Science.gov

Sample records for act target entities

  1. 48 CFR 952.226-71 - Utilization of Energy Policy Act target entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... that meets the requirements of 34 CFR 600.4(a) and has a student enrollment that consists of at least... CFR 608.2; and (3) Small business concerns, as defined under section 3 of the Small Business Act (15 U... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Utilization of...

  2. 48 CFR 952.226-71 - Utilization of Energy Policy Act target entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... that meets the requirements of 34 CFR 600.4(a) and has a student enrollment that consists of at least... CFR 608.2; and (3) Small business concerns, as defined under section 3 of the Small Business Act (15 U... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Utilization of...

  3. 48 CFR 952.226-71 - Utilization of Energy Policy Act target entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... that meets the requirements of 34 CFR 600.4(a) and has a student enrollment that consists of at least... CFR 608.2; and (3) Small business concerns, as defined under section 3 of the Small Business Act (15 U... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Utilization of...

  4. 48 CFR 952.226-71 - Utilization of Energy Policy Act target entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... that meets the requirements of 34 CFR 600.4(a) and has a student enrollment that consists of at least... CFR 608.2; and (3) Small business concerns, as defined under section 3 of the Small Business Act (15 U..., Eskimos, Aleuts, and Native Hawaiians, or any combination thereof; (2) Institutions of higher...

  5. 48 CFR 952.226-71 - Utilization of Energy Policy Act target entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... that meets the requirements of 34 CFR 600.4(a) and has a student enrollment that consists of at least... CFR 608.2; and (3) Small business concerns, as defined under section 3 of the Small Business Act (15 U..., Eskimos, Aleuts, and Native Hawaiians, or any combination thereof; (2) Institutions of higher...

  6. Microrobotic navigable entities for Magnetic Resonance Targeting.

    PubMed

    Martel, Sylvain

    2010-01-01

    Magnetic Resonance Targeting (MRT) uses MRI for gathering tracking data to determine the position of microscale entities with the goal of guiding them towards a specific target in the body accessible through the vascular network. At full capabilities, a MRT platform designed to treat a human would consist of a clinical MRI scanner running special algorithms and upgraded to provide propulsion gradient up to approximately 400mT/m to enable entities as small as a few tens of micrometers in diameter and containing magnetic nanoparticles (MNP) to be steered at vessel bifurcations based on tracking information. Indeed, using a clinical MRI system, we showed that such single entity with a diameter as small as 15microm is detectable in gradient-echo scans. Among many potential interventions, targeted cancer therapy is a good initial application for such new microrobotic approach since secondary toxicity for the patient could be reduced while increasing therapeutic efficacy using lower dosages. Although many types of such entities are needed to provide a larger set of tools, here, only three initial types designed with different functionalities and for different types of cancer are briefly described. Initially designed for targeted chemo-embolization of liver tumors, the first type known as Therapeutic Magnetic Micro-Carriers (TMMC) consists in its present form of approximately 50 microm PLGA microparticles containing therapeutics and approximately 180 nm FeCo MNP. For the second type, MNP are not only used for propulsion and tracking, but also actuation based on a local elevation of the temperature. In its simplest form, it consists of approxiamtely 20 nm MNP embedded in a thermo-sensitive hydrogel known as PNIPA, allowing additional functionalities such as computer triggered drug release and targeted hyperthermia. The third type initially considered to target colorectal tumors, consists of 1-2 microm MR-trackable and controllable MC-1 Magnetotactic Bacteria (MTB) with

  7. 17 CFR 230.157 - Small entities under the Securities Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Small entities under the Securities Act for purposes of the Regulatory Flexibility Act. 230.157 Section 230.157 Commodity and... General § 230.157 Small entities under the Securities Act for purposes of the Regulatory Flexibility...

  8. 17 CFR 230.157 - Small entities under the Securities Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Small entities under the Securities Act for purposes of the Regulatory Flexibility Act. 230.157 Section 230.157 Commodity and... General § 230.157 Small entities under the Securities Act for purposes of the Regulatory Flexibility...

  9. 17 CFR 230.157 - Small entities under the Securities Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Small entities under the Securities Act for purposes of the Regulatory Flexibility Act. 230.157 Section 230.157 Commodity and... General § 230.157 Small entities under the Securities Act for purposes of the Regulatory Flexibility...

  10. 17 CFR 230.157 - Small entities under the Securities Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Small entities under the Securities Act for purposes of the Regulatory Flexibility Act. 230.157 Section 230.157 Commodity and... General § 230.157 Small entities under the Securities Act for purposes of the Regulatory Flexibility...

  11. 17 CFR 230.157 - Small entities under the Securities Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Small entities under the Securities Act for purposes of the Regulatory Flexibility Act. 230.157 Section 230.157 Commodity and... General § 230.157 Small entities under the Securities Act for purposes of the Regulatory Flexibility...

  12. 17 CFR 260.0-7 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Small entities for purposes of the Regulatory Flexibility Act. 260.0-7 Section 260.0-7 Commodity and Securities Exchanges SECURITIES... of the Commission § 260.0-7 Small entities for purposes of the Regulatory Flexibility Act....

  13. 17 CFR 260.0-7 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Small entities for purposes of the Regulatory Flexibility Act. 260.0-7 Section 260.0-7 Commodity and Securities Exchanges SECURITIES... of the Commission § 260.0-7 Small entities for purposes of the Regulatory Flexibility Act....

  14. 17 CFR 260.0-7 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Small entities for purposes of the Regulatory Flexibility Act. 260.0-7 Section 260.0-7 Commodity and Securities Exchanges SECURITIES... of the Commission § 260.0-7 Small entities for purposes of the Regulatory Flexibility Act....

  15. 17 CFR 260.0-7 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Small entities for purposes of the Regulatory Flexibility Act. 260.0-7 Section 260.0-7 Commodity and Securities Exchanges SECURITIES... of the Commission § 260.0-7 Small entities for purposes of the Regulatory Flexibility Act....

  16. 17 CFR 260.0-7 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Small entities for purposes of the Regulatory Flexibility Act. 260.0-7 Section 260.0-7 Commodity and Securities Exchanges SECURITIES... of the Commission § 260.0-7 Small entities for purposes of the Regulatory Flexibility Act....

  17. 17 CFR 270.0-10 - Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act. 270.0-10 Section 270.0-10 Commodity... Regulatory Flexibility Act. (a) General. For purposes of Commission rulemaking in accordance with...

  18. 17 CFR 270.0-10 - Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act. 270.0-10 Section 270.0-10 Commodity... Regulatory Flexibility Act. (a) General. For purposes of Commission rulemaking in accordance with...

  19. 17 CFR 270.0-10 - Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act. 270.0-10 Section 270.0-10 Commodity... Regulatory Flexibility Act. (a) General. For purposes of Commission rulemaking in accordance with...

  20. 17 CFR 270.0-10 - Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act. 270.0-10 Section 270.0-10 Commodity... Regulatory Flexibility Act. (a) General. For purposes of Commission rulemaking in accordance with...

  1. 17 CFR 270.0-10 - Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Small entities under the Investment Company Act for purposes of the Regulatory Flexibility Act. 270.0-10 Section 270.0-10 Commodity... Regulatory Flexibility Act. (a) General. For purposes of Commission rulemaking in accordance with...

  2. 17 CFR 23.440 - Requirements for swap dealers acting as advisors to Special Entities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the swap dealer recommends a swap or trading strategy involving a swap that is tailored to the particular needs or characteristics of the Special Entity. (b) Safe harbors. A swap dealer will not “act as... evaluated by a fiduciary before the transaction occurs; or (B) That any recommendation the Special...

  3. Genetic discrimination and the public entities and public accommodations titles of the americans with disabilities act

    SciTech Connect

    Alper, J.S. ); Natowicz, M.R. Shriver Center for Mental Retardation, Waltham, MA )

    1993-07-01

    The introduction of newly developed medical genetic diagnostic tests has been accompanied by social problems involving privacy issues and genetic discrimination. Previous studies of genetic discrimination have focused on the areas of employment and insurance. In this paper, the authors provide six hypothetical illustrative cases of genetic discrimination involving access to public entities and to private entities considered to be public accommodations. They argue that many of these forms of genetic discrimination that arise in both the public and private sectors should be prohibited by Titles II and III, respectively, of the Americans with Disabilities Act of 1990.

  4. Genetic discrimination and the public entities and public accommodations Titles of the Americans with Disabilities Act.

    PubMed

    Alper, J S; Natowicz, M R

    1993-07-01

    The introduction of newly developed medical genetic diagnostic tests has been accompanied by social problems involving privacy issues and genetic discrimination. Previous studies of genetic discrimination have focused on the areas of employment and insurance. In this paper, we provide six hypothetical illustrative cases of genetic discrimination involving access to public entities and to private entities considered to be public accommodations. We argue that many of these forms of genetic discrimination that arise in both the public and private sectors should be prohibited by Titles II and III, respectively, of the Americans with Disabilities Act of 1990.

  5. 76 FR 18821 - Persons and Entities on Whom Sanctions Have Been Imposed Under the Iran Sanctions Act of 1996

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... State in the Presidential Memorandum of November 21, 1996, 61 FR 64249 (the ``Delegation Memorandum... and Entities on Whom Sanctions Have Been Imposed Under the Iran Sanctions Act of 1996 AGENCY... engaged in a sanctionable investment described in section 5(a)(1) of the Iran Sanctions Act of 1996...

  6. 15 CFR 744.11 - License requirements that apply to entities acting contrary to the national security or foreign...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... entities acting contrary to the national security or foreign policy interests of the United States. 744.11...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY... national security or foreign policy interests of the United States. BIS may impose foreign policy...

  7. 15 CFR 744.11 - License requirements that apply to entities acting contrary to the national security or foreign...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... entities acting contrary to the national security or foreign policy interests of the United States. 744.11...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY... national security or foreign policy interests of the United States. BIS may impose foreign policy...

  8. 15 CFR 744.11 - License requirements that apply to entities acting contrary to the national security or foreign...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... entities acting contrary to the national security or foreign policy interests of the United States. 744.11...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS CONTROL POLICY... national security or foreign policy interests of the United States. BIS may impose foreign policy...

  9. 75 FR 62916 - Persons and Entities on Whom Sanctions Have Been Imposed Under the Iran Sanctions Act of 1996

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... authority delegated to the Secretary of State in the Presidential Memorandum of November 21, 1996, 61 FR... and Entities on Whom Sanctions Have Been Imposed Under the Iran Sanctions Act of 1996 AGENCY... Intertrade Company (NICO) has engaged in a sanctionable investment described in section 5(a)(1) of the...

  10. Drug discovery alliances in India--indications, targets, and new chemical entities.

    PubMed

    Differding, Edmond

    2014-01-01

    Global pharmaceutical and biotechnology companies have been building increasingly on the skills and services offered by Indian biotech companies through strategic collaborative partnerships and alliances to fuel their in-house discovery and development pipelines. With the exception of generic press releases, however, very little has been published on the process and progress of drug discovery itself, such as the targets or modes of action involved, nor on the scientific output of such collaborations, and therefore on new chemical entities coming out of India through research collaborations. This Essay provides an analytical review of recent patents, patent applications, and peer-reviewed publications of major research alliances. It aims at highlighting their scientific output as well as the considerable bandwidth of targets and therapeutic areas involved. PMID:24136820

  11. 78 FR 42484 - Small Entity Size Standards Under the Regulatory Flexibility Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... carriers with revenues that would bring them within the Class III definition. 68 FR 24,891 (2003); see also 62 FR 43,024 (1997). The SBA's Office of Advocacy has been consulted with respect to the Board's... Surface Transportation Board 49 CFR Chapter X Small Entity Size Standards Under the Regulatory...

  12. 15 CFR 744.11 - License requirements that apply to entities acting contrary to the national security or foreign...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... section by adding an entity to the Entity List (Supp. No. 4 to this part) with a reference to this section and by stating on the Entity List the license requirements and license application review policy that apply to that entity. BIS may remove an entity from the Entity List if it is no longer engaged in...

  13. 17 CFR 275.0-7 - Small entities under the Investment Advisers Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... annual updating amendment to Form ADV (17 CFR 279.1), of less than $25 million, or such higher amount as... Investment Advisers Act for purposes of the Regulatory Flexibility Act. 275.0-7 Section 275.0-7 Commodity and... Regulatory Flexibility Act. (a) For purposes of Commission rulemaking in accordance with the provisions...

  14. 17 CFR 275.0-7 - Small entities under the Investment Advisers Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... annual updating amendment to Form ADV (17 CFR 279.1), of less than $25 million, or such higher amount as... Investment Advisers Act for purposes of the Regulatory Flexibility Act. 275.0-7 Section 275.0-7 Commodity and... Regulatory Flexibility Act. (a) For purposes of Commission rulemaking in accordance with the provisions...

  15. 17 CFR 275.0-7 - Small entities under the Investment Advisers Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... annual updating amendment to Form ADV (17 CFR 279.1), of less than $25 million, or such higher amount as... Investment Advisers Act for purposes of the Regulatory Flexibility Act. 275.0-7 Section 275.0-7 Commodity and... Regulatory Flexibility Act. (a) For purposes of Commission rulemaking in accordance with the provisions...

  16. 17 CFR 275.0-7 - Small entities under the Investment Advisers Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... annual updating amendment to Form ADV (17 CFR 279.1), of less than $25 million, or such higher amount as... Investment Advisers Act for purposes of the Regulatory Flexibility Act. 275.0-7 Section 275.0-7 Commodity and... Regulatory Flexibility Act. (a) For purposes of Commission rulemaking in accordance with the provisions...

  17. 17 CFR 275.0-7 - Small entities under the Investment Advisers Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... annual updating amendment to Form ADV (17 CFR 279.1), of less than $25 million, or such higher amount as... Investment Advisers Act for purposes of the Regulatory Flexibility Act. 275.0-7 Section 275.0-7 Commodity and... Regulatory Flexibility Act. (a) For purposes of Commission rulemaking in accordance with the provisions...

  18. Organizational integrity of entities that are implementing programs and activities under the Leadership Act. Final rule.

    PubMed

    2010-04-13

    The Department is issuing a final rule establishing the organizational integrity requirements for Federal funding recipients under the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act of 2003 (Leadership Act). This rule requires that funding announcements and agreements with funding recipients include a clause that states that the recipient is opposed to prostitution and sex trafficking because of the psychological and physical risks they pose for women, men and children. This rule also modifies the requirements for recipient-affiliate separation and eliminates the requirement for an additional certification by funding recipients.

  19. Organizational integrity of entities that are implementing programs and activities under the Leadership Act. Final rule.

    PubMed

    2010-04-13

    The Department is issuing a final rule establishing the organizational integrity requirements for Federal funding recipients under the United States Leadership Against HIV/AIDS, Tuberculosis, and Malaria Act of 2003 (Leadership Act). This rule requires that funding announcements and agreements with funding recipients include a clause that states that the recipient is opposed to prostitution and sex trafficking because of the psychological and physical risks they pose for women, men and children. This rule also modifies the requirements for recipient-affiliate separation and eliminates the requirement for an additional certification by funding recipients. PMID:20387319

  20. Cell-targeting aptamers act as intracellular delivery vehicles.

    PubMed

    Gopinath, Subash C B; Lakshmipriya, Thangavel; Chen, Yeng; Arshad, M K Md; Kerishnan, Jesinda P; Ruslinda, A R; Al-Douri, Yarub; Voon, C H; Hashim, Uda

    2016-08-01

    Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

  1. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes

    PubMed Central

    Edagwa, Benson J.; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E.; Narayanasamy, Prabagaran

    2014-01-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.—Edagwa, B. J., Guo, D., Puligujja, P., Chen, H., McMillan, J., Liu, X., Gendelman, H. E., Narayanasamy, P. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. PMID:25122556

  2. Moving Hands, Moving Entities

    ERIC Educational Resources Information Center

    Setti, Annalisa; Borghi, Anna M.; Tessari, Alessia

    2009-01-01

    In this study we investigated with a priming paradigm whether uni and bimanual actions presented as primes differently affected language processing. Animals' (self-moving entities) and plants' (not self-moving entities) names were used as targets. As prime we used grasping hands, presented both as static images and videos. The results showed an…

  3. Trends In Orphan New Molecular Entities, 1983-2014: Half Were First In Class, And Rare Cancers Were The Most Frequent Target.

    PubMed

    Miller, Kathleen L; Lanthier, Michael

    2016-03-01

    The Orphan Drug Act was enacted in 1983 to stimulate drug development for rare diseases. How well this law has accomplished that goal is an important public health question. This study examined the characteristics of the 209 orphan drugs approved as new molecular entities in the period 1983-2014. As a whole, these drugs were highly innovative and provided substantial gains in reducing unmet medical needs for rare diseases: Over 50 percent of the drugs were first in class, and 78 percent received a priority review. Drugs approved as either therapeutic or supportive therapies for rare cancers represented the highest proportion of these drugs (35 percent). Additionally, in 2010-14 large companies became a strong presence in developing orphan new molecular entities for oncology indications. Overall, new orphan drugs appeared to be highly innovative and provided important advances in care for patients with rare diseases. PMID:26953301

  4. Trends In Orphan New Molecular Entities, 1983-2014: Half Were First In Class, And Rare Cancers Were The Most Frequent Target.

    PubMed

    Miller, Kathleen L; Lanthier, Michael

    2016-03-01

    The Orphan Drug Act was enacted in 1983 to stimulate drug development for rare diseases. How well this law has accomplished that goal is an important public health question. This study examined the characteristics of the 209 orphan drugs approved as new molecular entities in the period 1983-2014. As a whole, these drugs were highly innovative and provided substantial gains in reducing unmet medical needs for rare diseases: Over 50 percent of the drugs were first in class, and 78 percent received a priority review. Drugs approved as either therapeutic or supportive therapies for rare cancers represented the highest proportion of these drugs (35 percent). Additionally, in 2010-14 large companies became a strong presence in developing orphan new molecular entities for oncology indications. Overall, new orphan drugs appeared to be highly innovative and provided important advances in care for patients with rare diseases.

  5. 50 CFR 648.121 - Scup Annual Catch Target (ACT).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... shall identify and review the relevant sources of management uncertainty to recommend ACTs for the... Committee recommendations shall identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant...

  6. 50 CFR 648.121 - Scup Annual Catch Target (ACT).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... shall identify and review the relevant sources of management uncertainty to recommend ACTs for the... Committee recommendations shall identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant...

  7. 50 CFR 648.121 - Scup Annual Catch Target (ACT).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... shall identify and review the relevant sources of management uncertainty to recommend ACTs for the... Committee recommendations shall identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant...

  8. 50 CFR 648.291 - Tilefish Annual Catch Target (ACT).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Committee shall identify and review the relevant sources of management uncertainty to recommend an ACT as... identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the...

  9. 50 CFR 648.291 - Tilefish Annual Catch Target (ACT).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Committee shall identify and review the relevant sources of management uncertainty to recommend an ACT as... identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the...

  10. 50 CFR 648.291 - Tilefish Annual Catch Target (ACT).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Committee shall identify and review the relevant sources of management uncertainty to recommend an ACT as... identify the specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the...

  11. Conceptual Entities.

    ERIC Educational Resources Information Center

    Greeno, James G.

    Discussed is one "quite general" attribute that can differentiate problem representations: the kinds of entities that are included -- the cognitive objects that the system can reason about in a relatively direct way, and that are included continuously in the representation. The ontology of a domain is significant for four reasons. First, ontology…

  12. Dual-Acting Compounds Targeting Endocannabinoid and Endovanilloid Systems-A Novel Treatment Option for Chronic Pain Management.

    PubMed

    Malek, Natalia; Starowicz, Katarzyna

    2016-01-01

    Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment. Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments. The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects. Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target. A number of studies suggest the involvement of the cannabinoid and vanilloid receptors in pain. Interestingly cannabinoid system is in interrelation with other systems that comprise lipid mediators: prostaglandins, produced by COX enzyme. Therefore, in the present review, we summarize the role of dual-acting molecules (FAAH/TRPV1 and FAAH/COX-2 inhibitors) that interact with endocannabinoid and endovanillinoid systems and act as analgesics by elevating the endogenously produced endocannabinoids and dampening the production of pro-inflammatory prostaglandins. The plasticity of the endocannabinoid system (ECS) and the ability of a single chemical entity to exert an activity on two receptor systems has been developed and extensively investigated. Here, we review up-to-date pharmacological studies on compounds interacting with FAAH enzyme together with TRPV1 receptor or COX-2 enzyme respectively. Multi-target pharmacological intervention for treating pain may lead to the development of original and efficient treatments. PMID:27582708

  13. Dual-Acting Compounds Targeting Endocannabinoid and Endovanilloid Systems—A Novel Treatment Option for Chronic Pain Management

    PubMed Central

    Malek, Natalia; Starowicz, Katarzyna

    2016-01-01

    Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment. Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments. The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects. Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target. A number of studies suggest the involvement of the cannabinoid and vanilloid receptors in pain. Interestingly cannabinoid system is in interrelation with other systems that comprise lipid mediators: prostaglandins, produced by COX enzyme. Therefore, in the present review, we summarize the role of dual-acting molecules (FAAH/TRPV1 and FAAH/COX-2 inhibitors) that interact with endocannabinoid and endovanillinoid systems and act as analgesics by elevating the endogenously produced endocannabinoids and dampening the production of pro-inflammatory prostaglandins. The plasticity of the endocannabinoid system (ECS) and the ability of a single chemical entity to exert an activity on two receptor systems has been developed and extensively investigated. Here, we review up-to-date pharmacological studies on compounds interacting with FAAH enzyme together with TRPV1 receptor or COX-2 enzyme respectively. Multi-target pharmacological intervention for treating pain may lead to the development of original and efficient treatments. PMID:27582708

  14. 50 CFR 622.41 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... targets (ACTs), and accountability measures (AMs). 622.41 Section 622.41 Wildlife and Fisheries FISHERY....41 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). (a... projected to reach the annual catch target (ACT) specified in § 622.39(a)(1)(v)(commercial quota),...

  15. Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

    PubMed

    2006-11-13

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

  16. Discovery of New Chemical Entities for Old Targets: Insights on the Lead Optimization of Chromone-Based Monoamine Oxidase B (MAO-B) Inhibitors.

    PubMed

    Reis, Joana; Cagide, Fernando; Chavarria, Daniel; Silva, Tiago; Fernandes, Carlos; Gaspar, Alexandra; Uriarte, Eugenio; Remião, Fernando; Alcaro, Stefano; Ortuso, Francesco; Borges, Fernanda

    2016-06-23

    The discovery of new chemical entities endowed with potent, selective, and reversible monoamine oxidase B inhibitory activity is a clinically relevant subject. Therefore, a small library of chromone derivatives was synthesized and screened toward human monoamine oxidase isoforms (hMAO-A and hMAO-B). The structure-activity relationships studies strengthen the importance of the amide spacer and the direct linkage of carbonyl group to the γ-pyrone ring, along with the presence of meta and para substituents in the exocyclic ring. The most potent MAO-B inhibitors were N-(3'-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (20) (IC50 = 403 pM) and N-(3',4'-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (27) (IC50 = 669 pM), acting as competitive and noncompetitive reversible inhibitors, respectively. Computational docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed selectivity and potency. Compound 27 stands out due to its favorable toxicological profile and physicochemical properties, which pointed toward blood-brain barrier permeability, thus being a valid candidate for subsequent animal studies.

  17. Act-Up, other AIDS groups targeted for FBI surveillance. Federal Bureau of Investigations.

    PubMed

    1995-06-01

    Documents obtained by a civil rights group, the Center for Constitutional Rights, showed that the Federal Bureau of Investigations (FBI) monitored the activities of Act-Up, Gay Men's Health Crisis (GMHC), the Coalition for Lesbian and Gay Rights, and Senior Action in a Gay Environment. Act-Up was the main target from 1988 through 1992, the years it staged its most conspicuous demonstrations against the Federal government's policy on AIDS. According to one of the documents, George Bush, then president, complained about Act-Up holding protests and tossing condoms outside his summer home in Maine in 1992. The documents showed that the organization posed little threat of harm.

  18. 48 CFR 952.226-73 - Energy Policy Act target group certification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... is: (1) __ An institution of higher education that meets the requirements of 34 CFR 600.4(a), and has... and University by the Secretary of Education pursuant to 34 CFR 608.2; or (3) __ A small business....226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert...

  19. 48 CFR 952.226-73 - Energy Policy Act target group certification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... is: (1) __ An institution of higher education that meets the requirements of 34 CFR 600.4(a), and has... and University by the Secretary of Education pursuant to 34 CFR 608.2; or (3) __ A small business....226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert...

  20. 50 CFR 622.457 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.457 Section 622.457 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.457 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  1. 50 CFR 622.496 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.496 Section 622.496 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.496 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  2. 50 CFR 622.439 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.439 Section 622.439 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.439 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  3. 50 CFR 622.439 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.439 Section 622.439 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.439 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  4. 50 CFR 622.496 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.496 Section 622.496 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.496 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  5. 50 CFR 622.457 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs). 622.457 Section 622.457 Wildlife and Fisheries FISHERY.... Virgin Islands § 622.457 Annual catch limits (ACLs), annual catch targets (ACTs), and...

  6. 50 CFR 622.388 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... targets (ACTs), and accountability measures (AMs). 622.388 Section 622.388 Wildlife and Fisheries FISHERY... Mexico and South Atlantic) § 622.388 Annual catch limits (ACLs), annual catch targets (ACTs), and... tracking the ACL, recreational landings will be monitored based on the commercial fishing year, July...

  7. 17 CFR 229.1107 - (Item 1107) Issuing entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... capitalization of the issuing entity and the amount or nature of any equity contribution to the issuing entity by... loans originated under the Federal Family Education Loan Program of the Higher Education Act of 1965...

