WorldWideScience

Sample records for bona fides criteria

  1. 19 CFR 10.152 - Bona-fide gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Bona-fide gifts. 10.152 Section 10.152 Customs... and Bona Fide Gifts § 10.152 Bona-fide gifts. Subject to the conditions in § 10.153 of this part, the port director shall pass free of duty and tax any article sent as a bona-fide gift from a person in a...

  2. Fiat or bona fide boundary--a matter of granular perspective.

    Directory of Open Access Journals (Sweden)

    Lars Vogt

    Full Text Available Distinguishing bona fide (i.e. natural and fiat (i.e. artificial physical boundaries plays a key role for distinguishing natural from artificial material entities and is thus relevant to any scientific formal foundational top-level ontology, as for instance the Basic Formal Ontology (BFO. In BFO, the distinction is essential for demarcating two foundational categories of material entity: object and fiat object part. The commonly used basis for demarcating bona fide from fiat boundary refers to two criteria: (i intrinsic qualities of the boundary bearers (i.e. spatial/physical discontinuity, qualitative heterogeneity and (ii mind-independent existence of the boundary. The resulting distinction of bona fide and fiat boundaries is considered to be categorial and exhaustive.By Referring to various examples from biology, we demonstrate that the hitherto used distinction of boundaries is not categorial: (i spatial/physical discontinuity is a matter of scale and the differentiation of bona fide and fiat boundaries is thus granularity-dependent, and (ii this differentiation is not absolute, but comes in degrees. By reducing the demarcation criteria to mind-independence and by also considering dispositions and historical relations of the bearers of boundaries, instead of only considering their spatio-structural properties, we demonstrate with various examples that spatio-structurally fiat boundaries can nevertheless be mind-independent and in this sense bona fide.We argue that the ontological status of a given boundary is perspective-dependent and that the strictly spatio-structural demarcation criteria follow a static perspective that is ignorant of causality and the dynamics of reality. Based on a distinction of several ontologically independent perspectives, we suggest different types of boundaries and corresponding material entities, including boundaries based on function (locomotion, physiology, ecology, development, reproduction and common history

  3. 19 CFR 145.32 - Bona-fide gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Bona-fide gifts. 145.32 Section 145.32 Customs... (CONTINUED) MAIL IMPORTATIONS Special Classes of Merchandise § 145.32 Bona-fide gifts. The port director... as bona-fide gifts from persons in foreign countries to persons in the United States having an...

  4. 42 CFR 433.54 - Bona fide donations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Bona fide donations. 433.54 Section 433.54 Public... Financial Participation § 433.54 Bona fide donations. (a) A bona fide donation means a provider-related donation, as defined in § 433.52, made to the State or unit of local government, that has no direct or...

  5. Exploring key considerations when determining bona fide inadvertent errors resulting in understatements

    Directory of Open Access Journals (Sweden)

    Chrizanne de Villiers

    2016-03-01

    Full Text Available Chapter 16 of the Tax Administration Act (28 of 2011 (the TA Act deals with understatement penalties. In the event of an ‘understatement’, in terms of Section 222 of the TA Act, a taxpayer must pay an understatement penalty, unless the understatement results from a bona fide inadvertent error. The determining of a bona fide inadvertent error on taxpayers’ returns is a totally new concept in the tax fraternity. It is of utmost importance that this section is applied correctly based on sound evaluation principles and not on professional judgement when determining if the error was indeed the result of a bona fide inadvertent error. This research study focuses on exploring key considerations when determining bona fide inadvertent errors resulting in understatements. The role and importance of tax penalty provisions is explored and the meaning of the different components in the term ‘bona fide inadvertent error’ critically analysed with the purpose to find a possible definition for the term ‘bona fide inadvertent error’. The study also compares the provisions of other tax jurisdictions with regards to errors made resulting in tax understatements in order to find possible guidelines on the application of bona fide inadvertent errors as contained in Section 222 of the TA Act. The findings of the research study revealed that the term ‘bona fide inadvertent error’ contained in Section 222 of the TA Act should be defined urgently and that guidelines must be provided by SARS on the application of the new amendment. SARS should also clarify the application of a bona fide inadvertent error in light of the behaviours contained in Section 223 of the TA Act to avoid any confusion.

  6. 7 CFR 27.96 - Quotations in bona fide spot markets.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Quotations in bona fide spot markets. 27.96 Section 27... Differences § 27.96 Quotations in bona fide spot markets. The price or value and differences between the price... determined by the sale of spot cotton in such spot market. Quotations shall be determined and maintained in...

  7. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  8. 78 FR 9330 - Revision of Regulations Defining Bona Fide Cotton Spot Markets

    Science.gov (United States)

    2013-02-08

    ... Cotton Spot Markets AGENCY: Agricultural Marketing Service, USDA. ACTION: Proposed rule. SUMMARY: The... bona fide cotton spot markets in order to assure consistency with the revised Cotton Research and Promotion Act. Updated bona fide spot market definitions will allow for published spot quotes to consider...

  9. 7 CFR 15a.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Sex as a bona-fide occupational qualification. 15a.61... RECEIVING OR BENEFITTING FROM FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs and Activities Prohibited § 15a.61 Sex as a bona-fide occupational...

  10. Oportere ex fide bona. Una construcción decisiva de la jurisprudencia romana

    Directory of Open Access Journals (Sweden)

    Javier Humberto Facco

    2013-07-01

    Full Text Available Verificada la secularización de la antigua fides, asistimos al surgimiento de una construcción cuya valencia técnica parece concretarse en el específico ámbito del proceso. La fides resulta adjetivada con el calificativo de bona. A partir de entonces el sintagma bona fides significará una característica procesal, una cualidad de ciertas acciones que en la intentio de su fórmula se estructuraban en base al oportere ex fide bona. El núcleo de estas acciones estaba representado por los contratos sinalagmáticos, cuya fuerza obligatoria se fundaba en el consentimiento y pertenecían a la órbita del comercio internacional (ius gentium. Con todo, al margen de su aplicación pretoriana, la cláusula quidquid dare facere oportet ex fide bona fue una elaboración eminentemente jurisprudencial, producto del ingenio de los juristas romanos. Fueron ellos quienes idearon buena parte de las soluciones sobre cuestiones ligadas a la eficacia de los contratos consensuales que todavía hoy se consideran emanaciones de la buena fe-lealtad. Recuperar la trascendencia del rol de los juristas en la tarea de hacer que el derecho sea adherente a la realidad constituye la principal invitación que nace de este escrito.

  11. 7 CFR 27.93 - Bona fide spot markets.

    Science.gov (United States)

    2010-01-01

    ... Southwest Markets and the New Mexico counties of Union, Quay, Curry, Roosevelt and Lea. Desert Southwest The..., Hudspeth and El Paso, all New Mexico counties except those included in the West Texas market, all counties... 7 Agriculture 2 2010-01-01 2010-01-01 false Bona fide spot markets. 27.93 Section 27.93...

  12. 24 CFR 3.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Sex as a bona fide occupational... and Urban Development NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education...

  13. 38 CFR 23.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Sex as a bona fide... VETERANS AFFAIRS (CONTINUED) NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education...

  14. 45 CFR 2555.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 2555.550 Section 2555.550 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION... to such action is essential to successful operation of the employment function concerned. A recipient...

  15. 44 CFR 19.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Sex as a bona fide... MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  16. 10 CFR 5.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational qualification. 5.550 Section 5.550 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  17. 45 CFR 618.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 618.550 Section 618.550 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE... successful operation of the employment function concerned. A recipient shall not take action pursuant to this...

  18. 34 CFR 106.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Sex as a bona-fide occupational qualification. 106.61..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or...

  19. Comparing bona fide psychotherapies of depression in adults with two meta-analytical approaches.

    Directory of Open Access Journals (Sweden)

    Sarah R Braun

    Full Text Available OBJECTIVE: Despite numerous investigations, the question whether all bona fide treatments of depression are equally efficacious in adults has not been sufficiently answered. METHOD: We applied two different meta-analytical techniques (conventional meta-analysis and mixed treatment comparisons. Overall, 53 studies with 3,965 patients, which directly compared two or more bona fide psychotherapies in a randomized trial, were included. Meta-analyses were conducted regarding five different types of outcome measures. Additionally, the influence of possible moderators was examined. RESULTS: Direct comparisons of cognitive behavior therapy, behavior activation therapy, psychodynamic therapy, interpersonal therapy, and supportive therapies versus all other respective treatments indicated that at the end of treatment all treatments but supportive therapies were equally efficacious whereas there was some evidence that supportive therapies were somewhat less efficacious than all other treatments according to patient self-ratings and clinical significance. At follow-up no significant differences were present. Age, gender, comorbid mental disorders, and length of therapy session were found to moderate efficacy. Cognitive behavior therapy was superior in studies where therapy sessions lasted 90 minutes or longer, behavior activation therapy was more efficacious when therapy sessions lasted less than 90 minutes. Mixed treatment comparisons indicated no statistically significant differences in treatment efficacy but some interesting trends. CONCLUSIONS: This study suggests that there might be differential effects of bona fide psychotherapies which should be examined in detail.

  20. 17 CFR 240.16b-5 - Bona fide gifts and inheritance.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bona fide gifts and inheritance. 240.16b-5 Section 240.16b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... gifts and inheritance. Both the acquisition and the disposition of equity securities shall be exempt...

  1. 49 CFR 25.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 25... BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 25.550 Sex as a...

  2. 29 CFR 36.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Sex as a bona fide occupational qualification. 36.550 Section 36.550 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  3. 28 CFR 54.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Sex as a bona fide occupational... ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 54.550 Sex as a...

  4. 40 CFR 5.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 5.550 Sex as a...

  5. 6 CFR 17.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational qualification... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 17.550 Sex as a...

  6. 43 CFR 41.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 41.550 Sex as a...

  7. 45 CFR 86.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Sex as a bona-fide occupational qualification. 86... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 86.61 Sex as a...

  8. 31 CFR 28.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.550 Sex as a...

  9. 15 CFR 8a.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 8a.550 Sex as a...

  10. 29 CFR 1625.12 - Exemption for bona fide executive or high policymaking employees.

    Science.gov (United States)

    2010-07-01

    ... corporations [or other business organizations] are usually located at corporate or regional headquarters. With respect to employees whose duties are associated with corporate headquarters operations, such as finance..., would be covered by the term “bona fide executive.” Individuals at higher levels in the corporate...

  11. 29 CFR 516.3 - Bona fide executive, administrative, and professional employees (including academic...

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Bona fide executive, administrative, and professional... outside sales employees employed pursuant to section 13(a)(1) of the Act. 516.3 Section 516.3 Labor... professional employees (including academic administrative personnel and teachers in elementary or secondary...

  12. Law and culture: a theory of comparative variation in bona fide purchase rules

    NARCIS (Netherlands)

    Dari-Mattiacci, G.; Guerriero, C.

    2015-01-01

    A key question in comparative law is why different legal systems provide different legal solutions for the same problem. To answer this question, we use novel comparative evidence on how the conflict between the dispossessed original owner and the bona fide purchaser of a stolen good is resolved in

  13. On Improving Density Estimators which are not Bona Fide Functions

    OpenAIRE

    Gajek, Leslaw

    1986-01-01

    In order to improve the rate of decrease of the IMSE for nonparametric kernel density estimators with nonrandom bandwidth beyond $O(n^{-4/5})$ all current methods must relax the constraint that the density estimate be a bona fide function, that is, be nonnegative and integrate to one. In this paper we show how to achieve similar improvement without relaxing any of these constraints. The method can also be applied for orthogonal series, adaptive orthogonal series, spline, jackknife, and other ...

  14. Generating Bona Fide Mammalian Prions with Internal Deletions.

    Science.gov (United States)

    Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel

    2016-08-01

    Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative

  15. Discovery of a new Galactic bona fide luminous blue variable with Spitzer★

    Science.gov (United States)

    Gvaramadze, V. V.; Kniazev, A. Y.; Berdnikov, L. N.; Langer, N.; Grebel, E. K.; Bestenlehner, J. M.

    2014-11-01

    We report the discovery of a circular mid-infrared shell around the emission-line star Wray 16-137 using archival data of the Spitzer Space Telescope. Follow-up optical spectroscopy of Wray 16-137 with the Southern African Large Telescope revealed a rich emission spectrum typical of the classical luminous blue variables (LBVs) like P Cygni. Subsequent spectroscopic and photometric observations showed drastic changes in the spectrum and brightness during the last three years, meaning that Wray 16-137 currently undergoes an S Dor-like outburst. Namely, we found that the star has brightened by ≈1 mag in the V and Ic bands, while its spectrum became dominated by Fe II lines. Taken together, our observations unambiguously show that Wray 16-137 is a new member of the family of Galactic bona fide LBVs.

  16. WS1: one more new Galactic bona fide luminous blue variable★

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2015-04-01

    In this Letter, we report the results of spectroscopic and photometric monitoring of the candidate luminous blue variable (LBV) WS1, which was discovered in 2011 through the detection of a mid-infrared circular shell and follow-up optical spectroscopy of its central star. Our monitoring showed that WS1 brightened in the B, V and I bands by more than 1 mag during the last three years, while its spectrum revealed dramatic changes during the same time period, indicating that the star became much cooler. The light curve of WS1 demonstrates that the brightness of this star has reached maximum in 2013 December and then starts to decline. These findings unambiguously proved the LBV nature of WS1 and added one more member to the class of Galactic bona fide LBVs, bringing their number to sixteen (an updated census of these objects is provided).

  17. Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

    Science.gov (United States)

    Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

    2018-05-01

    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

  18. A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence

    Directory of Open Access Journals (Sweden)

    Georg Kuales

    2015-01-01

    Full Text Available Trophoblast stem cells (TSCs represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factors Cdx2, Eomes, and Elf5 in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles of Eomes or Cdx2, and EomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR and in situ hybridisation validated novel TSC- and chorion-specific marker genes, such as Bok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, and Sox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

  19. Discrimination-pregnancy leave-Pregnancy Discrimination Act not retroactive-bona fide seniority system. AT&T Corp. v. Hulteen, 2009 U.S. LEXIS 3470 (U.S. 5/18/2009).

    Science.gov (United States)

    2009-01-01

    A pension plan whose terms are those of a bona fide seniority system and which treats pregnancy leave, taken before the addition of the Pregnancy Discrimination Act (PDA) to Title VII, differently than other kinds of medical leave, does not amount to sex and pregnancy discrimination under Title VII because PDA does not apply retroactively.

  20. Discovery of a new bona fide luminous blue variable in Norma

    Science.gov (United States)

    Gvaramadze, V. V.; Kniazev, A. Y.; Berdnikov, L. N.

    2015-12-01

    We report the results of optical spectroscopy of the candidate evolved massive star MN44 revealed via detection of a circular shell with the Spitzer Space Telescope. First spectra taken in 2009 May-June showed the Balmer lines in emission as well as numerous emission lines of iron, which is typical of luminous blue variables (LBVs) near the visual maximum. New observations carried out in 2015 May-September detected significant changes in the spectrum, indicating that the star became hotter. We found that these changes are accompanied by significant brightness variability of MN44. In particular, the Ic-band brightness decreased by ≈ 1.6 mag during the last six years and after reaching its minimum in 2015 June has started to increase. Using archival data, we also found that the Ic-band brightness increased by ≈3 mag in ≈30 yr preceding our observations. MN44 therefore represents the 17th known example of the Galactic bona fide LBVs. We detected a nitrogen-rich knot to the north-west of the star, which might represent an interstellar cloudlet interacting with the circumstellar shell. We discuss a possible association between MN44 and the INTEGRAL transient source of hard X-ray emission IGR J16327-4940, implying that MN44 might be either a colliding-wind binary or a high-mass X-ray binary.

  1. MN48: a new Galactic bona fide luminous blue variable revealed by Spitzer and SALT

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2016-07-01

    In this paper, we report the results of spectroscopic and photometric observations of the candidate evolved massive star MN48 disclosed via detection of a mid-infrared circular shell around it with the Spitzer Space Telescope. Follow-up optical spectroscopy of MN48 with the Southern African Large Telescope (SALT) carried out in 2011-2015 revealed significant changes in the spectrum of this star, which are typical of luminous blue variables (LBVs). The LBV status of MN48 was further supported by photometric monitoring which shows that in 2009-2011 this star has brightened by ≈0.9 and 1 mag in the V and Ic bands, respectively, then faded by ≈1.1 and 1.6 mag during the next four years, and apparently started to brighten again recently. The detected changes in the spectrum and brightness of MN48 make this star the 18th known Galactic bona fide LBV and increase the percentage of LBVs associated with circumstellar nebulae to more than 70 per cent. We discuss the possible birth place of MN48 and suggest that this star might have been ejected either from a putative star cluster embedded in the H II region IRAS 16455-4531 or the young massive star cluster Westerlund 1.

  2. IC 3639 - A New Bona Fide Compton-Thick AGN Unveiled By NuSTAR

    Science.gov (United States)

    Boorman, Peter G.; Gandhi, P.; Alexander, D. M.; Annuar, A.; Ballantyne, D. R.; Bauer, F.; Boggs, S. E.; Brandt, W. N.; Brightman, M.; Christensen, F. E.; hide

    2016-01-01

    We analyze high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5-30 keV). Previous X-ray observations of the source below 10 keV indicated strong reflection/obscuration on the basis of a pronounced iron fluorescence line at 6.4 keV. The hard X-ray energy coverage of NuSTAR, together with self-consistent toroidal reprocessing models, enables direct broadband constraints on the obscuring column density of the source. We find the source to be heavily Compton-thick (CTK) with an obscuring column in excess of 3.6 x 10(exp 24) cm(exp -2), unconstrained at the upper end. We further find an intrinsic 2-10 keV luminosity of log(sub 10) (L(sub 2-10 keV) [erg s(exp -1)])= 43.4(+0.6/-1.1) to 90% confidence, almost 400 times the observed flux, and consistent with various multiwavelength diagnostics. Such a high ratio of intrinsic to observed flux, in addition to an Fe-K(alpha) fluorescence line equivalent width exceeding 2 keV, is extreme among known bona fide CTK AGNs, which we suggest are both due to the high level of obscuration present around IC 3639. Our study demonstrates that broadband spectroscopic modeling with NuSTAR enables large corrections for obscuration to be carried out robustly and emphasizes the need for improved modeling of AGN tori showing intense iron fluorescence.

  3. Experiment list: SRX190196 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNA mismatch repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS targe...h repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS target gene. (provided by RefSeq) || antibo...rimary microsatellite-instability (MSI), a form of genomic instability associated with defective DNA mismatc

  4. IC 3639—a New Bona Fide Compton-Thick AGN Unveiled by NuSTAR

    Science.gov (United States)

    Boorman, Peter G.; Gandhi, P.; Alexander, D. M.; Annuar, A.; Ballantyne, D. R.; Bauer, F.; Boggs, S. E.; Brandt, W. N.; Brightman, M.; Christensen, F. E.; Craig, W. W.; Farrah, D.; Hailey, C. J.; Harrison, F. A.; Hönig, S. F.; Koss, M.; LaMassa, S. M.; Masini, A.; Ricci, C.; Risaliti, G.; Stern, D.; Zhang, W. W.

    2016-12-01

    We analyze high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5-30 keV). Previous X-ray observations of the source below 10 keV indicated strong reflection/obscuration on the basis of a pronounced iron fluorescence line at 6.4 keV. The hard X-ray energy coverage of NuSTAR, together with self-consistent toroidal reprocessing models, enables direct broadband constraints on the obscuring column density of the source. We find the source to be heavily Compton-thick (CTK) with an obscuring column in excess of 3.6× {10}24 cm-2, unconstrained at the upper end. We further find an intrinsic 2-10 keV luminosity of {{log}}10({L}2{--10{keV}} [{erg} {{{s}}}-1])={43.4}-1.1+0.6 to 90% confidence, almost 400 times the observed flux, and consistent with various multiwavelength diagnostics. Such a high ratio of intrinsic to observed flux, in addition to an Fe-Kα fluorescence line equivalent width exceeding 2 keV, is extreme among known bona fide CTK AGNs, which we suggest are both due to the high level of obscuration present around IC 3639. Our study demonstrates that broadband spectroscopic modeling with NuSTAR enables large corrections for obscuration to be carried out robustly and emphasizes the need for improved modeling of AGN tori showing intense iron fluorescence.

  5. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng

    2015-01-01

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4–NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. PMID:25792601

  6. SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer.

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng; Sun, Luyang; Shang, Yongfeng

    2015-03-15

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1-Cul1-F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCF(JFK) as a bona fide E3 ligase for ING4 and unraveled the JFK-ING4-NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. © 2015 Yan et al.; Published by Cold Spring Harbor Laboratory Press.

  7. 26 CFR 1.132-5T - Working condition fringe-1985 through 1988 (temporary).

    Science.gov (United States)

    2010-04-01

    ... United States, a factor indicating a bona fide business-oriented security concern is threats on the life... is primarily personal. If, however, for bona fide business-oriented security concerns, the employee... have paid for the same mode of transportation absent the bona fide business-oriented security concerns...

  8. 76 FR 48884 - Stacey J. Webb, M.D.; Denial of Application

    Science.gov (United States)

    2011-08-09

    ... and maintain a bona fide doctor-patient relationship in order to act ``in the usual course of... whom they did not establish a bona-fide doctor-patient relationship, DEA has denied pending... prescriptions outside bona fide doctor-patient relationship with customers of a website); see also Ronald Lynch...

  9. Peaceful Uses Bona Fides: Criteria for Evaluation and Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ajemian, Chris K.; Hazel, Mike; Kessler, Carol E.; Mathews, Carrie E.; Morris, Fred A.; Seward, Amy M.; Peterson, Danielle J.; Smith, Brian W.

    2007-06-06

    This study applies a set of indicators to assess the peaceful nature of a state’s nuclear program. Evaluation of a country’s nuclear program relative to these indicators can help the international community to take appropriate actions to ensure that the growth of the global nuclear energy industry proceeds peacefully and to minimize nuclear proliferation risks.

  10. CRISPR/Cas9 Mediated GFP Knock-in at the MAP1LC3B Locus in 293FT Cells Is Better for Bona Fide Monitoring Cellular Autophagy.

    Science.gov (United States)

    Wu, Zhiqiang; Zhao, Jinlin; Qiu, Minghan; Mi, Zeyun; Meng, Maobin; Guo, Yu; Wang, Hui; Yuan, Zhiyong

    2018-04-19

    Accurately identifying and quantifying cellular autophagy is very important as the significance of autophagy in physiological and pathological processes becomes increasingly evident. Ectopically expressed fluorescent-tagged microtubule-associated protein light chain 3B (MAP1LC3B, LC3) is the most widely used reporter for monitoring autophagy activity thus far. However, this approach ignores the influence of constitutively overexpressed LC3 on autophagy itself and autophagy-related processes and its accuracy in indicating autophagy is questionable. Here, we generated a knock-in GFP-LC3 reporter via the CRISPR/Cas9 system in 293FT cells to add GFP to the N-terminal of and in frame with endogenous LC3. We proved that this knock-in GFP-LC3 was expressed at biological level driven by the endogenous transcriptional regulatory elements as the wild type alleles. Compared with the ectopically expressed GFP-LC3, the endogenous knock-in reporter exhibited much higher sensitivity and signal-to-noise ratio of GFP-LC3 puncta upon the induction or inhibition of autophagy at certain step for monitoring autophagy activity. Thus, according to the previous reported concerning and the results presented here, we suggest that this knock-in GFP-LC3 reporter is better for bona fide monitoring cellular autophagy and should be employed for further study of autophagy in vitro and in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Functional validation of putative toxin-antitoxin genes from the Gram-positive pathogen Streptococcus pneumoniae: phd-doc is the fourth bona-fide operon.

    Science.gov (United States)

    Chan, Wai Ting; Yeo, Chew Chieng; Sadowy, Ewa; Espinosa, Manuel

    2014-01-01

    Bacterial toxin-antitoxin (TAs) loci usually consist of two genes organized as an operon, where their products are bound together and inert under normal conditions. However, under stressful circumstances the antitoxin, which is more labile, will be degraded more rapidly, thereby unleashing its cognate toxin to act on the cell. This, in turn, causes cell stasis or cell death, depending on the type of TAs and/or time of toxin exposure. Previously based on in silico analyses, we proposed that Streptococcus pneumoniae, a pathogenic Gram-positive bacterium, may harbor between 4 and 10 putative TA loci depending on the strains. Here we have chosen the pneumococcal strain Hungary(19A)-6 which contains all possible 10 TA loci. In addition to the three well-characterized operons, namely relBE2, yefM-yoeB, and pezAT, we show here the functionality of a fourth operon that encodes the pneumococcal equivalent of the phd-doc TA. Transcriptional fusions with gene encoding Green Fluorescent Protein showed that the promoter was slightly repressed by the Phd antitoxin, and exhibited almost background values when both Phd-Doc were expressed together. These findings demonstrate that phd-doc shows the negative self-regulatory features typical for an authentic TA. Further, we also show that the previously proposed TAs XreA-Ant and Bro-XreB, although they exhibit a genetic organization resembling those of typical TAs, did not appear to confer a functional behavior corresponding to bona fide TAs. In addition, we have also discovered new interesting bioinformatics results for the known pneumococcal TAs RelBE2 and PezAT. A global analysis of the four identified toxins-antitoxins in the pneumococcal genomes (PezAT, RelBE2, YefM-YoeB, and Phd-Doc) showed that RelBE2 and Phd-Doc are the most conserved ones. Further, there was good correlation among TA types, clonal complexes and sequence types in the 48 pneumococcal strains analyzed.

  12. The LAMOST spectroscopic survey of globular clusters in M31 and M33. I. catalog and new identifications

    International Nuclear Information System (INIS)

    Chen, Bing-Qiu; Liu, Xiao-Wei; Xiang, Mao-Sheng; Huang, Yang; Sun, Ning-Chen; Wang, Chun; Ren, Juan-Juan; Zhang, Hua-Wei; Yuan, Hai-Bo; Rebassa-Mansergas, Alberto; Huo, Zhi-Ying; Yang, Ming; Zhang, Yong; Hou, Yong-Hui; Wang, Yue-Fei

    2015-01-01

    We present a catalog of 908 objects observed with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) in fields in the vicinity of M31 and M33, targeted as globular clusters (GCs) and candidates. The targets include known GCs and candidates selected from the literature, as well as new candidates selected from the Sloan Digital Sky Survey (SDSS). Analysis shows that 356 of them are likely GCs with various confidence levels, while the remaining ones turn out to be background galaxies and quasars, stars and H ii regions in M31 or foreground Galactic stars. The 356 likely GCs include 298 bona fide GCs and 26 candidates known in the literature. Three candidates, selected from the Revised Bologna Catalog of M31 GCs and candidates (RBC) and one possible cluster from Johnson et al., are confirmed to be bona fide clusters. We search for new GCs in the halo of the M31 among the new candidates selected from the SDSS photometry. Based on radial velocities yielded by LAMOST spectra and visual examination of the SDSS images, we find 28 objects, 5 bona fide and 23 likely GCs. Among the five bona fide GCs, three have been recently discovered independently by others, and the remaining 25 are our new identifications, including two bona fide ones. The newly identified objects fall at projected distances ranging from 13 to 265kpc from M31. Of the two newly discovered bona fide GCs, one is located near M33, probably a GC belonging to M33. The other bona fide GC falls on the Giant Stream with a projected distance of 78 kpc from M31. Of the 23 newly identified likely GCs, one has a projected distance of about 265 kpc from M31 and could be an intergalactic cluster. (paper)

  13. 7 CFR 905.23 - Selection.

    Science.gov (United States)

    2010-01-01

    ... affiliated with bona fide cooperative marketing organizations. (b) From the nominations made pursuant to... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... alternates to represent bona fide cooperative marketing organizations which are handlers, and the remaining...

  14. 39 CFR 320.4 - Suspension for certain letters of college and university organizations.

    Science.gov (United States)

    2010-07-01

    ... universities to carry in their internal mail systems the letters of their bona fide student or faculty... university. Colleges and universities choosing to provide their student or faculty organizations access to their internal mail systems are responsible for assuring that only letters of bona fide student or...

  15. 76 FR 24523 - Sun & Lake Pharmacy, Inc.; D/B/A the Medicine Shoppe; Revocation of Registration

    Science.gov (United States)

    2011-05-02

    ... fundamental that a physician practitioner must have established a bona fide doctor-patient relationship in... state law to determine whether a bona fide doctor patient relationship existed.'' Id. at 33-34... issued pursuant to a valid doctor-patient relationship. The ALJ noted that a DEA Diversion Investigator...

  16. 42 CFR 433.67 - Limitations on level of FFP for permissible provider-related donations.

    Science.gov (United States)

    2010-10-01

    ... provider-related donations. 433.67 Section 433.67 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... permissible provider-related donations. (a)(1) Limitations on bona fide donations. There are no limitations on the amount of bona fide provider-related donations that a State may receive without a reduction in FFP...

  17. 26 CFR 31.3401(a)(6)-1A - Remuneration for services of certain nonresident alien individuals paid before January 1, 1967.

    Science.gov (United States)

    2010-04-01

    ... follows: Sec. 101. Definitions. [Immigration and Nationality Act (66 Stat. 166)] (a) As used in this... has no intention of abandoning, who is a bona fide student qualified to pursue a full course of study... intention of abandoning who is a bona fide student, scholar, trainee, teacher, professor, research assistant...

  18. Office of International Affairs | NSU

    Science.gov (United States)

    Undergraduate Studies Overview Central Administration Administrative Services and Marketing Student Activity Fee valid advance parole and those with a bona fide relationship to a person or entity in the United States foreign nationals who have a credible claim of a bona fide relationship to an entity or person in the

  19. 76 FR 4289 - Honey From the People's Republic of China: Final Results and Rescission of Antidumping Duty New...

    Science.gov (United States)

    2011-01-25

    ... Fenglian Co., Ltd. (``Fenglian''), the Department finds that that sales under review are not bona fide... Shipper Reviews, 75 FR 55307 (September 10, 2010). Because the sales under review were made during the POR... Republic of China: Bona Fide Analysis of the Sale Under Review for Suzhou Shanding Honey Product Co., Ltd...

  20. 75 FR 55307 - Honey From the People's Republic of China: Preliminary Intent To Rescind New Shipper Reviews

    Science.gov (United States)

    2010-09-10

    ... Shipper Review, 75 FR 38980 (July 7, 2010). Expansion of the POR When the sale of the subject merchandise... review is based on a single sale, exclusion of that sale as non-bona fide necessarily must end the review... Shipper Review of Honey from the People's Republic of China: Bona Fide Analysis of the Sale Under Review...

  1. 19 CFR 10.153 - Conditions for exemption.

    Science.gov (United States)

    2010-04-01

    ... over $200 and Bona Fide Gifts § 10.153 Conditions for exemption. Customs officers shall be further... § 10.151 or § 10.152: (a) A “bona fide gift” for purposes of § 10.152 is an article formerly owned by a... promise of compensation. It does not include articles acquired by purchase, barter, promissory exchange...

  2. Hate Speech Provisions and Provisos: A Response to Marais and ...

    African Journals Online (AJOL)

    MJM Venter

    2017-11-06

    Nov 6, 2017 ... right to freedom of expression and the hate speech limitation in section ... important to take into account that the Act was enacted as a legal means to ...... Films and Publications Act,91 both of which exclude bona fide forms of ..... Likewise, in the context of a bona fide stand-up comedy production, a rude.

  3. Nuclear hazard/fire hazard: an elusive and important linkage

    International Nuclear Information System (INIS)

    Mariani, L.P.

    1977-01-01

    The Brown's Ferry Fire signaled a yellow alert for nuclear safety related fire protection and showed that fire protection engineering must be regarded as a bona fide nuclear discipline. A single-failure design criteria violation resulted in fire damage to plant systems and plant instrumentation. Localized damage lead to significant consequences. Although the linkage between fire and nuclear hazard is termed subtle, effective standards and criteria development must be aimed to future plants. Combined fire protection and nuclear engineering inspections are planned

  4. Generator exchange is associated with an increased rate of Sprint Fidelis lead failure.

    Science.gov (United States)

    Lovelock, Joshua D; Patel, Ayesha; Mengistu, Andenet; Hoskins, Michael; El-Chami, Mikhael; Lloyd, Michael S; Leon, Angel; DeLurgio, David; Langberg, Jonathan J

    2012-10-01

    The Medtronic Sprint Fidelis defibrillator lead is at an increased risk for failure and was recalled in October 2007. Approximately 268,000 leads were implanted, and more than 100,000 patients still have active Fidelis leads. A number of studies have examined the rate and clinical predictors of lead failure, but none has addressed the effect of an implantable cardioverter-defibrillator generator exchange on subsequent lead failure. Although the manufacturer asserts that "Sprint Fidelis performance after device change-out is similar to lead performance without device change-out," published data are lacking. To assess the effect of implantable cardioverter-defibrillator generator exchange on the rate of Fidelis lead failure. A chart review was conducted in patients who underwent implantation of a Fidelis lead. Patients with a functioning Fidelis lead at generator exchange were compared with controls with leads implanted for a comparable amount of time not undergoing ICD replacement. A total of 1366 patients received a Fidelis lead prior to the recall, of which 479 were still actively followed. Seventy-two patients with a functioning lead underwent generator exchange without lead replacement. Following generator replacement, 15 leads failed. Sixty percent of the Fidelis leads failed within 3 months. Generator exchange increased the rate of lead failure compared with matched controls (20.8% vs 2.54%; P exchange is associated with a higher than expected rate of Fidelis lead failure, often within 3 months. The risk-benefit ratio of Fidelis lead replacement at the time of generator exchange may be greater than appreciated. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. Travelling wave solutions of the generalized Benjamin-Bona-Mahony equation

    International Nuclear Information System (INIS)

    Estevez, P.G.; Kuru, S.; Negro, J.; Nieto, L.M.

    2009-01-01

    A class of particular travelling wave solutions of the generalized Benjamin-Bona-Mahony equation is studied systematically using the factorization technique. Then, the general travelling wave solutions of Benjamin-Bona-Mahony equation, and of its modified version, are also recovered.

  6. DZ Chamaeleontis: a bona fide photoevaporating disc

    Science.gov (United States)

    Canovas, H.; Montesinos, B.; Schreiber, M. R.; Cieza, L. A.; Eiroa, C.; Meeus, G.; de Boer, J.; Ménard, F.; Wahhaj, Z.; Riviere-Marichalar, P.; Olofsson, J.; Garufi, A.; Rebollido, I.; van Holstein, R. G.; Caceres, C.; Hardy, A.; Villaver, E.

    2018-02-01

    Context. DZ Cha is a weak-lined T Tauri star (WTTS) surrounded by a bright protoplanetary disc with evidence of inner disc clearing. Its narrow Hα line and infrared spectral energy distribution suggest that DZ Cha may be a photoevaporating disc. Aims: We aim to analyse the DZ Cha star + disc system to identify the mechanism driving the evolution of this object. Methods: We have analysed three epochs of high resolution optical spectroscopy, photometry from the UV up to the sub-mm regime, infrared spectroscopy, and J-band imaging polarimetry observations of DZ Cha. Results: Combining our analysis with previous studies we find no signatures of accretion in the Hα line profile in nine epochs covering a time baseline of 20 yr. The optical spectra are dominated by chromospheric emission lines, but they also show emission from the forbidden lines [SII] 4068 and [OI] 6300Å that indicate a disc outflow. The polarized images reveal a dust depleted cavity of 7 au in radius and two spiral-like features, and we derive a disc dust mass limit of Mdust 80 MJup) companions are detected down to 0.̋07 ( 8 au, projected). Conclusions: The negligible accretion rate, small cavity, and forbidden line emission strongly suggests that DZ Cha is currently at the initial stages of disc clearing by photoevaporation. At this point the inner disc has drained and the inner wall of the truncated outer disc is directly exposed to the stellar radiation. We argue that other mechanisms like planet formation or binarity cannot explain the observed properties of DZ Cha. The scarcity of objects like this one is in line with the dispersal timescale (≲105 yr) predicted by this theory. DZ Cha is therefore an ideal target to study the initial stages of photoevaporation. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 097.C-0536. Based on data obtained from the ESO Science Archive Facility under request number 250112.

  7. Comparison of Sprint Fidelis and Riata defibrillator lead failure rates.

    Science.gov (United States)

    Fazal, Iftikhar A; Shepherd, Ewen J; Tynan, Margaret; Plummer, Christopher J; McComb, Janet M

    2013-09-30

    Sprint Fidelis and Riata defibrillator leads are prone to early failure. Few data exist on the comparative failure rates and mortality related to lead failure. The aims of this study were to determine the failure rate of Sprint Fidelis and Riata leads, and to compare failure rates and mortality rates in both groups. Patients implanted with Sprint Fidelis leads and Riata leads at a single centre were identified and in July 2012, records were reviewed to ascertain lead failures, deaths, and relationship to device/lead problems. 113 patients had Sprint Fidelis leads implanted between June 2005 and September 2007; Riata leads were implanted in 106 patients between January 2003 and February 2008. During 53.0 ± 22.3 months of follow-up there were 13 Sprint Fidelis lead failures (11.5%, 2.60% per year) and 25 deaths. Mean time to failure was 45.1 ± 15.5 months. In the Riata lead cohort there were 32 deaths, and 13 lead failures (11.3%, 2.71% per year) over 54.8 ± 26.3 months follow-up with a mean time to failure of 53.5 ± 24.5 months. There were no significant differences in the lead failure-free Kaplan-Meier survival curve (p=0.77), deaths overall (p=0.17), or deaths categorised as sudden/cause unknown (p=0.54). Sprint Fidelis and Riata leads have a significant but comparable failure rate at 2.60% per year and 2.71% per year of follow-up respectively. The number of deaths in both groups is similar and no deaths have been identified as being related to lead failure in either cohort. Copyright © 2012. Published by Elsevier Ireland Ltd.

  8. 48 CFR 225.7303-4 - Contingent fees.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Contingent fees. 225.7303....7303-4 Contingent fees. (a) Except as provided in paragraph (b) of this subsection, contingent fees are generally allowable under DoD contracts, provided— (1) The fees are paid to a bona fide employee or a bona...

  9. 29 CFR 553.32 - Other FLSA exemptions.

    Science.gov (United States)

    2010-07-01

    ... a bona fide executive, administrative, professional, or outside sales capacity, as these terms are... helpers, loaders, and mechanics employed by a common carrier whose activities directly affect the safety...

  10. 27 CFR 6.101 - Merchandise.

    Science.gov (United States)

    2010-04-01

    ... member, who is also in business as a bona fide producer or vendor of other merchandise (for example..., fixtures, signs, glassware, supplies, services, and advertising specialties to retailers does not...

  11. 29 CFR 1625.8 - Bona fide seniority systems.

    Science.gov (United States)

    2010-07-01

    ... equitable allocation of available employment opportunities and prerogatives among younger and older workers. (b) Adoption of a purported seniority system which gives those with longer service lesser rights, and... upon the circumstances, be a “subterfuge to evade the purposes” of the Act. (c) Unless the essential...

  12. 48 CFR 809.406-4 - Period of debarment.

    Science.gov (United States)

    2010-10-01

    ... indicated after the DSPE reviews documentary evidence submitted by or on behalf of the contractor setting... evidence, reversal of a conviction, bona fide change of ownership or management, elimination of the cause...

  13. 15 CFR 315.2 - Definitions.

    Science.gov (United States)

    2010-01-01

    ..., part 6, schedule 6, of the Tariff Schedules of the United States (excluding an electric trolley bus and a three-wheeled vehicle) or an automotive truck tractor. (d) Bona fide motor-vehicle manufacturer...

  14. 18 CFR 366.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... NATURAL GAS ACT BOOKS AND RECORDS Definitions and Provisions Under PUHCA 2005, the Federal Power Act and... with the bona fide intention of effecting distribution within 12 months of the specific securities so...

  15. 20 CFR 655.736 - What are H-1B-dependent employers and willful violators?

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... not include bona fide consultants and independent contractors. For purposes of this section, the...

  16. 20 CFR 655.22 - Obligations of H-2B employers.

    Science.gov (United States)

    2010-04-01

    ..., salary, or benefits), kickbacks, bribes, tributes, in kind payments, and free labor. (k) If the employer... makes a written bona fide inquiry as to whether the other employer has displaced or intends to displace...

  17. Soil as a Sustainable Resource for the Bioeconomy - BonaRes

    Science.gov (United States)

    Wollschläger, Ute; Amelung, Wulf; Brüggemann, Nicolas; Brunotte, Joachim; Gebbers, Robin; Grosch, Rita; Heinrich, Uwe; Helming, Katharina; Kiese, Ralf; Leinweber, Peter; Reinhold-Hurek, Barbara; Veldkamp, Edzo; Vogel, Hans-Jörg; Winkelmann, Traud

    2017-04-01

    Fertile soils are a fundamental resource for the production of biomass and provision of food and energy. A growing world population and latest climate targets lead to an increasing demand for bio-based products which require preserving and - ideally - improving the long-term productivity of soils as a bio-economic resource. At the same time, other soil functions and ecosystem services need to be maintained: filter for clean water, carbon sequestration, provision and recycling of nutrients, and habitat for biological activity. All these soil functions result from the interaction of a multitude of physical, chemical and biological processes which are insufficiently understood. In addition, we lack understanding about the interplay between the socio-economic system and the soil system and how soil functions benefit human wellbeing, including SDGs. However, a solid and integrated assessment of soil quality requires the consideration of the ensemble of soil functions and its relation to soil management. To make soil management sustainable, we need to establish a scientific knowledge base of complex soil system processes that allows for developing models and tools to quantitatively predict the impact of a multitude of management measures on soil functions. This will finally allow for the provision of options for a site-specific, sustainable soil management. To face this challenge, the German Federal Ministry of Education and Research (BMBF) recently launched the funding program "Soil as a Sustainable Resource for the Bioeconomy - BonaRes". In a joint effort, ten collaborative projects and the coordinating BonaRes Centre are engaged to close existing knowledge gaps for a profound and systemic assessment and understanding of soil functions and their sensitivity to soil management. In BonaRes, the complete process chain of sustainable soil use in the context of a sustainable bio-economy is being addressed: from understanding of soil processes using state-of the art and

  18. 41 CFR 60-20.2 - Recruitment and advertisement.

