sixty nine older people have participated in the course and most plan to continue using a computer.

  13. Exploration of offering photoelectric experimental general elective courses for college students of science and technology

    Science.gov (United States)

    Tao, Shen; Sun, Binchao

    2017-08-01

    The necessity of offering photoelectric experiment general elective courses, such as the experiments of modern optical and innovational photoelectric design for non optic-electric's science and engineering students were discussed based on the analysis of the status quo and problems in experimental general elective course in science and engineering colleges of our country. And the characters of photoelectric disciplines, the goal of science and engineering quality-oriented education and the reform of science education at home and abroad were also considered. The instructional objectives, contents and characteristics of the courses were investigated. The specific methods, the CDIO (conceive, design, implement and operate) mode in the general courses has been proposed; the experiences and practical effects of offering these courses were concluded.

  14. Technological entrepreneurship : technology transfer from academia to new firms

    NARCIS (Netherlands)

    Prodan, I.

    2007-01-01

    This doctoral dissertation aims to do the following: 1. Develop the conceptual model of technological entrepreneurship 2. Position technology transfer from academia to new firms in a newly developed conceptual model of technological entrepreneurship 3. Develop the model of technology transfer from

  15. Estrogen modulates potassium currents and expression of the Kv4.2 subunit in GT1-7 cells.

    Science.gov (United States)

    Farkas, Imre; Varju, Patricia; Liposits, Zsolt

    2007-03-01

    The proper maintenance of reproduction requires the pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is ensured by synchronized periodic firing of multiple GnRH neurons. Both hormone secretion and electrophysiological properties of GnRH cells are influenced by estrogen. The impact of 17beta-estradiol treatment on the function of voltage gated A- and K-type potassium channels, known modulators of firing rate, was therefore examined in our experiments using immortalized GnRH-producing GT1-7 neurons. Whole cell patch clamp recordings showed the absence of the A-type current in GT1-7 cells cultured in estrogen-free medium and after 8h 17beta-estradiol treatment. Exposure of the cells to 17beta-estradiol for 24 and 48 h, respectively, resulted in the appearance of the A-type current. The induction of the A-type current by 17beta-estradiol was dose-related (50 pM to 15 nM range). In contrast, the K-type potassium current was apparent in the estrogen-free environment and 17beta-estradiol administration significantly decreased its amplitude. Co-administration of 17beta-estradiol and estrogen receptor blocker, Faslodex (ICI 182,780; 1 microM) abolished the occurrence of the A-type current. Real-time PCR data demonstrated that expression of the Kv4.2 subunit of the A-type channel was low at 0, 0.5, 2 and 8h, peaked at 24h and diminished at 48 h 17beta-estradiol treatment (15 nM). These data indicate that potassium channels of GT1-7 neurons are regulated by estrogen a mechanism that might contribute to modulation of firing rate and hormone secretion in GnRH neurons.

  16. The Co59 nuclear magnetic resonances in (Ysub(1-x)Gdsub(x))2Co17

    International Nuclear Information System (INIS)

    Nagai, Hiroyuki; Yoshie, Hiroshi; Unate, Takao; Tsujimura, Akira; Deportes, J.

    1976-01-01

    The nuclear magnetic resonances of Co 59 in (Ysub(1-x)Gdsub(x)) 2 Co 17 have been observed at 77 K as a function of x (0 2 Co 17 and Gd 2 Co 17 is at most 7 kOe in magnitude, which is comparable to that obtained in GdCo 5 . The sign of the obtained difference depends on the Co sites. The difference is qualitatively explained as the contribution of 4f electrons of Gd atoms to the hyperfine field. The temperature dependence of the resonance frequencies in Gd 2 Co 17 has also been measured. (auth.)

  17. Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine

    Science.gov (United States)

    Ross, Pádraig J.; Allen, Aideen C.; Walsh, Kevin; Misiak, Alicja; Lavelle, Ed C.; McLoughlin, Rachel M.; Mills, Kingston H. G.

    2013-01-01

    Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells. PMID:23592988

  18. Using Technology to Expand the Classroom in Time, Space, and Diversity.

    Science.gov (United States)

    Drew, Joshua

    2015-11-01

    Diverse classrooms offer distinct advantages over homogeneous classrooms, for example by providing a greater diversity of perspectives and opportunities. However, there is substantial underrepresentation of numerous groups throughout science, technology, engineering, and mathematics (STEM) education, from secondary schools through professional ranks and academia. In this piece I offer a critical analysis of three worked examples of how technology can be used to expand traditional definitions of the classroom environment. In doing so I show how technology can be used to help make STEM classrooms more expansive, equitable, and effective learning environments. First I highlight how peer-to-peer learning was used to foster knowledge of marine conservation with high school youth across Fiji and Chicago. Second I show how social media can be used to facilitate conversations in New York City after a natural disaster. Finally, I show how integrating digital and real-world learning can help a diverse group of students from the Pacific islands gain field-based STEM techniques in an extended workshop format. Taken together these examples show how digital technology could expand the fixed walls of the academy and that technology can help show students the vivid splendor of life outside the classroom. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  19. 17 CFR 240.12d2-1 - Suspension of trading.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Suspension of trading. 240... Securities Exchange Act of 1934 Suspension of Trading, Withdrawal, and Striking from Listing and Registration § 240.12d2-1 Suspension of trading. (a) A national securities exchange may suspend from trading a...

  20. Does NASA's Constellation Architecture Offer Opportunities to Achieve Multiple Additional Goals in Space?

    Science.gov (United States)

    Thronson, Harley; Lester, Daniel F.

    2008-01-01

    Every major NASA human spaceflight program in the last four decades has been modified to achieve goals in space not incorporated within the original design goals: the Apollo Applications Program, Skylab, Space Shuttle, and International Space Station. Several groups in the US have been identifying major future science goals, the science facilities necessary to investigate them, as well as possible roles for augmented versions of elements of NASA's Constellation program. Specifically, teams in the astronomy community have been developing concepts for very capable missions to follow the James Webb Space Telescope that could take advantage of - or require - free-space operations by astronauts and/or robots. Taking as one example, the Single-Aperture Far-InfraRed (SAFIR) telescope with a approx. 10+ m aperture proposed for operation in the 2020 timeframe. According to current NASA plans, the Ares V launch vehicle (or a variant) will be available about the same time, as will the capability to transport astronauts to the vicinity of the Moon via the Orion Crew Exploration Vehicle and associated systems. [As the lunar surface offers no advantages - and major disadvantages - for most major optical systems, the expensive system for landing and operating on the lunar surface is not required.] Although as currently conceived, SAFIR and other astronomical missions will operate at the Sun-Earth L2 location, it appears trivial to travel for servicing to the more accessible Earth-Moon L1,2 locations. Moreover. as the recent Orbital Express and Automated Transfer Vehicle missions have demonstrated, future robotic capabilities should offer capabilities that would (remotely) extend human presence far beyond the vicinity of the Earth. In addition to multiplying the value of NASA's architecture for future human spaceflight to achieve the goals multiple major stakeholders. if humans one day travel beyond the Earth-Moon system - say, to Mars - technologies and capabilities for operating