  8. 17 CFR 229.1107 - (Item 1107) Issuing entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... capitalization of the issuing entity and the amount or nature of any equity contribution to the issuing entity by... loans originated under the Federal Family Education Loan Program of the Higher Education Act of 1965...

  9. 48 CFR 926.7005 - Preferences under the Energy Policy Act.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Policy Act target groups. The evaluation criteria shall provide that in instances in which two or more... Policy Act target group that offeror will be selected for award. (b) Subcontracts. (1) The contracting... offerors have provided for subcontracting opportunities to entities from among the Energy Policy Act...

  10. SLC7A5 act as a potential leukemic transformation target gene in myelodysplastic syndrome

    PubMed Central

    Ma, Yan; Song, Jing; Chen, Bobin; Xu, Xiaoping; Lin, Guowei

    2016-01-01

    Objective Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders characterized by increased risk of leukemic transformation. This study identifies microRNAs(miRNA) and miRNA targets that might represent leukemic transformation markers for MDS. Methods Based on our previously established nested case-control study cohort of MDS patients, we chose paired patients to undergo Angilent 8 × 15K human miRNA microarrays. Target prediction analysis was administrated using targetscan 5.1 software. We further investigated the function of target gene in MDS cell line using siRNA method, including cell proliferation, cell apoptosis, cell cycle and electron microscope. Results Finally we screened a subset of 7 miRNAs to be significantly differentially expressed between the case (at the end of follow up with leukemic transformation) and control group (at the end of follow up without leukemic transformation). Target prediction analysis revealed SLC7A5 was the common target gene of these 7 miRNAs. Further study on the function of SLC7A5 gene in SKM-1 cell line showed that downregulation of SLC7A5 inhibited SKM-1 cells proliferation, increased apoptosis and caused cell cycle arrest in the G0/G1 stage. Conclusion Our data indicate that SLC7A5 gene may act as a potential leukemic transformation target gene in MDS. PMID:26657287

  11. First-in-Humans Study of the Safety, Tolerability, and Pharmacokinetics of ACT-451840, a New Chemical Entity with Antimalarial Activity

    PubMed Central

    Bruderer, Shirin; Hurst, Noémie; de Kanter, Ruben; Miraval, Tommaso; Pfeifer, Thomas; Donazzolo, Yves

    2014-01-01

    Emerging resistance to antimalarial agents raises the need for new drugs. ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum. No (serious) adverse events leading to discontinuation were reported. At the highest dose level, the peak drug concentration (Cmax) and the area under the plasma concentration-time curve from zero to infinity of ACT-451840 under fasted conditions reached 11.9 ng/ml and 100.6 ng · h/ml, respectively, and these were approximately 13-fold higher under fed conditions. Food did not affect the half-life (approximately 34 h) of the drug, while the Cmax was attained 2.0 and 3.5 h postdose under fasted and fed conditions, respectively. The plasma concentrations estimated by the bioassay were approximately 4-fold higher than those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several potentially active metabolites were also identified. ACT-451840 was well tolerated across all doses. Exposure to ACT-451840 significantly increased with food. The bioassay indicated the presence of circulating active metabolites. (This study has been registered at ClinicalTrials.gov under registration no. NCT02186002.) PMID:25421475

  12. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity.

    PubMed

    Bruderer, Shirin; Hurst, Noémie; de Kanter, Ruben; Miraval, Tommaso; Pfeifer, Thomas; Donazzolo, Yves; Dingemanse, Jasper

    2015-02-01

    Emerging resistance to antimalarial agents raises the need for new drugs. ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum. No (serious) adverse events leading to discontinuation were reported. At the highest dose level, the peak drug concentration (Cmax) and the area under the plasma concentration-time curve from zero to infinity of ACT-451840 under fasted conditions reached 11.9 ng/ml and 100.6 ng·h/ml, respectively, and these were approximately 13-fold higher under fed conditions. Food did not affect the half-life (approximately 34 h) of the drug, while the Cmax was attained 2.0 and 3.5 h postdose under fasted and fed conditions, respectively. The plasma concentrations estimated by the bioassay were approximately 4-fold higher than those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several potentially active metabolites were also identified. ACT-451840 was well tolerated across all doses. Exposure to ACT-451840 significantly increased with food. The bioassay indicated the presence of circulating active metabolites. (This study has been registered at ClinicalTrials.gov under registration no. NCT02186002.). PMID:25421475

  13. The science of direct-acting antiviral and host-targeted agent therapy.

    PubMed

    Pawlotsky, Jean-Michel

    2012-01-01

    Direct-acting antiviral drugs targeting two major steps of the HCV life cycle, polyprotein processing and replication, and cyclophilin inhibitors, that target a host cell protein required to interact with the replication complex, have reached clinical development. In order to achieve a sustained virological response, that is, a cure of the HCV infection, it is necessary to shut down virus production, to maintain viral inhibition throughout treatment and to induce a significant, slower second-phase decline in HCV RNA levels that leads to definitive clearance of infected cells. Recent findings suggest that the interferon era is coming to an end in hepatitis C therapy and HCV infection can be cured by all-oral interferon-free treatment regimens within 12 to 24 weeks. Further results are awaited that will allow the establishment of an ideal first-line all-oral, interferon-free treatment regimen for patients with chronic HCV infection.

  14. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  15. Artemisinins act through at least two targets in a yeast model.

    PubMed

    Moore, Catherine M; Hoey, Elizabeth M; Trudgett, Alan; Timson, David J

    2011-03-01

    Artemisinin and related compounds are potent and widely used antimalarial drugs but their biochemical mode of action is not clear. There is strong evidence that ATP-dependent calcium transporters are a key target in the malarial parasite. However, work using Saccharomyces cerevisiae suggests that disruption of mitochondrial function is critical in the cell killing activity of these compounds. Here it is shown that, in the absence of reducing agents, artemisinin and artesunate targeted the S. cerevisiae calcium channels Pmr1p and Pmc1p. Both compounds affected the growth of yeast on fermentable and nonfermentable media. This growth inhibition was not seen in a yeast strain in which the genes encoding both calcium channels were deleted. In the presence of reducing agents, which break the endoperoxide bridge in the drugs, growth inhibition was only observed in nonfermentable media. This inhibition could be partially relieved by the addition of a free radical scavenger. These results suggest that the drugs have two biochemical modes of action - one acting by specific binding to calcium channels and one involving free radical production in the mitochondria.

  16. In Vivo Pharmacodynamic Target Investigation of Two Bacterial Topoisomerase Inhibitors, ACT-387042 and ACT-292706, in the Neutropenic Murine Thigh Model against Streptococcus pneumoniae and Staphylococcus aureus.

    PubMed

    Lepak, A J; Seiler, P; Surivet, J P; Ritz, D; Kohl, C; Andes, D R

    2016-06-01

    ACT-387042 and ACT-292706 are two novel bacterial topoisomerase inhibitors with broad-spectrum activity against Gram-positive and -negative bacteria, including methicillin-resistant Staphylococcus aureus and penicillin- and fluoroquinolone-resistant Streptococcus pneumoniae We used the neutropenic murine thigh infection model to characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of these investigational compounds against a group of 10 S. aureus and S. pneumoniae isolates with phenotypic resistance to beta-lactams and fluoroquinolones. The in vitro activities of the two compounds were very similar (MIC range, 0.03 to 0.125 mg/liter). Plasma pharmacokinetics were determined for each compound by using four escalating doses administered by the subcutaneous route. In treatment studies, mice had 10(7.4) to 10(8) CFU/thigh at the start of therapy with ACT-387042 and 10(6.7) to 10(8.3) CFU/thigh at the start of therapy with ACT-292706. A dose-response relationship was observed with all isolates over the dose range. Maximal kill approached 3 to 4 log10 CFU/thigh compared to the burden at the start of therapy for the highest doses examined. There was a strong relationship between the PK/PD index AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) and therapeutic efficacy in the model (R(2), 0.63 to 0.82). The 24-h free-drug AUC/MIC ratios associated with net stasis for ACT-387042 against S. aureus and S. pneumoniae were 43 and 10, respectively. The 24-h free-drug AUC/MIC ratios associated with net stasis for ACT-292706 against S. aureus and S. pneumoniae were 69 and 25, respectively. The stasis PD targets were significantly lower for S. pneumoniae (P < 0.05) for both compounds. The 1-log-kill AUC/MIC ratio targets were ∼2- to 4-fold higher than stasis targets. Methicillin, penicillin, or ciprofloxacin resistance did not alter the magnitude of the AUC/MIC ratio required for efficacy. These results should be

  17. 50 CFR 648.141 - Black sea bass Annual Catch Target (ACT).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the black sea... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  18. 50 CFR 648.141 - Black sea bass Annual Catch Target (ACT).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the black sea... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  19. 50 CFR 648.141 - Black sea bass Annual Catch Target (ACT).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the black sea... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  20. 50 CFR 648.101 - Summer flounder Annual Catch Target (ACT).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the summer... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  1. 50 CFR 648.101 - Summer flounder Annual Catch Target (ACT).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the summer... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  2. 50 CFR 648.101 - Summer flounder Annual Catch Target (ACT).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... uncertainty to recommend ACTs for the commercial and recreational fishing sectors as part of the summer... specific sources of management uncertainty that were considered, technical approaches to mitigating these sources of uncertainty, and any additional relevant information considered in the ACT...

  3. 18 CFR 46.5 - Covered entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Covered entities. 46.5 Section 46.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT PUBLIC UTILITY FILING REQUIREMENTS AND FILING...

  4. 50 CFR 648.71 - Surfclam and ocean quahog Annual Catch Targets (ACT).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Surfclam and ocean quahog Annual Catch... Management Measures for the Atlantic Surf Clam and Ocean Quahog Fisheries § 648.71 Surfclam and ocean quahog... management uncertainty to recommend ACTs to the MAFMC as part of the surfclam and ocean quahog...

  5. 50 CFR 648.71 - Surfclam and ocean quahog Annual Catch Targets (ACT).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Surfclam and ocean quahog Annual Catch... Management Measures for the Atlantic Surf Clam and Ocean Quahog Fisheries § 648.71 Surfclam and ocean quahog... management uncertainty to recommend ACTs to the MAFMC as part of the surfclam and ocean quahog...

  6. 50 CFR 648.71 - Surfclam and ocean quahog Annual Catch Targets (ACT).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Surfclam and ocean quahog Annual Catch... Management Measures for the Atlantic Surf Clam and Ocean Quahog Fisheries § 648.71 Surfclam and ocean quahog... management uncertainty to recommend ACTs to the MAFMC as part of the surfclam and ocean quahog...

  7. 48 CFR 952.226-73 - Energy Policy Act target group certification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... is: (1) __ An institution of higher education that meets the requirements of 34 CFR 600.4(a), and has... and University by the Secretary of Education pursuant to 34 CFR 608.2; or (3) __ A small business... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Energy Policy Act...

  8. 48 CFR 952.226-73 - Energy Policy Act target group certification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... is: (1) __ An institution of higher education that meets the requirements of 34 CFR 600.4(a), and has... and University by the Secretary of Education pursuant to 34 CFR 608.2; or (3) __ A small business... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Energy Policy Act...

  9. 48 CFR 952.226-73 - Energy Policy Act target group certification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... is: (1) __ An institution of higher education that meets the requirements of 34 CFR 600.4(a), and has... and University by the Secretary of Education pursuant to 34 CFR 608.2; or (3) __ A small business... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Energy Policy Act...

  10. 77 FR 30433 - Privacy Act of 1974: Implementation of Exemptions; Automated Targeting System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-23

    ... system. DHS and CBP, however, will consider each request for access to records maintained in ATS to... taken on this system of records they are providing access and amendment to passenger name records (PNR... the source system of records already provides access and/or amendment under the Privacy Act....

  11. Acting Diverse: Target Group Orientation as Key Competence in Engineering Education

    ERIC Educational Resources Information Center

    Ihsen, S.; Buschmeyer, A.

    2007-01-01

    International companies are recognised by equity between men and women as well as between other different groups (Diversity) as an economic factor and incorporate it into their company visions. Mixed teams are set up to design target group-oriented products, for example in automotive engineering. Therefore they need employees who represent the…

  12. From adversary to target market: the ACT-UP boycott of Philip Morris

    PubMed Central

    Offen, N; Smith, E; Malone, R

    2003-01-01

    Background: In 1990, the AIDS Coalition to Unleash Power (ACT-UP) sparked a year long boycott of Philip Morris's Marlboro cigarettes and Miller beer. The boycott protested the company's support of Senator Jesse Helms (R-North Carolina), a leading opponent of AIDS funding and civil rights for lesbian, gay, bisexual and transgender (LGBT) people. ACT-UP demanded that Philip Morris sever its ties with Helms and acknowledge its responsibility to the LGBT community and to people with AIDS. Objective: To assess the impact of the boycott on the LGBT community, the tobacco industry, and the tobacco control movement; and to determine what lessons tobacco control advocates can extract from this case. Data sources: Internal tobacco industry documents and newspaper archives. Methods: Search of tobacco industry documents websites using "boycott", "ACT-UP", "gay", and other terms. Results: Philip Morris used the boycott to its own advantage. It exploited differences within the community and settled the boycott by pledging large donations to combat AIDS. Through corporate philanthropy, Philip Morris gained entrée to the LGBT market without appearing gay friendly. Many LGBT organisations, thirsty for recognition and funding from mainstream corporations, welcomed Philip Morris's overtures without considering the health hazards of tobacco. Conclusions: Unless the goal of a boycott is to convince the tobacco industry to abandon tobacco altogether, such actions invite the industry to expand its marketing under the guise of philanthropy. Tobacco control advocates should be clear about goals and acceptable settlement terms before participating in a boycott of a tobacco company. PMID:12773732

  13. RNA editing in plant mitochondria—connecting RNA target sequences and acting proteins.

    PubMed

    Takenaka, Mizuki; Verbitskiy, Daniil; Zehrmann, Anja; Härtel, Barbara; Bayer-Császár, Eszter; Glass, Franziska; Brennicke, Axel

    2014-11-01

    RNA editing changes several hundred cytidines to uridines in the mRNAs of mitochondria in flowering plants. The target cytidines are identified by a subtype of PPR proteins characterized by tandem modules which each binds with a specific upstream nucleotide. Recent progress in correlating repeat structures with nucleotide identities allows to predict and identify target sites in mitochondrial RNAs. Additional proteins have been found to play a role in RNA editing; their precise function still needs to be elucidated. The enzymatic activity performing the C to U reaction may reside in the C-terminal DYW extensions of the PPR proteins; however, this still needs to be proven. Here we update recent progress in understanding RNA editing in flowering plant mitochondria.

  14. 77 FR 31806 - Changes to Implement Micro Entity Status for Paying Patent Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ... United States Patent and Trademark Office 37 CFR Part 1 RIN 0651-AC78 Changes to Implement Micro Entity... to amend the rules of practice in patent cases to implement the micro entity provision of the Leahy... Leahy-Smith America Invents Act will be reduced by seventy-five percent for micro entities. The...

  15. Introducing endo-xylanase activity into an exo-acting arabinofuranosidase that targets side chains.

    PubMed

    McKee, Lauren S; Peña, Maria J; Rogowski, Artur; Jackson, Adam; Lewis, Richard J; York, William S; Krogh, Kristian B R M; Viksø-Nielsen, Anders; Skjøt, Michael; Gilbert, Harry J; Marles-Wright, Jon

    2012-04-24

    The degradation of the plant cell wall by glycoside hydrolases is central to environmentally sustainable industries. The major polysaccharides of the plant cell wall are cellulose and xylan, a highly decorated β-1,4-xylopyranose polymer. Glycoside hydrolases displaying multiple catalytic functions may simplify the enzymes required to degrade plant cell walls, increasing the industrial potential of these composite structures. Here we test the hypothesis that glycoside hydrolase family 43 (GH43) provides a suitable scaffold for introducing additional catalytic functions into enzymes that target complex structures in the plant cell wall. We report the crystal structure of Humicola insolens AXHd3 (HiAXHd3), a GH43 arabinofuranosidase that hydrolyses O3-linked arabinose of doubly substituted xylans, a feature of the polysaccharide that is recalcitrant to degradation. HiAXHd3 displays an N-terminal five-bladed β-propeller domain and a C-terminal β-sandwich domain. The interface between the domains comprises a xylan binding cleft that houses the active site pocket. Substrate specificity is conferred by a shallow arabinose binding pocket adjacent to the deep active site pocket, and through the orientation of the xylan backbone. Modification of the rim of the active site introduces endo-xylanase activity, whereas the resultant enzyme variant, Y166A, retains arabinofuranosidase activity. These data show that the active site of HiAXHd3 is tuned to hydrolyse arabinofuranosyl or xylosyl linkages, and it is the topology of the distal regions of the substrate binding surface that confers specificity. This report demonstrates that GH43 provides a platform for generating bespoke multifunctional enzymes that target industrially significant complex substrates, exemplified by the plant cell wall.

  16. The Circular RNA Cdr1as Act as an Oncogene in Hepatocellular Carcinoma through Targeting miR-7 Expression.

    PubMed

    Yu, Lei; Gong, Xuejun; Sun, Lei; Zhou, Qiying; Lu, Baoling; Zhu, Liying

    2016-01-01

    CircRNAs are a class of endogenous RNA that regulates gene expression at the post-transcriptional or transcriptionallevel through interacting with other molecules or microRNAs. Increasing studies have demonstrated that circRNAs play a crucial role in biology processes. CircRNAs are proved as potentialbiomarkers in many diseases including cancers. However, the role of Cdr1as in Hepatocellular carcinoma (HCC) remains to be elucidated. We demonstrated that Cdr1as expression was upregulated in HCC tissues compared with the adjacent non-tumor tissues. In addtion, miR-7 expression was downregulated in HCC tissues compared with the adjacent non-tumor tissues. Moreover, the expression level of miR-7 was inversely correlated with that in HCC tissues. Knockdown of Cdr1as suppressed the HCC cell proliferation and invasion. Overexpression of miR-7 inhibited the HCC cell proliferation and invasion. Overexpression of miR-7 could suppress the direct target gene CCNE1 and PIK3CD expression. Knockdown of Cdr1as suppressed the expression of miR-7 and also inhibited the CCNE1 and PIK3CD expression. Furthermore, knockdown of Cdr1as suppressed the HCC cell proliferation and invasion through targeting miR-7. These data suggested that Cdr1as acted as an oncogene partly through targeting miR-7 in HCC. PMID:27391479

  17. The Circular RNA Cdr1as Act as an Oncogene in Hepatocellular Carcinoma through Targeting miR-7 Expression

    PubMed Central

    Yu, Lei; Gong, Xuejun; Sun, Lei; Zhou, Qiying; Lu, Baoling; Zhu, Liying

    2016-01-01

    CircRNAs are a class of endogenous RNA that regulates gene expression at the post-transcriptional or transcriptionallevel through interacting with other molecules or microRNAs. Increasing studies have demonstrated that circRNAs play a crucial role in biology processes. CircRNAs are proved as potentialbiomarkers in many diseases including cancers. However, the role of Cdr1as in Hepatocellular carcinoma (HCC) remains to be elucidated. We demonstrated that Cdr1as expression was upregulated in HCC tissues compared with the adjacent non-tumor tissues. In addtion, miR-7 expression was downregulated in HCC tissues compared with the adjacent non-tumor tissues. Moreover, the expression level of miR-7 was inversely correlated with that in HCC tissues. Knockdown of Cdr1as suppressed the HCC cell proliferation and invasion. Overexpression of miR-7 inhibited the HCC cell proliferation and invasion. Overexpression of miR-7 could suppress the direct target gene CCNE1 and PIK3CD expression. Knockdown of Cdr1as suppressed the expression of miR-7 and also inhibited the CCNE1 and PIK3CD expression. Furthermore, knockdown of Cdr1as suppressed the HCC cell proliferation and invasion through targeting miR-7. These data suggested that Cdr1as acted as an oncogene partly through targeting miR-7 in HCC. PMID:27391479

  18. Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass

    PubMed Central

    Decker, Corinne E.; Yang, Zhengfeng; Rimer, Ryan; Park-Min, Kyung-Hyun; Macaubas, Claudia; Mellins, Elizabeth D.; Novack, Deborah V.; Faccio, Roberta

    2015-01-01

    Phospholipase C gamma-2 (PLCγ2)-dependent calcium (Ca2+) oscillations are indispensable for nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation and downstream gene transcription driving osteoclastogenesis during skeletal remodeling and pathological bone loss. Here we describe, to our knowledge, the first known function of transmembrane protein 178 (Tmem178), a PLCγ2 downstream target gene, as a critical modulator of the NFATc1 axis. In surprising contrast to the osteopetrotic phenotype of PLCγ2−/− mice, Tmem178−/− mice are osteopenic in basal conditions and are more susceptible to inflammatory bone loss, owing to enhanced osteoclast formation. Mechanistically, Tmem178 localizes to the ER membrane and regulates RANKL-induced Ca2+ fluxes, thus controlling NFATc1 induction. Importantly, down-regulation of Tmem178 is observed in human CD14+ monocytes exposed to plasma from systemic juvenile idiopathic arthritis patients. Similar to the mouse model, reduced Tmem178 expression in human cells correlates with excessive osteoclastogenesis. In sum, these findings identify an essential role for Tmem178 to maintain skeletal mass and limit pathological bone loss. PMID:26644563

  19. MicroRNA-503 acts as a tumor suppressor in osteosarcoma by targeting L1CAM.

    PubMed

    Chong, Yang; Zhang, Jie; Guo, Xinzhen; Li, Guojun; Zhang, Shiqian; Li, Chao; Jiao, Zhijian; Shao, Ming

    2014-01-01

    Deregulated microRNAs and their roles in tumorigenesis have attracted much attention in recent years. Although miR-503 was shown to be important in tumorigenesis, its role in osteosarcoma remains unknown. In this study, we focused on the expression and mechanisms of miR-503 in osteosarcoma development. We found that miR-503 was down-regulated in osteosarcoma cell lines and primary tumor samples, and the restoration of miR-503 reduced cell proliferation, migration and invasion. Low level of miR-503 in patients with osteosarcoma was associated with considerably shortened disease-free survival. Furthermore, bioinformatic prediction and experimental validation revealed that the anti-tumor effect of miR-503 was probably exerted through targeting and repressing of L1CAM expression. L1CAM was up-regulated in osteosarcoma cell lines and primary tumor samples and the expression level of L1CAM were negatively correlated with miR-503 levels in osteosarcoma tissues. Collectively, our data identify the important roles of miR-503 in osteosarcoma pathogenesis, indicating its potential application in cancer therapy. PMID:25536034

  20. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia.

    PubMed

    Xishan, Zhu; Ziying, Lin; Jing, Du; Gang, Liu

    2015-07-31

    Accumulating evidences demonstrated that the induction of epithelial-mesenchymal transition (EMT) and aberrant expression of microRNAs (miRNAs) are associated with tumorigenesis, tumor progression, metastasis and relapse in cancers, including chronic myeloid leukemia (CML). We found that miR-320a expression was reduced in K562 and in CML cancer stem cells. Moreover, we found that miR-320a inhibited K562 cell migration, invasion, proliferation and promoted apoptosis by targeting BCR/ABL oncogene. As an upstream regulator of BCR/ABL, miR-320a directly targets BCR/ABL. The enhanced expression of miR-320a inhibited the phosphorylation of PI3K, AKT and NF-κB; however, the expression of phosphorylated PI3K, AKT and NF-κB were restored by the overexpression of BCR/ABL. In K562, infected with miR-320a or transfected with SiBCR/ABL, the protein levels of fibronectin, vimentin, and N-cadherin were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-320a-expressing cells was restored to normal levels by the restoration of BCR/ABL expression. Generally speaking, miR-320a acts as a novel tumor suppressor gene in CML and miR-320a can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as CML EMT, by attenuating the expression of BCR/ABL oncogene.

  1. Learning plan applicability through active mental entities

    NASA Astrophysics Data System (ADS)

    Baroni, Pietro; Fogli, Daniela; Guida, Giovanni

    1999-03-01

    This paper aims at laying down the foundations of a new approach to learning in autonomous mobile robots. It is based on the assumption that robots can be provided with built-in action plans and with mechanisms to modify and improve such plans. This requires that robots are equipped with some form of high-level reasoning capabilities. Therefore, the proposed learning technique is embedded in a novel distributed control architecture featuring an explicit model of robot's cognitive activity. In particular, cognitive activity is obtained by the interaction of active mental entities, such as intentions, persuasions and expectations. Learning capabilities are implemented starting from the interaction of such mental entities. The proposal is illustrated through an example concerning a robot in charge of reaching a target in an unknown environment cluttered with obstacles.