    Science.gov (United States)

    2010-07-01

    ... engaged in recruiting activity must recruit employees of both sexes for all jobs unless sex is a bona fide... advertisement in columns headed “Male” or “Female” will be considered an expression of a preference, limitation...

  19. 对物权法草案的不同意见及建议%Some opinions and suggestions on the draft of real property law

    Institute of Scientific and Technical Information of China (English)

    梁慧星

    2007-01-01

    It is suggested in the article that exclusivity should be added to the definition of the real property right; the following clauses should be revised: the definition of the real property right, the competency of evidence of the register of immovables, the effectiveness of the bona fide protection of real property registration, the tort liabilities of the registration authority, possession reformula- tion, state ownership of water resources and wildlife resources and public utilities, bona fide acquisition, transfer of contracting and operational rights, and mortgage. The following provisions should be added: the ownership of religious property, the acquisitive prescription, and the pledge on business. It is also suggested that the provisions on claims in rem prescribed in Article 39 and Article 42 be deleted, and the provision on dwelling rights, that is, Chapter XV, also be deleted.

  20. Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development

    DEFF Research Database (Denmark)

    Petkov, Stoyan; Freude, Kristine; Mashayekhi-Nezamabadi, Kaveh

    2017-01-01

    The lack in production of bona fide porcine pluripotent stem cells has definitely been hampered by a lack of research into porcine embryo development. Embryonic development in mammals is the extraordinary transition of a single-celled fertilized zygote into a complex fetus, which occurs...... in the uterus of the maternal adult during the early stages of gestation. Biomedical pig models could serve as genetic backgrounds for establishment of embryonic stem cells (ESCs) or other pluripotent stem cells (such as iPSC), which may be used to model and study diseases in vitro. This chapter provides...... insight into the current knowledge of pluripotent states in the developing pig embryo and the current status in establishment of bona fide porcine ESC (pESC) and piPSCs. It reflects the potential causes underlying the difficulty in establishing pluripotent stem cells and reviews recent data on global...

  1. Educating for Professional Identity Development

    NARCIS (Netherlands)

    C.P. Tan (Chin Peil)

    2014-01-01

    markdownabstract__Abstract__ In preparing students for their role in their respective communities, vocational and professional education should provide for learning experiences that acculturate them to become the new and bona fide practitioners. In addition to acquiring pre-requisite knowledge

  2. Economics | Page 12 | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The book is a bona fide crystal ball. It will be a must read for the next decade. David Bloom, Clarence James Gamble Professor of Economics and Demography and ... of Global Health and Population, Harvard School of Public Health, USA.

  3. Population Aging and the Generational Economy: A Global ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    31 oct. 2011 ... The book is a bona fide crystal ball. It will be a must read for the next decade. David Bloom, Clarence James Gamble Professor of Economics and ... of Global Health and Population, Harvard School of Public Health, USA.

  4. 42 CFR 3.20 - Definitions.

    Science.gov (United States)

    2010-10-01

    ..., clinical laboratory, or health center; or (ii) A physician, physician assistant, registered nurse, nurse practitioner, clinical nurse specialist, certified registered nurse anesthetist, certified nurse midwife... the Secretary, which issues decisions in panels of three. Bona fide contract means: (1) A written...

  5. Bona Fide Thermodynamic Temperature in Nonequilibrium Kinetic Ising Models

    OpenAIRE

    Sastre, Francisco; Dornic, Ivan; Chaté, Hugues

    2003-01-01

    We show that a nominal temperature can be consistently and uniquely defined everywhere in the phase diagram of large classes of nonequilibrium kinetic Ising spin models. In addition, we confirm the recent proposal that, at critical points, the large-time ``fluctuation-dissipation ratio'' $X_\\infty$ is a universal amplitude ratio and find in particular $X_\\infty \\approx 0.33(2)$ and $X_\\infty = 1/2$ for the magnetization in, respectively, the two-dimensional Ising and voter universality classes.

  6. The Benjamin-Bona-Mahony equation with dissipative memory

    Czech Academy of Sciences Publication Activity Database

    Dell'Oro, Filippo; Mammeri, Y.; Pata, V.

    2015-01-01

    Roč. 22, č. 4 (2015), s. 899-910 ISSN 1021-9722 Institutional support: RVO:67985840 Keywords : Benjamin-Bona-Mahony equation * dissipative memory * exponential stability * nonlinear contraction semigroup Subject RIV: BA - General Mathematics Impact factor: 0.797, year: 2015 http://link.springer.com/article/10.1007%2Fs00030-014-0308-8

  7. 29 CFR 541.0 - Introductory statement.

    Science.gov (United States)

    2010-07-01

    ... DELIMITING THE EXEMPTIONS FOR EXECUTIVE, ADMINISTRATIVE, PROFESSIONAL, COMPUTER AND OUTSIDE SALES EMPLOYEES... employee employed in a bona fide executive, administrative, or professional capacity (including any... secondary schools), or in the capacity of an outside sales employee, as such terms are defined and delimited...

  8. The CRAPome: a contaminant repository for affinity purification–mass spectrometry data

    NARCIS (Netherlands)

    Mellacheruvu, D.; Wright, Z.; Couzens, A.L.; Low, T.Y.|info:eu-repo/dai/nl/411298437; Halim, V.A.|info:eu-repo/dai/nl/326157441; Heck, A.J.R.|info:eu-repo/dai/nl/105189332; Mohammed, S.|info:eu-repo/dai/nl/30483632X; Nesvizhskii, A.

    2013-01-01

    Affinity purification coupled with mass spectrometry (AP-MS) is a widely used approach for the identification of protein-protein interactions. However, for any given protein of interest, determining which of the identified polypeptides represent bona fide interactors versus those that are background

  9. Long-term Field Experiments as Important Source of Knowledge - Aims of the BonaRes Data Centre

    Science.gov (United States)

    Grosse, Meike; Hierold, Wilfried

    2017-04-01

    BonaRes is short for "soil as a sustainable resource for the bioeconomy". It is funded by the German Federal Ministry of Education and Research (BMBF) under the umbrella of the National Research Strategy BioEconomy 2030. BonaRes consists of ten interdisciplinary research project consortia and the 'BonaRes - Centre for Soil Research' (see also Wollschläger et al 2016). It is one task of the BonaRes Data Centre as part of the 'BonaRes - Centre for Soil Research', to collect data and meta-data of agricultural long-term field experiments (LTFE) in Germany. The definition of LTFE in the context of BonaRes is a minimum duration of twenty years and a static design. LTFE are essential research infrastructures for agricultural sciences and soil sciences amongst other disciplines. Some LTFE run since a very long time; the start of the oldest one in Germany was 1878. Therefore, in many cases valuable time series exist. Data sets of LTFE shall be compiled and made publicly available by the BonaRes Data Centre. The public availability together with an easy access will lead to an enhanced usability of the data. This probably makes the LTFE itself more valuable through an improved visibility and may also help to maintain the LTFE. Beyond the data compilation there is the possibility for every data owner to make a data publication, which offers an additional value for the data owner after his first right of use. A first step towards a joint database is a compilation of all existing LTFE in Germany with meta information to each trial. This information is shown in an interactive web map, what is completely new in that context. Besides the exact position of the LTFE the following metadata are shown: name of the LTFE, website (if available), institution, land use category, participation in existing networks, research theme, start (and maybe end) of the trial, and research parameters. Details on the meta information will be presented in the speech. Literature Wollschläger, U; Helming

  10. 26 CFR 1.911-7 - Procedural rules.

    Science.gov (United States)

    2010-04-01

    ... effective; (v) The exclusion or exclusions the individual is electing; (vi) The foreign country or countries...) The status (either bona fide residence or physical presence) under which the individual claims the exclusion; (viii) The individual's qualifying period of residence or presence; (ix) The individual's foreign...

  11. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Tubsuwan, Alisa; Schmid, Benjamin

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  12. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  13. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  14. 29 CFR 5.2 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... mental or managerial. The term laborer or mechanic includes apprentices, trainees, helpers, and, in the..., rather than manual. Persons employed in a bona fide executive, administrative, or professional capacity... apprentice, trainee, and helper are defined as follows: (1) Apprentice means (i) a person employed and...

  15. 75 FR 475 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-01-05

    ... such member's financial condition as disclosed in its most recent balance sheet prepared either in... satisfying the requirement that members make balance sheet information available to bona fide regular... most recent balance sheet . * * *'' FINRA is proposing to provide members with the option of delivering...

  16. 76 FR 48887 - Liddy's Pharmacy, L.L.C. Denial of Application

    Science.gov (United States)

    2011-08-09

    ... doctors who did not appear to have valid physician-patient relationships with the recipients of the... prescriptions pursuant to a legitimate doctor-patient relationship. \\5\\ He also issued eight prescriptions to... persons and established bona fide doctor-patient relationships with them. Here again, Respondent clearly...

  17. 75 FR 65663 - Gilbert Eugene Johnson, M.D.; Revocation of Registration

    Science.gov (United States)

    2010-10-26

    ... doctor-patient relationship and a legitimate medical need for the prescription) and directed the employee... practitioner must establish a bona fide doctor-patient relationship in order to act `in the usual course of... patient relationship''; (2) Respondent ``engaged in indiscriminate or excessive prescribing, dispensing or...

  18. 75 FR 4529 - Circular Welded Carbon Steel Pipes and Tubes From Thailand: Final Results of Antidumping Duty New...

    Science.gov (United States)

    2010-01-28

    ... Compliance Analyst, Office 6, Verification of the Sales Response of Pacific Pipe Public Company, Limited in... Pipe Public Company, Limited, dated August 24, 2009 (Bona Fides Preliminary Memorandum). The Department... Circular Welded Carbon Steel Pipes and Tubes from Thailand: Pacific Pipe Public Company, Limited, dated...

  19. Good faith limitations on protected investments and corporate structuring

    NARCIS (Netherlands)

    Schill, S.W.; Bray, H.L.; Mitchell, A.D.; Sornarajah, M.; Voon, T.

    2015-01-01

    On numerous occasions, investment treaty tribunals have relied—and in some cases refused to rely—on the principle of good faith to ensure that only bona fide investments and investors are protected under the relevant investment treaty. This chapter reviews the jurisprudence on illegal investments

  20. Structure of the DNA-bound BRCA1 C-terminal region from human replication factor C p140 and model of the protein-DNA complex

    NARCIS (Netherlands)

    Kobayashi, M.; AB, E.; Bonvin, A.M.J.J.; Siegal, G.

    2010-01-01

    BRCA1 C-terminal domain (BRCT)-containing proteins are found widely throughout the animal and bacteria kingdoms where they are exclusively involved in cell cycle regulation and DNA metabolism. Whereas most BRCT domains are involved in protein-protein interactions, a small subset has bona fide DNA

  1. 22 CFR 61.5 - Authentication procedures-Imports.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication procedures-Imports. 61.5 Section... AUDIO-VISUAL MATERIALS § 61.5 Authentication procedures—Imports. (a) Applicants seeking Department authentication of foreign produced audio-visual materials shall submit to the Department a bona fide foreign...

  2. 75 FR 66138 - George Mathew, M.D.; Denial of Application

    Science.gov (United States)

    2010-10-27

    ... controlled substances to Internet customers despite never establishing a genuine doctor-patient relationship...'' and thus did not establish ``a valid doctor- patient relationship.'' Id. at 29. Based on an undercover... be a bona fide doctor/patient relationship.'' Id. at 21182. The Agency further noted that ``many...

  3. 26 CFR 1.410(b)-4 - Nondiscriminatory classification test.

    Science.gov (United States)

    2010-04-01

    ..., nature of compensation (i.e., salaried or hourly), geographic location, and similar bona fide business... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.410(b)-4 Nondiscriminatory classification test. (a) In general. A plan satisfies the nondiscriminatory classification test of...

  4. Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis

    DEFF Research Database (Denmark)

    Tafesse, Fikadu G.; Vacaru, Ana M.; Bosma, Elleke Fenna

    2014-01-01

    ceramide-induced cell death and that SMSr-mediated ceramide homeostasis requires the N-terminal sterile a-motif, or SAM domain, of the enzyme. These results define ER ceramides as bona fide transducers of mitochondrial apoptosis and indicate a primary role of SMSr in monitoring ER ceramide levels...

  5. 77 FR 25136 - Seamless Refined Copper Pipe and Tube From Mexico: Preliminary Results of Antidumping Duty New...

    Science.gov (United States)

    2012-04-27

    ... for convenience and customs purposes, the written description of the scope of the order is dispositive... business proprietary, see ``Bona Fides Analysis Memorandum'' dated April 23, 2012, for a detailed... appropriate, from the starting price for international freight, inland insurance, U.S. warehouse expenses, U.S...

  6. 12 CFR 563b.530 - What other requirements apply after I convert?

    Science.gov (United States)

    2010-01-01

    ... quotations for the security in a recognized inter-dealer quotation system; (2) Furnishes bona fide competitive bid and offer quotations for the security on request; or (3) May effect transactions for the... Securities Dealers Automated Quotation system. (d) File all post-conversion reports that OTS requires...

  7. 78 FR 69823 - Atlantic Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering...

    Science.gov (United States)

    2013-11-21

    ... display and educational activities with respect to Atlantic HMS. Since the Magnuson-Stevens Act does not... during that research, NMFS may consider those vessels as bona fide research platforms while conducting..., NMFS review of public comments received on this notice, an applicant's reporting history on past...

  8. BANYAN. XII. New Members of Nearby Young Associations from GAIA–Tycho Data

    Science.gov (United States)

    Gagné, Jonathan; Roy-Loubier, Olivier; Faherty, Jacqueline K.; Doyon, René; Malo, Lison

    2018-06-01

    We present a search for stellar members of young associations within 150 pc of the Sun, based on TGAS and an updated version of the BANYAN Σ software to determine Bayesian membership probabilities that includes Gaia–2MASS color-magnitude diagrams. We identify 32 new F0–M3-type bona fide members of the 10–200 Myr old Sco-Cen, Carina, Tucana-Horologium, Columba, and Octans associations and the AB Doradus, β Pictoris, and Carina-Near moving groups. These new bona fide members have measurements of their full kinematics and literature data consistent with a young age. We also confirm the membership of 66 previously known candidate members using their Gaia–Tycho trigonometric distances or new literature radial velocities, and identify 219 additional new candidate members, most of which do not yet have a radial velocity measurement. This work is the first step toward a completeness-corrected survey of young association members based on Gaia DR2 in the near future.

  9. The Impossibility of Capitalist Markets in Higher Education

    Science.gov (United States)

    Marginson, Simon

    2013-01-01

    For more than two decades, governments around the world, led by the English-speaking polities, have moved higher education systems closer to the forms of textbook economic markets. Reforms include corporatisation, competitive funding, student charges, output formats and performance reporting. But, no country has established a bona fide economic…

  10. 26 CFR 1.170-2 - Charitable deductions by individuals; limitations (before amendment by Tax Reform Act of 1969).

    Science.gov (United States)

    2010-04-01

    ... community in which the organization operates or if it makes a bona fide dissemination of a brochure... charitable purposes by a single impartial committee. The M Organization, by distribution of pamphlets to the... a brochure containing a financial statement of its operations including a list of all receipts and...

  11. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells

    NARCIS (Netherlands)

    Maldonado, Paloma P; Angulo, María Cecilia

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity

  12. 48 CFR 52.203-5 - Covenant Against Contingent Fees.

    Science.gov (United States)

    2010-10-01

    ... REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and... employed or retained to solicit or obtain this contract upon an agreement or understanding for a contingent fee, except a bona fide employee or agency. For breach or violation of this warranty, the Government...

  13. 77 FR 79 - Honey From the People's Republic of China: Preliminary Rescission of the Administrative Review

    Science.gov (United States)

    2012-01-03

    ... dispositive. Bona Fide Analysis In this administrative review, Petitioners alleged that the sales of Dongtai... these sales the Department undertook that analysis in this review. Where all of the sales in a review... whether a sale in a review is unrepresentative or extremely distortive, and therefore excludable as non...

  14. β-Peptoid Foldamers at Last

    DEFF Research Database (Denmark)

    Laursen, Jonas S; Engel-Andreasen, Jens; Olsen, Christian A

    2015-01-01

    in this journal in the late 1990s. Oligomers of N-alkylated 3-aminopropionic acid residues have been called β-peptoids due to their structural similarity to β-peptides and peptoids (N-alkylglycines), respectively. Because bona fide foldamer behavior has been demonstrated for both parent architectures, we wondered...

  15. 16 CFR 238.1 - Bait advertisement.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Bait advertisement. 238.1 Section 238.1 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES AGAINST BAIT ADVERTISING... when the offer is not a bona fide effort to sell the advertised product. [Guide 1] ...

  16. 24 CFR 3500.15 - Affiliated business arrangements.

    Science.gov (United States)

    2010-04-01

    ... § 3500.14(g) is a return on an ownership interest or franchise relationship. (i) In an affiliated... interest or franchise relationship, between entities in an affiliate relationship, are permissible; and (B... franchise agreement, will determine whether it is a bona fide return on an ownership interest or franchise...

  17. DSS1/Sem1, a multifunctional and intrinsically disordered protein

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Schenstrøm, Signe Marie; Rebula, Caio A.

    2016-01-01

    DSS1/Sem1 is a versatile intrinsically disordered protein. Besides being a bona fide subunit of the 26S proteasome, DSS1 associates with other protein complexes, including BRCA2-RPA, involved in homologous recombination; the Csn12-Thp3 complex, involved in RNA splicing; the integrator, involved...

  18. 75 FR 28068 - Christopher Henry Lister, P.A.; Revocation of Registration

    Science.gov (United States)

    2010-05-19

    ... that a practitioner must establish and maintain a bonafide doctor-patient relationship in order to act... prescription requirement * * * ensures patients use controlled substances under the supervision of a doctor so... generally looks to state law to determine whether a doctor and patient have established a bona fide doctor...

  19. Knowledge at work: learning and transferring expert reasoning through storytelling

    NARCIS (Netherlands)

    Hernandez-Serrano, J.; Stefanou, S.E.

    2009-01-01

    There is plenty of evidence in many fields of knowledge that storytelling is a bona fide human activity for problem-solving. We believe that a storytelling model for problem-solving can be constructed to organize this discourse. To that end, we carried out a qualitative study using the Grounded

  20. 7 CFR 27.100 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 27.100 Section 27.100 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Administration. The details of the method of carrying out the provisions of this subpart in each bona fide spot...

  1. 36 CFR 5.4 - Commercial passenger-carrying motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... chartered or rented in good faith to the operator, by the owner, for general use at a charge based upon time... initiated, organized, and directed by an established bona fide school or college, institution, society or... group that arranges for the transportation, assumes responsibility for financial risk and management...

  2. RNA/DNA co-analysis from human menstrual blood and vaginal secretion stains

    DEFF Research Database (Denmark)

    Haas, Claus; Hanson, E; Anjos, M J

    2014-01-01

    housekeeping genes for their suitability as reference genes. Six menstrual blood and six vaginal secretion stains, two dilution series (1/4-1/64 pieces of a menstrual blood/vaginal swab) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 24 participating...

  3. When Graduate Degrees Prostitute the Educational Process: Degrees Gone Wild

    Science.gov (United States)

    Lumadue, Richard T.

    2006-01-01

    Graduate degrees prostitute the educational process when they are sold to consumers by unaccredited degree/diploma mills as being equivalent to legitimate, bona-fide degrees awarded by accredited graduate schools. This article carefully analyzes the serious problems of bogus degrees and their association with the religious higher education…

  4. 17 CFR 150.3 - Exemptions.

    Science.gov (United States)

    2010-04-01

    ... this part may be exceeded to the extent such position are: (1) Bona fide hedging transactions as defined in § 1.3(z) of this chapter; (2) [Reserved] (3) Spread or arbitrage positions between single... month, in the same crop year; provided however, That such spread or arbitrage positions, when combined...

  5. 17 CFR 150.5 - Exchange-set speculative position limits.

    Science.gov (United States)

    2010-04-01

    ..., straddles, or arbitrage,” of from fixing limits which apply to such positions which are different from... opportunity for arbitrage between the futures market and the cash market in the commodity underlying the... pursuant to this section shall apply to bona fide hedging positions as defined by a contract market in...

  6. 77 FR 32522 - Tapered Roller Bearings and Parts Thereof, Finished and Unfinished From the People's Republic of...

    Science.gov (United States)

    2012-06-01

    ... is renumbered as 8708.99.8180; see Id. Bona Fides Sale Analysis For this review, consistent with the... POR. In evaluating whether or not a sale in a new shipper review is commercially reasonable, and... Shipper Review, 67 FR 11283 (March 13, 2002)). The Department preliminarily finds that the sales of...

  7. 26 CFR 1.132-5 - Working condition fringes.

    Science.gov (United States)

    2010-04-01

    ... exist unless the employee's employer establishes to the satisfaction of the Commissioner that an overall... example, threats are made on the life of an employee), the bona fide business-oriented security concern is... condition fringe. A “working condition fringe” is any property or service provided to an employee of an...

  8. 76 FR 78062 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2011-12-15

    ... Commission (``Commission'') the proposed rule change as described in Items I, II, and III below, which Items... Fees and Cancellation Fees if one or more ATP Firms or the Exchange experiences a bona fide systems... Excessive Bandwidth Utilization Fees and Cancellation Fees if one or more ATP Firms or the Exchange...

  9. 26 CFR 1.409A-1 - Definitions and covered plans.

    Science.gov (United States)

    2010-04-01

    ... short-term deferral rule set forth in paragraph (b)(4) of this section, the inclusion in income of an... plan provides bona fide vacation leave, sick leave, compensatory time, disability pay, or death benefits. For these purposes, the terms “disability pay” and “death benefits” have the same meanings as...

  10. 12 CFR Appendix A to Part 3 - Risk-Based Capital Guidelines

    Science.gov (United States)

    2010-01-01

    ... (as defined in section 2 of this appendix A) by its risk-weighted assets (as calculated pursuant to... customer at the time of the extension or renewal and upon a new, bona fide credit analysis utilizing... organizations that were taken in satisfaction of debts previously contracted, provided that the reporting...

  11. 7 CFR 27.95 - Spot markets to conform to Act and regulations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Spot markets to conform to Act and regulations. 27.95 Section 27.95 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE... and Differences § 27.95 Spot markets to conform to Act and regulations. Every bona fide spot market...

  12. 18 CFR 367.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... company. (6) Book cost means the amount at which property is recorded in these accounts without deduction... with the bona fide intention of effecting distribution within 12 months of the specific securities so... notes or by book accounts only, with respect to which it is mutually agreed or intended between the...

  13. 38 CFR 11.116 - Death of veteran before final settlement.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death of veteran before... Death of veteran before final settlement. If the veteran dies after making application under the... considered valid if found to bear the bona-fide signature of the applicant, discloses an intention to claim...

  14. 27 CFR 22.102 - Prohibited uses.

    Science.gov (United States)

    2010-04-01

    ...-free alcohol. A separate charge may be made by a hospital, sanitarium or clinic for medicines... and 22.106. Hospitals may not furnish tax-free alcohol for use of physicians in their private practice....106, clinics operated for charity and not for profit may compound bona fide medicines with tax-free...

  15. RNA/DNA co-analysis from blood stains--Results of a second collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, C.; Hanson, E.; Anjos, M.J.

    2012-01-01

    A second collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Six human blood stains, two blood dilution series (5-0.001 [mu]l blood) and, optionally, bona fide or mock casework samples of human or...

  16. 42 CFR 413.85 - Cost of approved nursing and allied health education activities.

    Science.gov (United States)

    2010-10-01

    ... education activities. (a) Statutory basis. This section implements section 1861(v)(1)(A) of the Act and... registered nurse anesthetist (CRNA) education programs that are determined on a reasonable cost basis are... subchapter. They include: (1) Orientation and on-the-job training. (2) Part-time education for bona fide full...

  17. 17 CFR 19.00 - General provisions.

    Science.gov (United States)

    2010-04-01

    ... and derivation of such conversion factors. (Approved by the Office of Management and Budget under... to the following: (1) Excluding products or byproducts of the cash commodity hedged. If the regular... cash positions for bona fide hedging (as defined in § 1.3(z) of this chapter), the same shall be...

  18. 29 CFR 779.401 - Statutory provision.

    Science.gov (United States)

    2010-07-01

    ... elementary or secondary schools), or in the capacity of outside salesman (as such terms are defined and... definition of employee employed in a bona fide executive or administrative capacity because of the number of hours in his workweek which he devotes to activities not directly or closely related to the performance...

  19. Discriminating strength: a bona fide measure of non-classical correlations

    Science.gov (United States)

    Farace, A.; De Pasquale, A.; Rigovacca, L.; Giovannetti, V.

    2014-07-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary {{R}_{A}} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B).

  20. Discriminating strength: a bona fide measure of non-classical correlations

    Energy Technology Data Exchange (ETDEWEB)

    Farace, A; De Pasquale, A; Giovannetti, V [NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, I-56126 Pisa (Italy); Rigovacca, L [Scuola Normale Superiore, I-56126 Pisa (Italy)

    2014-07-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R{sub A} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

  1. Discriminating strength: a bona fide measure of non-classical correlations

    International Nuclear Information System (INIS)

    Farace, A; De Pasquale, A; Giovannetti, V; Rigovacca, L

    2014-01-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R A whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

  2. A bona fide baby boom for the Baltics / Aleksei Gunter

    Index Scriptorium Estoniae

    Gunter, Aleksei, 1979-

    2004-01-01

    Seoses jaanuaris alanud vanemahüvitise programmiga ennustatakse sel aastal sündide arvu tõusu. Rahvastikuminister Paul-Eerik Rummo kommentaare. Tabel: Eesti rahvastikuandmed aprill 2003 - aprill 2004

  3. 26 CFR 1.933-1 - Exclusion of certain income from sources within Puerto Rico.

    Science.gov (United States)

    2010-04-01

    ... Puerto Rico. 1.933-1 Section 1.933-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Exclusion of certain income from sources within Puerto Rico. (a) General rule. (1) An individual (whether a United States citizen or an alien), who is a bona fide resident of Puerto Rico during the entire taxable...

  4. Salivary agglutinin/DMBT1SAG expression is up-regulated in the presence of salivary gland tumors

    DEFF Research Database (Denmark)

    Bikker, F J; van der Wal, J E; Ligtenberg, A J M

    2004-01-01

    Salivary agglutinin (SAG) is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1) and represents the salivary variant of DMBT1 (DMBT1(SAG)). While SAG is a bona fide anti-caries factor, DMBT1 was proposed as a candidate tumor-suppressor for brain, digestive tract, and lung cancer. Thou...

  5. 5 CFR 551.432 - Sleep time.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Sleep time. 551.432 Section 551.432... FAIR LABOR STANDARDS ACT Hours of Work Special Situations § 551.432 Sleep time. (a) Except as provided in paragraph (b) of this section, bona fide sleep time that fulfills the following conditions shall...

  6. 29 CFR 541.101 - Business owner.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Business owner. 541.101 Section 541.101 Labor Regulations... Executive Employees § 541.101 Business owner. The term “employee employed in a bona fide executive capacity... equity interest in the enterprise in which the employee is employed, regardless of whether the business...

  7. 75 FR 81677 - Pendency of Request for Exemption From the Bond/Escrow Requirement Relating to the Sale of Assets...

    Science.gov (United States)

    2010-12-28

    ... Requirement Relating to the Sale of Assets by an Employer Who Contributes to a Multiemployer Plan: Rangers... for the five-plan-year period beginning after the sale. PBGC is authorized to grant individual and... Plan Amendments Act of 1980 (``ERISA'' or the ``Act''), provides that a bona fide arm's length sale of...

  8. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Persson, Morten; Haldager, L

    2011-01-01

    PA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X...

  9. 16 CFR 308.3 - Advertising of pay-per-call services.

    Science.gov (United States)

    2010-01-01

    ... services to children under the age of 12, unless the service is a bona fide educational service. (2) For...-prepared video directed to children under 12, or preceding a movie directed to children under 12 shown in a movie theater; (vi) Whether the advertisement or promotion appears on product packaging directed to...

  10. 29 CFR 778.327 - Temporary or sporadic reduction in schedule.

    Science.gov (United States)

    2010-07-01

    ... rate at $6 per hour for all workweeks in which the employee worked 40 hours or less, approximately $5... at a bona fide $6 rate usually working 50 hours and taking home $330 as total straight time and... Section 778.327 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  11. 77 FR 26175 - Section 42 Qualified Contract Provisions

    Science.gov (United States)

    2012-05-03

    ... indebtedness under general principles of Federal income tax law, and (3) upon the sale of the building, are... building for sale to the general public at the determined qualified contract price upon receipt of a... because of variations under State laws concerning the terms of a bona fide contract and methods for...

  12. Truancy Reduction: Keeping Students in School. Juvenile Justice Bulletin.

    Science.gov (United States)

    Baker, Myriam L.; Sigmon, Jane Nady; Nugent, M. Elaine

    Each school day, hundreds of thousands of students are missing from their classrooms--many without a bona fide excuse. Left unchecked, truancy is a risk factor for serious juvenile delinquency. Truancy's impact also extends into the adult years where it has been linked to numerous negative outcomes. Consequently, it is critical to identify…

  13. Derivation of quantum statistics from Gauss's principle and the second law

    International Nuclear Information System (INIS)

    Lavenda, B.H.

    1988-01-01

    Quantum statistical laws are derived from bona fide stationary probability distributions of physical stochastic processes. These distributions are shown to be the laws of error for which the average occupation numbers are the most probable values. They determine uniquely the statistical entropy functions and the second law gives the quantum statistical distributions

  14. Simpson's Paradox and Confounding Factors in University Rankings: A Demonstration Using QS 2011-12 Data

    Science.gov (United States)

    Soh, Kay Cheng

    2012-01-01

    University ranking has become ritualistic in higher education. Ranking results are taken as bona fide by rank users. Ranking systems usually use large data sets from highly heterogeneous universities of varied backgrounds. This poses the problem of Simpson's Paradox and the lurking variables causing it. Using QS 2011-2012 Ranking data, the dual…

  15. 78 FR 27953 - Reorganization of Foreign-Trade Zone 147 Under Alternative Site Framework Reading, Pennsylvania

    Science.gov (United States)

    2013-05-13

    ... terminate authority for Sites 20-22 if no foreign-status merchandise is admitted for a bona fide customs... Zone 147 Under Alternative Site Framework Reading, Pennsylvania Pursuant to its authority under the... application to the Board (FTZ Docket B-79-2012, docketed 11-1-2012) for authority to reorganize under the ASF...

  16. Structural analysis of the active site architecture of the VapC toxin from Shigella flexneri

    DEFF Research Database (Denmark)

    Xu, Kehan; Dedic, Emil; Brodersen, Ditlev Egeskov

    2016-01-01

    The VapC toxin from the Shigella flexneri 2a virulence plasmid pMYSH6000 belongs to the PIN domain protein family, which is characterized by a conserved fold with low amino acid sequence conservation. The toxin is a bona fide Mg2+-dependent ribonuclease and has been shown to target initiator t...

  17. 17 CFR 242.505 - Exclusion for news media.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exclusion for news media. 242...-Analyst Certification § 242.505 Exclusion for news media. No provision of this Regulation AC shall apply to any person who: (a) Is the publisher of any bona fide newspaper, news magazine or business or...

  18. 26 CFR 20.2056A-4 - Procedures for conforming marital trusts and nontrust marital transfers to the requirements of a...

    Science.gov (United States)

    2010-04-01

    ... that, to the best of my knowledge and belief, the information reported in this Information Statement is... revoked. For example, if a protective assignment is made because a bona fide question exists as to the... payable monthly, quarterly, or at some other interval, and a description of any scheduled changes in the...

  19. 19 CFR Appendix B to Part 171 - Customs Regulations, Guidelines for the Imposition and Mitigation of Penalties for Violations of...

    Science.gov (United States)

    2010-04-01

    ... prior to liquidation. In addition, a potential loss of duty exists where Customs discovers the violation... statement or omission that is based on a bona fide erroneous belief as to the facts, so long as the belief... that do not change the admissibility or entry status of merchandise or its appraised value or...

  20. Fides: Lightweight Authenticated Cipher with Side-Channel Resistance for Constrained Hardware

    DEFF Research Database (Denmark)

    Bilgin, Begul; Bogdanov, Andrey; Knezevic, Miroslav

    2013-01-01

    In this paper, we present a novel lightweight authenticated cipher optimized for hardware implementations called Fides. It is an online nonce-based authenticated encryption scheme with authenticated data whose area requirements are as low as 793 GE and 1001 GE for 80-bit and 96-bit security...

  1. 19 CFR 148.13 - Written declarations.

    Science.gov (United States)

    2010-04-01

    ...) When required. Unless an oral declaration is accepted under § 148.12, the declaration required of a..., HTSUS, for articles to be disposed of as bona fide gifts; or subheading 9804.00.40, HTSUS, for articles... passenger shall state either: (1) The price actually paid for the article in the currency of purchase, or...

  2. 26 CFR 1.141-12 - Remedial actions.

    Science.gov (United States)

    2010-04-01

    ...) Reasonable expectations test met. The issuer reasonably expected on the issue date that the issue would meet... tests or the private loan financing test are bona fide and arm's-length, and the new user pays fair..., is sufficient to pay all the principal of, and interest and call premium on, bonds from the date the...

  3. 76 FR 28242 - Proposed Extension of the Approval of Information Collection Requirements

    Science.gov (United States)

    2011-05-16

    ... Reduction Act of 1995 (PRA95). 44 U.S.C. 3056(c)(2)(A). This program helps to ensure that requested data can..., collection instruments are clearly understood, and the impact of collection requirements on respondents can... part 549, Requirements of a ``Bona Fide Profit-Sharing Plan or Trust''. A copy of the proposed...

  4. 29 CFR 778.407 - The nature of the section 7(f) contract.

    Science.gov (United States)

    2010-07-01

    ... it is not in written form. Furthermore, the contract must be “bona fide.” This implies that both the making of the contract and the settlement of its terms were done in good faith. ... 29 Labor 3 2010-07-01 2010-07-01 false The nature of the section 7(f) contract. 778.407 Section...

  5. 26 CFR 31.3402(f)(2)-1 - Withholding exemption certificates.

    Science.gov (United States)

    2010-04-01

    ... specifies the marital status for Employee C. Employee C began a 4-month unpaid maternity leave of absence... maternity leave ends, Employer W must withhold based on the notice. Example 4. Employer X receives a notice... is on a bona fide leave of absence if the period of such leave does not exceed twelve months or the...

  6. Coaching for ADHD

    Science.gov (United States)

    Murphy, Kevin; Ratey, Nancy; Maynard, Sandy; Sussman, Susan; Wright, Sarah D.

    2010-01-01

    Despite limited scientific study on ADHD coaching as an intervention for adults with ADHD, the field of ADHD coaching has grown significantly and gained popularity in recent years. ADHD coaching is becoming a bona fide profession where one must advance through a rigorous training process, in order to be certified as a professional ADHD coach.…

  7. 19 CFR 148.44 - Gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Gifts. 148.44 Section 148.44 Customs Duties U.S...) PERSONAL DECLARATIONS AND EXEMPTIONS Exemptions for Nonresidents § 148.44 Gifts. (a) Exemption. An arriving... and are to be disposed of by him as bona fide gifts. See § 148.43(b) for limitations on cigars under...

  8. Planck early results. XXVI. Detection with Planck and confirmation by XMM-Newton of PLCK G266.6-27.3, an exceptionally X-ray luminous and massive galaxy cluster at z ~ 1

    DEFF Research Database (Denmark)

    Lähteenmäki, A.; Poutanen, T.; Natoli, P.

    2011-01-01

    We present first results on PLCKG266.6-27.3, a galaxy cluster candidate detected at a signal-to-noise ratio of 5 in the Planck All Sky survey. An XMM-Newton validation observation has allowed us to confirm that the candidate isa bona fide galaxy cluster. With these X-ray data we measure an accurate...

  9. The Characteristics of an Abstract System for the Transfer of ...

    African Journals Online (AJOL)

    The mutual intention to transfer and to receive real rights is not construed as an independent real agreement as it is contained in the obligatory agreement. In a causal system the transferor finds himself in a favourable position in relation to other parties while bona fide third parties undoubtedly get the worst of the deal since ...

  10. 77 FR 42737 - Patient Safety Organizations: Delisting for Cause for The Steward Group PSO

    Science.gov (United States)

    2012-07-20

    ... good faith effort to correct the deficiency. Accordingly, AHRQ has revoked the listing of The Steward... The Patient Safety Act, Public Law 109-41, 42 U.S.C. 299b-21--b-26, provides for the formation of PSOs... 24-month period following the PSO's date of initial listing, at least two bona fide contracts with...

  11. Yet Another Call for a Greater Role for Good Faith in the South ...

    African Journals Online (AJOL)

    This article examines the current approach of the South African courts to the role of good faith or bona fides in contracts, as well as the courts' stated reasons for this approach. The article specifically examines how arguments based on good faith have fared in the Constitutional Court to date, and the prospects for law reform ...

  12. 29 CFR 785.19 - Meal.

    Science.gov (United States)

    2010-07-01

    .... For example, an office employee who is required to eat at his desk or a factory worker who is required to be at his machine is working while eating. (Culkin v. Glenn L. Martin, Nebraska Co., 97 F. Supp... enough for a bona fide meal period. A shorter period may be long enough under special conditions. The...

  13. 29 CFR 549.3 - Distinction between plan and trust.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Distinction between plan and trust. 549.3 Section 549.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS REQUIREMENTS OF A âBONA FIDE PROFIT-SHARING PLAN OR TRUSTâ § 549.3 Distinction between plan and trust. As used in this part: (a) Profit-sharing plan...

  14. Regulatory Fit and Equal Opportunity/Diversity: Implications for DEOMI

    Science.gov (United States)

    2013-01-01

    sustains regulatory fit (Lee & Aaker , 2004), and greater psychological value is ascribed to expected outcomes when outcomes are pursued in a manner...groups and women. In the military, policy also delineates bona fide occupational qualifications (BFOQs) that specify the personal characteristics...that fails to create regulatory fit (Cesario, Grant, & Higgins, 2004; Cesario, Higgins, & Scholer, 2008; Lee & Aaker , 2004). Training EOA

  15. Sex Discrimination in Employment: What to Know About It, What to Do About It. Second Edition.

    Science.gov (United States)

    National Organization for Women, Boston, MA. Eastern Massachusetts Chapter.

    The opening question in this document is: Have you ever been confronted with sex discrimination? If you can answer yes to any of 42 more specific questions on discriminatory acts, you have a bona fide complaint. From this point the document serves as a guide on what evidence is needed in a complaint, where the complaint is to be filed, and sources…

  16. 29 CFR 1604.2 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... narrowly. Label—“Men's jobs” and “Women's jobs”—tend to deny employment opportunities unnecessarily to one... example, the assumption that the turnover rate among women is higher than among men. (ii) The refusal to hire an individual based on stereotyped characterizations of the sexes. Such stereotypes include, for...

  17. 26 CFR 1.937-1 - Bona fide residency in a possession.

    Science.gov (United States)

    2010-04-01

    ... time during the day. Notwithstanding the preceding sentence, the following days will not count as days... organizations in State C. Z receives mail in State C, including brokerage statements, credit card bills, and...

  18. In the arbitration under Chapter 11 of the North American Free Trade Agreement and the UNCITRAL arbitration rules between Methanex Corp, claimant/investor and United States of America, respondent/party : joint post-hearing submission by AMICI to the Tribunal

    Energy Technology Data Exchange (ETDEWEB)

    Mann, H.; Wagner, M.

    2004-06-29

    Canada-based Methanex Corporation is a major producer of methanol, a key component of methyl tertiary butyl ether (MTBE) which is used in unleaded gasoline. Methanex launched an international arbitration against the United States in response to California's ban of MTBE. California argues that MTBE poses a significant risk to human health and safety and the environment. Methanex claims that the the ban is an expropriation of the company's investment and a violation of Chapter 11 of the North American Free Trade Agreement. Methanex is seeking financial compensation under NAFTA's Article 1110. This document represents the International Institute for Sustainable Development (IISD) in its intervention in the Methanex versus United States dispute. IISD was granted Amicus status (friend of the court) in the Tribunal hearing. As such, IISD represents public interest and builds confidence in the dispute settlement system. This post hearing submission addresses the legal consequences of California's measure to ban MTBE as a bona fide (non-health) environmental issue or as a bona fide public heath measure, and determines whether such measures constitute a violation of NAFTA's Article 1110. 1 ref.

  19. A MOOC for Introductory Physics

    Science.gov (United States)

    Schatz, Michael

    2014-03-01

    We describe an effort to develop and to implement a college-level introductory physics (mechanics) MOOC that offers bona fide laboratory experiences. We also discuss efforts to use MOOC curricular materials to ``flip'' the classroom in a large lecture introductory physics course offered on-campus at Georgia Tech. Preliminary results of assessments and surveys from both MOOC and on-campus students will be presented.

  20. Level up Book Club

    Science.gov (United States)

    LaGarde, Jennifer; Winner, Matthew C.

    2012-01-01

    Like all great ideas, Level Up Book Club grew out of a genuine need, the spontaneous firing of a few brain sparks, and the kind of luck that comes from being "in the right place at the right time." By mid-June 2011 the authors were already "bona fide" wonder twins--two educators who, although they'd never met, had stumbled upon each other through…

  1. Our Energy For The Country Project Started Our Via Bona

    International Nuclear Information System (INIS)

    Anon

    2014-01-01

    Slovenske Elektrarne received the main Via Bona award for its complex and extraordinary approach to responsible business. Non-profit fund Pontis has been granting this award since 1998 to companies voluntarily contributing to the mitigation of negative trends and the improvement of positive business aspects beyond legislative requirements. We won with our Energy for the Country programme. The award was given to Paolo Ruzzini, SE CEO and Chairman of the Board of Directors by Andrej Kiska, the new Slovak President.

  2. Impossible Certainty: Cost Risk Analysis for Air Force Systems

    Science.gov (United States)

    2006-01-01

    activities remain separate so that a risk assessment is not Introduction 5 tailored (intentionally or even subconsciously ) to fit a predetermined...set- ting aside risk funding was desirable. Under current PPBS and con- gressional rules, some minor reprogramming of funds during the Decisionmaker...available in a timely manner to programs with a bona fide need, without the delays or risks associ- ated with reprogramming . This could encourage program

  3. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

    OpenAIRE

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-01-01

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expres...