  2. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia

    PubMed Central

    Xishan, Zhu; Ziying, Lin; Jing, Du; Gang, Liu

    2015-01-01

    Accumulating evidences demonstrated that the induction of epithelial-mesenchymal transition (EMT) and aberrant expression of microRNAs (miRNAs) are associated with tumorigenesis, tumor progression, metastasis and relapse in cancers, including chronic myeloid leukemia (CML). We found that miR-320a expression was reduced in K562 and in CML cancer stem cells. Moreover, we found that miR-320a inhibited K562 cell migration, invasion, proliferation and promoted apoptosis by targeting BCR/ABL oncogene. As an upstream regulator of BCR/ABL, miR-320a directly targets BCR/ABL. The enhanced expression of miR-320a inhibited the phosphorylation of PI3K, AKT and NF-κB; however, the expression of phosphorylated PI3K, AKT and NF-κB were restored by the overexpression of BCR/ABL. In K562, infected with miR-320a or transfected with SiBCR/ABL, the protein levels of fibronectin, vimentin, and N-cadherin were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-320a-expressing cells was restored to normal levels by the restoration of BCR/ABL expression. Generally speaking, miR-320a acts as a novel tumor suppressor gene in CML and miR-320a can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as CML EMT, by attenuating the expression of BCR/ABL oncogene. PMID:26228085

  3. Novel Nor-Homo- and Spiro-Oxetan- Steroids Target the Human Androgen Receptor and Act as Antiandrogens.

    PubMed

    Thiele, Marie; Rabe, Sebastian; Hessenkemper, Wiebke; Roell, Daniela; Bartsch, Sophie; Kraft, Florian; Abraham, Tsion E; Houtsmuller, Adriaan B; van Royen, Martin E; Giannis, Athanassios; Baniahmad, Aria

    2014-06-01

    The prostate adenocarcinoma is the cancer with the highest incidence for men in Western countries. Targeting the androgen receptor (AR) by antagonists is used as hormone therapy for prostate cancer (PCa), however, eventually therapy resistance occurs in most patients. In most of these cancer the AR signaling is active and thus AR remains an important drug target. Since many years we are characterizing novel chemical structural platforms to provide a broader possibility for compounds that bind to and act as AR antagonists. Here, we describe the chemical synthesis of a battery of novel steroidal derivatives as nor-homo-, spiro-oxolan- and spiro-oxetan- steroids. They modulate the transcriptional activity of the human AR. As AR antagonists, the spiro-oxetan- steroid derivatives seem to be the most potent steroid derivatives. They inhibit the transcriptional activity of both wild-type AR as well as the AR mutant T877A. In line with this, these compounds bind to the human AR and inhibit the proliferation of the human androgen-dependent growing PCa cell line LNCaP. Interestingly, the castration-resistant AR expressing human PC3-AR cells are also growth inhibited. On mechanistic level, fluorescence resonance energy transfer (FRET) assays with living cells indicate that the androgen-induced N/C terminal interaction of the AR is inhibited by the investigated compounds. Using fluorescence recovery after photobleaching (FRAP) assays in living cells suggest a higher mobility of the AR in the cell nuclei in the presence of spiro-oxetan- steroidal antagonists. Together, these findings suggest that spiro-oxetan- steroids are very useful as a chemical platform for novel AR antagonists.

  4. Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure

    PubMed Central

    Ray, Heather J.; Niswander, Lee A.

    2016-01-01

    The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. PMID:26903501

  5. Targeting Scarce Resources under the Older Americans Act. Hearing before the Subcommittee on Aging of the Committee on Labor and Human Resources. United States Senate, Ninety-Eighth Congress, First Session on Examination of the Targeting of Services Needed to Maintain Economic and Social Independence of Older People as Mandated in Title III of the Older Americans Act.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    This document presents prepared statements and witness testimony from the Congressional hearing on the Older Americans Act. An opening statement by Senator Charles Grassley, subcommittee chairman, contains a brief overview of the Older Americans Act. An extensive statement on the proposed targeting of services mandated under Title III of the Older…

  6. [Fatal nanism: 3 different entities].

    PubMed

    Escrivá Tomás, P; Clemente Yago, F; López Peña, L F; Cidras Pidre, M; Orts Serrano, F; Serrano Martínez, J L; Jiménez Cobo, B

    1991-04-01

    Three cases of congenital dwarfism are presented. All of them are lethal and represent the three better known nonviable nosologic entities: Achondrogenesis I, Achondrogesis II and Thanatophoric dwarfism. According to clinical features and radiologic data it is possible to approach the diagnosis accurately. We comment genetic, clinic, radiologic and histologic aspects of these processes. It is important to establish a differential diagnosis as these entities have different genetic basis, what influences genetic counsel. PMID:2069281

  7. Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity

    PubMed Central

    Worku, Netsanet; Stich, August; Daugschies, Arwid; Wenzel, Iris; Kurz, Randy; Thieme, Rene; Kurz, Susanne; Birkenmeier, Gerd

    2015-01-01

    Background Human African Trypanosomiasis (HAT) also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties. Results The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM). The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions. Conclusion Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to

  8. State and Local Implementation of the No Child Left Behind Act. Volume VI--Targeting and Uses of Federal Education Funds

    ERIC Educational Resources Information Center

    Chambers, Jay G.; Lam, Irene; Mahitivanichcha, Kanya; Esra, Phil; Shambaugh, Larisa; Stullich, Stephanie

    2009-01-01

    Achieving the goals of federal education legislation depends on how federal funds are distributed and used. Since the enactment of the Elementary and Secondary Education Act (ESEA) in 1965, various federal programs have been created to support educational improvement and target additional resources to meet the educational needs of children who are…

  9. Entity linking for biomedical literature

    PubMed Central

    2015-01-01

    Background The Entity Linking (EL) task links entity mentions from an unstructured document to entities in a knowledge base. Although this problem is well-studied in news and social media, this problem has not received much attention in the life science domain. One outcome of tackling the EL problem in the life sciences domain is to enable scientists to build computational models of biological processes with more efficiency. However, simply applying a news-trained entity linker produces inadequate results. Methods Since existing supervised approaches require a large amount of manually-labeled training data, which is currently unavailable for the life science domain, we propose a novel unsupervised collective inference approach to link entities from unstructured full texts of biomedical literature to 300 ontologies. The approach leverages the rich semantic information and structures in ontologies for similarity computation and entity ranking. Results Without using any manual annotation, our approach significantly outperforms state-of-the-art supervised EL method (9% absolute gain in linking accuracy). Furthermore, the state-of-the-art supervised EL method requires 15,000 manually annotated entity mentions for training. These promising results establish a benchmark for the EL task in the life science domain. We also provide in depth analysis and discussion on both challenges and opportunities on automatic knowledge enrichment for scientific literature. Conclusions In this paper, we propose a novel unsupervised collective inference approach to address the EL problem in a new domain. We show that our unsupervised approach is able to outperform a current state-of-the-art supervised approach that has been trained with a large amount of manually labeled data. Life science presents an underrepresented domain for applying EL techniques. By providing a small benchmark data set and identifying opportunities, we hope to stimulate discussions across natural language processing

  10. Medicare Program: Expanding Uses of Medicare Data by Qualified Entities. Final rule.

    PubMed

    2016-07-01

    This final rule implements requirements under Section 105 of the Medicare Access and CHIP Reauthorization Act of 2015 that expand how qualified entities may use and disclose data under the qualified entity program to the extent consistent with applicable program requirements and other applicable laws, including information, privacy, security and disclosure laws. This rule also explains how qualified entities may create non-public analyses and provide or sell such analyses to authorized users, as well as how qualified entities may provide or sell combined data, or provide Medicare claims data alone at no cost, to certain authorized users. In addition, this rule implements certain privacy and security requirements, and imposes assessments on qualified entities if the qualified entity or the authorized user violates the terms of a data use agreement required by the qualified entity program. PMID:27400462

  11. Medicare Program: Expanding Uses of Medicare Data by Qualified Entities. Final rule.

    PubMed

    2016-07-01

    This final rule implements requirements under Section 105 of the Medicare Access and CHIP Reauthorization Act of 2015 that expand how qualified entities may use and disclose data under the qualified entity program to the extent consistent with applicable program requirements and other applicable laws, including information, privacy, security and disclosure laws. This rule also explains how qualified entities may create non-public analyses and provide or sell such analyses to authorized users, as well as how qualified entities may provide or sell combined data, or provide Medicare claims data alone at no cost, to certain authorized users. In addition, this rule implements certain privacy and security requirements, and imposes assessments on qualified entities if the qualified entity or the authorized user violates the terms of a data use agreement required by the qualified entity program.

  12. 75 FR 11223 - Lifting of Nonproliferation Measures Against One Russian Entity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ... FR 42089). Dated: March 4, 2010. Vann H. Van Diepen, Acting Assistant Secretary of State for... of Nonproliferation Measures Against One Russian Entity AGENCY: Department of State. ACTION: Notice..., 1994, as amended, to remove nonproliferation measures on one Russian entity. DATES: Effective...

  13. 75 FR 5836 - Lifting of Nonproliferation Measures Against One Russian Entity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... July 30, 1998 (see 63 FR 42089). Dated: January 29, 2010. C.S. Eliot Kang, Acting Assistant Secretary... of Nonproliferation Measures Against One Russian Entity AGENCY: Department of State. ACTION: Notice..., 1994, as amended, to remove nonproliferation measures on one Russian entity. DATES: Effective...

  14. 20 CFR 662.210 - What other entities may serve as One-Stop partners?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What other entities may serve as One-Stop... LABOR DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.210 What other entities may serve as One-Stop partners?...

  15. 20 CFR 662.210 - What other entities may serve as One-Stop partners?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false What other entities may serve as One-Stop... LABOR (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.210 What other entities may serve as...

  16. 20 CFR 662.210 - What other entities may serve as One-Stop partners?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false What other entities may serve as One-Stop... LABOR (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.210 What other entities may serve as...

  17. 22 CFR 709.4 - Cause for suspension of entities from eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Cause for suspension of entities from eligibility. 709.4 Section 709.4 Foreign Relations OVERSEAS PRIVATE INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS FOREIGN CORRUPT PRACTICES ACT OF 1977 § 709.4 Cause for suspension of entities from...

  18. 22 CFR 709.4 - Cause for suspension of entities from eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Cause for suspension of entities from eligibility. 709.4 Section 709.4 Foreign Relations OVERSEAS PRIVATE INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS FOREIGN CORRUPT PRACTICES ACT OF 1977 § 709.4 Cause for suspension of entities from...

  19. 22 CFR 709.4 - Cause for suspension of entities from eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Cause for suspension of entities from eligibility. 709.4 Section 709.4 Foreign Relations OVERSEAS PRIVATE INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS FOREIGN CORRUPT PRACTICES ACT OF 1977 § 709.4 Cause for suspension of entities from...

  20. 22 CFR 709.4 - Cause for suspension of entities from eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Cause for suspension of entities from eligibility. 709.4 Section 709.4 Foreign Relations OVERSEAS PRIVATE INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS FOREIGN CORRUPT PRACTICES ACT OF 1977 § 709.4 Cause for suspension of entities from...

  1. 22 CFR 709.4 - Cause for suspension of entities from eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Cause for suspension of entities from eligibility. 709.4 Section 709.4 Foreign Relations OVERSEAS PRIVATE INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS FOREIGN CORRUPT PRACTICES ACT OF 1977 § 709.4 Cause for suspension of entities from...

  2. 29 CFR 1635.6 - Causing a covered entity to discriminate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Causing a covered entity to discriminate. 1635.6 Section 1635.6 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GENETIC INFORMATION NONDISCRIMINATION ACT OF 2008 § 1635.6 Causing a covered entity to discriminate. A covered...

  3. 29 CFR 1635.6 - Causing a covered entity to discriminate.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 4 2013-07-01 2013-07-01 false Causing a covered entity to discriminate. 1635.6 Section 1635.6 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GENETIC INFORMATION NONDISCRIMINATION ACT OF 2008 § 1635.6 Causing a covered entity to discriminate. A covered...

  4. 29 CFR 1635.6 - Causing a covered entity to discriminate.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 4 2014-07-01 2014-07-01 false Causing a covered entity to discriminate. 1635.6 Section 1635.6 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GENETIC INFORMATION NONDISCRIMINATION ACT OF 2008 § 1635.6 Causing a covered entity to discriminate. A covered...

  5. 29 CFR 1635.6 - Causing a covered entity to discriminate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Causing a covered entity to discriminate. 1635.6 Section 1635.6 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GENETIC INFORMATION NONDISCRIMINATION ACT OF 2008 § 1635.6 Causing a covered entity to discriminate. A covered...

  6. Ameloblastic fibroma: an uncommon entity.

    PubMed

    Vij, Ruchieka; Vij, Hitesh

    2013-07-09

    Ameloblastic fibroma is an uncommon mixed odontogenic tumour, which is often confused with ameloblastoma. It exhibits both epithelial and mesenchymal components with absence of any calcified dental structure. This paper presents two cases of this rare entity with detailed review of literature.

  7. 31 CFR 575.304 - Entity of the Government of Iraq; Iraqi Government entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity of the Government of Iraq... SANCTIONS REGULATIONS General Definitions § 575.304 Entity of the Government of Iraq; Iraqi Government entity. The term entity of the Government of Iraq or Iraqi Government entity includes: (a)...

  8. 42 CFR 411.8 - Services paid for by a Government entity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and Exclusion of Particular Services § 411.8 Services paid for by a Government entity. (a) Basic rule...) Services furnished under a title of the Social Security Act other than title XVIII. (3) Services...

  9. Entity- Version 1.0

    2012-09-13

    This package contains classes that capture high-level aspects of characters and vehicles. Vehicles manage seats and riders. Vehicles and characters now can be configured to compose different behaviors and have certain capabilities, by adding them through xml data. These behaviors and capabilities are not included in this package, but instead are part of other packages such as mobility behavior, path planning, sight, sound. Entity is not dependent on these other packages. This package also containsmore » the icons used for Umbra applications Dante Scenario Editor, Dante Tabletop and OpShed. This assertion includes a managed C++ wrapper code (EntityWrapper) to enable C# applications, such as Dante Scenario Editor, Dante Tabletop, and OpShed, to incorporate this library.« less

  10. Compulsive buying: an overlooked entity.

    PubMed

    Basu, Bishnupriya; Basu, Saikat; Basu, Jharna

    2011-08-01

    Compulsive buying is an under-recognised entity among Indian psychiatrists. A Medline search, hand searching of journals and direct communications with lead investigators in compulsive buying have generated numerous studies. Overseas data indicate a community prevalence between 1% and 8% . The phenomenon can be an independent entity or appears as a comorbidity with another axis I or axis II disorder. A degree of suspicion on part of clinician regarding its possible presence is the key to its detection. A few rating instruments are available to quantify the morbidity and screening for compulsive buying. Management involves pharmacotherapy with SSRIs, psychotherapy, self-help groups and self-help books. Epidemiological and clinical studies on compulsive buying should be undertaken by Indian psychiatrists to provide better services for people suffering from compulsive buying. PMID:22315867

  11. Compulsive buying: an overlooked entity.

    PubMed

    Basu, Bishnupriya; Basu, Saikat; Basu, Jharna

    2011-08-01

    Compulsive buying is an under-recognised entity among Indian psychiatrists. A Medline search, hand searching of journals and direct communications with lead investigators in compulsive buying have generated numerous studies. Overseas data indicate a community prevalence between 1% and 8% . The phenomenon can be an independent entity or appears as a comorbidity with another axis I or axis II disorder. A degree of suspicion on part of clinician regarding its possible presence is the key to its detection. A few rating instruments are available to quantify the morbidity and screening for compulsive buying. Management involves pharmacotherapy with SSRIs, psychotherapy, self-help groups and self-help books. Epidemiological and clinical studies on compulsive buying should be undertaken by Indian psychiatrists to provide better services for people suffering from compulsive buying.

  12. Entity- Version 1.0

    SciTech Connect

    Hart, Brian; Oppel, Fred; Rigdon, Brian; Whitfor, Gregg; Summers, Kenneth; Jungels, John

    2012-09-13

    This package contains classes that capture high-level aspects of characters and vehicles. Vehicles manage seats and riders. Vehicles and characters now can be configured to compose different behaviors and have certain capabilities, by adding them through xml data. These behaviors and capabilities are not included in this package, but instead are part of other packages such as mobility behavior, path planning, sight, sound. Entity is not dependent on these other packages. This package also contains the icons used for Umbra applications Dante Scenario Editor, Dante Tabletop and OpShed. This assertion includes a managed C++ wrapper code (EntityWrapper) to enable C# applications, such as Dante Scenario Editor, Dante Tabletop, and OpShed, to incorporate this library.

  13. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...). The ABC/ACL for the 2015 fishing year is subject to change through a future framework adjustment. (1... access fleet sub-ACL and ACT for the 2015 fishing year are subject to change through a future framework... issued an IFQ scallop permit may only harvest and land the total amount of scallop meats allocated...

  14. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... subject to change through a future framework adjustment. (1) ABC/ACL for fishing years 2011 through 2013... and ACT for the 2013 fishing year are subject to change through a future framework adjustment. (i) The... the 2013 fishing year are default allocations and are subject to change through a future...

  15. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...). The ABC/ACL for the 2014 fishing year is subject to change through a future framework adjustment. (1... access fleet sub-ACL and ACT for the 2014 fishing year are subject to change through a future framework... amount of scallop meats allocated in accordance with this subpart. Unless otherwise specified in...

  16. 47 CFR 27.1218 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1218 Designated entities. (a) Eligibility for small business provisions. (1) A small business is an entity that, together...

  17. 14 CFR 1-6 - Accounting entities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Accounting entities. Sec. 1-6 Section Sec... General Accounting Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be... forth above. (c) The records for each required accounting entity shall be maintained with...

  18. Evaluation Methods of The Text Entities

    ERIC Educational Resources Information Center

    Popa, Marius

    2006-01-01

    The paper highlights some evaluation methods to assess the quality characteristics of the text entities. The main concepts used in building and evaluation processes of the text entities are presented. Also, some aggregated metrics for orthogonality measurements are presented. The evaluation process for automatic evaluation of the text entities is…

  19. Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validation.

    PubMed

    Zhang, Yanqiong; Bai, Ming; Zhang, Bo; Liu, Chunfang; Guo, Qiuyan; Sun, Yanqun; Wang, Danhua; Wang, Chao; Jiang, Yini; Lin, Na; Li, Shao

    2015-03-30

    Wu-tou decoction (WTD) has been extensively used for the treatment of rheumatoid arthritis (RA). Due to lack of appropriate methods, pharmacological mechanisms of WTD acting on RA have not been fully elucidated. In this study, a list of putative targets for compositive compounds containing in WTD were predicted by drugCIPHER-CS. Then, the interaction network of the putative targets of WTD and known RA-related targets was constructed and hub nodes were identified. After constructing the interaction network of hubs, four topological features of each hub, including degree, node betweenness, closeness and k-coreness, were calculated and 79 major hubs were identified as candidate targets of WTD, which were implicated into the imbalance of the nervous, endocrine and immune (NEI) systems, leading to the main pathological changes during the RA progression. Further experimental validation also demonstrated the preventive effects of WTD on inflammation and joint destruction in collagen-induced arthritis (CIA) rats and its regulatory effects on candidate targets both in vitro and in vivo systems. In conclusion, we performed an integrative analysis to offer the convincing evidence that WTD may attenuate RA partially by restoring the balance of NEI system and subsequently reversing the pathological events during RA progression.

  20. Determining similarity of scientific entities in annotation datasets

    PubMed Central

    Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

    2015-01-01

    Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug–drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called ‘AnnSim’ that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1–1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

  1. Determining similarity of scientific entities in annotation datasets.

    PubMed

    Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

    2015-01-01

    Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

  2. Maxillary Osteomyelitis: A Rare Entity

    PubMed Central

    Sivaji, Nagaraj; Ashraf, Tauseef

    2016-01-01

    Osteomyelitis of the maxilla is now a rare event with the advent of antibiotics. The two predominant causes are odontogenic infections and sinusitis. Immunocompromised states such as diabetes, HIV, and malnutrition increase the risk of osteomyelitis. It is important to recognize this early as it is a difficult entity to treat with potentially serious consequences. We report an unusual case of right sided maxillary osteomyelitis in a lady with poorly controlled diabetes in rural Lincolnshire. Biopsy of the right maxillary bone showed features of acute osteomyelitis. This responded well to a prolonged course of oral antibiotics.

  3. Maxillary Osteomyelitis: A Rare Entity.

    PubMed

    Habib, Ayaaz; Sivaji, Nagaraj; Ashraf, Tauseef

    2016-01-01

    Osteomyelitis of the maxilla is now a rare event with the advent of antibiotics. The two predominant causes are odontogenic infections and sinusitis. Immunocompromised states such as diabetes, HIV, and malnutrition increase the risk of osteomyelitis. It is important to recognize this early as it is a difficult entity to treat with potentially serious consequences. We report an unusual case of right sided maxillary osteomyelitis in a lady with poorly controlled diabetes in rural Lincolnshire. Biopsy of the right maxillary bone showed features of acute osteomyelitis. This responded well to a prolonged course of oral antibiotics. PMID:27648332

  4. Maxillary Osteomyelitis: A Rare Entity

    PubMed Central

    Sivaji, Nagaraj; Ashraf, Tauseef

    2016-01-01

    Osteomyelitis of the maxilla is now a rare event with the advent of antibiotics. The two predominant causes are odontogenic infections and sinusitis. Immunocompromised states such as diabetes, HIV, and malnutrition increase the risk of osteomyelitis. It is important to recognize this early as it is a difficult entity to treat with potentially serious consequences. We report an unusual case of right sided maxillary osteomyelitis in a lady with poorly controlled diabetes in rural Lincolnshire. Biopsy of the right maxillary bone showed features of acute osteomyelitis. This responded well to a prolonged course of oral antibiotics. PMID:27648332

  5. MiR-422a acts as a tumor suppressor in glioblastoma by targeting PIK3CA

    PubMed Central

    Liang, Haiqian; Wang, Renjie; Jin, Ying; Li, Jianwei; Zhang, Sai

    2016-01-01

    Although surgical treatment, chemotherapy, and radiotherapy have improved the overall survival rate in glioblastoma multiforme (GBM), further intensive research of GBM’s molecular mechanism is still needed. In this study, we observed that miR-422a was downregulated in GBM tissues and cell lines by quantitative real-time polymerase chain reaction (PCR) and primer extension assay. Overexpression of miR-422a significantly reduced the cell proliferation, migration, and invasion of GBM cells. Functional study indicated that miR-422a inhibited cell proliferation, invasion, and migration by targeting PIK3CA, an important member of PI3K/Akt signal pathway. These results demonstrate that the miR-422a/PIK3CA axis may constitute a potential target for GBM therapy. PMID:27648359

  6. MiR-422a acts as a tumor suppressor in glioblastoma by targeting PIK3CA

    PubMed Central

    Liang, Haiqian; Wang, Renjie; Jin, Ying; Li, Jianwei; Zhang, Sai

    2016-01-01

    Although surgical treatment, chemotherapy, and radiotherapy have improved the overall survival rate in glioblastoma multiforme (GBM), further intensive research of GBM’s molecular mechanism is still needed. In this study, we observed that miR-422a was downregulated in GBM tissues and cell lines by quantitative real-time polymerase chain reaction (PCR) and primer extension assay. Overexpression of miR-422a significantly reduced the cell proliferation, migration, and invasion of GBM cells. Functional study indicated that miR-422a inhibited cell proliferation, invasion, and migration by targeting PIK3CA, an important member of PI3K/Akt signal pathway. These results demonstrate that the miR-422a/PIK3CA axis may constitute a potential target for GBM therapy.

  7. MiR-422a acts as a tumor suppressor in glioblastoma by targeting PIK3CA.

    PubMed

    Liang, Haiqian; Wang, Renjie; Jin, Ying; Li, Jianwei; Zhang, Sai

    2016-01-01

    Although surgical treatment, chemotherapy, and radiotherapy have improved the overall survival rate in glioblastoma multiforme (GBM), further intensive research of GBM's molecular mechanism is still needed. In this study, we observed that miR-422a was downregulated in GBM tissues and cell lines by quantitative real-time polymerase chain reaction (PCR) and primer extension assay. Overexpression of miR-422a significantly reduced the cell proliferation, migration, and invasion of GBM cells. Functional study indicated that miR-422a inhibited cell proliferation, invasion, and migration by targeting PIK3CA, an important member of PI3K/Akt signal pathway. These results demonstrate that the miR-422a/PIK3CA axis may constitute a potential target for GBM therapy. PMID:27648359

  8. miR-489 acts as a tumor suppressor in human gastric cancer by targeting PROX1

    PubMed Central

    Zhang, Bin; Ji, Sheqing; Ma, Fei; Ma, Qi; Lu, Xianzhi; Chen, Xiaobing

    2016-01-01

    Dysregulation of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. In this study, we examined the expression of miR-489 in gastric cancer tissues and cells. Loss- and gain-of-function experiments were done to determine the roles of miR-489 in gastric cancer cell proliferation and invasion. Bioinformatic prediction, luciferase reporter assays, and Western blot analysis were employed to identify the target gene(s) of miR-489. We found that miR-489 was significantly (P < 0.05) downregulated in human gastric cancer tissues and cell lines, compared to their non-malignant counterparts. Enforced expression of miR-489 significantly suppressed gastric cancer cell proliferation and invasion, while miR-489 knockdown enhanced the aggressive behaviors of gastric cancer cells. Prospero homeobox 1 (PROX1) was identified to be a direct target of miR-489. A significant negative correlation was seen between miR-489 and PROX1 protein expression in gastric cancer tissues (r = -0.462, P = 0.023). Silencing of PROX1 phenocopied the suppressive effects of miR-489 in gastric cancer cells. Rescue experiments demonstrated that overexpression of a miR-489-resistant form of PROX1 significantly prevented the reduction in cell proliferation and invasion induced by miR-489 overexpression. In vivo studies confirmed that miR-489 overexpression retarded the growth of xenograft tumors, which was accompanied by reduced PROX1 expression. Overall, these data provide evidence for the suppressive activity of miR-489 in gastric cancer, which is ascribed to targeting of PROX1. The miR-489/PROX1 axis may represent a potential therapeutic target for this disease. PMID:27725907

  9. MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer

    PubMed Central

    Zhou, Peng; Chen, Wei-Guo; Li, Xiao-Wei

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in cancer progression through regulating gene expression. Down-regulation of miR-143 has been reported in a number of cancers. However, the biological functions of miR-143 in prostate cancer remain largely unexplored. In this study, we showed that miR-143 expression was reduced in approximately 62.5% of the specimens examined. By loss-of-function and gain-of-function studies in human prostate cancer PC-3 cells, we demonstrated that miR-143 has an inhibitory effect on cell proliferation as evidenced by decreased cell viability, increased cell apoptosis and cell cycle arrest at the G1/S transition. Furthermore, we identified hexokinase 2 (HK2), a metabolic enzyme that executes the first step of aerobic glycolysis, as a target of miR-143 in prostate cancer. Knockdown of HK2 recapitulated the effects of miR-143 and accompanied with decreased glucose metabolism. Taken together, these data indicate that miR-143/HK2 axis plays an important role in the development of prostate cancer and represents a potential therapeutic target for prostate cancer. PMID:26269764

  10. miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1

    PubMed Central

    Kang, Min; Ren, Mei-Ping; Zhao, Lei; Li, Chang-Ping; Deng, Ming-Ming

    2015-01-01

    MicroRNAs (miRNAs) play important roles in cancer progression including gastric cancer. miR-485-5p is reported as a potential suppressor in breast cancer, but its expression, cellular function and clinic features in gastric cancer is not known. In our study, we found that miR-485-5p expression was down-regulated in gastric cancer cell lines. miR-485-5p could inhibit gastric cancer cell growth in vitro and in vivo. We also found that miR-485-5p suppressed gastric cancer cell metastasis and sphere formation. It was confirmed flotillin-1 (Flot1) as a direct target of miR-485-5p, and up-regulation of miR-485-5p could decrease expression of Flot1 in gastric cancer cells. Further investigation showed that ectopic expression of Flot1 partially reversed the inhibition effect of enforced miR-485-5p expression on the malignant phenotypes of gastric cancer cells. The low expression of miR-485-5p in gastric cancer tissues was related to advanced clinical features and poorer prognosis. Our study suggested that miR-485-5p could be a potential prognostic marker and functions as a tumor suppressor in human gastric cancer by post-transcriptionally targeting Flot1. PMID:26807169

  11. Medicaid Integrity Program; eligible entity and contracting requirements for the Medicaid Integrity audit program. Final rule.