  4. Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

    Science.gov (United States)

    Zhu, Dennis W X; Chu, Matthew M; House, Chad M

    2017-12-01

    In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure. During the procedure, the pace/sense IS-1 connection pin of the functional Fidelis lead was intentionally inserted into the LV port of the new CRT-D generator, while the existing bipolar LV lead IS-1 connection pin was inserted into the right ventricular (RV) pace/sense port. After such switching, the existing bipolar LV lead was used for functional LV pacing/sensing, while the Fidelis lead was used for functional RV pacing and high voltage shock only and could no longer be used for the purpose of sensing and detecting. This approach precluded oversensing and inappropriate shocks should the functional Fidelis lead fail in the future. Six fragile patients, who were not considered suitable candidates for lead replacement, underwent the alternative approach. During a follow-up of 35 ± 23 months, the CRT-D system functioned normally in five patients. The Fidelis lead fractured in one patient 7 months after generator replacement. The malfunction was detected promptly and the defected lead was replaced. No inappropriate detections or shock was triggered. In CRT-D patients with a functional Fidelis lead and a bipolar LV lead, switching of the Fidelis lead pace/sense IS-1 pin with the bipolar LV lead IS-1 pin at generator replacement did not affect normal system function. This novel approach may be valuable in fragile patients with high risk of sudden death for

  5. 78 FR 25181 - Revision of Regulations Defining Bona Fide Cotton Spot Markets

    Science.gov (United States)

    2013-04-30

    ...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0... amending references to the ``New York Cotton Exchange'' to read the ``Intercontinental Exchange.'' DATES...), AMS has considered the economic impact of this action on small entities and has determined that its...

  6. Human rights, public health and medicinal cannabis use

    OpenAIRE

    Bone, Melissa; Seddon, Toby

    2015-01-01

    This paper explores the interplay between the human rights and drug control frameworks, and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the St...

  7. Do all psychological treatments really work the same in posttraumatic stress disorder?

    OpenAIRE

    Ehlers, Anke; Bisson, Jonathan; Clark, David M.; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P.; Turner, Stuart; Yule, William

    2010-01-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746–758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not f...

  8. I-DIRT, a general method for distinguishing between specific and nonspecific protein interactions.

    Science.gov (United States)

    Tackett, Alan J; DeGrasse, Jeffrey A; Sekedat, Matthew D; Oeffinger, Marlene; Rout, Michael P; Chait, Brian T

    2005-01-01

    Isolation of protein complexes via affinity-tagged proteins provides a powerful tool for studying biological systems, but the technique is often compromised by co-enrichment of nonspecifically interacting proteins. We describe a new technique (I-DIRT) that distinguishes contaminants from bona fide interactors in immunopurifications, overcoming this most challenging problem in defining protein complexes. I-DIRT will be of broad value for studying protein complexes in biological systems that can be metabolically labeled.

  9. Nuclear terrorism and reality

    International Nuclear Information System (INIS)

    St Sauver, J.E.

    1983-01-01

    Unlike conventional terrorist violence, bona-fide nuclear terrorism is a self-publicizing phenomenon. It is a public event by the very scope of its impact. Apocalyptic and catastrophically destructive, a nuclear explosion is the ideal instrument of mass terror. Rational nuclear insurgents would not inform authorities that a nuclear device is about to be detonated. Advance warning of an impending nuclear explosion would reduce the maximum potential effectiveness of any response to such an event

  10. The Fate of a Healing Goddess: Ocular Pathologies, the Antonine Plague, and the Ancient Roman Cult of Bona Dea

    Directory of Open Access Journals (Sweden)

    Leonardo Ambasciano

    2016-05-01

    Full Text Available The aim of this article is to offer a diachronic and dynamic contextualisation of the ancient Roman cult of Bona Dea, connecting its cognitive underpinnings with its healing dimension. Special attention is devoted to the ocular concerns attested in the epigraphic inventory. The decline of the presence of Bona Dea on the religious scene, attested by the 3rd century CE, is considered to be the multi-causal result of the long-lasting, ocular side-effects of smallpox in the aftermath of the so-called Antonine Plague, which interacted with the correlated and prolonged lack of positive reinforcement concerning symptom relief and cognitive feedback.

  11. Fides et ratio: An early enlightenment defence of non-confessional religion by poiret and his circle

    NARCIS (Netherlands)

    H.A. Krop (Henri)

    2010-01-01

    textabstractIn 1707 an anonymous collection of treatises Fides et ratio was published in Amsterdam. The voluminous work of several authors contains a fierce critique of Locke's notion of faith and the moderate Enlightenment's conception of a reasonable Christianity. The sympathiser with mystic

  12. Secretome Analysis of Lipid-Induced Insulin Resistance in Skeletal Muscle Cells by a Combined Experimental and Bioinformatics Workflow

    DEFF Research Database (Denmark)

    Deshmukh, Atul S; Cox, Juergen; Jensen, Lars Juhl

    2015-01-01

    , in principle, allows an unbiased and comprehensive analysis of cellular secretomes; however, the distinction of bona fide secreted proteins from proteins released upon lysis of a small fraction of dying cells remains challenging. Here we applied highly sensitive MS and streamlined bioinformatics to analyze......-resistant conditions. Our study demonstrates an efficient combined experimental and bioinformatics workflow to identify putative secreted proteins from insulin-resistant skeletal muscle cells, which could easily be adapted to other cellular models....

  13. Polycythemia vera among participants of a nuclear weapons test

    International Nuclear Information System (INIS)

    Sobell, J.L.; Codd, M.B.; Silverstein, M.N.; Kurland, L.T.

    1987-01-01

    Three letters-to-the-editors discuss the finding of a statistically significant excess of polycythemia vera cases among participants in the Smoky detonation. Had population-based incidence rates from Rochester been used to derive an expected incidence, and had only bona fide polycythemia vera cases been considered, as is the rule in most epidemiologic studies, the observed frequency of polycythemia vera among participants in the Smoky test would have been found to be well within chance expectations

  14. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies

    OpenAIRE

    TARDIVEL , Meryem; Bégard , Séverine; Bousset , Luc; Dujardin , Simon; Coens , Audrey; Melki , Ronald; Buée , Luc; Colin , Morvane

    2016-01-01

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer?s disease, is a bona fide constituent of TNTs. This i...

  15. Confirming LBV Candidates Through Variability: A Photometric and Spectroscopic Monitoring Study

    Science.gov (United States)

    Stringfellow, Guy; Gvaramadze, Vasilii

    2013-02-01

    Luminous Blue Variable (LBV) stars represent an extremely rare class of luminous massive stars with high mass loss rates. The paucity ( 12) of confirmed Galactic LBV precludes determining a solid evolutionary connection between LBV and other intermediate (e.g. Ofpe/WN9, WNL) phases in the life of very massive stars. We've been conducting an optical/near-IR spectral survey of a large subset of central stars residing within newly discovered it Spitzer nebulae and have identified over two dozen new candidate LBVs (cLBVs) based on spectral similarity alone; confirming them as bona fide LBVs requires demonstrating 1-3 mag photometric and spectroscopic variability. This marks a significant advancement in the study of massive stars, far outweighing the return from many studies searching for LBVs and WRs the past several decades. Monitoring from semesters 2011B-2012A already has confirmed one new cLBV as a bona fide LBV. We propose to continue optical-IR photometric monitoring of these cLBVS with the 1.3m. Chiron, replacing the RC spectrograph on the 1.5m, now allows high-resolution optical spectroscopic monitoring of bright cLBVs, 11 of which are proposed herein. Spectra are important for understanding the physics driving photometric variability, properties of the wind, and allow analysis of line profiles.

  16. A novel Erm monomethyltransferase in antibiotic-resistant isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Desmolaize, Benoit; Rose, Simon; Warrass, Ralf

    2011-01-01

    Mannheimia haemolytica and Pasteurella multocida are aetiological agents commonly associated with respiratory tract infections in cattle. Recent isolates of these pathogens have been shown to be resistant to macrolides and other ribosome-targeting antibiotics. Direct analysis of the 23S r...... without any dimethyltransferase activity. Erm(42) is a novel addition to the Erm family: it is phylogenetically distant from the other Erm family members and it is unique in being a bona fide monomethyltransferase that is disseminated between bacterial pathogens....

  17. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Yue, Shijun

    2016-01-01

    gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....

  18. Nuclear power: Yes or no

    International Nuclear Information System (INIS)

    Strotmann, A.

    1979-01-01

    The author deals with the problems of nuclear energy by drawing many comparisons to other fields of engineering and causes of dangers and he does it in a way that the laity can understand him and is informed. Advocates and opponents would act bona fide: the ones were not in fear and would believe in the realization of nuclear energy; the others were in fear for themselves and their environment. So the layman too could either believe or not believe. (HSCH) [de

  19. Restricted intra-embryonic origin of bona fide hematopoietic stem cells in the chicken

    NARCIS (Netherlands)

    Yvernogeau, Laurent; Robin, Catherine

    2017-01-01

    Hematopoietic stem cells (HSCs), which are responsible for blood cell production, are generated during embryonic development. Human and chicken embryos share features that position the chicken as a reliable and accessible alternative model to study developmental hematopoiesis. However, the existence

  20. IC 3639 - A new bona fide Compton thick AGN unveiled by NuSTAR

    DEFF Research Database (Denmark)

    Boorman, Peter G.; Gandhi, P.; Alexander, D.

    2016-01-01

    We analyse high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5 -30 keV)....

  1. Keck Spectroscopy of Globular Clusters in the Elliptical Galaxy NGC 3610

    OpenAIRE

    Strader, Jay; Brodie, Jean P.; Schweizer, Francois; Larsen, Soeren S.; Seitzer, Patrick

    2002-01-01

    We present moderate-resolution Keck spectra of nine candidate globular clusters in the possible merger-remnant elliptical galaxy NGC 3610. Eight of the objects appear to be bona fide globular clusters of NGC 3610. We find that two of the clusters belong to an old metal-poor population, five to an old metal-rich population, and only one to an intermediate-age metal-rich population. The estimated age of the intermediate-age cluster is 1-5 Gyr, which is in agreement with earlier estimates of the...

  2. Comment on 'Correlative amplitude-operational phase entanglement embodied by the EPR-pair eigenstate ({eta})'[42.50.Dv Nonclassical states of the electromagnetic field, including entangled photon states; quantum state engineering and measurements; 03.65.Ud Entanglement and quantum nonlocality (e.g. EPR paradox, Bell's inequalities, GHZ states, etc.);

    Energy Technology Data Exchange (ETDEWEB)

    Luis, Alfredo [Departamento de Optica, Facultad de Ciencias Fisicas, Universidad Complutense, 28040 Madrid (Spain)

    2003-01-10

    In a recent paper in this journal Fan (Fan H 2002 J. Phys. A: Math. Gen.35 1007) discards the possibility of using a genuine phase-difference operator to investigate number-phase entanglement because of the lack of unitarity of the Susskind-Glogower phase operators. However, Fan overlooked the existence of a bona fide unitary operator exponential of the phase difference. Here we find the amplitude-phase maximally entangled states as the simultaneous eigenstates of the total number and the phase-difference operators. (comment)

  3. Comment on "Correlative amplitude-operational phase entanglement embodied by the EPR-pair eigenstate |eta) 42.50.Dv Nonclassical states of the electromagnetic field, including entangled photon states; quantum state engineering and measurements; 03.65.Ud Entanglement and quantum nonlocality (e.g. EPR paradox, Bell's inequalities, GHZ states, etc.)"

    CERN Document Server

    Luis, A

    2003-01-01

    In a recent paper in this journal Fan (Fan H 2002 J. Phys. A: Math. Gen.35 1007) discards the possibility of using a genuine phase-difference operator to investigate number-phase entanglement because of the lack of unitarity of the Susskind-Glogower phase operators. However, Fan overlooked the existence of a bona fide unitary operator exponential of the phase difference. Here we find the amplitude-phase maximally entangled states as the simultaneous eigenstates of the total number and the phase-difference operators. (comment)

  4. Joint Force Quarterly. Issue 62, 3rd Quarter, July 2011

    Science.gov (United States)

    2011-07-01

    Dividends: White Lobster on the Mosquito Coast,” Time, April 14, 2011. 10 “ El narcotráfico, una amenaza para FF.AA,” El Comercio , January 13, 2011...the same professional organization as bona fide member U.S . A rm y (M ic ha el L . C as te el ) Army senior NCO directs Soldiers from landing...generous appreciation of the valid ele - ments in the practices and institutions of other nations though they deviate from our own.21 And what of American

  5. Shakespeare in the Head for Health: A Reality Orientation Option for Alzheimer’s Worriers

    OpenAIRE

    Robert Oliphant

    2009-01-01

    By way of bona fides: As with many Americans, my own extended family has over the years given me plenty of direct contact with senile dementia, the general label for Alzheimer’s disease. In addition, a longish stay in a VA hospital (I’m a WWII vet) brought me into contact with the “reality orientation” anti-Alzheimer’s program developed some years back by Dr. Joseph Folsom, Dr. Arthur Cherkin, and others. On the basis of this experience I subsequently wrote a fictionalized case study about...

  6. Pengaruh Sosial Demografi terhadap Produktivitas Tenaga Kerja Perempuan Pengrajin Lontar di Desa Bona, Gianyar

    OpenAIRE

    Andari, Ni Putu Uti; Aswitari, Luh Putu

    2012-01-01

    Bali has many center of home industry. The development of home industry is expected to increase local entrepreneurs income and salary of employee. In palm leaf handicrafts, activities done by women. This study aims to determine the factors that impacted to women labour productivity. This research was conducted in the Bona Village Gianyar Regency. The number of sample is 93 which taken purposively. This study uses multiple linear regression analysis. Results showed that the factors that affect...

  7. A cost-effectiveness analysis of a proactive management strategy for the Sprint Fidelis recall: a probabilistic decision analysis model.

    Science.gov (United States)

    Bashir, Jamil; Cowan, Simone; Raymakers, Adam; Yamashita, Michael; Danter, Matthew; Krahn, Andrew; Lynd, Larry D

    2013-12-01

    The management of the recall is complicated by the competing risks of lead failure and complications that can occur with lead revision. Many of these patients are currently undergoing an elective generator change--an ideal time to consider lead revision. To determine the cost-effectiveness of a proactive management strategy for the Sprint Fidelis recall. We obtained detailed clinical outcomes and costing data from a retrospective analysis of 341 patients who received the Sprint Fidelis lead in British Columbia, where patients younger than 60 years were offered lead extraction when undergoing generator replacement. These population-based data were used to construct and populate a probabilistic Markov model in which a proactive management strategy was compared to a conservative strategy to determine the incremental cost per lead failure avoided. In our population, elective lead revisions were half the cost of emergent revisions and had a lower complication rate. In the model, the incremental cost-effectiveness ratio of proactive lead revision versus a recommended monitoring strategy was $12,779 per lead failure avoided. The proactive strategy resulted in 21 fewer failures per 100 patients treated and reduced the chance of an additional complication from an unexpected surgery. Cost-effectiveness analysis suggests that prospective lead revision should be considered when patients with a Sprint Fidelis lead present for pulse generator change. Elective revision of the lead is justified even when 25% of the population is operated on per year, and in some scenarios, it is both less costly and provides a better outcome. © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

  8. Spontaneous Vesicle Recycling in the Synaptic Bouton

    Directory of Open Access Journals (Sweden)

    Sven eTruckenbrodt

    2014-12-01

    Full Text Available The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.

  9. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    International Nuclear Information System (INIS)

    Chaturvedi, Sonali; Rao, A.L.N.

    2014-01-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER

  10. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Sonali; Rao, A.L.N., E-mail: arao@ucr.edu

    2014-09-15

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER.

  11. From Plant Infectivity to Growth Patterns: The Role of Blue-Light Sensing in the Prokaryotic World

    Directory of Open Access Journals (Sweden)

    Aba Losi

    2014-01-01

    Full Text Available Flavin-based photoreceptor proteins of the LOV (Light, Oxygen, and Voltage and BLUF (Blue Light sensing Using Flavins superfamilies are ubiquitous among the three life domains and are essential blue-light sensing systems, not only in plants and algae, but also in prokaryotes. Here we review their biological roles in the prokaryotic world and their evolution pathways. An unexpected large number of bacterial species possess flavin-based photosensors, amongst which are important human and plant pathogens. Still, few cases are reported where the activity of blue-light sensors could be correlated to infectivity and/or has been shown to be involved in the activation of specific genes, resulting in selective growth patterns. Metagenomics and bio-informatic analysis have only recently been initiated, but signatures are beginning to emerge that allow definition of a bona fide LOV or BLUF domain, aiming at better selection criteria for novel blue-light sensors. We also present here, for the first time, the phylogenetic tree for archaeal LOV domains that have reached a statistically significant number but have not at all been investigated thus far.

  12. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

    Science.gov (United States)

    Kim, Kitai; Zhao, Rui; Doi, Akiko; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Hongguang, Huo; Loh, Yuin-Han; Aryee, Martin J.; Lensch, M. William; Li, Hu; Collins, James J.; Feinberg, Andrew P.; Daley, George Q.

    2012-01-01

    We compared bona-fide human induced pluripotent stem cells (iPSC) derived from umbilical cord blood (CB) and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture didn't improve their epigenetic resemblance to ESC, implying that some human iPSC retain a residual “epigenetic memory” of their tissue of origin. PMID:22119740

  13. The BonaRes Centre - A virtual institute for soil research in the context of a sustainable bio-economy

    Science.gov (United States)

    Wollschläger, Ute; Helming, Katharina; Heinrich, Uwe; Bartke, Stephan; Kögel-Knabner, Ingrid; Russell, David; Eberhardt, Einar; Vogel, Hans-Jörg

    2016-04-01

    Fertile soils are central resources for the production of biomass and provision of food and energy. A growing world population and latest climate targets lead to an increasing demand for both, food and bio-energy, which require preserving and improving the long-term productivity of soils as a bio-economic resource. At the same time, other soil functions and ecosystem services need to be maintained. To render soil management sustainable, we need to establish a scientific knowledge base about complex soil system processes that allows for the development of model tools to quantitatively predict the impact of a multitude of management measures on soil functions. This, finally, will allow for the provision of site-specific options for sustainable soil management. To face this challenge, the German Federal Ministry of Education and Research recently launched the funding program "Soil as a Natural Resource for the Bio-Economy - BonaRes". In a joint effort, ten collaborative projects and the coordinating BonaRes Centre are engaged to close existing knowledge gaps for a profound and systemic understanding of soil functions and their sensitivity to soil management. This presentation provides an overview of the concept of the BonaRes Centre which is responsible for i) setting up a comprehensive data base for soil-related information, ii) the development of model tools aiming to estimate the impact of different management measures on soil functions, and iii) establishing a web-based portal providing decision support tools for a sustainable soil management. A specific focus of the presentation will be laid on the so-called "knowledge-portal" providing the infrastructure for a community effort towards a comprehensive meta-analysis on soil functions as a basis for future model developments.

  14. Improved decay rates for solutions for a multidimensional generalized Benjamin-Bona-Mahony equation

    KAUST Repository

    Said-Houari, Belkacem

    2014-01-01

    In this paper, we study the decay rates of solutions for the generalized Benjamin-Bona-Mahony equation in multi-dimensional space. For initial data in some L1-weighted spaces, we prove faster decay rates of the solutions. More precisely, using the Fourier transform and the energy method, we show the global existence and the convergence rates of the solutions under the smallness assumption on the initial data and we give better decay rates of the solutions. This result improves early works in J. Differential Equations 158(2) (1999), 314-340 and Nonlinear Anal. 75(7) (2012), 3385-3392. © 2014-IOS Press.

  15. Semper Fidelis: Some Values of The Marine Retiree Group

    Directory of Open Access Journals (Sweden)

    Virienia Puspita

    2016-01-01

    Full Text Available This research tried to reveal the group values of Marine retiree Depok, which has done by using symbolic convergence theory as the main theory. The aims of this research were to find and identify fantasy themes, rhetorical vision and group values of Marine retiree group in Depok. This study was based on a foundation of interpretative paradigm with qualitative research methods to find a fantasy theme that emerged in the group through the method of analysis of fantasy by Bormann. The results of the this study indicate the stories of Marine retiree in Depok are the bridge of experience of Marine retiree in the past with present time. Besides that, it is the formation of behavior in forms of values, culture and communication behavior of them. From the analysis theme shows that the group values of Marine retiree in Depok has manifested by universal's idealism value of Marines Semper Fidelis (loyalty, sacrifice, dedication, pride and self esteem. The group rhetorical visions are pride of the group, desire for being accepted and close to their group's identity. 

  16. La Graeca fides e la falsità moscovitanel discorso polacco premoderno. Storia di un topos ["Graeca fides and the Perfidy of the Muscovites in the Polish Early Modern Discourse. History of a Topos "

    Directory of Open Access Journals (Sweden)

    Roman Krzywy

    2015-12-01

    Full Text Available "The article discusses the usage of the classical topos Graeca fides to describe the citizens of the Grand Duchy of Moscow in early modern Polish literature (chronicles, diaries, journalistic writings, diplomatic reports etc.. This way of speaking was justified by the identification of the Eastern Orthodox Church with the Greek Byzantine Rite. The formula was used to deprecate Russians and became part of a negative stereotype. The author demonstrates, with diverse examples, how this formula became a constant topos in statements about a country considered hostile in Poland since the 16th century, and in which contexts it was developed."

  17. A GALEX-BASED SEARCH FOR THE SPARSE YOUNG STELLAR POPULATION IN THE TAURUS-AURIGAE STAR FORMING REGION

    International Nuclear Information System (INIS)

    Gómez de Castro, Ana I.; Lopez-Santiago, Javier; López-Martínez, Fatima; Sánchez, Néstor; Sestito, Paola; Gestoso, Javier Yañez; De Castro, Elisa; Cornide, Manuel

    2015-01-01

    In this work, we identify 63 bona fide new candidates to T Tauri stars (TTSs) in the Taurus-Auriga region, using its ultraviolet excess as our baseline. The initial data set was defined from the GALEX all sky survey (AIS). The GALEX satellite obtained images in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands where TTSs show a prominent excess compared with main-sequence or giants stars. GALEX AIS surveyed the Taurus-Auriga molecular complex, as well as a fraction of the California Nebula and the Perseus complex; bright sources and dark clouds were avoided. The properties of TTSs in the ultraviolet (GALEX), optical (UCAC4), and infrared (2MASS) have been defined using the TTSs observed with the International Ultraviolet Explorer reference sample. The candidates were identified by means of a mixed ultraviolet-optical-infrared excess set of colors; we found that the FUV-NUV versus J–K color-color diagram is ideally suited for this purpose. From an initial sample of 163,313 bona fide NUV sources, a final list of 63 new candidates to TTSs in the region was produced. The search procedure has been validated by its ability to detect all known TTSs in the area surveyed: 31 TTSs. Also, we show that the weak-lined TTSs are located in a well-defined stripe in the FUV-NUV versus J–K diagram. Moreover, in this work, we provide a list of TTSs photometric standards for future GALEX-based studies of the young stellar population in star forming regions

  18. A GALEX-BASED SEARCH FOR THE SPARSE YOUNG STELLAR POPULATION IN THE TAURUS-AURIGAE STAR FORMING REGION

    Energy Technology Data Exchange (ETDEWEB)

    Gómez de Castro, Ana I.; Lopez-Santiago, Javier; López-Martínez, Fatima; Sánchez, Néstor; Sestito, Paola; Gestoso, Javier Yañez [AEGORA Research Group, Universidad Complutense de Madrid, Plaza de Ciencias 3, E-28040 Madrid (Spain); De Castro, Elisa; Cornide, Manuel [Fac. de CC. Físicas, Universidad Complutense de Madrid, Plaza de Ciencias 1, E-28040 Madrid (Spain)

    2015-02-01

    In this work, we identify 63 bona fide new candidates to T Tauri stars (TTSs) in the Taurus-Auriga region, using its ultraviolet excess as our baseline. The initial data set was defined from the GALEX all sky survey (AIS). The GALEX satellite obtained images in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands where TTSs show a prominent excess compared with main-sequence or giants stars. GALEX AIS surveyed the Taurus-Auriga molecular complex, as well as a fraction of the California Nebula and the Perseus complex; bright sources and dark clouds were avoided. The properties of TTSs in the ultraviolet (GALEX), optical (UCAC4), and infrared (2MASS) have been defined using the TTSs observed with the International Ultraviolet Explorer reference sample. The candidates were identified by means of a mixed ultraviolet-optical-infrared excess set of colors; we found that the FUV-NUV versus J–K color-color diagram is ideally suited for this purpose. From an initial sample of 163,313 bona fide NUV sources, a final list of 63 new candidates to TTSs in the region was produced. The search procedure has been validated by its ability to detect all known TTSs in the area surveyed: 31 TTSs. Also, we show that the weak-lined TTSs are located in a well-defined stripe in the FUV-NUV versus J–K diagram. Moreover, in this work, we provide a list of TTSs photometric standards for future GALEX-based studies of the young stellar population in star forming regions.

  19. Do all psychological treatments really work the same in posttraumatic stress disorder?

    Science.gov (United States)

    Ehlers, Anke; Bisson, Jonathan; Clark, David M; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P; Turner, Stuart; Yule, William

    2010-03-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent. Copyright 2009 Elsevier Ltd. All rights reserved.

  20. Do all psychological treatments really work the same in posttraumatic stress disorder?

    Science.gov (United States)

    Ehlers, Anke; Bisson, Jonathan; Clark, David M.; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P.; Turner, Stuart; Yule, William

    2010-01-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746–758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent. PMID:20051310

  1. Plasma effects on subcellular structures

    International Nuclear Information System (INIS)

    Gweon, Bomi; Kim, Dan Bee; Jung, Heesoo; Choe, Wonho; Kim, Daeyeon; Shin, Jennifer H.

    2010-01-01

    Atmospheric pressure helium plasma treated human hepatocytes exhibit distinctive zones of necrotic and live cells separated by a void. We propose that plasma induced necrosis is attributed to plasma species such as oxygen radicals, charged particles, metastables and/or severe disruption of charged cytoskeletal proteins. Interestingly, uncharged cytoskeletal intermediate filaments are only minimally disturbed by plasma, elucidating the possibility of plasma induced electrostatic effects selectively destroying charged proteins. These bona fide plasma effects, which inflict alterations in specific subcellular structures leading to necrosis and cellular detachment, were not observed by application of helium flow or electric field alone.

  2. The phase diagram of high temperature QCD with three flavors of improved staggered quarks

    International Nuclear Information System (INIS)

    Bernard, C.; Burch, T.; DeTar, C.E.; Gottlieb, Steven; Gregory, E.B.; Heller, U.M.; Hetrick, J.E.; Sugar, R.L.; Toussaint, D.

    2004-01-01

    We report on progress in our study of high temperature QCD with three flavors of improved staggered quarks. Simulations are being carried out with three degenerate quarks with masses less than or equal to the strange quark mass, m s , and with degenerate up and down quarks with masses in the range 0.1 m s ≤ m u,d ≤ 0.6 m s , and the strange quark mass fixed near its physical value. For the quark masses studied to date we find rapid crossovers, which sharpen as the quark mass is reduced, rather than bona fide phase transitions

  3. In silico prediction of xenobiotic metabolism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Fangping [Los Alamos National Laboratory

    2009-01-01

    Xenobiotic metabolism in humans is catalyzed by a few enzymes with broad substrate specificities, which provide the overall broad chemical specificity for nearly all xenobiotics that humans encounter. Xenobiotic metabolism are classified into functional group biotransformations. Based on bona fide reactions and negative examples for each reaction class, support vector machine (SVM) classifiers are built. The input to SVM is a set of atomic and molecular features to define the electrostatic, steric, energetic, geometrical and topological environment of the atoms in the reaction center under the molecule. Results show that the overall sensitivity and specificity of classifiers is around 87%.

  4. Confirming the least massive members of the Pleiades star cluster

    Science.gov (United States)

    Zapatero Osorio, M. R.; Béjar, V. J. S.; Lodieu, N.; Manjavacas, E.

    2018-03-01

    We present optical photometry (i and Z band) and low-resolution spectroscopy (640-1015 nm) of very faint candidate members (J = 20.2-21.2 mag) of the Pleiades star cluster (120 Myr). The main goal is to address their cluster membership via photometric, astrometric, and spectroscopic studies, and to determine the properties of the least massive population of the cluster through the comparison of the data with younger and older spectral counterparts and state-of-the art model atmospheres. We confirm three bona fide Pleiades members that have extremely red optical and infrared colours, effective temperatures of ≈1150 and ≈1350 K, and masses in the interval 11-20 MJup, and one additional likely member that shares the same motion as the cluster but does not appear to be as red as the other members with similar brightness. This latter object requires further near-infrared spectroscopy to fully address its membership in the Pleiades. The optical spectra of two bona fide members were classified as L6-L7 and show features of K I, a tentative detection of Cs I, hydrides, and water vapour with an intensity similar to high-gravity dwarfs of related classification despite their young age. The properties of the Pleiades L6-L7 members clearly indicate that very red colours of L dwarfs are not a direct evidence of ages younger than ≈100 Myr. We also report on the determination of the bolometric corrections for the coolest Pleiades members. These data can be used to interpret the observations of the atmospheres of exoplanets orbiting stars.

  5. Properties of optically selected BL Lacertae candidates from the SDSS

    Science.gov (United States)

    Kügler, S. D.; Nilsson, K.; Heidt, J.; Esser, J.; Schultz, T.

    2014-09-01

    Context. Deep optical surveys open the avenue for finding large numbers of BL Lac objects that are hard to identify because they lack the unique properties classifying them as such. While radio or X-ray surveys typically reveal dozens of sources, recent compilations based on optical criteria alone have increased the number of BL Lac candidates considerably. However, these compilations are subject to biases and may contain a substantial number of contaminating sources. Aims: In this paper we extend our analysis of 182 optically selected BL Lac object candidates from the SDSS with respect to an earlier study. The main goal is to determine the number of bona fide BL Lac objects in this sample. Methods: We examine their variability characteristics, determine their broad-band radio-UV spectral energy distributions (SEDs), and search for the presence of a host galaxy. In addition we present new optical spectra for 27 targets with improved signal-to-noise ratio with respect to the SDSS spectra. Results: At least 59% of our targets have shown variability between SDSS DR2 and our observations by more than 0.1-0.27 mag depending on the telescope used. A host galaxy was detected in 36% of our targets. The host galaxy type and luminosities are consistent with earlier studies of BL Lac host galaxies. Simple fits to broad-band SEDs for 104 targets of our sample derived synchrotron peak frequencies between 13.5 ≤ log 10(νpeak) ≤ 16 with a peak at log 10 ~ 14.5. Our new optical spectra do not reveal any new redshift for any of our objects. Thus the sample contains a large number of bona fide BL Lac objects and seems to contain a substantial fraction of intermediate-frequency peaked BL Lacs. Based on observations collected with the NTT on La Silla (Chile) operated by the European Southern Observatory under proposal 082.B-0133.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA), operated jointly by the Max-Planck-Institut für Astronomie and the

  6. Catalytic activity of a novel serine/threonine protein phosphatase PP5 from Leishmania major

    Directory of Open Access Journals (Sweden)

    Norris-Mullins Brianna

    2014-01-01

    Full Text Available Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. Our knowledge of protein phosphatases (PPs and their implication in signaling events is very limited. Here we report the expression, characterization and mutagenesis analysis of a novel protein phosphatase 5 (PP5 in Leishmania major. Recombinant PP5 is a bona fide phosphatase and is enzymatically active. Site-directed mutagenesis revealed auto-inhibitory roles of the N-terminal region. This is a rational first approach to understand the role of PP5 in the biology of the parasite better as well as its potential future applicability to anti-parasitic intervention.

  7. Functions of the Drosophila JAK-STAT pathway

    Science.gov (United States)

    Amoyel, Marc; Bach, Erika A.

    2012-01-01

    JAK-STAT signaling has been proposed to act in numerous stem cells in a variety of organisms. Here we provide an overview of its roles in three well characterized stem cell populations in Drosophila, in the intestine, lymph gland and testis. In flies, there is a single JAK and a single STAT, which has made the genetic dissection of pathway function considerably easier and facilitated the analysis of communication between stem cells, their niches and offspring. Studies in flies have revealed roles for this pathway as diverse as regulating bona fide intrinsic self-renewal, integrating response to environmental cues that control quiescence and promoting mitogenic responses to stress. PMID:24058767

  8. The Role of PAS Kinase in PASsing the Glucose Signal

    Directory of Open Access Journals (Sweden)

    Julianne H. Grose

    2010-06-01

    Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

  9. What should we mean by empirical validation in hypnotherapy: evidence-based practice in clinical hypnosis.

    Science.gov (United States)

    Alladin, Assen; Sabatini, Linda; Amundson, Jon K

    2007-04-01

    This paper briefly surveys the trend of and controversy surrounding empirical validation in psychotherapy. Empirical validation of hypnotherapy has paralleled the practice of validation in psychotherapy and the professionalization of clinical psychology, in general. This evolution in determining what counts as evidence for bona fide clinical practice has gone from theory-driven clinical approaches in the 1960s and 1970s through critical attempts at categorization of empirically supported therapies in the 1990s on to the concept of evidence-based practice in 2006. Implications of this progression in professional psychology are discussed in the light of hypnosis's current quest for validation and empirical accreditation.

  10. pVHL's kryptonite: E2-EPF UCP.

    Science.gov (United States)

    Ohh, Michael

    2006-08-01

    E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome. UCP is overexpressed in common human cancers, suggesting its involvement in oncogenesis, but a physiologic target of UCP has not been identified. In a recent report published in Nature Medicine, Jung et al. identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL-HIF pathway-dependent role for UCP in cancer development.

  11. UTILIZING SYNTHETIC UV SPECTRA TO EXPLORE THE PHYSICAL BASIS FOR THE CLASSIFICATION OF LAMBDA BOÖTIS STARS

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kwang-Ping; Johnson, Dustin M.; Tarbell, Erik S.; Romo, Christopher A.; Prabhaker, Arvind [Cal. State Univ., Fullerton, Fullerton, CA (United States); Neff, James E.; Steele, Patricia A. [College of Charleston, Charleston, SC (United States); Gray, Richard O. [Appalachian State Univ., Boone, NC (United States); Corbally, Christopher J. [Vatican Observatory, Tucson, AZ (United States)

    2016-04-15

    Lambda Boo-type stars are a group of late B to early F-type Population I dwarfs that show mild to extreme deficiencies of iron-peak elements (up to 2 dex), but their C, N, O, and S abundances are near solar. This intriguing stellar class has recently regained the spotlight because of the directly imaged planets around a confirmed Lambda Boo star, HR 8799, and a suggested Lambda Boo star, Beta Pictoris. The discovery of a giant asteroid belt around Vega, another possible Lambda Boo star, also suggests hidden planets. The possible link between Lambda Boo stars and planet-bearing stars motivates us to study Lambda Boo stars systematically. Since the peculiar nature of the prototype Lambda Boötis was first noticed in 1943, Lambda Boo candidates published in the literature have been selected using widely different criteria. In order to determine the origin of Lambda Boo stars’ unique abundance pattern and to better discriminate between theories explaining the Lambda Boo phenomenon, a consistent working definition of Lambda Boo stars is needed. We have re-evaluated all published Lambda Boo candidates and their available ultraviolet and visible spectra. In this paper, using observed and synthetic spectra, we explore the physical basis for the classification of Lambda Boo stars, and develop quantitative criteria that discriminate metal-poor stars from bona fide Lambda Boo stars. Based on these stricter Lambda Boo classification criteria, we conclude that neither Beta Pictoris nor Vega should be classified as Lambda Boo stars.

  12. UTILIZING SYNTHETIC UV SPECTRA TO EXPLORE THE PHYSICAL BASIS FOR THE CLASSIFICATION OF LAMBDA BOÖTIS STARS

    International Nuclear Information System (INIS)

    Cheng, Kwang-Ping; Johnson, Dustin M.; Tarbell, Erik S.; Romo, Christopher A.; Prabhaker, Arvind; Neff, James E.; Steele, Patricia A.; Gray, Richard O.; Corbally, Christopher J.

    2016-01-01

    Lambda Boo-type stars are a group of late B to early F-type Population I dwarfs that show mild to extreme deficiencies of iron-peak elements (up to 2 dex), but their C, N, O, and S abundances are near solar. This intriguing stellar class has recently regained the spotlight because of the directly imaged planets around a confirmed Lambda Boo star, HR 8799, and a suggested Lambda Boo star, Beta Pictoris. The discovery of a giant asteroid belt around Vega, another possible Lambda Boo star, also suggests hidden planets. The possible link between Lambda Boo stars and planet-bearing stars motivates us to study Lambda Boo stars systematically. Since the peculiar nature of the prototype Lambda Boötis was first noticed in 1943, Lambda Boo candidates published in the literature have been selected using widely different criteria. In order to determine the origin of Lambda Boo stars’ unique abundance pattern and to better discriminate between theories explaining the Lambda Boo phenomenon, a consistent working definition of Lambda Boo stars is needed. We have re-evaluated all published Lambda Boo candidates and their available ultraviolet and visible spectra. In this paper, using observed and synthetic spectra, we explore the physical basis for the classification of Lambda Boo stars, and develop quantitative criteria that discriminate metal-poor stars from bona fide Lambda Boo stars. Based on these stricter Lambda Boo classification criteria, we conclude that neither Beta Pictoris nor Vega should be classified as Lambda Boo stars

  13. SLoWPoKES-II: 100,000 WIDE BINARIES IDENTIFIED IN SDSS WITHOUT PROPER MOTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Dhital, Saurav [Department of Physical Sciences, Embry-Riddle Aeronautical University, 600 South Clyde Morris Blvd., Daytona Beach, FL 32114 (United States); West, Andrew A.; Schluns, Kyle J.; Massey, Angela P. [Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States); Stassun, Keivan G., E-mail: dhitals@erau.edu [Department of Physics and Astronomy, Vanderbilt University, 6301 Stevenson Center, Nashville, TN, 37235 (United States)

    2015-08-15

    We present the Sloan Low-mass Wide Pairs of Kinematically Equivalent Stars (SLoWPoKES)-II catalog of low-mass visual binaries identified from the Sloan Digital Sky Survey (SDSS) by matching photometric distances. The candidate pairs are vetted by comparing the stellar information. The candidate pairs are vetted by comparing the stellar density at their respective Galactic positions to Monte Carlo realizations of a simulated Milky Way. In this way, we are able to identify large numbers of bona fide wide binaries without the need for proper motions. Here, 105,537 visual binaries with angular separations of ∼1–20″ were identified, each with a probability of chance alignment of ≤5%. This is the largest catalog of bona fide wide binaries to date, and it contains a diversity of systems—in mass, mass ratios, binary separations, metallicity, and evolutionary states—that should facilitate follow-up studies to characterize the properties of M dwarfs and white dwarfs. There is a subtle but definitive suggestion of multiple populations in the physical separation distribution, supporting earlier findings. We suggest that wide binaries are composed of multiple populations, most likely representing different formation modes. There are 141 M7 or later wide binary candidates, representing a seven-fold increase over the number currently known. These binaries are too wide to have been formed via the ejection mechanism. Finally, we found that 6% of spectroscopically confirmed M dwarfs are not included in the SDSS STAR catalog; they are misclassified as extended sources due to the presence of a nearby or partially resolved companion. The SLoWPoKES-II catalog is publicly available to the entire community on the World Wide Web via the Filtergraph data visualization portal.

  14. BANYAN. III. Radial velocity, rotation, and X-ray emission of low-mass star candidates in nearby young kinematic groups

    Energy Technology Data Exchange (ETDEWEB)

    Malo, Lison; Artigau, Étienne; Doyon, René; Lafrenière, David; Albert, Loïc; Gagné, Jonathan, E-mail: malo@astro.umontreal.ca, E-mail: doyon@astro.umontreal.ca [Département de physique and Observatoire du Mont-Mégantic, Université de Montréal, Montréal, QC H3C 3J7 (Canada)

    2014-06-10

    Based on high-resolution spectra obtained with PHOENIX at Gemini-South, CRIRES at VLT-UT1, and ESPaDOnS at the Canada-France-Hawaii Telescope, we present new measurements of the radial and projected rotational velocities of 219 low-mass stars. The target likely membership was initially established using the Bayesian analysis tool recently presented in Malo et al., taking into account only the position, proper motion, and photometry of the stars to assess their membership probability. In the present study, we include radial velocity as an additional input to our analysis, and in doing so we confirm the high membership probability for 130 candidates: 27 in β Pictoris, 22 in Tucana-Horologium, 25 in Columba, 7 in Carina, 18 in Argus and 18 in AB Doradus, and 13 with an ambiguous membership. Our analysis also confirms the membership of 57 stars proposed in the literature. A subsample of 16 candidates was observed at 3 or more epochs, allowing us to discover 6 new spectroscopic binaries. The fraction of binaries in our sample is 25%, consistent with values in the literature. Of the stars in our sample, 20% show projected rotational velocities (vsin i) higher than 30 km s{sup –1} and therefore are considered as fast rotators. A parallax and other youth indicators are still needed to fully confirm the 130 highly probable candidates identified here as new bona fide members. Finally, based on the X-ray emission of bona fide and highly probable group members, we show that for low-mass stars in the 12-120 Myr age range, the X-ray luminosity is an excellent indicator of youth and better than the more traditionally used R {sub X} parameter, the ratio of X-ray to bolometric luminosity.

  15. The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

    Science.gov (United States)

    Yu, Yiqun; Moberly, Andrew H; Bhattarai, Janardhan P; Duan, Chen; Zheng, Qian; Li, Fangqi; Huang, Hugh; Olson, William; Luo, Wenqin; Wen, Tieqiao; Yu, Hongmeng; Ma, Minghong

    2017-09-27

    Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5 + cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP + cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5 + cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons. Copyright © 2017 the authors 0270-6474/17/379403-12$15.00/0.