    PubMed

    2008-09-26

    Section 1936 of the Social Security Act (the Act) (as added by section 6034 of the Deficit Reduction Act of 2005 (DRA) established the Medicaid Integrity Program to promote the integrity of the Medicaid program by requiring CMS to enter into contracts with eligible entities to: (1) Review the actions of individuals or entities furnishing items or services (whether on a fee-for-service, risk, or other basis) for which payment may be made under an approved State plan and/or any waiver of such plan approved under section 1115 of the Act; (2) audit claims for payment of items or services furnished, or administrative services rendered, under a State plan; (3) identify overpayments to individuals or entities receiving Federal funds; and (4) educate providers of services, managed care entities, beneficiaries, and other individuals with respect to payment integrity and quality of care. This final rule will provide requirements for an eligible entity to enter into a contract under the Medicaid integrity audit program. The final rule will also establish the contracting requirements for eligible entities. The requirements will include procedures for identifying, evaluating, and resolving organizational conflicts of interest that are generally applicable to Federal acquisition and procurement; competitive procedures to be used; and procedures under which a contract may be renewed.

  12. Dementia: Continuum or Distinct Entity?

    PubMed Central

    Walters, Glenn D.

    2009-01-01

    The latent structure of dementia was examined in a group of 10,775 older adults with indicators derived from a neuropsychological test battery. Subjecting these data to taxometric analysis using mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode) produced results more consistent with dementia as a dimensional (lying along a continuum) than categorical (representing a distinct entity) construct. A second study conducted on a group of 2375 21-to-64-year olds produced similar results. These findings denote that dementia, as measured by deficits in episodic memory, attention/concentration, executive function, and language, differs quantitatively rather than qualitatively from the cognitive status of non-demented adults. The implications of these results for classification, assessment, etiology, and prevention are discussed. PMID:20677881

  13. Viruses: are they living entities?

    PubMed

    Pennazio, Sergio

    2011-01-01

    The essence (living or nonliving entities) of viruses has today become an aporia, i.e. a difficulty inherent in reasoning because they shared four fundamental characteristics with livings (multiplication, genetic information, mutation and evolution) without having the capacity to have an independent life. For much time, however, they were considered minuscule pathogenetic micro-organisms in observance of Koch and Pasteur's 'germ theory' albeit no microbiologist could show their existence except their filterability and pathogenetic action. Only some voices based on experimental results raised against this dogmatic view, in particular those of Beijerinck, Baur and Mrowka, without dipping effectively into the dominant theory. The discovery relative to their nucleoprotein nature made between 1934 and 1936 (Schlesinger as for the phage, and Bawden and co-operators as for Tobacco mosaic virus; TMV), together with the first demonstrations of their structures thanks to electron microscopy (from 1939 onwards) started on casting a new light on their true identity, which could be more clearly identified when, from 1955 onwards, phage and TMV proved to be decisive factors to understand the strategies of replication of the genetic material. Following the new knowledge, the theoretical view relative to viruses changed rather radically and the current view looks on these pathogenetic agents as nonliving aggregates of macromolecules provided with biological properties. There is, however, a current of thought, made explicitly by Lwoff that places viruses as compromise between living and non living and, perhaps, as primitive forms of life which have had great importance for the evolution of cellular life. At any rate, viruses are peculiar entities whose importance cannot be unacknowledged. PMID:22220354

  14. 75 FR 39420 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-44; Small Entity Compliance Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-08

    ... Administration (NASA). ACTION: Small Entity Compliance Guide. SUMMARY: This document is issued under the joint... of Federal Funding Accountability and Transparency Act of 2006 (Pub. L. 109-282), as amended by section 6202 of the Government Funding Transparency Act of 2008 (Pub. L. 110-252), which requires...

  15. 20 CFR 670.310 - How are entities selected to receive funding?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... to Federal Acquisition Regulation (48 CFR Chapter 1) and DOL Acquisition Regulation (48 CFR Chapter... LABOR (CONTINUED) THE JOB CORPS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Funding and Selection of... (c) and (d) of that Act apply. In selecting an entity, Job Corps issues requests for proposals...

  16. 20 CFR 670.310 - How are entities selected to receive funding?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... to Federal Acquisition Regulation (48 CFR Chapter 1) and DOL Acquisition Regulation (48 CFR Chapter... LABOR (CONTINUED) THE JOB CORPS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Funding and Selection of... (c) and (d) of that Act apply. In selecting an entity, Job Corps issues requests for proposals...

  17. 20 CFR 670.310 - How are entities selected to receive funding?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... to Federal Acquisition Regulation (48 CFR Chapter 1) and DOL Acquisition Regulation (48 CFR Chapter... LABOR (CONTINUED) THE JOB CORPS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Funding and Selection of... (c) and (d) of that Act apply. In selecting an entity, Job Corps issues requests for proposals...

  18. The neural representation of plural discourse entities.

    PubMed

    Boiteau, Timothy W; Bowers, Eric; Nair, Veena A; Almor, Amit

    2014-10-01

    Little is known about the underlying neural structures that mediate the generation and tracking of discourse referents. In two functional magnetic resonance imaging experiments, we examined the neural structures involved in generating and maintaining the representations of multiple referents. Experiment 1 used two-sentence discourses with singular and plural conditions linking back to single or conjoined subjects. In Experiment 2, conjunction type was manipulated in order to keep the number of discourse entities constant across the discourse. Both experiments found greater activation in the superior parietal lobule bilaterally for plural entities relative to singular entities in Experiment 1 and for unconjoined plural entities relative to conjoined plural entities in Experiment 2. This parietal activation suggests that referring to multiple entities evokes multiple representations that need to be integrated and tracked. We discuss these findings in terms of psycholinguistic theories of multiple referent representations.

  19. Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus

    PubMed Central

    van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

    2015-01-01

    Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. (Hepatology 2015;61:1174–1182) PMID:25482139

  20. Prolonged-acting, multi-targeting gallium nanoparticles potently inhibit growth of both HIV and mycobacteria in co-infected human macrophages.

    PubMed

    Narayanasamy, Prabagaran; Switzer, Barbara L; Britigan, Bradley E

    2015-03-06

    Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, macrophage and dendritic cell). Therefore, we hypothesized that one way this can be achieved is through drug-targeting by a nanoformulated drug that ideally would be active against both HIV and TB. Accordingly, we validated macrophage targeted long acting (sustained drug release) gallium (Ga) nanoformulation against HIV-mycobacterium co-infection. The multi-targeted Ga nanoparticle agent inhibited growth of both HIV and TB in the macrophage. The Ga nanoparticles reduced the growth of mycobacterium and HIV for up to 15 days following single drug loading. These results provide a potential new approach to treat HIV-TB co-infection that could eventually lead to improved clinical outcomes.

  1. Prolonged-acting, Multi-targeting Gallium Nanoparticles Potently Inhibit Growth of Both HIV and Mycobacteria in Co-Infected Human Macrophages

    PubMed Central

    Narayanasamy, Prabagaran; Switzer, Barbara L.; Britigan, Bradley E.

    2015-01-01

    Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, macrophage and dendritic cell). Therefore, we hypothesized that one way this can be achieved is through drug-targeting by a nanoformulated drug that ideally would be active against both HIV and TB. Accordingly, we validated macrophage targeted long acting (sustained drug release) gallium (Ga) nanoformulation against HIV-mycobacterium co-infection. The multi-targeted Ga nanoparticle agent inhibited growth of both HIV and TB in the macrophage. The Ga nanoparticles reduced the growth of mycobacterium and HIV for up to 15 days following single drug loading. These results provide a potential new approach to treat HIV-TB co-infection that could eventually lead to improved clinical outcomes. PMID:25744727

  2. Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target

    PubMed Central

    Chang, Chien-Yi; Krishnan, Thiba; Wang, Hao; Chen, Ye; Yin, Wai-Fong; Chong, Yee-Meng; Tan, Li Ying; Chong, Teik Min; Chan, Kok-Gan

    2014-01-01

    N-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach. PMID:25430794

  3. Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target.

    PubMed

    Chang, Chien-Yi; Krishnan, Thiba; Wang, Hao; Chen, Ye; Yin, Wai-Fong; Chong, Yee-Meng; Tan, Li Ying; Chong, Teik Min; Chan, Kok-Gan

    2014-01-01

    N-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography-mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach. PMID:25430794

  4. Entitymetrics: Measuring the Impact of Entities

    PubMed Central

    Ding, Ying; Song, Min; Han, Jia; Yu, Qi; Yan, Erjia; Lin, Lili; Chambers, Tamy

    2013-01-01

    This paper proposes entitymetrics to measure the impact of knowledge units. Entitymetrics highlight the importance of entities embedded in scientific literature for further knowledge discovery. In this paper, we use Metformin, a drug for diabetes, as an example to form an entity-entity citation network based on literature related to Metformin. We then calculate the network features and compare the centrality ranks of biological entities with results from Comparative Toxicogenomics Database (CTD). The comparison demonstrates the usefulness of entitymetrics to detect most of the outstanding interactions manually curated in CTD. PMID:24009660

  5. 7 CFR 1738.16 - Eligible entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... provide, broadband services in eligible rural communities. (1) Types of eligible entities include... services to the eligible rural community. RUS will determine whether the commitment is sufficient...

  6. 78 FR 53194 - Advisory Group to the Internal Revenue Service Tax Exempt and Government Entities Division (TE/GE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... Internal Revenue Service Advisory Group to the Internal Revenue Service Tax Exempt and Government Entities... Advisory Committee on Tax Exempt and Government Entities (ACT) will hold a public meeting on Thursday... Limited IRS Resources in the Tax Administration of Small Tax-Exempt Organizations Federal, State and...

  7. 45 CFR 1159.5 - What government entities will the Endowment notify of proposed changes to its systems of records?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false What government entities will the Endowment notify of proposed changes to its systems of records? 1159.5 Section 1159.5 Public Welfare Regulations... ENDOWMENT FOR THE ARTS IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1159.5 What government entities will...

  8. 17 CFR 1.44 - Records and reports of warehouses, depositories, and other similar entities; visitation of premises.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... warehouses, depositories, and other similar entities; visitation of premises. 1.44 Section 1.44 Commodity and... ACT Miscellaneous § 1.44 Records and reports of warehouses, depositories, and other similar entities; visitation of premises. Each contract market shall require the operators of warehouses, depositories...

  9. 22 CFR 96.5 - Requirement that accrediting entity be a nonprofit or public entity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... administering standards for entities providing child welfare services; or (b) A public entity (other than a... political subdivision, agency, or instrumentality thereof, that is responsible for licensing adoption... child welfare services....

  10. 22 CFR 96.5 - Requirement that accrediting entity be a nonprofit or public entity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... administering standards for entities providing child welfare services; or (b) A public entity (other than a... political subdivision, agency, or instrumentality thereof, that is responsible for licensing adoption... child welfare services....

  11. 47 CFR 101.538 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Designated entities. 101.538 Section 101.538 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.538 Designated entities....

  12. 47 CFR 101.538 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Designated entities. 101.538 Section 101.538 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.538 Designated entities....

  13. 47 CFR 27.807 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Designated entities. 27.807 Section 27.807 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.807 Designated entities. (a) Eligibility for small business...

  14. 47 CFR 27.906 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Designated entities. 27.906 Section 27.906 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.906 Designated entities. (a) Eligibility for small...

  15. 47 CFR 27.807 - Designated entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Designated entities. 27.807 Section 27.807 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.807 Designated entities. (a) Eligibility for small business...

  16. 47 CFR 27.906 - Designated entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Designated entities. 27.906 Section 27.906 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.906 Designated entities. (a) Eligibility for small...

  17. 47 CFR 22.229 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES...) Eligibility for small business provisions. (1) A very small business is an entity that, together with its... preceding three years. (2) A small business is an entity that, together with its controlling interests...

  18. 47 CFR 24.321 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS... for small business provisions. (1) A small business is an entity that, together with its controlling... years. (2) A very small business is an entity that, together with its controlling interests...

  19. 47 CFR 22.223 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Designated entities. 22.223 Section 22.223 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES... sections. (b) A small business is an entity that either: (1) Together with its affiliates and...

  20. 47 CFR 27.502 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-806 MHz Band § 27.502 Designated entities. Eligibility for small business provisions: (a)(1) A small business is an entity that, together with...

  1. 47 CFR 27.807 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.807 Designated entities. (a) Eligibility for small business provisions...-1392 MHz band. (1) A very small business is an entity that, together with its controlling interests...

  2. 47 CFR 27.702 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-746 MHz Band § 27.702 Designated entities. (a) Eligibility for small business provisions. (1) An entrepreneur is an entity that, together with...

  3. 47 CFR 27.906 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.906 Designated entities. (a) Eligibility for small business provisions. (1) A very small business is an entity that, together with its controlling interests...

  4. 46 CFR 67.41 - Governmental entity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Governmental entity. 67.41 Section 67.41 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS Citizenship Requirements for Vessel Documentation § 67.41 Governmental entity....

  5. 46 CFR 67.41 - Governmental entity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Governmental entity. 67.41 Section 67.41 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS Citizenship Requirements for Vessel Documentation § 67.41 Governmental entity....

  6. 47 CFR 27.702 - Designated entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Designated entities. 27.702 Section 27.702 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-746 MHz Band § 27.702 Designated entities....

  7. 47 CFR 27.702 - Designated entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Designated entities. 27.702 Section 27.702 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-746 MHz Band § 27.702 Designated entities....

  8. 47 CFR 27.906 - Designated entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Designated entities. 27.906 Section 27.906 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.906 Designated entities. (a) Eligibility for small...

  9. 47 CFR 27.807 - Designated entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Designated entities. 27.807 Section 27.807 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.807 Designated entities. (a) Eligibility for small business...

  10. 47 CFR 27.702 - Designated entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Designated entities. 27.702 Section 27.702 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-746 MHz Band § 27.702 Designated entities....

  11. 47 CFR 27.807 - Designated entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Designated entities. 27.807 Section 27.807 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.807 Designated entities. (a) Eligibility for small business...

  12. 47 CFR 27.702 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Designated entities. 27.702 Section 27.702 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-746 MHz Band § 27.702 Designated entities....

  13. 47 CFR 27.906 - Designated entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Designated entities. 27.906 Section 27.906 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.906 Designated entities. (a) Eligibility for small...

  14. 46 CFR 403.110 - Accounting entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Accounting entities. 403.110 Section 403.110 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.110 Accounting entities. Each Association shall be a separate...

  15. 46 CFR 403.110 - Accounting entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Accounting entities. 403.110 Section 403.110 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.110 Accounting entities. Each Association shall be a separate...

  16. 46 CFR 403.110 - Accounting entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Accounting entities. 403.110 Section 403.110 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.110 Accounting entities. Each Association shall be a separate...

  17. 18 CFR 46.5 - Covered entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... organization primarily engaged in the business of providing financial services or credit, a mutual savings bank... FOR PERSONS HOLDING INTERLOCKING POSITIONS § 46.5 Covered entities. Entities to which the general rule in § 46.4(b) applies are the following: (a) Any investment bank, bank holding company, foreign...

  18. 46 CFR 403.110 - Accounting entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Accounting entities. 403.110 Section 403.110 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.110 Accounting entities. Each Association shall be a separate...

  19. 46 CFR 403.110 - Accounting entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Accounting entities. 403.110 Section 403.110 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.110 Accounting entities. Each Association shall be a separate...

  20. MiR-138 Acts as a Tumor Suppressor by Targeting EZH2 and Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells

    PubMed Central

    Wang, Jianqiang; Duan, Gang; Zhou, Lei; Zhou, Xiaoqing

    2016-01-01

    Chemotherapeutic insensitivity remains a major obstacle to treating osteosarcoma effectively. Recently, increasing evidence has suggested that microRNAs (miRNAs) are involved in drug resistance. However, the effect of miR-138 on cisplatin chemoresistance in osteosarcoma has not been reported. We used real-time PCR to detect the expression of mature miR-138 in osteosarcoma tissues and cell lines. Cell proliferation, invasion, and migration assays were used to observe changes to the osteosarcoma malignant phenotype. MiR-138 was downregulated in osteosarcoma tissues and cell lines, and miR-138 overexpression negatively regulated osteosarcoma cell proliferation, migration, and invasion. We also verified that EZH2 is a direct target of miR-138. Furthermore, enhancing EZH2 expression reduced the inhibitory effects of miR-138 on osteosarcoma. Proliferation, apoptosis assays and caspase-3 activity assay confirmed that elevated miR-138 expression enhanced osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2. In conclusion, the present study demonstrates that miR-138 acts as a tumor suppressor by enhancing osteosarcoma cell chemosensitivity and supports its potential application for treating osteosarcoma in the future. PMID:27019355

  1. Modeling unmanned system collaborative target engagement

    NASA Astrophysics Data System (ADS)

    Jaenisch, Holger M.; Handley, James W.; Hicklen, Michael L.

    2007-04-01

    This paper describes a novel algorithm for collaborative target engagement by unmanned systems (UMS) resulting in emergent behavior. We demonstrate UMS collaborative engagement using a simulation testbed model of a road, convoy vehicles traveling along the road, a squadron of unmanned aerial vehicles (UAVs), and multiple unmanned ground vehicles (UGVs) which are set to detonate when within close proximity to a convoy vehicle. No explicit artificial intelligence or swarming algorithms were used. Collision avoidance was an intrinsic phenomena. All entities acted independently throughout the simulation, but were given similar local instructions for possible courses of action (COAs) depending on current situations. Our algorithm and results are summarized in this paper.

  2. Targeted Lethal Force Transparency Act

    THOMAS, 113th Congress

    Rep. Schiff, Adam B. [D-CA-28

    2014-04-02

    04/02/2014 Referred to the Committee on Intelligence (Permanent Select), and in addition to the Committee on Armed Services, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee... (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  3. Human subtilase SKI-1/S1P is a master regulator of the HCV Lifecycle and a potential host cell target for developing indirect-acting antiviral agents.

    PubMed

    Olmstead, Andrea D; Knecht, Wolfgang; Lazarov, Ina; Dixit, Surjit B; Jean, François

    2012-01-01

    HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs). One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1)--or site-1 protease (S1P). SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of

  4. Environmental Restoration of Corrective Action Unit 408: Bomblet Target Area, Tonopah Test Range, Nevada (Funded by the American Reinvestment and Recovery Act)

    SciTech Connect

    Kevin Cabble , Mark Burmeister and Mark Krauss

    2011-03-03

    The mission of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) Environmental Restoration Program is to address the environmental impacts of weapons testing conducted on the Nevada National Security Site and the Nevada Test and Training Range. The large physical size of these sites, along with limits on funding and other resources available for remediation efforts, means that environmental restoration activities must be prioritized and accomplished incrementally over time. The remediation of a bomblet target area on the Tonopah Test Range (TTR), which is located within the Nevada Test and Training Range, was originally planned in 2007 but was not carried out until funding became available in the summer of 2009 through the American Reinvestment and Recovery Act. This activity was implemented in accordance with the Federal Facility Agreement and Consent Order established between NNSA/NSO and the Nevada Division of Environmental Protection. This activity which was complete by the end of Fiscal Year 2010, involved the excavation of disposal pits suspected of containing submunitions and the surface clearance of submunitions on seven target areas amounting to approximately 6.7 square kilometers of land at the TTR. The TTR was used by Sandia National Laboratories from the late 1960s through the mid-1980s to conduct research into the deployment of submunitions. Although there were efforts to identify, collect, and dispose various amounts of unexploded ordnance on the TTR in the past, no comprehensive effort to remediate the entire flightline area for submunitions was undertaken before this project.

  5. Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea.

    PubMed

    Vendrell, Victor; López-Hernández, Iris; Durán Alonso, María Beatriz; Feijoo-Redondo, Ana; Abello, Gina; Gálvez, Héctor; Giráldez, Fernando; Lamonerie, Thomas; Schimmang, Thomas

    2015-08-15

    Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the re-specification of non-sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirror-image copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea. PMID:26160903

  6. Multitarget drugs of plants origin acting on Alzheimer's disease.

    PubMed

    Russo, P; Frustaci, A; Del Bufalo, A; Fini, M; Cesario, A

    2013-01-01

    The etiopathology of Alzheimer's disease (AD) is extremely complex and heterogeneous, often associated with comorbidities. As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target. The current tendency in drug design and discovery in AD is the rational design or "serendipitous" discovery of new drug entities challenging multiple targets. Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs. Multifunctional drugs often have their origin in natural sources. This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD.

  7. 7 CFR 25.401 - Responsibility of lead managing entity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... lead managing entity will be responsible for strategic plan program activities and monitoring the.... All entities with significant involvement in implementing the strategic plan shall cooperate with...

  8. 7 CFR 25.401 - Responsibility of lead managing entity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... lead managing entity will be responsible for strategic plan program activities and monitoring the.... All entities with significant involvement in implementing the strategic plan shall cooperate with...

  9. 7 CFR 25.401 - Responsibility of lead managing entity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... lead managing entity will be responsible for strategic plan program activities and monitoring the.... All entities with significant involvement in implementing the strategic plan shall cooperate with...

  10. 7 CFR 25.401 - Responsibility of lead managing entity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... lead managing entity will be responsible for strategic plan program activities and monitoring the.... All entities with significant involvement in implementing the strategic plan shall cooperate with...

  11. 7 CFR 25.401 - Responsibility of lead managing entity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... lead managing entity will be responsible for strategic plan program activities and monitoring the.... All entities with significant involvement in implementing the strategic plan shall cooperate with...

  12. 42 CFR 410.145 - Requirements for entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Outpatient Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.145 Requirements for entities. (a) Deemed entities. (1) Except...

  13. 42 CFR 410.145 - Requirements for entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Outpatient Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.145 Requirements for entities. (a) Deemed entities. (1) Except...

  14. 42 CFR 410.145 - Requirements for entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Outpatient Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.145 Requirements for entities. (a) Deemed entities. (1) Except...

  15. 42 CFR 410.145 - Requirements for entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Outpatient Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.145 Requirements for entities. (a) Deemed entities. (1) Except...

  16. 42 CFR 410.145 - Requirements for entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Outpatient Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.145 Requirements for entities. (a) Deemed entities. (1) Except...

  17. Functionalization of polydopamine coated magnetic nanoparticles with biological entities

    NASA Astrophysics Data System (ADS)

    Mǎgeruşan, Lidia; Mrówczyński, Radosław; Turcu, Rodica

    2015-12-01

    New hybrid materials, obtained through introduction of cysteine, lysine and folic acid as biological entities into polydopamine-coated magnetite nanoparticles, are reported. The syntheses are straight forward and various methods were applied for structural and morphological characterization of the resulting nanoparticles. XPS proved a very powerful tool for surface chemical analysis and it evidences the functionalization of polydopamine coated magnetite nanoparticles. The superparamagnetic behavior and the high values of saturation magnetization recommend all products for further application where magnetism is important for targeting, separation, or heating by alternative magnetic fields.

  18. 28 CFR 115.112 - Contracting with other entities for the confinement of detainees.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Contracting with other entities for the confinement of detainees. 115.112 Section 115.112 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Prevention Planning §...

  19. 28 CFR 115.112 - Contracting with other entities for the confinement of detainees.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Contracting with other entities for the confinement of detainees. 115.112 Section 115.112 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Prevention Planning §...

  20. 28 CFR 115.12 - Contracting with other entities for the confinement of inmates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Contracting with other entities for the confinement of inmates. 115.12 Section 115.12 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Adult Prisons and Jails Prevention Planning §...

  1. 28 CFR 115.312 - Contracting with other entities for the confinement of residents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Contracting with other entities for the confinement of residents. 115.312 Section 115.312 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Juvenile Facilities Prevention...

  2. 28 CFR 115.12 - Contracting with other entities for the confinement of inmates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Contracting with other entities for the confinement of inmates. 115.12 Section 115.12 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Adult Prisons and Jails Prevention Planning §...

  3. 28 CFR 115.12 - Contracting with other entities for the confinement of inmates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Contracting with other entities for the confinement of inmates. 115.12 Section 115.12 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Adult Prisons and Jails Prevention Planning §...