  16. A common pathway for charge transport through voltage-sensing domains.

    Science.gov (United States)

    Chanda, Baron; Bezanilla, Francisco

    2008-02-07

    Voltage-gated ion channels derive their voltage sensitivity from the movement of specific charged residues in response to a change in transmembrane potential. Several studies on mechanisms of voltage sensing in ion channels support the idea that these gating charges move through a well-defined permeation pathway. This gating pathway in a voltage-gated ion channel can also be mutated to transport free cations, including protons. The recent discovery of proton channels with sequence homology to the voltage-sensing domains suggests that evolution has perhaps exploited the same gating pathway to generate a bona fide voltage-dependent proton transporter. Here we will discuss implications of these findings on the mechanisms underlying charge (and ion) transport by voltage-sensing domains.

  17. Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins

    Science.gov (United States)

    Robertson, Ian B.; Rifkin, Daniel B.

    2016-01-01

    The bioavailability of members of the transforming growth factor β (TGF-β) family is controlled by a number of mechanisms. Bona fide TGF-β is sequestered into the matrix in a latent state and must be activated before it can bind to its receptors. Here, we review the molecules and mechanisms that regulate the bioavailability of TGF-β and compare these mechanisms with those used to regulate other TGF-β family members. We also assess the physiological significance of various latent TGF-β activators, as well as other extracellular modulators of TGF-β family signaling, by examining the available in vivo data from knockout mouse models and other biological systems. PMID:27252363

  18. Limitations of the government budget constraint: Users vs. issuers of the currency

    Directory of Open Access Journals (Sweden)

    Kelton Stephanie

    2011-01-01

    Full Text Available The financial crisis and ensuing economic meltdown has led to sharp increases in the deficits and debt levels of many advanced economies. The run-up in public sector indebtedness helped to restore private sector balance sheets, laying the foundation for economic recovery in these regions. But the so-called “sovereign” debt crisis in the Eurozone has undermined the fiscal resolve that has, thus far, kept truly sovereign governments from slipping into a bona fide depression. Fearful of becoming the next Greece, governments that could allow an unlimited fiscal adjustment to restore full employment, are methodically weakening their fiscal support mechanisms and setting themselves on a path to becoming the next Japan.

  19. A Gaia DR2 Confirmation that 2MASS J12074836–3900043 is a Member of the TW HYA Association

    Science.gov (United States)

    Gagné, Jonathan; Gonzales, Eileen C.; Faherty, Jacqueline K.

    2018-05-01

    We use new data from Gaia DR2 to confirm that the young L1 $\\gamma$ candidate member of the TW Hya association (TWA) is now a bona fide member with a model-dependent mass estimate of ~15 $M_{Jup}$. The ambiguous M9 $\\gamma$ candidate member 2MASS J12474428---3816464 also gets a higher Bayesian membership probability for TWA membership as a result of Gaia DR2 data and a new radial velocity measurement, but it remains unclear whether it is a true member of TWA or if it is an unrelated young interloper, because it is separated by 4.6 km/s from the locus of TWA members in UVW space.

  20. Theologies, ideologies and evolutionary biology.

    Science.gov (United States)

    Scudo, Francesco M

    2010-01-01

    Since a century evolution has mostly been interpreted by two simple, "opposite" kinds of "theories" — i.e. as due either to fitness differences among genotypes or to some other simple mechanism — while bona fide, more complex theories were less popular throughout. In particular by far the most complete theories ever produced were suddenly, almost universally abandoned just after World War II, though not as a consequence of major breakthroughs. The causes of this situation are examined by analogy with much earlier developments and their demise by Cartesianism. The down to earth solutions these "complete" theories provide to the problems of "speciation" and the origins of cells are contrasted with the "miraculous" approaches by systemic neo-Darwinists.

  1. Dispute resolutions from the field of economy via contracting competence through Arbitration in the republic of Kosovo

    Directory of Open Access Journals (Sweden)

    Krenare Vokshi

    2016-03-01

    Full Text Available In terms of globalized economy, the integration trade cooperation process between state institutions, international organizations, and business entities are being followed by a dynamism regarding creation, modification, and termination of relations through the contracts which are now more standardized. Good business practices offered a good experience in terms of solving disputes on business transactions, local or international, security, efficiency and speed of trailing are enforced only if this issue is foreseen and contracted with special courts of arbitration. The role of arbitration on international trade is not only the solution of disputes. The arbitration has as its mission before the building of a fair trade and legal practice such as bona fides.

  2. Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.

    Science.gov (United States)

    Garg, Abhishek D; More, Sanket; Rufo, Nicole; Mece, Odeta; Sassano, Maria Livia; Agostinis, Patrizia; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2017-01-01

    The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

  3. Influenza-associated thrombotic microangiopathies.

    Science.gov (United States)

    Bitzan, Martin; Zieg, Jakub

    2017-09-07

    Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity rational treatment approaches.

  4. Integrin-linked kinase: a Scaffold protein unique among its ilk.

    Science.gov (United States)

    Dagnino, Lina

    2011-06-01

    Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be the next key step to understand its distinct biological roles across tissues and species.

  5. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology

    Science.gov (United States)

    Mallet, François; Bouton, Olivier; Prudhomme, Sarah; Cheynet, Valérie; Oriol, Guy; Bonnaud, Bertrand; Lucotte, Gérard; Duret, Laurent; Mandrand, Bernard

    2004-01-01

    The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5′ LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology. PMID:14757826

  6. Nonlocal Symmetries, Conservation Laws and Interaction Solutions of the Generalised Dispersive Modified Benjamin-Bona-Mahony Equation

    Science.gov (United States)

    Yan, Xue-Wei; Tian, Shou-Fu; Dong, Min-Jie; Wang, Xiu-Bin; Zhang, Tian-Tian

    2018-05-01

    We consider the generalised dispersive modified Benjamin-Bona-Mahony equation, which describes an approximation status for long surface wave existed in the non-linear dispersive media. By employing the truncated Painlevé expansion method, we derive its non-local symmetry and Bäcklund transformation. The non-local symmetry is localised by a new variable, which provides the corresponding non-local symmetry group and similarity reductions. Moreover, a direct method can be provided to construct a kind of finite symmetry transformation via the classic Lie point symmetry of the normal prolonged system. Finally, we find that the equation is a consistent Riccati expansion solvable system. With the help of the Jacobi elliptic function, we get its interaction solutions between solitary waves and cnoidal periodic waves.

  7. 1500 Years of Annual Climate and Environmental Variability as Recorded in Bona-Churchill (Alaska) Ice Cores

    Science.gov (United States)

    Thompson, L. G.; Mosley-Thompson, E. S.; Zagorodnov, V.; Davis, M. E.; Mashiotta, T. A.; Lin, P.

    2004-12-01

    In 2003, six ice cores measuring 10.5, 11.5, 11.8, 12.4, 114 and 460 meters were recovered from the col between Mount Bona and Mount Churchill (61° 24'N; 141° 42'W; 4420 m asl). These cores have been analyzed for stable isotopic ratios, insoluble dust content and concentrations of major chemical species. Total Beta radioactivity was measured in the upper sections. The 460-meter core, extending to bedrock, captured the entire depositional record at this site where ice temperatures ranged from -24° C at 10 meters to -19.8° C at the ice/bedrock contact. The shallow cores allow assessment of surface processes under modern meteorological conditions while the deep core offers a ˜1500-year climate and environmental perspective. The average annual net balance is ˜~1000 mm of water equivalent and distinct annual signals in dust and calcium concentrations along with δ 18O allow annual resolution over most of the core. The excess sulfate record reflects many known large volcanic eruptions such as Katmai, Krakatau, Tambora, and Laki which allow validation of the time scale in the upper part of the core. The lower part of the core yields a history of earlier volcanic events. The 460-m Bona-Churchill ice core provides a detailed history of the `Little Ice Age' and medieval warm periods for southeastern Alaska. The source of the White River Ash will be discussed in light of the evidence from this core. The 460-m core also provides a long-term history of the dust fall that originates in north-central China. The annual ice core-derived climate records from southeastern Alaska will facilitate an investigation of the likelihood that the high resolution 1500-year record from the tropical Quelccaya Ice Cap (Peru) preserves a history of the variability of both the PDO and the Aleutian Low.

  8. MicroRNA-27a Is Induced by Leucine and Contributes to Leucine-Induced Proliferation Promotion in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Guangmang Liu

    2013-07-01

    Full Text Available Leucine, a branched chain amino acid, is well known to stimulate protein synthesis in skeletal muscle. However, the role of leucine in myoblast proliferation remains unclear. In this study, we found that leucine could promote proliferation of C2C12 cells. Moreover, expressions of miR-27a and myostatin (a bona fide target of miR-27a were upregulated and downregulated, respectively, following leucine treatment. We also found that miR-27a loss-of-function by transfection of a miR-27a inhibitor suppressed the promotion of myoblast proliferation caused by leucine. Our results suggest that miR-27a is induced by leucine and contributes to leucine-induced proliferation promotion of myoblast.

  9. Metabolic engineering with plants for a sustainable biobased economy.

    Science.gov (United States)

    Yoon, Jong Moon; Zhao, Le; Shanks, Jacqueline V

    2013-01-01

    Plants are bona fide sustainable organisms because they accumulate carbon and synthesize beneficial metabolites from photosynthesis. To meet the challenges to food security and health threatened by increasing population growth and depletion of nonrenewable natural resources, recent metabolic engineering efforts have shifted from single pathways to holistic approaches with multiple genes owing to integration of omics technologies. Successful engineering of plants results in the high yield of biomass components for primary food sources and biofuel feedstocks, pharmaceuticals, and platform chemicals through synthetic biology and systems biology strategies. Further discovery of undefined biosynthesis pathways in plants, integrative analysis of discrete omics data, and diversified process developments for production of platform chemicals are essential to overcome the hurdles for sustainable production of value-added biomolecules from plants.

  10. Nuclear-industry employee protection provisions of federal law

    International Nuclear Information System (INIS)

    Fidell, E.R.; Marcoux, W.C.

    1982-01-01

    Legislation enacted by Congress in 1978 to provide protection for those employed in the construction or operation of civil nuclear projects who express concerns to employers or others about the propriety of procedures in their places of employment from the standpoint of safety is summarized. The authors describe some recent and anticipated developments in the implementation of the law and offer practical suggestions for the avoidance of particular problems under the law. They counsel that the prudent utility company or other firm involved with nuclear energy will see the statute as another reason for facilitating the flow of bona fide safety concerns rather than as a vehicle for the expression of generalized complaints by malcontents and a convenient shield for substandard performers in the work force

  11. Critical string from non-Abelian vortex in four dimensions

    Directory of Open Access Journals (Sweden)

    M. Shifman

    2015-11-01

    Full Text Available In a class of non-Abelian solitonic vortex strings supported in certain N=2 super-Yang–Mills theories we search for the vortex which can behave as a critical fundamental string. We use the Polchinski–Strominger criterion of the ultraviolet completeness. We identify an appropriate four-dimensional bulk theory: it has the U(2 gauge group, the Fayet–Iliopoulos term and four flavor hypermultiplets. It supports semilocal vortices with the world-sheet theory for orientational (size moduli described by the weighted CP(2,2 model. The latter is superconformal. Its target space is six-dimensional. The overall Virasoro central charge is critical. We show that the world-sheet theory on the vortex supported in this bulk model is the bona fide critical string.

  12. Bona fide colour: DNA prediction of human eye and hair colour from ancient and contemporary skeletal remains

    NARCIS (Netherlands)

    J. Draus-Barini (Jolanta); S. Walsh (Susan); E. Pośpiech (Ewelina); T. Kupiec (Tomasz); H. Głab (Henryk); W. Branicki (Wojciech); M.H. Kayser (Manfred)

    2013-01-01

    textabstractBackground: DNA analysis of ancient skeletal remains is invaluable in evolutionary biology for exploring the history of species, including humans. Contemporary human bones and teeth, however, are relevant in forensic DNA analyses that deal with the identification of perpetrators, missing

  13. La autonomía en Finlandia: la autonomía territorial de las islas Aland y la autonomía cultural del pueblo indígena saami

    Directory of Open Access Journals (Sweden)

    Lauri Hannikainen

    2013-04-01

    Full Text Available Finland offers two interesting cases of special autonomy, territorial and cultural,regarding Åland Islands and the indigenous Saami people. Åland islocated in the Baltic Sea, between Finland and Sweden. Circa 94% of itspopulation are Swedish speaking. This article examines its autonomy system,that is about 90 years old and is functioning quite well. Main reasons of theapparent success of the autonomy system are its well protected status in theconstitutional system of Finland and its fairly clear scope. Autonomy disputesbetween Åland and the State are solved according to legal criteria. The Statehas had a bona fide attitude at the Åland autonomy; even the Autonomy Actprovides that the language of communication between the authorities ofthe State and Åland is Swedish, and not the leading national language, Finnish.The vast Saami Home Territory forms the northernmost part of Finland(Lapland, but only about a third of its population are Saami. Altogether theSaami make circa 8,500, but only about a half of them live in the Territory.The scope of its cultural autonomy is quite limited. The system provides theexistence of a democratic Saami Parliament as the representative of theentire Saami people and its powers with regard to the Saami language.However, the indigenous Saami have virtually no special rights with regardto their traditional lands and waters and their natural resources.

  14. Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay

    Directory of Open Access Journals (Sweden)

    Zavolan Mihaela

    2010-10-01

    Full Text Available Abstract Background In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate. Results In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs. Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1's role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3' UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms. Conclusions Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels.

  15. Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities.

    Science.gov (United States)

    Soll, Jennifer M; Sobol, Robert W; Mosammaparast, Nima

    2017-03-01

    Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so-called 'epigenetic' adducts. Here, we discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Temporal repression of endogenous pluripotency genes during reprogramming of porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane; Christensen, Marianne; Rasmussen, Mikkel Aabech

    2012-01-01

    Porcine induced pluripotent stem cells (piPSCs) have the capacity to differentiate in vitro and in vivo and form chimeras. However, the lack of transgene silencing of exogenous DNA integrated into the genome and the inability of cells to proliferate in the absence of transgene expression...... pluripotency in the pig. This may help to explain the difficulties in producing stable piPSCs and bona fide embryonic stem cell lines in this species....... transgenes on the expression of the porcine endogenous pluripotency machinery. Endogenous and exogenous gene expression of OCT4, NANOG, SOX2, KLF4, and cMYC was determined at passages 5, 10, 15, and 20, both in cells cultured at 1¿µg/mL doxycycline or 4¿µg/mL doxycycline. Our results revealed that endogenous...

  17. Identification of SUMO conjugation sites in the budding yeast proteome

    Directory of Open Access Journals (Sweden)

    Miguel Esteras

    2017-10-01

    Full Text Available Post-translational modification by the small ubiquitin-like modifier (SUMO is an important mechanism regulating protein function. Identification of SUMO conjugation sites on substrates is a challenging task. Here we employed a proteomic method to map SUMO acceptor lysines in budding yeast proteins. We report the identification of 257 lysine residues where SUMO is potentially attached. Amongst the hits, we identified already known SUMO substrates and sites, confirming the success of the approach. In addition, we tested several of the novel substrates using SUMO immunoprecipitation analysis and confirmed that the SUMO acceptor lysines identified in these proteins are indeed bona fide SUMOylation sites. We believe that the collection of SUMO sites presented here is an important resource for future functional studies of SUMOylation in yeast.

  18. Experience of action depends on intention, not body movement

    DEFF Research Database (Denmark)

    Jensen, Mads; Vagnoni, Eleonora; Overgaard, Morten

    2014-01-01

    in memory. We found that recall of a voluntary action was unaffected by an incongruent involuntary movement. In contrast, recall of an involuntary movement was strongly influenced by an incongruent voluntary action. Our results demonstrate an “intentional capture” of body movement by voluntary actions......, in support of intentional theories of agency, but contrary to reconstructive theories. When asked to recall both actions and movements, people's responses are shaped by memory of what they intended to do, rather than by how their body moved....... effects that they produce. Intentions would then be mere confabulations, and not bona fide experiences. Previous work on voluntary action has focused on immediate experiences of authorship, and few studies have considered memory for voluntary actions. We devised an experiment in which both voluntary...

  19. Mimivirus inaugurated in the 21st century the beginning of a reclassification of viruses.

    Science.gov (United States)

    Sharma, Vikas; Colson, Philippe; Pontarotti, Pierre; Raoult, Didier

    2016-06-01

    Mimivirus and other giant viruses are visible by light microscopy and bona fide microbes that differ from other viruses and from cells that have a ribosome. They can be defined by: giant virion and genome sizes; their complexity, with the presence of DNA and mRNAs and dozens or hundreds of proteins in virions; the presence of translation-associated components; a mobilome including (pro)virophages (and a defence mechanism, named MIMIVIRE, against them) and transpovirons; their monophyly; the presence of the most archaic protein motifs they share with cellular organisms but not other viruses; a broader host range than other viruses. These features show that giant viruses are specific, autonomous, biological entities that warrant the creation of a new branch of microbes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Characterization of dry globular proteins and protein fibrils by synchrotron radiation vacuum UV circular dichroism

    DEFF Research Database (Denmark)

    Nesgaard, Lise W.; Hoffmann, Søren Vrønning; Andersen, Christian Beyschau

    2008-01-01

    Circular dichroism using synchrotron radiation (SRCD) can extend the spectral range down to approximately 130 nm for dry proteins, potentially providing new structural information. Using a selection of dried model proteins, including alpha-helical, beta-sheet, and mixed-structure proteins, we...... with previously published theoretical calculations related to pi-orbital transitions. We also show that drying does not lead to large changes in the secondary structure and does not induce orientational artifacts. In combination with principal component analysis, our SRCD data allow us to distinguish between two...... different types of protein fibrils, highlighting that bona fide fibrils formed by lysozyme are structurally more similar to the nonclassical fibrillar aggregates formed by the SerADan peptide than with the amyloid formed by alpha-synuclein. Thus, despite the lack of direct structural conclusions...

  1. Resonant behavior of the generalized Langevin system with tempered Mittag–Leffler memory kernel

    Science.gov (United States)

    Chen, Yao; Wang, Xudong; Deng, Weihua

    2018-05-01

    The generalized Langevin equation describes anomalous dynamics. Noise is not only the origin of uncertainty but also plays a positive role in helping to detect signals with information, termed stochastic resonance (SR). This paper analyzes the anomalous resonant behaviors of the generalized Langevin system with a multiplicative dichotomous noise and an internal tempered Mittag–Leffler noise. For a system with a fluctuating harmonic potential, we obtain the exact expressions of several types of SR such as the first moment, the amplitude and autocorrelation function for the output signal as well as the signal–noise ratio. We analyze the influence of the tempering parameter and memory exponent on the bona fide SR and the general SR. Moreover, it is detected that the critical memory exponent changes regularly with the increase of the tempering parameter. Almost all the theoretical results are validated by numerical simulations.

  2. Documentation and localization of force-mediated filamin A domain perturbations in moving cells

    Science.gov (United States)

    Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

    2014-08-01

    Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

  3. Initial embryology and pluripotent stem cells in the pig - the quest for establishing the pig as a model for cell therapy

    DEFF Research Database (Denmark)

    Secher, Jan; Callesen, Henrik; Freude, Karla Kristine

    2016-01-01

    genetically modified pigs emerged. Over the past years, renewed interest in porcine PSCs has sparked activities in deriving in particular porcine induced pluripotent stem cells to develop the pig as a faithful model for studying the potentials and risks associated with induced pluripotent stem cell......The quest for porcine pluripotent stem cells (PSCs) was initiated in the early 90s. Initially, it was the intention to benefit from these cells for production of genetically modified pigs using homologous recombination followed by derivation of chimeric offspring; a technology that has been used...... to produce genetically modified mice since the mid-80s. However, no convincing reports on the generation of bona fide porcine embryonic stem cells or embryonic germ cells resulted from these activities, and with the advent of somatic cell nuclear transfer during the late 90s, alternative methods for creating...

  4. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin

    2016-02-12

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  5. A variational approach to niche construction.

    Science.gov (United States)

    Constant, Axel; Ramstead, Maxwell J D; Veissière, Samuel P L; Campbell, John O; Friston, Karl J

    2018-04-01

    In evolutionary biology, niche construction is sometimes described as a genuine evolutionary process whereby organisms, through their activities and regulatory mechanisms, modify their environment such as to steer their own evolutionary trajectory, and that of other species. There is ongoing debate, however, on the extent to which niche construction ought to be considered a bona fide evolutionary force, on a par with natural selection. Recent formulations of the variational free-energy principle as applied to the life sciences describe the properties of living systems, and their selection in evolution, in terms of variational inference. We argue that niche construction can be described using a variational approach. We propose new arguments to support the niche construction perspective, and to extend the variational approach to niche construction to current perspectives in various scientific fields. © 2018 The Authors.

  6. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  7. Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2

    DEFF Research Database (Denmark)

    Ueda, Takeshi; Nagamachi, Akiko; Takubo, Keiyo

    2015-01-01

    We previously reported deficiency for Samd9L, which was cloned as a candidate gene for -7/7q- syndrome, accelerated leukemia cooperatively with enhanced expression of a histone demethylase F-box and leucine-rich repeat protein 10 (Fbxl10, also known as Jhdm1b, Kdm2b, and Ndy1). To further...... with a normal G0 to G1 entry, resulting in pleiotropic progenitor cell expansion. Fbxl10 Tg HSCs displayed enhanced expression of neuron specific gene family member 2 (Nsg2) and forced expression of Nsg2 in primary bone marrow cells resulted in expansion of immature cells. In addition, the genes involved....... These findings define Fbxl10 as a bona fide oncogene, whose deregulated expression contributes to the development of leukemia involving metabolic proliferative advantage and Nsg2-mediated impaired differentiation....

  8. Assessing the physical nature of near-Earth asteroids through their dynamical histories

    Science.gov (United States)

    Fernández, Julio A.; Sosa, Andrea; Gallardo, Tabaré; Gutiérrez, Jorge N.

    2014-08-01

    We analyze a sample of 139 near-Earth asteroids (NEAs), defined as those that reach perihelion distances q4.8 au), having Tisserand parameters 2family comets (JFCs) in near-Earth orbits, i.e. with q4.8 au of cometary origin, but it could be even lower if the NEAs in unstable orbits listed before turn out to be bona fide asteroids from the main belt. This study strengthens the idea that NEAs and comets essentially are two distinct populations, and that periods of dormancy in comets must be rare. Most likely, active comets in near-Earth orbits go through a continuous erosion process in successive perihelion passages until disintegration into meteoritic dust and fragments of different sizes. In this scenario, 289P/Blanpain might be a near-devolatized fragment from a by now disintegrated parent comet.

  9. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin; Ryu, Tae Woo; Aranda, Manuel; Ravasi, Timothy

    2016-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  10. Shouldering the load: A review of Joan Stevenson's work on occupational lifting and design evaluation of load carriage equipment.

    Science.gov (United States)

    Costigan, Patrick A; Morin, Evelyn L; Reid, Susan A

    2014-01-01

    In this paper, Dr. Joan Stevenson's work on assessment of the effects of lifting, supporting and transporting loads is reviewed. A defining attribute of this work is the use of objective, biomechanical measures as the basis from which a fuller understanding of all factors affecting worker performance can be obtained, and how such performance should be measured and evaluated. The central objectives and conclusions of Dr. Stevenson's research programs spanning the years from 1985 through 2012 are summarized and discussed in terms of an overall research trajectory. The guiding principle of Dr. Stevenson's work is to reduce the potential harm to which workers are exposed through the development of bona fide occupational standards, a better understanding of risk factors leading to low back pain, and the establishment of an enhanced objective design process for functional load-bearing clothing and equipment.

  11. 21st International Conference on Few-Body Problems in Physics

    CERN Document Server

    2015-01-01

    The 21st International Conference on Few-Body Problems in Physics (FB21) will take place at the Crowne Plaza Chicago Metro Downtown Hotel in the West Loop area of Chicago, Illinois, USA, from May 18th to 22nd, 2015. The first conference of this series took place in London in 1959 and subsequent meetings were held in Brela (1967), Birmingham (1969), Budapest (1971), Los Angeles (1972), Laval (1974), Delhi (1976), Graz (1978), Eugene (1980), Karlsruhe (1983), Sendai (1986), Vancouver (1989), Adelaide (1992), Williamsburg (1994), Groningen (1997), Taipei (2000), Durham (2003),Santos (2006),Bonn (2009),and Fukuoka (2012) see also "History". FB21 will be conducted with the principles passed by the General Assembly in 2008. In particular, no bona fide scientist will be excluded from participation on the grounds of national origin, nationality, or political considerations unrelated to science.

  12. Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q10 deficiency harboring a heterozygous mutation in COQ4 gene

    Directory of Open Access Journals (Sweden)

    Damià Romero-Moya

    2017-10-01

    Full Text Available We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G > C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G > C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation. The COQ4 mutation was CRISPR/Cas9 edited resulting in isogenic, diploid and off-target free COQ4-corrected iPSCs.

  13. Archaeal origin of tubulin

    Directory of Open Access Journals (Sweden)

    Yutin Natalya

    2012-03-01

    Full Text Available Abstract Tubulins are a family of GTPases that are key components of the cytoskeleton in all eukaryotes and are distantly related to the FtsZ GTPase that is involved in cell division in most bacteria and many archaea. Among prokaryotes, bona fide tubulins have been identified only in bacteria of the genus Prosthecobacter. These bacterial tubulin genes appear to have been horizontally transferred from eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results are compatible with the origin of eukaryotic tubulins from artubulins. These findings expand the emerging picture of the origin of key components of eukaryotic functional systems from ancestral forms that are scattered among the extant archaea. Reviewers This article was reviewed by Gáspár Jékely and J. Peter Gogarten.

  14. Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

    2012-12-13

    The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

  15. Aminoacyl-tRNA-charged eukaryotic elongation factor 1A is a bona fide substrate for Legionelle pneumophila effector glucosyltransferases

    DEFF Research Database (Denmark)

    Tzivelekidis, Tina; Jank, Thomas; Pohl, Corinna

    2011-01-01

    Legionella pneumophila, which is the causative organism of Legionnaires disease, translocates numerous effector proteins into the host cell cytosol by a type IV secretion system during infection. Among the most potent effector proteins of Legionella are glucosyltransferases (Lgt’s), which...

  16. 23rd June 2010 - IATA Director-General and CEO G. Bisignani signing the guest book with Research and Computing Director S. Bertolucci; visiting the LHC superconducting magnet test hall with L. Bottura; throughout accompanied by Adviser for International relations M. Bona.

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    23rd June 2010 - IATA Director-General and CEO G. Bisignani signing the guest book with Research and Computing Director S. Bertolucci; visiting the LHC superconducting magnet test hall with L. Bottura; throughout accompanied by Adviser for International relations M. Bona.

  17. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells.

    Science.gov (United States)

    Maldonado, Paloma P; Angulo, María Cecilia

    2015-06-01

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity is a signaling pathway controlling OPC proliferation/differentiation, influencing the myelination process. However, new evidences describing non-synaptic mechanisms of communication between neurons and OPCs have revealed that neuron-OPC interactions are more complex than expected. The activation of extrasynaptic receptors by ambient neurotransmitter or local spillover and the ability of OPCs to sense neuronal activity through a potassium channel suggest that distinct modes of communication mediate different functions of OPCs in the CNS. This review discusses different mechanisms used by OPCs to interact with neurons and their potential roles during postnatal development and in brain disorders. © The Author(s) 2014.

  18. A case of misconstrued Rock Military Style

    DEFF Research Database (Denmark)

    Langkjær, Michael Alexander

    2012-01-01

    The motives behind the bona fide uniform derivation represented by The Rolling Stones lead, Mick Jagger, in his white 'frock-dress' worn in 1969 are complex. Jagger wore the white voile, Michael Fish-designed frock at the July 5 memorial concert in Hyde Park, just 48 hours after the death of fellow...... about Jagger's motivations in thus 'cross-dressing'. A notable British precedent for wearing the fustanella, viz. that of Lord Byron back in the 1820s in the Greek War of Independence, which, although a myth (since Byron never actualy wore the fustanella apart from an 1814 London portrait-sitting of him...... Richard, Mick Jagger and Brian Jones back in 1967), Jagger's wearing the costume on the occasion of a memorial concert for Jones was also meant to be symbolic, drawing on English romanticism in a special pleading on behalf of the rock star as a persecuted artist....

  19. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

  20. Imaging hydrated microbial extracellular polymers: Comparative analysis by electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dohnalkova, A.C.; Marshall, M. J.; Arey, B. W.; Williams, K. H.; Buck, E. C.; Fredrickson, J. K.

    2011-01-01

    Microbe-mineral and -metal interactions represent a major intersection between the biosphere and geosphere but require high-resolution imaging and analytical tools for investigating microscale associations. Electron microscopy has been used extensively for geomicrobial investigations and although used bona fide, the traditional methods of sample preparation do not preserve the native morphology of microbiological components, especially extracellular polymers. Herein, we present a direct comparative analysis of microbial interactions using conventional electron microscopy approaches of imaging at room temperature and a suite of cryogenic electron microscopy methods providing imaging in the close-to-natural hydrated state. In situ, we observed an irreversible transformation of the hydrated bacterial extracellular polymers during the traditional dehydration-based sample preparation that resulted in their collapse into filamentous structures. Dehydration-induced polymer collapse can lead to inaccurate spatial relationships and hence could subsequently affect conclusions regarding nature of interactions between microbial extracellular polymers and their environment.

  1. High Precision Renormalization Group Study of the Roughening Transition

    CERN Document Server

    Hasenbusch, M; Pinn, K

    1994-01-01

    We confirm the Kosterlitz-Thouless scenario of the roughening transition for three different Solid-On-Solid models: the Discrete Gaussian model, the Absolute-Value-Solid-On-Solid model and the dual transform of the XY model with standard (cosine) action. The method is based on a matching of the renormalization group flow of the candidate models with the flow of a bona fide KT model, the exactly solvable BCSOS model. The Monte Carlo simulations are performed using efficient cluster algorithms. We obtain high precision estimates for the critical couplings and other non-universal quantities. For the XY model with cosine action our critical coupling estimate is $\\beta_R^{XY}=1.1197(5)$. For the roughening coupling of the Discrete Gaussian and the Absolute-Value-Solid-On-Solid model we find $K_R^{DG}=0.6645(6)$ and $K_R^{ASOS}=0.8061(3)$, respectively.

  2. A role for the transcription factor HEY1 in glioblastoma

    DEFF Research Database (Denmark)

    Hulleman, Esther; Quarto, Micaela; Vernell, Richard

    2009-01-01

    Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes......, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically upregulated in glioma...... and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally...

  3. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells.

  4. The first optical spectra of Wolf-Rayet stars in M101 revealed with Gemini/GMOS

    Science.gov (United States)

    Pledger, J. L.; Shara, M. M.; Wilde, M.; Crowther, P. A.; Long, K. S.; Zurek, D.; Moffat, A. F. J.

    2018-01-01

    Deep narrow-band Hubble Space Telescope (HST) imaging of the iconic spiral galaxy M101 has revealed over a thousand new Wolf-Rayet (WR) candidates. We report spectrographic confirmation of 10 He II-emission line sources hosting 15 WR stars. We find WR stars present at both sub- and super-solar metallicities with WC stars favouring more metal-rich regions compared to WN stars. We investigate the association of WR stars with H II regions using archival HST imaging and conclude that the majority of WR stars are in or associated with H II regions. Of the 10 emission lines sources, only one appears to be unassociated with a star-forming region. Our spectroscopic survey provides confidence that our narrow-band photometric candidates are in fact bona fide WR stars, which will allow us to characterize the progenitors of any core-collapse supernovae that erupt in the future in M101.

  5. Functional genomics of probiotic Escherichia coli Nissle 1917 and 83972, and UPEC strain CFT073: comparison of transcriptomes, growth and biofilm formation

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Vejborg, Rebecca Munk; Klemm, Per

    2010-01-01

    Strain CFT073 is a bona fide uropathogen, whereas strains 83972 and Nissle 1917 are harmless probiotic strains of urinary tract and faecal origin, respectively. Despite their different environmental origins and dispositions the three strains are very closely related and the ancestors of 83972...... of the three strains are closely related. The data demonstrate that the distance from a pathogen to a probiotic strain can be surprisingly short. We demonstrate that Nissle 1917, in spite of its intestinal niche origin, grows well in urine, and is a good biofilm former in this medium in which it also out...... accounting for the impaired biofilm formation. Although the three strains have very different strategies vis-à-vis the human host their functional gene profiles are surprisingly similar. It is also interesting to note that the only two Escherichia coli strains used as probiotics are in fact deconstructed...

  6. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

    International Nuclear Information System (INIS)

    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon

    2008-01-01

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells

  7. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.

    Science.gov (United States)

    Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-04-01

    The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

  8. Electronic relaxation processes in polyatomic molecules. Progress report, October 1, 1975--September 30, 1976

    International Nuclear Information System (INIS)

    Lim, E.C.

    1976-09-01

    Excitation energy dependence of radiationless decay rate under collision-free conditions was utilized as a probe of intramolecular vibrational relaxation in tetracene and pentacene. The results give evidence of vibrational relaxation which competes with electronic relaxation. The substitution dependence of T 1 (nπ*) → S 0 radiationless transition in monocyclic diazines and the temperature dependence of S 1 non-radiative decay rate in alcoholic solutions of polycyclic monoazines indicate that the vibronic interaction between the lowest energy nπ* and ππ* states leads to a rapid radiationless deactivation of the lower of the two electronic states. Finally, a photon-counting spectrofluorometer of very high sensitivity was constructed, and it was used to record T 2 → T 1 fluorescence in bromoanthracenes and S 2 → S 1 fluorescence in azulene. These spectra represent the first bona-fide, or the most convincing, observation of fluorescence between excited electronic states

  9. Examining the process of de novo gene birth: an educational primer on "integration of new genes into cellular networks, and their structural maturation".

    Science.gov (United States)

    Frietze, Seth; Leatherman, Judith

    2014-03-01

    New genes that arise from modification of the noncoding portion of a genome rather than being duplicated from parent genes are called de novo genes. These genes, identified by their brief evolution and lack of parent genes, provide an opportunity to study the timeframe in which emerging genes integrate into cellular networks, and how the characteristics of these genes change as they mature into bona fide genes. An article by G. Abrusán provides an opportunity to introduce students to fundamental concepts in evolutionary and comparative genetics and to provide a technical background by which to discuss systems biology approaches when studying the evolutionary process of gene birth. Basic background needed to understand the Abrusán study and details on comparative genomic concepts tailored for a classroom discussion are provided, including discussion questions and a supplemental exercise on navigating a genome database.

  10. Quasiadiabatic modes from viscous inhomogeneities

    CERN Document Server

    Giovannini, Massimo

    2016-04-20

    The viscous inhomogeneities of a relativistic plasma determine a further class of entropic modes whose amplitude must be sufficiently small since curvature perturbations are observed to be predominantly adiabatic and Gaussian over large scales. When the viscous coefficients only depend on the energy density of the fluid the corresponding curvature fluctuations are shown to be almost adiabatic. After addressing the problem in a gauge-invariant perturbative expansion, the same analysis is repeated at a non-perturbative level by investigating the nonlinear curvature inhomogeneities induced by the spatial variation of the viscous coefficients. It is demonstrated that the quasiadiabatic modes are suppressed in comparison with a bona fide adiabatic solution. Because of its anomalously large tensor to scalar ratio the quasiadiabatic mode cannot be a substitute for the conventional adiabatic paradigm so that, ultimately, the present findings seems to exclude the possibility of a successful accelerated dynamics solely...

  11. Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

    Science.gov (United States)

    Sánchez, Miguel A; Parrott, Wayne A

    2017-10-01

    GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  12. 15 February 2012 - Geneva United Nations Office Director-General K.-J. Tokayev in the LHC tunnel with Adviser for Relations with international organisations M. Bona and Technology Department Head F. Bordry.

    CERN Multimedia

    Jean-claude Gadmer

    2012-01-01

    Kassym-Jomart Tokayev, director-general of the United Nations Office at Geneva, (centre picture 02), visited CERN on 15 February. He toured the LHC tunnel with Maurizio Bona, CERN’s adviser to the director-general, relations with international organizations, left, and Frédérick Bordry, CERN’s technology department head. He also visited the ATLAS underground experimental area, as well as the exhibition at the Globe of Science and Innovation.

  13. The effects of cognitive-behavioral therapy for eating disorders on quality of life: A meta-analysis.

    Science.gov (United States)

    Linardon, Jake; Brennan, Leah

    2017-07-01

    Meta-analyses have documented the efficacy of cognitive-behavioral therapy (CBT) for reducing symptoms of eating disorders. However, it is not known whether CBT for eating disorders can also improve quality of life (QoL). This meta-analysis therefore examined the effects of CBT for eating disorders on subjective QoL and health-related quality of life (QoL). Studies that assessed QoL before and after CBT for eating disorders were searched in the PsycInfo and Medline database. Thirty-four articles met inclusion criteria. Pooled within and between-groups Hedge's g were calculated at post-treatment and follow-up for treatment changes on both subjective and HRQoL using a random effects model. CBT led to significant and modest improvements in subjective QoL and HRQoL from pre to post-treatment and follow-up. CBT led to greater subjective QoL improvements than inactive (i.e., wait-list) and active (i.e., a combination of bona fide therapies, psychoeducation) comparisons. CBT also led to greater HRQoL improvements than inactive, but not active, comparisons. Prepost QoL improvements were larger in studies that delivered CBT individually and by a therapist or according to the cognitive maintenance model of eating disorders (CBT-BN or CBT-E); though this was not replicated at follow-up CONCLUSIONS: Findings provide preliminary evidence that CBT for eating disorders is associated with modest improvements in QOL, and that CBT may be associated with greater improvements in QOL relative to comparison conditions. © 2017 Wiley Periodicals, Inc.

  14. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Science.gov (United States)

    Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

  15. New Insights into the Role of the Immune Microenvironment in Breast Carcinoma

    Science.gov (United States)

    de la Cruz-Merino, Luis; Barco-Sánchez, Antonio; Henao Carrasco, Fernando; Nogales Fernández, Esteban; Vallejo Benítez, Ana; Brugal Molina, Javier; Martínez Peinado, Antonio; Grueso López, Ana; Ruiz Borrego, Manuel; Codes Manuel de Villena, Manuel; Sánchez-Margalet, Víctor; Nieto-García, Adoración; Alba Conejo, Emilio; Casares Lagar, Noelia; Ibáñez Martínez, José

    2013-01-01

    Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future. PMID:23861693

  16. A novel expansin protein from the white-rot fungus Schizophyllum commune.

    Directory of Open Access Journals (Sweden)

    Omar Eduardo Tovar-Herrera

    Full Text Available A novel expansin protein (ScExlx1 was found, cloned and expressed from the Basidiomycete fungus Schizophylum commune. This protein showed the canonical features of plant expansins. ScExlx1 showed the ability to form "bubbles" in cotton fibers, reduce the size of avicel particles and enhance reducing sugar liberation from cotton fibers pretreated with the protein and then treated with cellulases. ScExlx1 was able to bind cellulose, birchwood xylan and chitin and this property was not affected by different sodium chloride concentrations. A novel property of ScExlx1 is its capacity to enhance reducing sugars (N-acetyl glucosamine liberation from pretreated chitin and further added with chitinase, which has not been reported for any expansin or expansin-like protein. To the best of our knowledge, this is the first report of a bona fide fungal expansin found in a basidiomycete and we could express the bioactive protein in Pichia pastoris.

  17. The HectoMAP Cluster Survey. I. redMaPPer Clusters

    Science.gov (United States)

    Sohn, Jubee; Geller, Margaret J.; Rines, Kenneth J.; Hwang, Ho Seong; Utsumi, Yousuke; Diaferio, Antonaldo

    2018-04-01

    We use the dense HectoMAP redshift survey to explore the properties of 104 redMaPPer cluster candidates. The redMaPPer systems in HectoMAP cover the full range of richness and redshift (0.08 systems included in the Subaru/Hyper Suprime-Cam public data release are bona fide clusters. The median number of spectroscopic members per cluster is ∼20. We include redshifts of 3547 member candidates listed in the redMaPPer catalog whether they are cluster members or not. We evaluate the redMaPPer membership probability spectroscopically. The purity (number of real systems) in redMaPPer exceeds 90% even at the lowest richness. Three massive galaxy clusters (M ∼ 2 × 1013 M ⊙) associated with X-ray emission in the HectoMAP region are not included in the public redMaPPer catalog with λ rich > 20, because they lie outside the cuts for this catalog.

  18. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Science.gov (United States)

    Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

    2012-01-01

    Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  19. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Directory of Open Access Journals (Sweden)

    Andreas Jurgeit

    Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  20. Yet another call for a greater Role for good Faith in the South African Law of Contract: Can we banish the Law of the Jungle, while avoiding the Elephant in the Room?

    Directory of Open Access Journals (Sweden)

    Andre M Louw

    2013-12-01

    Full Text Available This article examines the current approach of the South African courts to the role of good faith or bona fides in contracts, as well as the courts’ stated reasons for this approach. The article specifically examines how arguments based on good faith have fared in the Constitutional Court to date, and the prospects for law reform to emanate from that court in the near future. The author suggests an understanding of good faith which he believes is in line with the Constitution of the Republic of South Africa, 1996 and argues that in terms of such an understanding of a robust good faith doctrine the legal fraternity or the courts can avoid some of the dangers that the judges of the Supreme Court of Appeal have warned about in this context in recent years. The author shares some concluding thoughts on the pressing need for law reform with respect to the role and presence of good faith in contracts.

  1. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Directory of Open Access Journals (Sweden)

    Venturina Stagni

    2014-03-01

    Full Text Available Ataxia-telangiectasia mutated (ATM kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR. The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer.

  2. Cell cloning-on-the-spot by using an attachable silicone cylinder.

    Science.gov (United States)

    Park, Hong Bum; Son, Wonseok; Chae, Dong Han; Lee, Jisu; Kim, Il-Woung; Yang, Woomi; Sung, Jae Kyu; Lim, Kyu; Lee, Jun Hee; Kim, Kyung-Hee; Park, Jong-Il

    2016-06-10

    Cell cloning is a laboratory routine to isolate and keep particular properties of cultured cells. Transfected or other genetically modified cells can be selected by the traditional microbiological cloning. In addition, common laboratory cell lines are prone to genotypic drift during their continual culture, so that supplementary cloning steps are often required to maintain correct lineage phenotypes. Here, we designed a silicone-made attachable cloning cylinder, which facilitated an easy and bona fide cloning of interested cells. This silicone cylinder was easy to make, showed competent stickiness to laboratory plastics including culture dishes, and hence enabled secure isolation and culture for days of selected single cells, especially, on the spots of preceding cell-plating dishes under microscopic examination of visible cellular phenotypes. We tested the silicone cylinder in the monoclonal subcloning from a heterogeneous population of a breast cancer cell line, MDA-MB-231, and readily established independent MDA-MB-231 subclones showing different sublineage phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. B Cell Help by CD1d-Rectricted NKT Cells

    Directory of Open Access Journals (Sweden)

    Livia Clerici

    2015-10-01

    Full Text Available B cell activation and antibody production against foreign antigens is a central step of host defense. This is achieved via highly regulated multi-phase processes that involve a variety of cells of both innate and adaptive arms of the immune system. MHC class II-restricted CD4+ T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. Recent data, however, challenge this paradigm by showing the existence of other helper cell types. CD1d restricted NKT cells specific for lipid antigens are one such new player and can coopt bona fide follicular helper phenotypes. Their role in helping antigen-specific B cell response to protein antigens, as well as to the so called “help-less” antigens that cannot be recognized by T follicular helper cells, is being increasingly elucidated, highlighting their potential pathophysiological impact on the immune response, as well as on the design of improved vaccine formulations.

  4. Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Courtney M. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Hu, Jianxin [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Thomas, Reuben [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Gainous, T. Blair [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Celona, Barbara [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Sinha, Tanvi [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Dickel, Diane E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Heidt, Analeah B. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Xu, Shan-Mei [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Bruneau, Benoit G. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pollard, Katherine S. [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pennacchio, Len A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Black, Brian L. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Dept. of

    2017-03-28

    Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

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

    Science.gov (United States)

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

    2014-01-01

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

  6. MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Mets, E; Van der Meulen, J; Van Peer, G; Boice, M; Mestdagh, P; Van de Walle, I; Lammens, T; Goossens, S; De Moerloose, B; Benoit, Y; Van Roy, N; Clappier, E; Poppe, B; Vandesompele, J; Wendel, H-G; Taghon, T; Rondou, P; Soulier, J; Van Vlierberghe, P; Speleman, F

    2015-04-01

    The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.

  7. A Single Aplysia Neurotrophin Mediates Synaptic Facilitation via Differentially Processed Isoforms Secreted as Mature or Precursor Forms

    Science.gov (United States)

    Kassabov, Stefan R.; Choi, Yun-Beom; Karl, Kevin A.; Vishwasrao, Harshad D.; Bailey, Craig H.; Kandel, Eric R.

    2014-01-01

    Summary Neurotrophins control the development and adult plasticity of the vertebrate nervous system. Failure to identify invertebrate neurotrophin orthologs, however, has precluded studies in invertebrate models, limiting understanding of fundamental aspects of neurotrophin biology and function. We identified a neurotrophin (ApNT) and Trk receptor (ApTrk) in the mollusk Aplysia and find they play a central role in learning related synaptic plasticity. ApNT increases the magnitude and lowers the threshold for induction of long-term facilitation and initiates the growth of new synaptic varicosities at the monosynaptic connection between sensory and motor neurons of the gill-withdrawal reflex. Unlike vertebrate neurotrophins, ApNT has multiple coding exons and exerts distinct synaptic effects through differentially processed and secreted splice isoforms. Our findings demonstrate the existence of bona-fide neurotrophin signaling in invertebrates and reveal a novel, post-transcriptional mechanism, regulating neurotrophin processing and the release of pro- and mature neurotrophins which differentially modulate synaptic plasticity. PMID:23562154

  8. 235Cf anti ν discrepancy and the sulfur discrepancy

    International Nuclear Information System (INIS)

    Smith, J.R.

    1979-01-01

    The cantankerous discrepancy among measured values of anti ν for 235 Cf appears at last to be nearing a final resolution. A recent review has summarized the progress that has been achieved through revaluation upward by 0.5% of two manganese bath values anti ν and the performance of a new liquid scintillator measurement. A new manganese bath measurement at INEL is in reasonably good agreement with previous manganese bath values of 235 Cf anti ν. It now appears that the manganese bath values could still be systematically low by as much as 0.4% because the BNL-325 thermal absorption cross section for sulfur may be as much as 10% low. There is a bona fide discrepancy between measurements of the sulfur cross section by pile oscillators and the values derived from transmission measurements. The resolution of this discrepancy is a prerequisite to the final resolution of the 235 Cf anti ν discrepancy. 22 references

  9. Ultimately short ballistic vertical graphene Josephson junctions

    Science.gov (United States)

    Lee, Gil-Ho; Kim, Sol; Jhi, Seung-Hoon; Lee, Hu-Jong

    2015-01-01

    Much efforts have been made for the realization of hybrid Josephson junctions incorporating various materials for the fundamental studies of exotic physical phenomena as well as the applications to superconducting quantum devices. Nonetheless, the efforts have been hindered by the diffusive nature of the conducting channels and interfaces. To overcome the obstacles, we vertically sandwiched a cleaved graphene monoatomic layer as the normal-conducting spacer between superconducting electrodes. The atomically thin single-crystalline graphene layer serves as an ultimately short conducting channel, with highly transparent interfaces with superconductors. In particular, we show the strong Josephson coupling reaching the theoretical limit, the convex-shaped temperature dependence of the Josephson critical current and the exceptionally skewed phase dependence of the Josephson current; all demonstrate the bona fide short and ballistic Josephson nature. This vertical stacking scheme for extremely thin transparent spacers would open a new pathway for exploring the exotic coherence phenomena occurring on an atomic scale. PMID:25635386

  10. Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes.

    Science.gov (United States)

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2017-09-29

    Giant viruses of amoebae were discovered serendipitously in 2003; they are visible via optical microscopy, making them bona fide microbes. Their lifestyle, structure, and genomes break the mold of classical viruses. Giant viruses of amoebae are complex microorganisms. Their genomes harbor between 444 and 2,544 genes, including many that are unique to viruses, and encode translation components; their virions contain >100 proteins as well as mRNAs. Mimiviruses have a specific mobilome, including virophages, provirophages, and transpovirons, and can resist virophages through a system known as MIMIVIRE (mimivirus virophage resistance element). Giant viruses of amoebae bring upheaval to the definition of viruses and tend to separate the current virosphere into two categories: very simple viruses and viruses with complexity similar to that of other microbes. This new paradigm is propitious for enhanced detection and characterization of giant viruses of amoebae, and a particular focus on their role in humans is warranted.

  11. CK2—An Emerging Target for Neurological and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Julia Castello

    2017-01-01

    Full Text Available Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full and conditional CK2 knockout mice have further elucidated the importance of CK2 in brain development, neuronal activity, and behavior. This review will discuss recent advances in the field that point to CK2 as a regulator of neuronal functions and as a potential novel target to treat neurological and psychiatric disorders.

  12. Separate and Unequal: Judicial Culture, Employment Qualifications and Muslim Headscarf Debates

    Directory of Open Access Journals (Sweden)

    Joyce Marie Mushaben

    2013-09-01

    Full Text Available Few European lawmakers have analyzed the implications of Muslim headscarf bans for equal employment opportunity. EU anti-discrimination directives suggest that contradictory member-state approaches will eventually invoke a judicial Community response at national expense. Drawing on the bona fide occupational qualification (BFOQ standard, this study compares the “judicial cultures” of the U.S. Supreme Court, the German Constitutional Court, the European Court of Human Rights (ECHR and the European Court of Justice (ECJ. It argues that while the ECJ initially invoked Roman law precepts shared by a majority of its member-states through the 1980s, it has come to embrace Anglo-American norms stressing individual freedoms over state interests. Given their strong support for equal treatment and social inclusion, EU justices will be more likely than member-state or ECHR judges to overturn existing bans on hejab at the workplace, once such a case makes its way onto the ECJ docket.

  13. Records, record linkage, and the identification of long term environmental hazards

    Energy Technology Data Exchange (ETDEWEB)

    Acheson, E. D.

    1978-11-15

    Long-term effects of toxic substances in man which have been recognized so far have been noticed because they have involved gross relative risks, or bizarre effects, or have been stumbled upon by chance or because of special circumstances. These facts and some recent epidemiological evidence together suggest that a systematic approach with more precise methods and data would almost certainly reveal the effects of many more toxic substances, particularly in workers exposed in manufacturing industry. Additional ways are suggested in which record linkage techniques might be used to identify substances with long-term toxic effects. Obstacles to further progress in the field of monitoring for long-term hazards in man are: lack of a public policy dealing with confidentiality and informed consent in the use of identifiable personal records, which balances the needs of bona fide research workers with proper safeguards for the privacy of the individual, and lack of resources to improve the quality, accessibility and organization of the appropriate data. (PCS)

  14. Human rights, public health and medicinal cannabis use.

    Science.gov (United States)

    Bone, Melissa; Seddon, Toby

    2016-01-01

    This paper explores the interplay between the human rights and drug control frameworks and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of 'health'. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the State and the individual within the drug policy field. The leading medicinal cannabis case in the UK highlights the judiciary's failure to engage with an individual's human right to health as they adopt an arbitrary, externalist view, focussing on the legality of cannabis to the exclusion of other concerns. Drawing on some international comparisons, the paper considers how a human rights perspective can lead to an approach to medicinal cannabis use which facilitates a holistic understanding of public health.

  15. Autologous blood cell therapies from pluripotent stem cells

    Science.gov (United States)

    Lengerke, Claudia; Daley, George Q.

    2010-01-01

    Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

  16. Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

    DEFF Research Database (Denmark)

    Jacobsen, Mette Juul; Cirera Salicio, Susanna; Joller, David

    2011-01-01

    by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes. FINDINGS: The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence...... polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac...... of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might...

  17. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  18. Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing.

    Science.gov (United States)

    Hong, Jungeui; Gresham, David

    2017-11-01

    Quantitative analysis of next-generation sequencing (NGS) data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are identified as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. Misidentification of these molecules as PCR duplicates can introduce unforeseen biases during analyses. Here, we developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed, single-index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters) enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of PCR duplicates results in improved accuracy of both allele frequency (AF) estimation in heterogeneous populations using DNA sequencing and gene expression quantification using RNA-Seq.

  19. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.

    Science.gov (United States)

    Tardivel, Meryem; Bégard, Séverine; Bousset, Luc; Dujardin, Simon; Coens, Audrey; Melki, Ronald; Buée, Luc; Colin, Morvane

    2016-11-04

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

  20. Semi-supervised Learning Predicts Approximately One Third of the Alternative Splicing Isoforms as Functional Proteins

    Directory of Open Access Journals (Sweden)

    Yanqi Hao

    2015-07-01

    Full Text Available Alternative splicing acts on transcripts from almost all human multi-exon genes. Notwithstanding its ubiquity, fundamental ramifications of splicing on protein expression remain unresolved. The number and identity of spliced transcripts that form stably folded proteins remain the sources of considerable debate, due largely to low coverage of experimental methods and the resulting absence of negative data. We circumvent this issue by developing a semi-supervised learning algorithm, positive unlabeled learning for splicing elucidation (PULSE; http://www.kimlab.org/software/pulse, which uses 48 features spanning various categories. We validated its accuracy on sets of bona fide protein isoforms and directly on mass spectrometry (MS spectra for an overall AU-ROC of 0.85. We predict that around 32% of “exon skipping” alternative splicing events produce stable proteins, suggesting that the process engenders a significant number of previously uncharacterized proteins. We also provide insights into the distribution of positive isoforms in various functional classes and into the structural effects of alternative splicing.

  1. Identifying New Members of Nearby Moving Groups

    Science.gov (United States)

    Holmbeck, Erika; Vican, Laura

    2014-06-01

    Our group has assembled a sample of 14,000 stars of spectral types B9-M9 with measured UVW Galactic space velocities and lying within 125 pc of Earth. We have identified candidate members of three nearby young (less than 100 Myr) moving groups. For stars of spectral types G5 and later, we have used the Kast spectrometer on the Shane 3m telescope at Lick Observatory to measure lithium abundance in order to determine stellar ages. With the data we have obtained from this run, we will be able to establish whether our candidates are bona fide members of the moving groups in question. I will be presenting the preliminary results from this survey, including spectra of the ~50 stars observed thus far. These nearby young stars will make excellent targets for direct imaging followup surveys, since any giant planets around young stars will still be warm, and will therefore be bright enough to detect with instruments like GPI.

  2. Phosphorylation of ARD1 by IKKβ contributes to its destabilization and degradation

    International Nuclear Information System (INIS)

    Kuo, Hsu-Ping; Lee, Dung-Fang; Xia, Weiya; Lai, Chien-Chen; Li, Long-Yuan; Hung, Mien-Chie

    2009-01-01

    IκB kinase β (IKKβ), a major kinase downstream of various proinflammatory signals, mediates multiple cellular functions through phosphorylation and regulation of its substrates. On the basis of protein sequence analysis, we identified arrest-defective protein 1 (ARD1), a protein involved in apoptosis and cell proliferation processes in many human cancer cells, as a new IKKβ substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKβ. IKKβ physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKβ destabilized ARD1 and induced its proteasome-mediated degradation. Impaired growth suppression was observed in ARD1 phosphorylation-mimic mutant (S209E)-transfected cells as compared with ARD1 non-phosphorylatable mutant (S209A)-transfected cells. Our findings of molecular interactions between ARD1 and IKKβ may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKβ.

  3. Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

    Science.gov (United States)

    Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

    2009-09-01

    Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

  4. Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve.

    Directory of Open Access Journals (Sweden)

    Takahiro Matsuki

    Full Text Available In an attempt to identify and characterize how symbiotic bacteria of the gut microbiota affect the molecular and cellular mechanisms of epithelial homeostasis, intestinal epithelial cells were co-cultured with either Lactobacillus or Bifidobacterium as bona fide symbionts to examine potential gene modulations. In addition to genes involved in the innate immune response, genes encoding check-point molecules controlling the cell cycle were among the most modulated in the course of these interactions. In the m-ICcl2 murine cell line, genes encoding cyclin E1 and cyclin D1 were strongly down regulated by L. casei and B. breve respectively. Cell proliferation arrest was accordingly confirmed. Short chain fatty acids (SCFA were the effectors of this modulation, alone or in conjunction with the acidic pH they generated. These results demonstrate that the production of SCFAs, a characteristic of these symbiotic microorganisms, is potentially an essential regulatory effector of epithelial proliferation in the gut.

  5. Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target.

    Science.gov (United States)

    Cook, Peter J; Thomas, Rozario; Kannan, Ram; de Leon, Esther Sanchez; Drilon, Alexander; Rosenblum, Marc K; Scaltriti, Maurizio; Benezra, Robert; Ventura, Andrea

    2017-07-11

    The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and describes a general strategy to define the oncogenic potential of novel glioma-associated genomic rearrangements and to generate accurate preclinical models of this lethal human cancer.

  6. Towards Holography via Quantum Source-Channel Codes

    Science.gov (United States)

    Pastawski, Fernando; Eisert, Jens; Wilming, Henrik

    2017-07-01

    While originally motivated by quantum computation, quantum error correction (QEC) is currently providing valuable insights into many-body quantum physics, such as topological phases of matter. Furthermore, mounting evidence originating from holography research (AdS/CFT) indicates that QEC should also be pertinent for conformal field theories. With this motivation in mind, we introduce quantum source-channel codes, which combine features of lossy compression and approximate quantum error correction, both of which are predicted in holography. Through a recent construction for approximate recovery maps, we derive guarantees on its erasure decoding performance from calculations of an entropic quantity called conditional mutual information. As an example, we consider Gibbs states of the transverse field Ising model at criticality and provide evidence that they exhibit nontrivial protection from local erasure. This gives rise to the first concrete interpretation of a bona fide conformal field theory as a quantum error correcting code. We argue that quantum source-channel codes are of independent interest beyond holography.

  7. Nucleon form factors and hidden symmetry in holographic QCD

    International Nuclear Information System (INIS)

    Hong, D.K.; Rho, M.; Yee, H.-U.; Yi, P.

    2007-10-01

    The vector dominance of the electromagnetic (EM) form factors both for mesons and baryons arises naturally in holographic QCD, where both the number of colors and the 't Hooft coupling are taken to be very large, offering a bona-fide derivation of the notion of vector dominance. The crucial ingredient for this is the infinite tower of vector mesons in the approximations made which share features that are characteristic of the quenched approximation in lattice QCD. We approximate the infinite sum by contributions from the lowest four vector mesons of the tower which turn out to saturate the charge and magnetic moment sum rules within a few % and compute them totally free of unknown parameters for momentum transfers Q 2 approx.= 1 GeV 2 . We identify certain observables that can be reliably computed within the approximations and others that are not, and discuss how the improvement of the latter can enable one to bring holographic QCD closer to QCD proper. (author)

  8. Qualitative Methods in Patient-Centered Outcomes Research.

    Science.gov (United States)

    Vandermause, Roxanne; Barg, Frances K; Esmail, Laura; Edmundson, Lauren; Girard, Samantha; Perfetti, A Ross

    2017-02-01

    The Patient-Centered Outcomes Research Institute (PCORI), created to fund research guided by patients, caregivers, and the broader health care community, offers a new research venue. Many (41 of 50) first funded projects involved qualitative research methods. This study was completed to examine the current state of the science of qualitative methodologies used in PCORI-funded research. Principal investigators participated in phenomenological interviews to learn (a) how do researchers using qualitative methods experience seeking funding for, implementing and disseminating their work; and (b) how may qualitative methods advance the quality and relevance of evidence for patients? Results showed the experience of doing qualitative research in the current research climate as "Being a bona fide qualitative researcher: Staying true to research aims while negotiating challenges," with overlapping patterns: (a) researching the elemental, (b) expecting surprise, and (c) pushing boundaries. The nature of qualitative work today was explicitly described and is rendered in this article.

  9. RNA/DNA co-analysis from human saliva and semen stains--results of a third collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, Claus; Hanson, E; Anjos, M J

    2013-01-01

    samples of human or non-human origin were analyzed by 20 participating laboratories using an RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2, PSA, SEMG1 and TGM4). The laboratories used......A third collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 µl saliva, 5-0.01 µl semen) and, optionally, bona fide or mock casework...... different chemistries and instrumentation and a majority (16/20) were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from individual stains not only permitted a confirmation of the presence of saliva/semen (i.e. tissue/fluid source of origin...

  10. Subversion of inflammasome activation and pyroptosis by pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Larissa D Cunha

    2013-11-01

    Full Text Available Activation of the inflammasome occurs in response to a notably high number of pathogenic microbes and is a broad innate immune response that effectively contributes to restriction of pathogen replication and generation of adaptive immunity. Activation of these platforms leads to caspase-1- and/or caspase-11-dependent secretion of proteins, including cytokines, and induction of a specific form of cell death called pyroptosis, which directly or indirectly contribute for restriction of pathogen replication. Not surprisingly, bona fide intracellular pathogens developed strategies for manipulation of cell death to guarantee intracellular replication. In this sense, the remarkable advances in the knowledge of the inflammasome field have been accompanied by several reports characterizing the inhibition of this platform by several pathogenic bacteria. Herein, we review some processes used by pathogenic bacteria, including Yersinia spp., Pseudomonas aeruginosa, Vibrio parahaemolyticus, Chlamydia trachomatis, Francisella tularensis, Shigella flexneri, Legionella pneumophila and Coxiella burnetii to evade the activation of the inflammasome and the induction of pyroptosis.

  11. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

    Science.gov (United States)

    Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong

    2016-03-16

    Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. An Annotation Agnostic Algorithm for Detecting Nascent RNA Transcripts in GRO-Seq.

    Science.gov (United States)

    Azofeifa, Joseph G; Allen, Mary A; Lladser, Manuel E; Dowell, Robin D

    2017-01-01

    We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA-seq, measure steady state RNA levels which are affected by transcription, post-transcriptional processing, and RNA stability. GRO-seq data, however, presents unique analysis challenges that are only beginning to be addressed. Here, we describe a new algorithm, Fast Read Stitcher (FStitch), that takes advantage of two popular machine-learning techniques, hidden Markov models and logistic regression, to classify which regions of the genome are transcribed. Given a small user-defined training set, our algorithm is accurate, robust to varying read depth, annotation agnostic, and fast. Analysis of GRO-seq data without a priori need for annotation uncovers surprising new insights into several aspects of the transcription process.

  13. Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function.

    Science.gov (United States)

    Largo, Eneko; Gladue, Douglas P; Huarte, Nerea; Borca, Manuel V; Nieva, José L

    2014-01-01

    Viroporins are small integral membrane proteins functional in viral assembly and egress by promoting permeabilization. Blocking of viroporin function therefore constitutes a target for antiviral development. Classical swine fever virus (CSFV) protein p7 has been recently regarded as a class II viroporin. Here, we sought to establish the determinants of the CSFV p7 permeabilizing activity in a minimal model system. Assessment of an overlapping peptide library mapped the porating domain to the C-terminal hydrophobic stretch (residues 39-67). Pore-opening dependence on pH or sensitivity to channel blockers observed for the full protein required the inclusion of a preceding polar sequence (residues 33-38). Effects of lipid composition and structural data further support that the resulting peptide (residues 33-67), may comprise a bona fide surrogate to assay p7 activity in model membranes. Our observations imply that CSFV p7 relies on genus-specific structures-mechanisms to perform its viroporin function. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 26th August 2010 - World Meteorological Organization Secretary-General M. Jarraud signing the guest book with CERN Director-General R. Heuer and visiting the LHC superconducting magnet test hall with Technology Department Head F. Bordry; throughout accompanied by M. Bona, CERN Relations with International Organisations

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    26th August 2010 - World Meteorological Organization Secretary-General M. Jarraud signing the guest book with CERN Director-General R. Heuer and visiting the LHC superconducting magnet test hall with Technology Department Head F. Bordry; throughout accompanied by M. Bona, CERN Relations with International Organisations

  15. Protection of Fundamental Rights Post-Lisbon:The Interaction between the EU Charter of Fundamental Rights, the European Convention on Human Rights (ECHR) and National Constitutions (FIDE National Report for the United Kingdom)

    OpenAIRE

    Lock, Tobias; Layden, Patrick

    2011-01-01

    This is the United Kingdom national report for the FIDE XXV Congress on the 'Protection of Fundamental Rights Post-Lisbon'. The national report consist of answers from a UK perspective to questions posed by the general rapporteur on the following general topics: Nature and scope of fundamental rights protected; Horizontal Effect and Collision of rights; Consequences of the entry into force of the EU Charter of Fundamental Rights; Consequences of the accession of the EU to the ECHR; The future...

  16. The β Pictoris association low-mass members: Membership assessment, rotation period distribution, and dependence on multiplicity

    Science.gov (United States)

    Messina, S.; Lanzafame, A. C.; Malo, L.; Desidera, S.; Buccino, A.; Zhang, L.; Artemenko, S.; Millward, M.; Hambsch, F.-J.

    2017-10-01

    Context. Low-mass members of young loose stellar associations and open clusters exhibit a wide spread of rotation periods. Such a spread originates from the distributions of masses and initial rotation periods. However, multiplicity can also play a significant role. Aims: We aim to investigate the role played by physical companions in multiple systems in shortening the primordial disk lifetime, anticipating the rotation spin up with respect to single stars. Methods: We have compiled the most extensive list to date of low-mass bona fide and candidate members of the young 25-Myr β Pictoris association. We have measured from our own photometric time series or from archival time series the rotation periods of almost all members. In a few cases the rotation periods were retrieved from the literature. We used updated UVWXYZ components to assess the membership of the whole stellar sample. Thanks to the known basic properties of most members we built the rotation period distribution distinguishing between bona fide members and candidate members and according to their multiplicity status. Results: We find that single stars and components of multiple systems in wide orbits (>80 AU) have rotation periods that exhibit a well defined sequence arising from mass distribution with some level of spread likely arising from initial rotation period distribution. All components of multiple systems in close orbits (Pleiades shows that whereas the evolution of F-G stars is well reproduced by angular momentum evolution models, this is not the case for the slow K and early-M stars. Finally, we find that the amplitude of their light curves is correlated neither with rotation nor with mass. Conclusions: Once single stars and wide components of multiple systems are separated from close components of multiple systems, the rotation period distributions exhibit a well defined dependence on mass that allows us to make a meaningful comparison with similar distributions of either younger or older

  17. ‘Ekhaya: Human displacement and the yearning for familial homecoming. From Throne (Cathedra to Home (Oikos in a grassroots ecclesiology of place and space: Fides Quaerens Domum et Locum [Faith Seeking Home and Space

    Directory of Open Access Journals (Sweden)

    Daniel J. Louw

    2017-04-01

    Full Text Available The classical definition of theology is ‘faith-seeking understanding’ (fides quaerens intellectum. The focus is on the understanding/interpretation of the object of Christian faith: God. There is another root for the quest for understanding, namely the praxis situation of faith. People live in particular historical contexts that have their own distinctive problems and possibilities; thus, the focus on place and space in a theology of home. A praxis approach is to learn life and the gospel from below, thus the emphasis on a grassroots ecclesiology that is structured like an oikos, a familial dwelling place. This understanding of the dynamics of the fellowship of believers as  oikodomein is captured by the Zulu notion for the yearning for home (home sickness: Ekhaya. It is argued that Ekhaya thinking is an alternative route for an operative ecclesiology that caters for the need of marginalised, oppressed, displaced and homeless people. Practical theology is thus described as fides  quaerens domum et locum [faith-seeking home and place], namely to inhabit. An Ekhaya approach to practical theological ecclesiology is about critical reflection through the eyes of those who are weak and who don’t count for much by the standards of successful people and institutions.

  18. TAF9b (Formerly TAF9L) Is a Bona Fide TAF That Has Unique and Overlapping Roles with TAF9

    OpenAIRE

    Frontini, Mattia; Soutoglou, Evi; Argentini, Manuela; Bole-Feysot, Christine; Jost, Bernard; Scheer, Elisabeth; Tora, Làszlò

    2005-01-01

    TFIID plays a key role in transcription initiation of RNA polymerase II preinitiation complex assembly. TFIID is comprised of the TATA box binding protein (TBP) and 14 TBP-associated factors (TAFs). A second set of transcriptional regulatory multiprotein complexes containing TAFs has been described (called SAGA, TFTC, STAGA, and PCAF/GCN5). Using matrix-assisted laser desorption ionization mass spectrometry, we identified a novel TFTC subunit, human TAF9Like, encoded by a TAF9 paralogue gene....

  19. Cellular repressor of E1A-stimulated genes is a bona fide lysosomal protein which undergoes proteolytic maturation during its biosynthesis

    International Nuclear Information System (INIS)

    Schaehs, Philipp; Weidinger, Petra; Probst, Olivia C.; Svoboda, Barbara; Stadlmann, Johannes; Beug, Hartmut; Waerner, Thomas; Mach, Lukas

    2008-01-01

    Cellular repressor of E1A-stimulated genes (CREG) has been reported to be a secretory glycoprotein implicated in cellular growth and differentiation. We now show that CREG is predominantly localized within intracellular compartments. Intracellular CREG was found to lack an N-terminal peptide present in the secreted form of the protein. In contrast to normal cells, CREG is largely secreted by fibroblasts missing both mannose 6-phosphate receptors. This is not observed in cells lacking only one of them. Mass spectrometric analysis of recombinant CREG revealed that the protein contains phosphorylated oligosaccharides at either of its two N-glycosylation sites. Cellular CREG was found to cosediment with lysosomal markers upon subcellular fractionation by density-gradient centrifugation. In fibroblasts expressing a CREG-GFP fusion construct, the heterologous protein was detected in compartments containing lysosomal proteins. Immunolocalization of endogenous CREG confirmed that intracellular CREG is localized in lysosomes. Proteolytic processing of intracellular CREG involves the action of lysosomal cysteine proteinases. These results establish that CREG is a lysosomal protein that undergoes proteolytic maturation in the course of its biosynthesis, carries the mannose 6-phosphate recognition marker and depends on the interaction with mannose 6-phosphate receptors for efficient delivery to lysosomes

  20. 15th December 2010 - World Intellectual Property Organization Director-General F. Gurry signing the guest book with CERN Director-General R. Heuer; visiting CMS control room, experimental cavern and LHC tunnel with Collaboration Deputy Spokesperson J. Incandela, accompanied by M. Bona.

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    CERN-HI-1012325 36, from left to right: WIPO Arbitration and Mediation Center, Global Issues Sector Director E. Wilbers; CERN Adviser, Relations with International Organisations, M. Bona; CMS Collaboration Deputy Spokesperson, University of California Santa Barbara J. Incandela; WIPO Deputy Director General, Global Issues Sector J. C. Wichard; WIPO Director-General F. Gurry; WIPO Executive Director and Chief of Staff, Office of the Director General N. Prasad.

  1. The learning curve for hip arthroscopy: a systematic review.

    Science.gov (United States)

    Hoppe, Daniel J; de Sa, Darren; Simunovic, Nicole; Bhandari, Mohit; Safran, Marc R; Larson, Christopher M; Ayeni, Olufemi R

    2014-03-01

    The learning curve for hip arthroscopy is consistently characterized as "steep." The purpose of this systematic review was to (1) identify the various learning curves reported in the literature, (2) examine the evidence supporting these curves, and (3) determine whether this evidence supports an accepted number of cases needed to achieve proficiency. The electronic databases Embase and Medline were screened for any clinical studies reporting learning curves in hip arthroscopy. Two reviewers conducted a full-text review of eligible studies and a hand search of conference proceedings and reference sections of the included articles. Inclusion/exclusion criteria were applied, and a quality assessment was completed for each included article. Descriptive statistics were compiled. We identified 6 studies with a total of 1,063 patients. Studies grouped surgical cases into "early" versus "late" in a surgeon's experience, with 30 cases being the most common cutoff used. Most of these studies used descriptive statistics and operative time and complication rates as measures of competence. Five of 6 studies showed improvement in these measures between early and late experience, but only one study proposed a bona fide curve. This review shows that when 30 cases was used as the cutoff point to differentiate between early and late cases in a surgeon's experience, there were significant reductions in operative time and complication rates. However, there was insufficient evidence to quantify the learning curve and validate 30, or any number of cases, as the point at which the learning curve plateaus. As a result, this number should be interpreted with caution. Level IV, systematic review of Level IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  2. Interlopers at the Fringes of Empire: The Procurators of the Propaganda Fide Papal Congregation in Canton and Macao, 1700-1823

    Directory of Open Access Journals (Sweden)

    Eugenio Menegon

    2017-12-01

    Full Text Available The office of the procurator of the papal Sacred Congregation for the Propagation of the Faith (Sacra Congregatio de Propaganda Fide offers a unique case study of noncommercial interloping in the long eighteenth century in the Pearl River Delta, and reveals the complexity and fluidity of life at the intersection of Asian and European maritime environments in that special human ecosystem. The oceanic infrastructure of the Age of Sail and the Sino-Western trade system in Canton sustained the Catholic missionary enterprise in Asia, and the professional figure of the procurator represented its economic and political linchpin. Procurators were agents connected with both European and Qing imperial formations, yet not directly at their service. They utilized existing maritime trade networks to their own advantage without being integral parts of those networks’ economic mechanisms. All the while, they subverted Qing prohibitions against Christianity. Using sources preserved in Rome, this article offers new insights into the global mechanisms of trade, communication, and religious exchange embodied by the procurators-interlopers and their networks, with significant implications for the history of the Sino-Western trade system, Qing policies toward the West and Christianity, and the history of Asian Catholic missions.

  3. Probing the Topology of Density Matrices

    Directory of Open Access Journals (Sweden)

    Charles-Edouard Bardyn

    2018-02-01

    Full Text Available The mixedness of a quantum state is usually seen as an adversary to topological quantization of observables. For example, exact quantization of the charge transported in a so-called Thouless adiabatic pump is lifted at any finite temperature in symmetry-protected topological insulators. Here, we show that certain directly observable many-body correlators preserve the integrity of topological invariants for mixed Gaussian quantum states in one dimension. Our approach relies on the expectation value of the many-body momentum-translation operator and leads to a physical observable—the “ensemble geometric phase” (EGP—which represents a bona fide geometric phase for mixed quantum states, in the thermodynamic limit. In cyclic protocols, the EGP provides a topologically quantized observable that detects encircled spectral singularities (“purity-gap” closing points of density matrices. While we identify the many-body nature of the EGP as a key ingredient, we propose a conceptually simple, interferometric setup to directly measure the latter in experiments with mesoscopic ensembles of ultracold atoms.

  4. Confirmation of the Luminous Blue Variable Status of MWC 930

    Directory of Open Access Journals (Sweden)

    A. S. Miroshnichenko

    2014-01-01

    Full Text Available We present spectroscopic and photometric observations of the emission-line star MWC 930 (V446 Sct during its long-term optical brightening in 2006–2013. Based on our earlier data we suggested that the object has features found in Luminous Blue Variables (LBV, such as a high luminosity (~3 105 L⊙, a low wind terminal velocity (~140 km s−1, and a tendency to show strong brightness variations (~1 mag over 20 years. For the last ~7 years it has been exhibiting a continuous optical and near-IR brightening along with a change of the emission-line spectrum appearance and cooling of the star’s photosphere. We present the object’s V-band light curve, analyze the spectral variations, and compare the observed properties with those of other recognized Galactic LBVs, such as AG Car and HR Car. Overall we conclude the MWC 930 is a bona fide Galactic LBV that is currently in the middle of an S Dor cycle.

  5. Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter

    International Nuclear Information System (INIS)

    Dahabieh, Matthew S.; Ooms, Marcel; Malcolm, Tom; Simon, Viviana; Sadowski, Ivan

    2011-01-01

    Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutations in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.

  6. Time evolution in quantum cosmology

    International Nuclear Information System (INIS)

    Lawrie, Ian D.

    2011-01-01

    A commonly adopted relational account of time evolution in generally covariant systems, and more specifically in quantum cosmology, is argued to be unsatisfactory, insofar as it describes evolution relative to observed readings of a clock that does not exist as a bona fide observable object. A modified strategy is proposed, in which evolution relative to the proper time that elapses along the worldline of a specific observer can be described through the introduction of a ''test clock,'' regarded as internal to, and hence unobservable by, that observer. This strategy is worked out in detail in the case of a homogeneous cosmology, in the context of both a conventional Schroedinger quantization scheme, and a 'polymer' quantization scheme of the kind inspired by loop quantum gravity. Particular attention is given to limitations placed on the observability of time evolution by the requirement that a test clock should contribute only a negligible energy to the Hamiltonian constraint. It is found that suitable compromises are available, in which the clock energy is reasonably small, while Dirac observables are reasonably sharply defined.

  7. AGN outflows as neutrino sources: an observational test

    Science.gov (United States)

    Padovani, P.; Turcati, A.; Resconi, E.

    2018-04-01

    We test the recently proposed idea that outflows associated with Active Galactic Nuclei (AGN) could be neutrino emitters in two complementary ways. First, we cross-correlate a list of 94 "bona fide" AGN outflows with the most complete and updated repository of IceCube neutrinos currently publicly available, assembled by us for this purpose. It turns out that AGN with outflows matched to an IceCube neutrino have outflow and kinetic energy rates, and bolometric powers larger than those of AGN with outflows not matched to neutrinos. Second, we carry out a statistical analysis on a catalogue of [O III] λ5007 line profiles using a sample of 23,264 AGN at z values (˜6 and 18 per cent respectively, pre-trial) for relatively high velocities and luminosities. Our results are consistent with a scenario where AGN outflows are neutrino emitters but at present do not provide a significant signal. This can be tested with better statistics and source stacking. A predominant role of AGN outflows in explaining the IceCube data appears in any case to be ruled out.

  8. Comments on open-quotes interpretations of quantum mechanics, joint measurement of incompatible observables, and counterfactual definitenessclose quotes

    International Nuclear Information System (INIS)

    Stapp, H.P.

    1994-01-01

    Some seeming logical deficiencies in a recent paper are described. The author responds to the arguments of the work by de Muynck, De Baere, and Martens (MDM), who argue it is widely accepted today that some sort of nonlocal effect is needed to resolve the problems raised by the works of Einstein, Podolsky, and Rosen (EPR) and John Bell. In MBM a variety of arguments are set forth that aim to invalidate the existing purported proofs of nonlocality and to provide, moreover, a local solution to the problems uncovered by EPR and Bell. Much of the argumentation in MBM is based on the idea of introducing 'nonideal' measurements, which, according to MBM, allow one to construct joint probability distributions for incompatible observables. The existence of a bona fide joint probability distribution for the incompatible observables occurring in the EPRB experiments would entail that Bell's inequalities can be satisfied, and hence that the mathematical basis for the nonlocal effects would disappear. This relult would apparently allow one to eliminate the need for nonlocal effects by considering experiments of this new kind

  9. Safeguards Culture: lesson learned

    International Nuclear Information System (INIS)

    Frazar, S.; Mladineo, S.V.

    2010-01-01

    After the discovery of Iraq's clandestine nuclear program in 1991, the international community developed new tools for evaluating and demonstrating states' nuclear intentions. The International Atomic Energy Agency (IAEA) developed a more holistic approach toward international safeguards verification to garner more complete information about states' nuclear activities. This approach manifested itself in State Level Evaluations, using information from a variety of sources, including the implementation of integrated safeguards in Member States, to reach a broader conclusion. Those wishing to exhibit strong nonproliferation postures to a more critical international community took steps to demonstrate their nonproliferation 'bona fides'. As these Member States signed and brought into force the Additional Protocol, submitted United Nations Security Council Resolution 1540 reports and strengthened their export control laws, the international community began to consider the emergence of so-called safeguards cultures. Today, safeguards culture can be a useful tool for measuring nonproliferation postures, but so far its impact on the international safeguards regime has been under appreciated. There is no agreed upon definition for safeguards culture nor agreement on how it should be measured.

  10. Circadian remodeling of neuronal circuits involved in rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    María Paz Fernández

    2008-03-01

    Full Text Available Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

  11. Glioblastoma formation from cell population depleted of Prominin1-expressing cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nishide

    2009-08-01

    Full Text Available Prominin1 (Prom1, also known as CD133 in human has been widely used as a marker for cancer stem cells (CSCs, which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM. However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreER(TM, and generated glioma-initiating cells (GICs-LD by overexpressing both the SV40 Large T antigen and an oncogenic H-Ras(L61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

  12. Endothelial Progenitor Cells as Shuttle of Anticancer Agents.

    Science.gov (United States)

    Laurenzana, Anna; Margheri, Francesca; Chillà, Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario

    2016-10-01

    Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining cell-based therapy with gene therapy or with nanomedicine. The first approach is based on the possibility of engineering EPCs to express different transgenes, and the second is based on the capacity of EPCs to take up nanomaterials. Here we review the most important progress covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularization and metastasis, and preclinical data about their use in cell-based tumor therapy, considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in terms of plasmonic-dependent thermoablation and molecular imaging.

  13. Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

    Science.gov (United States)

    Uthe, Henriette; Vanselow, Jens T; Schlosser, Andreas

    2017-02-27

    Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15 N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis.

  14. Tissue-specific RNA expression marks distant-acting developmental enhancers.

    Directory of Open Access Journals (Sweden)

    Han Wu

    2014-09-01

    Full Text Available Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.

  15. New N-Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Brian; Cobb, Ryan E.; DeSieno, Matthew A.; Zhao, Huimin; Nair, Satish K. (UIUC)

    2015-10-15

    The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 {angstrom} resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098.

  16. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

    Science.gov (United States)

    Ortega-Molina, Ana; Boss, Isaac W; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A; Gascoyne, Randy D; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M; Wendel, Hans-Guido

    2015-10-01

    The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

  17. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Shijun, Yue

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer causing high mortality rates world-wide. Delineating the molecular mechanisms leading to CRC development and progression, including the role of microRNAs (miRNAs), are currently being unravelled at a rapid rate. Here, we report frequent down...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....... mice. Global gene expression analysis in CRC cells over-expressing miR-320c, combined with in silico prediction identified 84 clinically-relevant potential gene targets for miR-320 in CRC. Using a series of biochemical assays and functional validation, SOX4, FOXM1, and FOXQ1 were validated as novel...... gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...

  18. The Number of Neutrinos and the Z Line Shape

    CERN Document Server

    Blondel, Alain

    2016-01-01

    The Standard Theory can fit any number of fermion families, as long as the number of leptons and quark families are the same. At the time of the conception of LEP, the number of such families was unknown, and it was feared that the Z resonance would be washed out by decaying into so many families of neutrinos! It took only a few weeks in the fall of 1989 to determine that the number is three. The next six years (from 1990 to 1995) were largely devoted to the accurate determination of the Z line shape, with a precision that outperformed the most optimistic expectations by a factor of 10. The tale of these measurements is a bona fide mystery novel, the precession of electrons being strangely perturbed by natural phenomena, such as tides, rain, hydroelectric power, fast trains, not to mention vertical electrostatic separators. The number hidden in the loops of this treasure hunt was 179, the first estimate of the mass of the top quark; then, once that was found, where predicted, the next number was close to zero...

  19. A HST/WFC3 Search for Substellar Companions in the Orion Nebula Cluster

    Science.gov (United States)

    Strampelli, Giovanni Maria; Aguilar, Jonathan; Aparicio, Antonio; Piotto, Giampaolo; Pueyo, Laurent; Robberto, Massimo

    2018-01-01

    We present new results relative to the population of substellar binaries in the Orion Nebula Cluster. We reprocessed HST/WFC3 data using an analysis technique developed to detect close companions in the wings of the stellar PSFs, based on the PyKLIP implementation of the KLIP PSF subtraction algorithm. Starting from a sample of ~1200 stars selected over the range J=11-15 mag, we were able to uncover ~80 candidate companions in the magnitude range J=16-23 mag. We use the presence of the 1.4 micron H2O absorption feature in the companion photosphere to discriminate 32 bona-fide substellar candidates from a population of reddened background objects. We derive an estimate of the companion mass assuming a 2Myr isochrone and the reddening of their primary. With 8 stellar companions, 19 brown dwarfs and 5 planetary mass objects, our study provide us with an unbiased sample of companions at the low-mass end of the IMF, probing the transition from binary to planetary systems.