  4. 28 CFR 115.312 - Contracting with other entities for the confinement of residents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Contracting with other entities for the confinement of residents. 115.312 Section 115.312 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Juvenile Facilities Prevention...

  5. 28 CFR 115.112 - Contracting with other entities for the confinement of detainees.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Contracting with other entities for the confinement of detainees. 115.112 Section 115.112 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Lockups Prevention Planning §...

  6. 28 CFR 115.312 - Contracting with other entities for the confinement of residents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Contracting with other entities for the confinement of residents. 115.312 Section 115.312 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PRISON RAPE ELIMINATION ACT NATIONAL STANDARDS Standards for Juvenile Facilities Prevention...

  7. 20 CFR 668.410 - What entities are eligible to receive supplemental youth services funding?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... supplemental youth services funding? 668.410 Section 668.410 Employees' Benefits EMPLOYMENT AND TRAINING... WORKFORCE INVESTMENT ACT Supplemental Youth Services § 668.410 What entities are eligible to receive supplemental youth services funding? Eligible recipients for supplemental youth services funding are limited...

  8. 20 CFR 668.410 - What entities are eligible to receive supplemental youth services funding?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... supplemental youth services funding? 668.410 Section 668.410 Employees' Benefits EMPLOYMENT AND TRAINING... WORKFORCE INVESTMENT ACT Supplemental Youth Services § 668.410 What entities are eligible to receive supplemental youth services funding? Eligible recipients for supplemental youth services funding are limited...

  9. 20 CFR 668.410 - What entities are eligible to receive supplemental youth services funding?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... supplemental youth services funding? 668.410 Section 668.410 Employees' Benefits EMPLOYMENT AND TRAINING... WORKFORCE INVESTMENT ACT Supplemental Youth Services § 668.410 What entities are eligible to receive supplemental youth services funding? Eligible recipients for supplemental youth services funding are limited...

  10. 16 CFR 802.41 - Corporations or unincorporated entities at time of formation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION RULES § 802.41 Corporations or unincorporated entities at time of formation. Whenever any person(s... corporation C for in excess of $50 million (as adjusted). Because N's purchase of C is not a transaction...

  11. 16 CFR 802.41 - Corporations or unincorporated entities at time of formation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION RULES § 802.41 Corporations or unincorporated entities at time of formation. Whenever any person(s... corporation C for in excess of $50 million (as adjusted). Because N's purchase of C is not a transaction...

  12. 16 CFR 802.40 - Exempt formation of corporations or unincorporated entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Exempt formation of corporations or unincorporated entities. 802.40 Section 802.40 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION...

  13. 16 CFR 802.40 - Exempt formation of corporations or unincorporated entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Exempt formation of corporations or unincorporated entities. 802.40 Section 802.40 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION...

  14. 20 CFR 668.410 - What entities are eligible to receive supplemental youth services funding?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... supplemental youth services funding? 668.410 Section 668.410 Employees' Benefits EMPLOYMENT AND TRAINING... ACT Supplemental Youth Services § 668.410 What entities are eligible to receive supplemental youth services funding? Eligible recipients for supplemental youth services funding are limited to those...

  15. 20 CFR 668.410 - What entities are eligible to receive supplemental youth services funding?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... supplemental youth services funding? 668.410 Section 668.410 Employees' Benefits EMPLOYMENT AND TRAINING... ACT Supplemental Youth Services § 668.410 What entities are eligible to receive supplemental youth services funding? Eligible recipients for supplemental youth services funding are limited to those...

  16. 76 FR 29183 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ... services for HIV disease); (4) A state-operated AIDS drug purchasing assistance program receiving financial... Affordable Care Act, orphan drugs, when used for the rare condition or disease for which that orphan drug was... an orphan drug when used for a rare disease or condition. The entity types added to the list...

  17. 45 CFR 155.110 - Entities eligible to carry out Exchange functions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... TO HEALTH CARE ACCESS EXCHANGE ESTABLISHMENT STANDARDS AND OTHER RELATED STANDARDS UNDER THE AFFORDABLE CARE ACT General Standards Related to the Establishment of an Exchange § 155.110 Entities eligible... experience in health benefits administration, health care finance, health plan purchasing, health...

  18. 45 CFR 155.110 - Entities eligible to carry out Exchange functions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... TO HEALTH CARE ACCESS EXCHANGE ESTABLISHMENT STANDARDS AND OTHER RELATED STANDARDS UNDER THE AFFORDABLE CARE ACT General Standards Related to the Establishment of an Exchange § 155.110 Entities eligible... experience in health benefits administration, health care finance, health plan purchasing, health...

  19. 22 CFR 96.25 - Access to information and documents requested by the accrediting entity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Access to information and documents requested by the accrediting entity. 96.25 Section 96.25 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED SERVICES ACCREDITATION OF AGENCIES AND APPROVAL OF PERSONS UNDER THE INTERCOUNTRY ADOPTION ACT...

  20. 20 CFR 662.210 - What other entities may serve as One-Stop partners?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) WIA provides that other entities that carry out a human resource program, including Federal, State, or... partners? 662.210 Section 662.210 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... Act (42 U.S.C. 601 et seq.); (2) Employment and training programs authorized under section 6(d)(4)...

  1. A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

    PubMed

    Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

    2016-08-01

    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

  2. A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

    PubMed

    Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

    2016-08-01

    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment. PMID:27035618

  3. A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

    PubMed Central

    Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

    2016-01-01

    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment. PMID:27035618

  4. 12 CFR 1237.10 - Limited-life regulated entities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Limited-life regulated entities. 1237.10... RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status. The United... liquidity portfolio of a limited-life regulated entity. (c) Policies and procedures. The Agency may...

  5. 12 CFR 1237.10 - Limited-life regulated entities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Limited-life regulated entities. 1237.10... RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status. The United... liquidity portfolio of a limited-life regulated entity. (c) Policies and procedures. The Agency may...

  6. 12 CFR 1237.10 - Limited-life regulated entities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Limited-life regulated entities. 1237.10... RECEIVERSHIP Limited-Life Regulated Entities § 1237.10 Limited-life regulated entities. (a) Status. The United... liquidity portfolio of a limited-life regulated entity. (c) Policies and procedures. The Agency may...

  7. 37 CFR 1.29 - Micro entity status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Micro entity status. 1.29... Micro entity status. (a) To establish micro entity status under this paragraph, the applicant must... establish micro entity status under this paragraph, the applicant must certify that: (1) The...

  8. 37 CFR 1.29 - Micro entity status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Micro entity status. 1.29... Micro entity status. (a) To establish micro entity status under this paragraph, the applicant must... establish micro entity status under this paragraph, the applicant must certify that: (1) The...

  9. 20 CFR 662.220 - What entity serves as the One-Stop partner for a particular program in the local area?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What entity serves as the One-Stop partner... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.220 What entity...

  10. 20 CFR 662.220 - What entity serves as the One-Stop partner for a particular program in the local area?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What entity serves as the One-Stop partner... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.220 What entity...

  11. 31 CFR 536.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 536.303 Section 536.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NARCOTICS TRAFFICKING SANCTIONS REGULATIONS General Definitions §...

  12. 31 CFR 536.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 536.303 Section 536.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NARCOTICS TRAFFICKING SANCTIONS REGULATIONS General Definitions §...

  13. 31 CFR 536.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 536.303 Section 536.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NARCOTICS TRAFFICKING SANCTIONS REGULATIONS General Definitions §...

  14. 31 CFR 536.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 536.303 Section 536.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NARCOTICS TRAFFICKING SANCTIONS REGULATIONS General Definitions §...

  15. 31 CFR 536.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 536.303 Section 536.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NARCOTICS TRAFFICKING SANCTIONS REGULATIONS General Definitions §...

  16. 31 CFR 589.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 589.303 Section 589.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY UKRAINE RELATED SANCTIONS REGULATIONS General Definitions §...

  17. 77 FR 56571 - Unincorporated Business Entities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... Institutions, dated October 14, 2010, and published in the Federal Register at 75 FR 64728 on October 20, 2010... 12 CFR Parts 604, 611, 612, 619, 620, 621, 622, 623, and 630 RIN 3052-AC65 Unincorporated Business...) institutions' use of unincorporated business entities (UBEs) organized under State law for certain...

  18. 31 CFR 588.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 588.303 Section 588.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WESTERN BALKANS STABILIZATION REGULATIONS General Definitions §...

  19. 47 CFR 27.1218 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Designated entities. 27.1218 Section 27.1218 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1218 Designated...

  20. 31 CFR 593.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 593.303 Section 593.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES TAYLOR SANCTIONS REGULATIONS...

  1. 31 CFR 800.212 - Foreign entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Foreign entity. 800.212 Section 800.212 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS,...

  2. 31 CFR 800.211 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 800.211 Section 800.211 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND TAKEOVERS...

  3. 31 CFR 596.308 - Person; entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Person; entity. 596.308 Section 596.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS...

  4. 31 CFR 596.308 - Person; entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Person; entity. 596.308 Section 596.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS...

  5. 31 CFR 596.308 - Person; entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Person; entity. 596.308 Section 596.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS...

  6. 31 CFR 596.308 - Person; entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Person; entity. 596.308 Section 596.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS...

  7. 31 CFR 596.308 - Person; entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Person; entity. 596.308 Section 596.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM LIST GOVERNMENTS SANCTIONS...

  8. 47 CFR 22.882 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Air...) Eligibility for small business provisions in the commercial Air-Ground Radiotelephone Service. (1) A small business is an entity that, together with its affiliates, its controlling interests and the affiliates...

  9. 31 CFR 592.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 592.303 Section 592.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS General Definitions §...

  10. 31 CFR 592.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 592.303 Section 592.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS General Definitions §...

  11. 31 CFR 592.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 592.303 Section 592.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS General Definitions §...

  12. 31 CFR 592.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 592.303 Section 592.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS General Definitions §...

  13. 31 CFR 592.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 592.303 Section 592.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS General Definitions §...

  14. 31 CFR 586.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 586.303 Section 586.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FEDERAL REPUBLIC OF YUGOSLAVIA (SERBIA & MONTENEGRO) KOSOVO...

  15. 31 CFR 587.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 587.303 Section 587.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FEDERAL REPUBLIC OF YUGOSLAVIA (SERBIA AND MONTENEGRO)...

  16. 31 CFR 597.306 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 597.306 Section 597.306 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN TERRORIST ORGANIZATIONS SANCTIONS REGULATIONS...

  17. 31 CFR 551.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 551.303 Section 551.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS General Definitions § 551.303...

  18. 31 CFR 541.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 541.303 Section 541.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ZIMBABWE SANCTIONS REGULATIONS General Definitions § 541.303...

  19. 31 CFR 597.306 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 597.306 Section 597.306 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN TERRORIST ORGANIZATIONS SANCTIONS REGULATIONS...

  20. 31 CFR 597.306 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 597.306 Section 597.306 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN TERRORIST ORGANIZATIONS SANCTIONS REGULATIONS...

  1. 31 CFR 597.306 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 597.306 Section 597.306 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN TERRORIST ORGANIZATIONS SANCTIONS REGULATIONS...

  2. 31 CFR 597.306 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 597.306 Section 597.306 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN TERRORIST ORGANIZATIONS SANCTIONS REGULATIONS...

  3. 31 CFR 551.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 551.303 Section 551.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS General Definitions § 551.303...

  4. 31 CFR 551.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 551.303 Section 551.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS General Definitions § 551.303...

  5. 31 CFR 551.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 551.303 Section 551.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS General Definitions § 551.303...

  6. 31 CFR 551.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 551.303 Section 551.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS General Definitions § 551.303...

  7. 47 CFR 27.502 - Designated entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Designated entities. 27.502 Section 27.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-806 MHz Band § 27.502 Designated...

  8. 47 CFR 27.1218 - Designated entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Designated entities. 27.1218 Section 27.1218 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1218 Designated...

  9. 47 CFR 27.502 - Designated entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Designated entities. 27.502 Section 27.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-806 MHz Band § 27.502 Designated...

  10. 47 CFR 27.1218 - Designated entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Designated entities. 27.1218 Section 27.1218 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1218 Designated...

  11. 47 CFR 27.502 - Designated entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Designated entities. 27.502 Section 27.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-806 MHz Band § 27.502 Designated...

  12. 47 CFR 27.1218 - Designated entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Designated entities. 27.1218 Section 27.1218 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27.1218 Designated...

  13. 47 CFR 27.502 - Designated entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Designated entities. 27.502 Section 27.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Competitive Bidding Procedures for the 698-806 MHz Band § 27.502 Designated...

  14. Pelvic fibromatoses--a rare gynecological entity.

    PubMed

    Buckshee, K; Mittal, S; Agarwal, N; Chellani, M

    1988-06-01

    A rare case of pelvic fibromatoses is reported. This condition is rarely encountered in gynecological practice but when encountered, creates a diagnostic and therapeutic challenge. The reported patient highlights the difficulties encountered in surgical excision (done twice) and illustrates the local aggressive growth behavior of this entity.

  15. 31 CFR 548.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 548.303 Section 548.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS REGULATIONS General Definitions § 548.303...

  16. 31 CFR 548.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 548.303 Section 548.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS REGULATIONS General Definitions § 548.303...

  17. 31 CFR 548.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 548.303 Section 548.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS REGULATIONS General Definitions § 548.303...

  18. 31 CFR 548.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 548.303 Section 548.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS REGULATIONS General Definitions § 548.303...

  19. 31 CFR 548.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 548.303 Section 548.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BELARUS SANCTIONS REGULATIONS General Definitions § 548.303...

  20. 31 CFR 510.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 510.303 Section 510.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.303...

  1. 31 CFR 510.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 510.303 Section 510.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.303...

  2. 31 CFR 510.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 510.303 Section 510.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.303...

  3. 31 CFR 510.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 510.303 Section 510.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.303...

  4. 31 CFR 545.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 545.303 Section 545.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN) SANCTIONS REGULATIONS General Definitions §...

  5. 31 CFR 598.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 598.303 Section 598.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS..., organization, network, group, or subgroup, or any form of business collaboration....

  6. 31 CFR 594.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 594.303 Section 594.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions §...

  7. 31 CFR 594.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 594.303 Section 594.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions §...

  8. 31 CFR 594.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 594.303 Section 594.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions §...

  9. 31 CFR 594.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 594.303 Section 594.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions §...

  10. 31 CFR 544.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 544.303 Section 544.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION PROLIFERATORS SANCTIONS...

  11. 31 CFR 539.303 - Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Entity. 539.303 Section 539.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION TRADE CONTROL REGULATIONS...

  12. 13 CFR 130.200 - Eligible entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Eligible entities. 130.200 Section 130.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS DEVELOPMENT... or university; (3) A college or school of business, engineering, commerce or agriculture; (4)...

  13. 13 CFR 130.200 - Eligible entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Eligible entities. 130.200 Section 130.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS DEVELOPMENT... or university; (3) A college or school of business, engineering, commerce or agriculture; (4)...

  14. 31 CFR 576.304 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 576.304 Section 576.304 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY SANCTIONS REGULATIONS...

  15. 31 CFR 576.304 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 576.304 Section 576.304 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY SANCTIONS REGULATIONS...

  16. 31 CFR 576.304 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 576.304 Section 576.304 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY SANCTIONS REGULATIONS...

  17. 31 CFR 576.304 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 576.304 Section 576.304 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRAQ STABILIZATION AND INSURGENCY SANCTIONS REGULATIONS...

  18. 31 CFR 562.303 - Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Entity. 562.303 Section 562.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General...

  19. 31 CFR 562.303 - Entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Entity. 562.303 Section 562.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General...

  20. 31 CFR 562.303 - Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Entity. 562.303 Section 562.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General...

  1. 31 CFR 562.303 - Entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Entity. 562.303 Section 562.303 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS General...

  2. 47 CFR 101.1429 - Designated entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for the preceding three years. (3) An entrepreneur is an entity that, together with its controlling... this chapter. A winning bidder that qualifies as an entrepreneur, as defined in this section, or a consortium of entrepreneurs may use the bidding credit specified in § 1.2110(f)(2)(iii) of this chapter....

  3. Microwave assisted total synthesis of a benzothiophene-based new chemical entity (NCE)

    EPA Science Inventory

    Pharmaceutical scientists are required to generate diverse arrays of complex targets in short span of time, which can now be achieved by microwave-assisted organic synthesis. New chemical entities (NCE) can be built in a fraction of the time using this technique. However, there a...

  4. Using nanoinformatics methods for automatically identifying relevant nanotoxicology entities from the literature.

    PubMed

    García-Remesal, Miguel; García-Ruiz, Alejandro; Pérez-Rey, David; de la Iglesia, Diana; Maojo, Víctor

    2013-01-01

    Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a "proof of concept" that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine.

  5. Using nanoinformatics methods for automatically identifying relevant nanotoxicology entities from the literature.

    PubMed

    García-Remesal, Miguel; García-Ruiz, Alejandro; Pérez-Rey, David; de la Iglesia, Diana; Maojo, Víctor

    2013-01-01

    Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a "proof of concept" that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine. PMID:23509721

  6. Using Nanoinformatics Methods for Automatically Identifying Relevant Nanotoxicology Entities from the Literature

    PubMed Central

    García-Remesal, Miguel; García-Ruiz, Alejandro; Pérez-Rey, David; de la Iglesia, Diana; Maojo, Víctor

    2013-01-01

    Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a “proof of concept” that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine. PMID:23509721

  7. Civil money penalties for referrals to entities and for prohibited arrangements and schemes--HHS. Final rule with comment period.

    PubMed

    1995-03-31

    This final rule implements the civil money penalty (CMP) provisions established through sections 1877(g)(3) and 1877(g)(4) of the Social Security Act. Specifically, in accordance with section 1877(g)(3), these regulations set forth CMPs, assessments and an exclusion against any person who presents, or causes to be presented, a bill or claim the person knows or should know is for a service unlawfully referred under section 1877(a)(1)(A) of the Act, or has not refunded amounts inappropriately collected for a prohibited referral. In addition, in accordance with section 1877(g)(4), these regulations set forth CMPs, assessments and an exclusion in cases where a physician or entity enters into an arrangement or scheme in which the physician or entity knows, or should have known, that the principal purpose is to assure referrals by the physician which, if made directly to a particular entity, would violate the prohibition on referrals described in section 1877(a) of the Act.

  8. 75 FR 64782 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... Act. The list of designees is as follows: Entities 1. GENETICA GANADERA RANCHO ALEJANDRA S.P.R. DE R...; (ENTITY) . 2. GENETICA IMPORT-EXPORT S.P.R. DE R.L. DE C.V., Calle Alvarado No. 143, Local 5-J, Zona...- 690830 (Mexico); (INDIVIDUAL) . 14. OLVERA ESTRADA, Rodolfo, c/o GENETICA GANADERA RANCHO ALEJANDRA...

  9. 77 FR 30297 - Privacy Act of 1974; U.S. Customs and Border Protection, DHS/CBP-006-Automated Targeting System...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... titled, U.S. Customs and Border Protection, DHS/CBP-006--Automated Targeting System (ATS) 72 FR 43650.... Customs and Border Protection, DHS/CBP-006--Automated Targeting System (ATS) 72 FR 43650, August 6, 2007... crossing card, birth certificate, certificate of naturalization, re-entry permit, military card)...

  10. On Carcinomas and Other Pathological Entities

    PubMed Central

    Kumar, Anand; Ceusters, Werner; Rosse, Cornelius

    2005-01-01

    Tumours, abscesses, cysts, scars and fractures are familiar types of what we shall call pathological continuant entities. The instances of such types exist always in or on anatomical structures, which thereby become transformed into pathological anatomical structures of corresponding types: a fractured tibia, a blistered thumb, a carcinomatous colon. In previous work on biomedical ontologies we showed how the provision of formal definitions for relations such as is_a, part_of and transformation_of can facilitate the integration of such ontologies in ways which have the potential to support new kinds of automated reasoning. We here extend this approach to the treatment of pathologies, focusing especially on those pathological continuant entities which arise when organs become affected by carcinomas. PMID:18629199

  11. Generic Entity Resolution in Relational Databases

    NASA Astrophysics Data System (ADS)

    Sidló, Csaba István

    Entity Resolution (ER) covers the problem of identifying distinct representations of real-world entities in heterogeneous databases. We consider the generic formulation of ER problems (GER) with exact outcome. In practice, input data usually resides in relational databases and can grow to huge volumes. Yet, typical solutions described in the literature employ standalone memory resident algorithms. In this paper we utilize facilities of standard, unmodified relational database management systems (RDBMS) to enhance the efficiency of GER algorithms. We study and revise the problem formulation, and propose practical and efficient algorithms optimized for RDBMS external memory processing. We outline a real-world scenario and demonstrate the advantage of algorithms by performing experiments on insurance customer data.

  12. Software Engineering Support Activities for Very Small Entities

    NASA Astrophysics Data System (ADS)

    Ribaud, Vincent; Saliou, Philippe; O'Connor, Rory V.; Laporte, Claude Y.

    The emerging ISO/IEC 29110 standard Lifecycle profiles for Very Small Entities has at its core a Management and Engineering Guides which is targeted at very small entity (enterprise, organization, department or project) having up to 25 people, to assist them unlock the potential benefits of using standards which are specifically designed to address there needs. The developers of the standard, ISO/IEC JCT1/SC7 Working Group 24 (WG24), recommend the use of pilot projects as a mean to trial the adoption of the new International standard in small organisations. Accordingly an ISO/IEC 29110 pilot project has been established between the Software Engineering group of Brest University and a 14 person company with the aim of establishing an engineering discipline for a new web-based project. This paper details the lessons learned from the pilot project and based on our experiences with using ISO/IEC 29110 we identify a potential deficiency and accordingly propose new process area, "Infrastructure and Support" for include in the future evolution of ISO/IEC 29110 Process Profiles.

  13. 7 CFR 63.4 - Eligible entity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) NATIONAL SHEEP INDUSTRY... promotes the betterment of the United States sheep or goat industries and that is a public, private,...

  14. 7 CFR 63.4 - Eligible entity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) NATIONAL SHEEP INDUSTRY... promotes the betterment of the United States sheep or goat industries and that is a public, private,...

  15. 7 CFR 63.4 - Eligible entity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) NATIONAL SHEEP INDUSTRY... promotes the betterment of the United States sheep or goat industries and that is a public, private,...

  16. 7 CFR 63.4 - Eligible entity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) NATIONAL SHEEP INDUSTRY... promotes the betterment of the United States sheep or goat industries and that is a public, private,...

  17. Central neurocytoma: establishment of the disease entity.

    PubMed

    Kim, Dong Gyu; Park, Chul-Kee

    2015-01-01

    The establishment and identification of central neurocytoma as a distinct disease entity are invaluable in catalyzing investigations of neuronal differentiation in central nervous system tumors. The discovery of neuronal differentiation in neuroepithelial tumors has been extended to extraventricular tumors and potentially to various glial tumors undergoing neuronal differentiation. Understanding the disease spectrum of neuronal and mixed neuronal-glial tumors is important for deciphering the mechanism of gliomagenesis.

  18. Is Alzheimer's disease a homogeneous disease entity?

    PubMed

    Korczyn, Amos D

    2013-10-01

    The epidemic proportions of dementia in old age are a cause of great concern for the medical profession and the society at large. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, and vascular dementia (VaD) as being the second. This dichotomous view of a primary neurodegenerative disease as opposed to a disorder where extrinsic factors cause brain damage led to separate lines of research in these two entities. New biomarkers, particularly the introduction of modern neuroimaging and cerebrospinal fluid changes, have, in recent years, helped to identify anatomical and chemical changes of VaD and of AD. Nevertheless, there is a substantial difference between the two entities. While it is clear that VaD is a heterogeneous entity, AD is supposed to be a single disorder. Nobody attempts to use CADASIL as a template to develops treatment for sporadic VaD. On the other hand, early-onset AD is used to develop therapy for sporadic AD. This paper will discuss the problems relating to this false concept and its consequences. PMID:23933662

  19. The preclinical testing strategy for the development of novel chemical entities for the treatment of asthma.

    PubMed

    Hahn, Christian; Erb, Klaus Joseph

    2008-06-01

    Identifying and developing novel chemical entities (NCE) for the treatment of asthma is a time-consuming process and liabilities that endanger the successful progression of a compound from research into the patient are found throughout all phases of drug discovery. In particular the failure of advanced compounds in clinical studies due to lack of efficacy and/or safety concerns is tremendously costly. Therefore, in order to try and reduce the failure rate in clinical trials various in vitro and in vivo tests are performed during preclinical development, to rapidly identify liabilities, eliminate high risk compounds and promote promising potential drug candidates. To achieve this objective, numerous prerequisites have to be met regarding the physico-chemical properties of the compound, and bioactivity or model systems are needed to rate the therapeutic potential of new compounds. Drug liabilities such as target and species specificity, formulation issues, pharmacokinetics as well as pharmacodynamics and the toxic potential of the compound have to be analyzed in great detail before a compound can enter a clinical trial. A particularly challenging aspect of developing novel NCEs for the treatment of asthma is choosing and setting up in vivo models believed to be predictive for human disease. Numerous companies have in the past and are currently developing NCEs targeting many different pathways and cells with the aim to treat asthma. However, currently the only NCE having a significant market share are long-acting beta-agonists (LABA), inhaled and orally active steroids and leukotriene receptor antagonists. In the past many novel NCE for the treatment of asthma were effective in animal models but failed in the clinic. In this review we outline the prerequisites of novel NCE needed for clinical development. PMID:18537583

  20. 14 CFR 252.19 - Single-entity charters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.19 Single-entity charters. On single-entity charters... flights is given notice of the smoking procedures for the flight at the time he or she first...

  1. 14 CFR 252.19 - Single-entity charters.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.19 Single-entity charters. On single-entity charters... flights is given notice of the smoking procedures for the flight at the time he or she first...