  20. Human ecology, statistical analysis, and the logic of valid correlations DOI:10.5007/2175-7984.2011v10n19p57

    Directory of Open Access Journals (Sweden)

    Fernando Dias de Avila-Pires

    2011-10-01

    Full Text Available Human health ecology is an expanding field of interdisciplinary research, combining knowledge drawn from distinct areas. Human ecology is essentially interdisciplinary. The search for the origin and distribution of diseases demands a combination of theories and methods from both natural and social sciences. There is a limit to the replication and repetition of observations and experiments in scientific research: hence the importance of statistics. As a tool, statistical analyses are usually based upon selected samples and samples must be representative of the whole. Irrelevant, erroneous, false, and misleading, information based on flawed interpretation of statistics has always plagued scientific publications. In some cases, not only professional ethics has been breached, but risks to well-being and health has been fostered. In this article I will not deal with fraud, but with bona fide errors of judgment and the use of erroneous statistical concepts. My objective in this article is to caution against a common practice adopted by researchers while using qualitative as well as quantitative methods of analysis to establish demographic categories.

  1. Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.

    Science.gov (United States)

    Rabadán, M Angeles; Herrera, Antonio; Fanlo, Lucia; Usieto, Susana; Carmona-Fontaine, Carlos; Barriga, Elias H; Mayor, Roberto; Pons, Sebastián; Martí, Elisa

    2016-06-15

    Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination. © 2016. Published by The Company of Biologists Ltd.

  2. D-branes in a non-critical superstrings and minimal super Yang-Mills in various dimensions

    International Nuclear Information System (INIS)

    Ashok, S.K.; Murthy, S.; Troost, J.

    2005-11-01

    We construct and analyze D-branes in superstring theories in even dimensions less than ten. The backgrounds under study are supersymmetric R d-1,1 x SL(2,R) k /U(1) where the level of the supercoset is tuned such as to provide bona fide string theory backgrounds. We provide exact boundary states for D-branes that are localized at the tip of the cigar SL(2,R)/U(1) supercoset conformal field theory. We analyze the spectra of open strings on these D-branes and show explicitly that they are consistent with supersymmetry in d = 2,4 and 6. The low energy theory on the world-volume of the D-brane in each case is pure Yang-Mills theory with minimal supersymmetry. In the case with four macroscopic flat directions d = 4, we realize an N = 1 super Yang-Mills theory, and we interpret the backreaction for the dilaton as the running of the gauge coupling, and study the relation between R-symmetry breaking in the gauge theory and the backreaction on the Rr axion. (author)

  3. Evolution and phylogeny of B lymphocytes

    Directory of Open Access Journals (Sweden)

    Fabiola Claudio-Piedras

    2016-05-01

    Full Text Available B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  4. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

    Science.gov (United States)

    Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

    2018-01-29

    Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

  5. New Markov Model Approaches to Deciphering Microbial Genome Function and Evolution: Comparative Genomics of Laterally Transferred Genes

    Energy Technology Data Exchange (ETDEWEB)

    Borodovsky, M.

    2013-04-11

    Algorithmic methods for gene prediction have been developed and successfully applied to many different prokaryotic genome sequences. As the set of genes in a particular genome is not homogeneous with respect to DNA sequence composition features, the GeneMark.hmm program utilizes two Markov models representing distinct classes of protein coding genes denoted "typical" and "atypical". Atypical genes are those whose DNA features deviate significantly from those classified as typical and they represent approximately 10% of any given genome. In addition to the inherent interest of more accurately predicting genes, the atypical status of these genes may also reflect their separate evolutionary ancestry from other genes in that genome. We hypothesize that atypical genes are largely comprised of those genes that have been relatively recently acquired through lateral gene transfer (LGT). If so, what fraction of atypical genes are such bona fide LGTs? We have made atypical gene predictions for all fully completed prokaryotic genomes; we have been able to compare these results to other "surrogate" methods of LGT prediction.

  6. Discovery of novel small molecule activators of β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Folkert Verkaar

    Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

  7. INTRIGOSS: A new Library of High Resolution Synthetic Spectra

    Science.gov (United States)

    Franchini, Mariagrazia; Morossi, Carlo; Di Marcancantonio, Paolo; Chavez, Miguel; GES-Builders

    2018-01-01

    INTRIGOSS (INaf Trieste Grid Of Synthetic Spectra) is a new High Resolution (HiRes) synthetic spectral library designed for studying F, G, and K stars. The library is based on atmosphere models computed with specified individual element abundances via ATLAS12 code. Normalized SPectra (NSP) and surface Flux SPectra (FSP), in the 4800-5400 Å wavelength range, were computed by means of the SPECTRUM code. The synthetic spectra are computed with an atomic and bi-atomic molecular line list including "bona fide" Predicted Lines (PLs) built by tuning loggf to reproduce very high SNR Solar spectrum and the UVES-U580 spectra of five cool giants extracted from the Gaia-ESO survey (GES). The astrophysical gf-values were then assessed by using more than 2000 stars with homogenous and accurate atmosphere parameters and detailed chemical composition from GES. The validity and greater accuracy of INTRIGOSS NSPs and FSPs with respect to other available spectral libraries is discussed. INTRIGOSS will be available on the web and will be a valuable tool for both stellar atmospheric parameters and stellar population studies.

  8. Saving money on rig refurbishments through foreign trade zones or duty-drawback

    International Nuclear Information System (INIS)

    Ward, R.J. Jr.

    1997-01-01

    The recent boom in day rates for rigs capable of drilling in deep water and harsh environments has created a frenzy of rig refurbishment activity in shipyards located in US Gulf states. In most instances, the destination for the rigs upon completion is the US Outer Continental Shelf (USOCS) in the Gulf of Mexico. The problem faced by contractors/operators planning to use US shipyards is that this circumstance has caused difficulty in shielding rigs and their foreign-sourced components from US Customs duties. Under US Customs law, a bona fide exportation requires severance from US commerce and joining to the commerce of some foreign country or, in the case of a vessel supply, a qualifying international voyage. The USOCS does not qualify as an exportation, nor do movements to drilling sites located on it qualify as an international voyage. Described here are two possible solutions to this economic dilemma and an example of how the foreign trade zone solution was applied by Global marine in its plans for upgrading some of its semisubmersible drilling rigs for deepwater USOCS work

  9. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels.

    Science.gov (United States)

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-11-27

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

  10. Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin.

    Science.gov (United States)

    Gilbert, Andrea R; Zaky, Wafik; Gokden, Murat; Fuller, Christine E; Ocal, Eylem; Leeds, Norman E; Fuller, Gregory N

    2018-01-01

    Diffuse midline glioma, H3-K27M mutant (DMG-K27M) is a newly described, molecularly distinct infiltrative glioma that almost exclusively arises in midline CNS structures, including the brain stem, especially the pons, as well as the thalamus and spinal cord with rare examples seen in the cerebellum, third ventricle, and hypothalamus. To our knowledge, only 1 case of a molecularly confirmed DMG-K27M arising in the pineal region has been previously reported. We present the second occurrence of a tissue-confirmed DMG-K27M of the pineal region, which, to our knowledge, is the first case reported in a child and the first case with documented preoperative MRI. This case, in addition to a prior report described in an adult, defines the lower end of a broad age range of DMG-K27M onset (12-65 years) and establishes the pineal gland as a bona fide site of origin for this newly codified midline glioma. © 2017 S. Karger AG, Basel.

  11. Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Daniel Lepe-Soltero

    2017-12-01

    Full Text Available The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana, ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

  12. Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana.

    Science.gov (United States)

    Lepe-Soltero, Daniel; Armenta-Medina, Alma; Xiang, Daoquan; Datla, Raju; Gillmor, C Stewart; Abreu-Goodger, Cei

    2017-12-01

    The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana , ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

  13. Combining the IADPSG criteria with the WHO diagnostic criteria for ...

    African Journals Online (AJOL)

    Macrosomia or at least one adverse outcome were more likely in GDM patients who met the diagnostic criteria by both the IADPSG and WHO criteria (P = 0.001). Conclusion: A diagnosis of GDM that meets both the WHO and IADPSG criteria provides stronger prediction for adverse pregnancy outcome than a diagnosis that ...

  14. Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome.

    Science.gov (United States)

    Harden, R Norman; Bruehl, Stephen; Perez, Roberto S G M; Birklein, Frank; Marinus, Johan; Maihofner, Christian; Lubenow, Timothy; Buvanendran, Asokumar; Mackey, Sean; Graciosa, Joseph; Mogilevski, Mila; Ramsden, Christopher; Chont, Melissa; Vatine, Jean-Jacques

    2010-08-01

    Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the "Budapest Criteria") regarding diagnostic accuracy. Structured evaluations of CRPS-related signs and symptoms were conducted in 113 CRPS-I and 47 non-CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. NWTS program criteria for mined geologic disposal of nuclear wasite: site performance criteria

    International Nuclear Information System (INIS)

    1981-02-01

    This report states ten criteria governing the suitability of sites for mined geologic disposal of high-level radioactive waste. The Department of Energy will use these criteria in its search for sites and will reevaluate their use when the Nuclear Regulatory Commission issues radioactive waste repository rules. These criteria encompass site geometry, geohydrology, geochemistry, geologic characteristics, tectonic environment, human intrusion, surface characteristics, environment, and potential socioeconomic impacts. The contents of this document include background discussion, site performance criteria, and appendices. The background section describes the waste disposal system, the application of the site criteria, and applicable criteria from NWTS-33(1) - Program Objectives, Functional Requirements and System Performance Criteria. Appendix A, entitled Comparison with Other Siting Criteria compares the NWTS criteria with those recommended by other agencies. Appendix B contains DOE responses to public comments received on the January 1980 draft of this document. Appendix C is a glossary

  16. A CENSUS OF ROTATION AND VARIABILITY IN L1495: A UNIFORM ANALYSIS OF TRANS-ATLANTIC EXOPLANET SURVEY LIGHT CURVES FOR PRE-MAIN-SEQUENCE STARS IN TAURUS

    International Nuclear Information System (INIS)

    Xiao Hongyu; Covey, Kevin R.; Lloyd, James P.; Rebull, Luisa; Charbonneau, David; Mandushev, Georgi; O'Donovan, Francis; Slesnick, Catherine

    2012-01-01

    We analyze light curves obtained by the Trans-atlantic Exoplanet Survey (TrES) for a field centered on the L1495 dark cloud in Taurus. The Spitzer Taurus Legacy Survey catalog identifies 179 bona fide Taurus members within the TrES field; 48 of the known Taurus members are detected by TrES, as well as 26 candidate members identified by the Spitzer Legacy team. We quantify the variability of each star in our sample using the ratio of the standard deviation of the original light curve (σ orig. ) to the standard deviation of a light curve that has been smoothed by 9 or 1001 epochs (σ 9 and σ 1001 , respectively). Known Taurus members typically demonstrate (σ orig. /σ 9 ) orig. /σ 1001 ) orig. /σ 9 ) ∼ 3.0 and (σ orig. /σ 1001 ) ∼ 10, as expected for light curves dominated by unstructured white noise. Of the 74 Taurus members/candidates with TrES light curves, we detect significant variability in 49 sources. Adapting a quantitative metric originally developed to assess the reliability of transit detections, we measure the amount of red and white noise in each light curve and identify 18 known or candidate Taurus members with highly significant period measurements. These appear to be the first periods measured for four of these sources (HD 282276, CX Tau, FP Tau, TrES J042423+265008), and in two other cases, the first non-aliased periods (LkCa 21 and DK Tau AB). For the remainder, the TrES measurements typically agree very well (δP < 1%) with previously reported values. Including periods measured at lower confidence for 15 additional sources, we report periods for 11 objects where no previous periods were found, including 8 confirmed Taurus members. We also identify 10 of the 26 candidate Taurus members that demonstrate variability levels consistent with being bona fide T Tauri stars. A Kolomgorov-Smirnov (K-S) test confirms that these new periods confirm the distinction between the rotation period distributions of stars with and without circumstellar

  17. Plutonium storage criteria

    Energy Technology Data Exchange (ETDEWEB)

    Chung, D. [Scientech, Inc., Germantown, MD (United States); Ascanio, X. [Dept. of Energy, Germantown, MD (United States)

    1996-05-01

    The Department of Energy has issued a technical standard for long-term (>50 years) storage and will soon issue a criteria document for interim (<20 years) storage of plutonium materials. The long-term technical standard, {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides,{close_quotes} addresses the requirements for storing metals and oxides with greater than 50 wt % plutonium. It calls for a standardized package that meets both off-site transportation requirements, as well as remote handling requirements from future storage facilities. The interim criteria document, {open_quotes}Criteria for Interim Safe Storage of Plutonium-Bearing Solid Materials{close_quotes}, addresses requirements for storing materials with less than 50 wt% plutonium. The interim criteria document assumes the materials will be stored on existing sites, and existing facilities and equipment will be used for repackaging to improve the margin of safety.

  18. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte.

    Science.gov (United States)

    Hengstler, Jan G; Brulport, Marc; Schormann, Wiebke; Bauer, Alexander; Hermes, Matthias; Nussler, Andreas K; Fandrich, Fred; Ruhnke, Maren; Ungefroren, Hendrik; Griffin, Louise; Bockamp, Ernesto; Oesch, Franz; von Mach, Marc-Alexander

    2005-06-01

    Since 1999, numerous articles have reported the generation of hepatocytes from different types of extrahepatic stem or precursor cells. This opens exciting new possibilities for pharmacology and toxicology, as well as for cell therapy. Hepatocyte marker expression, including albumin, cytokeratin 18, c-met, alpha-fetoprotein and cytochrome P450 3A4 and -2B6, has been observed after transplantation of different types of human stem cells into the liver of laboratory animals or in vitro after incubation with cytokines. These intriguing observations have prompted scientists to classify stem cell-derived cell populations as hepatocytes. However, this conclusion may be premature. It has been shown that factors of the liver microenvironment can induce expression of a limited number of hepatocyte marker genes in nonhepatic cell types. To conclude on the grounds of a limited number of markers that these cells are true hepatocytes is not indicated. In this case one should carefully evaluate crucial hepatocyte-defining enzymatic properties. The present article: i) reviews studies describing the fate of extrahepatic human stem and precursor cells in livers of laboratory animals, including the possibility of cell fusion; and ii) critically discusses the phenotype of stem cells after application of various differentiation protocols aimed at generating human hepatocytes. In addition, the necessary criteria needed for defining a true hepatocyte are suggested. Establishing the necessary properties for stem cell-derived hepatocytes is timely and reasonable, and thus avoids further misleading semantic confusion. Finally, it is essential to understand that the definition of a bona fide hepatocyte should not be limited to qualitative assays, such as reverse transcriptase polymerase chain reaction and immunohistochemistry, but has to include a quantitative analysis of enzymatic activities, which allows direct comparison with primary hepatocytes. Although the stem cell

  19. Combining Results from Distinct MicroRNA Target Prediction Tools Enhances the Performance of Analyses

    Directory of Open Access Journals (Sweden)

    Arthur C. Oliveira

    2017-05-01

    Full Text Available Target prediction is generally the first step toward recognition of bona fide microRNA (miRNA-target interactions in living cells. Several target prediction tools are now available, which use distinct criteria and stringency to provide the best set of candidate targets for a single miRNA or a subset of miRNAs. However, there are many false-negative predictions, and consensus about the optimum strategy to select and use the output information provided by the target prediction tools is lacking. We compared the performance of four tools cited in literature—TargetScan (TS, miRanda-mirSVR (MR, Pita, and RNA22 (R22, and we determined the most effective approach for analyzing target prediction data (individual, union, or intersection. For this purpose, we calculated the sensitivity, specificity, precision, and correlation of these approaches using 10 miRNAs (miR-1-3p, miR-17-5p, miR-21-5p, miR-24-3p, miR-29a-3p, miR-34a-5p, miR-124-3p, miR-125b-5p, miR-145-5p, and miR-155-5p and 1,400 genes (700 validated and 700 non-validated as targets of these miRNAs. The four tools provided a subset of high-quality predictions and returned few false-positive predictions; however, they could not identify several known true targets. We demonstrate that union of TS/MR and TS/MR/R22 enhanced the quality of in silico prediction analysis of miRNA targets. We conclude that the union rather than the intersection of the aforementioned tools is the best strategy for maximizing performance while minimizing the loss of time and resources in subsequent in vivo and in vitro experiments for functional validation of miRNA-target interactions.

  20. Trace Amine-Associated Receptor 1 – Family Archetype or Iconoclast?

    Science.gov (United States)

    Grandy, David K.

    2009-01-01

    Interest has recently been rekindled in receptors that are activated by low molecular weight, non-catecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the ‘trace amines’ (TAs) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of two publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers as TA1 (Borowsky et al., 2001) and TAR1 (Bunzow et al., 2001). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines recombinant rodent and human TA receptors dose-dependently couple to the stimulation of cAMP production. Structure-activity profiling based on this functional response has revealed that in addition to the TAs, other biologically active compounds containing a 2 carbon aliphatic side chain linking an amino group to at least one benzene ring are potent and efficacious TA receptor agonists with amphetamine, methamphetamine, 3-iodothyronamine, thyronamine, and dopamine among the most notable. Almost 100 years after the search for TA receptors began numerous TA1/TAR1-related sequences, now called Trace Amine-Associated Receptors (TAARs), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TA receptor a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCRs. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast. PMID:17888514

  1. Trace amine-associated receptor 1-Family archetype or iconoclast?

    Science.gov (United States)

    Grandy, David K

    2007-12-01

    Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the "trace amines" (TA) beta-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of 2 publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers Borowsky et al. as TA1 and Bunzow et al. as TA receptor 1 (TAR1). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines, recombinant rodent and human TAR dose-dependently couple to the stimulation of adenosine 3',5'-monophosphate (cAMP) production. Structure-activity profiling based on this functional response has revealed that in addition to the TA, other biologically active compounds containing a 2-carbon aliphatic side chain linking an amino group to at least 1 benzene ring are potent and efficacious TA receptor agonists with amphetamine (AMPH), methamphetamine, 3-iodothyronamine, thyronamine, and dopamine (DA) among the most notable. Almost 100 years after the search for TAR began, numerous TA1/TAR1-related sequences, now called TA-associated receptors (TAAR), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TAR, a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCR. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

  2. The MMPI-2/MMPI-2-RF Symptom Validity Scale (FBS/FBS-r) is not a measure of 'litigation response syndrome': commentary on Nichols and Gass (2015).

    Science.gov (United States)

    Larrabee, Glenn J; Bianchini, Kevin J; Boone, Kyle B; Rohling, Martin L

    2017-11-01

    To address (1) Whether there is empirical evidence for the contention of Nichols and Gass that the MMPI-2/MMPI-2-RF FBS/FBS-r Symptom Validity Scale is a measure of Litigation Response Syndrome (LRS), representing a credible set of responses and reactions of claimants to the experience of being in litigation, rather than a measure of non-credible symptom report, as the scale is typically used; and (2) to address their stated concerns about the validity of FBS/FBS-r meta-analytic results, and the risk of false positive elevations in persons with bona-fide medical conditions. Review of published literature on the FBS/FBS-r, focusing in particular on associations between scores on this symptom validity test and scores on performance validity tests (PVTs), and FBS/FBS-r score elevations in patients with genuine neurologic, psychiatric and medical problems. (1) several investigations show significant associations between FBS/FBS-r scores and PVTs measuring non-credible performance; (2) litigants who pass PVTs do not produce significant elevations on FBS/FBS-r; (3) non-litigating medical patients (bariatric surgery candidates, persons with sleep disorders, and patients with severe traumatic brain injury) who have multiple physical, emotional and cognitive symptoms do not produce significant elevations on FBS/FBS-r. Two meta-analytic studies show large effect sizes for FBS/FBS-r of similar magnitude. FBS/FBS-r measures non-credible symptom report rather than legitimate experience of litigation stress. Importantly, the absence of significant FBS/FBS-r elevations in litigants who pass PVTs demonstrating credible performance, directly contradicts the contention of Nichols and Gass that the scale measures LRS. These data, meta-analytic publications, and recent test use surveys support the admissibility of FBS/FBS-r under both Daubert and the older Frye criteria.

  3. Repository operational criteria analysis

    International Nuclear Information System (INIS)

    Hageman, J.P.; Chowdhury, A.H.

    1992-08-01

    The objective of the ''Repository Operational Criteria (ROC) Feasibility Studies'' (or ROC task) was to conduct comprehensive and integrated analyses of repository design, construction, and operations criteria in 10 CFR Part 60 regulations, considering the interfaces and impacts of any potential changes to those regulations. The study addresses regulatory criteria related to the preclosure aspects of the geologic repository. The study task developed regulatory concepts or potential repository operational criteria (PROC) based on analysis of a repository's safety functions and other regulations for similar facilities. These regulatory concepts or PROC were used as a basis to assess the sufficiency and adequacy of the current criteria in 10 CFR Part 60. Where the regulatory concepts were same as current operational criteria, these criteria were referenced. The operations criteria referenced or the PROC developed are given in this report. Detailed analyses used to develop the regulatory concepts and any necessary PROC for those regulations that may require a minor change are also presented. The results of the ROC task showed a need for further analysis and possible major rule change related to the design bases of a geologic repository operations area, siting, and radiological emergency planning

  4. CpG island mapping by epigenome prediction.

    Directory of Open Access Journals (Sweden)

    Christoph Bock

    2007-06-01

    Full Text Available CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1 reliance on arbitrary threshold parameters that bear little biological justification, (2 failure to account for widespread heterogeneity among CpG islands, and (3 apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to

  5. CpG island mapping by epigenome prediction.

    Science.gov (United States)

    Bock, Christoph; Walter, Jörn; Paulsen, Martina; Lengauer, Thomas

    2007-06-01

    CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1) reliance on arbitrary threshold parameters that bear little biological justification, (2) failure to account for widespread heterogeneity among CpG islands, and (3) apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to their characteristic

  6. Наблюдения върху лексикалната вариативност при библейските цитати в Йоан-Екзарховия превод на De Fide Orthodoxa

    Directory of Open Access Journals (Sweden)

    Татяна [Tatiana] Илиева [Ilieva

    2016-10-01

    Full Text Available Observations on the theological terminology in the biblical quotations in John the Exarch’s translation of De Fide Orthodoxa The paper presented here aims at comparing the theological terms as used, on the one hand, in the biblical quotations in John the Exarch’s translation of De fide orthodoxa and, on the other, in the Old Bulgarian (Grigirovich Prophetologion, Codex Marianus, Codex Zographiensis, Sinai Psalter, Enina Apostolos as well as in some Middle Bulgarian (Bologna Psalter, Karpinski Apostolos, Ohridski Apostolos Old Russian (Mstislav Gospels, Yurievski Gospels, Pogodinov Psalter, Chudov Psalter, Tolstoev Apostolos, Hristinopol Apostolos and Old Serbia (Shishatovatski Apostolos, Matich Apostolos monuments. Also taken in consideration are the respective parts in certain theological writings associated with the Preslav Literary Centre.   Uwagi o terminologii teologicznej w cytatach z Biblii w przekładzie De Fide Orthodoxa Jana Egzarchy Celem artykułu jest porównanie terminologii teologicznej w cytatach biblijnych w przekładzie De fide othodoxa Jana Egzarchy, w starobułgarskich zabytkach językowych (Lekcjonarz Grigorowizca, Kodeks Mariański, Kodeks Zografski, Psałterz Synajski, Apostoł Eniński, w wybranych zabytkach średniobułgarskich (Psałterz Boloński, Apostoł Karpinski, Apostoł Ohrydzki, staroruskich (Ewangeliarz Mścisława, Ewangeliarz Jurjewski, Psałterz Pogodina, Psałterz Chłudowa, Apostoł Tołstoja, Apostoł Krystynopolski i staroserbskich (Apostoł Sziszatowacki, Apostoł Maticia. Analizie poddano także poszczególne części wybranych pism teologicznych powstałych w presławskiej szkole piśmienniczej.

  7. Criteria CSR

    OpenAIRE

    Vovk, V.; Zateyshikova, O.

    2014-01-01

    In the article the theoretical aspects regarding criteria for assessing CSR proposed by A. Carroll, including: economic, legal, ethical, philanthropic. Based on this, it is proposed to characterize these criteria with respect to the interested parties (stakeholders), including: investors, shareholders suppliers, customers, employees, society and the state. This will make a qualitative assessment of the presence and depth using social responsibility in the company, as well as determine the ext...

  8. Scientific progress and the prospects for culture-bound syndromes.

    Science.gov (United States)

    Blease, Charlotte

    2010-12-01

    This paper aims to show that the classification by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM) of a distinct listing of disorders known as Culture-Bound Syndromes (CBS) is misguided. I argue that the list of CBS (in Appendix I of the manual) comprises either (a) genuine disorders that should be included within the main body of the DSM; or (b) ersatz-disorders that serve a practical role for psychiatrists dealing with patients from certain cultures but will one day be eliminated or assimilated by bona fide DSM classifications. In support of these views I draw on claims from two key themes in the philosophy of science: (1) the claim that all folk (that is, non-scientific) explanations for phenomena are thoroughly theoretical and therefore fallible; and (2) the occurrence of theoretical elimination in the history of science. I contend that any ersatz-disorders located in the DSM that are judged to be radically false do not differ in kind from eliminated theories in the history of pre-science. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Fourier transform inequalities for phylogenetic trees.

    Science.gov (United States)

    Matsen, Frederick A

    2009-01-01

    Phylogenetic invariants are not the only constraints on site-pattern frequency vectors for phylogenetic trees. A mutation matrix, by its definition, is the exponential of a matrix with non-negative off-diagonal entries; this positivity requirement implies non-trivial constraints on the site-pattern frequency vectors. We call these additional constraints "edge-parameter inequalities". In this paper, we first motivate the edge-parameter inequalities by considering a pathological site-pattern frequency vector corresponding to a quartet tree with a negative internal edge. This site-pattern frequency vector nevertheless satisfies all of the constraints described up to now in the literature. We next describe two complete sets of edge-parameter inequalities for the group-based models; these constraints are square-free monomial inequalities in the Fourier transformed coordinates. These inequalities, along with the phylogenetic invariants, form a complete description of the set of site-pattern frequency vectors corresponding to bona fide trees. Said in mathematical language, this paper explicitly presents two finite lists of inequalities in Fourier coordinates of the form "monomial < or = 1", each list characterizing the phylogenetically relevant semialgebraic subsets of the phylogenetic varieties.

  10. In silico ionomics segregates parasitic from free-living eukaryotes.

    Science.gov (United States)

    Greganova, Eva; Steinmann, Michael; Mäser, Pascal; Fankhauser, Niklaus

    2013-01-01

    Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

  11. Validation of Kepler's multiple planet candidates. II. Refined statistical framework and descriptions of systems of special interest

    International Nuclear Information System (INIS)

    Lissauer, Jack J.; Bryson, Stephen T.; Rowe, Jason F.; Jontof-Hutter, Daniel; Borucki, William J.; Marcy, Geoffrey W.; Kolbl, Rea; Agol, Eric; Carter, Joshua A.; Torres, Guillermo; Ford, Eric B.; Gilliland, Ronald L.; Star, Kimberly M.; Steffen, Jason H.

    2014-01-01

    We extend the statistical analysis performed by Lissauer et al. in 2012, which demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) represents true transiting planets, and we develop therefrom a procedure to validate large numbers of planet candidates in multis as bona fide exoplanets. We show that this statistical framework correctly estimates the abundance of false positives already identified around Kepler targets with multiple sets of transit-like signatures based on their abundance around targets with single sets of transit-like signatures. We estimate the number of multis that represent split systems of one or more planets orbiting each component of a binary star system. We use the high reliability rate for multis to validate more than one dozen particularly interesting multi-planet systems herein. Hundreds of additional multi-planet systems are validated in a companion paper by Rowe et al. We note that few very short period (P < 1.6 days) planets orbit within multiple transiting planet systems and discuss possible reasons for their absence. There also appears to be a shortage of planets with periods exceeding a few months in multis.

  12. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: implications for replication and genome packaging.

    Science.gov (United States)

    Chaturvedi, Sonali; Rao, A L N

    2014-09-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein-protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Latin American social medicine across borders: South-South cooperation and the making of health solidarity.

    Science.gov (United States)

    Birn, Anne-Emanuelle; Muntaner, Carles

    2018-02-22

    Latin American social medicine efforts are typically understood as national endeavours, involving health workers, policymakers, academics, social movements, unions, and left-wing political parties, among other domestic actors. But Latin America's social medicine trajectory has also encompassed considerable between-country solidarity, building on early twentieth century interchanges among a range of players who shared approaches for improving living and working conditions and instituting protective social policies. Since the 1960s, Cuba's country-to-country solidarity has stood out, comprising medic exchanges, training, and other forms of support for the health and social struggles of oppressed peoples throughout Latin America and around the world, recently via Misión Barrio Adentro in Venezuela. These efforts strive for social justice-oriented health cooperation based on horizontal power relations, shared political values, a commitment to social and economic redistribution, bona fide equity, and an understanding of the societal determination of health that includes, but goes well beyond, public health and medical care. With Latin America's left-wing surge now receding, this article traces the provenance, dynamics, impact, challenges, and legacy of health solidarity across Latin American borders and its prospects for continuity.

  14. Not so sweet refrain: sugar-sweetened beverage taxes, industry opposition and harnessing the lessons learned from tobacco control legal challenges.

    Science.gov (United States)

    George, Anita

    2018-05-21

    As a growing number of countries implement, or announce plans to introduce, a sugar-sweetened beverage (SSB) tax, this paper explores the public health rationale for such a tax and provides an overview of the international normative and policy instruments supporting the introduction of fiscal measures on sugary drinks. After examining parallels between the legal arguments raised by the food and beverage industry in opposition to SSB taxes and those raised by the tobacco industry in response to tobacco control measures, this paper draws four key lessons that will assist countries to design effective and robust SSB tax measures and counter food and beverage industry opposition: regulatory distinctions in tax coverage should be based on bona fide, evidence-based reasoning; evidence-based measures need to be tailored to a country's public health objectives as part of a comprehensive strategy to address unhealthy diet consumption; procedural requirements and due process should be observed in the drafting and implementation of the measure; and regulatory space exists within domestic constitutions, laws and international trade and investment agreements recognising the sovereign right of states to regulate in the interests of public health.

  15. A novel small molecule methyltransferase is important for virulence in Candida albicans.

    Science.gov (United States)

    Lissina, Elena; Weiss, David; Young, Brian; Rella, Antonella; Cheung-Ong, Kahlin; Del Poeta, Maurizio; Clarke, Steven G; Giaever, Guri; Nislow, Corey

    2013-12-20

    Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates, and regulating intra- and interspecies interactions. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro and interacts genetically with genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.

  16. Regulation of mIκBNS stability through PEST-mediated degradation by proteasome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Koog Chan; Jeong, Jiyeong; Kim, Keun Il, E-mail: kikim@sookmyung.ac.kr

    2014-01-24

    Highlights: • mIκBNS is degraded rapidly by proteasome without ubiquitylation. • N-terminal PEST sequence is responsible for the unstable nature of mIκBNS. • PEST sequence is not critical for nuclear localization of mIκBNS. • There is single bona fide NLS at the C-terminus of mIκBNS. - Abstract: Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be removed rapidly from cells to respond properly to the next incoming signal. A nuclear IκB protein called IκBNS is known to inhibit a subset of NF-κB target genes upon its expression by NF-κB activation. Here, we show a mechanism to control the stability of mIκBNS which might be important for cells to prepare the next round signaling. We found that mIκBNS is a short-lived protein of which the stability is controlled by proteasome, independent of ubiquitylation process. We identified that the N-terminal PEST sequence in mIκBNS was critical for the regulation of stability.

  17. Oxygen isotopic anomalies in Allende inclusion HAL

    International Nuclear Information System (INIS)

    Lee, T.; Mayeda, T.K.; Clayton, R.N.

    1980-01-01

    The oxygen isotopic composition has been measured on the constituent phases of Allende inclusion HAL, which has unusual mineralogical, chemical, and calcium isotopic compositions. The oxygen in HAL is heterogeneous, with the rim showing more ''normal'' composition and the hibonite core showing large deviation from both the terrestrial material and the usual inclusions. The observed pattern indicates that HAL is a bona fide and more devious member of the rare ''FUN'' family, whose isotopic composition is characterized by correlated nuclear effects and extreme mass fractionation. The data imply that HAL has suffered a large oxygen mass fractionation of 25% 0 per mass unit, followed by exchange with oxygen in a second reservoir. The present experiment supports the identification of two distinct reservoirs from which all refractory inclusions in carbonaceous meteorites derived their oxygen. The required fractionation process seems to operate according to the volatility of various elements and could have been caused by evaporation during a heating event. Nuclear anomalies can be produced in the same heating event if the progenitors of the refractory inclusions were macroscopic aggregates of tiny pre-solar interstellar dust grains and if these grains were destroyed differentially during the evaporation

  18. Validation of Kepler's multiple planet candidates. II. Refined statistical framework and descriptions of systems of special interest

    Energy Technology Data Exchange (ETDEWEB)

    Lissauer, Jack J.; Bryson, Stephen T.; Rowe, Jason F.; Jontof-Hutter, Daniel; Borucki, William J. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Marcy, Geoffrey W.; Kolbl, Rea [Astronomy Department, University of California, Berkeley, CA 94720 (United States); Agol, Eric [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Carter, Joshua A.; Torres, Guillermo [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Ford, Eric B.; Gilliland, Ronald L.; Star, Kimberly M. [Department of Astronomy and Astrophysics, 525 Davey Laboratory, The Pennsylvania State University, University Park, PA 16802 (United States); Steffen, Jason H., E-mail: Jack.Lissauer@nasa.gov [Department of Physics and Astronomy/CIERA, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (United States)

    2014-03-20

    We extend the statistical analysis performed by Lissauer et al. in 2012, which demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) represents true transiting planets, and we develop therefrom a procedure to validate large numbers of planet candidates in multis as bona fide exoplanets. We show that this statistical framework correctly estimates the abundance of false positives already identified around Kepler targets with multiple sets of transit-like signatures based on their abundance around targets with single sets of transit-like signatures. We estimate the number of multis that represent split systems of one or more planets orbiting each component of a binary star system. We use the high reliability rate for multis to validate more than one dozen particularly interesting multi-planet systems herein. Hundreds of additional multi-planet systems are validated in a companion paper by Rowe et al. We note that few very short period (P < 1.6 days) planets orbit within multiple transiting planet systems and discuss possible reasons for their absence. There also appears to be a shortage of planets with periods exceeding a few months in multis.

  19. iPTF14yb: The First Discovery of a Gamma-Ray Burst Afterglow Independent of a High-Energy Trigger

    Science.gov (United States)

    Cenko, S. Bradley; Urban, Alex L.; Perley, Daniel A.; Horesh, Assaf; Corsi, Alessandra; Fox, Derek B.; Cao, Yi; Kasliwal, Mansi M.; Lien, Amy; Arcavi, Iair; hide

    2015-01-01

    We report here the discovery by the Intermediate Palomar Transient Factory (iPTF) of iPTF14yb, a luminous (Mr >> -27.8 mag), cosmological (redshift 1.9733), rapidly fading optical transient. We demonstrate, based on probabilistic arguments and a comparison with the broader population, that iPTF14yb is the optical afterglow of the long-duration gamma-ray burst GRB 140226A. This marks the first unambiguous discovery of a GRB afterglow prior to (and thus entirely independent of) an associated high-energy trigger. We estimate the rate of iPTF14yb-like sources (i.e., cosmologically distant relativistic explosions) based on iPTF observations, inferring an all-sky value of Rrel = 610/yr (68% confidence interval of 110-2000/yr). Our derived rate is consistent (within the large uncertainty) with the all-sky rate of on-axis GRBs derived by the Swift satellite. Finally, we briefly discuss the implications of the nondetection to date of bona fide "orphan" afterglows (i.e., those lacking detectable high-energy emission) on GRB beaming and the degree of baryon loading in these relativistic jets.

  20. Cilia are required for asymmetric nodal induction in the sea urchin embryo.

    Science.gov (United States)

    Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

    2016-08-23

    Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

  1. Logical reformulation of quantum mechanics. I. Foundations

    International Nuclear Information System (INIS)

    Omnes, R.

    1988-01-01

    The basic rules of quantum mechanics are reformulated. They deal primarily with individual systems and do not assume that every ket may represent a physical state. The customary kinematic and dynamic rules then allow to construct consistent Boolean logics describing the history of a system, following essentially Griffiths' proposal. Logical implication is defined within these logics, the multiplicity of which reflects the complementary principle. Only one interpretive rule of quantum mechanics is necessary in such a framework. It states that these logics provide bona fide foundations for the description of a quantum system and for reasoning about it. One attempts to build up classical physics, including classical logic, on these quantum foundations. The resulting theory of measurement needs not to state a priori that the eigenvalues of an observable have to be the results of individual measurements nor to assume wave packet reduction. Both these properties can be obtained as consequences of the basic rules. One also needs not to postulate that every observable is measurable, even in principle. A proposition calculus is obtained, allowing in principle the replacement of the discussion of problems concerned with the practical interpretation of experiments by due calculations

  2. To treat or not to treat with testosterone replacement therapy: a contemporary review of management of late-onset hypogonadism and critical issues related to prostate cancer.

    Science.gov (United States)

    Kava, Bruce R

    2014-07-01

    Over the last 10 years there has been a dramatic increase in the number of patients identified and treated with testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH). By virtue of age, race, and family history, many of these patients are concurrently at risk for harboring indolent prostate cancer. Other men are at increased risk for prostate cancer as a result of an elevated serum PSA level or having had a prior prostate biopsy showing prostatic intraepithelial neoplasia (PIN) or atypical small acinar proliferation (ASAP). The clinician is often challenged with the decision whether to initiate TRT in these patients. This review presents a contemporary overview of the rationale for TRT, as well as the relationship between testosterone (endogenous and exogenous) and premalignant and malignant lesions of the prostate. We will discuss preliminary data from several recent series demonstrating that TRT may be safely administered in select patients with certain premalignant and bona fide malignant tumors of the prostate. In the absence of a large randomized clinical trial with long-term outcome data evaluating TRT, we hope that this overview will provide clinicians with an evidence-based approach to managing these anxiety-provoking - and often frustrating - clinical scenarios.

  3. Ferritin associates with marginal band microtubules

    International Nuclear Information System (INIS)

    Infante, Anthony A.; Infante, Dzintra; Chan, M.-C.; How, P.-C.; Kutschera, Waltraud; Linhartova, Irena; Muellner, Ernst W.; Wiche, Gerhard; Propst, Friedrich

    2007-01-01

    We characterized chicken erythrocyte and human platelet ferritin by biochemical studies and immunofluorescence. Erythrocyte ferritin was found to be a homopolymer of H-ferritin subunits, resistant to proteinase K digestion, heat stable, and contained iron. In mature chicken erythrocytes and human platelets, ferritin was localized at the marginal band, a ring-shaped peripheral microtubule bundle, and displayed properties of bona fide microtubule-associated proteins such as tau. Red blood cell ferritin association with the marginal band was confirmed by temperature-induced disassembly-reassembly of microtubules. During erythrocyte differentiation, ferritin co-localized with coalescing microtubules during marginal band formation. In addition, ferritin was found in the nuclei of mature erythrocytes, but was not detectable in those of bone marrow erythrocyte precursors. These results suggest that ferritin has a function in marginal band formation and possibly in protection of the marginal band from damaging effects of reactive oxygen species by sequestering iron in the mature erythrocyte. Moreover, our data suggest that ferritin and syncolin, a previously identified erythrocyte microtubule-associated protein, are identical. Nuclear ferritin might contribute to transcriptional silencing or, alternatively, constitute a ferritin reservoir

  4. Prions, prion-like prionoids, and neurodegenerative disordersVacancy

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2016-01-01

    Full Text Available Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. α-synuclein (α-syn-associated multiple system atrophy has been recently shown to be caused by a bona fide α-syn prion strain. Several other misfolded native proteins such as β-amyloid, tau and TDP-43 share some aspects of prions although none of them is shown to be transmissible in nature or in experimental animals. However, these prion-like “prionoids” are causal to a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The remarkable recent discovery of at least two new α-syn prion strains and their transmissibility in transgenic mice and in vitro cell models raises a distinct question as to whether some specific strain of other prionoids could have the capability of disease transmission in a manner similar to prions. In this overview, we briefly describe human and other mammalian prion diseases and comment on certain similarities between prion and prionoid and the possibility of prion-like transmissibility of some prionoid strains.

  5. The genus Shewanella: from the briny depths below to human pathogen.

    Science.gov (United States)

    Janda, J Michael; Abbott, Sharon L

    2014-11-01

    The genus Shewanella is currently composed of more than 50 species that inhabit a range of marine environs and ecosystems. Several members of this genus, including S. oneidensis, have been identified that could potentially play key roles in environmental processes such as bioremediation of toxic elements and heavy metals and serving as microbial fuel cells. In contrast to this beneficial role, shewanellae are increasingly being implicated as human pathogens in persons exposed through occupational or recreational activities to marine niches containing shewanellae. Documented illnesses linked to Shewanella include skin and soft tissue infections, bacteremia, and otitis media. At present, it is unclear exactly how many Shewanella species are truly bona fide human pathogens. Recent advances in the taxonomy and phylogenetic relatedness of members of this genus, however, support the concept that most human infections are caused by a single species, S. algae. Some phylogenetic data further suggest that some current members of the genus are not true Shewanella species sensu stricto. The current review summarizes our present knowledge of the distribution, epidemiology, disease spectrum, and identification of microbial species focusing on a clinical perspective.

  6. Partial coherence with application to the monotonicity problem of coherence involving skew information

    Science.gov (United States)

    Luo, Shunlong; Sun, Yuan

    2017-08-01

    Quantifications of coherence are intensively studied in the context of completely decoherent operations (i.e., von Neuamnn measurements, or equivalently, orthonormal bases) in recent years. Here we investigate partial coherence (i.e., coherence in the context of partially decoherent operations such as Lüders measurements). A bona fide measure of partial coherence is introduced. As an application, we address the monotonicity problem of K -coherence (a quantifier for coherence in terms of Wigner-Yanase skew information) [Girolami, Phys. Rev. Lett. 113, 170401 (2014), 10.1103/PhysRevLett.113.170401], which is introduced to realize a measure of coherence as axiomatized by Baumgratz, Cramer, and Plenio [Phys. Rev. Lett. 113, 140401 (2014), 10.1103/PhysRevLett.113.140401]. Since K -coherence fails to meet the necessary requirement of monotonicity under incoherent operations, it is desirable to remedy this monotonicity problem. We show that if we modify the original measure by taking skew information with respect to the spectral decomposition of an observable, rather than the observable itself, as a measure of coherence, then the problem disappears, and the resultant coherence measure satisfies the monotonicity. Some concrete examples are discussed and related open issues are indicated.

  7. Flocking with discrete symmetry: The two-dimensional active Ising model.

    Science.gov (United States)

    Solon, A P; Tailleur, J

    2015-10-01

    We study in detail the active Ising model, a stochastic lattice gas where collective motion emerges from the spontaneous breaking of a discrete symmetry. On a two-dimensional lattice, active particles undergo a diffusion biased in one of two possible directions (left and right) and align ferromagnetically their direction of motion, hence yielding a minimal flocking model with discrete rotational symmetry. We show that the transition to collective motion amounts in this model to a bona fide liquid-gas phase transition in the canonical ensemble. The phase diagram in the density-velocity parameter plane has a critical point at zero velocity which belongs to the Ising universality class. In the density-temperature "canonical" ensemble, the usual critical point of the equilibrium liquid-gas transition is sent to infinite density because the different symmetries between liquid and gas phases preclude a supercritical region. We build a continuum theory which reproduces qualitatively the behavior of the microscopic model. In particular, we predict analytically the shapes of the phase diagrams in the vicinity of the critical points, the binodal and spinodal densities at coexistence, and the speeds and shapes of the phase-separated profiles.

  8. Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.

    Science.gov (United States)

    Gupta, A; Jha, S; Engel, D A; Ornelles, D A; Dutta, A

    2013-10-17

    Adenoviruses are linear double-stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor as mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus, degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.

  9. Antiplatelet antibody may cause delayed transfusion-related acute lung injury

    Directory of Open Access Journals (Sweden)

    Torii Y

    2011-09-01

    Full Text Available Yoshitaro Torii1, Toshiki Shimizu1, Takashi Yokoi1, Hiroyuki Sugimoto1, Yuichi Katashiba1, Ryotaro Ozasa1, Shinya Fujita1, Yasushi Adachi2, Masahiko Maki3, Shosaku Nomura11The First Department of Internal Medicine, Kansai Medical University, Osaka, 2Department of Clinical Pathology, Toyooka Hospital, Hyogo, 3First Department of Pathology, Kansai Medical University, Osaka, JapanAbstract: A 61-year-old woman with lung cancer developed delayed transfusion-related acute lung injury (TRALI syndrome after transfusion of plasma- and leukoreduced red blood cells (RBCs for gastrointestinal bleeding due to intestinal metastasis. Acute lung injury (ALI recurred 31 days after the first ALI episode. Both ALI episodes occurred 48 hours after transfusion. Laboratory examinations revealed the presence of various antileukocyte antibodies including antiplatelet antibody in the recipient's serum but not in the donors' serum. The authors speculate that antiplatelet antibodies can have an inhibitory effect in the recipient, which can modulate the bona fide procedure of ALI and lead to a delay in the onset of ALI. This case illustrates the crucial role of a recipient's platelets in the development of TRALI.Keywords: delayed TRALI syndrome, recurrence, anti-platelet antibody

  10. Isolation of sphere-forming stem cells from the mouse inner ear.

    Science.gov (United States)

    Oshima, Kazuo; Senn, Pascal; Heller, Stefan

    2009-01-01

    The mammalian inner ear has very limited ability to regenerate lost sensory hair cells. This deficiency becomes apparent when hair cell loss leads to hearing loss as a result of either ototoxic insult or the aging process. Coincidently, with this inability to regenerate lost hair cells, the adult cochlea does not appear to harbor cells with a proliferative capacity that could serve as progenitor cells for lost cells. In contrast, adult mammalian vestibular sensory epithelia display a limited ability for hair cell regeneration, and sphere-forming cells with stem cell features can be isolated from the adult murine vestibular system. The neonatal inner ear, however, does harbor sphere-forming stem cells residing in cochlear and vestibular tissues. Here, we provide protocols to isolate sphere-forming stem cells from neonatal vestibular and cochlear sensory epithelia as well as from the spiral ganglion. We further describe procedures for sphere propagation, cell differentiation, and characterization of inner ear cell types derived from spheres. Sphere-forming stem cells from the mouse inner ear are an important tool for the development of cellular replacement strategies of damaged inner ears and are a bona fide progenitor cell source for transplantation studies.

  11. Bayesian assessment of moving group membership: importance of models and prior knowledge

    Science.gov (United States)

    Lee, Jinhee; Song, Inseok

    2018-04-01

    Young nearby moving groups are important and useful in many fields of astronomy such as studying exoplanets, low-mass stars, and the stellar evolution of the early planetary systems over tens of millions of years, which has led to intensive searches for their members. Identification of members depends on the used models sensitively; therefore, careful examination of the models is required. In this study, we investigate the effects of the models used in moving group membership calculations based on a Bayesian framework (e.g. BANYAN II) focusing on the beta-Pictoris moving group (BPMG). Three improvements for building models are suggested: (1) updating a list of accepted members by re-assessing memberships in terms of position, motion, and age, (2) investigating member distribution functions in XYZ, and (3) exploring field star distribution functions in XYZ and UVW. The effect of each change is investigated, and we suggest using all of these improvements simultaneously in future membership probability calculations. Using this improved MG membership calculation and the careful examination of the age, 57 bona fide members of BPMG are confirmed including 12 new members. We additionally suggest 17 highly probable members.

  12. Intracellular vesicle acidification promotes maturation of infectious poliovirus particles.

    Directory of Open Access Journals (Sweden)

    Alexsia L Richards

    Full Text Available The autophagic pathway acts as part of the immune response against a variety of pathogens. However, several pathogens subvert autophagic signaling to promote their own replication. In many cases it has been demonstrated that these pathogens inhibit or delay the degradative aspect of autophagy. Here, using poliovirus as a model virus, we report for the first time bona fide autophagic degradation occurring during infection with a virus whose replication is promoted by autophagy. We found that this degradation is not required to promote poliovirus replication. However, vesicular acidification, which in the case of autophagy precedes delivery of cargo to lysosomes, is required for normal levels of virus production. We show that blocking autophagosome formation inhibits viral RNA synthesis and subsequent steps in the virus cycle, while inhibiting vesicle acidification only inhibits the final maturation cleavage of virus particles. We suggest that particle assembly, genome encapsidation, and virion maturation may occur in a cellular compartment, and we propose the acidic mature autophagosome as a candidate vesicle. We discuss the implications of our findings in understanding the late stages of poliovirus replication, including the formation and maturation of virions and egress of infectious virus from cells.

  13. Remarks on stable and quasi-stable k-strings at large N

    International Nuclear Information System (INIS)

    Armoni, A.; Shifman, M.

    2003-01-01

    We discuss k-strings in the large-N Yang-Mills theory and its supersymmetric extension. Whereas the tension of the bona fide (stable) QCD string is expected to depend only on the N-ality of the representation, tensions that depend on specific representation R are often reported in the lattice literature. In particular, adjoint strings are discussed and found in certain simulations. We clarify this issue by systematically exploiting the notion of the quasi-stable strings which becomes well-defined at large N. The quasi-stable strings with representation-dependent tensions decay, but the decay rate (per unit length per unit time) is suppressed as Λ 2 F(N) where F(N) falls off as a function of N. It can be determined on the case-by-case basis. The quasi-stable strings eventually decay into stable strings whose tension indeed depends only on the N-ality. We also briefly review large-N arguments showing why the Casimir formula for the string tension cannot be correct, and present additional arguments in favor of the sine formula. Finally, we comment on the relevance of our estimates to Euclidean lattice measurements

  14. A Historical Perspective on the Identification of Cell Types in Pancreatic Islets of Langerhans by Staining and Histochemical Techniques.

    Science.gov (United States)

    Baskin, Denis G

    2015-08-01

    Before the middle of the previous century, cell types of the pancreatic islets of Langerhans were identified primarily on the basis of their color reactions with histological dyes. At that time, the chemical basis for the staining properties of islet cells in relation to the identity, chemistry and structure of their hormones was not fully understood. Nevertheless, the definitive islet cell types that secrete glucagon, insulin, and somatostatin (A, B, and D cells, respectively) could reliably be differentiated from each other with staining protocols that involved variations of one or more tinctorial techniques, such as the Mallory-Heidenhain azan trichrome, chromium hematoxylin and phloxine, aldehyde fuchsin, and silver impregnation methods, which were popularly used until supplanted by immunohistochemical techniques. Before antibody-based staining methods, the most bona fide histochemical techniques for the identification of islet B cells were based on the detection of sulfhydryl and disulfide groups of insulin. The application of the classical islet tinctorial staining methods for pathophysiological studies and physiological experiments was fundamental to our understanding of islet architecture and the physiological roles of A and B cells in glucose regulation and diabetes. © The Author(s) 2015.

  15. LACEwING: A New Moving Group Analysis Code

    Energy Technology Data Exchange (ETDEWEB)

    Riedel, Adric R. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Blunt, Sarah C.; Faherty, Jacqueline K. [Department of Astrophysics, American Museum of Natural History, New York, NY 10024 (United States); Lambrides, Erini L. [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Rice, Emily L. [Department of Engineering Science and Physics, The College of Staten Island, Staten Island, NY 10314 (United States); Cruz, Kelle L., E-mail: arr@astro.caltech.edu [Department of Physics and Astronomy, Hunter College, New York, NY 10065 (United States)

    2017-03-01

    We present a new nearby young moving group (NYMG) kinematic membership analysis code, LocAting Constituent mEmbers In Nearby Groups (LACEwING), a new Catalog of Suspected Nearby Young Stars, a new list of bona fide members of moving groups, and a kinematic traceback code. LACEwING is a convergence-style algorithm with carefully vetted membership statistics based on a large numerical simulation of the Solar Neighborhood. Given spatial and kinematic information on stars, LACEwING calculates membership probabilities in 13 NYMGs and three open clusters within 100 pc. In addition to describing the inputs, methods, and products of the code, we provide comparisons of LACEwING to other popular kinematic moving group membership identification codes. As a proof of concept, we use LACEwING to reconsider the membership of 930 stellar systems in the Solar Neighborhood (within 100 pc) that have reported measurable lithium equivalent widths. We quantify the evidence in support of a population of young stars not attached to any NYMGs, which is a possible sign of new as-yet-undiscovered groups or of a field population of young stars.

  16. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  17. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence.

    Science.gov (United States)

    de Souza, Camila Ferreira; Sabedot, Thais S; Malta, Tathiane M; Stetson, Lindsay; Morozova, Olena; Sokolov, Artem; Laird, Peter W; Wiznerowicz, Maciej; Iavarone, Antonio; Snyder, James; deCarvalho, Ana; Sanborn, Zachary; McDonald, Kerrie L; Friedman, William A; Tirapelli, Daniela; Poisson, Laila; Mikkelsen, Tom; Carlotti, Carlos G; Kalkanis, Steven; Zenklusen, Jean; Salama, Sofie R; Barnholtz-Sloan, Jill S; Noushmehr, Houtan

    2018-04-10

    Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Green Supplier Selection Criteria

    DEFF Research Database (Denmark)

    Nielsen, Izabela Ewa; Banaeian, Narges; Golinska, Paulina

    2014-01-01

    Green supplier selection (GSS) criteria arise from an organization inclination to respond to any existing trends in environmental issues related to business management and processes, so GSS is integrating environmental thinking into conventional supplier selection. This research is designed...... to determine prevalent general and environmental supplier selection criteria and develop a framework which can help decision makers to determine and prioritize suitable green supplier selection criteria (general and environmental). In this research we considered several parameters (evaluation objectives......) to establish suitable criteria for GSS such as their production type, requirements, policy and objectives instead of applying common criteria. At first a comprehensive and deep review on prevalent and green supplier selection literatures performed. Then several evaluation objectives defined to assess the green...

  19. Combining the IADPSG criteria with the WHO diagnostic criteria for ...

    African Journals Online (AJOL)

    The International Association of Diabetes in Pregnancy Study Group (IADPSG) and World Health ... Macrosomia or at least one adverse outcome were more likely in GDM patients who ... criteria for GDM in the ADA's more recent position statement.[18] .... at risk for postpartum type 2 DM;[27] the IADPSG criteria on the other ...

  20. Decision criteria in PSA applications

    International Nuclear Information System (INIS)

    Holmberg, J.E.; Pulkkinen, U.; Rosqvist, T.; Simola, K.

    2001-11-01

    Along with the adoption of risk informed decision making principles, the need for formal probabilistic decision rule or criteria has been risen. However, there are many practical and theoretical problems in the application of probabilistic criteria. One has to think what is the proper way to apply probabilistic rules together with deterministic ones and how the criteria are weighted with respect to each other. In this report, we approach the above questions from the decision theoretic point of view. We give a short review of the most well known probabilistic criteria, and discuss examples of their use. We present a decision analytic framework for evaluating the criteria, and we analyse how the different criteria behave under incompleteness or uncertainty of the PSA model. As the conclusion of our analysis we give recommendations on the application of the criteria in different decision situations. (au)

  1. Continuity between DSM-5 Categorical Criteria and Traits Criteria for Borderline Personality Disorder.

    Science.gov (United States)

    Bach, Bo; Sellbom, Martin

    2016-08-01

    Borderline personality disorder (BPD) includes a heterogeneous constellation of symptoms operationalized with 9 categorical criteria. As the field of personality disorder (PD) research moves to emphasize dimensional traits in its operationalization, it is important to delineate continuity between the 9 DSM-IV/Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorical criteria for BPD and the trait dimensions in DSM-5 Section III. To date, no study has attempted such validation. We examined the associations between the 9 categorical DSM-IV/DSM-5 criteria for BPD and the trait dimensions of the alternative DSM-5 model for PDs in consecutively recruited psychiatric outpatients (N = 142; 68% female; age: mean 29.02, SD 8.38). This was investigated by means of bivariate correlations, followed by multiple logistic regression analysis. The categorical BPD criteria were associated with conceptually related DSM-5 Section III traits (P > 0.001), except for the criterion of chronic feelings of emptiness. Consistent with the proposed traits criteria for BPD in DSM-5 Section III, we found Emotional lability, Anxiousness, Separation insecurity, Depressivity, Impulsivity, Risk taking, and Hostility to capture conceptually coherent BPD categorical criteria, while Suspiciousness was also strongly associated with BPD criteria. At the domain level, this applied to Negative affectivity, Disinhibition, and Psychoticism. Notably, Emotional lability, Impulsivity, and Suspiciousness emerged as unique predictors of BPD (P > 0.05). In addition to the proposed BPD traits criteria, Suspiciousness and features of Psychoticism also augment BPD features. Provided that these findings are replicated in forthcoming research, a modified traits operationalization of BPD is warranted. © The Author(s) 2016.

  2. Rating of environmental criteria

    Energy Technology Data Exchange (ETDEWEB)

    Glueck, K; Krasser, G

    1980-01-01

    After a general theoretical discussion on the question of rating within a framework of cost-benefit studies, first trials as to the quantification and standardisation of twelve selected environmental criteria by means of an indicator system are worked out and compiled. The selection includes the criteria exhaust gas, dust, micro climate, water pollution, water regime, land requirement, vibrations, traffic noise, landscape scene, urban scene, effect of separation and safety risks. An insight is given of the rating practice using an evaluation of the available literature, of a household interview and of an interview of experts. The interviewing of 156 experts as to their rating conception of ten criteria in the second round has provided contributions to the general problem of the evaluation estimate based on multi criteria analysis as well as differentiation of the twelve or ten environmental criteria. The following criteria ratings given by the experts and which are averaged and smoothed are: traffic noise 20,0% +- 8,5; air pollution 15,0% +- 7,0; safety risk 13,0% +- 7,0; soil and water pollution 8,5% +- 5,0; landscape scene 8,0% +- 4,5; urban scene 8,0% +- 4,5; water regime 6,5% +- 3,5 and vibrations 4,5% +- 2,5.

  3. Analysing and Comparing Encodability Criteria

    Directory of Open Access Journals (Sweden)

    Kirstin Peters

    2015-08-01

    Full Text Available Encodings or the proof of their absence are the main way to compare process calculi. To analyse the quality of encodings and to rule out trivial or meaningless encodings, they are augmented with quality criteria. There exists a bunch of different criteria and different variants of criteria in order to reason in different settings. This leads to incomparable results. Moreover it is not always clear whether the criteria used to obtain a result in a particular setting do indeed fit to this setting. We show how to formally reason about and compare encodability criteria by mapping them on requirements on a relation between source and target terms that is induced by the encoding function. In particular we analyse the common criteria full abstraction, operational correspondence, divergence reflection, success sensitiveness, and respect of barbs; e.g. we analyse the exact nature of the simulation relation (coupled simulation versus bisimulation that is induced by different variants of operational correspondence. This way we reduce the problem of analysing or comparing encodability criteria to the better understood problem of comparing relations on processes.

  4. Diagnostic Criteria for Pediatric MS

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-06-01

    Full Text Available Investigators at Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital of Chicago review the diagnostic criteria for pediatric multiple sclerosis, the differential diagnosis, the 2010 McDonald criteria, and Callen criteria.

  5. Proposed Diagnostic Criteria for Smartphone Addiction.

    Science.gov (United States)

    Lin, Yu-Hsuan; Chiang, Chih-Lin; Lin, Po-Hsien; Chang, Li-Ren; Ko, Chih-Hung; Lee, Yang-Han; Lin, Sheng-Hsuan

    2016-01-01

    Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria. We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist's structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists' clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy. Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1) six symptom criteria, (2) four functional impairment criteria and (3) exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%), while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use. The diagnostic criteria of smartphone addiction demonstrated the core symptoms "impaired control" paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment.

  6. Proposed Diagnostic Criteria for Smartphone Addiction.

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Lin

    Full Text Available Global smartphone penetration has led to unprecedented addictive behaviors. The aims of this study are to develop diagnostic criteria of smartphone addiction and to examine the discriminative ability and the validity of the diagnostic criteria.We developed twelve candidate criteria for characteristic symptoms of smartphone addiction and four criteria for functional impairment caused by excessive smartphone use. The participants consisted of 281 college students. Each participant was systematically assessed for smartphone-using behaviors by psychiatrist's structured diagnostic interview. The sensitivity, specificity, and diagnostic accuracy of the candidate symptom criteria were analyzed with reference to the psychiatrists' clinical global impression. The optimal model selection with its cutoff point of the diagnostic criteria differentiating the smartphone addicted subjects from non-addicted subjects was then determined by the best diagnostic accuracy.Six symptom criteria model with optimal cutoff point were determined based on the maximal diagnostic accuracy. The proposed smartphone addiction diagnostic criteria consisted of (1 six symptom criteria, (2 four functional impairment criteria and (3 exclusion criteria. Setting three symptom criteria as the cutoff point resulted in the highest diagnostic accuracy (84.3%, while the sensitivity and specificity were 79.4% and 87.5%, respectively. We suggested determining the functional impairment by two or more of the four domains considering the high accessibility and penetration of smartphone use.The diagnostic criteria of smartphone addiction demonstrated the core symptoms "impaired control" paralleled with substance related and addictive disorders. The functional impairment involved multiple domains provide a strict standard for clinical assessment.

  7. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    International Nuclear Information System (INIS)

    Noda, Saori; Takahashi, Atsushi; Hayashi, Takeru; Tanuma, Sei-ichi; Hatakeyama, Masanori

    2016-01-01

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  8. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2016-01-22

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  9. Dual Criteria Decisions

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten Igel

    2014-01-01

    The most popular models of decision making use a single criterion to evaluate projects or lotteries. However, decision makers may actually consider multiple criteria when evaluating projects. We consider a dual criteria model from psychology. This model integrates the familiar tradeoffs between...... to the clear role that income thresholds play in such decision making, but does not rule out a role for tradeoffs between risk and utility or probability weighting....

  10. Failure Criteria for Reinforced Materials

    DEFF Research Database (Denmark)

    Rathkjen, Arne

    Failure of materials is often characterized as ductile yielding, brittle fracture, creep rupture, etc., and different criteria given in terms of different parameters have been used to describe different types of failure. Only criteria expressing failure in terms of stress are considered in what...... place until the matrix, the continuous component of the composite, fails. When an isotropic matrix is reinforced as described above, the result is an anisotropic composite material. Even if the material is anisotropic, it usually exhibits a rather high degree of symmetry and such symmetries place...... certain restrictions on the form of the failure criteria for anisotropic materials. In section 2, some failure criteria for homogenous materials are reviewed. Both isotropic and anisotropic materials are described, and in particular the constraints imposed on the criteria from the symmetries orthotropy...

  11. Defining criteria related to wastes for use in multi-criteria decision tool for nuclear accidents

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Diogo N.G.; Guimaraes, Jean R.D., E-mail: dneves@biof.ufrj.br, E-mail: jeanrdg@biof.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho; Rochedo, Elaine R.R.; De Luca, Christiano, E-mail: elainerochedo@gmail.com, E-mail: christiano_luca@hotmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Rochedo, Pedro R.R., E-mail: rochedopedro@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto Alberto Luiz Coimbra de Pos-Graduacao e Pesquisa de Engenharia

    2013-07-01

    The selection of protective measures and strategies for remediation of contaminated areas after a nuclear accident must be based on previously established criteria in order to prevent stress of the population and the unnecessary exposure of workers. After a nuclear accident resulting in environmental contamination, decisions on remediation of areas is complex due to the large numbers of factors involved in decontamination processes. This work is part of a project which aims to develop a multi-criteria tool to support a decision-making process in cases of a radiological or a nuclear accident in Brazil. First, a database of remediation strategies for contaminated areas was created. In this process, the most relevant aspects for the implementation of these strategies were considered, including technical criteria regarding aspects related to the generation of wastes in a reference urban area, which are discussed in this paper. The specific objective of this study is to define criteria for the aspects of radioactive wastes, resulted by the implementation of some urban measures, in order to be incorporated in a multi-criteria decision tool. Main aspects considered were the type, the amount and the type of treatment necessary for each procedure. The decontamination procedures are then classified according to the selected criteria in order to feed the multi-criteria decision tool. This paper describes the steps for the establishment of these criteria and evaluates the potential for future applications in order to improve predictions and to support the decisions to be made. (author)

  12. Defining criteria related to wastes for use in multi-criteria decision tool for nuclear accidents

    International Nuclear Information System (INIS)

    Silva, Diogo N.G.; Guimaraes, Jean R.D.; Rochedo, Elaine R.R.; De Luca, Christiano; Rochedo, Pedro R.R.

    2013-01-01

    The selection of protective measures and strategies for remediation of contaminated areas after a nuclear accident must be based on previously established criteria in order to prevent stress of the population and the unnecessary exposure of workers. After a nuclear accident resulting in environmental contamination, decisions on remediation of areas is complex due to the large numbers of factors involved in decontamination processes. This work is part of a project which aims to develop a multi-criteria tool to support a decision-making process in cases of a radiological or a nuclear accident in Brazil. First, a database of remediation strategies for contaminated areas was created. In this process, the most relevant aspects for the implementation of these strategies were considered, including technical criteria regarding aspects related to the generation of wastes in a reference urban area, which are discussed in this paper. The specific objective of this study is to define criteria for the aspects of radioactive wastes, resulted by the implementation of some urban measures, in order to be incorporated in a multi-criteria decision tool. Main aspects considered were the type, the amount and the type of treatment necessary for each procedure. The decontamination procedures are then classified according to the selected criteria in order to feed the multi-criteria decision tool. This paper describes the steps for the establishment of these criteria and evaluates the potential for future applications in order to improve predictions and to support the decisions to be made. (author)

  13. Comparing new diagnostic criteria of 2010 ACR/EULAR with 1987 ACR criteria in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Fatemeh Shirani

    2017-01-01

    Full Text Available Background: Rheumatoid Arthritis (RA is a chronic inflammatory disease presenting with inflammation, tenderness and destruction of the synovial joints, resulting in severe disability and early death due to complication of disease. Previous diagnostic criteria are not useful for identifying patients who need early treatment. Thus, new diagnostic criteria for faster diagnosis of disease are introduced in 2010. The aim of this study was to compared 1987 ACR (American College of Rheumatology criteria and 2010 ACR/EULAR (European League Against Rheumatism classification criteria for diagnosis of rheumatoid arthritis. Methods: In this Cohort prospective study, patients with early arthritis were evaluated   according to the old and new diagnostic criteria and followed-up every two monthly for one year (2012-2013 in Hazrat-e Rasool University Hospital, Tehran. Inclusion criteria of this study were age more than 18 year and indefinite diagnosis of arthritis. For all of patients physical examination by expert rheumatologist was done and lab data include erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, anti-cyclic citrullinated peptide (Anti-CCP and rheumatoid factor was requested. The sensitivity, specificity, positive and negative predictive values were then determined for each diagnostic criteria. Results: In this study 104 patients including 28 males (26.9% and 76 females (73.1% with the mean age of 44.2±13.7 years were included. At the end of one year follow-up, 82 were diagnosed to have RA while other 22 patients were not categorized as RA. Sensitivity for ESR, CRP, Anti-CCP and rheumatoid factor in 2010 ACR/EULAR criteria was 52%, 19%, 48%, 28% and specificity for them was 45%, 71%, 27%, 79% respectively. Number of small and large joint arthritis were more in patients with Rheumatoid Arthritis (RA rather than other arthritis (P=0.0001. Sensitivity and specificity for small joints involvement was 87% and 54% and for large joints

  14. Toxic chemical risk acceptance criteria

    International Nuclear Information System (INIS)

    Craig, D.K.; Davis, J.; Lee, L.; Lein, P.; Omberg, S.

    1992-01-01

    This paper presents recommendations of a subcommittee of the Westinghouse M ampersand 0 Nuclear Facility Safety Committee concerning toxic chemical risk acceptance criteria. Two sets of criteria have been developed, one for use in the hazard classification of facilities, and the second for use in comparing risks in DOE non-reactor nuclear facility Safety Analysis Reports. The Emergency Response Planning Guideline (ERPG) values are intended to provide estimates of concentration ranges for specific chemicals above which exposure would be expected to lead to adverse heath effects of increasing severity for ERPG-1, -2, and -3s. The subcommittee recommends that criteria for hazard class or risk range be based on ERPGs for all chemicals. Probability-based Incremental Cancer Risk (ICR) criteria are recommended for additional analyses of risks from all known or suspected human carcinogens. Criteria are given for both on-site and off-site exposure. The subcommittee also recommends that the 5-minute peak concentration be compared with the relevant criterion with no adjustment for exposure time. Since ERPGs are available for only a limited number of chemicals, the subcommittee has developed a proposed hierarchy of concentration limit parameters for the different criteria

  15. Dynamic criteria for partitioning and transmutation

    International Nuclear Information System (INIS)

    Lu, A.H.

    1991-11-01

    This paper addresses dynamic criteria intended to optimize partitioning and transmutation (P-T) concept development supporting improved nuclear waste management. Six criteria are proposed initially and the rationale for each is briefly explained. Each criterion is used as a measure (or dimension) on which the developed concepts can be evaluated. The criteria allow the P-T concepts to be evaluated in an integral system including long-term energy needs, fuel cycle, and waste management. New criteria will be identified along with the P-T concept development, and each criterion will be realistically weighted so that it is comparable in an overall criteria evaluation. The weights are subject to change as a result of technical advancements and public perception on various issues. Incomplete criteria will result in a poor choice because important factors may not be considered when the decision is made. A successful decision on the optimal P-T system depends on the completeness of criteria (dimensions) as well as realistic weights assigned to each criterion

  16. Photovoltaic system criteria documents. Volume 3: Environmental issues and evaluation criteria for photovoltaic applications

    Science.gov (United States)

    Koenig, John C.; Billitti, Joseph W.; Tallon, John M.

    1979-01-01

    The environmental issues and evaluation criteria relating to the suitability of sites proposed for photovoltaic (PV) system deployment are identified. The important issues are defined, briefly discussed and then developed into evaluation criteria. System designers are provided with information on the environmental sensitivity of PV systems in realistic applications, background material which indicates the applicability of the siting issues identified, and evaluation criteria are defined to facilitate the selection of sites that maximize PV system operation.

  17. Radiological design criteria

    International Nuclear Information System (INIS)

    Selby, J.M.; Andersen, B.V.; Carter, L.A.; Waite, D.A.

    1977-01-01

    Many new nuclear facilities are unsatisfactory from a radiation protection point of view, particularly when striving to maintain occupational exposure as low as practicable 'ALAP'. Radiation protection is achieved through physical protective features supplemented by administrative controls. Adequate physical protective feature should be achieved during construction so that supplemental administrative controls may be kept simple and workable. Many nuclear facilities fall short of adequate physical protective features, thus, remedial and sometimes awkward administrative procedures are required to safely conduct work. In reviewing the various handbooks, reports and regulations which deal with radiation protection, it may be noted that there is minimal radiological design guidance for application to nuclear facilities. A set of criteria or codes covering functional areas rather than specific nuclear facility types is badly needed. The following are suggested as functional areas to be considered: characterization of the Facility; siting and access; design exposure limits; layout (people and materials flow); ventilation and effluent control; radiation protection facilities and systems. The application of such radiological design criteria early in the design process would provide some assurance that nuclear facilities will be safe, flexible, and efficient with a minimum of costly retrofitting or administrative restrictions. Criteria which we have found helpful in these functional areas is discussed together with justification for adoption of such criteria and identification of problems which still require solution

  18. Sediment quality criteria: A review with recommendations for developing criteria for the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Driver, C.J.

    1994-05-01

    Criteria for determining the quality of liver sediment are necessary to ensure that concentrations of contaminants in aquatic systems are within acceptable limits for the protection of aquatic and human life. Such criteria should facilitate decision-making about remediation, handling, and disposal of contaminants. Several approaches to the development of sediment quality criteria (SQC) have been described and include both descriptive and numerical methods. However, no single method measures all impacts at all times to all organisms (U.S. EPA 1992b). The U.S. EPA`s interest is primarily in establishing chemically based, numerical SQC that are applicable nation-wide (Shea 1988). Of the approaches proposed for SQC development, only three are being considered for numerical SQC on a national level. These approaches include an Equilibrium Partitioning Approach, a site-specific method using bioassays (the Apparent Effects Threshold Approach), and an approach similar to EPA`s water quality criteria (Pavlou and Weston 1984). Although national (or even regional) criteria address a number of political, litigative, and engineering needs, some researchers feel that protection of benthic communities require site-specific, biologically based criteria (Baudo et al. 1990). This is particularly true for areas where complex mixtures of contaminants are present in sediments. Other scientifically valid and accepted procedures for freshwater SQC include a background concentration approach, methods using field or spiked bioassays, a screening level concentration approach, the Apparent Effects Threshold Approach, the Sediment Quality Triad, the International Joint Commission Sediment Assessment Strategy, and the National Status and Trends Program Approach. The various sediment assessment approaches are evaluated for application to the Hanford Reach and recommendations for Hanford Site sediment quality criteria are discussed.

  19. Action principle for the generalized harmonic formulation of general relativity

    International Nuclear Information System (INIS)

    Brown, J. David

    2011-01-01

    An action principle for the generalized harmonic formulation of general relativity is presented. The action is a functional of the spacetime metric and the gauge source vector. An action principle for the Z4 formulation of general relativity has been proposed recently by Bona, Bona-Casas, and Palenzuela. The relationship between the generalized harmonic action and the Bona, Bona-Casas, and Palenzuela action is discussed in detail.

  20. Criteria for Authorship in Bioethics

    OpenAIRE

    Resnik, David B.; Master, Zubin

    2011-01-01

    Multiple authorship is becoming increasingly common in bioethics research. There are well-established criteria for authorship in empirical bioethics research but not for conceptual research. It is important to develop criteria for authorship in conceptual publications to prevent undeserved authorship and uphold standards of fairness and accountability. This article explores the issue of multiple authorship in bioethics and develops criteria for determining who should be an author on a concept...

  1. Molecular Basis for Converting (2S-Methylsuccinyl-CoA Dehydrogenase into an Oxidase

    Directory of Open Access Journals (Sweden)

    Simon Burgener

    2017-12-01

    Full Text Available Although flavoenzymes have been studied in detail, the molecular basis of their dioxygen reactivity is only partially understood. The members of the flavin adenosine dinucleotide (FAD-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. However, both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases. We recently engineered (2S-methylsuccinyl-CoA dehydrogenase towards oxidase activity by rational mutagenesis. Here we characterized the (2S-methylsuccinyl-CoA dehydrogenase wild-type, as well as the engineered (2S-methylsuccinyl-CoA oxidase, in detail. Using stopped-flow UV-spectroscopy and liquid chromatography-mass spectrometry (LC-MS based assays, we explain the molecular base for dioxygen reactivity in the engineered oxidase and show that the increased oxidase function of the engineered enzyme comes at a decreased dehydrogenase activity. Our findings add to the common notion that an increased activity for a specific substrate is achieved at the expense of reaction promiscuity and provide guidelines for rational engineering efforts of acyl-CoA dehydrogenases and oxidases.

  2. Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

    International Nuclear Information System (INIS)

    Yang, Hanna; Kwon, Chang Seob; Choi, Yoonjung; Lee, Daeyoup

    2016-01-01

    Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

  3. Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells.

    Science.gov (United States)

    Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M

    2001-07-01

    On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.

  4. How carbon credits could drive the emergence of renewable energies

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, John A. [Macquarie Graduate School of Management, Macquarie University, Sydney, NSW 2109 (Australia)

    2008-10-15

    The shift to renewable energy options and low-carbon technologies, in response to the concerns over energy security and climate change, is proceeding more slowly than many would like. The usual argument against rapid deployment of new technologies is the costs imposed on the economy, commonly interpreted in terms of upfront costs to be borne or involving large cash transfers to fund, for example, efforts to preserve rainforests. In this contribution I argue that such a perspective provides a continuing barrier to taking effective action, whereas a perspective based on creation and use of carbon credits provides a means of avoiding the shock of abrupt industrial change. Carbon credits granted for bona fide carbon load reductions could be created through private initiative, for example by merchant banks, to constitute a market that will complement regulatory-based initiatives such as national emissions trading systems. This is not a novel idea; indeed it is the way that capitalism has funded every major change, including the Industrial Revolution, through the creation of credit. The emergence of a global carbon credit economy is likely to precede a global regulatory system governing climate change and will doubtless help to stimulate the emergence of such a global system. (author)

  5. Controlling the prion propensity of glutamine/asparagine-rich proteins.

    Science.gov (United States)

    Paul, Kacy R; Ross, Eric D

    2015-01-01

    The yeast Saccharomyces cerevisiae can harbor a number of distinct prions. Most of the yeast prion proteins contain a glutamine/asparagine (Q/N) rich region that drives prion formation. Prion-like domains, defined as regions with high compositional similarity to yeast prion domains, are common in eukaryotic proteomes, and mutations in various human proteins containing prion-like domains have been linked to degenerative diseases, including amyotrophic lateral sclerosis. Here, we discuss a recent study in which we utilized two strategies to generate prion activity in non-prion Q/N-rich domains. First, we made targeted mutations in four non-prion Q/N-rich domains, replacing predicted prion-inhibiting amino acids with prion-promoting amino acids. All four mutants formed foci when expressed in yeast, and two acquired bona fide prion activity. Prion activity could be generated with as few as two mutations, suggesting that many non-prion Q/N-rich proteins may be just a small number of mutations from acquiring aggregation or prion activity. Second, we created tandem repeats of short prion-prone segments, and observed length-dependent prion activity. These studies demonstrate the considerable progress that has been made in understanding the sequence basis for aggregation of prion and prion-like domains, and suggest possible mechanisms by which new prion domains could evolve.

  6. The perils of pathogen discovery: origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns.

    Science.gov (United States)

    Naccache, Samia N; Greninger, Alexander L; Lee, Deanna; Coffey, Lark L; Phan, Tung; Rein-Weston, Annie; Aronsohn, Andrew; Hackett, John; Delwart, Eric L; Chiu, Charles Y

    2013-11-01

    Next-generation sequencing was used for discovery and de novo assembly of a novel, highly divergent DNA virus at the interface between the Parvoviridae and Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV), is nearly identical by sequence to another DNA virus, NIH-CQV, previously detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we initially detected PHV in a wide range of clinical samples, with all strains sharing ∼99% nucleotide and amino acid identity with each other and with NIH-CQV, the exact origin of the virus was eventually traced to contaminated silica-binding spin columns used for nucleic acid extraction. Definitive confirmation of the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of water eluted through contaminated spin columns. Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture. The confirmation of PHV/NIH-CQV as laboratory reagent contaminants and not bona fide infectious agents of humans underscores the rigorous approach needed to establish the validity of new viral genomes discovered by next-generation sequencing.

  7. Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

    Science.gov (United States)

    Gupta, Payal; Dash, Prasanta K

    2017-09-11

    Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

  8. Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase C.

    Science.gov (United States)

    Tuteja, Narendra; Reddy, Malireddy Kodandarami; Mudgil, Yashwanti; Yadav, Badam Singh; Chandok, Meena Rani; Sopory, Sudhir Kumar

    2003-08-01

    DNA topoisomerase I catalyzes the relaxation of superhelical DNA tension and is vital for DNA metabolism; therefore, it is essential for growth and development of plants. Here, we have studied the phosphorylation-dependent regulation of topoisomerase I from pea (Pisum sativum). The purified enzyme did not show autophosphorylation but was phosphorylated in an Mg(2+)-dependent manner by endogenous protein kinases present in pea nuclear extracts. This phosphorylation was abolished with calf intestinal alkaline phosphatase and lambda phosphatase. It was also phosphorylated by exogenous casein kinase 2 (CK2), protein kinase C (PKC; from animal sources), and an endogenous pea protein, which was purified using a novel phorbol myristate acetate affinity chromatography method. All of these phosphorylations were inhibited by heparin (inhibitor of CK2) and calphostin (inhibitor of PKC), suggesting that pea topoisomerase I is a bona fide substrate for these kinases. Spermine and spermidine had no effect on the CK2-mediated phosphorylation, suggesting that it is polyamine independent. Phospho-amino acid analysis showed that only serine residues were phosphorylated, which was further confirmed using antiphosphoserine antibody. The topoisomerase I activity increased after phosphorylation with exogenous CK2 and PKC. This study shows that these kinases may contribute to the physiological regulation of DNA topoisomerase I activity and overall DNA metabolism in plants.

  9. Bonding and structure of copper nitrenes.

    Science.gov (United States)

    Cundari, Thomas R; Dinescu, Adriana; Kazi, Abul B

    2008-11-03

    Copper nitrenes are of interest as intermediates in the catalytic aziridination of olefins and the amination of C-H bonds. However, despite advances in the isolation and study of late-transition-metal multiply bonded complexes, a bona fide structurally characterized example of a terminal copper nitrene has, to our knowledge, not been reported. In anticipation of such a report, terminal copper nitrenes are studied from a computational perspective. The nitrene complexes studied here are of the form (beta-diketiminate)Cu(NPh). Density functional theory (DFT), complete active space self-consistent-field (CASSCF) electronic structure techniques, and hybrid quantum mechanical/molecular mechanical (QM/MM) methods are employed to study such species. While DFT methods indicate that a triplet (S = 1) is the ground state, CASSCF calculations indicate that a singlet (S = 0) is the ground state, with only a small energy gap between the singlet and triplet. Moreover, the ground-state (open-shell) singlet copper nitrene is found to be highly multiconfigurational (i.e., biradical) and to possess a bent geometry about the nitrene nitrogen, contrasting with the linear nitrene geometry of the triplet copper nitrenes. CASSCF calculations also reveal the existence of a closed-shell singlet state with some degree of multiple bonding character for the copper-nitrene bond.

  10. Implications of the interstellar object 1I/'Oumuamua for planetary dynamics and planetesimal formation

    Science.gov (United States)

    Raymond, Sean N.; Armitage, Philip J.; Veras, Dimitri; Quintana, Elisa V.; Barclay, Thomas

    2018-05-01

    'Oumuamua, the first bona fide interstellar planetesimal, was discovered passing through our Solar system on a hyperbolic orbit. This object was likely dynamically ejected from an extrasolar planetary system after a series of close encounters with gas giant planets. To account for 'Oumuamua's detection, simple arguments suggest that ˜1 M⊕ of planetesimals are ejected per solar mass of Galactic stars. However, that value assumes mono-sized planetesimals. If the planetesimal mass distribution is instead top-heavy, the inferred mass in interstellar planetesimals increases to an implausibly high value. The tension between theoretical expectations for the planetesimal mass function and the observation of 'Oumuamua can be relieved if a small fraction ({˜ } 0.1-1 {per cent}) of planetesimals are tidally disrupted on the pathway to ejection into 'Oumuamua-sized fragments. Using a large suite of simulations of giant planet dynamics including planetesimals, we confirm that 0.1-1 per cent of planetesimals pass within the tidal disruption radius of a gas giant on their pathway to ejection. 'Oumuamua may thus represent a surviving fragment of a disrupted planetesimal. Finally, we argue that an asteroidal composition is dynamically disfavoured for 'Oumuamua, as asteroidal planetesimals are both less abundant and ejected at a lower efficiency than cometary planetesimals.

  11. Globalization of Craniofacial Plastic Surgery: Foreign Mission Programs for Cleft Lip and Palate

    Science.gov (United States)

    Laub, Donald R.

    2015-01-01

    Abstract International Humanitarian Interchanges are a bona fide component of surgery and medicine. Additionally, these programs also provide substantial benefit both to the doers and the recipients. The foreign mission program is potentially a weapon of foreign policy which is underutilized and underestimated. Physician job dissatisfaction is increasing. However, the happiness and satisfaction of the participants in the short-term multidisciplinary trips, repeated, well-organized and respectful, with rather complete integration of the surgical system of the sister countries (“Plan B”), approaches 100%. The theory of the International Humanitarian Interchanges is based on substance, on medical theory. These trips are particularly successful in interchanges with medium-resourced countries. Furthermore, the academic visiting professor (“Plan A”: hi-resource place to hi-resource place), the One Man Can Save the World model (“Plan C”: to the low-resource place), and the intriguing Horton Peace Plan have possibilities for long-term benefit to the doer, recipient, the field of surgery, and the body of knowledge. In all of these, our country and the family of nations advance. The theoretical basis is not always religious nor the grand strategy plan; both have either proselytizing or political dominance as primary motives, and are mentioned as historically helpful. PMID:26080114

  12. Structural basis and functions of abscisic acid receptors PYLs

    Science.gov (United States)

    Zhang, Xing L.; Jiang, Lun; Xin, Qi; Liu, Yang; Tan, Jian X.; Chen, Zhong Z.