  2. 14 CFR 252.19 - Single-entity charters.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.19 Single-entity charters. On single-entity charters... flights is given notice of the smoking procedures for the flight at the time he or she first...

  3. 14 CFR 252.19 - Single-entity charters.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.19 Single-entity charters. On single-entity charters... flights is given notice of the smoking procedures for the flight at the time he or she first...

  4. 14 CFR 252.19 - Single-entity charters.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.19 Single-entity charters. On single-entity charters... flights is given notice of the smoking procedures for the flight at the time he or she first...

  5. Chemical Entity Recognition and Resolution to ChEBI

    PubMed Central

    Grego, Tiago; Pesquita, Catia; Bastos, Hugo P.; Couto, Francisco M.

    2012-01-01

    Chemical entities are ubiquitous through the biomedical literature and the development of text-mining systems that can efficiently identify those entities are required. Due to the lack of available corpora and data resources, the community has focused its efforts in the development of gene and protein named entity recognition systems, but with the release of ChEBI and the availability of an annotated corpus, this task can be addressed. We developed a machine-learning-based method for chemical entity recognition and a lexical-similarity-based method for chemical entity resolution and compared them with Whatizit, a popular-dictionary-based method. Our methods outperformed the dictionary-based method in all tasks, yielding an improvement in F-measure of 20% for the entity recognition task, 2–5% for the entity-resolution task, and 15% for combined entity recognition and resolution tasks. PMID:25937941

  6. 77 FR 36231 - Americans With Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-18

    ...The Architectural and Transportation Barriers Compliance Board (Access Board) proposes to amend the Americans with Disabilities Act (ADA) and Architectural Barriers Act (ABA) Accessibility Guidelines to specifically address emergency transportable housing units that are provided by the Federal Emergency Management Agency or other entities on a temporary site in response to an emergency need......

  7. Indian Child Welfare Act: Existing Information on Implementation Issues Could Be Used to Target Guidance and Assistance to States. GAO-05-290

    ERIC Educational Resources Information Center

    US Government Accountability Office, 2005

    2005-01-01

    The Indian Child Welfare Act (ICWA ) created important protections to prevent state child welfare agencies and courts from inappropriately separating American Indian children from their families. This report describes (1) the factors that influence placement decisions for children subject to ICWA; (2) the extent to which, if any, placements for…

  8. 17 CFR 202.8 - Small entity compliance guides.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Small entity compliance guides. 202.8 Section 202.8 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION INFORMAL AND OTHER PROCEDURES § 202.8 Small entity compliance guides. The following small entity compliance guides are available to the public from...

  9. 7 CFR 760.115 - Deceased individuals or dissolved entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Deceased individuals or dissolved entities. 760.115... Agricultural Disaster Assistance Programs § 760.115 Deceased individuals or dissolved entities. (a) Payments... or is a dissolved entity if a representative, who currently has authority to enter into a...

  10. 7 CFR 760.908 - Deceased individuals or dissolved entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Deceased individuals or dissolved entities. 760.908... § 760.908 Deceased individuals or dissolved entities. (a) Payments may be made for eligible losses suffered by an eligible participant who is now a deceased individual or is a dissolved entity if...

  11. 7 CFR 1413.113 - Deceased individuals or dissolved entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Deceased individuals or dissolved entities. 1413.113... PROGRAMS Durum Wheat Quality Program § 1413.113 Deceased individuals or dissolved entities. (a) Payment may... individual or is a dissolved entity if a representative who currently has authority to enter into a...

  12. 37 CFR 253.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... broadcasting entity. 253.2 Section 253.2 Patents, Trademarks, and Copyrights U.S. COPYRIGHT OFFICE, LIBRARY OF... CONNECTION WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational...

  13. 37 CFR 381.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... broadcasting entity. 381.2 Section 381.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY... WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 381.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational broadcast...

  14. 37 CFR 381.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... broadcasting entity. 381.2 Section 381.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY... WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 381.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational broadcast...

  15. 37 CFR 381.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... broadcasting entity. 381.2 Section 381.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY... WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 381.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational broadcast...

  16. 37 CFR 253.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... broadcasting entity. 253.2 Section 253.2 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF... CONNECTION WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational...

  17. 37 CFR 253.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... broadcasting entity. 253.2 Section 253.2 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF... CONNECTION WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational...

  18. 37 CFR 253.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... broadcasting entity. 253.2 Section 253.2 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF... CONNECTION WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational...

  19. 37 CFR 381.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... broadcasting entity. 381.2 Section 381.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY... WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 381.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational broadcast...

  20. 37 CFR 381.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... broadcasting entity. 381.2 Section 381.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY... WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 381.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational broadcast...

  1. 37 CFR 253.2 - Definition of public broadcasting entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... broadcasting entity. 253.2 Section 253.2 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF... CONNECTION WITH NONCOMMERCIAL EDUCATIONAL BROADCASTING § 253.2 Definition of public broadcasting entity. As used in this part, the term public broadcasting entity means a noncommercial educational...

  2. 7 CFR 795.6 - Multiple individuals or other entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Multiple individuals or other entities. 795.6 Section... Multiple individuals or other entities. The rules in §§ 795.5 through 795.16 shall be used to determine whether certain multiple individuals or legal entities are to be treated as one person or as...

  3. 17 CFR Appendix A to Part 420 - Separate Reporting Entity

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... separate reporting entity as described in Appendix A to 17 CFR Part 420. The above named entity also... pursuant to 31 CFR Part 356 is also recognized as a separate reporting entity without the need to request... Appendix A of 31 CFR Part 356....

  4. 17 CFR Appendix A to Part 420 - Separate Reporting Entity

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... separate reporting entity as described in Appendix A to 17 CFR Part 420. The above named entity also... pursuant to 31 CFR Part 356 is also recognized as a separate reporting entity without the need to request... Appendix A of 31 CFR Part 356....

  5. 17 CFR Appendix A to Part 420 - Separate Reporting Entity

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... separate reporting entity as described in Appendix A to 17 CFR Part 420. The above named entity also... pursuant to 31 CFR Part 356 is also recognized as a separate reporting entity without the need to request... Appendix A of 31 CFR Part 356....

  6. 17 CFR Appendix A to Part 420 - Separate Reporting Entity

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... separate reporting entity as described in Appendix A to 17 CFR Part 420. The above named entity also... pursuant to 31 CFR Part 356 is also recognized as a separate reporting entity without the need to request... Appendix A of 31 CFR Part 356....

  7. 17 CFR Appendix A to Part 420 - Separate Reporting Entity

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... separate reporting entity as described in Appendix A to 17 CFR Part 420. The above named entity also... pursuant to 31 CFR Part 356 is also recognized as a separate reporting entity without the need to request... Appendix A of 31 CFR Part 356....

  8. 31 CFR 535.301 - Iran; Iranian Entity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Iran; Iranian Entity. 535.301 Section... § 535.301 Iran; Iranian Entity. (a) The term Iran and Iranian Entity includes: (1) The state and the Government of Iran as well as any political subdivision, agency, or instrumentality thereof or any...

  9. 31 CFR 535.301 - Iran; Iranian Entity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Iran; Iranian Entity. 535.301 Section... § 535.301 Iran; Iranian Entity. (a) The term Iran and Iranian Entity includes: (1) The state and the Government of Iran as well as any political subdivision, agency, or instrumentality thereof or any...

  10. 31 CFR 535.301 - Iran; Iranian Entity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Iran; Iranian Entity. 535.301 Section... § 535.301 Iran; Iranian Entity. (a) The term Iran and Iranian Entity includes: (1) The state and the Government of Iran as well as any political subdivision, agency, or instrumentality thereof or any...

  11. 27 CFR 479.70 - Certain government entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Certain government entities... government entities. A firearm may be made without payment of the making tax by, or on behalf of, any State... organization of such a government entity engaged in criminal investigations. Any person making a firearm...

  12. 27 CFR 479.70 - Certain government entities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Certain government entities... government entities. A firearm may be made without payment of the making tax by, or on behalf of, any State... organization of such a government entity engaged in criminal investigations. Any person making a firearm...

  13. Meta-Analysis of Arabidopsis KANADI1 Direct Target Genes Identifies a Basic Growth-Promoting Module Acting Upstream of Hormonal Signaling Pathways1[OPEN

    PubMed Central

    Xie, Yakun; Straub, Daniel; Eguen, Tenai; Brandt, Ronny; Stahl, Mark; Martínez-García, Jaime F.; Wenkel, Stephan

    2015-01-01

    An intricate network of antagonistically acting transcription factors mediates the formation of a flat leaf lamina of Arabidopsis (Arabidopsis thaliana) plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here, we used a messenger RNA sequencing approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis combining our data sets with published genome-wide data sets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we found three YUCCA genes, YUC2, YUC5, and YUC8, to be transcriptionally up-regulated, which correlates with an increase in the levels of free auxin. When ectopically expressed, KAN1 is able to transcriptionally repress these three YUC genes and thereby block shade-induced auxin biosynthesis. Consequently, KAN1 is able to strongly suppress shade-avoidance responses. Taken together, we hypothesize that HD-ZIPIII/KAN form the basis of a basic growth-promoting module. Hypocotyl extension in the shade and outgrowth of new leaves both involve auxin synthesis and signaling, which are under the direct control of HD-ZIPIII/KAN. PMID:26246448

  14. 76 FR 28503 - Identification of Three Entities as Government of Libya Entities Pursuant to Executive Order 13566

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ... Office of Foreign Assets Control Identification of Three Entities as Government of Libya Entities... Transactions Related to Libya.'' DATES: The identification by the Director of OFAC of the three entities... issued Executive Order 13566, ``Blocking Property and Prohibiting Certain Transactions Related to...

  15. [Cutaneous lymphomas: new entities and rare variants].

    PubMed

    Kempf, W; Mitteldorf, C

    2015-02-01

    Primary cutaneous lymphomas are the second most common group of extranodal non-Hodgkin lymphomas. Recently several new variants and entities have been described but have not yet become part of the World Health Organization (WHO) classification. These forms include the granulomatous form of mycosis fungoides, which is associated with a poorer prognosis, as well as indolent CD8+ lymphoproliferations on the head and at acral localizations. Within the group of cutaneous CD30+ lymphoproliferative disorders, new histological types of lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic) and type E (angioinvasive) which simulate aggressive lymphomas. Cutaneous peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized form represents an indolent lymphoproliferation: the terminology, histogenesis and differentiation from nodular T-cell pseudolymphoma are still a matter of debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus (EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly and EBV-associated mucocutaneous ulcer. This review describes the clinical, histological and immunophenotypic features of new and rare entities and variants of cutaneous lymphomas and highlights the impact of the clinicopathological correlation in the diagnostic process.

  16. Unstable solar lentigo: A defined separate entity.

    PubMed

    Byrom, Lisa; Barksdale, Sarah; Weedon, David; Muir, Jim

    2016-08-01

    An unstable solar lentigo is a solar lentigo with areas of melanocytic hyperplasia not extending past the margin of the lesion. They are discrete, macular, pigmented lesions arising on sun-damaged skin and a subset of typical solar lentigos. Clinically they differ from usual solar lentigines in often being solitary or larger and darker than adjacent solar lentigines. These lesions are of clinical importance as they can arise in close proximity to lentigo maligna and in a single lesion there can be demonstrated changes of solar lentigo, unstable solar lentigo and lentigo maligna. These observations led us to conjecture that unstable solar lentigos could be a precursor lesion to lentigo maligna. In this article we examine the possibility that lentigo maligna can arise within a solar lentigo through an intermediate lesion, the unstable solar lentigo. We propose that the histopathological recognition of this entity will allow for future research into its behaviour and thus management. We review difficulties in the diagnosis of single cell predominant melanocytic proliferations and the concept of unstable lentigo in view of the literature and clinical experience supporting the proposal of its recognition as a separate entity.

  17. EFFECTS OF LASER RADIATION ON MATTER. LASER PLASMA: Emission of charged particles from the surface of a moving target acted on by cw CO2 laser radiation

    NASA Astrophysics Data System (ADS)

    Kuznetsov, S. I.; Petrov, A. L.; Shadrin, A. N.

    1990-06-01

    An experimental investigation was made of the emission of charged particles due to the irradiation of moving steel and graphite targets with cw CO2 laser radiation. The characteristics of the emission current signals were determined for different laser irradiation regimes. The maximum emission current density from the surface of a melt pool ( ~ 1.1 × 10 - 2 A/cm2) and the average temperature of the liquid metal (~ 2040 K) were measured for an incident radiation power density of 550 W and for horizontal and vertical target velocities of respectively ~ 1.5 mm/s and ~ 0.17 mm/s. The authors propose to utilize this phenomenon for monitoring the laser processing of materials.

  18. miR-130a acts as a potential diagnostic biomarker and promotes gastric cancer migration, invasion and proliferation by targeting RUNX3.

    PubMed

    Jiang, Hong; Yu, Wei-Wei; Wang, Lu-Lu; Peng, Yang

    2015-09-01

    MicroRNAs (miRNAs) are abnormally expressed in various types of cancer. miR-130a expression and function in gastric cancer has yet to be elucidated. The aim of the present study was to identify the miR-130a expression and function in gastric cancer. miR-130a expression was examined in gastric cancer cell lines and tissues by RT-qPCR. The diagnostic and prognostic significance of miR-130a in gastric cancer was analyzed by receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis. miR130a expression was identified and the diagnostic significance in the serum of gastric cancer patients and healthy controls was analyzed using RT-qPCR and ROC curves, respectively. A target gene for miR-130a was identified using luciferase reporter assays, and gastric cancer tumorigenesis ability was examined by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays. The results showed that miR‑130a was upregulated in gastric cancer. The low-miR-130a group had significantly improved overall survival compared to the high-miR-130a group. Furthermore, the expression of miR‑130a in plasma in gastric cancer patients was upregulated and diagnostic value for gastric cancer of miR-130a is more effective than the tumor markers carcinoembryonic antigen (CEA) and CA-199. miR-130a directly targeted runt‑related transcription factor 3 (RUNX3) and promoted gastric cancer tumorigenesis by targeting RUNX3. miR-130a may therefore be a useful marker for the diagnosis and prognosis of gastric cancer. Additionally, miR-130a was identified as an oncogene that promotes gastric cancer tumorigenesis by targeting RUNX3. PMID:26134263

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

    PubMed

    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. PMID:25231743

  20. 75 FR 53972 - Guidance for Industry; Small Entities Compliance Guide-The Index of Legally Marketed Unapproved...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Guidance for Industry; Small Entities Compliance Guide--The... Species Animal Health Act of 2004 (MUMS). DATES: Submit either electronic or written comments on...

  1. 45 CFR 1182.5 - Procedures for notifying government entities of the Institute's proposed changes to its systems...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the Institute's proposed changes to its systems of records. 1182.5 Section 1182.5 Public Welfare... INSTITUTE OF MUSEUM AND LIBRARY SERVICES IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1182.5 Procedures for notifying government entities of the Institute's proposed changes to its systems of records. When...

  2. 45 CFR 1182.5 - Procedures for notifying government entities of the Institute's proposed changes to its systems...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the Institute's proposed changes to its systems of records. 1182.5 Section 1182.5 Public Welfare... INSTITUTE OF MUSEUM AND LIBRARY SERVICES IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1182.5 Procedures for notifying government entities of the Institute's proposed changes to its systems of records. When...

  3. 45 CFR 1182.5 - Procedures for notifying government entities of the Institute's proposed changes to its systems...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the Institute's proposed changes to its systems of records. 1182.5 Section 1182.5 Public Welfare... INSTITUTE OF MUSEUM AND LIBRARY SERVICES IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1182.5 Procedures for notifying government entities of the Institute's proposed changes to its systems of records. When...

  4. 45 CFR 1182.5 - Procedures for notifying government entities of the Institute's proposed changes to its systems...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the Institute's proposed changes to its systems of records. 1182.5 Section 1182.5 Public Welfare... INSTITUTE OF MUSEUM AND LIBRARY SERVICES IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1182.5 Procedures for notifying government entities of the Institute's proposed changes to its systems of records. When...

  5. 77 FR 10806 - Designation of One Entity Pursuant to Executive Order 13224 of September 23, 2001, “Blocking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... Commit, or Support Terrorism'' AGENCY: Office of Foreign Assets Control, Treasury. ACTION: Notice... Commit, or Support Terrorism.'' DATES: The designation by the Director of OFAC of the entity in this... emergency to address grave acts of terrorism and threats of terrorism committed by foreign...

  6. 76 FR 64427 - Designation of One Entity Pursuant to Executive Order 13224 of September 23, 2001, “Blocking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... Commit, or Support Terrorism'' AGENCY: Office of Foreign Assets Control, Treasury. ACTION: Notice... Commit, or Support Terrorism.'' DATES: The designation by the Director of OFAC of the entity in this... emergency to address grave acts of terrorism and threats of terrorism committed by foreign...

  7. Encoding of Fundamental Chemical Entities of Organic Reactivity Interest using chemical ontology and XML.

    PubMed

    Durairaj, Vijayasarathi; Punnaivanam, Sankar

    2015-09-01

    Fundamental chemical entities are identified in the context of organic reactivity and classified as appropriate concept classes namely ElectronEntity, AtomEntity, AtomGroupEntity, FunctionalGroupEntity and MolecularEntity. The entity classes and their subclasses are organized into a chemical ontology named "ChemEnt" for the purpose of assertion, restriction and modification of properties through entity relations. Individual instances of entity classes are defined and encoded as a library of chemical entities in XML. The instances of entity classes are distinguished with a unique notation and identification values in order to map them with the ontology definitions. A model GUI named Entity Table is created to view graphical representations of all the entity instances. The detection of chemical entities in chemical structures is achieved through suitable algorithms. The possibility of asserting properties to the entities at different levels and the mechanism of property flow within the hierarchical entity levels is outlined. PMID:26188793

  8. Encoding of Fundamental Chemical Entities of Organic Reactivity Interest using chemical ontology and XML.

    PubMed

    Durairaj, Vijayasarathi; Punnaivanam, Sankar

    2015-09-01

    Fundamental chemical entities are identified in the context of organic reactivity and classified as appropriate concept classes namely ElectronEntity, AtomEntity, AtomGroupEntity, FunctionalGroupEntity and MolecularEntity. The entity classes and their subclasses are organized into a chemical ontology named "ChemEnt" for the purpose of assertion, restriction and modification of properties through entity relations. Individual instances of entity classes are defined and encoded as a library of chemical entities in XML. The instances of entity classes are distinguished with a unique notation and identification values in order to map them with the ontology definitions. A model GUI named Entity Table is created to view graphical representations of all the entity instances. The detection of chemical entities in chemical structures is achieved through suitable algorithms. The possibility of asserting properties to the entities at different levels and the mechanism of property flow within the hierarchical entity levels is outlined.

  9. Cardiac Pseudoaneurysm- A Death Defying Entity

    PubMed Central

    Gupta, Saryu

    2016-01-01

    A pseudoaneurysm refers to a contained rupture of the myocardium with a tenuous pericardium walling off the leak. It needs to be differentiated from a true aneurysm by the fact that there is lack of myocardial tissue in the wall of a pseudoaneurysm. The differentiation between the two is pertinent as true aneurysms can be treated medically while pseudoaneurysms require urgent surgical treatment. Untreated pseudoaneurysms carry a high risk of rupture and mortality. We report a case of cardiac pseudoaneurysm developing in a 46-year-old male who had suffered myocardial infarction four months back. The patient now presented with chest pain and dyspnoea. CECT chest revealed a partially thrombosed large pseudoaneurysm arising from the posterior wall of left ventricle. While the clinical diagnosis of this entity is difficult, CECT plays a pivotal role in the non-invasive detection of pseudoaneurysms. PMID:27504379

  10. Genome-Wide Characterization of cis-Acting DNA Targets Reveals the Transcriptional Regulatory Framework of Opaque2 in Maize[OPEN

    PubMed Central

    Li, Chaobin; Qiao, Zhenyi; Qi, Weiwei; Wang, Qian; Yuan, Yue; Yang, Xi; Tang, Yuanping; Mei, Bing; Lv, Yuanda; Zhao, Han; Xiao, Han; Song, Rentao

    2015-01-01

    Opaque2 (O2) is a transcription factor that plays important roles during maize endosperm development. Mutation of the O2 gene improves the nutritional value of maize seeds but also confers pleiotropic effects that result in reduced agronomic quality. To reveal the transcriptional regulatory framework of O2, we studied the transcriptome of o2 mutants using RNA sequencing (RNA-Seq) and determined O2 DNA binding targets using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq). The RNA-Seq analysis revealed 1605 differentially expressed genes (DEGs) and 383 differentially expressed long, noncoding RNAs. The DEGs cover a wide range of functions related to nutrient reservoir activity, nitrogen metabolism, stress resistance, etc. ChIP-Seq analysis detected 1686 O2 DNA binding sites distributed over 1143 genes. Overlay of the RNA-Seq and ChIP-Seq results revealed 35 O2-modulated target genes. We identified four O2 binding motifs; among them, TGACGTGG appears to be the most conserved and strongest. We confirmed that, except for the 16- and 18-kD zeins, O2 directly regulates expression of all other zeins. O2 directly regulates two transcription factors, genes linked to carbon and amino acid metabolism and abiotic stress resistance. We built a hierarchical regulatory model for O2 that provides an understanding of its pleiotropic biological effects. PMID:25691733

  11. MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme.

    PubMed

    Dai, Shouping; Wang, Xianjun; Li, Xiao; Cao, Yuandong

    2015-11-13

    MicroRNA-139-5p was identified to be significantly down-regulated in glioblastoma multiform (GBM) by miRNA array. In this report we aimed to clarify its biological function, molecular mechanisms and direct target gene in GBM. Twelve patients with GBM were analyzed for the expression of miR-139-5p by quantitative RT-PCR. miR-139-5p overexpression was established by transfecting miR-139-5p-mimic into U87MG and T98G cells, and its effects on cell proliferation were studied using MTT assay and colony formation assays. We concluded that ectopic expression of miR-139-5p in GBM cell lines significantly suppressed cell proliferation and inducing apoptosis. Bioinformatics coupled with luciferase and western blot assays also revealed that miR-139-5p suppresses glioma cell proliferation by targeting ELTD1 and regulating cell cycle. PMID:26449464

  12. MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway.

    PubMed

    Wang, Fang; Li, Lin; Chen, Zhuo; Zhu, Mingzhi; Gu, Yuanting

    2016-05-01

    Breast cancer ranks as the leading cause of cancer-related mortality in females worldwide. It has been proven that microRNAs (miRNAs or miRs), a type of non‑coding RNA, are involved in tumorigenesis. An increasing number of studies has confirmed the critical role of miR‑214 in certain types of cancer. Nevertheless, the biological function of miR‑214, as well as its underlying mechanisms of action in breast cancer remain largely unknown. In the present study, the expression of miR‑214 was found to be upregulated in four human breast cancer cell lines in contrast to its expression level in the non‑malignant breast epithelial cell line, MCF‑10A. Moreover, the overexpression of miR‑214 markedly increased cell viability and abrogated the apoptosis triggered by serum starvation, indicating that miR‑214 plays a pivotal role in breast cancer cell growth. Further analysis suggested that the upregulation of miR‑214 markedly induced the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, which largely accounted for the protective effects of miR‑124 on cancer cell growth. This was further confimed by pre‑treatment with the PI3K/Akt inhibitor, LY294002, which markedly attenuated the miR‑214‑induced increase in cell viability and resistance to apoptosis. Furthermore, the expression of phosphatase and tensin homolog (PTEN) was decreased following transfection wtih miR‑214 mimics and PTEN was confirmed as the direct target of miR‑214 by bioinformatics analysis and a dual‑firefly luciferase reporter assay. Importantly, the introduction of PTEN cDNA lacking the 3' untranslated region (3'UTR) significantly inhibited the miR‑214‑induced activation of the PI3K/Akt signaling pathway, and abrogated the protetive effects of miR‑214 on cell survival and resistance to apoptosis. Taken together, these findings suggest that miR‑214 possesses oncogenic activity and that its effects are mediated through the promotion of cell growth

  13. Context and Domain Knowledge Enhanced Entity Spotting in Informal Text

    NASA Astrophysics Data System (ADS)

    Gruhl, Daniel; Nagarajan, Meena; Pieper, Jan; Robson, Christine; Sheth, Amit

    This paper explores the application of restricted relationship graphs (RDF) and statistical NLP techniques to improve named entity annotation in challenging Informal English domains. We validate our approach using on-line forums discussing popular music. Named entity annotation is particularly difficult in this domain because it is characterized by a large number of ambiguous entities, such as the Madonna album "Music" or Lilly Allen's pop hit "Smile".

  14. MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6(STAT6)

    SciTech Connect

    Liu, Dachuang; Tao, Tao; Xu, Bin; Chen, Shuqiu; Liu, Chunhui; Zhang, Lei; Lu, Kai; Huang, Yeqing; Jiang, Liang; Zhang, Xiaowen; Huang, Xiaoming; Zhang, Lihua; Han, Conghui; Chen, Ming

    2014-02-28

    Highlights: • The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. • We found that the expression of miR-361-5p in CRPC was lower than in ADPC. • MiR-361-5p suppressed DU145 cell proliferation and triggered apoptosis. • STAT6 is a direct target of miR-361-5p. • STAT6 enhances the expression of Bcl-xL at the transcriptional level. - Abstract: Castration-resistant prostate cancer (CRPC), whose pathogenesis is known to be regulated by microRNAs (miRNAs), has a poor prognosis. In our present study, we found that the expression of miR-361-5p in CRPC was lower than in androgen-dependent prostate cancer (ADPC), indicating that miR-361-5p may play an important role in the progression of ADPC to CRPC. The role of miR-361-5p in prostate cancer (PCa) has not been evaluated until date. Our findings suggest that miR-361-5p is a suppressor in CRPC. Signal transducer and activator of transcription-6 (STAT6), a direct target of miR-361-5p, enhances the expression of B-cell lymphoma-extra large (Bcl-xL), while miR-361-5p inhibits its expression through STAT6. Therefore, miR-361-5p has great clinical significance in preventing the malignant progression of PCa.