    2015-01-01

    Abscisic acid (ABA) plays a key role in many developmental processes and responses to adaptive stresses in plants. Recently, a new family of nucleocytoplasmic PYR/PYL/RCAR (PYLs) has been identified as bona fide ABA receptors. PYLs together with protein phosphatases type-2C (PP2Cs), Snf1 (Sucrose-non-fermentation 1)-related kinases subfamily 2 (SnRK2s) and downstream substrates constitute the core ABA signaling network. Generally, PP2Cs inactivate SnRK2s kinases by physical interaction and direct dephosphorylation. Upon ABA binding, PYLs change their conformations and then contact and inhibit PP2Cs, thus activating SnRK2s. Here, we reviewed the recent progress in research regarding the structures of the core signaling pathways of ABA, including the (+)-ABA, (−)-ABA and ABA analogs pyrabactin as well as 6AS perception by PYLs, SnRK2s mimicking PYLs in binding PP2Cs. PYLs inhibited PP2Cs in both the presence and absence of ABA and activated SnRK2s. The present review elucidates multiple ABA signal perception and transduction by PYLs, which might shed light on how to design small chemical compounds for improving plant performance in the future. PMID:25745428

  13. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  14. Distinguishing quantum from classical oscillations in a driven phase qubit

    International Nuclear Information System (INIS)

    Shevchenko, S N; Omelyanchouk, A N; Zagoskin, A M; Savel'ev, S; Nori, Franco

    2008-01-01

    Rabi oscillations are coherent transitions in a quantum two-level system under the influence of a resonant drive, with a much lower frequency dependent on the perturbation amplitude. These serve as one of the signatures of quantum coherent evolution in mesoscopic systems. It was shown recently (Groenbech-Jensen N and Cirillo M 2005 Phys. Rev. Lett. 95 067001) that in phase qubits (current-biased Josephson junctions) this effect can be mimicked by classical oscillations arising due to the anharmonicity of the effective potential. Nevertheless, we find qualitative differences between the classical and quantum effects. Firstly, while the quantum Rabi oscillations can be produced by the subharmonics of the resonant frequency ω 10 (multiphoton processes), the classical effect also exists when the system is excited at the overtones, nω 10 . Secondly, the shape of the resonance is, in the classical case, characteristically asymmetric, whereas quantum resonances are described by symmetric Lorentzians. Thirdly, the anharmonicity of the potential results in the negative shift of the resonant frequency in the classical case, in contrast to the positive Bloch-Siegert shift in the quantum case. We show that in the relevant range of parameters these features allow us to distinguish confidently the bona fide Rabi oscillations from their classical Doppelgaenger

  15. Globalization of Craniofacial Plastic Surgery: Foreign Mission Programs for Cleft Lip and Palate.

    Science.gov (United States)

    Laub, Donald R

    2015-06-01

    International Humanitarian Interchanges are a bona fide component of surgery and medicine. Additionally, these programs also provide substantial benefit both to the doers and the recipients.The foreign mission program is potentially a weapon of foreign policy which is underutilized and underestimated.Physician job dissatisfaction is increasing. However, the happiness and satisfaction of the participants in the short-term multidisciplinary trips, repeated, well-organized and respectful, with rather complete integration of the surgical system of the sister countries ("Plan B"), approaches 100%.The theory of the International Humanitarian Interchanges is based on substance, on medical theory. These trips are particularly successful in interchanges with medium-resourced countries.Furthermore, the academic visiting professor ("Plan A": hi-resource place to hi-resource place), the One Man Can Save the World model ("Plan C": to the low-resource place), and the intriguing Horton Peace Plan have possibilities for long-term benefit to the doer, recipient, the field of surgery, and the body of knowledge. In all of these, our country and the family of nations advance.The theoretical basis is not always religious nor the grand strategy plan; both have either proselytizing or political dominance as primary motives, and are mentioned as historically helpful.

  16. Evolving a photosynthetic organelle

    Directory of Open Access Journals (Sweden)

    Nakayama Takuro

    2012-04-01

    Full Text Available Abstract The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles. The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis - the conversion of solar energy into chemical energy - and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  17. STarlight Absorption Reduction through a Survey of Multiple Occulting Galaxies (STARSMOG)

    Science.gov (United States)

    Holwerda, Benne

    2014-10-01

    Dust absorption remains the poorest constrained parameter in both Cosmological distances and multi-wavelength studies of galaxy populations. A galaxy's dust distribution can be measured to great accuracy in the case of an overlapping pair of galaxies, i.e., when a foreground spiral galaxy accidentally overlaps a more distant, preferably elliptical galaxy. We have identified over 300 bona-fide overlapping pairs --well separated in redshift but close on the sky-- in the GAMA spectroscopic survey, taking advantage of its high completeness (98%) on small scales. We propose to map the fine-scale (~50pc) dust structure in these occulting galaxies, using HST/WFC3 SNAP observations. The resulting dust maps will (1) serve as an extinction probability for supernova lightcurve fits in similar type host galaxies, (2) strongly constrain the role of ISM structure in Spectral Energy Distribution models of spiral galaxies, and (3) map the level of ISM turbulence (through the spatial power-spectrum). We ask for SNAP observations with a parent list of 355 targets to ensure a complete and comprehensive coverage of each foreground galaxy mass, radius and inclination. The resulting extinction maps will serve as a library for SNIa measurements, galaxy SED modelling and ISM turbulence measurements.

  18. Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication.

    Directory of Open Access Journals (Sweden)

    Karl Frontzek

    Full Text Available Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE, progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication.

  19. The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development.

    Science.gov (United States)

    Kostrouchová, Markéta; Kostrouch, David; Chughtai, Ahmed A; Kaššák, Filip; Novotný, Jan P; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W; Saudek, Vladimír; Kostrouchová, Marta; Kostrouch, Zdeněk

    2017-01-01

    The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

  20. Hearts and minds in the science classroom: The education of a confirmed evolutionist

    Science.gov (United States)

    Jackson, David F.; Doster, Elizabeth C.; Meadows, Lee; Wood, Teresa

    This study traces a heuristic inquiry process from the point of view of a science educator, from a secular-humanist background in the northern United States, attempting to better understand and appreciate a major aspect of religious-influenced culture in the southern United States which has a major bearing on science education in the region. The intellectual and emotional viewpoints of selected scientists, science educators, science teachers, and prospective science teachers are examined regarding the relationship between their orthodox Christian religious beliefs and biological evolutionary theory. We view the prospect of teaching evolution to students with such a religious commitment as a prime example of the severe limitations of cognitively-oriented conceptual change theory. We also view conflicts between religion and science regarding evolution as a bona fide example of a multicultural issue in education. These theoretical perspectives are inconsistent with the common tendency among science professionals to view or treat orthodox Christian students in a manner unconscionable with others - to disrespect their intellect or belittle their motivations, to offer judgments based on stereotypes and prejudices, to ignore threats to personal selfesteem, or to deny the de facto connection of some scientific conceptions to the morals, attitudes, and values of individuals with such religious commitments.Received: 14 June 1994; Revised: 7 November 1994;

  1. A sequence-based survey of the complex structural organization of tumor genomes

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

    2008-04-03

    The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

  2. Mammalian prions

    Science.gov (United States)

    Salamat, Muhammad Khalid; Munoz-Montesino, Carola; Moudjou, Mohammed; Rezaei, Human; Laude, Hubert; Béringue, Vincent; Dron, Michel

    2013-01-01

    Upon prion infection, abnormal prion protein (PrPSc) self-perpetuate by conformational conversion of α-helix-rich PrPC into β sheet enriched form, leading to formation and deposition of PrPSc aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrPSc and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region. PMID:23232499

  3. Mammalian prions: tolerance to sequence changes-how far?

    Science.gov (United States)

    Salamat, Muhammad Khalid; Munoz-Montesino, Carola; Moudjou, Mohammed; Rezaei, Human; Laude, Hubert; Béringue, Vincent; Dron, Michel

    2013-01-01

    Upon prion infection, abnormal prion protein (PrP (Sc) ) self-perpetuate by conformational conversion of α-helix-rich PrP (C) into β sheet enriched form, leading to formation and deposition of PrP (Sc) aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrP (Sc) and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region.

  4. High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

    Science.gov (United States)

    Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

    2015-01-01

    In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

  5. Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hanna [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kwon, Chang Seob [Department of Chemistry and Biology, Korea Science Academy of KAIST, Busan, 614-822 (Korea, Republic of); Choi, Yoonjung, E-mail: jjungii@kaist.ac.kr [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Daeyoup, E-mail: daeyoup@kaist.ac.kr [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

    2016-08-05

    Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

  6. Reverse engineering genius: historiometric studies of superlative talent.

    Science.gov (United States)

    Simonton, Dean Keith

    2016-08-01

    Although genius has been defined in the dictionary as requiring an IQ above 140, this definition depends on an arbitrary methodological decision made by Lewis Terman for his longitudinal study of more than 1500 intellectually gifted children, a study that occupies four of the five volumes of Genetic Studies of Genius. Yet, only the second volume, by Catharine Cox, studied bona fide geniuses, by applying historiometric methods to 301 highly eminent creators and leaders. After defining historiometric research, I examine the difference between historical genius and intellectual giftedness with respect to heterogeneous intellects, personality differences, and early development and show that the actual relation between IQ and genius is small and heavily contingent on domain-specific assessment, the operation of traits like persistence and openness to experience, and the impact of diversifying experiences, including both developmental adversity and subclinical psychopathology. Hence, the dictionary definition of "genius" has minimal, if any, justification. If, using historiometric methods, one works backward from recognized geniuses, such as those studied by Cox, one might not obtain the kind of sample that Terman obtained for his longitudinal study. The two methods produce two distinct subgroups of the larger population. © 2016 New York Academy of Sciences.

  7. Evolving a photosynthetic organelle.

    Science.gov (United States)

    Nakayama, Takuro; Archibald, John M

    2012-04-24

    The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles.The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis--the conversion of solar energy into chemical energy--and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  8. Cellular Kinetics of Perivascular MSC Precursors

    Directory of Open Access Journals (Sweden)

    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  9. Co-release of glutamate and GABA from single vesicles in GABAergic neurons exogenously expressing VGLUT3

    Directory of Open Access Journals (Sweden)

    Johannes eZimmermann

    2015-09-01

    Full Text Available The identity of the vesicle neurotransmitter transporter expressed by a neuron largely corresponds with the primary neurotransmitter that cell releases. However, the vesicular glutamate transporter subtype 3 (VGLUT3 is mainly expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or GABAergic neurons. Though a functional role for glutamate release from these non-glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the neuron’s characteristic neurotransmitter transporter, particularly in the case of GABAergic neurons, at the synaptic and vesicular level is less clear. In this study, we explore how exogenous expression of VGLUT3 in striatal GABAergic neurons affects the packaging and release of glutamate and GABA in synaptic vesicles. We found that VGLUT3 expression in isolated, autaptic GABAergic neurons leads to action potential evoked release of glutamate. Under these conditions, glutamate and GABA could be packaged together in single vesicles release either spontaneously or asynchronously. However, the presence of glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting a lack of synergy in vesicle filling for these transmitters. Finally, we found postsynaptic detection of glutamate released from GABAergic terminals difficult when bona fide glutamatergic synapses were present, suggesting that co-released glutamate cannot induce postsynaptic glutamate receptor clustering.

  10. Strong Generative Capacity and the Empirical Base of Linguistic Theory

    Directory of Open Access Journals (Sweden)

    Dennis Ott

    2017-09-01

    Full Text Available This Perspective traces the evolution of certain central notions in the theory of Generative Grammar (GG. The founding documents of the field suggested a relation between the grammar, construed as recursively enumerating an infinite set of sentences, and the idealized native speaker that was essentially equivalent to the relation between a formal language (a set of well-formed formulas and an automaton that recognizes strings as belonging to the language or not. But this early view was later abandoned, when the focus of the field shifted to the grammar's strong generative capacity as recursive generation of hierarchically structured objects as opposed to strings. The grammar is now no longer seen as specifying a set of well-formed expressions and in fact necessarily constructs expressions of any degree of intuitive “acceptability.” The field of GG, however, has not sufficiently acknowledged the significance of this shift in perspective, as evidenced by the fact that (informal and experimentally-controlled observations about string acceptability continue to be treated as bona fide data and generalizations for the theory of GG. The focus on strong generative capacity, it is argued, requires a new discussion of what constitutes valid empirical evidence for GG beyond observations pertaining to weak generation.

  11. ARID1B is a specific vulnerability in ARID1A-mutant cancers.

    Science.gov (United States)

    Helming, Katherine C; Wang, Xiaofeng; Wilson, Boris G; Vazquez, Francisca; Haswell, Jeffrey R; Manchester, Haley E; Kim, Youngha; Kryukov, Gregory V; Ghandi, Mahmoud; Aguirre, Andrew J; Jagani, Zainab; Wang, Zhong; Garraway, Levi A; Hahn, William C; Roberts, Charles W M

    2014-03-01

    Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.

  12. Clustering of Tissue-Specific Sub-TADs Accompanies the Regulation of HoxA Genes in Developing Limbs

    Science.gov (United States)

    Berlivet, Soizik; Paquette, Denis; Dumouchel, Annie; Langlais, David; Dostie, Josée; Kmita, Marie

    2013-01-01

    HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs). We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet “DNA loops”. Interestingly, there is no obvious relationship between the functional domains of the enhancers within the limb and how they are partitioned among the topological domains, suggesting that sub-TAD formation does not rely on enhancer activity. Moreover, we show that suppressing the transcriptional activity of enhancers does not abrogate their contacts with HoxA genes. Based on these data, we propose a model whereby chromatin architecture defines the functional landscapes of enhancers. From an evolutionary standpoint, our data points to the convergent evolution of HoxA and HoxD regulation in the fin-to-limb transition, one of the major morphological innovations in vertebrates. PMID:24385922

  13. The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.

    Science.gov (United States)

    Su, Yunshu; Wang, Xiaoli; Li, Jun; Xu, Junming; Xu, Lijun

    2015-01-01

    FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, Panalysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.

  14. A PROFILE ANALYSIS OF RAMAN-SCATTERED O VI BANDS AT 6825 Å AND 7082 Å IN SANDULEAK’S STAR

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Jeong-Eun; Lee, Hee-Won [Department of Physics and Astronomy, Sejong University, Seoul (Korea, Republic of); Angeloni, Rodolfo [Gemini Observatory, Casilla 603, La Serena (Chile); Mille, Francesco Di [Las Campanas Observatory, Carnegie Observatories, Casilla 601, La Serena (Chile); Palma, Tali, E-mail: jeung6145@gmail.com [Departamento de Ciencias Físicas, Universidad Andrés Bello, Fernández Concha 700, Las Condes, Santiago (Chile)

    2016-12-20

    We present a detailed modeling of the two broad bands observed at 6825 and 7082 Å in Sanduleak’s star, a controversial object in the Large Magellanic Cloud. These bands are known to originate from Raman scattering of O vi  λ λ 1032 and 1038 photons with atomic hydrogen and are only observed in bona fide symbiotic stars. Our high-resolution spectrum obtained with the Magellan Inamori Kyocera Echelle spectrograph at the Magellan-Clay Telescope reveals, quite surprisingly, that the profiles of the two bands look very different: while the Raman 6825 Å band shows a single broad profile with a redward extended bump, the Raman 7082 Å band exhibits a distinct triple-peak profile. Our model suggests that the O vi emission nebula can be decomposed into a red, blue, and central emission region from an accretion disk, a bipolar outflow, and a further compact, optically thick region. We also perform Monte Carlo simulations with the aim of fitting the observed flux ratio F (6825)/ F (7082) ∼ 4.5, which indicates that the neutral region in Sanduleak’s star is characterized by the column density N{sub Hi} ∼ 1 × 10{sup 23} cm{sup −2}.

  15. How carbon credits could drive the emergence of renewable energies

    International Nuclear Information System (INIS)

    Mathews, John A.

    2008-01-01

    The shift to renewable energy options and low-carbon technologies, in response to the concerns over energy security and climate change, is proceeding more slowly than many would like. The usual argument against rapid deployment of new technologies is the costs imposed on the economy, commonly interpreted in terms of upfront costs to be borne or involving large cash transfers to fund, for example, efforts to preserve rainforests. In this contribution I argue that such a perspective provides a continuing barrier to taking effective action, whereas a perspective based on creation and use of carbon credits provides a means of avoiding the shock of abrupt industrial change. Carbon credits granted for bona fide carbon load reductions could be created through private initiative, for example by merchant banks, to constitute a market that will complement regulatory-based initiatives such as national emissions trading systems. This is not a novel idea; indeed it is the way that capitalism has funded every major change, including the Industrial Revolution, through the creation of credit. The emergence of a global carbon credit economy is likely to precede a global regulatory system governing climate change and will doubtless help to stimulate the emergence of such a global system

  16. Regulation of the hematopoietic stem cell lifecycle by the endothelial niche.

    Science.gov (United States)

    Ramalingam, Pradeep; Poulos, Michael G; Butler, Jason M

    2017-07-01

    Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions. Studies employing genetic vascular models have unequivocally confirmed that ECs provide the essential instructive cues for HSC emergence during embryonic development as well as adult HSC maintenance during homeostasis and regeneration. Aging of ECs may impair their ability to maintain HSC function contributing to the development of aging-associated hematopoietic deficiencies. These findings have opened up new avenues to explore the therapeutic application of ECs. ECs can be adapted to serve as an instructive platform to expand bona fide HSCs and also utilized as a cellular therapy to promote regeneration of the hematopoietic system following myelosuppressive and myeloablative injuries. ECs provide a fertile niche for maintenance of functional HSCs throughout their lifecycle. An improved understanding of the EC-HSC cross-talk will pave the way for development of EC-directed strategies for improving HSC function during aging.

  17. A conserved tad pilus promotes Vibrio vulnificus oyster colonization.

    Science.gov (United States)

    Pu, Meng; Duriez, Patrick; Arazi, Mattan; Rowe-Magnus, Dean A

    2018-02-01

    Vibrio vulnificus has the highest death rate (>35%) and per-case economic burden ($3.3 million) of any foodborne pathogen in the United States. Infections occur via open wounds or following ingestion of contaminated seafood, most infamously oysters. We isolated a 1000th generation descendant, designated NT that exhibited increased biofilm and aggregate formation relative to its parent. We identified two significant causal changes underlying these phenotypes. First, the entire 24-kb capsular polysaccharide biosynthesis locus, which is essential for virulence but inhibits biofilm formation, had been purged from the genome. However, NT formed more extensive biofilms and aggregates than a defined cps mutant, suggesting that additional factor(s) contributed to its phenotypes. Second, the expression of a tight adherence (tad) pilus locus was elevated in NT. Deletion of the associated pilin (flp) decreased NT biofilm and aggregate formation. Furthermore, NTΔflp strains were deficient relative to NT in an oyster colonization model, demonstrating a positive correlation between the biofilm and aggregation phenotypes associated with Tad pilus production and efficient bacterial retention by feeding oysters. Despite being widely distributed in the Vibrionaceae, this is the first demonstration of a bona fide physiological role for a Tad pilus in this bacterial family. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  18. Clustering of tissue-specific sub-TADs accompanies the regulation of HoxA genes in developing limbs.

    Directory of Open Access Journals (Sweden)

    Soizik Berlivet

    Full Text Available HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs. We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet "DNA loops". Interestingly, there is no obvious relationship between the functional domains of the enhancers within the limb and how they are partitioned among the topological domains, suggesting that sub-TAD formation does not rely on enhancer activity. Moreover, we show that suppressing the transcriptional activity of enhancers does not abrogate their contacts with HoxA genes. Based on these data, we propose a model whereby chromatin architecture defines the functional landscapes of enhancers. From an evolutionary standpoint, our data points to the convergent evolution of HoxA and HoxD regulation in the fin-to-limb transition, one of the major morphological innovations in vertebrates.

  19. New Parallaxes and a Convergence Analysis for the TW Hya Association

    Science.gov (United States)

    Donaldson, J. K.; Weinberger, A. J.; Gagné, J.; Faherty, J. K.; Boss, A. P.; Keiser, S. A.

    2016-12-01

    The TW Hya Association (TWA) is a nearby stellar association with an age of ˜5-10 Myr. This is an important age for studying the late stages of star and planet formation. We measure the parallaxes of 14 candidate members of TWA. That brings to 38 the total number of individual stars with fully measured kinematics, I.e., proper motion, radial velocity, and parallax, to describe their motions through the Galaxy. We analyze these kinematics to search for convergence to a smaller volume in the past, but we find that the association is never much more compact than it is at present. We show that it is difficult to measure traceback ages for associations such as TWA that have expected velocity dispersions of 1-2 km s-1 with typical measurement uncertainties. We also use our stellar distances and pre-main-sequence evolutionary tracks to find the average age of the association of 7.9 ± 1.0 Myr. Additionally, our parallax measurement of TWA 32 indicates that it should be considered a bona fide member of TWA. Two new candidate members have high membership probabilities, and we assign them TWA numbers: TWA 45 for 2MASS J11592786-4510192 and TWA 46 for 2MASS J12354615-4115531.

  20. Expression dynamics of self-renewal factors for spermatogonial stem cells in the mouse testis.

    Science.gov (United States)

    Sakai, Mizuki; Masaki, Kaito; Aiba, Shota; Tone, Masaaki; Takashima, Seiji

    2018-04-16

    Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self-renewal factors for spermatogonial stem cells (SSCs). Although GDNF is indispensable for the maintenance of SSCs, the role of FGF2 in the testis remains to be elucidated. To clarify this, the expression dynamics and regulatory mechanisms of Fgf2 and Gdnf in the mouse testes were analyzed. It is well known that Sertoli cells express Gdnf, and its receptor is expressed in a subset of undifferentiated spermatogonia, including SSCs. However, we found that Fgf2 was mainly expressed in the germ cells and its receptors were expressed not only in the cultured spermatogonial cell line, but also in testicular somatic cells. Aging, hypophysectomy, retinoic acid treatment, and testicular injury induced distinct Fgf2 and Gdnf expression dynamics, suggesting a difference in the expression mechanism of Fgf2 and Gdnf in the testis. Such differences might cause a dynamic fluctuation of Gdnf/Fgf2 ratio depending on the intrinsic/extrinsic cues. Considering that FGF2-cultured spermatogonia exhibit more differentiated phenotype than those cultured with GDNF, FGF2 might play a role distinct from that of GDNF in the testis, despite the fact that both factors are self-renewal factor for SSC in vitro.

  1. Identification of a novel intergenic miRNA located between the human DDC and COBL genes with a potential function in cell cycle arrest.

    Science.gov (United States)

    Hoballa, Mohamad Hussein; Soltani, Bahram M; Mowla, Seyed Javad; Sheikhpour, Mojgan; Kay, Maryam

    2018-07-01

    Frequent abnormalities in 7p12 locus in different tumors like lung cancer candidate this region for novel regulatory elements. MiRNAs as novel regulatory elements encoded within the human genome are potentially oncomiRs or miR suppressors. Here, we have used bioinformatics tools to search for the novel miRNAs embedded within human chromosome 7p12. A bona fide stem loop (named mirZa precursor) had the features of producing a real miRNA (named miRZa) which was detected through RT-qPCR following the overexpression of its precursor. Then, endogenous miRZa was detected in human cell lines and tissues and sequenced. Consistent to the bioinformatics prediction, RT-qPCR as well as dual luciferase assay indicated that SMAD3 and IGF1R genes were targeted by miRZa. MiRZa-3p and miRZa-5p were downregulated in lung tumor tissue samples detected by RT-qPCR, and mirZa precursor overexpression in SW480 cells resulted in increased sub-G1 cell population. Overall, here we introduced a novel miRNA which is capable of targeting SMAD3 and IGF1R regulatory genes and increases the cell population in sub-G1 stage.

  2. The C-terminal region of the non-structural protein 2B from Hepatitis A Virus demonstrates lipid-specific viroporin-like activity

    Science.gov (United States)

    Shukla, Ashutosh; Dey, Debajit; Banerjee, Kamalika; Nain, Anshu; Banerjee, Manidipa

    2015-10-01

    Viroporins are virally encoded, membrane-active proteins, which enhance viral replication and assist in egress of viruses from host cells. The 2B proteins in the picornaviridae family are known to have viroporin-like properties, and play critical roles during virus replication. The 2B protein of Hepatitis A Virus (2B), an unusual picornavirus, is somewhat dissimilar from its analogues in several respects. HAV 2B is approximately 2.5 times the length of other 2B proteins, and does not disrupt calcium homeostasis or glycoprotein trafficking. Additionally, its membrane penetrating properties are not yet clearly established. Here we show that the membrane interacting activity of HAV 2B is localized in its C-terminal region, which contains an alpha-helical hairpin motif. We show that this region is capable of forming small pores in membranes and demonstrates lipid specific activity, which partially rationalizes the intracellular localization of full-length 2B. Using a combination of biochemical assays and molecular dynamics simulation studies, we also show that HAV 2B demonstrates a marked propensity to dimerize in a crowded environment, and probably interacts with membranes in a multimeric form, a hallmark of other picornavirus viroporins. In sum, our study clearly establishes HAV 2B as a bona fide viroporin in the picornaviridae family.

  3. 1970 British Cohort Study

    Directory of Open Access Journals (Sweden)

    Matt Brown

    2014-10-01

    Full Text Available The 1970 British Cohort Study (BCS70 is one of Britain’s world famous national longitudinal birth cohort studies, three of which are run by the Centre for Longitudinal Studies at the Institute of Education, University of London.  BCS70 follows the lives of more than 17,000 people born in England, Scotland and Wales in a single week of 1970. Over the course of cohort members lives, the BCS70 has collected information on health, physical, educational and social development, and economic circumstances among other factors. Since the birth survey in 1970, there have been nine ‘sweeps’ of all cohort members at ages 5, 10, 16, 26, 30, 34, 38 and most recently at 42. Data has been collected from a number of different sources (the midwife present at birth, parents of the cohort members, head and class teachers, school health service personnel and the cohort members themselves. The data has been collected in a variety of ways including via paper and electronic questionnaires, clinical records, medical examinations, physical measurements, tests of ability, educational assessments and diaries. The majority of BCS70 survey data can be accessed by bona fide researchers through the UK Data Service at the University of Essex.

  4. The properties of the gas around beta Pictoris

    Science.gov (United States)

    Roberge, A.

    2014-09-01

    Debris disks are often described as gas-free. Compared to protoplanetary disks, they do in general have low gas abundances, as evidenced by the very few detections of sub-mm CO emission from bona fide debris disks to date. However, some debris disks do contain low levels of detectable gas, typically seen in absorption against the stellar spectrum at UV and optical wavelengths. Of all debris disks, the gas in the Beta Pic disk is the best characterized and understood. Here, I describe those characteristics and explain our current understanding of the nature of the gas. Like the dust, the gas is secondary material coming from planetesimal destruction, and provides opportunities for sensitive probes of the bulk composition of young planetary bodies. The gas can also be a sensitive tracer of disk asymmetries and dynamical interactions, as shown by new ALMA observations of CO emission from Beta Pic (see attached infographic and YouTube video explaining the discovery). Very likely, every debris disk contains its due portion of gas, but how much that is, we do not yet know. We are poised to answer this question with the advent of ALMA. With its unprecedented sensitivity and spatial resolution, ALMA may usher in a golden age for general studies of debris gas.

  5. IRAS 18113-2503: THE WATER FOUNTAIN WITH THE FASTEST JET?

    International Nuclear Information System (INIS)

    Gomez, Jose F.; Guerrero, MartIn A.; Ricardo Rizzo, J.; Suarez, Olga; Miranda, Luis F.; Ramos-Larios, Gerardo

    2011-01-01

    We present Expanded Very Large Array water maser observations at 22 GHz toward the source IRAS 18113-2503. Maser components span over a very high velocity range of ≅ 500 km s -1 , the second largest found in a Galactic maser, only surpassed by the high-mass star-forming region W49N. Maser components are grouped into a blueshifted and a redshifted cluster, separated by 0.''12. Further mid-IR and radio data suggest that IRAS 18113-2503 is a post-asymptotic giant branch star, thus a new bona fide member of the rare class of 'water fountains' (WFs). It is the evolved object with the largest total velocity spread in its water masers and with the highest velocity dispersion within its redshifted and blueshifted lobes (≅ 170 km s -1 ). The large total velocity range of emission probably indicates that IRAS 18113-2503 has the fastest jet among the known WF stars. On the other hand, the remarkably high velocity dispersion within each lobe may be interpreted in terms of shocks produced by an episode of mass ejection whose velocity increased up to very high values or, alternatively, by projection effects in a jet with a large opening angle and/or precessing motions.

  6. Third party objection and action against enforcement: Request for exclusion

    Directory of Open Access Journals (Sweden)

    Salma Marija

    2014-01-01

    Full Text Available This paper deals with a right of a third party to prevent enforcement on the basis of a claim and evidence that rights or assets seized in enforcement proceeding belong to him (third party and not to the enforcement debtor. In most of jurisdictions that were subject of analysis of this paper, this right of a third party is exercised by filing an objection to the court conducting enforcement proceedings. The claim of the third party is directed towards the enforcement creditor as well as against the enforcement debtor. In the event the claim of the third party is being contested, the court instructs the third party to initiate litigation proceedings for determining whether the third party is entitled to exclusion of such rights or assets from enforcement, especially if such third party holds property rights or some other rights over the assets that are being subject to enforcement proceedings. In majority of analyzed jurisdictions, enforcement proceedings are being suspended provided the third party, in the objection being filed makes prima facie likely, on the basis of credible evidence, that his assets were seized in the enforcement proceedings. However, according to the law of the Republic of Serbia, a credible objection of a third party does not result in suspension of enforcement proceedings, something that is being criticized in this paper. As a result of this provision of the law, a bona fide third party is forced to endure the enforcement although his claim has been made likely and subsequently confirmed in the litigation proceedings. The author, in particular, points to the legal consequences of mala fide enforcement creditor that knew that the assets that are being subject of the enforcement proceedings do not belong to the enforcement debtor. The author is of the opinion that, in such cases, the enforcement creditor should be obliged to pay to the third party damages that such party suffered as a result of enforcement proceedings being

  7. National Recommended Water Quality Criteria

    Data.gov (United States)

    U.S. Environmental Protection Agency — The National Recommended Water Quality Criteria is a compilation of national recommended water quality criteria for the protection of aquatic life and human health...

  8. Water quality criteria for lead

    Energy Technology Data Exchange (ETDEWEB)

    Nagpal, N.K.

    1987-01-01

    This report is one in a series that establishes water quality criteria for British Columbia. The report sets criteria for lead to protect a number of water uses, including drinking water, freshwater and marine aquatic life, wildlife, livestock, irrigation, and recreation. The criteria are set as either maximum concentrations of total lead that should not be exceeded at any time, or average concentrations that should not be exceeded over a 30-day period. Actual values are summarized.

  9. 46 CFR 385.51 - Criteria: Projects.

    Science.gov (United States)

    2010-10-01

    ... results; (iii) The extent of the problems treated and whether the objectives sought by the undertaking are... MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MISCELLANEOUS RESEARCH AND DEVELOPMENT GRANT AND COOPERATIVE AGREEMENTS REGULATIONS Criteria for Award § 385.51 Criteria: Projects. The criteria to be used by...

  10. Criteria for saturated magnetization loop

    International Nuclear Information System (INIS)

    Harres, A.; Mikhov, M.; Skumryev, V.; Andrade, A.M.H. de; Schmidt, J.E.; Geshev, J.

    2016-01-01

    Proper estimation of magnetization curve parameters is vital in studying magnetic systems. In the present article, criteria for discrimination non-saturated (minor) from saturated (major) hysteresis loops are proposed. These employ the analysis of (i) derivatives of both ascending and descending branches of the loop, (ii) remanent magnetization curves, and (iii) thermomagnetic curves. Computational simulations are used in order to demonstrate their validity. Examples illustrating the applicability of these criteria to well-known real systems, namely Fe_3O_4 and Ni fine particles, are provided. We demonstrate that the anisotropy-field value estimated from a visual examination of an only apparently major hysteresis loop could be more than two times lower than the real one. - Highlights: • Proper estimation of hysteresis-loop parameters is vital in magnetic studies. • We propose criteria for discrimination minor from major hysteresis loops. • The criteria analyze magnetization, remanence and ZFC/FC curves and/or their derivatives. • Examples of their application on real nanoparticles systems are given. • Using the criteria could avoid twofold or bigger saturation-field underestimation errors.

  11. Criteria for saturated magnetization loop

    Energy Technology Data Exchange (ETDEWEB)

    Harres, A. [Departamento de Física, UFSM, Santa Maria, 97105-900 Rio Grande do Sul (Brazil); Mikhov, M. [Faculty of Physics, University of Sofia, 1164 Sofia (Bulgaria); Skumryev, V. [Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona (Spain); Departament de Física, Universitat Autònoma de Barcelona, 08193 Barcelona (Spain); Andrade, A.M.H. de; Schmidt, J.E. [Instituto de Física, UFRGS, Porto Alegre, 91501-970 Rio Grande do Sul (Brazil); Geshev, J., E-mail: julian@if.ufrgs.br [Departament de Física, Universitat Autònoma de Barcelona, 08193 Barcelona (Spain); Instituto de Física, UFRGS, Porto Alegre, 91501-970 Rio Grande do Sul (Brazil)

    2016-03-15

    Proper estimation of magnetization curve parameters is vital in studying magnetic systems. In the present article, criteria for discrimination non-saturated (minor) from saturated (major) hysteresis loops are proposed. These employ the analysis of (i) derivatives of both ascending and descending branches of the loop, (ii) remanent magnetization curves, and (iii) thermomagnetic curves. Computational simulations are used in order to demonstrate their validity. Examples illustrating the applicability of these criteria to well-known real systems, namely Fe{sub 3}O{sub 4} and Ni fine particles, are provided. We demonstrate that the anisotropy-field value estimated from a visual examination of an only apparently major hysteresis loop could be more than two times lower than the real one. - Highlights: • Proper estimation of hysteresis-loop parameters is vital in magnetic studies. • We propose criteria for discrimination minor from major hysteresis loops. • The criteria analyze magnetization, remanence and ZFC/FC curves and/or their derivatives. • Examples of their application on real nanoparticles systems are given. • Using the criteria could avoid twofold or bigger saturation-field underestimation errors.

  12. 45 CFR 1176.3 - Criteria.

    Science.gov (United States)

    2010-10-01

    ... ENDOWMENT FOR THE HUMANITIES PART-TIME CAREER EMPLOYMENT § 1176.3 Criteria. Positions becoming vacant... to part-time. Among the criteria which may be used when conducting this review are: (a) Mission...

  13. 10 CFR 905.36 - Marketing criteria.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Marketing criteria. 905.36 Section 905.36 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Power Marketing Initiative § 905.36 Marketing criteria. Western shall retain applicable provisions of existing marketing criteria for projects where...

  14. A bona fide two-dimensional percolation model: an insight into the optimum photoactivator concentration in La2/3-xEuxTa2O7 nanosheets

    Directory of Open Access Journals (Sweden)

    Tadashi C Ozawa, Katsutoshi Fukuda, Yasuo Ebina, Kosuke Kosuda, Akira Sato, Yuichi Michiue, Keiji Kurashima and Takayoshi Sasaki

    2011-01-01

    Full Text Available La–Eu solid solution nanosheets La2/3−xEuxTa2O7 have been synthesized, and their photoluminescence properties have been investigated. La2/3−xEuxTa2O7 nanosheets were prepared from layered perovskite compounds Li2La2/3−xEuxTa2O7 as the precursors by soft chemical exfoliation reactions. Both the precursors and the exfoliated nanosheets exhibit a decrease in intralayer lattice parameters as the Eu contents increase. However, there is a discontinuity in this trend between the nominal Eu content ranges x≤ 0.3 and x ≥ 0.4. This discontinuity is attributed to the difference in degree of TaO6 octahedra tilting for the La- and Eu-rich phases. La2/3−xEuxTa2O7 nanosheets exhibit red emission, characteristic of the f–f transitions in Eu3+ photoactivators. The photoluminescence emission can be obtained from both host and direct photoactivator excitation. However, photoluminescence emission through host excitation is much more dominant than that through direct photoactivator excitation, and this behavior is consistent with that of all the other rare-earth photoactivated nanosheets reported previously. The absolute photoluminescence quantum efficiency of the La2/3−xEuxTa2O7 nanosheets increases as the experimentally determined Eu contents increase up to x=0.45 and decrease above it. This result is in good agreement with the optimum photoactivator concentration expected from the percolation theory. These solid solution La2/3−xEuxTa2O7 nanosheets are excellent models for validating the theory of optimum photoactivator concentration in the truly two-dimensional photoactivator matrix.

  15. Characteristics of women in a prison mental health assessment unit in England and Wales (2008-2010).

    Science.gov (United States)

    Hales, Heidi; Somers, Nadia; Reeves, Chrissy; Bartlett, Annie

    2016-04-01

    The high prevalence of mental disorders among women in prison is recognised worldwide. In England and Wales, successive governments and independent reports have argued that the equivalent of community care in prisons is acceptable but that some mental health assessment units (MHAUs), staffed by professional clinicians, should remain. These have not been researched. This paper aimed to explore patterns of use of a MHAU in a women's prison in England and to test the hypothesis that it was being used only, as intended--to hold women pending transfer to a health service hospital or in a bona fide crisis. Anonymised data on all women transferred to one MHAU between 1 January 2008 and 31 August 2010 were obtained from the prison files and subjected to descriptive analysis. Less than a third of these women were transferred to an outside hospital; this group stayed longest in the unit. An overlapping group of 52% of the women was under a special assessment, care in custody and teamwork protocol because of suicide or serious self-harm risk. Thus, 188 (68%) admissions fulfilled national protocol criteria for MHAU admissions. Two in five women admitted were released or returned to ordinary prison locations. Nevertheless, over 80% of the women were known to external mental health services, and 64 (30%) were so unwell on arrival in prison that they were transferred directly to the MHAU. Over a third of admissions were of women admitted more than once during the 32 months of study, and this was significantly more likely after release from prison directly to the community. Our hypothesis was not sustained, and it seems unlikely that this prison MHAU is unique in being used outside its strict remit. A shift from studying the epidemiology of mental disorder in prisons to the epidemiology of mental health needs could benefit this vulnerable group and the wider community alike. Copyright © 2015 John Wiley & Sons, Ltd.

  16. User-Centric Multi-Criteria Information Retrieval

    Science.gov (United States)

    Wolfe, Shawn R.; Zhang, Yi

    2009-01-01

    Information retrieval models usually represent content only, and not other considerations, such as authority, cost, and recency. How could multiple criteria be utilized in information retrieval, and how would it affect the results? In our experiments, using multiple user-centric criteria always produced better results than a single criteria.

  17. Criteria for operator review of workplace changes

    International Nuclear Information System (INIS)

    Davey, E.

    2000-01-01

    A set of criteria for reviewing workplace changes has been developed for use by plant Operations staff. The criteria were developed to provide Operations staff with a practical framework for structuring assessments and subsequent review comments with regard to control room modifications and innovations that impact their work environment. The criteria were assembled from design, operations and human factors engineering principles, and system review experiences with plant Operations staff over the past ten years. Operations staff at several CANDU stations helped shape the emphasis for initial criteria definition and have assisted with criteria refinement through trial applications. Use of the criteria is expected to lead to more effective and task relevant equipment evaluations by Operations staff, and ultimately lead to system modifications and innovations that better serve plant operation needs. The paper begins with a discussion of the rationale for criteria development and the attributes of 'good' design. The balance of the paper outlines the project objectives, describes the approach applied in assembling, structuring, and refining the review criteria, and illustrates the application of the criteria in the review of a proposed control room innovation. (author)

  18. Quality criteria for chest X-ray image

    International Nuclear Information System (INIS)

    Krieg, R.

    1985-01-01

    A distinction has to be made between invariable and variable criteria in the determination of chest X-ray picture quality criteria. The invariable criteria are defined by the properties of the object and the psychophysiological laws of perception and cognition, and the variable criteria are determined by the prevailing state of the art of technology. An agreement on these criteria is based on the knowledge of the nature and the technical conditions of X-ray picture production and reproduction. The slogan 'the best picture at the lowest dose' dominates, too, the discussion centering around the X-ray picture of the chest, its quality and criteria. (orig./MG) [de

  19. CCS site characterisation criteria

    Energy Technology Data Exchange (ETDEWEB)

    Bachu, S.; Hawkes, C.; Lawton, D.; Pooladi-Darvish, M.; Perkins, E.

    2009-12-15

    IEA GHG recently commissioned the Alberta Research Counil in Canada to conduct a review of storage site selection criteria and site characterisation methods in order to produce a synthesis report. This report reviews the literature on the subject on the site seleciton and characterisation since the publication of the IPCC Special Report on CCS, and provides a synthesis and classification of criteria. 161 refs.

  20. Risk assessment of soil contamination criteria

    International Nuclear Information System (INIS)

    King, C.M.; Marter, W.L.; Montaque, D.F.; Holton, G.A.

    1987-06-01

    Criteria have been developed to select radioactive and nonradioactive contaminants at waste sites detailed analysis and risk assessment. These criteria were based on soil and water quality guidelines developed by various government agencies to determine if the criteria were appropriate. We performed a risk assessment of a hypothetical site which contained radioactive and nonradioactive contaminants at levels equal to the criteria values. Risks to the public from atmospheric, surface water, and groundwater exposure pathways were examined. Health risks to the public from atmospheric releases of radioactive and nonradioactive materials from a waste at soil criteria contamination levels are low. Health risks to the maximally exposed individual to chemical carcinogens are considerably below traditional EPA action levels. And health risks to the maximally exposed individual to atmospherically released radioactive contaminants is 1.88 x 10 -7 , more than a factor of 5 less than 10 -6 . Based on our atmospheric exposure pathways analysis and risk assessment, the applied soil criteria are appropriate for screening out unimportant risk contributors to human health from atmospheric exposure pathways. 13 refs., 3 figs., 7 tabs