  15. miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

    PubMed Central

    Feliciano, Andrea; Castellvi, Josep; Artero-Castro, Ana; Leal, Jose A.; Romagosa, Cleofé; Hernández-Losa, Javier; Peg, Vicente; Fabra, Angels; Vidal, Francisco; Kondoh, Hiroshi; Ramón y Cajal, Santiago; LLeonart, Matilde E.

    2013-01-01

    MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3’-UTRs of ENPEP, CK2-α, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-α, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40–56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-α was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-α, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-α, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer. PMID:24098452

  16. Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long-acting antipsychotics

    PubMed Central

    de Bartolomeis, Andrea; Fagiolini, Andrea; Vaggi, Marco; Vampini, Claudio

    2016-01-01

    Purpose This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI) antipsychotics. Methods Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate). Results The two most important factors determining therapy success were efficacy (75% of responses) and tolerability (45%) followed by global functioning (24%) and quality of life (17%). LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%), and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options. Conclusion Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important. PMID:26811682

  17. Central nervous system injury in utero: selected entities.

    PubMed

    Naidich, Thomas P; Griffiths, Paul D; Rosenbloom, Lorne

    2015-09-01

    This report discusses the syndrome of amnionic bands, anencephaly, schizencephaly and hydranencephaly, four entities whose pathogenesis includes significant injury to the fetus in utero. PMID:26346151

  18. ACT: Acting Out Central Theme.

    ERIC Educational Resources Information Center

    Kise, Joan Duff

    1982-01-01

    The author describes ACT (Acting Out Central Theme), a method for dealing with psychomotor, cognitive, and affective domains in slow readers. The ACT approach involves three sessions which focus on discussion of a theme such as friendship, presentaton of the theme as a skit, and assignment of topics to individual students. (SW)

  19. MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.

    PubMed

    Wang, Lin; Shi, Zhu-Mei; Jiang, Cheng-Fei; Liu, Xue; Chen, Qiu-Dan; Qian, Xu; Li, Dong-Mei; Ge, Xin; Wang, Xie-Feng; Liu, Ling-Zhi; You, Yong-Ping; Liu, Ning; Jiang, Bing-Hua

    2014-07-30

    Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in a manner associated with N-RAS downregulation in vitro and in vivo. Finally, miR-143 also sensitizes glioma cells to temozolomide (TMZ),the first-line drug for glioma treatment. Taken together, for the first time, our results demonstrate that miR-143 plays a significant role in inactivating the RAS signaling pathway through the inhibition of N-RAS, which may provide a novel therapeutic strategy for treatment of glioma and other RAS-driven cancers.

  20. Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

    PubMed

    Liang, Xiao-Huan; Deng, Wen-Bo; Li, Ming; Zhao, Zhen-Ao; Wang, Tong-Song; Feng, Xu-Hui; Cao, Yu-Jing; Duan, En-Kui; Yang, Zeng-Ming

    2014-08-22

    Embryo implantation is a highly synchronized process between an activated blastocyst and a receptive uterus. Successful implantation relies on the dynamic interplay of estrogen and progesterone, but the key mediators underlying embryo implantation are not fully understood. Here we show that transcription factor early growth response 1 (Egr1) is regulated by estrogen as a downstream target through leukemia inhibitory factor (LIF) signal transducer and activator of transcription 3 (STAT3) pathway in mouse uterus. Egr1 is localized in the subluminal stromal cells surrounding the implanting embryo on day 5 of pregnancy. Estrogen rapidly, markedly, and transiently enhances Egr1 expression in uterine stromal cells, which fails in estrogen receptor α knock-out mouse uteri. STAT3 is phosphorylated by LIF and subsequently recruited on Egr1 promoter to induce its expression. Our results of Egr1 expression under induced decidualization in vivo and in vitro show that Egr1 is rapidly induced after deciduogenic stimulus. Egr1 knockdown can inhibit in vitro decidualization of cultured uterine stromal cells. Chromatin immunoprecipitation data show that Egr1 is recruited to the promoter of wingless-related murine mammary tumor virus integration site 4 (Wnt4). Collectively, our study presents for the first time that estrogen regulates Egr1 expression through LIF-STAT3 signaling pathway in mouse uterus, and Egr1 functions as a critical mediator of stromal cell decidualization by regulating Wnt4. PMID:25012664

  1. Lipid rafts and raft-mediated supramolecular entities in the regulation of CD95 death receptor apoptotic signaling.

    PubMed

    Gajate, Consuelo; Mollinedo, Faustino

    2015-05-01

    Membrane lipid rafts are highly ordered membrane domains enriched in cholesterol, sphingolipids and gangliosides that have the property to segregate and concentrate proteins. Lipid and protein composition of lipid rafts differs from that of the surrounding membrane, thus providing sorting platforms and hubs for signal transduction molecules, including CD95 death receptor-mediated signaling. CD95 can be recruited to rafts in a reversible way through S-palmitoylation following activation of cells with its physiological cognate ligand as well as with a wide variety of inducers, including several antitumor drugs through ligand-independent intracellular mechanisms. CD95 translocation to rafts can be modulated pharmacologically, thus becoming a target for the treatment of apoptosis-defective diseases, such as cancer. CD95-mediated signaling largely depends on protein-protein interactions, and the recruitment and concentration of CD95 and distinct downstream apoptotic molecules in membrane raft domains, forming raft-based supramolecular entities that act as hubs for apoptotic signaling molecules, favors the generation and amplification of apoptotic signals. Efficient CD95-mediated apoptosis involves CD95 and raft internalization, as well as the involvement of different subcellular organelles. In this review, we briefly summarize and discuss the involvement of lipid rafts in the regulation of CD95-mediated apoptosis that may provide a new avenue for cancer therapy.

  2. Monitoring named entity recognition: the League Table

    PubMed Central

    2013-01-01

    Background Named entity recognition (NER) is an essential step in automatic text processing pipelines. A number of solutions have been presented and evaluated against gold standard corpora (GSC). The benchmarking against GSCs is crucial, but left to the individual researcher. Herewith we present a League Table web site, which benchmarks NER solutions against selected public GSCs, maintains a ranked list and archives the annotated corpus for future comparisons. Results The web site enables access to the different GSCs in a standardized format (IeXML). Upon submission of the annotated corpus the user has to describe the specification of the used solution and then uploads the annotated corpus for evaluation. The performance of the system is measured against one or more GSCs and the results are then added to the web site (“League Table”). It displays currently the results from publicly available NER solutions from the Whatizit infrastructure for future comparisons. Conclusion The League Table enables the evaluation of NER solutions in a standardized infrastructure and monitors the results long-term. For access please go to http://wwwdev.ebi.ac.uk/Rebholz-srv/calbc/assessmentGSC/. Contact: rebholz@ifi.uzh.ch. PMID:24034148

  3. Prolonged ulcerative laryngitis: a new disease entity.

    PubMed

    Hsiao, Tzu-Yu

    2011-03-01

    Over the last decade, a new disease entity, prolonged ulcerative laryngitis (PUL), with unique clinical presentation and prolonged disease course, has been recognized. Until now, very few studies dealing with this disease have been reported in the literature. From 1999 to 2008, we analyzed clinical data from a series of 39 PUL patients who were treated with an observational approach without implementing specific treatments. This disease affects adults, predominantly females. The age of patients in our series ranged from 26 to 76 years with a median of 49.5 years. This disease is characterized by ulcers and signs of acute inflammation on the membranous portion of the vocal folds with a prolonged clinical course. The recovery times of patients ranged from 4 to 20 weeks with an average of 9.4 weeks. The data in this study may reflect a natural history of this disease. PUL seems to be a self-limited disease, but the etiology of this disease is unknown. Specific infections or systemic inflammatory processes involving the larynx must be ruled out before diagnosis, and conservative treatments are suggested.

  4. Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy.

    PubMed

    Wang, Xiao-Bing; Jiang, Xing-Ran; Yu, Xi-Ying; Wang, Lin; He, Shun; Feng, Fei-Yue; Guo, Li-Ping; Jiang, Wei; Lu, Shih-Hsin

    2014-02-01

    Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.

  5. 78 FR 45051 - Unincorporated Business Entities; Effective Date

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-26

    ..., 622, 623, and 630 published on May 28, 2013 (78 FR 31822) is effective July 22, 2013. FOR FURTHER..., 612, 619, 620, 621, 622, 623, and 630 RIN 3052-AC65 Unincorporated Business Entities; Effective Date... institutions' use of unincorporated business entities organized under State law for certain business...

  6. 42 CFR 401.705 - Eligibility criteria for qualified entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... efficiency, effectiveness, or resource use measures from claims data, including the following: (A... that is projected to cover the costs of performing the required functions, including the fee for the... other entities if the applicant is the lead entity and includes documentation in its application of...

  7. 78 FR 22270 - Special Fraud Alert: Physician-Owned Entities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... correction to the OIG Federal Register ] notice published on March 29, 2012 (78 FR 19271), on our recently issued Special Fraud Alert on Physician-Owned Entities. Specifically, the Special Fraud Alert addressed... HUMAN SERVICES Office of Inspector General Special Fraud Alert: Physician-Owned Entities AGENCY:...

  8. 49 CFR 37.29 - Private entities providing taxi service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Private entities providing taxi service. 37.29 Section 37.29 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Applicability § 37.29 Private entities providing taxi service....

  9. When Depression Mediates the Relationship between Entity Beliefs and Performance

    ERIC Educational Resources Information Center

    Da Fonseca, David; Cury, Francois; Santos, Andreia; Payen, Vincent; Bounoua, Lenda; Brisswalter, Jeannick; Rufo, Marcel; Poinso, Francois; Deruelle, Christine

    2009-01-01

    The aim of this study was to determine whether depression can explain the negative relationship between academic performance and the belief that intelligence is a fixed trait, i.e., entity belief. A sample of 353 French volunteer adolescents (age 11-16) completed questionnaires assessing entity theory and depressive symptoms (Children Depression…

  10. 14 CFR Sec. 1-6 - Accounting entities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Accounting entities. Sec. 1-6 Section 1-6... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be maintained for each...

  11. 14 CFR Sec. 1-6 - Accounting entities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Accounting entities. Sec. 1-6 Section 1-6... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be maintained for each...

  12. 31 CFR 306.88 - Political entities and public corporations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Political entities and public... GOVERNING U.S. SECURITIES Assignments in Behalf of Private or Public Organizations § 306.88 Political..., city, town, village, school district or other political entity, public body or corporation, may...

  13. 31 CFR 306.88 - Political entities and public corporations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Political entities and public... GOVERNING U.S. SECURITIES Assignments in Behalf of Private or Public Organizations § 306.88 Political..., city, town, village, school district or other political entity, public body or corporation, may...

  14. 31 CFR 306.88 - Political entities and public corporations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Political entities and public... GOVERNING U.S. SECURITIES Assignments in Behalf of Private or Public Organizations § 306.88 Political..., city, town, village, school district or other political entity, public body or corporation, may...

  15. 31 CFR 306.88 - Political entities and public corporations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Political entities and public... GOVERNING U.S. SECURITIES Assignments in Behalf of Private or Public Organizations § 306.88 Political..., city, town, village, school district or other political entity, public body or corporation, may...

  16. 31 CFR 306.88 - Political entities and public corporations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Political entities and public... GOVERNING U.S. SECURITIES Assignments in Behalf of Private or Public Organizations § 306.88 Political..., city, town, village, school district or other political entity, public body or corporation, may...

  17. 43 CFR 426.8 - Nonresident aliens and foreign entities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in...

  18. 43 CFR 426.8 - Nonresident aliens and foreign entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in...

  19. 43 CFR 426.8 - Nonresident aliens and foreign entities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in...

  20. 43 CFR 426.8 - Nonresident aliens and foreign entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in...

  1. 43 CFR 426.8 - Nonresident aliens and foreign entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in...

  2. 27 CFR 479.90 - Certain government entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Certain government entities. 479.90 Section 479.90 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO... government entities. (a) A firearm may be transferred without payment of the transfer tax to or from...

  3. 22 CFR 140.6 - Foreign government entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Foreign government entities. 140.6 Section 140... Enforcement § 140.6 Foreign government entities. (a) Determination Procedures. (1) The Country Narcotics... allegations that a key individual who is a senior government official of the host nation has been convicted...

  4. 27 CFR 479.90 - Certain government entities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Certain government entities. 479.90 Section 479.90 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS... government entities. (a) A firearm may be transferred without payment of the transfer tax to or from...

  5. 22 CFR 140.6 - Foreign government entities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Foreign government entities. 140.6 Section 140... Enforcement § 140.6 Foreign government entities. (a) Determination Procedures. (1) The Country Narcotics... allegations that a key individual who is a senior government official of the host nation has been convicted...

  6. 22 CFR 140.6 - Foreign government entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Foreign government entities. 140.6 Section 140... Enforcement § 140.6 Foreign government entities. (a) Determination Procedures. (1) The Country Narcotics... allegations that a key individual who is a senior government official of the host nation has been convicted...

  7. 27 CFR 479.70 - Certain government entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Certain government... Certain government entities. A firearm may be made without payment of the making tax by, or on behalf of... police organization of such a government entity engaged in criminal investigations. Any person making...

  8. 27 CFR 479.90 - Certain government entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Certain government entities. 479.90 Section 479.90 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS... government entities. (a) A firearm may be transferred without payment of the transfer tax to or from...

  9. 14 CFR Sec. 1-6 - Accounting entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Accounting entities. Sec. 1-6 Section 1-6... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be maintained for each...

  10. 14 CFR Sec. 1-6 - Accounting entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Accounting entities. Sec. 1-6 Section 1-6 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC... Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be maintained for each...

  11. 76 FR 44776 - Provisions Common to Registered Entities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ... part 40 Provisions Common to Registered Entities, 75 FR 67282 (Nov. 2, 2010). The Commission's final... mandatory clearing; 75 FR 67277 (Nov. 2, 2010)). Paragraph (j)(2)(ii) refers to `` otional amounts, quantity... Registered Entities, 75 FR 57282 (Nov. 2, 2010). In this regard, the Commission continues to view its...

  12. 18 CFR 39.8 - Delegation to a Regional Entity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... THE ELECTRIC RELIABILITY ORGANIZATION; AND PROCEDURES FOR THE ESTABLISHMENT, APPROVAL, AND ENFORCEMENT OF ELECTRIC RELIABILITY STANDARDS § 39.8 Delegation to a Regional Entity. (a) The Electric Reliability Organization may enter into an agreement to delegate authority to a Regional Entity for...

  13. A Closer Look: The American Taxpayer Relief Act of 2012

    ERIC Educational Resources Information Center

    Balmer, Mary

    2013-01-01

    School districts may be affected by the American Taxpayer Relief Act of 2012 with regard to fixed assets management and education entities. The act avoids the scheduled increases to individual income tax rates for most Americans and extends a host of expired and expiring tax provisions for both individuals and businesses. The provisions described…

  14. Juggling Act

    ERIC Educational Resources Information Center

    Rudalevige, Andrew

    2009-01-01

    Two education bills from George W. Bush's first term are long overdue for reauthorization. One, of course, is the No Child Left Behind Act (NCLB), passed in late 2001. The other is the Education Sciences Reform Act (ESRA), which in November 2002 replaced the Office of Educational Research and Improvement (OERI) with a new Institute of Education…

  15. [A little known entity: aggressive fibromatosis].

    PubMed

    Marqúes Gubern, A; Pérez Payarols, J; Sánchez de Toledo, J; Martínez Ibáñez, V; Moraga, F; de Torres Ramírez, I M

    1991-01-01

    Aggressive fibromatosis is an unfrequent and little known entity, which in spite of being a histologically benign tumoration with scarce mitosis and without metastasis at distance, frequently presents with a high degree of local malignancy that can cause serious functional and aesthetical disturbance for the patient and even lead to death if infiltration of vital organs is presented, above all in cases of abdominal or maxillo-facial mass localization. The authors present their experience with 17 cases of aggressive fibromatosis observed in our centre: four of abdominal localization, six in extremities, five in the maxillo-facial mass, one in the torax and one in the lumbo-sacral region. Histological diagnosis, either by puncture or biopsy, is complemented by studies of extension of the tumour based on ecography and TAC. All cases were treated according to the classical criteria of ample resection of the lesion, always when practicable, except in one infant case and in the torax, in which only a biopsy was effected. Of the 15 cases resected, nine cases had local relapses, six of which remained free of disease with a second operation, another two required a third operation and the remaining case needed five interventions. In six children chemotherapy was applied with vincristina, cyclophosphamide and adriamicina. A follow up was carried out in 14 patients, one of which died and the remaining 13 are free of disease. In spite of the fact that progestagene receptors were not evidenced in two of our cases, one presented complete remission of the tumor after treatment with medroxyprogesterone. In this case the coincidence of Gardner's syndrome arises in the family history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043434

  16. BEST: Next-Generation Biomedical Entity Search Tool for Knowledge Discovery from Biomedical Literature

    PubMed Central

    Lee, Kyubum; Choi, Jaehoon; Kim, Seongsoon; Jeon, Minji; Lim, Sangrak; Choi, Donghee; Kim, Sunkyu; Tan, Aik-Choon

    2016-01-01

    As the volume of publications rapidly increases, searching for relevant information from the literature becomes more challenging. To complement standard search engines such as PubMed, it is desirable to have an advanced search tool that directly returns relevant biomedical entities such as targets, drugs, and mutations rather than a long list of articles. Some existing tools submit a query to PubMed and process retrieved abstracts to extract information at query time, resulting in a slow response time and limited coverage of only a fraction of the PubMed corpus. Other tools preprocess the PubMed corpus to speed up the response time; however, they are not constantly updated, and thus produce outdated results. Further, most existing tools cannot process sophisticated queries such as searches for mutations that co-occur with query terms in the literature. To address these problems, we introduce BEST, a biomedical entity search tool. BEST returns, as a result, a list of 10 different types of biomedical entities including genes, diseases, drugs, targets, transcription factors, miRNAs, and mutations that are relevant to a user’s query. To the best of our knowledge, BEST is the only system that processes free text queries and returns up-to-date results in real time including mutation information in the results. BEST is freely accessible at http://best.korea.ac.kr. PMID:27760149

  17. 78 FR 75458 - Addition of Certain Persons to the Entity List; Amendment of Entity List Entries; and Removal of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... on the Entity List since May 2001 (see 66 FR 24266). As a result of its inclusion on the Entity List... BIS's Denied Persons List since 2008. See 78 FR 48138 (August 7, 2008). Pursuant to Sec. 744.11(b)(4... CFR, 2001 Comp., p. 783 (2002), as amended by Executive Order 13637 of March 8, 2013, 78 FR...

  18. 77 FR 24587 - Addition of Certain Persons to the Entity List; and Implementation of Entity List Annual Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ..., Egypt, Germany, Iran, Ireland, Israel, Kuwait, Lebanon, Norway, Russia, South Korea, Syria, the United... amendments to the Entity List including: The removal of three entries (one each in Germany, South Korea, and... review for entities listed under Armenia, Germany, Iran, Lebanon, South Korea, Syria, and the U.A.E....

  19. The Arabidopsis bHLH Transcription Factors MYC3 and MYC4 Are Targets of JAZ Repressors and Act Additively with MYC2 in the Activation of Jasmonate Responses[C][W

    PubMed Central

    Fernández-Calvo, Patricia; Chini, Andrea; Fernández-Barbero, Gemma; Chico, José-Manuel; Gimenez-Ibanez, Selena; Geerinck, Jan; Eeckhout, Dominique; Schweizer, Fabian; Godoy, Marta; Franco-Zorrilla, José Manuel; Pauwels, Laurens; Witters, Erwin; Puga, María Isabel; Paz-Ares, Javier; Goossens, Alain; Reymond, Philippe; De Jaeger, Geert; Solano, Roberto

    2011-01-01

    Jasmonates (JAs) trigger an important transcriptional reprogramming of plant cells to modulate both basal development and stress responses. In spite of the importance of transcriptional regulation, only one transcription factor (TF), the Arabidopsis thaliana basic helix-loop-helix MYC2, has been described so far as a direct target of JAZ repressors. By means of yeast two-hybrid screening and tandem affinity purification strategies, we identified two previously unknown targets of JAZ repressors, the TFs MYC3 and MYC4, phylogenetically closely related to MYC2. We show that MYC3 and MYC4 interact in vitro and in vivo with JAZ repressors and also form homo- and heterodimers with MYC2 and among themselves. They both are nuclear proteins that bind DNA with sequence specificity similar to that of MYC2. Loss-of-function mutations in any of these two TFs impair full responsiveness to JA and enhance the JA insensitivity of myc2 mutants. Moreover, the triple mutant myc2 myc3 myc4 is as impaired as coi1-1 in the activation of several, but not all, JA-mediated responses such as the defense against bacterial pathogens and insect herbivory. Our results show that MYC3 and MYC4 are activators of JA-regulated programs that act additively with MYC2 to regulate specifically different subsets of the JA-dependent transcriptional response. PMID:21335373

  20. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  1. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  2. BDDCS class prediction for new molecular entities.

    PubMed

    Broccatelli, Fabio; Cruciani, Gabriele; Benet, Leslie Z; Oprea, Tudor I

    2012-03-01

    The Biopharmaceutics Drug Disposition Classification System (BDDCS) was successfully employed for predicting drug-drug interactions (DDIs) with respect to drug metabolizing enzymes (DMEs), drug transporters and their interplay. The major assumption of BDDCS is that the extent of metabolism (EoM) predicts high versus low intestinal permeability rate, and vice versa, at least when uptake transporters or paracellular transport is not involved. We recently published a collection of over 900 marketed drugs classified for BDDCS. We suggest that a reliable model for predicting BDDCS class, integrated with in vitro assays, could anticipate disposition and potential DDIs of new molecular entities (NMEs). Here we describe a computational procedure for predicting BDDCS class from molecular structures. The model was trained on a set of 300 oral drugs, and validated on an external set of 379 oral drugs, using 17 descriptors calculated or derived from the VolSurf+ software. For each molecule, a probability of BDDCS class membership was given, based on predicted EoM, FDA solubility (FDAS) and their confidence scores. The accuracy in predicting FDAS was 78% in training and 77% in validation, while for EoM prediction the accuracy was 82% in training and 79% in external validation. The actual BDDCS class corresponded to the highest ranked calculated class for 55% of the validation molecules, and it was within the top two ranked more than 92% of the time. The unbalanced stratification of the data set did not affect the prediction, which showed highest accuracy in predicting classes 2 and 3 with respect to the most populated class 1. For class 4 drugs a general lack of predictability was observed. A linear discriminant analysis (LDA) confirming the degree of accuracy for the prediction of the different BDDCS classes is tied to the structure of the data set. This model could routinely be used in early drug discovery to prioritize in vitro tests for NMEs (e.g., affinity to transporters

  3. 26 CFR 301.7701-3 - Classification of certain business entities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... January 1, 1997. (2) Prior treatment of existing entities. In the case of a business entity that is not... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Classification of certain business entities... of certain business entities. (a) In general. A business entity that is not classified as...

  4. Controlled mutual quantum entity authentication using entanglement swapping

    NASA Astrophysics Data System (ADS)

    Min-Sung, Kang; Chang-Ho, Hong; Jino, Heo; Jong-In, Lim; Hyung-Jin, Yang

    2015-09-01

    In this paper, we suggest a controlled mutual quantum entity authentication protocol by which two users mutually certify each other on a quantum network using a sequence of Greenberger-Horne-Zeilinger (GHZ)-like states. Unlike existing unidirectional quantum entity authentication, our protocol enables mutual quantum entity authentication utilizing entanglement swapping; moreover, it allows the managing trusted center (TC) or trusted third party (TTP) to effectively control the certification of two users using the nature of the GHZ-like state. We will also analyze the security of the protocol and quantum channel. Project supported by the Research Foundation of Korea University.

  5. Overview of the INEX 2008 Entity Ranking Track

    NASA Astrophysics Data System (ADS)

    Demartini, Gianluca; de Vries, Arjen P.; Iofciu, Tereza; Zhu, Jianhan

    In many contexts a search engine user would prefer to retrieve entities instead of just documents. Example queries include “Italian nobel prize winners”, “Formula 1 drivers that won the Monaco Grand Prix”, or “German spoken Swiss cantons”. The XML Entity Ranking (XER) track at INEX creates a discussion forum aimed at standardizing evaluation procedures for entity retrieval. This paper describes the XER tasks and the evaluation procedure used at the XER track in 2008, focusing specifically on the sampled pooling strategy applied first this year. We conclude with a brief discussion of the predominant participant approaches and their effectiveness.

  6. Target Practice and Marksmanship Training Support Act

    THOMAS, 112th Congress

    Sen. Udall, Mark [D-CO

    2011-06-22

    04/24/2012 Committee on Environment and Public Works Subcommittee on Water and Wildlife. Hearings held. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  7. 17 CFR 240.0-10 - Small entities under the Securities Exchange Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... interrogation devices or moving tickers at all times during the preceding fiscal year (or in the time that it... purposes of paragraph (g) of this section, “interrogation device” shall refer to any device that may...

  8. 17 CFR 240.0-10 - Small entities under the Securities Exchange Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... interrogation devices or moving tickers at all times during the preceding fiscal year (or in the time that it... purposes of paragraph (g) of this section, “interrogation device” shall refer to any device that may...

  9. 17 CFR 240.0-10 - Small entities under the Securities Exchange Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... interrogation devices or moving tickers at all times during the preceding fiscal year (or in the time that it... purposes of paragraph (g) of this section, “interrogation device” shall refer to any device that may...

  10. 17 CFR 240.0-10 - Small entities under the Securities Exchange Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... interrogation devices or moving tickers at all times during the preceding fiscal year (or in the time that it... purposes of paragraph (g) of this section, “interrogation device” shall refer to any device that may...

  11. 17 CFR 240.0-10 - Small entities under the Securities Exchange Act for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... liabilities) of less than $500,000 on the date in the prior fiscal year as of which its audited financial... dealer that had total capital (net worth plus subordinated liabilities) of less than $500,000 on the last... this section; (f) When used with reference to a municipal securities dealer that is a bank...

  12. 42 CFR 401.705 - Eligibility criteria for qualified entities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... HUMAN SERVICES GENERAL PROVISIONS GENERAL ADMINISTRATIVE REQUIREMENTS Availability of Medicare Data for Performance Measurement § 401.705 Eligibility criteria for qualified entities. (a) Eligibility criteria: To be... data. (iii) Successfully combining claims data from different payers to calculate performance...

  13. 42 CFR 401.705 - Eligibility criteria for qualified entities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... HUMAN SERVICES GENERAL PROVISIONS GENERAL ADMINISTRATIVE REQUIREMENTS Availability of Medicare Data for Performance Measurement § 401.705 Eligibility criteria for qualified entities. (a) Eligibility criteria: To be... data. (iii) Successfully combining claims data from different payers to calculate performance...

  14. Data Base Design Using Entity-Relationship Models.

    ERIC Educational Resources Information Center

    Davis, Kathi Hogshead

    1983-01-01

    The entity-relationship (ER) approach to database design is defined, and a specific example of an ER model (personnel-payroll) is examined. The requirements for converting ER models into specific database management systems are discussed. (Author/MSE)

  15. 78 FR 21603 - Proposed Reporting Entity; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Proposed Reporting Entity; Request for Comments AGENCY: Federal Accounting Standards..., notice is hereby given that the Federal Accounting Standards Advisory Board is seeking input on...

  16. Ambulatory surgery center joint ventures involving tax-exempt entities.

    PubMed

    Becker, S; Pristave, R J; McConnell, W

    1999-01-01

    This article provides an overview of the tax-exempt related issues for ambulatory surgery center joint ventures involving tax-exempt entities. The article analyzes the key points of analysis of the guidance released by the IRS, in particular General Counsel Memorandum 39862, Revenue Ruling 98-15, and Redlands Surgical Services v. Commissioner of the Internal Revenue Service. These key points include whether the venture results in private inurement to insiders and whether the venture furthers the charitable purposes of the tax-exempt entity. The article also provides practical guidance to analyze the documents and structure of the joint venture to ensure compliance with the IRS guidance. These practical considerations include, among other things, whether the charitable purposes of the tax-exempt entity are clearly expressed in the documents and whether the tax-exempt entity has sufficient control over the joint venture to ensure the charitable purposes are being adhered to.

  17. 7 CFR 760.908 - Deceased individuals or dissolved entities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... dissolved entity must be provided. (c) If a participant is now a dissolved general partnership or joint venture, all members of the general partnership or joint venture at the time of dissolution or their...

  18. Rediscovering Perifollicular Elastolysis: A Hitherto Undocumented Entity in India

    PubMed Central

    Verma, Shyam B; Nandkumar, Gopinath

    2015-01-01

    Perifollicular elastolysis, also known as papular acne scars is a common but taken for granted entity. It appears as asymptomatic whitish yellow papules on the trunk and proximal arms. Histologically there is loss of elastin around the pilosebaceous follicles. The lesions are the result of a scarring process that appear as papules and are often mistaken for papules of acne and are treated. A knowledge of this entity which has never been described before in India is being reiterated. PMID:26677277

  19. Considering the health care entity C corporation conversion to tax pass-through entity status.

    PubMed

    Reilly, Robert F

    2012-01-01

    The double taxation of C corporation income from operations and from the ultimate sale of its assets makes the C corporation an inefficient tax status for many health care entities. At the time of this writing, the changes in the federal tax law that are scheduled to take effect in 2013 will increase this level of double-taxation inefficiency. The owners of a C corporation practice can avoid the C corporation status tax inefficiency by converting the practice to either (1) S corporation status or (2) LLC status. The conversion of the health care C corporation to an S corporation may be accomplished without a current tax cost. However, the conversion of a health care C corporation to an LLC status can result in a current tax at both the corporation level and the shareholder level. Nonetheless, the current conversion tax cost may be less than the future tax cost (1) of operating the practice as a C corporation and incurring double taxation at what may be higher tax rates or (2) of incurring the higher tax cost (or reduced price) on the ultimate disposition of the practice assets and the attendant double taxation of the appreciation in the value of the practice assets. Since individual income tax rates on qualifying dividends from C corporations and on capital gains are currently at very low rates, this may be a good time for C corporation practice owners to consider the costs and benefits of a conversion to either S corporation status or LLC status. The practice owners should consult with their accounting, legal, and valuation advisors in order to consider all of the costs and benefits of a possible corporate tax status conversion. An estimation of both the costs and benefits of the corporate tax status conversion depends on the concluded fair market values of the medical practice, dental practice, or other health care entity assets. And, that practice asset appraisal should encompass all of the practice assets, both tangible assets and intangible assets.

  20. 76 FR 41246 - Pesticide Program Dialogue Committee, Pesticide Registration Improvement Act Process Improvement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... implementation issues. In meeting its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Endangered... affected by this action. Other types of entities not listed in this unit could also be affected. The...

  1. 17 CFR 250.110 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... from sales of electric energy or of natural or manufactured gas distributed at retail for its previous... electric energy or natural or manufactured gas to tenants or employees of any operating subsidiary...

  2. 17 CFR 250.110 - Small entities for purposes of the Regulatory Flexibility Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from sales of electric energy or of natural or manufactured gas distributed at retail for its previous... electric energy or natural or manufactured gas to tenants or employees of any operating subsidiary...

  3. 78 FR 45464 - Broadband Data Improvement Act; Eligible Entities Aggregate Form 477 Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ... Funding Availability (NOFA), 74 FR 32545, on funding this program, which defined several key terms for the... service. NTIA later issued a clarification of the Technical Appendix to the NOFA, 74 FR 40569, and later... provider of broadband service, it could unfairly use these aggregated data in marketing its own services...

  4. 78 FR 3317 - Removal of Persons From the Entity List Based on Removal Request; Implementation of Entity List...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-16

    ... Certain Persons to the Entity List'' in the Federal Register (77 FR 61249). This rule amends the Entity... CFR, 2001 Comp., p. 783 (2002), as extended by the Notice of August 15, 2012, 77 FR 49699 (August 16.... 7201 et seq.; 22 ] U.S.C. 7210; E.O. 12058, 43 FR 20947, 3 CFR, 1978 Comp., p. 179; E.O. 12851, 58...

  5. Considering the health care entity C corporation conversion to tax pass-through entity status.

    PubMed

    Reilly, Robert F

    2012-01-01

    The double taxation of C corporation income from operations and from the ultimate sale of its assets makes the C corporation an inefficient tax status for many health care entities. At the time of this writing, the changes in the federal tax law that are scheduled to take effect in 2013 will increase this level of double-taxation inefficiency. The owners of a C corporation practice can avoid the C corporation status tax inefficiency by converting the practice to either (1) S corporation status or (2) LLC status. The conversion of the health care C corporation to an S corporation may be accomplished without a current tax cost. However, the conversion of a health care C corporation to an LLC status can result in a current tax at both the corporation level and the shareholder level. Nonetheless, the current conversion tax cost may be less than the future tax cost (1) of operating the practice as a C corporation and incurring double taxation at what may be higher tax rates or (2) of incurring the higher tax cost (or reduced price) on the ultimate disposition of the practice assets and the attendant double taxation of the appreciation in the value of the practice assets. Since individual income tax rates on qualifying dividends from C corporations and on capital gains are currently at very low rates, this may be a good time for C corporation practice owners to consider the costs and benefits of a conversion to either S corporation status or LLC status. The practice owners should consult with their accounting, legal, and valuation advisors in order to consider all of the costs and benefits of a possible corporate tax status conversion. An estimation of both the costs and benefits of the corporate tax status conversion depends on the concluded fair market values of the medical practice, dental practice, or other health care entity assets. And, that practice asset appraisal should encompass all of the practice assets, both tangible assets and intangible assets. PMID

  6. 20 CFR 662.220 - What entity serves as the One-Stop partner for a particular program in the local area?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false What entity serves as the One-Stop partner... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.220...

  7. 20 CFR 662.220 - What entity serves as the One-Stop partner for a particular program in the local area?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false What entity serves as the One-Stop partner... TRAINING ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Partners and the Responsibilities of Partners § 662.220...

  8. 20 CFR 664.810 - How does a Local Board or other entity become eligible to receive a Youth Opportunity Grant?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... eligible to receive a Youth Opportunity Grant? 664.810 Section 664.810 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR YOUTH ACTIVITIES UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Youth Opportunity Grants § 664.810 How does a Local Board or other entity become eligible to receive...

  9. 20 CFR 664.810 - How does a Local Board or other entity become eligible to receive a Youth Opportunity Grant?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... eligible to receive a Youth Opportunity Grant? 664.810 Section 664.810 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR YOUTH ACTIVITIES UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Youth Opportunity Grants § 664.810 How does a Local Board or other entity become eligible to receive...

  10. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Application of section 199 to pass-thru entities for taxable years beginning on or before May 17, 2006, the enactment date of the Tax Increase Prevention and Reconciliation Act of 2005. 1.199-9 Section 1.199-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED)...

  11. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Application of section 199 to pass-thru entities for taxable years beginning on or before May 17, 2006, the enactment date of the Tax Increase Prevention and Reconciliation Act of 2005. 1.199-9 Section 1.199-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED)...

  12. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Application of section 199 to pass-thru entities for taxable years beginning on or before May 17, 2006, the enactment date of the Tax Increase Prevention and Reconciliation Act of 2005. 1.199-9 Section 1.199-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED)...

  13. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Application of section 199 to pass-thru entities for taxable years beginning on or before May 17, 2006, the enactment date of the Tax Increase Prevention and Reconciliation Act of 2005. 1.199-9 Section 1.199-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED)...

  14. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Application of section 199 to pass-thru entities for taxable years beginning on or before May 17, 2006, the enactment date of the Tax Increase Prevention and Reconciliation Act of 2005. 1.199-9 Section 1.199-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED)...

  15. Entity versus incremental theories predict older adults' memory performance.

    PubMed

    Plaks, Jason E; Chasteen, Alison L

    2013-12-01

    The authors examined whether older adults' implicit theories regarding the modifiability of memory in particular (Studies 1 and 3) and abilities in general (Study 2) would predict memory performance. In Study 1, individual differences in older adults' endorsement of the "entity theory" (a belief that one's ability is fixed) or "incremental theory" (a belief that one's ability is malleable) of memory were measured using a version of the Implicit Theories Measure (Dweck, 1999). Memory performance was assessed with a free-recall task. Results indicated that the higher the endorsement of the incremental theory, the better the free recall. In Study 2, older and younger adults' theories were measured using a more general version of the Implicit Theories Measure that focused on the modifiability of abilities in general. Again, for older adults, the higher the incremental endorsement, the better the free recall. Moreover, as predicted, implicit theories did not predict younger adults' memory performance. In Study 3, participants read mock news articles reporting evidence in favor of either the entity or incremental theory. Those in the incremental condition outperformed those in the entity condition on reading span and free-recall tasks. These effects were mediated by pretask worry such that, for those in the entity condition, higher worry was associated with lower performance. Taken together, these studies suggest that variation in entity versus incremental endorsement represents a key predictor of older adults' memory performance. PMID:24128076

  16. Entity versus incremental theories predict older adults' memory performance.

    PubMed

    Plaks, Jason E; Chasteen, Alison L

    2013-12-01

    The authors examined whether older adults' implicit theories regarding the modifiability of memory in particular (Studies 1 and 3) and abilities in general (Study 2) would predict memory performance. In Study 1, individual differences in older adults' endorsement of the "entity theory" (a belief that one's ability is fixed) or "incremental theory" (a belief that one's ability is malleable) of memory were measured using a version of the Implicit Theories Measure (Dweck, 1999). Memory performance was assessed with a free-recall task. Results indicated that the higher the endorsement of the incremental theory, the better the free recall. In Study 2, older and younger adults' theories were measured using a more general version of the Implicit Theories Measure that focused on the modifiability of abilities in general. Again, for older adults, the higher the incremental endorsement, the better the free recall. Moreover, as predicted, implicit theories did not predict younger adults' memory performance. In Study 3, participants read mock news articles reporting evidence in favor of either the entity or incremental theory. Those in the incremental condition outperformed those in the entity condition on reading span and free-recall tasks. These effects were mediated by pretask worry such that, for those in the entity condition, higher worry was associated with lower performance. Taken together, these studies suggest that variation in entity versus incremental endorsement represents a key predictor of older adults' memory performance.

  17. Enhanced Named Entity Extraction via Error-Driven Aggregation

    SciTech Connect

    Lemmond, T D; Perry, N C; Guensche, J W; Nitao, J J; Glaser, R E; Kidwell, P; Hanley, W G

    2010-02-22

    Despite recent advances in named entity extraction technologies, state-of-the-art extraction tools achieve insufficient accuracy rates for practical use in many operational settings. However, they are not generally prone to the same types of error, suggesting that substantial improvements may be achieved via appropriate combinations of existing tools, provided their behavior can be accurately characterized and quantified. In this paper, we present an inference methodology for the aggregation of named entity extraction technologies that is founded upon a black-box analysis of their respective error processes. This method has been shown to produce statistically significant improvements in extraction relative to standard performance metrics and to mitigate the weak performance of entity extractors operating under suboptimal conditions. Moreover, this approach provides a framework for quantifying uncertainty and has demonstrated the ability to reconstruct the truth when majority voting fails.

  18. Of substance: the nature of language effects on entity construal.

    PubMed

    Li, Peggy; Dunham, Yarrow; Carey, Susan

    2009-06-01

    Shown an entity (e.g., a plastic whisk) labeled by a novel noun in neutral syntax, speakers of Japanese, a classifier language, are more likely to assume the noun refers to the substance (plastic) than are speakers of English, a count/mass language, who are instead more likely to assume it refers to the object kind [whisk; Imai, M., & Gentner, D. (1997). A cross-linguistic study of early word meaning: Universal ontology and linguistic influence. Cognition, 62, 169-200]. Five experiments replicated this language type effect on entity construal, extended it to quite different stimuli from those studied before, and extended it to a comparison between Mandarin speakers and English speakers. A sixth experiment, which did not involve interpreting the meaning of a noun or a pronoun that stands for a noun, failed to find any effect of language type on entity construal. Thus, the overall pattern of findings supports a non-Whorfian, language on language account, according to which sensitivity to lexical statistics in a count/mass language leads adults to assign a novel noun in neutral syntax the status of a count noun, influencing construal of ambiguous entities. The experiments also document and explore cross-linguistically universal factors that influence entity construal, and favor Prasada's [Prasada, S. (1999). Names for things and stuff: An Aristotelian perspective. In R. Jackendoff, P. Bloom, & K. Wynn (Eds.), Language, logic, and concepts (pp. 119-146). Cambridge, MA: MIT Press] hypothesis that features indicating non-accidentalness of an entity's form lead participants to a construal of object kind rather than substance kind. Finally, the experiments document the age at which the language type effect emerges in lexical projection. The details of the developmental pattern are consistent with the lexical statistics hypothesis, along with a universal increase in sensitivity to material kind.

  19. 40 CFR 33.205 - How does an entity become certified by EPA?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... basis of present circumstances. An entity shall not be denied certification based solely on historical... disadvantaged individuals at some time in the past, if the entity currently meets the ownership and/or control... equipment owned by or available to the entity and the licenses the entity and its key personnel possess...

  20. 40 CFR 33.205 - How does an entity become certified by EPA?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... basis of present circumstances. An entity shall not be denied certification based solely on historical... disadvantaged individuals at some time in the past, if the entity currently meets the ownership and/or control... equipment owned by or available to the entity and the licenses the entity and its key personnel possess...

  1. Solitary fibrous tumour of lacrimal gland: a rare entity.

    PubMed

    Narang, Vikram; Singh, Nagi Anitaraj Rajendra; Bajwa, Gurkirat Singh; Sood, Neena

    2015-03-01

    Solitary fibrous tumour (SFT) is a rare spindle cell tumour of mesenchymal origin most commonly encountered in pleura. It can affect the orbital region but SFT of lacrimal gland is rare. We hereby report of a SFT of lacrimal gland in a 50-year-old male presenting with slow growing swelling in left superolateral orbital region. The preliminary fine needle aspiration cytology (FNAC) could not reveal any definite diagnosis. Excision biopsy and immunohistochemistry (IHC) confirmed the diagnosis. Therefore, clinician and pathologist should be aware of this entity and biopsy along with IHC is required to rule out other entities which can mimic it clinically and histopathologically.

  2. Solitary fibrous tumour of lacrimal gland: a rare entity.

    PubMed

    Narang, Vikram; Singh, Nagi Anitaraj Rajendra; Bajwa, Gurkirat Singh; Sood, Neena

    2015-03-01

    Solitary fibrous tumour (SFT) is a rare spindle cell tumour of mesenchymal origin most commonly encountered in pleura. It can affect the orbital region but SFT of lacrimal gland is rare. We hereby report of a SFT of lacrimal gland in a 50-year-old male presenting with slow growing swelling in left superolateral orbital region. The preliminary fine needle aspiration cytology (FNAC) could not reveal any definite diagnosis. Excision biopsy and immunohistochemistry (IHC) confirmed the diagnosis. Therefore, clinician and pathologist should be aware of this entity and biopsy along with IHC is required to rule out other entities which can mimic it clinically and histopathologically. PMID:25954627

  3. Twisted speckle entities inside wave-front reversal mirrors

    SciTech Connect

    Okulov, A. Yu

    2009-07-15

    The previously unknown property of the optical speckle pattern reported. The interference of a speckle with the counterpropagating phase-conjugated (PC) speckle wave produces a randomly distributed ensemble of a twisted entities (ropes) surrounding optical vortex lines. These entities appear in a wide range of a randomly chosen speckle parameters inside the phase-conjugating mirrors regardless to an internal physical mechanism of the wave-front reversal. These numerically generated interference patterns are relevant to the Brillouin PC mirrors and to a four-wave mixing PC mirrors based upon laser trapped ultracold atomic cloud.

  4. Ossification of the bilateral Achilles tendon: a rare entity.

    PubMed

    Arora, Abhishek J; Arora, Richa

    2015-09-01

    Ossification of the Achilles tendon is a rare clinical entity comprising of one or more segments of variable sized ossified masses in the fibrocartilaginous substance of the tendon. The etiology of ossification of the Achilles tendon is multifactorial with recurrent trauma and surgery comprising major predisposing factors, with others being metabolic, systemic, and infectious diseases. The possibility of a genetic predisposition towards this entity has also been raised, but has not yet been proven. We present a rare case of ossification of the bilateral Achilles tendons without any history of trauma or surgery in a 48-year-old female patient. PMID:26413314

  5. The sky entities as represented in African literature

    NASA Astrophysics Data System (ADS)

    Urama, Evelyn N.

    2011-06-01

    Astronomical observations used by the ancient people of Africa were developed out of the people's desire to have concrete manifestations of their gods and religious beliefs as well as for time-keeping - day, night and calendar for agricultural and festive seasons. The sky entities (the solar and stellar systems) observed become part of the lives and events here on Earth and so are also part of the context of African literature. This paper examines the ways in which different African peoples have reflected on the role of the sky entities in their literature.

  6. Relevant factors to consider prior to an investor-owned acquisition of a nonprofit healthcare entity.

    PubMed

    Ault, Kelvin; Childs, Brad; Wainright, Charles F; Young, Marilyn

    2011-01-01

    The purpose of this article is to explore the factors that affect the negotiations for an acquisition of a nonprofit system by an investor-owned entity. The recent economic downturn, accompanying credit crisis, and healthcare reform legislation will likely encourage and accelerate the pace of merger and acquisition (M&A) transactions between investor-owned entities and nonprofit hospitals. As many nonprofits are smaller, more financially vulnerable, and more limited in their access to capital than their investor-owned counterparts, nonprofits could be prime targets for investor-owned acquirers during the healthcare reform implementation period. In M&A transactions of this type, the investor-owned acquirer typically is motivated to pursue an acquisition when the deal promises an acceptable return on investment and decreased operating costs from economies of scale. Alternatively, the nonprofit target is typically seeking funding for upgrades to facilities and information technology systems as well as a continued commitment to charity care and managed-care contracting leverage. A successful acquisition of a nonprofit hospital by an investor-owned company requires a careful analysis of relevant tax, economic, and strategic factors prior to closing the deal. This article lists the most significant factors to consider in these deals and explains how these factors should influence the purchase price and postacquisition cash flow.

  7. Recreation of the 28-entity IGES test file using the ComputerVision CADDS 4X

    NASA Technical Reports Server (NTRS)

    Kuan, Anchyi; Shah, Saurin; Smith, Kevin

    1987-01-01

    An Initial Graphics Exchange Specification (IGES) test file is called the 28 Entity IGES Test File. This file contains 28 geometric and annotation entities which are considered the basic entities that an IGES translator for any CAD system should support. The main purpose was to determine how the IGES preprocessor supports the 28 entities through recreation of the 28 Entity IGES Test File on the ComputerVision CADDS 4X. Test procedure is described and test results are presented.

  8. Business Entity Selection: Why It Matters to Healthcare Practitioners. Part II--Corporations, Limited Liability Companies, and Professional Entities.

    PubMed

    Nithman, Robert W

    2015-01-01

    The Bureau of Labor statistics indicates only a 50% four-year survivability rate among businesses classified as "education and health services." Gaining knowledge of IRS business entities can result in cost savings, operational efficiency, reduced liability, and enhanced sustainability. Each entity has unique disadvantages, depending on size, diversity of ownership, desire to expand, and profitability. Business structures should be compatible with organizational mission or vision statements, services and products, and professional codes of ethics. Healthcare reform will require greater business acumen. We have an ethical duty to disseminate and acquire the knowledge to properly establish and manage healthcare practices to ensure sustainable services that protect and serve the community.

  9. 76 FR 9849 - Privacy Act of 1974: System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... policies that ensure commercial motor vehicle (CMV) drivers engaged in interstate commerce are physically... exemption information in Medical Exemption Program. A request from any other individual or entity (e.g., a... Transportation Equity Act for the 21st Century (TEA-21)--amends Section 31315 and Section 31136(e) of Title 49...

  10. Contained Entity of an Educational Innovation: The Realities of Micropolitics

    ERIC Educational Resources Information Center

    Raksit, Mandira

    2006-01-01

    This study was about a single case of educational innovation and excellence in educational technology in a secondary school in Ontario. The researcher explored the question of how the innovation resulted from an individual effort and attainment remained a "contained entity" after its decade-long existence. From the lenses of multiple realities,…

  11. Integrating Real World Entities into an Academic Curriculum

    ERIC Educational Resources Information Center

    Tompkins, Terrance; Schlesinger, Marc

    2010-01-01

    This research will demonstrate how an experiential learning practicum can be successfully implemented into an academic curriculum, using Drexel University's (Philadelphia, PA) award-winning student-run record label, MAD Dragon Records, as a case study. It will describe the components necessary to implement and operate a real-world entity within…

  12. Ambras Syndrome with Gingival Hyperplasia: A Rare Entity.

    PubMed

    Reddy Kundoor, Vinay Kumar; Maloth, Kotya Naik; Kesidi, Sunitha; Moni, Thakur

    2016-01-01

    Ambras syndrome is a rare and special form of congenital hypertrichosis, characterized by dysmorphic facial features and familial pattern of inheritance. It is rarely associated with gingival hyperplasia. We report such a rare entity in a 38-year-old female patient with a history of consanguinity and positive family history. PMID:27601862

  13. 42 CFR 438.808 - Exclusion of entities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Conditions for Federal Financial Participation § 438.808..., directly or indirectly, for the furnishing of health care, utilization review, medical social work, or administrative services, with one of the following: (i) Any individual or entity excluded from participation...

  14. Ambras Syndrome with Gingival Hyperplasia: A Rare Entity

    PubMed Central

    Reddy Kundoor, Vinay Kumar; Maloth, Kotya Naik; Kesidi, Sunitha; Moni, Thakur

    2016-01-01

    Ambras syndrome is a rare and special form of congenital hypertrichosis, characterized by dysmorphic facial features and familial pattern of inheritance. It is rarely associated with gingival hyperplasia. We report such a rare entity in a 38-year-old female patient with a history of consanguinity and positive family history.

  15. 7 CFR 1450.203 - Eligible persons and legal entities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Eligible persons and legal entities. 1450.203 Section 1450.203 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE...

  16. 7 CFR 1450.203 - Eligible persons and legal entities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Eligible persons and legal entities. 1450.203 Section 1450.203 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE...

  17. 7 CFR 1450.203 - Eligible persons and legal entities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Eligible persons and legal entities. 1450.203 Section 1450.203 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE...

  18. 7 CFR 1450.203 - Eligible persons and legal entities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Eligible persons and legal entities. 1450.203 Section 1450.203 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOMASS CROP ASSISTANCE...

  19. 17 CFR 45.6 - Legal entity identifiers

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... identity of the counterparty's ultimate parent, shall be reported, by means of self-registration, third... identity of the legal entity's ultimate parent. Parent means, for the purposes of § 45.6, a legal person... identifier system designated by the Commission pursuant to this section. Self-registration means...

  20. 24 CFR 578.69 - Cooperation among entities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Cooperation among entities. 578.69 Section 578.69 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING...